Background: While survival has considerably improved in paediatric oncology, the neurotoxicity of treatments compromise functional prognosis. Chemotherapy-induced peripheral neuropathy (CIPN) is an under-rated adverse effect in clinical practice. CIPN is even more difficult to assess in paediatrics. Objectives was to describe the prevalence of CIPN at the end of oncological treatment in children, and to observe the impact on quality of life (QoL). Procedure: A retrospective, observational, monocentric analysis at end-of-treatment oncology assessment was performed in a paediatric haematology-oncology department. We reported the prevalence of CIPN, neuropathic pain, global health assessment and QoL in patients with haematologic malignancies or cancer before the age of 15, exposed to neurotoxic chemotherapies, over the period July 2021 to July 2022. Results: We included 23 patients. 30.4% had symptoms of CIPN at the end of oncological treatment. Of these, 54.1% had neuropathic pain; overall, QoL was compromised (PedsQL median: 60% versus 77% for those without CIPN), with preferential impairment in the ”physical health”, ”emotional functioning” and ”school functioning” spheres. Conclusions: During oncology course, CIPN is a common adverse effect in the paediatric population. It may persist at the end of treatment, and it is a cause of chronic pain. Therefore, CIPN has a significant negative effect on patients’ QoL.

Bingham plastic fluids display solid-like characteristics when subjected to stress below a critical threshold while behaving more like fluids when the stress exceeds that barrier. Gaining a comprehensive understanding of the behaviour of fluids when they are confined is crucial for numerous commercial applications, including food processing, oil drilling, and pharmaceutical production. This study examines the characteristics of non-Newtonian fluid flow between two parallel plates under two distinct situations. In the first scenario, the plates remain in their existing positions, whereas in the second scenario, the plates need to move in opposite directions. Both of these events are feasible. The research comprehensively analyses the effects of compression and temperature changes in both scenarios. Furthermore, this method is employed to examine the characteristics of velocity, pressure, and temperature. Developing relevant assumptions that can convert a nonlinear coupled problem into a linear equation is essential to simplify the ensuing analysis. Subsequently, a semi-analytical approach is employed to solve the equations of motion, continuity, and energy derived from the preceding stage. The R.K. Fehlberg approach utilizes dimensionless equations at every stage to achieve its objectives. This research aims to comprehend the influence of pressure, temperature, and compression on the issue under investigation. Before commencing the procedure, multiple parameters are considered when representing the velocity, pressure, and temperature profiles.

Background and purpose Currently, the clinical benefits of liver cancer treatment are still limited. Emerging evidences have highlighted that paraptosis may be an effective strategy to threapy liver cancer. In our previous studies, compound 4a was found to induce paraptosis in cancer cells. Here, the characteristics of compound 4a induced paraptosis were further revealed, and for the first time, the target and related molecular mechanisms of compound 4a induced paraptosis in liver cancer were explored. Study design and methods The effect and mechanism of compound 4a on liver cancer cells both in vitro and in vivo. And the targets of compound 4a that triggering paraptosis, were identified and confirmed by using the technology of mass spectrometry-based drug affinity responsive target stability(DARTS), siRNA, and Cellular thermal Shift Assay(CETSA). Intracellular calcium concentration and protein distribution were detected by Cal520-AM and immunofluorescence, respectively. Results We found that compound 4a can effectively induce paraptosis-like cell death in liver cancer both in vitro and in vivo, and its effect is comparable to the first-line anti-liver cancer drugs oxaliplatin while with higher safety. We identified that Calreticulin(CRT) protein as a target of compound 4a, which causing cellular endoplasmic reticulum(ER) stress and calcium overload. CRT knockdown increased cell proliferation and reduced cytoplasmic vacuoles, which was associated with inhibited ER stress and paraptosis. Conclusions Our study provides a potential safe and effective agent for the treatment of liver cancer. Moreover, we have clarified characteristics of compound 4a-triggered paraptosis and revealed a unique function of CRT in paraptosis.

Aim: This review aimed to synthesise the evidence related to the incidence of serious and non-serious adverse events with the use of monoclonal antibodies (mAbs) among COVID-19 patients. Methods: Databases were searched from January 2020 to September 2023 for randomized clinical trials (RCTs) that used mAbs for the treatment of COVID-19 regardless of disease severity. Study screening, data extraction, and data analysis were done independently by two reviewers. The Cochrane risk of bias 1.0 tool was used for methodological quality assessment. Results: Twenty-three studies were identified for analysis with 20,099 participants in the treatment arm and 20191 participants in the controlled arm. Seven trials reported hepatoxicity and there was a statistically significant increase in the chance of hepatoxicity among patients treated with mAbs compared to those given standard of care (SoC) or placebo with RR = 1.70, 95% CI 1.29 – 2.24. Five trials reported neutropenia and there was a statistically significant association of neutropenia with the use of mAbs compared to SoC or placebo with RR = 4.03, 95% CI 1.74- 9.34. Ten trials reported any disease-related serious adverse events related to disease and there was a reduction of risk compared to SoC/placebo, but was not statistically significant (RR = 0.88, 95% CI 0.70-1.11). Conclusion: The use of mAbs was found to be associated with an increased risk of hepatoxicity and neutropenia compared to SoC/placebo among COVID-19 patients with moderate certainty of evidence. Long-term observational studies are recommended to observe post-COVID adverse events related to mAbs.

Background and Purpose: Acute graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT). Gastrointestinal damage is a priority target of acute GVHD, presented as intestinal barrier dysfunction. The first-line treatment for acute GVHD is glucocorticoid, which, however, brings inevitable side effects. A search for alternative or supplementary therapy has been ongoing. Experimental Approach: Acute GVHD mice were treated with artesunate (ART), dexamethasone (DXM) or ART combined with DXM. The progression and severity of acute GVHD was evaluated by weight loss, clinical scores and survival. Intestinal permeability was assessed by FD-4 leakage. Colonic tissues were analyzed by qPCR, western blotting and staining techniques. Th17 and Treg cells were analyzed by flow cytometry. Key Results: ART alleviated acute GVHD and prolonged survival. Damages in intestinal tract, liver and skin of acute GVHD mice were evidently mitigated by ART. Tight junction proteins Claudin-1/3 were increased while Claudin-2 decreased in intestinal epithelium, intestinal epithelial cell renewal was accelerated, mucus lining the epithelium was thickened, and intestinal permeability was decreased in the ART-treated acute GVHD mice. ART induced allo-T cells to differentiate to Treg instead of Th17 through inhibiting mTOR pathway. Significantly, half-dose DXM combined with ART showed potent protective effect on intestinal barrier comparable to full-dose DXM did. Conclusion and Implications: ART ameliorated intestinal damages in acute GVHD mice through restoring tight junctions and Th17/Treg balance. Moreover, ART synergized DXM against immune attack on intestinal barrier, indicating ART could be a supplementary strategy that reduced DXM-related side effects.

Background and Purpose The G protein-coupled receptor GPR173 (SREB3) regulates gonadotropin secretion and ovarian cyclicity. However, the identity of a ligand for this receptor remains uncertain. Recently, it was proposed that the cholecystokinin octapeptide CCK8 is a ligand for GPR173. Experimental Approach Here, comparison of responses to CCK8 in CHO-K1 cells transfected with human GPR173 or with with an empty vector indicate that responses to CCK8 are mediated by endogenous CCK receptors. Therefore, to further investigate CCK-type peptides as candidate ligands for GPR173-type receptors, we employed an evolutionary approach, informed by the ancient origin and co-evolution of neuropeptides and their cognate receptors. GPR173-type receptors were identified in two invertebrate species, the starfish Asterias rubens and the octopus Octopus vulgaris, and effects of CCK-type peptides from these species on CHO-K1 cells transfected with respective GPR173-type receptors or empty vectors were investigated Key Results Starfish and octopus CCK-type peptides had no effect on CHO-K1 cells transfected with empty vectors or with respective GPR173-type receptors. However, positive control experiments demonstrated that starfish and octopus CCK-type peptides triggered responses in CHO-K1 cells transfected with respective orthologs of mammalian CCKA/CCKB-type receptors. Conclusion and Implications Our findings indicate that CCK-type neuropeptides do not act as ligands for GPR173 in humans or GPR173-type receptors in other taxa. Furthermore, this study underscores the importance of an evolutionary approach in assessing candidate ligands for orphan receptors, informed by phylogenetic analysis of the distribution of ligands and receptors, thereby avoiding challenges associated with endogenous receptor expression in mammalian cell lines

Detergent-mediated viral inactivation is an important process step for ensuring viral safety of parenteral biotherapeutics, including plasma proteins and monoclonal antibodies (mAb). The conventional Triton™ X-100 detergent has ecological toxicity concerns and REACH classification that mandate replacement in the biopharmaceutical industry. Criteria for a replacement detergent include viral inactivation efficacy, acceptable safety and biodegradation profile, process removal and quality suitable for parenteral drug product manufacturing. A non-ionic, C11-15 secondary alcohol ethoxylate, Deviron ® 13-S9 detergent, has been demonstrated to meet the necessary requirements for detergent performance. Benchmarking studies with Triton™ X-100 demonstrate comparable performance with a panel of enveloped viruses in multiple matrices, including human IgG, clarified cell culture harvest, and fractionated plasma. Deviron ® 13-S9 detergent demonstrated viral inactivation efficiency comparable to or better than, Triton™ X-100 detergent, achieving > 5 log reduction values (LRV). Critical micelle concentration (CMC) was determined across different temperatures and media. Deviron ® 13-S9 detergent was demonstrated to be readily biodegradable according to OECD 301B guidelines. Effective removal with typical chromatography processes used in downstream purification was confirmed. These findings support Deviron ® 13-S9 detergent as a viable alternative to Triton™ X-100 detergent, ensuring robust viral inactivation, environmental compatibility, and alignment with regulatory requirements.

The predictive link between the spatial demographic changes of a species and its environment is complex and difficult to detect without detailed models and data from multiple sources. Integrative distributional, demographic, and coalescent modeling (iDDC) integrates simulation-based spatial population genetic and species distribution models (SDMs) to enable testing eco-evolutionary hypotheses given geo-referenced genetic data. Integral to iDDC is the transformation between habitat suitability values and local deme sizes, a key parameter that has not been thoroughly explored or used to test eco-evolutionary hypotheses. In this study, we investigate this parameter’s influence on spatiotemporal demographic inference in two Enyalius lizard species in the Brazilian Atlantic Forest, one with a high-elevation distribution, Enyalius iheringii, and another having a low-elevation distribution, Enyalius catenatus. Since environmental tolerances in high-elevation species are generally broader than in low-elevation species, we test two hypotheses: (1) E. iheringii has higher effective migration compared to E. catenatus; and (2) the relationship between habitat suitability and local deme size is non-linear for E. iheringii and linear for E. catenatus. We find support for (1) and mixed support for (2), where we find strong model support for a non-linear transformation for E. iheringii but also find support (although weak) for a non-linear transformation for E. catenatus. We also generate landscape-wide maps of predicted genetic diversity for both target species. We find that genetic diversity predictions for the E. iheringii correspond with predicted patterns of range stability, while predictions for E. catenatus are distinct from predictions of range-wide stability.

Evaluating Waterbirth Risks: A Deep Dive into the POOL Cohort Study’s Research GapsWei-Zhen Tang a, Tai-Hang Liu a,**, Xia Lan a,*

While a best practice for evaluating the behavior of genetic clustering algorithms on empirical data is to conduct parallel analyses on simulated data, these types of simulation techniques often involve sampling genetic data with replacement. In this paper we demonstrate that sampling with replacement, especially with large marker sets, inflates the perceived statistical power to correctly assign individuals (or the alleles that they carry) back to source populations—a phenomenon we refer to as resampling-induced, spurious power inflation (RISPI). To address this issue, we present gscramble a simulation approach in R for creating biologically informed individual genotypes from empirical data that: 1) samples alleles from populations without replacement, 2) segregates alleles based on species-specific recombination rates. This framework makes it possible to simulate admixed individuals in a way that respects the physical linkage between markers on the same chromosome and which does not suffer from RISPI. This is achieved in gscramble by allowing users to specify pedigrees of varying complexity in order to simulate admixed genotypes, segregating and tracking haplotype blocks from different source populations through those pedigrees, and then sampling—using a variety of permutation schemes—alleles from empirical data into those haplotype blocks. We demonstrate the functionality of gscramble with both simulated and empirical data sets and highlight additional uses of the package that users may find valuable.

The adsorption behaviors of Hg2+ ions on adsorbents, salicylaldehyde modified amino-terminated polymers (denoted as SiO2-APTS-SA, SiO2-EDA-SA, SiO2-DETA-SA, SiO2-TETA-SA and SiO2-TEPA-SA, respectively), were studied. The prepared five resins were characterized by Fourier transform-infrared spectra (FTIR), elemental analysis and nitrogen adsorption–desorption. The maximum adsorption capacity of SiO2-APTS-SA, SiO2-EDA-SA, SiO2-DETA-SA, SiO2-TETA-SA and SiO2-TEPA-SA for Hg2+ ions reached 0.2416, 0.2603, 0.2655, 0.2769 and 0.2915 mmol g-1, respectively.

Structural modulation of pristine graphitic carbon nitride presents a significant challenge in the rational design of catalysts for efficient degradation of small organic pollutants under visible light. In this study, we combining first-principles calculations and structure-function relationship to predict a high-performance catalyst. The results indicate that CN-8 exhibits a significant degree of separation between electrons and holes, the CN-8 exhibits exceptional degradation efficiency towards rhodamine B, tetracycline, bisphenol A, and fluralaner under visible light irradiation. The degradation rate constants are 11, 4, 12, and 32 times (0.6353 min-1, 0.1947 min-1, 0.1993 min-1, and 0.2847 min-1) higher than that of bulk g-C3N4 (0.0561 min-1, 0.0575 min-1, 0.0169 min-1, and 0.0089 min-1), respectively. Density functional theory calculations, and structure-function relationship investigations confirm that the superior catalytic activity of CN-8, modifying the amino position changes the electron cloud distribution, promoting efficient separation of photo-generated electron-hole pairs. This study offers valuable insights for developing eco-friendly and efficient photocatalysts for environmental remediation.

A case report of acute mental behavioral abnormality resulting in death 1 year after rabies virus infectionLan Mou1 Hong Wang1 Jianhua Li1 Shikai Wang1*Department of Psychiatry, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang,313000, China*Corresponding author:Shikai Wang ORCID：0000-0002-2321-0524Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University.Huzhou, Zhejiang, China.E-mail addresses: wang-shikai@163.comKey Clinical MessageRabies is a fatal zoonotic disease. Acute mental behavioral abnormalities 1 year after infection with rabies virus are rare, but are medical emergencies that require prompt recognition.Keywords: rabies virus, mental behavioral abnormality,case report,death,acute medicine1.INTRODUCTIONRabies, a fatal zoonotic disease, is typically transmitted through the bite, scratch, or lick of an infected animal(Organization, 2018). Approximately 80% of cases present as encephalitic (rabid or typical) forms. When humans contract rabies, 50-80% develop typical symptoms such as hydrophobia and agoraphobia(Jackson, 2016). Unfortunately, the disease is usually incurable and ultimately fatal once clinical symptoms appear(Kumar et al., 2023). The glycoproteins on the surface of the rabies virus (RABV) genome have the ability to infiltrate large amounts of neuronal tissue in virtually any mammal(Fisher et al., 2018). After infecting peripheral nerves, RABV spreads through retrograde axonal transport to the central nervous system, where it replicates and spreads, eventually causing severe neurological symptoms and fatal outcomes(Yamaoka et al., 2013).The incubation period of RABV typically ranges from 20 to 90 days, although it can be as long as 20 years, depending on the viral entry site and viral load(Tajmalzai & Zarabi, 2024). Once the virus reaches the central nervous system, it often presents with neuropsychiatric symptoms. However, due to the lengthy incubation period and atypical symptoms, there is a risk of misdiagnosis in clinical settings, leading to delays in treatment. Here, we present a case of acute psychiatric behavioral abnormalities, along with hydrophobia, photophobia, and spasmodic seizures occurring a year after a dog bite, ultimately resulting in death.2. CASE HISTORY/EXAMINATION/PRESENTATIONThe patient, a 45-year-old male farmer, was involuntarily brought to the emergency department of a psychiatric hospital by his family while under restraint. He initially presented with symptoms such as insomnia, self-talk, inattention, and incoherent psychomotor arousal, accompanied by irritability, high agitation, and shouting. Over the course of two days, his symptoms escalated to include delusions of victimization and relationship, leading to aggressive behavior towards family members. However, the specific delusional content appeared inconsistent and varied upon further questioning. On physical examination, the patient exhibited normal bilateral pupils, equal in size and round, with a diameter of 3 mm, responsive to light reflexes, and no signs of facial palsy. Despite difficulties in cooperation during sensory and motor exams, he displayed strong spontaneous limb movements and normal muscle tone without any apparent abnormalities or signs of meningeal irritation. There were no signs of fever, seizures, nausea, vomiting, or hydrophobia upon admission. The patient denied any significant medical history. Results from electrocardiogram, electroencephalogram, and head and chest CT scans were all within normal limits.Routine laboratory tests revealed a white blood cell count of 22.14*10^9/L, with neutrophils at 20.49*10^9/L. Other blood cell counts, hemoglobin levels, and additional indexes were within normal limits. Furthermore, blood biochemical tests, including liver and renal function tests, electrolytes, glucose levels, and whole blood rapid C-reactive protein, all fell within the normal range.3.METHODS (DIFFERENTIAL DIAGNOSIS, INVESTIGATIONS AND TREATMENT)Given the patient’s unstable and aggressive behavior prior to admission, a diazepam injection of 10 mg IV was administered for rapid sedation, along with ribavirin 0.15 g for empirical antiviral therapy on the day of the emergency room visit. The patient’s symptoms showed slight improvement and there was no further aggressive behavior observed. However, later in the evening of the same day, the patient developed a low-grade fever, skin itching, hydrophobia, photophobia, intermittent and inconspicuous spasmodic episodes, and vomiting of coffee-like liquid. Upon further investigation into the patient’s medical history, it was revealed by the family and confirmed by neighbors that the patient had been bitten by a dog in the village a year prior and had not received rabies vaccination at that time.4.OUTCOME AND FOLLOW‐UPSubsequently, the patient was promptly transferred to the Infectious Diseases Hospital in the city. The following morning, the patient experienced a high fever, profuse salivation, and paroxysmal convulsions of the muscles throughout the body. His condition deteriorated rapidly, leading to his eventual death following cardiac and respiratory arrest. Viral antigens were identified in the saliva through direct immunofluorescence analysis5. DISCUSSIONRabies is a rare but fatal disease that causes approximately 59,000 deaths and more than 3.7 million disabilities each year, particularly prevalent in developing countries(Hampson et al., 2015). In China, around 40 million people are bitten by dogs annually(Shen et al., 2023; Tu et al., 2018), with dog-associated RABV being the primary pathogen responsible for human rabies cases in inland provinces of China(Wang et al., 2014).Its typical symptoms usually last no more than a month and can be divided into three main phases(Depani et al., 2012; Depani et al., 2013; Wang et al., 2015) : (1) In the prodromal phase, most patients experience fever, some may have other flu-like symptoms, and many report abnormal sensations around the wound, such as numbness, pain, itching, and ants. (2) During the excitatory phase, patients become hydrophobic and may experience spasms of the pharyngeal muscles, difficulty breathing, urination and defecation issues, excessive sweating, and saliva retention. (3) In the paralytic phase, the patient becomes quiet and develops flaccid paralysis, especially in the extremities; involvement of facial muscles can lead to irregular eye movements, jaw tension, mouth drooping, and lack of facial expression. The most common symptoms include aggression, hydrophobia, fear of wind, and progressive paralytic paralysis(Carrara et al., 2013; Gilbert et al., 2015; Tian et al., 2019).The time interval between exposure to RABV and the onset of symptoms typically ranges from 3 weeks to 4 months(Laryea et al., 2017). In the case of our patient, the acute onset of the disease one year after the dog bite may be attributed to the slow replication of the virus and the establishment of latent infection following the initial exposure. It is possible that the virus was reactivated due to neurotropic viral infection at a later time(Amoako et al., 2021).Before the development of typical symptoms of aggression and hydrophobia, the emergency examination did not reveal any obvious abnormalities, except for an abnormally elevated blood image. The diagnosis was confirmed post-mortem only through the detection of rabies virus antigen in saliva via direct immunofluorescence. The patient initially exhibited acute psychobehavioral abnormalities, characterized by psychomotor instability and psychotic symptoms, indicative of a manic rabies type. Research has shown that patients with manic rabies experience more severe damage to pyramidal neuronal cell bodies in the hippocampal corners compared to those with paralytic rabies(Shuangshoti et al., 2013). Additionally, various components of the hippocampus, where limbic symptoms are prominent, are more impacted(Shuangshoti et al., 2016). The progression of symptoms in this case appears atypical, with a prodromal phase featuring insignificant symptoms, followed by a rapid onset of impaired consciousness and death during an excitatory phase, skipping the paralytic phase typically observed.Throughout the course of the disease, the case was marked by psychiatric symptoms. The patient exhibited nonsensical speech and provided unintelligible answers, complicating clinical questioning and hindering a thorough history-taking process. Moreover, the patient experienced an unusually long incubation period for rabies, atypical symptoms in the prodromal stage, and no apparent abnormalities in the EEG and CT scans of the skull. These factors, coupled with healthcare workers’ limited familiarity with the clinical presentation of rabies, the family’s initial denial of a history of dog injury, and the absence of further cranial MRI examination, were the primary contributors to the misdiagnosis. Clinicians should enhance their understanding and prioritize differential diagnosis.6.CONCLUSIONIt is imperative to heighten awareness of rabies, particularly its psychiatric behavioral manifestations, as delayed or incorrect diagnosis can lead to crucial treatment opportunities being overlooked. Therefore, psychiatrists should consistently consider rabies as a differential diagnosis, especially for new patients hailing from rural regions.AUTHOR CONTRIBUTIONSLan Mou: Data curation; Project administration;Investigation; Visualization;writing – original draft.Hong Wang,Jianhua Li: formal analysis; supervision. Shikai Wang: Conceptualization; supervision; writing – review and editing.FUNDING INFORMATION None.CONFLICT OF INTEREST STATEMENT None declared.CONSENT Written informed consent was obtained from the patient’s relative.ReferencesAmoako, Y. A., El-Duah, P., Sylverken, A. A., Owusu, M., Yeboah, R., Gorman, R., Adade, T., Bonney, J., Tasiame, W., Nyarko-Jectey, K., Binger, T., Corman, V. M., Drosten, C., & Phillips, R. O. (2021). Rabies is still a fatal but neglected disease: a case report. J Med Case Rep , 15 (1), 575. https://doi.org/10.1186/s13256-021-03164-yCarrara, P., Parola, P., Brouqui, P., & Gautret, P. (2013). Imported human rabies cases worldwide, 1990-2012. PLoS Negl Trop Dis ,7 (5), e2209. https://doi.org/10.1371/journal.pntd.0002209Depani, S., Mallewa, M., Kennedy, N., & Molyneux, E. (2012). World Rabies Day: evidence of rise in paediatric rabies cases in Malawi.Lancet , 380 (9848), 1148. https://doi.org/10.1016/s0140-6736(12)61668-7Depani, S., Mallewa, M., Kennedy, N., Molyneux, E., & Warrell, M. (2013). Systems thinking needed for rabies control - Authors’ reply.Lancet , 381 (9862), 200-201. https://doi.org/10.1016/s0140-6736(13)60083-5Fisher, C. R., Streicker, D. G., & Schnell, M. J. (2018). 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Pear anthracnose, caused by Colletotrichum fructicola, is a devastating disease that seriously affects most pear varieties, thereby compromising their yield and quality. However, effective control of this pathogen is lacking. To investigate these resistance mechanisms of pear against C. fructicola, transcriptomic and metabolomic were performed in pear anthracnose-resistant pear variety ‘Seli’ and the susceptible variety ‘Cuiguan’ after infection with C. fructicola, respectively. The differentially expressed genes and differentially accumulated metabolites (DAMs) were mainly related to metabolism and secondary metabolite synthetic pathways, including alpha-linoleic acid and phenylalanine biosynthesis metabolism, unsaturated fatty acids biosynthesis, and amino acids and derivatives biosynthesis etc. In particular, the accumulation of unsaturated fatty acids, amino acids and derivatives, such as linoleic acid and derivatives, lauric acid, N-acetyl-L-glutamic acid and L-proline were significantly increased in ‘Seli’ upon C. fructicola infection, while the amino acids of oxiglutatione and N-acetyl-L-glutamic acid, as well as the proanthocyanidins were significantly decreased in ‘Cuiguan’ upon C. fructicola infection, indicating that these metabolites were responsible for the different levels of resistance to anthracnose in ‘Seli’ and ‘Cuiguan’. Overall, our results provided new insights into pear anthracnose resistance regulation, and this may assist in developing new strategies to control pear anthracnose.

Programmed cell death (PCD) is a ubiquitous phenomenon in eukaryotic cells but is less understood in bacteria, where limited instances such as endospore formation in Bacillus subtilis have been experienced earlier. In our study, we investigated the induction of PCD in Pseudomonas aeruginosa triggered by colistin exposure which leads to generation of the increased number of persister cells under biofilm embeded conditions. Interestingly, when colistin was combined with nitroxoline, a transition from apoptosis to necrosis was noted, rendering the cells more vulnerable to damage. Gene expression analyses revealed that overproduction of recA, typically involved in bacterial DNA repair pathways, facilitated PCD induction under colistin stress. The primary mode of damage was mediated by reactive oxygen species (ROS), which caused genomic DNA destruction, protein damage, and bacterial membrane disruption through lipid peroxidation. As a possible effect of PCD, a higher number of persister cells was evident in the multicellular organization such as biofilm in the colistin-treated sample. Furthermore, in the presence of the colistin-nitroxoline combination, severe membrane damage was observed due to cation chelation, leading to cell death from significant osmotic shock. Understanding these mechanisms of antibiotic-mediated killing is crucial for selecting effective treatments in clinical settings.

Objective To investigate the causes, diagnostic approaches, management strategies, and outcomes of primary amenorrhea (PA) within the Saudi population. Design Retrospective study. Setting Tertiary and secondary-level hospitals in Riyadh, Saudi Arabia. Population or Sample A total of 72 patients diagnosed with PA between July 2013 and July 2023. Methods Descriptive and inferential statistics were used to analyze patient information, risk factors, investigations, management plans, and outcomes. Data were analyzed using IBM’s SPSS software version 29, employing Fisher’s exact tests and binary logistic regression to identify significant associations and predictors for different PA categories. Main Outcome Measures Etiolgies, diagnostic approaches, management strategies, and outcomes. Results The results indicate primary ovarian failure as the leading cause of PA (31.9%), followed by central hypogonadism (18.1%) and Turner’s syndrome (16.7%). Diagnostic processes included comprehensive patient histories, physical examinations, hormonal assays, imaging, and karyotyping. Medical therapy was the primary treatment approach in 69.4% of cases, with conjugated estrogens being the most prescribed medication. Surgical interventions, including hymenectomy, were significantly associated with positive outcomes like withdrawal bleeding. The study also found specific associations between age, LH levels, and the likelihood of PA, particularly in cases of primary ovarian failure and Turner syndrome. Conclusions This study’s findings provide a comprehensive overview and contribute to the limited literature on PA in Saudi Arabia, highlighting the need for increased awareness and research to improve clinical understanding and patient care.

In this paper, we consider the following 2D incompressible chemotaxis-Navier-Stokes equations with the fractional diffusion { ∂ t n + u · ∇ n − ∆ n = − ∇ · ( n ∇ c )+ n ( 1 − n )( n − a ) , ∂ t c + u · ∇ c − ∆ c = − cn , ∂ t u + u · ∇ u + ∧ 2 α u + ∇ P = − n ∇ ϕ , where ∧ : = ( − ∆ ) 1 2 and α ∈ [ 1 2 , 1 ] . By establishing the new priori estimates, we get the global well-posedness for the above system with large initial data.

Model predictive control (MPC) has been widely applied in the field of autonomous driving; however, it still suffers from poor control accuracy in extreme conditions. To improve the smoothness and robustness of intelligent vehicle trajectory tracking, this study tries to investigate an improved MPC trajectory tracking control for intelligent vehicle, fuzzy adaptive dynamic model predictive control (FADMPC), with prediction time-domain dynamic optimization and objective function weight adaptive regulation. First, in the improved MPC framework, a vehicle dynamics model with three degrees of freedom is established as the theoretical vehicle model of MPC controller, and the recursive least square method (RLS) with forgetting factor is used to timely estimate tire cornering stiffness considering nonlinear error of the control-oriented vehicle model. Second, the relationship between the prediction time domain of the model and factors such as vehicle speed and road adhesion coefficient is analyzed through simulation. Then, a dynamic time-domain regulation scheme is determined by using the whale optimization algorithm (WOA). Third, a fuzzy controller is used to dynamically adjust the weight coefficient of the lateral displacement tracking error in the objective function. Last, a series of experiments is performed on a hardware-in-the-loop platform to validate the comparison effect of different trajectory tracking controllers on jointed and bisected adhesion condition roads. Results indicate that the proposed FADMPC can effectively improve trajectory tracking accuracy and vehicle stability compared with LQR and even ADMPC controller.

For linked Fractional modified Korteweg-de Vries (mKdV) systems, in which the coefficient is a time-dependent variable, we investigate the exact multiple soliton solutions. Based on the similarity transformation and Hirota bilinear technique, we report both multiple wave kink and wave single kink solutions for two different models of fractional mKdV with time dependent variable coefficient. We use the fractional Hirota bilinear technique to compute analytical solutions for modified coupled space–time–fractional KdV systems. We construct many kink waves for the proposed fractional differential models that are being studied. For the treatment of nonlinear differential models of integer and fractional orders, the Hirota bilinear technique provides a straightforward and promising method. Recently, researchers have been using symbolic computation—like maple—to perform these calculations. We investigated if the results demonstrate the simplicity, effectiveness, and ease of computation of the approach for a range of engineering and physics models. The flexible and random selection of the fractional orders allows us to build deeper structures. Soliton modifications based on fractional order changes enable further applications in the applied science

Parkinson’s disease (PD) is neuropathologically characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), affecting 10 million people worldwide. Rosmarinic acid (RA), a polyphenol found in plants like rosemary (Rosmarinus officinalis), is known for its intriguing biological properties and potential antioxidant and neuroprotective effects. In a previous study we showed that RA treatment prevented hyperlocomotion in mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced parkinsonism and improved the monoaminergic system in healthy animals. However, the molecular mechanisms underlying RA’s action in PD remain unclear. In this study, we treated MPTP-induced PD animals (C57BL/6 male mice) with RA orally at a dose of 100 mg/kg for 15 days and examined the proteome of substantia nigra (SN) to identify possible regulatory targets of RA treatment to shed some lights into its neuroprotective effects. Quantitative proteomics revealed that RA treatment regulated proteins associated with oxidative phosphorylation (OXPHOS), glutamatergic synapse, and vesicular cycle signaling pathway. We identified 371 proteins significantly regulated in response to RA administration (255 upregulated and 116 downregulated). Notably, some cellular targets of RA treatment reported here, including mGluR2/mGluR3/EAAT - proteins from the glutamatergic system - and proteins from the Complex I of the electron transport chain are promising targets for therapeutic intervention. These findings highlight the molecular differences between MPTP-induced PD mice and those treated with RA, providing insights on the molecular basis behind the neuroprotective effects of RA and revealing potential PD signatures that warrant further investigation.

Objective:Sjögren’s syndrome is a complex autoimmune disorder characterized by a multifaceted pathogenesis that encompasses immune dysregulation and metabolic abnormalities. In this study, advanced proteomic and bioinformatics methodologies were used to explore the molecular mechanisms underlying SS. Our study specifically targeted the roles of three pivotal proteins —IFI30, Ndufv3, and Ndufs6, in the pathophysiology of SS. Methods: High-throughput proteomic technology was used to analyze salivary gland tissue samples from four groups of treated mice: normal, non-obese diabetic, STD, and hydroxychloroquine. The biological functions of differentially expressed proteins were elucidated using Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Results: In this study, 3274 proteins were quantified. Among the 82 DEPs, eight were notably upregulated in the SS group, while nine exhibited decreased expression compared to the other groups. Notably, we observed the significant upregulation of IFI30 in the SS model, which is indicative of immune system activation and exacerbation of inflammatory pathways in patients with SS. Conclusion: A comparative analysis of the protein constituents in mouse salivary glands from four groups was conducted using label-free proteomics. Proteins involved in immune dysregulation and disrupted energy metabolism were significantly altered after STD intervention.

This paper presents a detailed examination of the convergence properties of algorithms used for approximating feedback Nash equilibria in nonlinear dynamic games. Specifically, we extend the Value Iteration for Games (VIt-G) algorithm by incorporating Radial Basis Functions (RBFs) to improve the approximation of value functions. The resulting algorithm, RaBVIt-G, is rigorously analyzed for its convergence properties. Our findings are compared with results presented in the literature, particularly those that utilize the Chebyshev spectral collocation method combined with policy iteration, focusing on the convergence of algorithms for linear-quadratic games.

Labor actions by healthcare workers are increasing in frequency and quantity, particularly throughout the United States. Regardless of their cause and size, these strikes have the potential to disrupt normal hospital operations and could impact patient access to care, quality of care, and costs. Strikes resemble other large-scale incidents like natural disasters, pandemics, or terrorist attacks in that they shrink a hospital’s capacity to care for patients, force hospitals to pursue logistically complicated actions like finding replacement providers, and impact nearby facilities due to the offloading of patients. In contrast to these incidents, however, strikes are unique because they often come with months of advanced notice, they reduce capacity by precise amounts with predictable provider losses, they occur over defined periods of time, and they do not necessarily increase the demand for patient care. To maximize efficiency and minimize disruption in response to strikes, hospitals must properly plan ahead and successfully execute their plans. Drawing on the recent planning and response to a resident physician strike at a New York hospital, this paper recounts the experience while describing six core strategies and a planning template that other hospitals can use to prepare for and respond to healthcare provider strikes. These strategies include strike aversion, increasing coverage, decreasing demand, internal and external messaging, creating external partnerships, and demobilization. When properly planned for using Appendix A: Strike Planning Template, strike consequences can be mitigated to ensure that patient care and hospital operations can continue with minimal impact to access, quality, or cost.

Rare Presentation of Adult-Onset Still’s Disease Complicated by Acute Severe Hepatitis Refractory to Medical Treatment: A Case ReportMajed Ali1, Karam Karam2, Emanuel-Youssef Dib3, Elias Fiani4*[1] Department of Internal Medicine, University of Balamand, Beirut, Lebanon. Email: majed.ali@std.balamand.edu.lb[2] Department of Gastroenterology, University of Balamand, Beirut, Lebanon. Email: Karamek7@gmail.com[3] Department of Internal Medicine, University of Balamand, Beirut, Lebanon. Email: emanuelyoussef.dib@std.balamand.edu.lb