Advances and mechanisms of fungal symbionts in improving the salt tolerance of crops.

Soil salinization leads to reduced crop yields and waste of land resources, thereby impacting global food security. To meet the increasing demand for food and simultaneously alleviate pressure on soil resources, the development of sustainable agriculture is imperative. In contrast to physical and chemical methods, bioremediation represents an efficient and environmentally friendly approach. Fungal symbionts have been found to be associated with most plants in natural ecosystems, colonizing and residing within the internal tissues of host plants. Moreover, the potential of fungal symbionts in improving saline-alkaline soil has been widely recognized and confirmed. Numerous reports have documented the effectiveness of arbuscular mycorrhizal fungi in alleviating salt stress in plants. Meanwhile, research on other endophytic fungi for mitigating plant salt stress has emerged in recent years, which contributes to refining mechanisms for enhancing plant salt tolerance. In this review, we summarized various mechanisms by which endophytic fungi enhance plant salt tolerance. We also provided an overview of the challenges and development directions in the field of fungal symbiosis, with the aim of offering a viable strategy for the bioremediation of saline-alkali soils.

Biodegradation of four polyolefin plastics in superworms (Larvae of Zophobas atratus) and effects on the gut microbiome.

Recent studies have demonstrated superworms (larvae of Zophobas atratus) ability to degrade polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polypropylene (PP) within their digestive system. This study aimed to compare the ability of superworms to degrade the above four polyolefin plastics over a duration of 30 days. In this study, the degradation rate of PE was the highest, and the final average weight of superworms, as well as the final plastic mass loss consumed by them, significantly increased (73.38 % and 52.33 %, respectively) when PE was fed with wheat bran (1:1 [w/w]). FTIR and TGA indicated the occurrence of oxidation and biodegradation processes in the four polyolefin plastics when exposed to superworms. In addition, the molecular weights (Mw and Mn) of excreted polymer residues decreased by 3.1 % and 2.87 % in PE-fed superworms, suggesting that the depolymerization of PE was not entirely dependent on the gut microbial community. The analysis of the gut microbial communities revealed that the dominant microbial community were different for each type of plastic. The results indicate that the gut microbiome of superworms exhibited remarkable adaptability in degrading various types of plastics, and the intake preferences and efficiency of different plastics are associated with different dominant microbial community species.

Tracing the Evolution: A Comprehensive Bibliometric Analysis of Drug Interaction Clinical Studies.

This study aims to meticulously map the bibliometric landscape of drug-drug interactions (DDIs) in clinical research. This represents the first use of bibliometric analysis to comprehensively highlight the evolutionary trends and core themes in this critical field of pharmacology. An exhaustive bibliometric search was performed within the Web of Science Core Collection, aiming to comprehensively gather literature on DDIs in clinical settings. A combination of sophisticated analytical tools including DIKW, VOSviewer, and Citespace was utilized for an in-depth exploration of bibliometric patterns and trends. Of the 3421 initially identified articles, 2622 were considered relevant. The analysis revealed a marked escalation in DDIs publications, with a peak observed in 2020. Five principal thematic clusters emerged: Safety and Adverse Reactions, Drug Metabolism and Efficacy, Disease and Drug Treatment, Research Methods and Practices, and Special Populations and Combined Medication. Key insights included the escalating significance of drug metabolism in pharmacokinetics, heightened focus on cardiovascular and antiviral therapeutics, and the advancing frontier of personalized medicine. Additionally, the analysis underscored the necessity for strategic attention to vulnerable populations and innovative methodological approaches. This study calls for the global harmonization of research methods in DDIs clinical investigations, advocating for the integration of personalized medicine paradigms and the implementation of cutting-edge computational analytics. It highlights the imperative for inclusive and collaborative research approaches to adeptly address the intricate challenges of contemporary pharmacotherapy.

Global Trends in mHealth and Medical Education Research: Bibliometrics and Knowledge Graph Analysis.

Background: Mobile health (mHealth) is an emerging mobile communication and networking technology for health care systems. The integration of mHealth in medical education is growing extremely rapidly, bringing new changes to the field. However, no study has analyzed the publication and research trends occurring in both mHealth and medical education. Objective: The aim of this study was to summarize the current application and development trends of mHealth in medical education by searching and analyzing published articles related to both mHealth and medical education. Methods: The literature related to mHealth and medical education published from 2003 to 2023 was searched in the Web of Science core database, and 790 articles were screened according to the search strategy. The HistCite Pro 2.0 tool was used to analyze bibliometric indicators. VOSviewer, Pajek64, and SCImago Graphica software were used to visualize research trends and identify hot spots in the field. Results: In the past two decades, the number of published papers on mHealth in medical education has gradually increased, from only 3 papers in 2003 to 130 in 2022; this increase became particularly evident in 2007. The global citation score was determined to be 10,600, with an average of 13.42 citations per article. The local citation score was 96. The United States is the country with the most widespread application of mHealth in medical education, and most of the institutions conducting in-depth research in this field are also located in the United States, closely followed by China and the United Kingdom. Based on current trends, global coauthorship and research exchange will likely continue to expand. Among the research journals publishing in this joint field, journals published by JMIR Publications have an absolute advantage. A total of 105 keywords were identified, which were divided into five categories pointing to different research directions. Conclusions: Under the influence of COVID-19, along with the popularization of smartphones and modern communication technology, the field of combining mHealth and medical education has become a more popular research direction. The concept and application of digital health will be promoted in future developments of medical education.

METTL3 inhibits BMSC apoptosis and facilitates osteonecrosis repair via an m6A-IGF2BP2-dependent mechanism.

Hypoxia-induced apoptosis of bone marrow mesenchymal stem cells (BMSCs) limits the efficacy of their transplantation for steroid-induced osteonecrosis of the femoral head (SONFH). As apoptosis and RNA methylation are closely related, exploring the role and mechanism of RNA methylation in hypoxic apoptosis of BMSCs is expected to identify new targets for transplantation of BMSCs for SONFH and enhance transplantation efficacy. We performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA-seq on a hypoxia-induced apoptosis BMSC model and found that the RNA methyltransferase-like 3 (METTL3) is involved in hypoxia-induced BMSC apoptosis. The expression of METTL3 was downregulated in BMSCs after hypoxia and in BMSCs implanted in osteonecrosis areas. Knockdown of METLL3 under normoxic conditions promoted apoptosis of BMSCs. In contrast, overexpression of METTL3 promoted the survival of BMSCs under hypoxic conditions, and overexpression of METTL3 promoted the survival of BMSCs in the osteonecrosis area and the repair of the osteonecrosis area. Regarding the mechanism, the m6A levels of the mRNAs of anti-apoptotic genes Bcl-2, Mcl-1, and BIRC5 were significantly increased upon the overexpression of METTL3 under hypoxic conditions, which promoted the binding of Bcl-2, Mcl-1, and BIRC5 mRNAs to IGF2BP2, enhanced the mRNA stability, and increased the protein expression of the three anti-apoptotic genes. In conclusion, overexpression of METTL3 promoted m6A modification of mRNAs of Bcl-2, Mcl-1, and BIRC5, promoted the binding of IGF2BP2 to the above-mentioned mRNAs, enhanced mRNA stability, inhibited hypoxia-induced BMSC apoptosis, and promoted repair of SONFH, thereby providing novel targets for transplantation of BMSCs for SONFH.

Total testosterone plays a crucial role in the pathway from hypothyroidism to broad depression in women.

BACKGROUND: Depression tends to develop in correlation with hypothyroidism, however it's unclear how testosterone traits contribute to this association. We examined the causal association between depression, testosterone traits, and hypothyroidism using Mendelian randomization (MR). METHOD: We conducted univariable and multivariable MR studies using summary-level statistics from genome-wide association studies (GWAS) of Hypothyroidism (n = 213,990), broad depression (n = 322,580), probable major depressive disorder (probable MDD) (n = 174,519), and International Classification of Diseases (ICD)-9 or ICD-10-coded MDD (n = 217,584) from European ancestry. The inverse variance weighted (IVW) method was used as the main MR analysis. RESULTS: In univariate MR analysis, there is a positive causal relationship between hypothyroidism and broad depression (P = 0.0074; OR = 1.0066; 95%CI: 1.0018-1.0114) and probable MDD (P = 0.0242; OR = 1.0056; 95%CI: 1.0007-1.0105). In females, there is a causal relationship between hypothyroidism and decreased total testosterone (P < 0.001; OR = 0.9747; 95%CI: 0.9612-0.9885) and sex hormone binding globulin (SHBG) levels (P = 0.0418; OR = 0.9858; 95%CI: 0.9723-0.9995). In females, there is an inverse causal relationship between total testosterone and broad depression (P = 0.0349; OR = 0.9898; 95%CI: 0.9804-0.9993). Furthermore, in multivariate MR analysis, after adjusting for total testosterone in females, hypothyroidism only has a positive causal relationship with probable MDD, and the relationship with broad depression is no longer significant. Most notably, after adjusting for hypothyroidism, the inverse causal effect of female total testosterone levels on broad depression becomes more significant (P = 0.0154; OR = 0.9878; 95%CI: 0.9780-0.9977). CONCLUSION: Hypothyroidism increases the risk of broad depression and probable MDD development. Total Testosterone appears to play an important role in the relationship between hypothyroidism and broad depression in female.

Regulatory roles of the second messenger c-di-GMP in beneficial plant-bacteria interactions.

The rhizosphere system of plants hosts a diverse consortium of bacteria that confer beneficial effects on plant, such as plant growth-promoting rhizobacteria (PGPR), biocontrol agents with disease-suppression activities, and symbiotic nitrogen fixing bacteria with the formation of root nodule. Efficient colonization in planta is of fundamental importance for promoting of these beneficial activities. However, the process of root colonization is complex, consisting of multiple stages, including chemotaxis, adhesion, aggregation, and biofilm formation. The secondary messenger, c-di-GMP (cyclic bis-(3'-5') dimeric guanosine monophosphate), plays a key regulatory role in a variety of physiological processes. This paper reviews recent progress on the actions of c-di-GMP in plant beneficial bacteria, with a specific focus on its role in chemotaxis, biofilm formation, and nodulation.

Mitigating microplastic stress on peanuts: The role of biochar-based synthetic community in the preservation of soil physicochemical properties and microbial diversity.

Tire-derived rubber crumbs (RC), as a new type of microplastics (MPs), harms both the environment and human health. Excessive use of plastic, the decomposition of which generates microplastic particles, in current agricultural practices poses a significant threat to the sustainability of agricultural ecosystems, worldwide food security and human health. In this study, the application of biochar, a carbon-rich material, to soil was explored, especially in the evaluation of synthetic biochar-based community (SynCom) to alleviate RC-MP-induced stress on plant growth and soil physicochemical properties and soil microbial communities in peanuts. The results revealed that RC-MPs significantly reduced peanut shoot dry weight, root vigor, nodule quantity, plant enzyme activity, soil urease and dehydrogenase activity, as well as soil available potassium, and bacterial abundance. Moreover, the study led to the identification highly effective plant growth-promoting rhizobacteria (PGPR) from the peanut rhizosphere, which were then integrated into a SynCom and immobilized within biochar. Application of biochar-based SynCom in RC-MPs contaminated soil significantly increased peanut biomass, root vigor, nodule number, and antioxidant enzyme activity, alongside enhancing soil enzyme activity and rhizosphere bacterial abundance. Interestingly, under high-dose RC-MPs treatment, the relative abundance of rhizosphere bacteria decreased significantly, but their diversity increased significantly and exhibited distinct clustering phenomenon. In summary, the investigated biochar-based SynCom proved to be a potential soil amendment to mitigate the deleterious effects of RC-MPs on peanuts and preserve soil microbial functionality. This presents a promising solution to the challenges posed by contaminated soil, offering new avenues for remediation.

USP18 Curbs the Progression of Metabolic Hypertension by Suppressing JAK/STAT Pathway.

Hypertension is a pathological state of the metabolic syndrome that increases the risk of cardiovascular disease. Managing hypertension is challenging, and we aimed to identify the pathogenic factors and discern therapeutic targets for metabolic hypertension (MHR). An MHR rat model was established with the combined treatment of a high-sugar, high-fat diet and ethanol. Histopathological observations were performed using hematoxylin-eosin and Sirius Red staining. Transcriptome sequencing was performed to screen differentially expressed genes. The role of ubiquitin-specific protease 18 (USP18) in the proliferation, apoptosis, and oxidative stress of HUVECs was explored using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. Moreover, USP18 downstream signaling pathways in MHR were screened, and the effects of USP18 on these signaling pathways were investigated by western blotting. In the MHR model, total cholesterol and low-density lipoprotein levels increased, while high-density lipoprotein levels decreased. Moreover, high vessel thickness and percentage of collagen were noted along with increased malondialdehyde, decreased superoxide dismutase and catalase levels. The staining results showed that the MHR model exhibited an irregular aortic intima and disordered smooth muscle cells. There were 78 differentially expressed genes in the MHR model, and seven hub genes, including USP18, were identified. USP18 overexpression facilitated proliferation and reduced apoptosis and oxidative stress in HUVECs treated with Ang in vitro. In addition, the JAK/STAT pathway was identified as a USP18 downstream signaling pathway, and USP18 overexpression inhibited the expression of JAK/STAT pathway-related proteins. Conclusively, USP18 restrained MHR progression by promoting cell proliferation, reversing apoptosis and oxidative stress, and suppressing the JAK/STAT pathway.

Purines enrich root-associated Pseudomonas and improve wild soybean growth under salt stress.

The root-associated microbiota plays an important role in the response to environmental stress. However, the underlying mechanisms controlling the interaction between salt-stressed plants and microbiota are poorly understood. Here, by focusing on a salt-tolerant plant wild soybean (Glycine soja), we demonstrate that highly conserved microbes dominated by Pseudomonas are enriched in the root and rhizosphere microbiota of salt-stressed plant. Two corresponding Pseudomonas isolates are confirmed to enhance the salt tolerance of wild soybean. Shotgun metagenomic and metatranscriptomic sequencing reveal that motility-associated genes, mainly chemotaxis and flagellar assembly, are significantly enriched and expressed in salt-treated samples. We further find that roots of salt stressed plants secreted purines, especially xanthine, which induce motility of the Pseudomonas isolates. Moreover, exogenous application for xanthine to non-stressed plants results in Pseudomonas enrichment, reproducing the microbiota shift in salt-stressed root. Finally, Pseudomonas mutant analysis shows that the motility related gene cheW is required for chemotaxis toward xanthine and for enhancing plant salt tolerance. Our study proposes that wild soybean recruits beneficial Pseudomonas species by exudating key metabolites (i.e., purine) against salt stress.

The Complete Genome Sequence of Bacillus toyonensis Cbmb3 with Polyvinyl Chloride-Degrading Properties.

The accumulation of high amounts of plastic waste in the environment has raised ecological and health concerns, particularly in croplands, and biological degradation presents a promising approach for the sustainable treatment of this issue. In this study, a polyvinyl chloride (PVC)-degrading bacterium was isolated from farmland soil samples attached to waste plastic, utilizing PVC as the sole carbon source. The circular chromosome of the strain Cbmb3, with a length of 5,768,926 bp, was subsequently sequenced. The average GC content was determined to be 35.45%, and a total of 5835 open reading frames were identified. The strain Cbmb3 was designated as Bacillus toyonensis based on phylogenomic analyses and genomic characteristics. The bioinformatic analysis of the Cbmb3 genome revealed putative genes encoding essential enzymes involved in PVC degradation. Additionally, the potential genomic characteristics associated with phytoprobiotic effects, such as the synthesis of indole acetic acid and secondary metabolite synthesis, were also revealed. Overall, the present study provides the first complete genome of Bacillus toyonensis with PVC-degrading properties, suggesting that Cbmb3 is a potential strain for PVC bioremediation and application.

A self-amplifying loop of TP53INP1 and P53 drives oxidative stress-induced apoptosis of bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cell (BMSC) transplantation is a promising regenerative therapy; however, the survival rate of BMSCs after transplantation is low. Oxidative stress is one of the main reasons for the high apoptosis rate of BMSCs after transplantation, so there is an urgent need to explore the mechanism of oxidative stress-induced apoptosis of BMSCs. Our previous transcriptome sequencing results suggested that the expression of P53-induced nuclear protein 1 (TP53INP1) and the tumor suppressor P53 (P53) was significantly upregulated during the process of oxidative stress-induced apoptosis of BMSCs. The present study further revealed the role and mechanism of TP53INP1 and P53 in oxidative stress-induced apoptosis in BMSCs. Overexpression of TP53INP1 induced apoptosis of BMSCs, knockdown of TP53INP1 alleviated oxidative stress apoptosis of BMSCs. Under oxidative stress conditions, P53 is regulated by TP53INP1, while P53 can positively regulate the expression of TP53INP1, so the two form a positive feedback loop. To clarify the mechanism of feedback loop formation. We found that TP53INP1 inhibited the ubiquitination and degradation of P53 by increasing the phosphorylation level of P53, leading to the accumulation of P53 protein. P53 can act on the promoter of the TP53INP1 gene and increase the expression of TP53INP1 through transcriptional activation. This is the first report on a positive feedback loop formed by TP53INP1 and P53 under oxidative stress. The present study clarified the formation mechanism of the positive feedback loop. The TP53INP1-P53 positive feedback loop may serve as a potential target for inhibiting oxidative stress-induced apoptosis in BMSCs.

The impact of arbuscular mycorrhizal fungi and endophytic bacteria on peanuts under the combined pollution of cadmium and microplastics.

It remains unclear how symbiotic microbes impact the growth of peanuts when they are exposed to the pollutants cadmium (Cd) and microplastics (MPs) simultaneously. This study aimed to investigate the effects of endophytic bacteria Bacillus velezens SC60 and arbuscular mycorrhizal fungus Rhizophagus irregularis on peanut growth and rhizosphere microbial communities in the presence of Cd at 40 (Cd40) or 80 (Cd80) mg kg-1 combined without MP or the presence of low-density polyethylene (LDPE) and poly butyleneadipate-co-terephthalate (PBAT). This study assessed soil indicators, plant parameters, and Cd accumulation indicators. Results showed that the application of R. irregularis and B. velezens significantly enhanced soil organic carbon and increased Cd content under the conditions of Cd80 and MPs co-pollution. R. irregularis and B. velezens treatment increased peanut absorption and the enrichment coefficient for Cd, with predominate concentrations localized in the peanut roots, especially under combined pollution by Cd and MPs. Under treatments with Cd40 and Cd80 combined with PBAT pollution, soil microbes Proteobacteria exhibited a higher relative abundance, while Actinobacteria showed a higher relative abundance under treatments with Cd40 and Cd80 combined with LDPE pollution. In conclusion, under the combined pollution conditions of MPs and Cd, the co-treatment of R. irregularis and B. velezens effectively immobilized Cd in peanut roots, impeding its translocation to the shoot.

Biodeterioration of polyethylene by Bacillus cereus and Rhodococcus equi isolated from soil.

Polyethylene (PE), a non-biodegradable plastic, is widely used in agriculture as a mulch material, which causes serious plastic pollution when it is discarded. Recent studies have described the biodeterioration of PE by bacteria, but it is difficult for a single bacterial species to effectively degrade PE plastic. We isolated two strains with PE-degrading ability, Bacillus cereus (E1) and Rhodococcus equi (E3), from the soil attached to plastic waste on the south side of Mount Tai, China, using a medium with PE plastic as the only carbon source. By clear zone area analysis, we found that E1 mixed with E3 could improve the degradation of PE plastics. The mixture of E1 and E3 was incubated for 110 days in a medium containing PE and mulch film as the only carbon source, respectively. After 110 days, a decrease in pH and mass was observed. Obvious slits and depressions were observed on the surface of the PE film and the mulch films using scanning electron microscopy. The surface hydrophobicity of both films decreased, and FTIR revealed the formation of new oxidation groups on their surfaces during the degradation process and the destruction of the original CH2 long chains of PE. Besides, we found that surface of the mulch films contained more viable bacteria than the liquid medium. In conclusion, we identified two PE-degrading strains whose mixture can effectively degrade mulch film than pure PE film. Our results provide a reference for understanding PE plastic degradation pathways and their associated degradation processes.

Global trends in PANoptosis research: bibliometrics and knowledge graph analysis.

PANoptosis has recently been discovered as a new type of cell death. PANoptosis mainly refers to the significant interaction among the three programmed cell death pathways of apoptosis, necroptosis, and pyroptosis. Despite this, only a few studies have examined the systematic literature in this area. By analyzing the bibliometric data for PANoptosis, we can visualize the current hotspots and predicted trends in research. This study analyzed bibliometric indicators using the Histcite Pro 2.0 tool, which searches the Web of Science for PANoptosis literature published between 2016 and 2022. A bibliometric analysis was performed using Histcite Pro 2.0, while research trends and hotspots were visualized using VOSviewer, CiteSpace and BioBERT. The output of related literature was low in the four years from the first presentation of PANoptosis in 2016 to 2020. The volume of relevant literature grew exponentially between 2020 and 2022. The United States and China play a leading role in this field. Although China started late, its research in this field is developing rapidly. As research progressed, more focus was placed on the relationship between PANoptosis and pyroptosis, as well as apoptosis and necrosis. Now is a rapid development stage of PANoptosis research. Most of the research focuses on the cellular level, and the focus is more on the treatment of tumor-related diseases. The current focus of this area is PANoptosis mechanisms in cancer and inflammation. It can be seen from the burst analysis of keywords that caspase1 and host defense have consistently been research hotspots in the field of PANoptosis, while the frequency of NLRC4, causes of autoinflammation, recognition, NLRP3, and Gasdermin D has gradually increased, all of which have become research hotspots in recent years. Finally, we used the BioBERT biomedical language model to mine the most documented genes and diseases in the PANoptosis field articles, pointing out the direction for subsequent research steps. According to a bibliometric analysis, researchers have shown an increased interest in PANoptosis over the past few years. Researchers initially focused on the molecular mechanism of PANoptosis and pyroptosis, apoptosis, and necroptosis. The role of PANoptosis in diseases and conditions such as inflammation and tumors is one of the current research hotspots in this area. The focus is more on treating inflammation-related diseases, which will become the key development direction of future research.

The volatile organic compound acetoin enhances the colonization of Azorhizobium caulinodans ORS571 on Sesbania rostrata.

Chemoreceptors play a crucial role in assisting bacterial sensing and response to environmental stimuli. Genome analysis of Azorhizobium caulinodans ORS571 revealed the presence of 43 putative chemoreceptors, but their biological functions remain largely unknown. In this study, we identified the chemoreceptor AmaP (methyl-accepting protein of A. caulinodans), characterized by the presence of the CHASE3 domain and exhibited a notable response to acetoin. Thus, we investigated the effect of acetoin sensing on its symbiotic association with the host. Our findings uncovered a compelling role for acetoin as a key player in enhancing various facets of A. caulinodans ORS571's performance including biofilm formation, colonization, and nodulation abilities. Notably, acetoin bolstered A. caulinodans ORS571's efficacy in promoting the growth of S. rostrata, even under moderate salt stress conditions. This study not only broadens our understanding of the AmaP protein with its distinctive CHASE3 domain but also highlights the promising potential of acetoin in fortifying the symbiotic relationship between A. caulinodans and Sesbania rostrata.

Association between the use of lipid-lowering drugs and the risk of inflammatory bowel disease.

BACKGROUND: Observational studies have suggested an association between lipid-lowering drugs and inflammatory bowel disease (IBD) risk. This study aimed to assess the causal influence of lipid-lowering agents on IBD risk using Mendelian randomization analysis. METHOD: In a population of 173,082 individuals of European ancestry, 55 single-nucleotide polymorphisms were identified as instrumental variables for 6 lipid-lowering drug targets (HMGCR, NPC1LC, PCSK9, LDLR, CETP and APOB). Summary statistics for the genome-wide association study of IBD, ulcerative colitis (UC) and Crohn's disease (CD) were obtained from the FinnGen consortium, Program in Complex Trait Genomics and UK Biobank. Inverse-variance weighted was employed as the primary MR method, and odds ratios (ORs) with 95% confidence intervals were reported as the results. Sensitivity analyses using conventional MR methods were conducted to assess result robustness. RESULTS: Gene-proxied inhibition of Niemann-Pick C1-like 1 (NPC1L1) was associated with an increased IBD risk (OR [95% CI]: 2.31 [1.38, 3.85]; p = .001), particularly in UC (OR [95% CI]: 2.40 [1.21, 4.74], p = .012), but not in CD. This finding was replicated in the validation cohort. Additionally, gene-proxied inhibition of low-density lipoprotein receptor was associated with reduced IBD (OR [95% CI]: .72 [.60, .87], p < .001) and UC risk (OR [95% CI]: .74 [.59, .92], p = .006), although this result was not replicated in the validation cohort. Other drug targets did not show significant associations with IBD, UC or CD risk. CONCLUSION: Inhibition of the lipid-lowering drug-target NPC1L1 leads to an increased IBD risk, mainly in the UC population.

Randomized, Placebo-Controlled, Multicenter Clinical Study on the Efficacy and Safety of Lidocaine Patches in Chinese Patients with Postherpetic Neuralgia.

INTRODUCTION: To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). METHODS: Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. RESULTS: Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. CONCLUSIONS: Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

FAR591 promotes the pathogenesis and progression of SONFH by regulating Fos expression to mediate the apoptosis of bone microvascular endothelial cells.

The specific pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH) is still not fully understood, and there is currently no effective early cure. Understanding the role and mechanism of long noncoding RNAs (lncRNAs) in the pathogenesis of SONFH will help reveal the pathogenesis of SONFH and provide new targets for its early prevention and treatment. In this study, we first confirmed that glucocorticoid (GC)-induced apoptosis of bone microvascular endothelial cells (BMECs) is a pre-event in the pathogenesis and progression of SONFH. Then, we identified a new lncRNA in BMECs via lncRNA/mRNA microarray, termed Fos-associated lincRNA ENSRNOT00000088059.1 (FAR591). FAR591 is highly expressed during GC-induced BMEC apoptosis and femoral head necrosis. Knockout of FAR591 effectively blocked the GC-induced apoptosis of BMECs, which then alleviated the damage of GCs to the femoral head microcirculation and inhibited the pathogenesis and progression of SONFH. In contrast, overexpression of FAR591 significantly promoted the GC-induced apoptosis of BMECs, which then aggravated the damage of GCs to the femoral head microcirculation and promoted the pathogenesis and progression of SONFH. Mechanistically, GCs activate the glucocorticoid receptor, which translocates to the nucleus and directly acts on the FAR591 gene promoter to induce FAR591 gene overexpression. Subsequently, FAR591 binds to the Fos gene promoter (-245∼-51) to form a stable RNA:DNA triplet structure and then recruits TATA-box binding protein associated factor 15 and RNA polymerase II to promote Fos expression through transcriptional activation. Fos activates the mitochondrial apoptotic pathway by regulating the expression of Bcl-2 interacting mediator of cell death (Bim) and P53 upregulated modulator of apoptosis (Puma) to mediate GC-induced apoptosis of BMECs, which leads to femoral head microcirculation dysfunction and femoral head necrosis. In conclusion, these results confirm the mechanistic link between lncRNAs and the pathogenesis of SONFH, which helps reveal the pathogenesis of SONFH and provides a new target for the early prevention and treatment of SONFH.