Magnetothermal neuromodulation is a minimally-invasive, deep-brain accessible and tether-free technique. The precisely timed activation of thermosensitive ion channels, such as TRPV1, with local heat generated using magnetic nanoparticles is crucial for efficient neuromodulation. Nevertheless, this technique is greatly hindered by its long stimulus-response time and high safety risks due to the poor heat-generating performance of the nanomediators. Herein, we report the establishment of a ferrimagnetic vortex iron oxide nanoring (FVIO)-mediated magnetothermal neurostimulation technique that is efficient and safe. Compared with widely used superparamagnetic iron oxide nanomediators (SPIOs), the FVIOs triggered Ca2+ influx into HEK293T cells and cortical neurons at an Fe concentration of 54 μg/mL, which is 20.27-fold lower than that needed for SPIOs. In vivo magnetothermal stimulation in the central nucleus of the amygdala of mice further demonstrated that FVIOs with the optimal dose of 0.05 μg evoked fear behaviors with an average latency of 2.51 s, which was 2.3-fold faster than that in the SPIO (0.8 μg)-treated group. More importantly, FVIOs-mediated stimulation not only exhibited negligible histopathological alterations and proinflammatory cytokine expression, but also successfully elicited fear behaviors in transgene-free mice. The FVIO-mediated efficient and safe neuromodulation has the potential for future neuroscience exploitation and neurological disease treatment.

A 62-Year-Old Man with Recent Onset of Muscle-Specific Tyrosine Kinase (MuSK)-Negative Thymomatous Myasthenia Gravis Presenting with Bradycardia Due to High-degree Atrioventricular Block Associated with Pyridostigmine Treatment

Acute myeloid leukemia (AML) is a blood cancer characterized by uncontrolled proliferation of leukemic stem/progenitor cells. The retention and chemoresistance of AML cells in the bone marrow microenvironment are mediated by stromal cell-derived factor-1(SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis. We recently developed a novel small molecule CXCR4 antagonist (designated HF51116) with a higher affinity than AMD3100 specifically for improving AML chemotherapy. Competitive binding assays confirmed that HF51116 bound to the surface of malignant U937 and HL60 cells with high affinities. Transwell assay results demonstrated that HF51116 blockade inhibited the SDF-1induced migration of U937 and HL60 cells with a concentration-dependent manner, as well as the migration induced by BMSCs. The mechanism for HF51116 in U937 and HL-60 cells migration appeared to involve attenuation of the SDF-1induced cytoskeletal re-arrangement and phosphorylation of AKT (S437) and ERK1/2 (Thr202/Tyr204). In addition, HF51116 reversed the chemoresistance of U937 cells co-cultured with BMSCs by increasing Annexin V expression and caspase-3 activity, resulting in decreased cell viability. In vivo experiments on AML xenograft mice revealed that subcutaneous administration of HF51116 mobilized the engrafted U937-Luc/EGFP cells from the bone marrow and spleen into the peripheral blood. Co-administrating HF51116 and cytarabine (Ara-C) further reduced the in vivo AML burden and expanded the lifespan of AML xenograft mice beyond that seen with Ara-C monotherapy. These results demonstrated that the novel CXCR4 antagonist HF51116 has potent anti-leukemic effects both in vitro and in vivo.

Non-invasive brain stimulation (NIBS) is an emerging treatment for mental disorders that is painlessness and easy to administer. However, its effectiveness for treating fear extinction requires further elucidation. We searched eight bibliographical databases and identified randomized controlled trials of NIBS interventions for fear extinction in healthy populations. Outcomes were evaluated based on skin conductance response (SCR) under three experimental conditions: threat condition stimulation (CS+), safe condition stimulation (CS−), and their discrimination (CS+ minus CS−). We applied a random-effects model to determine effect sizes (Hedge’s g) post-intervention and assessed article quality using Physiotherapy evidence database (PEDro) scale. Twenty-one studies meeting systematic review criteria were included in this analysis, incorporating 40 independent effect sizes and data from 11 studies (n = 632) in the meta-analysis. Compared with the control group, the intervention group exhibited significant reductions SCRs: CS+ (g = −0.32, 95% confidence interval (CI) [−0.56, −0.07]) and discrimination (g = −0.35; 95% CI [−0.55, −0.15]). Fear extinction was more effective in the 24-hour test than immediately after NIBS. In conclusion, NIBS enhanced fear extinction, and the time interval between stimulus and testing may serve as a moderating variable.

This research explored the microbial diversity in two underexplored natural springs, Arincho Chumik and Chutron, located in the Shigar Valley, Gilgit Baltistan, utilizing a culture-centered method combined with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). The outcomes revealed a diverse microbial landscape, with a total of 18 unique bacterial strains isolated, comprising nine from each spring. From the total 18 isolated strains, 7 (39%) were noticed to be gram-positive while 11 (61%) were gram-negative. Interestingly, species like Brevundimonas and Acinetobacter were present in Arincho and Chutron springs, respectively, highlighting the unique physiochemical environments and their impact on microbial populations. The examination also uncovers the existence of pigment-producing bacteria, suggesting potential biotechnological applications. The chilly freshwater spring of Arincho possessed certain opportunistic bacteria, including Bacillus cereus, Dietzia cinnamea, and Microbacterium species. Likewise, Human-related microorganisms like Micrococcus leuteus were also identified in samples from the Chutron thermal spring. Additionally, the recognition of opportunistic pathogens among the strains underlines the health effects for the local communities, especially for old aged and immune-deficient individuals. The quality of these water resources ought to be supervised by regulatory authorities to decrease public health risks and pathogen transmission.

This paper presents a wideband and low phase noise voltage controlled oscillator (VCO). The proposed tri-core tri-mode VCO was designed and fabricated in a 65nm CMOS process. The sixth-order resonant network of the tri-mode inductor is utilized to broaden the VCO operating frequency band; VCO output amplitude control is achieved through automatic amplitude control (AAC) to ensure good phase noise characteristics of the VCO; The frequency range has been further expanded through variable capacitors and 3-bit switched capacitor arrays; Phase noise performance is improved through Class-C operation. The proposed VCO can be tuned from 3.75GHz to 12.9GHz with an 109.9% frequency tuning range (FTR). The output amplitude is stabilized at 1.27V throughout the band with an error of no more than 2%, the phase noise at 1MHz frequency offset is less than -110.7dBc/Hz, the power consumption is less than 8.8mA, and the bandwidth-integrated optimum value FoMT is better than 200dBc/Hz.

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post-menopausal women. Bone loss has been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mechanisms are well documented but the causal connectivity of events to bone loss development remains incompletely understood. Herein, the adverse outcome pathway (AOP) framework was used to organize data and develop a qualitative AOP beginning from deposition of energy (the molecular initiating event) to bone loss (the adverse outcome). A literature review was conducted to compile and evaluate the state of knowledge based on the modified Bradford Hill criteria. Following review of 1865 studies, an empirically supported AOP was developed, showing the progression to bone loss through many factors affecting the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The structural, functional, and quantitative basis of each proposed relationship was defined, for inference of causal changes between key events. Current knowledge and its gaps relating to dose-, time- and incidence-concordance across the key events were identified, as well as modulating factors that influence linkages. The new priorities for research informed by the AOP highlight areas for improvement to enable development of a quantitative AOP used to support risk assessment strategies for space travel or cancer radiotherapy.

Introduction :Chronic cholecystitis is a common gastrointestinal pathology all around the world.1 Hyalinizing cholecystitis (HC) was first described by Patel et al characterizes by dense paucicellular hyalinizing sclerosis effacing the gall bladder wall transforming it into a thin uniform band.2 It is recognized as a distinct entity compared to the more heavily calcified “porcelain” gallbladder (PGB).3 Although traditionally associated with higher risk of gallbladder carcinoma (GBC), the association of PGB has recently been brought into question.4,5 On the other hand HC, reported in about 1.6% of cholecystectomy specimens is more consistently associated with GBC.2 Hence identification of radiological as well as histopathological features of HC along with close follow up of patients even after surgery is imperative.

A Case of Breast Filariasis Diagnosed on Fine Needle Aspiration CytologyBirhanu Kassie Reta1 , Biruk Legesse Tadesse2, Eleni Getahun Kebede3, Atsede Birhanu Worku3, Michael Teklehaimanot Abera4Aksum University College of Health Science, Department of Pathology, Aksum, EthiopiaArsi university College of health Science, Department of Pathology, Asella, EthiopiaWoldia University, Woldia, EthiopiaAddis Ababa University, College of Health Sciences, Addis Ababa UniversityAuthors contact Address1. Birhanu Kassie Reta, MD,birexkassie24@gmail.com (ORCHID ID: 0009-0001-1897-9072)2.. Biruk Legesse Tadesse, MD, brooktade12@gmail.com(ORCHID ID: 0000-0001-6889-5320)3. Eleni Getahun Kebede, MD, getahuneleni@gmail.com (ORCHID ID: 0009-0004-8676-1691)4. Atsede Birhanu Worku, MD, atsedemaryamfabb@gmail.com( ORCHID ID: 0009-0006-0050-9634)5. Michael Teklehaimanot Abera, MD michael.teklehaimanot@aau.edu.et, th.miki8441@gmail.com

Pollinators are unquestionably declining, however, current knowledge on the rate of decline is biased in two aspects which are fragmented (West-dominated) geographic scope and narrow taxonomic focus of studies dominated by bees and agriculturally relevant species. This bias has resulted in an unfortunate imbalance, whereby the most biodiverse regions and insect groups have less diversified data. We suggest the evaluation of four drivers of this bias and propose solutions to deal with (i) concept generalization, (ii) data accessibility, (iii) scattered environmental regulations, and (iv) shifted infrastructure and funding resources. Research and legislation focused on pollinator taxonomic, functional, and environmental diversity, and the involvement of scientists in policymaking, can help balance knowledge on the topic. Using search engines in different languages, assistance of Artificial Intelligence, facilitating Open Access research/data publishing, and closer cooperation between developed and developing countries may help to overcome geographic bias in ecological research and pollination.

Background: Epidemiological evidence hints at a connection between thyroid dysfunction and chronic spontaneous urticaria (CSU), but the causality is obscure. This study applies a two-sample Mendelian randomization (MR) method to explore the causality between them. Methods: We utilized bidirectional MR to explore the causality between CSU and thyroid autoimmunity in Europeans and East Asians. The SNPs examined in this study were sourced from the Open GWAS database, the ThyroidOmics Consortium, the FinnGen Consortium, and BioBank Japan. In the forward MR analysis, we considered thyroid dysfunction, AITD, and thyroid function indicators—FT3, FT4, TT3, ln (FT3/FT4), ln (TT3/FT4), TSH and TPOab—as exposures, with CSU as the outcome in a cohort of 398,763 individuals. Conversely, in the reverse MR analysis, CSU served as the exposure, and thyroid function phenotypes were the outcomes. The primary analytical method was IVW, complemented by sensitivity analyses to evaluate pleiotropy and robustness. Results: IVW analysis indicates that genetic predisposition to thyroid disorders is linked to increase CSU risk in Europeans, with significant odds ratios noted for Graves’ disease, hyperthyroidism, and Hashimoto’s disease. Reverse MR suggests possible causal links between a genetic propensity for CSU and a decrease in hyperthyroidism and the ln (FT3/FT4) ratio. No evidence was found linking thyroid function phenotypes with CSU in East Asians. Conclusion: Our research indicates that genetic susceptibilities to thyroid disorders are associated with a higher risk of CSU in European populations, with no observed link in East Asian populations. These findings may offer new avenues for future investigation into the relationship between thyroid autoimmunity and CSU.

not-yet-known not-yet-known not-yet-known unknown Title: Elagolix to treat menstrual related symptom exacerbations in early onset Parkinson disease: A Case Report Authors: Hajjar Rima MD¹, Sangadi Akhila ¹, Villafuerte-Trisolini Brian MD², Lydia A. Fein MD MPH¹* Department of Obstetrics and Gynecology, University of Miami, Miami, Florida Department of Neurology, Design Neuroscience Center, Miami, Florida * Corresponding author: Rima Hajjar MD Email: rima.hajjar@jhsmiami.org Tel: +1 786-229-9722 Address: 1321 NW 14th St, Miami, FL 33125 Short Title: Parkinson Disease and Elagolix Word Count: 1385 Title: Elagolix to treat menstrual related symptom exacerbations in early onset Parkinson disease: A Case Report

Background: There are approximately 15 million individuals co-infected with HBV and HDV spread across several countries in the world, however this number is underestimated. HDV superinfection is more frequently associated with liver failure, cirrhosis and even the development of hepatocellular carcinoma (HCC) when compared to HBV. Objective: This report presents cases of three young patients with possible superinfection who showed rapid development of liver disease in the severe form of HDV infection. Methods: Samples were collected at Ambulatório especializado em Hepatites Virais on July 31, 2023 and processed by Laboratório de Virologia Molecular da Fundação Oswaldo Cruz/Rondônia. The clinical and laboratory data of participants was collected through electronic medical records. To characterize HDV genotype, a Nested-PCR was used to obtain a 406 bp fragment of the HDV genome and subsequent genetic sequencing was performed. Results: Three individuals from a rural community in municipality of Lábrea/Amazonas showed a profile of rapid progression to chronic liver disease. Phylogenetic analysis showed that the sequences of all the cases were classified as HDV genotype 3. Conclusion: This case report demonstrates the impact of Delta Hepatitis as important public health problem for young-adult population and major challenge in the context of Brazilian Western Amazon region.

This study presents a novel approach in nanomedicine for targeted cancer therapy by leveraging folic acid-receptor (FR) interactions and reactive oxygen species (ROS)-responsive nanocarriers. Utilizing big data to advance nanomedicine, we developed an innovative amphiphilic conjugate, folic acid (FA) decorated dextran-block-poly copolymer (FA-Dex-b-PPS), designed to serve as ROS-responsive nanocarriers specifically for prostate cancer treatment. The chemical structure of FA-Dex-b-PPS was confirmed via Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. The self-assembly into ROS-responsive nanoparticles and subsequent degradation were characterized through fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. Therapeutic nanocarriers encapsulating doxorubicin (Dox) were prepared via dialysis, demonstrating efficient oxidant-triggered Dox release in vitro. Cytotoxicity assays revealed high biocompatibility, with cell survival rates exceeding 85% at 400 μg/mL. Confocal laser scanning microscopy confirmed the efficient internalization of FA-Dex-b-PPS-Dox nanoparticles by PC3 cells via FR-mediated endocytosis, surpassing non-targeted Dex-b-PPS-Dox nanoparticles. Furthermore, in vitro and in vivo xenograft mouse model analyses consistently demonstrated that FA-Dex-b-PPS-Dox nanoparticles exhibited superior anti-tumor efficacy against PC3 cells compared to non-targeted and free Dox counterparts. These findings underscore the potential of tumor-targeted, ROS-responsive nanocarriers in enhancing the efficacy of cancer therapy.

Cholesterol sulfate (CS) is a naturally occurring cholesterol derivative that is widely distributed in a variety of tissues and body fluids. In humans, CS is mediated primarily by the sulfotransferase (SULT) 2B1b (SULT2B1b). Over the years, CS has been revealed to be involved in various physiological processes, such as epidermal cell adhesion, sperm capacitation, platelet adhesion, coagulation, glucolipid metabolism, bone metabolism, gut microbiota metabolism, neurosteroid biosynthesis, T-cell receptor signaling, and immune cell migration. In this review, we first introduce the endogenous regulation of CS biosynthesis and metabolism and then highlight current advances in the understanding of the physiological roles of CS. Finally, we focused on the implications of CS in various diseases, predominantly considering its mechanism of action, and potential therapeutic application.

not-yet-known not-yet-known not-yet-known unknown The brush straw checkerboard barrier offers a novel approach to sand control and features 60% higher design efficiency and a longer lifespan of 6 years compared to the traditional artificial straw checkerboard barrier. The wind tunnel test and field observation confirmed that the brush straw checkerboard barrier has high sand fixation efficiency. But how do these two sand barriers perform in terms of restoring soil function? How does the effectiveness of restoring soil function change as the service life of the straw checkerboard barrier increases? These questions still need to be clarified further. This study, conducted in Zhongwei, Ningxia, China, examined plots with brush straw checkerboard barrier, artificial straw checkerboard barrier, and bare sand. The results show that the brush straw checkerboard barrier is superior in improving soil moisture, organic matter, total nitrogen and electrical conductivity compared to the artificial straw checkerboard barrier. In addition, the brush straw checkerboard barrier has a positive impact on microbial diversity and community composition. Increasing sand fixation year through the brush straw checkerboard barrier correlates with improved soil properties and microbial indexes, suggesting that it has the potential for widespread application in desertification mitigation.

The recent death of a 3-year-old boy in Henan, China, has brought national attention to the systemic shortcomings in the management of zoonotic diseases in the China’s rural healthcare system, despite the child having had a full course of RIG treatment and post-exposure vaccination. This case reveals poor vaccination and RIG reserves, inadequate readiness in accordance with WHO guidelines, low-quality wound care, and postponed treatment, all of which are made even worse by the difficulty in accessing healthcare and the low level of public health literacy in rural areas. In an effort to achieve health equity in rural public health systems, this paper promotes the following measures to help prevent future tragedies: increasing the availability of medical resources; improving the capacity of rural healthcare workers to manage high-risk zoonoses; enhancing health education; and putting strict animal control measures in place.

not-yet-known not-yet-known not-yet-known unknown ABO blood group antigens (namely, A, B, and H antigens) are carbohydrate epitopes on cell surface that play important roles in biological processes and diseases. The structure diversity of ABH antigens structures is associated with susceptibility to different pathogen infections. Advanced synthetic methodologies are required for studying and applying ABO blood group antigens. The existing methods include chemical, enzymatic and chemoenzymatic synthesis. As an alternative approach to chemical synthesis, enzymatic synthesis provides a simple pathway to access oligosaccharide antigens under extremely mild reaction conditions, thereby avoiding laborious protecting group manipulation procedures. Enzymatic synthesis of human blood group antigens primarily relied on Leloir glycosyltransferases, alongside several glycosidases and glycoside phosphorylases. This review aims to discuss recent advancements in chemical, enzymatic and chemoenzymatic synthesis of human ABH antigens, with a particular focus on novel developments in enzymatic assembly of naturally occurring ABH antigens.

Abstract: Recent research has shown a strong link between Th17 cells and their cytokine IL-17, and various cardiovascular diseases such as myocarditis, myocardial infarction, and atherosclerosis. Moreover, Th17 cell signalling is likely to be a key factor in cardiovascular disease. Here, we summarize recent advances in the source, function, regulation, and the effects of Th17 signaling in cardiovascular disease. Research on Th17 will suggest more specific strategies to manipulate these functions. Thus, effective treatment of cardiovascular disease and future clinical treatment will be possible.

Ecosystems may exist in alternative stable states and thereby extremely differ in ecosystem structure and functions, including gross primary productivity (GPP), which is crucial for assessing an ecosystem’s ability to capture atmospheric carbon dioxide, especially under the context of climate change. This study applied alternative stable states theory to evaluate GPP in global dryland forests, and analyzed multi-year average GPP data alongside environmental factors such as the Aridity Index and mean annual precipitation. Here, we found the existence of alternative stable states of GPP along the aridity gradient. Mean GPP were 893.12 gC/m²/year and 1539.86 gC/m²/year under lower and higher branches of alternative stable states, respectively, compared to the current mean value of 1203.02 gC/m²/year. Notably, we observed striking regional disparities in GPP, with Africa and Oceania predominantly in the higher alternative stable state, while North America and Asia were in the lower alternative stable state. However, GPP along mean annual precipitation did not exhibit alternative stable states, but a significant variation during the medium range of mean annual precipitation (241-402 mm year-1). The relationships between GPP data and environmental factors were consistent across different forest types. This study sheds light on dryland forest productivity and indicates adaptive management strategies that should be used to bolster ecosystem function in the context of climate change.

Brassinosteroids (BR) are small endogenous phytohormones that are key regulators of plant growth, development, and stress resistance. They fulfil this role partially by modulating cell wall structure and composition through the control of genes involved in primary and secondary cell wall biosynthesis and metabolism. This affects the deposition of cellulose, lignin, and other components, and modifies the inner architecture of the wall, allowing it to adapt to the developmental status and environmental conditions. Here, we review the role of BR in cell wall modifications, highlighting recently described functions of BR in model plants in development and growth, such as cell layers interaction to regulate coordinated growth and tissue development for organ shape, skotomorphogenesis, and regulation of gravitropism for the orientation of plant growth direction against gravity. We also discuss the potential use of BR in crops to address current problems such as the need to maintain crop yield, quality, and wood production while increasing stress resistance. Among these approaches are the modification of BR biosynthesis and upregulated BR signalling, leading to increased crop development or wood deposition. We will also highlight how the use of exogenous BR applications can promote BR-related responses to improve plant fitness and productivity.

A document by Behnam Shakiba. Click on the document to view its contents.

Abiotic stress is one of the most important factors in reducing crop yield. Eukaryotic initiation factor (eIF) virtually regulates cellular activities and signaling in eukaryotic systems; it has been reported in monocotyledonous plants, however, its role in dicotyledonous plant adversity stress remains scarce. Here, we identified GmseIF2B5 gene and created the editing lines ( sp1 and sp4) by CRISPR/Cas9 technology in soybean. sp1 and sp4 lines boost tolerance to drought stress; RNA sequence analysis revealed that the differential gene was significantly enriched in the phenylpropanoid biosynthesis metabolic pathway; GmeIF2B5 interacts with GmPOD4 in vitro and in vivo, which encodes peroxidase, the last enzyme that catalyzes lignin synthesis. In addition, sp1 and sp4 lines also improved salt tolerance in soybean by increasing peroxidase activity and balancing Na +/K + ratio. Intriguingly, gmeif2b5 single and eif2b5pod4 double gene-edited lines both enhanced tolerances to salt and drought stress. Collectively, the findings reveal that the GmeIF2B5-GmPOD4 module mediates drought tolerance through lignin biosynthesis and increases salt tolerance by balancing the Na +/K + ratio in soybeans. The discovery fills the role of eIF-like genes in soybeans, and it provides an avenue for the genetic improvement of salt- and drought-tolerant soybean varieties.

not-yet-known not-yet-known not-yet-known unknown Cause analysis and nursing experience of a case of thrombus on Eustachian valve after PICC catheterization Guan-Jun Ye, Qian-Ru Zhu, Yan-Fen Yu, Chun-Ying Wang, Su-Pei Hu, Qin Zhou, Juan He Department of Nursing, No.2 Hospital, Ningbo, Zhejiang, China Address correspondence to: Guan-Jun Ye, Department of Nursing, No.2 Hospital, No. 41 Xibei Street, Ningbo 315000, Zhejiang, China. Tel: (86)-13958229524;E-mail: 17108879@qq.com [Abstract] In this article, we have summarized and analyzed the causes and nursing experience of thrombosis on the eustachian valve in the right atrium of a patient with advanced gastric cancer during chemotherapy after PICC insertion. The nursing points included organizing multi-disciplinary joint consultation, vigilance against pulmonary embolism, nursing with anticoagulant drugs, and individualized psychological nursing. Finally, after 22 days of active treatment, the thrombus almost disappeared. [Key words] PICC; Complications; Right atrial thrombus; Eustachian valve; Nursing Care