Effectiveness of eHealth interventions for HIV prevention, testing and management: An umbrella review.

BACKGROUND: Human immunodeficiency virus (HIV) infection has become a major contributor to the global burden of disease. Globally, the number of cases of HIV continues to increase. Electronic health (eHealth) interventions have emerged as promising tools to support disease self-management among people living with HIV. The purpose of this umbrella review is to systematically evaluate and summarize the evidence and results of published systematic reviews and meta-analyses on the effectiveness of eHealth interventions for HIV prevention, testing and management. METHODS: PubMed, Embase and the Cochrane Library were searched for reviews. The methodological quality of the included studies was assessed using AMSTAR-2. RESULTS: A total of 22 systematic reviews were included. The methodological quality of the reviews was low or critically low. EHealth interventions range from Internet, computer, or mobile interventions to websites, programs, applications, email, video, games, telemedicine, texting, and social media, or a combination of them. The majority of the reviews showed evidence of effectiveness (including increased participation in HIV management behaviours, successfully changed HIV testing behaviours, and reduced risk behaviours). EHealth interventions were effective in the short term. CONCLUSIONS: Ehealth interventions have the potential to improve HIV prevention, HIV testing and disease management. Due to the limitations of the low methodological quality of the currently available systematic reviews, more high-quality evidence is needed to develop clear and robust recommendations.

EGF-like growth factors upregulate pentraxin 3 expression in human granulosa-lutein cells.

The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essential ovulatory protein, is necessary for maintaining extracellular matrix (ECM) stability during cumulus expansion. The aim of this study was to investigate the impact of EGF-like factors, AREG, BTC, and EREG on the expression and production of PTX3 in human granulosa-lutein (hGL) cells and the molecular mechanisms involved. Our results demonstrated that AREG, BTC, and EREG could regulate follicular function by upregulating the expression and increasing the production of PTX3 in both primary (obtained from 20 consenting patients undergoing IVF treatment) and immortalized hGL cells. The upregulation of PTX3 expression was primarily facilitated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway, induced by these EGF-like factors. In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3.

Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Effects of geopolitical risk on environmental sustainability and the moderating role of environmental policy stringency.

This study investigates the impact of geopolitical risk (GPR) on consumption-based carbon (CCO2) emissions as well as the moderating role of environmental policy stringency (EPS) on the above relationship. Based on data collected from 27 countries from 1990 to 2020, the basic results from the sample of the study indicate that GPR accelerates CCO2 emissions. Quantile regression results reveal that the effect of GPR is more pronounced in countries with higher CCO2 emissions. Moreover, EPS weakens the escalating effect of GPR on CCO2 emissions. The robust test results validate the findings reported in the basic regression model. The heterogeneity test indicates that the impact of GPR on CCO2 emissions is greater in developing countries compared in developed countries. The study also proposes these policy implications based on the findings: (1) countries should ensure a stable political environment, establish a robust legal system and promote energy transition; and (2) the scope of environmental taxes should be expanded where different tax rates should be imposed in order to be useful in reducing CCO2 emissions.

OsJAZ10 negatively modulates the drought tolerance by integrating hormone signaling with systemic electrical activity in rice.

Jasmonic acid (JA) plays crucial functions in plant stress response, and the synergistic interaction between JA and abscisic acid (ABA) signaling is implicated to help plants adapt to environmental challenges, whereas the underlying molecular mechanism still needs to be revealed. Here, we report that OsJAZ10, a repressor in the JA signaling, represses rice drought tolerance via inhibition of JA and ABA biosynthesis. Function loss of OsJAZ10 markedly enhances, while overexpression of OsJAZ10ΔJas reduces rice drought tolerance. The osjaz10 mutant is more sensitive to exogenous ABA and MeJA, and produces higher levels of ABA and JA after drought treatment, indicating OsJAZ10 represses the biosynthesis of these two hormones. Mechanistic study demonstrated that OsJAZ10 physically interacts with OsMYC2. Transient transcriptional regulation assays showed that OsMYC2 activates the expression of ABA-biosynthetic gene OsNCED2, JA-biosynthetic gene OsAOC, and drought-responsive genes OsRAB21 and OsLEA3, while OsJAZ10 prevents OsMYC2 transactivation of these genes. Further, the electrophoretic mobility shift assay (EMSA) confirmed that OsMYC2 directly binds to the promoters of OsNCED2 and OsRAB21. Electrical activity has been proposed to activate JA biosynthesis. Interestingly, OsJAZ10 inhibits the propagation of osmotic stress-elicited systemic electrical signals, indicated by the significantly increased PEG-elicited slow wave potentials (SWPs) in osjaz10 mutant, which is in accordance with the elevated JA levels. Collectively, our findings establish that OsJAZ10 functions as a negative regulator in rice drought tolerance by repressing JA and ABA biosynthesis, and reveal an important mechanism that plants integrate electrical events with hormone signaling to enhance the adaption to environmental stress.

Comprehensive molecular characterization of long-term glioblastoma survivors.

Fewer than 5% glioblastoma (GBM) patients survive over five years and are termed long-term survivors (LTS), yet their molecular background is unclear. The present cohort included 72 isocitrate dehydrogenase (IDH)-wildtype GBM patients, consisting of 35 LTS and 37 short-term survivors (STS), and we employed whole exome sequencing, RNA-seq and DNA methylation array to delineate this largest LTS cohort to date. Although LTS and STS demonstrated analogous clinical characters and classical GBM biomarkers, CASC5 (P = 0.002) and SPEN (P = 0.013) mutations were enriched in LTS, whereas gene-to-gene fusions were concentrated in STS (P = 0.007). Importantly, LTS exhibited higher tumor mutation burden (P < 0.001) and copy number (CN) increase (P = 0.013), but lower mutant-allele tumor heterogeneity score (P < 0.001) and CN decrease (P = 0.026). Additionally, LTS demonstrated hypermethylated genome (P < 0.001) relative to STS. Differentially expressed and methylated genes both enriched in olfactory transduction. Further, analysis of the tumor microenvironment revealed higher infiltration of M1 macrophages (P = 0.043), B cells (P = 0.016), class-switched memory B cells (P = 0.002), central memory CD4+ T cells (P = 0.031) and CD4+ Th1 cells (P = 0.005) in LTS. We also separately analyzed a subset of patients who were methylation class-defined GBM, contributing 70.8% of the entire cohort, and obtained similar results relative to prior analyses. Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM.

Baicalein inhibits biofilm formation of avian pathogenic Escherichia coli in vitro mainly by affecting adhesion.

Avian pathogenic Escherichia coli (APEC) is a widespread bacterium that causes significant economic losses to the poultry industry. APEC biofilm formation may result in chronic, persistent, and recurrent infections in clinics, making treatment challenging. Baicalein is a natural product that exhibits antimicrobial and antibiofilm activities. This study investigates the inhibitory effect of baicalein on APEC biofilm formation at different stages. The minimum inhibitory concentration (MIC) of baicalein on APEC was determined, and the growth curve of APEC biofilm formation was determined. The effects of baicalein on APEC biofilm adhesion, accumulation, and maturation were observed using optical microscopy, confocal laser scanning microscopy, and scanning electron microscopy. The biofilm inhibition rate of baicalein was calculated at different stages. The MIC of baicalein against APEC was 256 µg/mL. The process of APEC biofilm maturation takes approximately 48 h after incubation, with initial adhesion completed at 12 h, and cell accumulation finished at 24 h. Baicalein had a significant inhibitory effect on APEC biofilm formation at concentrations above 1 µg/mL (p < 0.01). Notably, baicalein had the highest rate of biofilm formation inhibition when added at the adhesion stage. Therefore, it can be concluded that baicalein is a potent inhibitor of APEC biofilm formation in vitro and acts, primarily by inhibiting cell adhesion. These findings suggests that baicalein has a potential application for inhibiting APEC biofilm formation and provides a novel approach for the prevention and control APEC-related diseases.

Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy.

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.

NLRP3 inflammasome and its role in autoimmune diseases: A promising therapeutic target.

The NOD-like receptor protein 3 (NLRP3) inflammasome is a protein complex that regulates innate immune responses by activating caspase-1 and the inflammatory cytokines IL-1ß and IL-18. Numerous studies have highlighted its crucial role in the pathogenesis and development of inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid diseases, and other autoimmune diseases. Therefore, investigating the underlying mechanisms of NLRP3 in disease and targeted drug therapies holds clinical significance. This review summarizes the structure, assembly, and activation mechanisms of the NLRP3 inflammasome, focusing on its role and involvement in various autoimmune diseases. This review also identifies studies where the involvement of the NLRP3 inflammasome in the disease mechanism within the same disease appears contradictory, as well as differences in NLRP3-related gene polymorphisms among different ethnic groups. Additionally, the latest therapeutic advances in targeting the NLRP3 inflammasome for autoimmune diseases are outlined, and novel clinical perspectives are discussed. Conclusively, this review provides a consolidated source of information on the NLRP3 inflammasome and may guide future research efforts that have the potential to positively impact patient outcomes.

Artificial intelligence for diagnosis and prognosis prediction of natural killer/T cell lymphoma using magnetic resonance imaging.

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.

Dietary additive ferulic acid alleviated oxidative stress, inflammation, and apoptosis induced by chronic exposure to avermectin in the liver of common carp (Cyprinus carpio).

Avermectin (AVM) has been utilized extensively in agricultural production since it is a low-toxicity pesticide. However, the pollution caused by its residues to fisheries aquaculture has been neglected. As an abundant polyphenolic substance in plants, ferulic acid (FA) possesses anti-inflammatory and antioxidant effects. The goal of the study is to assess the FA's ability to reduce liver damage in carp brought on by AVM exposure. Four groups of carp were created at random: the control group; the AVM group; the FA group; and the FA + AVM group. On day 30, and the liver tissues of carp were collected and examined for the detection of four items of blood lipid as well as the activity of the antioxidant enzymes catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in carp liver tissues by biochemical kits, and the transcript levels of indicators of oxidative stress, inflammation and apoptosis by qPCR. The results showed that liver injury, inflammation, oxidative stress, and apoptosis were attenuated in the FA+AVM group compared to the AVM group. In summary, dietary addition of FA could ameliorate the hepatotoxicity caused by AVM in carp by alleviating oxidative stress, inflammation, apoptosis in liver tissues.

Selective production of IL-33-neutralizing autoantibody ameliorates asthma responses and severity.

BACKGROUND: Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance. METHODS: A Luciferase Immunoprecipitation System was used to screen serum autoantibodies against 11 key cytokines in patients with allergic asthma and healthy donors. The antigen-specificity, immunomodulatory functions and clinical significance of anti-cytokine autoantibodies were determined by ELISA, qPCR, neutralization assays and statistical analysis, respectively. Potential conditions for autoantibody induction were revealed by in vitro immunization. RESULTS: Of 11 cytokines tested, only anti-IL-33 autoantibody was significantly increased in asthma, compare to healthy controls, and the proportion positive was higher in patients with mild-to-moderate than severe allergic asthma. In allergic asthma patients, the anti-IL-33 autoantibody level correlated negatively with serum concentration of pathogenic cytokines (e.g., IL-4, IL-13, IL-25 and IL-33), IgE, and blood eosinophil count, but positively with mid-expiratory flow FEF25-75%. The autoantibodies were predominantly IgG isotype, polyclonal and could neutralize IL-33-induced pathogenic responses in vitro and in vivo. The induction of the anti-IL-33 autoantibody in blood B-cells in vitro required peptide IL-33 antigen along with a stimulation cocktail of TLR9 agonist and cytokines IL-2, IL-4 or IL-21. CONCLUSIONS: Serum natural anti-IL-33 autoantibodies are selectively induced in some asthma patients. They ameliorate key asthma inflammatory responses, and may improve lung function of allergic asthma.

Combination of S1-N-Terminal and S1-C-Terminal Domain Antigens Targeting Double Receptor-Binding Domains Bolsters Protective Immunity of a Nanoparticle Vaccine against Porcine Epidemic Diarrhea Virus.

Variants of coronavirus porcine epidemic diarrhea virus (PEDV) frequently emerge, causing an incomplete match between the vaccine and variant strains, which affects vaccine efficacy. Designing vaccines with rapidly replaceable antigens and high efficacy is a promising strategy for the prevention of infection with PEDV variant strains. In our study, three different types of self-assembled nanoparticles (nps) targeting receptor-binding N-terminal domain (NTD) and C-terminal domain (CTD) of S1 protein, named NTDnps, CTDnps, and NTD/CTDnps, were constructed and evaluated as vaccine candidates against PEDV. NTDnps and CTDnps vaccines mediated significantly higher neutralizing antibody (NAb) titers than NTD and CTD recombinant proteins in mice. The NTD/CTDnps in varying ratios elicited significantly higher NAb titers when compared with NTDnps and CTDnps alone. The NTD/CTDnps (3:1) elicited NAb with titers up to 92.92% of those induced by the commercial vaccine. Piglets immunized with NTD/CTDnps (3:1) achieved a passive immune protection rate of 83.33% of that induced by the commercial vaccine. NTD/CTDnps (3:1) enhanced the capacity of mononuclear macrophages and dendritic cells to take up and present antigens by activating major histocompatibility complex I and II molecules to stimulate humoral and cellular immunity. These data reveal that a combination of S1-NTD and S1-CTD antigens targeting double receptor-binding domains strengthens the protective immunity of nanoparticle vaccines against PEDV. Our findings will provide a promising vaccine candidate against PEDV.

Exploring Antiviral Drugs on Monolayer Black Phosphorene: Atomistic Theory and Explainable Machine Learning-Assisted Platform.

Favipiravir (FP) and ebselen (EB) belong to a diverse class of antiviral drugs known for their significant efficacy in treating various viral infections. Utilizing molecular dynamics (MD) simulations, machine learning, and van der Waals density functional theory, we accurately elucidate the binding properties of these antiviral drugs on a phosphorene single-layer. To further investigate these characteristics, this study employs four distinct machine learning models-Random Forest, Gradient Boosting, XGBoost, and CatBoost. The Hamiltonian of antiviral molecules within a monolayer of phosphorene is appropriately trained. The key aspect of utilizing machine learning (ML) in drug design revolves around training models that are efficient and precise in approximating density functional theory (DFT). Furthermore, the study employs SHAP (SHapley Additive exPlanations) to elucidate model predictions, providing insights into the contribution of each feature. To explore the interaction characteristics and thermodynamic properties of the hybrid drug, we employ molecular dynamics and DFT calculations in a vacuum interface. Our findings suggest that this functionalized 2D complex exhibits robust thermostability, indicating its potential as an effective and enabled entity. The observed variations in free energy at different surface charges and temperatures suggest the adsorption potential of FP and EB molecules from the surrounding environment.

Vitamin D status, vitamin D receptor polymorphisms, and risk of type 2 diabetes: A prospective cohort study.

CONTEXT: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status. OBJECTIVE: To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR). METHODS: This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes. CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.

Advancing phytomining: Harnessing plant potential for sustainable rare earth element extraction.

Rare earth elements (REEs) are pivotal for advanced technologies, driving a surge in global demand. Import dependency on clean energy minerals raises concerns about supply chain vulnerabilities and geopolitical risks. Conventional REEs productionis resource-intensive and environmentally harmful, necessitating a sustainable supply approach. Phytomining (agromining) utilizes plants for eco-friendly REE extraction, contributing to the circular economy and exploiting untapped metal resources in enriched soils. Critical parameters like soil pH, Casparian strip, and REE valence influence soil and plant uptake bioavailability. Hyperaccumulator species efficiently accumulate REEs, serving as energy resources. Despite a lack of a comprehensive database, phytomining exhibits lower environmental impacts due to minimal chemical usage and CO2 absorption. This review proposes phytomining as a system for REEs extraction, remediating contaminated areas, and rehabilitating abandoned mines. The phytomining of REEs offers a promising avenue for sustainable REEs extraction but requires technological advancements to realize its full potential.

Molecular docking and molecular dynamics simulation decoding molecular mechanism of EDCs binding to hERRγ.

CONTEXT: Human estrogen-related receptor γ (hERRγ) is a key protein involved in various endocrines and metabolic signaling. Numerous environmental endocrine-disrupting chemicals (EDCs) can impact related physiological activities through receptor signaling pathways. Focused on hERRγ with 4-isopropylphenol, bisphenol-F (BPF), and BP(2,2)(Un) complexes, we executed molecular docking and multiple molecular dynamics (MD) simulations along with molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) and solvation interaction energy (SIE) calculation to study the detailed dynamical structural characteristics and interactions between them. Molecular docking showed that hydrogen bonds and hydrophobic interactions were the prime interactions to keep the stability of BPF-hERRγ and hERRγ-BP(2,2)(Un) complexes. Through MD simulations, we observed that all complexes reach equilibrium during the initial 50 ns of simulation, but these three EDCs lead to local structure changes in hERRγ. Energy results further identified key residues L268, V313, L345, and F435 around the binding pockets through CH-π, π-π, and hydrogen bonds interactions play an important stabilizing role in the recognition with EDCs. And most noticeable of all, hydrophobic methoxide groups in BP(2,2)(Un) is useful for decreasing the binding ability between EDCs and hERRγ. These results may contribute to evaluate latent diseases associated with EDCs exposure at the micro level and find potential substitutes. METHOD: Autodock4.2 was used to conduct the molecular docking, sietraj program was performed to calculate the energy, and VMD software was used to visualize the structure. Amber18 was conducted to perform the MD simulation and other analyses.

Current advances in human-induced pluripotent stem cell-based models and therapeutic approaches for congenital heart disease.

Congenital heart disease (CHD) represents a significant risk factor with profound implications for neonatal survival rates and the overall well-being of adult patients. The emergence of induced pluripotent stem cells (iPSCs) and their derived cells, combined with CRISPR technology, high-throughput experimental techniques, and organoid technology, which are better suited to contemporary research demands, offer new possibilities for treating CHD. Prior investigations have indicated that the paracrine effect of exosomes may hold potential solutions for therapeutic intervention. This review provides a summary of the advancements in iPSC-based models and clinical trials associated with CHD while elucidating potential therapeutic mechanisms and delineating clinical constraints pertinent to iPSC-based therapy, thereby offering valuable insights for further deliberation.

Semi-supervised model based on implicit neural representation and mutual learning (SIMN) for multi-center nasopharyngeal carcinoma segmentation on MRI.

BACKGROUND: The issue of using deep learning to obtain accurate gross tumor volume (GTV) and metastatic lymph nodes (MLN) segmentation for nasopharyngeal carcinoma (NPC) on heterogeneous magnetic resonance imaging (MRI) images with limited labeling remains unsolved. METHOD: We collected 918 patients with MRI images from three hospitals to develop and validate models and proposed a semi-supervised framework for the fine delineation of multi-center NPC boundaries by integrating uncertainty-based implicit neural representations named SIMN. The framework utilizes the deep mutual learning approach with CNN and Transformer, incorporating dynamic thresholds. Additionally, domain adaptive algorithms are employed to enhance the performance. RESULTS: SIMN predictions have a high overlap ratio with the ground truth. Under the 20 % labeled cases, for the internal test cohorts, the average DSC in GTV and MLN are 0.7981 and 0.7804, respectively; for external test cohort Wu Zhou Red Cross Hospital, the average DSC in GTV and MLN are 0.7217 and 0.7581, respectively; for external test cohorts First People Hospital of Foshan, the average DSC in GTV and MLN are 0.7004 and 0.7692, respectively. No significant differences are found in DSC, HD95, ASD, and Recall for patients with different clinical categories. Moreover, SIMN outperformed existing classical semi-supervised methods. CONCLUSIONS: SIMN showed a highly accurate GTV and MLN segmentation for NPC on multi-center MRI images under Semi-Supervised Learning (SSL), which can easily transfer to other centers without fine-tuning. It suggests that it has the potential to act as a generalized delineation solution for heterogeneous MRI images with limited labels in clinical deployment.

MEF2C contributes to axonal branching by regulating Kif2c transcription.

Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.