Expression of the immediate early gene Arc/Arg3.1 (Arc), a key mediator of synaptic plasticity, is enhanced by neural activity and then reduced by proteasome-dependent degradation. We have previously shown that disruption of Arc degradation, in an Arc knock-in mouse (ArcKR), where the predominant Arc ubiquitination sites were mutated, reduced the threshold to induce, and also enhanced, the strength of Group I metabotropic glutamate receptor-mediated long-term depression (DHPG-LTD). Here we have investigated if ArcKR expression changes long-term potentiation (LTP) in CA1 area of the hippocampus. As previously reported, there was no change in basal synaptic transmission at Schaffer collateral/commissural-CA1 (SC-CA1) synapses in ArcKR versus wild-type (WT) mice. There was however a significant increase in the amplitude of synaptically-induced (with low frequency paired-pulse stimulation) LTD in ArcKR mice. Theta burst stimulation-evoked LTP at SC-CA1 synapses was significantly reduced in ArcKR versus WT mice (after 2 hours). Group 1 mGluR priming of LTP was abolished in ArckR mice, which could also potentially contribute to a depression of LTP. Although high frequency-stimulation (HFS)-induced LTP was not significantly different in ArcKR compared to WT mice (after 1 hour) there was a phenotype in environmentally enriched mice, with the ratio of LTP to short-term potentiation (STP) significantly reduced in ArcKR mice. These findings support the hypothesis that Arc ubiquitination supports the induction and expression of LTP, likely via limiting Arc-dependent removal of AMPA receptors at synapses.

We report a case of atrial fibrillation with frequent monomorphic atrial premature contractions (APCs) in which P-wave morphology was negative in II, III, and aVF and positive in I and aVL leads. After pulmonary vein isolation using a cryoballoon, high-resolution electroanatomical mapping revealed ectopic beats from the posteroseptal area within the inferior vena cava (IVC) with concealed bigeminy. Catheter ablation just above the ectopic focus eliminated the APC with residual dissociated activity inside the IVC. This is the first report to reveal continuous ectopic bigeminy definitely originating from the tiny area within the IVC by detailed three-dimensional mapping.

Chronic urticaria (CU) is a common clinical disease that seriously affects the quality of life of patients, but its pathogenesis is still not fully understood. The autoimmunity of chronic spontaneous urticaria (CSU) has been highly concerned and intensively studied in the past. Atopy is also one of the important characteristics of CU, but it has not been fully recognized. Atopy is a predisposition to respond immunologically to allergens, leading to type 2 inflammation and overproduction of immunoglobulin E (IgE). Compared with the healthy population, patients with CU have a higher proportion of atopy, and atopic background is correlated with the clinical characteristics of CU. The total IgE level of CU patients is significantly higher than that of healthy people. Although it is not higher than that of classic allergic diseases, its level is also closely related to CU. Exogenous allergens, autoallergens and their specific IgE, which are closely related to atopy, have been gradually discovered in CU, and their roles in the pathogenesis of CU are also being studied. Atopic inflammation is equally present in CU, both locally and systemically. This review summarizes up-to-date knowledge regarding atopy and CU, and speculates that atopic CSU or atopic CIndU indeed exists, providing a fresh perspective for comprehensively understanding the clinical characteristics of CU and further studying its pathogenesis.

Background Activation of mast cells through IgE results in secretion and shedding of mast cell proteins and in vivo models suggest that these processes are governed by IgE antibody affinity. Methods We passively sensitized cultured primary human mast cells with recombinant human IgE clones with either high or low affinity for Der p 2, with a 200-fold affinity difference, and activated them with recombinant allergen. Activation was assessed by CD63 upregulation and PGD 2 secretion. Supernatants collected from mast cells activated for 0, 3, 6 and 24 hours were assessed for PGD 2 and inflammatory mediators on the OLINK platform at repeated time points. Results CD63 upregulation and PGD 2 synthesis scaled with affinity, as did secretion of cytokines like IL-8 and IL-13. Secretion of chemokines like CCL3 and CCL4 appeared to depend less on affinity, whereas shedding of surface markers CD40, SLAMF4 and CD5, and secretion of intracellular markers SIRT2 and CASP-8, were elevated by stimulation through low affinity IgE compared with high affinity IgE, illustrating differential responses dependent on the affinity of IgE. Conclusion Cytokine secretion and shedding of surface receptors of sensitized, cultured primary human mast cells is differentially regulated depending on the affinity of IgE for the Der p 2 allergen and may shape the chronic response to repeated allergic activation.

In recent years, flexible photodetectors (FPDs) have received increasing attention due to their applications in electronic eyes, flexible sensing, terminal devices, and wearable devices. In addition, metallic halide perovskite materials are considered as future materials for FPDs due to their compatibility with flexible substrates, low cost, simple synthesis methods, and superior optoelectronic properties. This review provides a comprehensive overview of the relevant cutting-edge research in the field of flexible perovskite photodetectors (FPPDs) from 2020 to 2022. First, the evaluation criteria for FPPDs are discussed and the development of perovskite stability criteria is emphatically described. Afterwards, the synthesis methods and device construction processes of metal halide perovskite materials commonly used by researchers in the past three years were described. These include single crystals and low-dimensional materials. Moreover, we have elaborated on the research of self-powered FPPD and its contributions in wearability, terminals, and portability. Finally, a summary of developments and possibilities in the field of FPPDs from 2020 to 2022 is provided.

In recent years, extreme focus on renewable energy has intensified due to environmental concerns and the depletion of fossil fuel supplies. In a DC micro grid that includes photovoltaic (PV), wind, and battery storage systems, this research proposes an integrated strategy for energy management and battery management. The Robust Model Predictive Control (RMPC) method is proposed to deal with uncertainties and disturbances while offering the best possible control options. A comparison of the two algorithms reveals that the RMPC performs better than the conventional MPC method. To harvest the most solar electricity from the PV system, a sophisticated MPPT optimisation technique called Muddled Tuna Swarm Optimisation (MTSO) is applied. Drone Squadron Optimisation (DSO) and Slime Mould Optimisation (SMO) are outperformed by MTSO in terms of dynamic performance, effectively monitoring the maximum power point (MPP) of the PV system, and increasing overall energy output. The suggested RMPC approach and MTSO technique are effective in achieving optimal energy and battery management as well as maximum solar power extraction, according to the simulation findings. On the OPAL-RT platform, real-time simulation is used to test the control strategy.

The hybrid cascaded high-voltage direct-current (HC-HVDC) links is recently introduced for ultra-high voltage bulky power transmissions. However, as wind power becomes more prevalent, the grid is gradually weakened and will faces voltage stability issues. This paper proposes a coordinated reactive power control strategy for HC-HVDC links to enhance the voltage stability of AC bus. Firstly, the impact of HC-HVDC on the static voltage stability of the AC bus is studied by the voltage sensitivity coefficient. Then, the limitation of reactive power capability of modular multilevel converter (MMC) in the hybrid cascaded structure is identified. Based on the analysis results, a coordinated reactive power control strategy based on adaptive voltage droop is proposed. In the strategy, the DC voltage ratio is regulated according to the fluctuation degree of the AC bus voltage to adjust the reactive power of HC-HVDC, which realized the dynamic voltage support for the AC bus. Finally, electromagnetic simulations in PSCAD/EMTDC are performed, and the results validate the theoretical findings and the effectiveness of the control strategy.

Considering the low identification accuracy of single-phase-to-ground(SLG) fault in distribution systems with the neural point small-current grounded, breaking through the traditional fault identification method based on voltage or current, this paper focuses on mining the features of electric field variation when SLG fault occurs. Firstly, based on the charge simulation method, the electric field at the same height under three-phase distribution lines and that on the line surface during SLG fault are respectively calculated. Accordingly, the variation law of electric field in small-current grounded distribution systems during SLG fault is obtained theoretically, and the corresponding relationship between the variation mode of electric field and the occurrence of SLG fault is established. Besides, MEMS sensor is innovatively adopted for electric field measurement in distribution systems by taking advantage of its small size, low power consumption and high accuracy, and its integration scheme with fault indicator is formed. On this basis, a SLG fault identification method and corresponding devices based on the variation of electric field are proposed, and the effectiveness is verified by experiments.

We explain the impacts of credit expansion on social trust from the perspective of Austrian economics, and get the conclusion that credit expansion will lower social trust whether or not the masses are familiar with Austrian economics. Even if the public are not familiar with Austrian economics, the problems such as corporate default and unemployment, which resulted from economic bust caused by credit expansion, will lead to the reduction of trust between different individuals and the creation of self-doubt. If the masses have known Austrian economics, then they would know that the nature of fractional reserve system is to infringe on private property rights, that credit expansion triggers inflation which will cause income and wealthy redistribution, that credit expansion is a way to consolidate the common interests between state, banks and industrialists. All those known knowledge will make the masses reduce their trusts to the state, bankers and the industrialists, which ultimately reduces social trust. To eliminate credit expansion from its roots, we have to implement the system of free banking on the gold standard accompanied with a 100 percent reserve system which not only involves banknotes' issuing but also demand deposits

Fluid mechanics is a field rife with diverse units of measure and, consequently, potential for errors. Unlike their experience in mathematics, undergraduate students must learn to manipulate both numbers and units in order to satisfy dimensional homogeneity and succeed in engineering. Using written exam responses from students in an undergraduate fluid mechanics class, this paper 1) compares scores according to whether students carefully handled units or not and 2) provides examples of mistakes that may have been avoided by analyzing units. In the exams, students who consistently tracked units scored higher and with less variance than those who did not; both results are statistically significant. The selected examples highlight errors in algebra, fluid properties, and geometry that may have been detected had students properly handled units. The findings suggest that the habit of analyzing units is desirable for students to develop, helping them both understand concepts and check their work as they become engineers.

Iterative learning control (ILC) is an advantage control strategy widely used in batch systems. Nevertheless, designing an effective iterative learning control scheme is still a critical problem for complex batch processes with non-repetitive nature and model mismatch. In this paper, we propose a two-dimensional iterative learning control-reinforcement learning (2D ILC-RL) control scheme composed of a two-dimensional ILC controller and a two-dimensional DRL compensator. Based on the 2D system theory, the 2D ILC controller is proposed to ensure the primary control performance and its stability and convergence are verified. Meanwhile, the DRL compensator counteracts the negative impact of the model mismatch and the non-repetitive nature. In addition, we proposed a real-time implementation scheme to guarantee the safety of the practical batch systems compared to the conventional online training method. Finally, the simulation results in two chemical batch processes demonstrate the proposed control method’s effectiveness, significant control performance, and strong robustness.

This study evaluated the performance of biofilm reactors inoculated with azo dye degrading Shewanella for the decolorization of Reactive Black 5 (RB5), using three different carrier materials, namely almond shell biochar, moving bed biofilm reactor (MBBR), and polypropylene carrier (PPC). The reactors were fed with low-nutrient artificial wastewater containing RB5 for a long term, and all three carriers showed good RB5 decolorization performance, with varying efficiencies. LC-MS analysis revealed significant differences in the degradation pathways of RB5 among the carriers, indicating the role of carrier materials and microbial communities. The MBBR carrier exhibited good stability due to its rough surface and microbial aggregates. Sequencing results revealed significant differences in the microbial community structure among the carriers. Shewanella was the dominant functional bacteria in the MBBR and PPC carriers, while highly efficient degrading microbial communities were observed on the biochar carrier. Overall, the physicochemical properties of the carrier materials had a significant impact on the microbial community in the reactor, which affected the degradation efficiency of RB5. These findings provide valuable insights into the optimization of biofilm reactors for dye-containing wastewater treatment.

Objective: To report clinical characteristics, surgical management, and medium-term outcomes of 3 Arabian neonatal foals with meniscal disruption associated with septic arthritis of the lateral femorotibial joint. Methods: Three neonatal Arabian foals with septic arthritis of the lateral femorotibial joint (LFTJ), were diagnosed with lateral meniscal (LM) tears, based on persistent lameness despite improving synovial parameters, ultrasound (US) findings (protrusion of meniscal tissue beyond the level of the condyles, with hypoechoic regions), contrast Computed Tomography findings, and confirmed on arthroscopy. Treatment included arthroscopic debridement and lavage of the joint with debridement of the meniscal tear. Postoperative care included systemic and intra-articular antimicrobials, based on culture and sensitivity results. Two of the foals received intra-articular injections of autologous mesenchymal stem cells. Results: Grade III meniscal tears were observed in the LFTJ of the affected joints of all foals, involving the meniscal body (n=3) and caudal horn (n=1). Purulent material within the torn tissue, was debrided with a synovial resector. Foal 1 was lame-free as a yearling. Foal 2 was lame at walk at 7.5 months and euthanatized due to poor prognosis. Foal 3 showed mild lameness at trot in a straight line at 6 months. Disruption of the LM continued to be visible on US in both foals at these time-points. Conclusion: Meniscal disruption and infection should be considered a differential in neonatal foals with persistent femorotibial septic arthritis. In such cases, the LM could be the primary nidus of infection.

Shigella flexneri type III effector OspC3 was recently found to evade host pyroptosis by targeting caspase-11 for ADP-riboxanation. The ADP-riboxanase activity was shared by its paralogues, OspC1 and OspC2, whereas the host substrates of them are still unknown. To solve this problem, we employed eAf1521 enrichment coupled with mass spectrometry (MS)-based proteomics to profile the host substrates of OspC1. In this study, we identified HERC5 as a host target of OspC1. As described previously, HERC5 functions as an E3 ISG15 ligase and catalyzes the ISGylation of a huge subset of host and pathogen proteins upon bacterial infection. Here, we show that S. flexneri hijacks host ISGylation pathway by OspC1-catalyzed ADP-riboxanation of HERC5 to promote its own survival and proliferation in host cells.

Objective: To assess the impact of skeletal muscle ryanodine receptor ( RYR1) variants, a common cause of neuromuscular disorders, on smooth muscle function, bleeding, obstetric, and gynaecological outcomes. Design: Questionnaire study. Setting: Online via the RYR1-Foundation patient support group covering countries across the world. Population or Sample: 154 women consisting of 66 RYR1-variant carrying participants and 88 controls. Methods: Online questionnaire designed to investigate symptoms of abnormal smooth muscle function, obstetric and gynaecological outcomes in women with RYR1 variants. Questions were developed using a modified version of the MCMDM-1VWD questionnaire, and the NHS-heavy periods self-assessment tool. Obstetric and gynaecological symptoms explored include pregnancy-related complications, gestation length, parturition duration, post-partum haemorrhage and offspring birthweight. Main Outcome Measures: Bleeding scores were measured using a modified MCMDM-1VWD scale. Significance between groups were analysed using Fisher exact tests, Chi Square tests, and Welch’s t-tests. Results: Women with RYR1 variants exhibited a higher incidence of pathological bleeding scores (p<0.0001), severe menstrual bleeding, complications during pregnancy (preeclampsia and placenta praevia), post-partum haemorrhage, shorter pregnancies, frequent planned Caesarean sections, and offspring with lower birthweight, compared to controls. Gastrointestinal symptoms were also more common. Conclusions: RYR1 mutated females exhibit a bleeding disorder and frequent gynaecological and obstetric complications. Considering their population frequency in otherwise pauci-symptomatic individuals, RYR1 variants ought to be considered as a cause of otherwise unexplained menorrhagia and other gynaecological and obstetric manifestations. Funding: King’s Health Partners Institute of Women and Children’s Health Keywords: skeletal muscle ryanodine receptor (RYR1) gene; questionnaire; bleeding; menorrhagia; post-partum haemorrhage Tweetable abstract: RYR1 mutated females exhibit a bleeding disorder. RYR1 variants ought to be considered as a cause of otherwise unexplained menorrhagia, PPH and obstetric complications.

Dear sir,The Nobel Prize is an esteemed award that recognizes outstanding achievements in Physics, Chemistry, Medicine or Physiology, Literature, and Peace. The will of Nobel states that ‘prizes to those who, during the preceding year, shall have conferred the greatest benefit on mankind in the field of medicine and physiology’(1). Despite the significant contributions of surgery to the advancement of medical science, only five surgical papers have been awarded the Nobel Prize (Table 1).One reason for this is that surgical papers tend to focus on technique-based advancements rather than fundamental discoveries in medicine or physiology. While surgical techniques can be innovative and improve patient outcomes, they may not be applicable to a wide set of patients, and their effectiveness may depend on the skill of the operating surgical team. This makes it difficult to establish a universal standard of evaluation for surgical papers(2).Moreover, there is a high risk of selection and reporting bias in surgical papers. Surgeons may choose to report on their successes and not their failures, making it challenging to assess the true efficacy of a surgical technique(3). Additionally, an alternative surgical technique may already be established, rendering the new technique less impactful.It is worth noting that ground-breaking surgical research can still be impactful and recognized in the field of medicine. For instance, if a surgical research study can demonstrate a significant improvement in patient outcomes or revolutionize the practice of surgery, it may be considered for recognition. Moreover, surgical research that incorporates the latest advancements in technology, such as AI, nanotechnology, tissue engineering, and gene therapy, can also be impactful. These advancements have the potential to improve surgical techniques, increase the accuracy of diagnoses, and enhance patient outcomes.Additionally, the practice of basic translational research in surgery, which aims to translate basic scientific discoveries into clinical applications, can be valuable. Research studies that explore the molecular cross-talk between different cell types and the signaling pathways involved in tissue repair can provide insights into the mechanisms of disease and lead to the development of novel surgical interventions. It is essential to recognize that a researcher’s ultimate goal should not be to win the Nobel Prize. While it is a prestigious award, it should not be the primary motivation for conducting research. Instead, a researcher should strive to adhere to ethical standards and follow in the footsteps of great Nobel laureates who have made significant contributions to science and society.A surgeon’s focus should be on conducting meaningful research that can have a positive impact on patient well-being. Ethical research practices that prioritize patient safety and respect for human dignity are crucial. Moreover, the research should be designed to address important medical problems, and the results should be applicable to a broad population of patients. While the Nobel Prize is undoubtedly the greatest honor, the real prize for surgeons is transforming patient care and improving the lives of individuals suffering from disease and illness. The blessings of patients and their families, as well as the recognition and respect of one’s peers, seniors and colleagues, are far more valuable than any award.The surgeons should strive to conduct ethical research that can make a meaningful impact on patient well-being. While the Nobel Prize is a significant recognition, the true prize for researchers is improving patient care and earning the respect and gratitude of those they serve.

Recent studies have demonstrated the effectiveness of hybrid SARS-CoV-2 vaccines that combine the wild-type nucleocapsid (N) and Spike (S) proteins. Based on this strategy, we have further enhanced the idea by incorporating the spike protein with mutations from delta and post-delta omicron variants of concern (VOC). Both delta and omicron mark the transition of vaccine driven viral immunity and resistance, so their mutations are highly crucial for future viral variants also. Additionally, we have included certain nucleocapsid peptides, which have clinically shown superior T-cell immunity being similar to homologous sequences from other Human Coronaviruses (HuCoV). We have also carefully selected an envelope peptide that elicits strong T-cell immune response. These peptides are clustered in the hybrid spike’s cytoplasmic region with non-immunogenic helical linkers, enabling systematic arrangement. Through AlphaFold analysis, we have determined that the resulting domain folds more efficiently when the construct lacks the transmembrane domain. The AlphaFold designs were validated using the molecular dynamics (MD) simulations and assessed various parameters of root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg) and weighed the structural stability and conformational dynamics. Interestingly, the dynamics revealed more insights into the conformational changes in the structure overtime, more flexibility in the C-terminus region, and overall compactness of the structures in a time-based gradient indicating less fluctuation and transition in terms of structure mobility and maintained a relatively compact fold conformation throughout the simulation. Our proposed approach may provide option for incorporating diverse anti-viral T-cell peptides, similar to HuCoV, into linker regions, offering a versatile solution to address outbreaks and challenges posed by various viruses, thereby enabling effective management through multiepitope strategies in this era of innovative vaccines.

Genetic diversity is a fundamental component of biodiversity and the medium for speciation events. Examination of global patterns of genetic diversity can help highlight mechanisms underlying species diversity. Here, we compiled 6862 observations of genetic diversity from 492 species of marine fish globally, assessed their associations with macroecological drivers, and tested among three hypotheses for diversity gradients: the founder effect hypothesis, the kinetic energy hypothesis, and the productivity-richness hypothesis. We found that mitochondrial genetic diversity follows latitudinal and longitudinal gradients similar to those of species diversity, being highest near the equator, particularly in the Coral Triangle, while nuclear genetic diversity did not follow clear geographic patterns. Despite these differences, all genetic diversity metrics were positively correlated with chlorophyll, while mitochondrial diversity was also positively associated with sea surface temperature. These findings provide support for the kinetic energy hypothesis, which predicts that elevated metabolic and mutation rates at higher temperatures should increase mitochondrial diversity, and the productivity-richness hypothesis, which posits that resource-rich regions support larger populations with greater genetic diversity. Overall, these findings reveal how environmental controls on mutation and drift in the ocean combine to establish global gradients of genetic diversity within species, and in turn, community assemblages.

The study of ichthyoplankton is paramount to understanding fish assemblages’ reproductive dynamics. DNA metabarcoding has been applied as a rapid, cost-effective, and accurate taxonomy tool, allowing the identification of multiple individuals simultaneously. However, there remain significant challenges when using DNA metabarcoding, such as molecular marker choice according to the taxonomic resolution and length of the fragment to be sequenced, primer bias, incomplete reference databases, and qualitative inferences incongruences. Here, 30 ichthyoplankton pools collected from a Neotropical River were identified at a molecular level using DNA metabarcoding to compare the resolution, sensibility, specificity and relative read abundance (RRA) recovery of three molecular markers: the standard COI fragment (650pb, with each strand analyzed individually) and two short 12S rRNA genes markers ( 200bp - NeoFish and MiFish markers). The combined use of the three markers increased the genera detection rates by 25% to 87.5%, allowing an increased taxonomic coverage and robust taxonomic identification of complex neotropical ichthyoplankton communities. RRA is marker-dependent, indicating caution is still needed whilst inferring species abundance based on DNA metabarcoding data when using PCR-dependent protocols.

The human population is growing rapidly, increasing pressure on natural habitats. Suitable habitats for resident and migratory waterbirds are, therefore, more threatened. This study analyses how the presence of anthropogenic land cover (urban area and cropland) on multiple spatial scales affects the community composition of waterbirds along the Nile in Egypt. We analysed data collected during the international waterbird census, 2017-2018, combined with data from satellite images on land cover at a multi-spatial scale. The census covered 970 km, compromising 194 shoreline transects of 5 km along the River Nile, Egypt. The area includes a broad gradient of human disturbance, making this dataset ideal for assessing effects of anthropogenic land cover on waterbird community composition. We tested whether the waterbird community indices and guild composition were associated with urban area and cropland, and other land covers (e.g., grassland, wetland) at spatial scales of 100, 500, 1,000 and 5,000 m. We recorded over 96,000 waterbirds and show that landscape characteristics at larger spatial scales (5,000 m) explained more of the species and guilds’ presence than smaller scales. Species richness increased with increasing water surface area of the river within the transect and decreased with increasing urban area and cropland. Waders were negatively associated with urban area. Overall, the guilds’ composition was poorly predicted by anthropogenic land cover and other landscape compositions, probably because species within a guild do not react similarly to increasing human disturbance. The probability of observing red-listed species decreased with increasing urban area. With this study, we expand on the existing evidence by showing that species richness negatively correlates with anthropogenic pressure, and we highlight the importance of studying the responses of species rather than guilds. Our study shows the relevance of considering the landscape at larger scales while planning for conservation measures, especially in such human-dominated landscapes.

Smoking causes several diseases such as chronic obstructive pulmonary disease (COPD). Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. Here we evaluated the role of AT-RvD1 (100nM) in bronchial epithelial cells (BEAS-2B) stimulated by cigarette smoke extract (CSE; 1%; 1 cigarette) for 24h. CSE induced the productions of IL-1β, TNF-α, IL-10, IL-4 and IFN-γ as well as the activations of NF-κB and STAT3 and the expression of ALX/FPR2 receptor. AT-RvD1 reduced the IL-1β and TNF-α production and increased the production of IFN-γ, while the production of IL-4 and IL-10 were not altered, in the cells stimulated by CSE when compared to CSE group. These effects were reversed BOC2, an antagonist of ALX/FPR2 receptor for AT-RvD1. In addition, AT-RvD1 reduced the phosphorylation of NF-κB and STAT3 when compared to CSE-stimulated BEAS-2B cells. No alteration of ALX/FPR2 expression was observed by AT-RvD1 when compared to CSE group. In the human monocytic leukemia cell line, the relative number of copies of IL-1β and IL-4 was significantly higher in CSE + AT-RvD1 group compared CSE group, however, the expression of M1 cytokine is more pronounced than M2 profile. AT-RvD1 could be an important target for the reduction of inflammation in the airways associated with smoking.

This paper handles the identification of nonlinear systems through linear time-varying (LTV) approximation. The mathematical form of the nonlinear system is unknown and regenerated through an experiment followed by LTV and linear parameter-varying (LPV) estimation and integration. By employing a well-designed experiment the linearized model of the nonlinear system around a time-varying trajectory is obtained. The result is an LTV approximation of the nonlinear system around that trajectory. Having estimated the LTV model, an LPV model is identified. It is shown that the parameter-varying (PV) coefficients of this LPV model are partial derivatives of the nonlinear system evaluated at the trajectory. In this paper, we will show that there exists a relation between the LPV coefficients. This structural relation in the LPV model ensures the integrability of PV coefficients for nonlinear reconstruction. Indeed, the vector of the LPV coefficients is the gradient of the nonlinear system evaluated at the trajectory. Then, the nonlinear system is reconstructed through symbolic integration of the coefficients. The proposed method is a data-driven scheme that can reconstruct an estimate of the nonlinear system and its mathematical form using input-output measurements. Finally, the use of the proposed method is illustrated via a simulation example.

Silver arowana, Osteoglossum bicirrhosum, is sexually monomorphic, and its sex determination mechanism is still poorly understood, posing a significant challenge to its captive breeding efforts. To this end, we assembled two high-quality chromosome-level genomes for both female and male silver arowana, with scaffold N50 values of 10.6 Mb and 10.4 Mb for female and male individuals, respectively. Combining re-sequencing data of 109 individuals, we identified two sex-specific SNPs and confirmed a ZW model of sex-determination in this ancient species. Both sex-specific SNPs are located in about 26-kb upstream of foxl2 gene. We subsequently propose a complex gene network in the sex determination process of silver arowana, with foxl2 acting as the central player. The sex chromosomes are homomorphic with a potentially recent origin, as linkage disequilibrium analysis showed minor recombination suppression. Furthermore, we successfully developed accurate molecular markers for sex identification of silver arowana at each developmental stage, significantly improving the reproductive efficiency and further promoting the industrial development.

Introduction Noonan syndrome is a multisystem, genetic, developmental disorder occurring with the incidence of 1 case per 1000 to 1 case per 2500 live births in the United -States. The condition occurs either in a sporadic or autosomal dominant manner and affects both males and females equally. [1] Ullrich (1930) and Turner (1938) described females with a syndrome of short stature, sexual infantilism, and a pattern of characteristic minor anomalies like pterygium colli. This syndrome originally named Ullrich-Turner syndrome was later called Noonan syndrome. It was first reported by Kobylinski (1883), but it was first recognized as a unique entity in 1963 when Pediatrician and Heart specialist Jacqueline Noonan and Ehmke described a series of patients with unusual facies and multiple malformations, including congenital heart defects. The characteristic abnormalities resemble those in Turner syndrome, which only affects females and so Noonan syndrome was used to be called ”Male Turner syndrome”. This term is no longer used because Noonan syndrome can affect females also. Noonan syndrome is also called Webbed neck syndrome, Pseudo-Ullrich Turner syndrome, Female Pseudo-Turner syndrome, or Turner-like syndrome.[2]The condition is mainly characterized by facial dysmorphism, congenital heart defects, growth hormone deficiencies, webbed neck, wide space nipples, and musculoskeletal, renal, genital, and bleeding abnormalities. Mental retardation can also occur in about 25% of patients with Noonan syndrome. Facial abnormalities include hypertelorism, down-slanting eyes, webbed neck, eyelid abnormalities, and skin manifestations. Prenatally the presentation of Noonan syndrome is not unremarkable, however, some cases are often complicated by polyhydramnios, fetal edema, increased nuchal translucency, and cystic hygroma. [3,4,5]. Very little is known about the occurrence of hypothyroidism in patients with Noon syndrome, this case report highlights the concomitant occurrence of hypothyroidism in a patient with Noonan syndrome, and stresses that further research should be done to find the association of these two.Case presentation : A 15 -year-old female patient was presented to the outpatient department of a tertiary care hospital for bilateral eye puffiness, easy fatiguability, and generalized body weakness. The patient’s condition started 6 months back and it gradually worsened. On further inquiry, the patient has a history of constipation on and off which relieves with laxatives. The past medical history of the patient was significant for acute hepatitis A and COVID-19 infection 3 and 1 year back respectively. The patient was born through a normal vaginal delivery at the hospital and she was the 7th child of his parents. The medical record of the patient showed that all the developmental milestones were up to date, and the patient received all the childhood vaccination. Family history was not significant for congenital heart defects, mental retardation, short stature, or unusual facial features. She was 135 cm tall and had 32 kg weight with vital signs of blood pressure of 100/70 mm Hg, pulse rate of 65 beats per minute, and respiratory rate of 15 breaths per minute. Examination revealed pale conjunctive, down slanting eyes, hypertelorism, webbed neck, shield chest with wide space nipple as shown in Figure.1. Systemic examination was unremarkable except for decreased muscles power in both upper and lower limb with a positive Gower’s sign. The patient examination findings were suggestive of some congenital syndrome and initially both Turner’s and Noonan were suspected. Karyotyping was done which showed normal 46 XX chromosomes as shown in Figure.2 A diagnosis of Noonan syndrome was made based on the clinical features and chromosomal analysis. The patient was further evaluated for recurrent eye puffiness and easy fatiguability and the laboratory results revealed anemia, hypothyroidism, and increased creatinine kinase as shown in Table. 1. A nerve conduction test and electromyography of both the upper and lower limb were done for progressive weakness that was consistent with mild myopathy, without evidence of spontaneous activity, mainly affecting the proximal muscles. A final diagnosis of Noonan syndrome with hypothyroidism that led to proximal myopathy was made. The patient was further evaluated for cardiac, ophthalmologic, hearing, renal and genital, and coagulation abnormalities that were all normal. The patient and her parents were counseled about the condition, she was started on levothyroxine 50mg OD, cap Iron sulfate 1 cap daily for two months, and tablet opendrine and paracetamol 35/450 mg SOS for muscular pain and weakness. She was referred to a pediatric endocrinologist for growth and development assessment and was instructed to do close follow-up with repeat thyroid function tests in 6 weeks and coagulation profile and echocardiography when symptoms develop.