Constructing and validating a risk model based on neutrophil-related genes for evaluating prognosis and guiding immunotherapy in colon cancer.

BACKGROUND: Colon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients. METHODS: We first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues. RESULTS: We established and validated a risk scoring model based on neutrophil-related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high-risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy. CONCLUSIONS: The low-risk group showed better OS and PFS than the high-risk group in the neutrophil-related gene-based risk model. Patients in the high-risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

The Promising Seesaw Relationship Between Activity and Stability of Ru-Based Electrocatalysts for Acid Oxygen Evolution and Proton Exchange Membrane Water Electrolysis.

The development of electrocatalysts that are not reliant on iridium for efficient acid-oxygen evolution is a critical step towards the proton exchange membrane water electrolysis (PEMWE) and green hydrogen industry. Ruthenium-based electrocatalysts have garnered widespread attention due to their remarkable catalytic activity and lower commercial price. However, the challenge lies in balancing the seesaw relationship between activity and stability of these electrocatalysts during the acid-oxygen evolution reaction (OER). This review delves into the progress made in Ru-based electrocatalysts with regards to acid OER and PEMWE applications. It highlights the significance of customizing the acidic OER mechanism of Ru-based electrocatalysts through the coordination of adsorption evolution mechanism (AEM) and lattice oxygen oxidation mechanism (LOM) to attain the ideal activity and stability relationship. The promising tradeoffs between the activity and stability of different Ru-based electrocatalysts, including Ru metals and alloys, Ru single-atomic materials, Ru oxides, and derived complexes, and Ru-based heterojunctions, as well as their applicability to PEMWE systems, are discussed in detail. Furthermore, this paper offers insights on in situ control of Ru active sites, dynamic catalytic mechanism, and commercial application of PEMWE. Based on three-way relationship between cost, activity, and stability, the perspectives and development are provided.

Dopamine ß-hydroxylase shapes intestinal inflammation through modulating T cell activation.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined. METHODS: CD4+CD45RBhighT cell adoptive transfer, and 2,4-dinitrobenzene sulfonic acid (DNBS) or dextran sodium sulfate (DSS)-induced colitis were collectively conducted to uncover the effects of DBH inhibition by nepicastat, a DBH inhibitor, in mucosal ulceration, disease severity, and T cell function. RESULTS: Inhibition of DBH by nepicastat triggered therapeutic effects on T cell adoptive transfer induced chronic mouse colitis model, which was consistent with the gene expression of DBH in multiple cell populations including T cells. Furthermore, DBH inhibition dramatically ameliorated the disease activity and colon shortening in chemically induced acute and chronic IBD models, as evidenced by morphological and histological examinations. The reshaped systemic inflammatory status was largely associated with decreased pro-inflammatory mediators, such as TNF-α, IL-6 and IFN-γ in plasma and re-balanced Th1, Th17 and Tregs in mesenteric lymph nodes (MLNs) upon colitis progression. Additionally, the conversion from dopamine (DA) to norepinephrine (NE) was inhibited resulting in increase in DA level and decrease in NE level and DA/NE showed immune-modulatory effects on the activation of immune cells. CONCLUSION: Modulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation.

Roles of vaporization and thermal decomposition in the dynamic evolution of laser-induced bubble on the surface of a submerged metal plate.

This paper aims to explain when the vaporization or thermal decomposition prevails during laser-induced bubble growth and how they influence bubble morphology. Bubbles were generated by irradiating a 304 stainless steel plate submerged in degassed water using millisecond lasers with a pulse width of 0.4 ms and powers of 1.6 kW and 3.2 kW, respectively. The dynamic evolution of bubbles was recorded by a high-speed camera. Moreover, the numerical models were developed to obtain a vaporization model and a decomposition model by incorporating the source terms due to the vaporization and decomposition mass fluxes into the governing equations, respectively. The simulated dynamic bubble evolution is consistent with the experimental results. When the laser power is 1.6 kW, a thin-layer bubble is formed, which gradually shrinks and eventually disappears after the laser stops irradiating. When the laser power is 3.2 kW, a spherical bubble is formed, and its volume decreases significantly after the laser stops irradiating. Subsequently, it remains relatively stable during the observation period. The fundamental reason for the difference between the bubble morphologies obtained from the vaporization model and the decomposition model lies in the presence of a condensation zone in the gas phase. When water vaporization or thermal decomposition dominates, the temperatures obtained from the models align with the decomposition ratios at varying temperatures reported in the literature. Our findings are significant for understanding the dynamic behavior of bubbles, with implications for various laser processing underwater.

A single-center, multi-factor, retrospective study to improve the diagnostic accuracy of primary prostate cancer using [68Ga]Ga-PSMA-11 total-body PET/CT imaging.

PURPOSE: To improve the diagnostic accuracy of initial detection in patients with suspected primary prostate cancer (PCa). METHODS: Eighty-four patients who underwent Gallium-68-labeled prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) total-body positron emission tomography/computed tomography (PET/CT) imaging before treatment in our department were enrolled. The maximum standard uptake value (SUVmax) of the prostate (SUVmax-PSMA), liver (SUVmax-PSMA-L), and mediastinal blood pool (SUVmax-PSMA-M) was measured using [68Ga]Ga-PSMA-11 total-body PET/CT imaging. The [68Ga]Ga-PSMA-11 derived metabolic tumor volume (MTV), the total lesion (TLP), and the cross-sectional areas of focal concentration in the prostate (CAP) were also determined. Besides, the prostate-specific antigen (PSA) levels and the above imaging characteristics were analyzed using receiver operating characteristic curves to identify the cutoff value to improve the diagnostic accuracy of suspected PCa. Finally, a multivariate regression analysis was conducted to discover the independent predictor to improve the diagnostic accuracy on [68Ga]Ga-PSMA-11 total-body imaging. RESULTS: There was no significant difference between the PCa and Non-PCa groups in age, height, weight, injected dose, except for the PSA levels, the SUVmax-PSMA, TLP, MTV, and CAP. Besides, the SUVmax-PSMA-T/L and SUVmax-PSMA-T/M derived from SUVmax-PSMA were both significantly different. In addition, the areas under the curve of PSA levels, SUVmax-PSMA, SUVmax-PSMA-T/L, SUVmax-PSMA-T/M, TLP, MTV, and CAP to predict PCa on [68Ga]Ga-PSMA-11 imaging were 0.620 (95% confidence interval (CI) 0.485-0.755), 0.864 (95% CI 0.757-0.972), 0.819 (95% CI 0.704-0.935), 0.876 (95% CI 0.771-0.980), 0.845 (95% CI 0.741-0.949), 0.820 (95% CI 0.702-0.938), 0.627 (95% CI 0.499-0.754), respectively. However, a multivariate regression analysis showed that SUVmax-PSMA was an independent predictor, with a cutoff value of 11.5 and an odds ratio of 1.221. CONCLUSION: The SUVmax-PSMA with a cutoff value of 11.5 was an independent predictor to improve the diagnostic accuracy of PCa on [68Ga]Ga-PSMA-11 total-body imaging.

The Effect of Local Steroid Administration on Idiopathic Granulomatous Mastitis: A Systematic Review andMeta-Analysis.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast disease. Corticosteroids and surgery are the primary treatment options, and a growing number of publications have shown the effectiveness of local steroid administration (intralesional injection and topical corticosteroids). However, less is known about the specific details and effects of this treatment approach. The purpose of this meta-analysis was to summarize the details and evaluate the efficacy of local steroid administration for IGM. METHODS: The PubMed, Embase, Cochrane Library, and SinoMed databases were systematically searched from inception to July 2023 to identify relevant randomized controlled trials. The quality of the included studies was assessed, and meta-analysis and subgroup analysis were conducted to obtain the pooled effect sizes of the outcomes of interest. RESULTS: Eight trials comprising 613 patients were included. Local steroid administration included intralesional injection and topical steroid ointment, and control groups were mainly given systemic therapy (oral steroid) and surgical treatment. The meta-analysis showed that local steroid administration had a significant effect on the response rate (risk ratio [RR] = 1.35, 95% CI = [1.14-1.59], P = 0.0004). The incidence of side effects was also lower than that of systemic treatment (RR = 0.24, 95% CI = [0.13-0.43], P＜0.0001). There was no difference in the recurrence rate (RR = 0.8, 95% CI = [1.42-1.51], P = 0.48). CONCLUSIONS: Local steroid administration can increase the RR and decrease the incidence of side effects for IGM patients. There is no significant difference in the recurrence rate between the local steroid administration group and the control group. Further studies are needed to identify the effect in different stages and among pregnant women.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism. METHODS: First, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4-10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity. CONCLUSIONS: A new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

Adsorption and activation of small molecules on boron nitride catalysts.

Hexagonal boron nitride possesses a unique layered structure, high specific surface area and similar electronic properties as graphene, which makes it not only a promising catalyst support, but also a highly effective metal-free catalyst in the booming field of green chemistry. Reactions involving small molecules (e.g., oxygen, low carbon alkanes, nitrogen and carbon dioxide) have always been a hot topic in catalytic research, especially associated with the adsorption and activation regime of different forms of small molecules on catalysts. In this review, we have investigated the adsorption of different small molecules and the relevant activation mechanisms of four typical chemical bonds (OO, C-H, NN, CO) on hexagonal boron nitride. Recent progress on approaches adopted to enhance the activation capacity such as doping, defect engineering and heterostructuring are summarized, highlighting the potential applications of nonmetallic hexagonal boron nitride catalysts in various reactions. This comprehensive investigation offers a reference point for the enhanced mechanistic understanding and future design of effective and sustainable catalytic systems based on boron nitride.

Factors Associated with Dialysis Initiation in Patients with Predialysis Arteriovenous Fistula.

INTRODUCTION: A large proportion of patients initiated hemodialysis with a central vein catheter rather than a permanent vascular access which was recommended by guidelines. One major barrier was the paucity of evidence regarding the optimal timing of vascular access creation in predialysis patients. METHODS: Our study prospectively enrolled 300 patients undergoing predialysis arteriovenous fistula (AVF) creation in our center from 2015 to 2018. Cox proportional hazard regression was performed to identify which demographic and clinical factors were associated with the initiation of hemodialysis after AVF surgery. A receiver operating characteristic area under the curve (AUC) was used to assess the predictive power of preoperative factors for the likelihood of hemodialysis initiation. RESULTS: Overall, 163 (54.3%), 214 (71.3%), and 275 (91.7%) patients initiated hemodialysis within 3 months, 6 months, and 1 year, respectively, after AVF creation. The median time between AVF creation and hemodialysis start was 71.5 days. Using multivariate Cox regression analysis, three factors were associated with hemodialysis initiation within 1 year: serum phosphorus (HR = 1.407, p = 0.021), diabetic kidney disease (DKD) (HR = 1.429, p = 0.039), and cystatin C (HR = 1.179, p = 0.009). Cystatin C alone had a moderate predictive value for dialysis initiation (AUC = 0.746; p < 0.001), whereas the full model had a higher predictive value (AUC = 0.800; p < 0.001). CONCLUSION: DKD, serum cystatin C, and phosphorus at access surgery were associated with hemodialysis initiation within 1 year of the predialysis AVF creation. Our findings provide a basis for a more customized approach to planning AVF placement in patients with chronic kidney disease.

Nomogram to Estimate the Risk of Chronic Kidney Disease-associated Pruritus in Patients with End-Stage Renal Disease Undergoing Peritoneal Dialysis: Model Development and Validation Study.

INTRODUCTION: Chronic kidney disease associated pruritus (CKD-aP) frequently occurs in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) and presents a therapeutic challenge to physicians owing to the diversity of its pathogenesis. Herein, we developed and validated a nomogram model for individualized risk estimation of CKD-aP and investigate the possible causes of CKD-aP in PD patients. METHODS: We retrospectively screened patients with CKD-aP who underwent PD between 2021 and 2023 at the First Affiliated Hospital of Xi'an Jiaotong University Peritoneal Dialysis Center. Nomograms for each outcome were computed from multivariate logistic regression models with the least absolute shrinkage and selection operator regression and univariate logistic regression for variable selection. The discriminative ability was estimated by Harrell's C-index, and the accuracy was assessed graphically with a calibration curve plot. Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. Decision curve analysis was used to assess the model's clinical usefulness. RESULTS: In all, a total of 487 patients were entered in the analysis, including 325 in the development cohort and 162 in the validation cohort. The final nomogram incorporated four variables: age, interleukin-6, hemoglobin, residual urine volume, and renal Kt/V. The C-index of the model was 0.733 (95% CI 0.679-0.787), and the calibration curve was a straight line with a slope close to 1. Both internal and external validations confirmed the model's good performance, with C-index of 0.725 (95% CI 0.662-0.774) and 0.706 (95% CI 0.623-0.789), respectively. Decision curve analysis showed that the nomogram had good clinical benefits. CONCLUSION: Our study proposes a nomogram model for CKD-aP risk assessment in ESRD patients with PD. This nomogram might help in clinical decision-making and evidence-based selection of therapy.

The developmental characteristics of proactive and reactive aggression in late childhood: The effect of parental control.

Previous research has confirmed that parental control is related to children's aggressive behavior. However, few studies have focused on proactive and reactive aggression to distinguish the different effects of parental psychological and behavioral control. Moreover, additional longitudinal evidence is needed to understand these links. In the current paper, a three-wave longitudinal study was conducted to examine the developmental characteristics of proactive and reactive aggression and the role of parental control in China. A total of 484 4th- and 7th-grade students participated at wave 1 (51.65% in 4th-grade, Mage = 11.66 ± 1.52 years), 465 students (52.04% in 4th-grade) at wave 2, and 447 children (51.90% in 4th-grade) at wave 3. The results showed that: (1) Proactive aggression in late childhood remained stable overall, while reactive aggression displayed a clear upward trend. (2) In proactive aggression, boys and girls had a consistent developmental trend. The initial level of boys was higher than that of girls. In reactive aggression, the growth rate was inversely associated with their initial level and the initial level of boys in 7th-grade was significantly higher than that of girls. (3) Both parental psychological and behavioral control positively predicted students' reactive aggression in 4th- and 7th-grade, whereas only parental behavioral control positively predicted proactive aggression in 7th-grade students, with no gender differences.

Two-dimensional Cu Plates with Steady Fluid Fields for High-rate Nitrate Electroreduction to Ammonia and Efficient Zn-Nitrate Batteries.

Nitrate electroreduction reaction (eNO3 -RR) to ammonia (NH3) provides a promising strategy for nitrogen utilization, while achieving high selectivity and durability at an industrial scale has remained challenging. Herein, we demonstrated that the performance of eNO3 -RR could be significantly boosted by introducing two-dimensional Cu plates as electrocatalysts and eliminating the general carrier gas to construct a steady fluid field. The developed eNO3 -RR setup provided superior NH3 Faradaic efficiency (FE) of 99 %, exceptional long-term electrolysis for 120 h at 200 mA cm-2, and a record-high yield rate of 3.14 mmol cm-2 h-1. Furthermore, the proposed strategy was successfully extended to the Zn-nitrate battery system, providing a power density of 12.09 mW cm-2 and NH3 FE of 85.4 %, outperforming the state-of-the-art eNO3 -RR catalysts. Coupled with the COMSOL multiphysics simulations and in situ infrared spectroscopy, the main contributor for the high-efficiency NH3 production could be the steady fluid field to timely rejuvenate the electrocatalyst surface during the electrocatalysis.

Generation of an Aptamer Targeting Receptor-Type Tyrosine-Protein Phosphatase F.

Cell-SELEX is a powerful tool to generate aptamers that specifically bind the native molecules on living cells. Here, we report an aptamer ZAJ4a generated by cell-SELEX. The molecular target of ZAJ4a was pulled down by the enriched cell-SELEX pool and identified to be the receptor-type tyrosine-protein phosphatase F (PTPRF) through a stable isotope labeling using amino acids in cell culture (SILAC)-based quantitative proteomic method. ZAJ4a showed high binding affinity with nanomolar range to cancer cells expressing PTPRF. Meanwhile, PTPRF was proven to highly express on several cancer cell lines using ZAJ4a as a molecular probe and to highly express in many kinds of cancer samples using gene expression profiling interactive analysis (GEPIA2) from the TCGA and GTEx databases. These results indicate that the aptamer generated by cell-SELEX showed good specificity at the molecular level. This cell-SELEX and target identification strategies show great potential for identifying biomarkers on the cell surface.

Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.

BACKGROUND: The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS: This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS: GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS: This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .

The spatiotemporal matching pattern of Ezrin/Periaxin involved in myoblast differentiation and fusion and Charcot-Marie-Tooth disease-associated muscle atrophy.

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.

Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

Surface-Stabilized CsPbI3 Nanocrystals with Tailored Organic Polymer Ligand Binding.

Perovskite nanocrystals (NCs) exhibit attractive photophysical properties by combining the excellent optoelectronic properties of bulk perovskites with the strong quantum confinement effect at the nanoscale. However, CsPbI3 NCs easily transform into a non-perovskite phase because of the ionic lattice and dynamic ligand binding. Herein, stable black-phase CsPbI3 NCs capped with a new organic ligand, HO-PS-N3 (HOPS), which consists of a polystyrene segment with hydroxyl and azide end groups, are reported. This organic polymer ligand passivated the surface defects and enhanced the stability of CsPbI3 NCs by exposing the linking hydrophobic polystyrene segment. Consequently, the optimized CsPbI3 NCs exhibit significantly improved resistance to moisture or light and maintained 70 % of the original luminous intensity after immersion in water for two months. The theoretical results revealed that the binding energy of the HOPS ligand on the surface of the CsPbI3 NCs is higher than that of the commonly used oleic acid, alleviating the defects-induced degradation during purification. Thus, surface-stabilized CsPbI3 NCs are beneficial for a broad range of optoelectronic applications.

Purinoceptor: a novel target for hypertension.

Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. A1R, A2AR, A2BR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.

Synthesis of a water-soluble naphthalene-based macrocycle and its host-guest properties.

Reported here is the synthesis of a naphthalene-based macrocycle bearing anionic carboxylato groups on the rims along with its complexation with cationic guests in aqueous media. The macrocycle could strongly bind guests in a molecular clip model with association constants of 106-107 M-1.