Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Changes in technological innovation efficiency and influencing factors of listed textile and apparel companies research--Based on three-stage DEA with Tobit modeling.

The key to high-quality development in the textile and apparel industry lies in enhancing technological innovation and optimizing the efficiency of technological innovation. Based on data from 60 A-share listed companies in the textile and apparel sector in China from 2013 to 2022, this study employs a three-stage DEA model and the Malmquist index model to measure changes in technological innovation efficiency from static and dynamic perspectives. Additionally, it uses a Tobit model to analyze the impact and mechanisms of management and financial factors on technological innovation efficiency. The results indicate that: (1) Compared to the manufacturing industry and its sub-sectors, the overall technological innovation efficiency of listed textile and apparel companies was relatively low and showed a declining trend between 2013 and 2022; (2) Over the decade, the average total factor productivity of these listed companies increased by 1.7%, exhibiting a "W" shaped fluctuation, with technological progress, pure technical efficiency, and scale efficiency all showing weak improvement; (3) Management and financial factors significantly influence technological innovation efficiency. Specifically, employee quality, profitability, and operational capability are positively correlated with technological innovation efficiency and have long-term effectiveness, while firm age, management costs, equity concentration, development ability, and debt repayment capacity are negatively correlated with technological innovation efficiency; (4) Different types of enterprises show differences in the significance of management factors, while whether the same person holds both managerial positions significantly affects financial factors.

Revolutionizing early Alzheimer's disease and mild cognitive impairment diagnosis: a deep learning MRI meta-analysis.

BACKGROUND: The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. OBJECTIVE: A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. METHODS: A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. RESULTS: A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. CONCLUSION: Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

ANTECEDENTES: O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. OBJETIVO: Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. MéTODOS: Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. RESULTADOS: Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. CONCLUSãO: Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.

A new canthinone glycoside isolated from the root barks of Ailanthus altissima with NO inhibitory activity.

One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.

Polyketides from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Seven polyketides, including an undescribed depsidone (1) and six previously reported 3,6,8-trihydroxy-1-methylxanthone (2), 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3), methyl3-chloro-6-hydroxy-2-(4-hy-droxy-2-methoxy-6-methylphenoxy)-4- methoxybenzoate (4), xylarianin A (5), 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydro-xymethyl-2-cyclohexen-1-one (6) and alternariol (7), have been isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. The structure of compound 1 was elucidated by extensive spectroscopic analysis and X-ray crystallography. Furthermore, all the compounds were evaluated their cytotoxic activities, and compounds 1 and 7 showed weak cytotoxicity against two cell lines Vero and A549 with IC50 values ranging from 95.6 and 296.5 µM, relative to the positive control Etoposide phosphate with IC50 values of 24.5 and 18.7 µM, respectively.

Systematic Mendelian Randomization Exploring Druggable Genes for Hemorrhagic Strokes.

Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.

Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart-brain axis.

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.

Yishen Tongbi decoction attenuates inflammation and bone destruction in rheumatoid arthritis by regulating JAK/STAT3/SOCS3 pathway.

Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear. Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS). Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-ß (TGF-ß). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated. Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.

Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

[Two new pinophol derivatives from endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal].

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).

[Study on anti-inflammatory activity of phenolic acids from Leucas ciliata].

The chemical constituents from Leucas ciliata belonging to Leucas genus in Lamiaceae were systematically explored by silica gel column chromatography, ODS column chromatography, Sephadex LH-20 gel column chromatography, and preparative high performance liquid chromatography, and seventeen phenolic acids were isolated. The chemical structures of the compounds were identified by their physicochemical properties, spectroscopic data, and literature. They were 4-hydroxyphenethyl ethyl succinate(1), 4-hydroxyphenethyl methyl succinate(2), 2-(4-hydroxyphenyl) ethyl acetate(3), p-hydroxyphenylethyl anisate(4), cassia cis-trans diphenylpropanoid(5), p-coumaric acid(6), 3,4-dihydroxybenzenepropionic acid methyl ester(7), caffeic acid(8), trans-p-hydroxyl ethyl cinnamate(9), methyl p-hydroxybenzeneacetate(10), 4-hydroxyphenethyl alcohol(11), syringic acid(12), vanillin(13), protocatechuic acid(14), salicylic acid(15), p-hydroxybenzaldehyde(16), and diorcinol(17). Among them, compound 1 was new, and compounds 2-10, 12, 14, and 16-17 were isolated from the plants belonging to Leucas genus for the first time. All compounds were obtained from L. ciliata for the first time. The anti-inflammatory activity of compounds 1-17 on NO production in lipopolysaccharide(LPS)-induced mouse leukemia cells of monocyte macrophage(RAW264. 7) cells was evaluated. The results showed that compounds 5, 7, and 9 exhibited significant anti-inflammatory activity, with IC50values of(10. 14±0. 36)-(21. 17±0. 11) µmol·L~(-1).

The Balloon Catheter Method and the End-hole Catheter Method in the Measurement of Hepatic Venous Pressure Gradient: a Comparative Study.

OBJECTIVE: This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients. METHODS: From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed. RESULTS: The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%). CONCLUSION: HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method.

Systematic evaluation of the meat qualities of free-range chicken (Xuan-Zhou) under different ages explored the optimal slaughter age.

Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

[Mechanism of Huangqin Qingre Chubi Capsules in improving rheumatoid arthritis based on METTL3-SFRP4/Wnt/ß-catenin pathway].

The effect and mechanism of Huangqin Qingre Chubi Capsules(HQC) on rheumatoid arthritis(RA) were studied.Seventy male SPF rats were randomly divided into normal group, model group, low-(0. 18 g·kg~(-1)), middle-(0. 36 g·kg~(-1)), and high-(0. 72 g·kg~(-1)) dose groups of HQC, methotrexate group(MTX, 0. 75 mg·kg~(-1)), and negative control group(NC group, model +saline). Adjuvant arthritis fibroblast-like synoviocytes(AA-FLS) were divided into normal group, model group, low-, middle-, and high-dose groups of HQC, and negative control group. RT-qPCR and Western blot were used to detect the m RNA and protein expressions of METTL3, SFRP4, ß-catenin, CCND1, c-Myc, MMP3, and fibronectin. The protein expression of MMP3 and ß-catenin was detected by immunofluorescence. The gene expression level of METTL3 on AA-FLS was knocked down to further examine the expression of each gene. ELISA measured the levels of IL-1ß, IL-6, and IL-8. The results showed that compared with the normal group, rats in the model group found redness and swelling in their limbs and significantly increased joint swelling. Compared with the model group, the joint swelling degree of each treatment group significantly decreased(P<0. 05). The paw retraction threshold and body weight mass index both significantly increased(P<0. 05). METTL3 was highly expressed on AA and negatively correlated with the expression of SFRP4. After treatment, the m RNA and protein expression of METTL3, ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 were significantly decreased on AA-FLS(P< 0. 05). Compared with the model group, knocking down METTL3 resulted in reduced m RNA and protein expression of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3(P< 0. 05). At the same time, the m RNA and protein expressions of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 in the HQC+METTL3 knockdown group were significantly lower than those in the METTL3 knockdown group(P<0. 05). HQC could reduce the levels of IL-1ß, IL-6, and IL-8 to varying degrees(P<0. 05). The results indicate that HQC has a significant improvement effect on arthritis in AA rats. The expression of METTL3 is significantly increased in synovial tissue and AA-FLS of AA rats, which may be a potential target for the diagnosis and treatment of RA. HQC improves RA through the METTL3-SFRP4/Wnt/ß-catenin signaling pathway and has significant antiinflammatory and anti-rheumatic effects.

Aqueous alternating electrolysis prolongs electrode lifespans under harsh operation conditions.

It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.

Synthesis of oligosaccharides from terminal B. pertussis LPS pentasaccharide and definition of the minimal epitope recognized by anti-pertussis antibodies.

Pertussis vaccines have been very effective in controlling whooping-cough epidemics but are ineffective in controlling circulation in older children and adults, thus facilitating the onset of future outbreaks. Antibodies against the lipopolysaccharide could reduce the carriage of the bacteria, its circulation, and transmission. The oligosaccharide fragments from the lipopolysaccharide may become a potential complement to existing vaccines in the form of protein glycoconjugates. An important step in the development of this type of vaccine is defining the minimal oligosaccharide epitope recognized by B. pertussis anti-lipopolysaccharide antibodies. This paper describes the complete synthesis of oligosaccharides containing two to five monosaccharide units corresponding to the pentasaccharide at the nonreducing end of the lipooligosaccharide and their recognition by mice and rabbit antibodies elicited against whole-cell B. pertussis. For the first time, we report that the terminal disaccharide, α-D-GlcNAcp-(1 → 4)-(2,3-di-NAc)-D-ManAp acid is the minimal structure recognized by antibodies induced by B. pertussis.