ISL1 and POU4F1 Directly Interact to Regulate the Differentiation and Survival of Inner Ear Sensory Neurons.

The inner ear sensory neurons play a pivotal role in auditory processing and balance control. Though significant progresses have been made, the underlying mechanisms controlling the differentiation and survival of the inner ear sensory neurons remain largely unknown. During development, ISL1 and POU4F transcription factors are co-expressed and are required for terminal differentiation, pathfinding, axon outgrowth and the survival of neurons in the central and peripheral nervous systems. However, little is understood about their functional relationship and regulatory mechanism in neural development. Here, we have knocked out Isl1 or Pou4f1 or both in mice of both sexes. In the absence of Isl1, the differentiation of cochleovestibular ganglion (CVG) neurons is disturbed and with that Isl1-deficient CVG neurons display defects in migration and axon pathfinding. Compound deletion of Isl1 and Pou4f1 causes a delay in CVG differentiation and results in a more severe CVG defect with a loss of nearly all of spiral ganglion neurons (SGNs). Moreover, ISL1 and POU4F1 interact directly in developing CVG neurons and act cooperatively as well as independently in regulating the expression of unique sets of CVG-specific genes crucial for CVG development and survival by binding to the cis-regulatory elements including the promoters of Fgf10, Pou4f2, and Epha5 and enhancers of Eya1 and Ntng2 These findings demonstrate that Isl1 and Pou4f1 are indispensable for CVG development and maintenance by acting epistatically to regulate genes essential for CVG development.

FOXS1 is increased in liver fibrosis and regulates TGFß responsiveness and proliferation pathways in human hepatic stellate cells.

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFß) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFß induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFß to activate fibrotic pathways, and FOXS1 mRNA was significantly increased. To study TGFß-FOXS1 signaling, we developed human LX2 FOXS1 CRISPR KO and scrambled control HSCs. To determine differentially expressed gene transcripts controlled by TGFß-FOXS1, we performed RNA-seq in the FOXS1 KO and control cells and over 400 gene responses were attenuated in the FOXS1 KO HSCs with TGFß-activation. To validate the RNA-seq findings, we used our state-of-the-art PamGene PamStation kinase activity technology that measures hundreds of signaling pathways nonselectively in real time. Using our RNA-seq data, kinase activity data, and descriptive measurements, we found that FOXS1 controls pathways mediating TGFß responsiveness, protein translation, and proliferation. Our study is the first to identify that FOXS1 may serve as a biomarker for liver fibrosis and HSC activation, which may help with early detection of hepatic fibrosis or treatment options for end-stage liver disease.

AP1/2ß-mediated exocytosis of tapetum-specific transporters is required for pollen development in Arabidopsis thaliana.

AP-1 and AP-2 adaptor protein (AP) complexes mediate clathrin-dependent trafficking at the trans-Golgi network (TGN) and the plasma membrane, respectively. Whereas AP-1 is required for trafficking to plasma membrane and vacuoles, AP-2 mediates endocytosis. These AP complexes consist of four subunits (adaptins): two large subunits (ß1 and γ for AP-1 and ß2 and α for AP-2), a medium subunit µ, and a small subunit σ. In general, adaptins are unique to each AP complex, with the exception of ß subunits that are shared by AP-1 and AP-2 in some invertebrates. Here, we show that the two putative Arabidopsis thaliana AP1/2ß adaptins co-assemble with both AP-1 and AP-2 subunits and regulate exocytosis and endocytosis in root cells, consistent with their dual localization at the TGN and plasma membrane. Deletion of both ß adaptins is lethal in plants. We identified a critical role of ß adaptins in pollen wall formation and reproduction, involving the regulation of membrane trafficking in the tapetum and pollen germination. In tapetal cells, ß adaptins localize almost exclusively to the TGN and mediate exocytosis of the plasma membrane transporters such as ATP-binding cassette (ABC)G9 and ABCG16. This study highlights the essential role of AP1/2ß adaptins in plants and their specialized roles in specific cell types.

Comparing the gut microbiota of Sichuan golden monkeys across multiple captive and wild settings: roles of anthropogenic activities and host factors.

BACKGROUND: Captivity and artificial food provision are common conservation strategies for the endangered golden snub-nosed monkey (Rhinopithecus roxellana). Anthropogenic activities have been reported to impact the fitness of R. roxellana by altering their gut microbiota, a crucial indicator of animal health. Nevertheless, the degree of divergence in gut microbiota between different anthropogenically-disturbed (AD) R. roxellana and their counterparts in the wild has yet to be elucidated. Here, we conducted a comparative analysis of the gut microbiota across nine populations of R. roxellana spanning China, which included seven captive populations, one wild population, and another wild population subject to artificial food provision. RESULTS: Both captivity and food provision significantly altered the gut microbiota. AD populations exhibited common variations, such as increased Bacteroidetes and decreased Firmicutes (e.g., Ruminococcus), Actinobacteria (e.g., Parvibacter), Verrucomicrobia (e.g., Akkermansia), and Tenericutes. Additionally, a reduced Firmicutes/Bacteroidetes ratiosuggested diminished capacity for complex carbohydrate degradation in captive individuals. The results of microbial functional prediction suggested that AD populations displayed heightened microbial genes linked to vitamin and amino acid metabolism, alongside decreased genes associated antibiotics biosynthesis (e.g., penicillin, cephalosporin, macrolides, and clavulanic acid) and secondary metabolite degradation (e.g., naphthalene and atrazine). These microbial alterations implied potential disparities in the health status between AD and wild individuals. AD populations exhibited varying degrees of microbial changes compared to the wild group, implying that the extent of these variations might serve as a metric for assessing the health status of AD populations. Furthermore, utilizing the individual information of captive individuals, we identified associations between variations in the gut microbiota of R. roxellana and host age, as well as pedigree. Older individuals exhibited higher microbial diversity, while a closer genetic relatedness reflected a more similar gut microbiota. CONCLUSIONS: Our aim was to assess how anthropogenic activities and host factors influence the gut microbiota of R. roxellana. Anthropogenic activities led to consistent changes in gut microbial diversity and function, while host age and genetic relatedness contributed to interindividual variations in the gut microbiota. These findings may contribute to the establishment of health assessment standards and the optimization of breeding conditions for captive R. roxellana populations.

Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper-responsiveness in asthmatic mice by altering intestinal microbiota.

Host immunity can influence the composition of the gut microbiota and consequently affect disease progression. Previously, we reported that a Mycobacterium vaccae vaccine could ameliorate allergic inflammation in asthmatic mice by regulating inflammatory immune processes. Here, we investigated the anti-inflammatory effects of M. vaccae on allergic asthma via gut microbiota modulation. An ovalbumin (OVA)-induced asthmatic murine model was established and treated with M. vaccae. Gut microbiota profiles were determined in 18 BALB/c mice using 16S rDNA gene sequencing and metabolomic profiling was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Mycobacterium vaccae alleviated airway hyper-reactivity and inflammatory infiltration in mice with OVA-induced allergic asthma. The microbiota of asthmatic mice is disrupted and that this can be reversed with M. vaccae. Additionally, a total of 24 differential metabolites were screened, and the abundance of PI(14:1(9Z)/18:0), a glycerophospholipid, was found to be correlated with macrophage numbers (r = 0.52, p = 0.039). These metabolites may affect chemokine (such as macrophage chemoattractant protein-1) concentrations in the serum, and ultimately affect pulmonary macrophage recruitment. Our data demonstrated that M. vaccae might alleviate airway inflammation and hyper-responsiveness in asthmatic mice by reversing imbalances in gut microbiota. These novel mechanistic insights are expected to pave the way for novel asthma therapeutic strategies.

Cross-talk between clathrin-dependent post-Golgi trafficking and clathrin-mediated endocytosis in Arabidopsis root cells.

Coupling of post-Golgi and endocytic membrane transport ensures that the flow of materials to/from the plasma membrane (PM) is properly balanced. The mechanisms underlying the coordinated trafficking of PM proteins in plants, however, are not well understood. In plant cells, clathrin and its adaptor protein complexes, AP-2 and the TPLATE complex (TPC) at the PM, and AP-1 at the trans-Golgi network/early endosome (TGN/EE), function in clathrin-mediated endocytosis (CME) and post-Golgi trafficking. Here, we utilized mutants with defects in clathrin-dependent post-Golgi trafficking and CME, in combination with other cytological and pharmacological approaches, to further investigate the machinery behind the coordination of protein delivery and recycling to/from the TGN/EE and PM in Arabidopsis (Arabidopsis thaliana) root cells. In mutants with defective AP-2-/TPC-dependent CME, we determined that clathrin and AP-1 recruitment to the TGN/EE as well as exocytosis are significantly impaired. Likewise, defects in AP-1-dependent post-Golgi trafficking and pharmacological inhibition of exocytosis resulted in the reduced association of clathrin and AP-2/TPC subunits with the PM and a reduction in the internalization of cargoes via CME. Together, these results suggest that post-Golgi trafficking and CME are coupled via modulation of clathrin and adaptor protein complex recruitment to the TGN/EE and PM.

Cognitive Effects Following Offline High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) in Healthy Populations: A Systematic Review and Meta-Analysis.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a commonly used form of rTMS to treat neuropsychiatric disorders. Emerging evidence suggests that 'offline' HF-rTMS may have cognitive enhancing effects, although the magnitude and moderators of these effects remain unclear. We conducted a systematic review and meta-analysis to clarify the cognitive effects of offline HF-rTMS in healthy individuals. A literature search for randomised controlled trials with cognitive outcomes for pre and post offline HF-rTMS was performed across five databases up until March 2022. This study was registered on the PROSPERO international prospective protocol for systematic reviews (PROSPERO 2020 CRD 42,020,191,269). The Risk of Bias 2 tool was used to assess the risk of bias in randomised trials. Separate analyses examined the cognitive effects of excitatory and inhibitory forms of offline HF-rTMS on accuracy and reaction times across six cognitive domains. Fifty-three studies (N = 1507) met inclusion criteria. Excitatory offline HF-rTMS showed significant small sized effects for improving accuracy (k = 46, g = 0.12) and reaction time (k = 44, g = -0.13) across all cognitive domains collapsed. Excitatory offline HF-rTMS demonstrated a relatively greater effect for executive functioning in accuracy (k = 24, g = 0.14). Reaction times were also improved for the executive function (k = 21, g = -0.11) and motor (k = 3, g = -0.22) domains following excitatory offline HF-rTMS. The current review was restricted to healthy individuals and future research is required to examine cognitive enhancement from offline HF-rTMS in clinical cohorts.

Baicalin - 2- ethoxyethyl ester alleviates renal fibrosis by inhibiting PI3K/AKT/NF-κB signaling pathway.

With the increasing incidence of chronic kidney disease (CKD), the development of safe and effective anti-renal fibrosis drugs is particularly urgent. Recently, Baicalin has been considered to have a renal protective effect, but its bioavailability is too low. Therefore, we synthesized baicalin-2-ethoxyethyl ester (BAE) by esterification of baicalin. We hope that this experiment will demonstrate the anti-renal fibrosis effect of BAE and explain its molecular mechanism. In this study, the chronic kidney injury model of SD rats was established by 5/6 nephrectomy, and BAE was given for 28 days. The results showed that after BAE treatment, the serum creatinine and urea nitrogen levels decreased significantly, and the pathological changes in kidneys were improved. In addition, RNA-seq analysis showed that the mechanism of BAE in relieving renal fibrosis was related to the ECM receptor, PI3K/AKT signaling pathway, and inflammatory reaction. The western blotting analysis confirmed that BAE could inhibit the expression of α-SMA, TGF-ß1, p-PI3K, p-AKT, p-IκBα, and NF-κB p65. We found that BAE can inhibit the inflammatory reaction and promote the degradation of the extracellular matrix by inhibiting the activation of the PI3K/AKT/NF-κB pathway, thus alleviating the symptoms of renal fibrosis in 5/6Nx rats, which revealed BAE was a potential compound to relieve renal fibrosis effect.

Production of recombinant HPV11/16 E6/E7-MBP-His6 fusion proteins and their potential to induce cytokine secretion by immune cells in peripheral blood.

Human papillomavirus (HPV) infection poses a significant threat to public health worldwide. Targeting the function of HPV E6 and E7 proteins and activating the host immune response against these proteins represent promising therapeutic strategies for combating HPV-related diseases. Consequently, the efficient production of soluble, high-purity E6 and E7 proteins is crucial for function and host immune response studies. In this context, we selected the pMCSG19 protein expression vector for Escherichia coli to produce soluble MBP-His6 tagged HPV11/16 E6/E7 proteins, achieving relatively high purity and yield. Notably, these proteins exhibited low toxicity to peripheral blood mononuclear cells (PBMCs) and did not compromise their viability. Additionally, the recombinant proteins were capable of inducing the secretion of multiple cytokines by immune cells in peripheral blood, indicating their potential to elicit immune responses. In conclusion, our study offers a novel approach for the production of HPV11/16 E6/E7 fusion proteins with relatively high purity and yield. The fusing HPV11/16 E6/E7 proteins to MBP-His6 tag may serve as a valuable method for large-scale protein production in future research endeavors.

First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

Lipid droplet accumulation in Wdr45-deficient cells caused by impairment of chaperone-mediated autophagic degradation of Fasn.

BACKGROUND: ß-Propeller protein-associated neurodegeneration (BPAN) is a genetic neurodegenerative disease caused by mutations in WDR45. The impairment of autophagy caused by WDR45 deficiency contributes to the pathogenesis of BPAN; however, the pathomechanism of this disease is largely unknown. Lipid dyshomeostasis is involved in neurogenerative diseases, but whether lipid metabolism is affected by Wdr45 deficiency and whether lipid dyshomeostasis contributes to the progression of BPAN are unclear. METHODS: We generated Wdr45 knockout SN4741 cell lines using CRISPR‒Cas9-mediated genome editing, then lipid droplets (LDs) were stained using BODIPY 493/503. Chaperone-mediated autophagy was determined by RT-qPCR and western blotting. The expression of fatty acid synthase (Fasn) was detected by western blot in the presence or absence of the lysosomal inhibitor NH4Cl and the CMA activator AR7. The interaction between Fasn and HSC70 was analyzed using coimmunoprecipitation (Co-IP) assay. Cell viability was measured by a CCK-8 kit after treatment with the Fasn inhibitor C75 or the CMA activator AR7. RESULTS: Deletion of Wdr45 impaired chaperone-mediated autophagy (CMA), thus leading to lipid droplet (LD) accumulation. Moreover, Fasn can be degraded via CMA, and that defective CMA leads to elevated Fasn, which promotes LD formation. LD accumulation is toxic to cells; however, cell viability was not rescued by Fasn inhibition or CMA activation. Inhibition of Fasn with a low concentration of C75 did not affect cell viability but decreases LD density. CONCLUSIONS: These results suggested that Fasn is essential for cell survival but that excessive Fasn leads to LD accumulation in Wdr45 knockout cells.

Association between cooking patterns and the prevalence of hyperlipidemia in Eastern China.

BACKGROUND: Hyperlipidemia is a major risk factor for many diseases. Previous studies have shown that diet is closely associated with hyperlipidemia. However, the relationship between cooking methods and hyperlipidemia remains unclear. The objective of this study was to identify the major cooking patterns existing in the Eastern Chinese population and evaluate their association with the prevalence of hyperlipidemia. METHODS: We interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when they prepare food at home or when eating out and regarding the prevalence of hyperlipidemia. Factor analysis, Chi-square tests, analysis of variance, and binary logistic regression analysis were used to identify the cooking patterns and analyze the characteristics of participants' categories of cooking patterns and the relationship between different cooking patterns and prevalence of hyperlipidemia. RESULTS: Three major cooking patterns were identified: Traditional Chinese, Bland (little or no oil is used to process the food), and High-temperature cooking patterns. After controlling for potential confounders, participants in the highest quartile of the Bland cooking pattern had lower odds of hyperlipidemia than those in the lowest quartile. Nevertheless, no significant associations were observed between the Traditional Chinese and High-temperature cooking patterns and the prevalence of hyperlipidemia. CONCLUSIONS: This study confirms the association between cooking patterns and the prevalence of hyperlipidemia and indicates that the Bland cooking pattern is associated with a reduced prevalence of hyperlipidemia.

Increased indexed proximal aortic diameter is a predictor of poor prognosis in maintenance hemodialysis patients.

Background: Recent studies have shown that the baseline values of absolute aortic root diameter (ARD) and indexed diameter are associated with all-cause mortality and cardiovascular events in the general population, even in the absence of aneurysmal aortic disease. However, there is limited available data on the association between ARD and prognosis in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Accordingly, the purpose of this study is to investigate the predictive value of ARD for all-cause mortality and cardiovascular events in this specific population.Methods: ARD was measured by echocardiography at the level of the sinuses of Valsalva at end diastole and indexed to body surface area (BSA). The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction and stroke. Cox proportional hazards models were conducted to evaluate the association between baseline ARD/BSA and clinical outcomes.Results: A total of 391 patients were included in this study. The primary endpoint occurred in 95 (24.3%) patients while the secondary endpoint occurred in 71 (18.2%) patients. Multivariate Cox regression analysis showed that ARD/BSA was an independent prognostic factor for all-cause mortality (HR, per 1-SD increase, 1.403; 95% CI, 1.118-1.761; p = 0.003) as well as MACE (HR, per 1-SD increase, 1.356; 95% CI, 1.037-1.772; p = 0.026).Conclusions: Our results show that ARD/BSA is predictive of all-cause mortality and MACE in MHD patients with ESRD and support the view that assessment of ARD/BSA may refine risk stratification and preventive strategies in this population.

The impact of regional policy implementation on the decoupling of carbon emissions and economic development.

The contradiction between economic growth demands and the achievement of the "dual-carbon" goals at the regional level is a pressing issue in China. As a significant economic and cultural center in the western region of China, the Guanzhong Plain urban agglomeration has experienced rapid development and urbanization, making it one of the key areas for national development. Therefore, greater attention should be given to carbon emission reduction in this region. This study focuses on the dataset from 2010 to 2019 in the Guanzhong Plain urban agglomeration, utilizing an input-output table to construct a carbon dioxide emission inventory. The research investigates the impact of regional classification on carbon emission levels within the Guanzhong Plain urban agglomeration. Furthermore, the Tapio decoupling analysis method is employed to assess the decoupling coefficient between regional economic development and carbon emissions. Additionally, the Theil index inequality analysis method is utilized to measure the disparities in per capita carbon emissions among cities within the region. Research findings indicate the following: 1) The regional classification of the Guanzhong Plain urban agglomeration is an effective policy for reducing regional carbon emissions and promoting carbon emissions reduction. 2) There exist variations in energy and industrial structures among cities within the urban agglomeration, necessitating tailored measures for low-carbon transition based on the specific circumstances of each city. 3) The regional classification of the urban agglomeration significantly influences the degree of decoupling between economic development and carbon emissions, with a trend towards stronger decoupling. The study suggests that cities within the Guanzhong Plain urban agglomeration should adopt measures aligned with their natural conditions and economic characteristics to achieve a low-carbon transition. Leveraging the regional cooperation capacity of the urban agglomeration is crucial to decouple economic development from carbon emissions, thereby promoting sustainable economic growth and environmental protection in a mutually beneficial manner.

A Prediction Rule for Occurrence of Chronic Thromboembolic Disease After Acute Pulmonary Embolism.

BACKGROUND: Occurrence of chronic thromboembolic disease (CTED) after 3 or 6 months of standard and effective anticoagulation is not uncommon in patients with acute pulmonary embolism (PE). To date, there has been no scoring model for the prediction of CTED occurrence. METHODS: A Prediction Rule for CTED (PRC) was established in the establishment cohort (n=1,124) and then validated in the validation cohort (n=211). Both original and simplified versions of the PRC score were provided by using different scoring and cut-offs. RESULTS: The PRC score included 10 items: active cancer (3.641; 2.338-4.944; p<0.001), autoimmune diseases (2.218; 1.545-2.891; p=0.001), body mass index >30 kg/m2 (2.186; 1.573-2.799; p=0.001), chronic immobility (2.135; 1.741-2.529; p=0.001), D-dimer >2,000 ng/mL (1.618; 1.274-1.962; p=0.005), PE with deep vein thrombosis (3.199; 2.356-4.042; p<0.001), previous venous thromboembolism (VTE) history (5.268; 3.472-7.064; p<0.001), thromboembolism besides VTE (4.954; 3.150-6.758; p<0.001), thrombophilia (3.438; 2.573-4.303; p<0.001), and unprovoked VTE (2.227; 1.471-2.983; p=0.001). In the establishment cohort, the sensitivity, specificity, Youden index (YI), and C-index were 85.5%, 79.7%, 0.652, and 0.821 (0.732-0.909) when using the original PRC score, whereas they were 87.9%, 74.6%, 0.625, and 0.807 (0.718-0.897) when using the simplified one, respectively (Kappa coefficient 0.819, p-value of McNemar's test 0.786). In the validation cohort, the sensitivity, specificity, YI, and C-index were 86.3%, 76.3%, 0.626, and 0.815 (0.707-0.923) when using the original PRC score, whereas they were 85.0%, 78.6%, 0.636, and 0.818 (0.725-0.911) when using the simplified one, respectively (Kappa coefficient 0.912, p-value of McNemar's test 0.937); both were better than that of the DASH score (72.5%, 69.5%, 0.420, and 0.621 [0.532-0.710]). CONCLUSIONS: A prediction score for CTED occurrence, termed PRC, predicted the likelihood of CTED occurrence after 3 or 6 months of standard anticoagulation in hospitalised patients with a diagnosis of acute PE.

Identifying Potential Sources of Phthalate Contamination in the Leaves of Stevia Rebaudiana (Bertoni) and the Development of Removal Technology.

Steviosides extracted from the leaves of the plant Stevia rebaudiana are increasingly used in the food industry as natural low-calorie sweeteners. Phthalates in food are often assumed to arise from food containers or packaging materials. Here, experiments were carried out to identify the potential sources of DMP, DBP, DIBP, and DEHP in the leaves of stevioside through investigation of their content in native stevioside tissues, soils, and associated agronomic materials. The results show that phthalate contamination was present in all the samples tested, and the influence of regional factors at the provincial level on the content of plasticizers in stevia leaves was not significant. Phthalates in stevia leaves can be absorbed into the plant body through leaves and roots. Using resin removal, the phthalate content in stevioside glycosides was reduced to less than 0.05 ppm, and some indicators were far lower than the limit standard in EU food.

Sarcopenia and treatment failure in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: The association between sarcopenia and treatment outcomes in inflammatory bowel disease (IBD) is currently a subject of controversy. METHODS: A systematic search was performed of PubMed, Embase, Web of Science, and the Cochrane Library for studies published until April 2023. The quality assessment of each included study was performed using the Newcastle-Ottawa Scale. RESULTS: Seventeen studies were included with 2,895 IBD patients. Sarcopenia exhibited an increased risk of treatment failure (OR=2.00, 95% CI: 1.43-2.79) and notably increased the need for surgery (OR=1.54,95%CI:1.06-2.23) as opposed to a pharmacologic treatment plan change (OR=1.19, 95% CI:0.71-2.01) among IBD patients. However, no significant association was found between sarcopenia and treatment failure in corticosteroid (OR=1.21, 95% CI: 0.55-2.64) or biologic agent (OR=1.65, 95% CI: 0.93-2.92) cohorts. Sarcopenia was also linked to elevated treatment failure risks in patients with Crohn's disease (OR=1.82, 95% CI: 1.15-2.90) and those diagnosed with ulcerative colitis (OR=2.55, 95% CI: 1.05-6.21), spanning both Asian (OR=1.88, 95% CI: 1.29-2.74) and non-Asian regions (OR=2.17, 95% CI: 1.48-3.18). CONCLUSIONS: Sarcopenia was considered a novel marker for use in clinical practice to predict treatment failure, specifically, the need for surgery in IBD patients. This distinct cohort necessitates clinical attention and tailored care strategies.

Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification.

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas. METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test. RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

[Association between the structure of intestinal flora and inflammatory response in children with sepsis: a prospective cohort study]. / è„“æ¯’ç—‡æ‚£å„¿è‚ é“èŒç¾¤ç»“æž„ä¸Žç‚Žç—‡ååº”ç›¸å ³æ€§çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response. METHODS: A prospective cohort study was conducted. The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group, and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group. The two groups were compared in terms of the distribution characteristics of intestinal flora, peripheral white blood cell count (WBC), C reactive protein (CRP), and cytokines, and the correlation of the relative abundance of fecal flora with WBC, CRP, and cytokines was analyzed. RESULTS: At the genus level, compared with the non-sepsis group, the sepsis group had significantly lower relative abundance of Akkermansia, Ruminococcus, and Alistipes and significantly higher relative abundance of Enterococcus, Streptococcus, and Staphylococcus (P<0.05). At the phylum level, Proteobacteria was the dominant phylum (37.46%) in the group of children with a score of ≤70 from the Pediatric Critical Illness Score (PICS), and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS (72.20% and 43.88%, respectively). At the genus level, among the 18 specimens, 5 had a relative abundance of >50% for a single flora. Compared with the non-sepsis group, the sepsis group had significant higher levels of WBC, CRP, interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (P<0.05). The Spearman's rank correlation analysis showed that at the genus level, the relative abundance of Ruminococcus, Alistipes, and Parasutterella in the sepsis group was negatively correlated with the levels of WBC, CRP, and IL-6 (P<0.05); the relative abundance of Enterococcus was positively correlated with the CRP level (P<0.01); the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6 (P<0.05); the relative abundance of Streptococcus was positively correlated with WBC (P<0.05). CONCLUSIONS: Intestinal flora disturbance is observed in children with sepsis, and its characteristics vary with the severity of the disease. The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.

Hepatic kinome atlas: An in-depth identification of kinase pathways in liver fibrosis of humans and rodents.

BACKGROUND AND AIMS: Resolution of pathways that converge to induce deleterious effects in hepatic diseases, such as in the later stages, have potential antifibrotic effects that may improve outcomes. We aimed to explore whether humans and rodents display similar fibrotic signaling networks. APPROACH AND RESULTS: We assiduously mapped kinase pathways using 340 substrate targets, upstream bioinformatic analysis of kinase pathways, and over 2000 random sampling iterations using the PamGene PamStation kinome microarray chip technology. Using this technology, we characterized a large number of kinases with altered activity in liver fibrosis of both species. Gene expression and immunostaining analyses validated many of these kinases as bona fide signaling events. Surprisingly, the insulin receptor emerged as a considerable protein tyrosine kinase that is hyperactive in fibrotic liver disease in humans and rodents. Discoidin domain receptor tyrosine kinase, activated by collagen that increases during fibrosis, was another hyperactive protein tyrosine kinase in humans and rodents with fibrosis. The serine/threonine kinases found to be the most active in fibrosis were dystrophy type 1 protein kinase and members of the protein kinase family of kinases. We compared the fibrotic events over four models: humans with cirrhosis and three murine models with differing levels of fibrosis, including two models of fatty liver disease with emerging fibrosis. The data demonstrate a high concordance between human and rodent hepatic kinome signaling that focalizes, as shown by our network analysis of detrimental pathways. CONCLUSIONS: Our findings establish a comprehensive kinase atlas for liver fibrosis, which identifies analogous signaling events conserved among humans and rodents.