Boosted hydrogen evolution kinetics of heteroatom-doped carbons with isolated Zn as an accelerant.

Carbon-based single-atom catalysts, a promising candidate in electrocatalysis, offer insights into electron-donating effects of metal center on adjacent atoms. Herein, we present a practical strategy to rationally design a model catalyst with a single zinc (Zn) atom coordinated with nitrogen and sulfur atoms in a multilevel carbon matrix. The Zn site exhibits an atomic interface configuration of ZnN4S1, where Zn's electron injection effect enables thermal-neutral hydrogen adsorption on neighboring atoms, pushing the activity boundaries of carbon electrocatalysts toward electrochemical hydrogen evolution to an unprecedented level. Experimental and theoretical analyses confirm the low-barrier Volmer-Tafel mechanism of proton reduction, while the multishell hollow structures facilitate the hydrogen evolution even at high current intensities. This work provides insights for understanding the actual active species during hydrogen evolution reaction and paves the way for designing high-performance electrocatalysts.

Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

BACKGROUNDS & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.

BACKGROUND & AIMS: Endoplasmic reticulum (ER) stress of hepatocytes plays a causative role in non-alcoholic fatty liver disease (NAFLD). Reduced expression of hepatic nuclear factor 4α (HNF4α) is a critical event in the pathogenesis of NAFLD and other liver diseases. Whether ER stress regulates HNF4α expression remains unknown. The aim of this study was to delineate the machinery of HNF4α protein degradation and explore a therapeutic strategy based on protecting HNF4α stability during NAFLD progression. METHODS: Correlation of HNF4α and tribbles homologue 3 (TRIB3), an ER stress sensor, was evaluated in human and mouse NAFLD tissues. RNA-sequencing, mass spectrometry analysis, co-immunoprecipitation, in vivo and in vitro ubiquitination assays were used to elucidate the mechanisms of TRIB3-mediated HNF4α degradation. Molecular docking and co-immunoprecipitation analyses were performed to identify a cell-penetrating peptide that ablates the TRIB3-HNF4α interaction. RESULTS: TRIB3 directly interacts with HNF4α and mediates ER stress-induced HNF4α degradation. TRIB3 recruits tripartite motif containing 8 (TRIM8) to form an E3 ligase complex that catalyzes K48-linked polyubiquitination of HNF4α on lysine 470. Abrogating the degradation of HNF4α attenuated the effect of TRIB3 on a diet-induced NAFLD model. Moreover, the TRIB3 gain-of-function variant p.Q84R is associated with NAFLD progression in patients, and induces lower HNF4α levels and more severe hepatic steatosis in mice. Importantly, disrupting the TRIB3-HNF4α interaction using a cell-penetrating peptide restores HNF4α levels and ameliorates NAFLD progression in mice. CONCLUSIONS: Our findings unravel the machinery of HNF4α protein degradation and indicate that targeting TRIB3-TRIM8 E3 complex-mediated HNF4α polyubiquitination may be an ideal strategy for NAFLD therapy. IMPACT AND IMPLICATIONS: Reduced expression of hepatic nuclear factor 4α (HNF4α) is a critical event in the pathogenesis of NAFLD and other liver diseases. However, the mechanism of HNF4α protein degradation remains unknown. Herein, we reveal that TRIB3-TRIM8 E3 ligase complex is responsible for HNF4α degradation during NAFLD. Inhibiting the TRIB3-HNF4α interaction effectively stabilized HNF4α protein levels and transcription factor activity in the liver and ameliorated TRIB3-mediated NAFLD progression. Our findings demonstrate that disturbing the TRIM8-TRIB3-HNF4α interaction may provide a novel approach to treat NAFLD and even other liver diseases by stabilizing the HNF4α protein.

Ultrafine Pt Nanoparticles on Defective Tungsten Oxide for Photocatalytic Ethylene Synthesis.

The selective conversion of ethane (C2H6) to ethylene (C2H4) under mild conditions is highly wanted, yet very challenging. Herein, it is demonstrated that a Pt/WO3-x catalyst, constructed by supporting ultrafine Pt nanoparticles on the surface of oxygen-deficient tungsten oxide (WO3-x) nanoplates, is efficient and reusable for photocatalytic C2H6 dehydrogenation to produce C2H4 with high selectivity. Specifically, under pure light irradiation, the optimized Pt/WO3-x photocatalyst exhibits C2H4 and H2 yield rates of 291.8 and 373.4 µmol g-1 h-1, respectively, coupled with a small formation of CO (85.2 µmol g-1 h-1) and CH4 (19.0 µmol g-1 h-1), corresponding to a high C2H4 selectivity of 84.9%. Experimental and theoretical studies reveal that the vacancy-rich WO3-x catalyst enables broad optical harvesting to generate charge carriers by light for working the redox reactions. Meanwhile, the Pt cocatalyst reinforces adsorption of C2H6, desorption of key reaction species, and separation and migration of light-induced charges to promote the dehydrogenation reaction with high productivity and selectivity. In situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory calculation expose the key intermediates formed on the Pt/WO3-x catalyst during the reaction, which permits the construction of the possible C2H6 dehydrogenation mechanism.

miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.

BACKGROUND: The activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis. However, its role in liver cirrhosis has not been reported. METHODS: Real-time PCR was used to detect miR-541 expression in the liver tissues and sera of liver cirrhosis patients and in the human LX-2. Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the activation of LX-2. Bioinformatics analysis and a luciferase reporter assay were conducted to investigate the target gene of miR-541. RESULTS: miR-541 was downregulated in the tissues and sera of patients with liver cirrhosis, which was exacerbated by deteriorating disease severity. Importantly, the lower expression of miR-541 was associated with more episodes of complications including ascites and hepatic encephalopathy, a shorter overall lifespan, and decompensation-free survival. Moreover, multivariate Cox's regression analysis verified lower serum miR-541 as an independent risk factor for liver-related death in cirrhotic patients (HR = 0.394; 95% CI: 0.164-0.947; P = 0.037). miR-541 was also decreased in LX-2 cells activated by TGF-ß and the overexpression of miR-541 inhibited the proliferation, activation and hydroxyproline secretion of LX-2 cells. JAG2 is an important ligand of Notch signaling and was identified as a direct target gene of miR-541. The expression of JAG2 was upregulated in the liver tissues of cirrhotic patients and was inversely correlated with miR-541 levels. A rescue assay further confirmed that JAG2 was involved in the function of miR-541 when regulating LX-2 activation and Notch signaling. CONCLUSIONS: Dysregulation of miR-541/JAG2 axis might be a as a new mechanism of liver fibrosis, and miR-541 could serve as a novel non-invasive biomarker and therapeutic targets for liver cirrhosis.

Rifaximin treatment shapes a unique metagenome-metabolism network in patients with decompensated cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis face poor prognosis and increased mortality risk. Rifaximin, a non-absorbable antibiotic, has been shown to have beneficial effects in preventing complications and improving survival in these patients. However, the underlying mechanisms of rifaximin's effects remain unclear. METHODS: We obtained fecal samples from decompensated cirrhotic patients undergoing rifaximin treatment and controls, both at baseline and after 6 months of treatment. Shotgun metagenome sequencing profiled the gut microbiome, and untargeted metabolomics analyzed fecal metabolites. Linear discriminant and partial least squares discrimination analyses were used to identify differing species and metabolites between rifaximin-treated patients and controls. RESULTS: Forty-two patients were enrolled and divided into two groups (26 patients in the rifaximin group and 16 patients in the control group). The gut microbiome's beta diversity changed in the rifaximin group but remained unaffected in the control group. We observed 44 species with reduced abundance in the rifaximin group, including Streptococcus_salivarius, Streptococcus_vestibularis, Haemophilus_parainfluenzae, etc. compared to only four in the control group. Additionally, six species were enriched in the rifaximin group, including Eubacterium_sp._CAG:248, Prevotella_sp._CAG:604, etc., and 14 in the control group. Furthermore, rifaximin modulated different microbial functions compared to the control. Seventeen microbiome-related metabolites were altered due to rifaximin, while six were altered in the control group. CONCLUSION: Our study revealed distinct microbiome-metabolite networks regulated by rifaximin intervention in patients with decompensated cirrhosis. These findings suggest that targeting these specific metabolites or related bacteria might be a potential therapeutic strategy for decompensated cirrhosis.

Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

Efficacy of Core Muscle Exercise Combined with Interferential Therapy in Alleviating Chronic Low Back Pain in High-Performance Fighter Pilots: A Randomized Controlled Trial.

BACKGROUND: Chronic low back pain (LBP) related to flight is a prevalent health issue in military aviation, impacting pilots. The objective of this investigation was to ascertain if the application of core muscle training in conjunction with interferential current (IFC) therapy results in a reduction in pain severity and associated disability, consequently enhancing core muscle functionality in Chinese Air Force high-performance fighter pilots experiencing chronic LBP. METHODS: Fifty-three fighter pilots with chronic LBP were randomized into 3 groups: a core muscle exercise combined with IFC group (CG, n = 19), a core muscle exercise group (EG, n = 19), and an IFC group (IG, n = 15). The three groups underwent therapeutic intervention 5 times a week for 12 weeks. The primary outcomes were pain intensity, Oswestry Disability Index (ODI) score and SF-12 health-related quality of life (PCS and MCS) score. Secondary outcomes included evaluations of trunk muscle strength, endurance, and range of motion (ROM) during medial/lateral rotation to assess muscle functionality. Measurements were obtained both before and after the implementation of the intervention therapy. RESULTS: After 12 weeks of intervention therapy, all the health condition parameters significantly improved among the three groups. However, the CG had a significant improvement in pain intensity compared to the EG (MD = - 0.84 scores; 95% CI = - 1.54 to - 0.15; p = 0.013) and the IG (MD = - 1.22 scores; 95% CI = - 1.96 to - 0.48; p = 0.000). Additionally, the CG led to greater conservation of ODI and improved SF-12 PCS scores than did the IG (p < 0.05). Finally, compared with those at baseline, the core muscle function parameters in the CG and EG improved significantly at the end of the study, but no statistically significant differences were observed between the two groups (p > 0.05). CONCLUSION: Among participants with chronic LBP, three intervention therapies appear effective in reducing pain, diminishing disability, and enhancing quality of life. Also, combined therapy significantly improved pain and disability compared to the other two monotherapies; moreover, combined therapy and core muscle exercise provided similar benefits in terms of core muscle function after 12 weeks of intervention therapy.

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

A qualitative study of the experiences of interdisciplinary nurses during the COVID-19 outbreak following the announcement of the "Ten new guidelines" in China.

BACKGROUND: On December 7, 2022, the Joint Prevention and Control Mechanism of China's State Council released the "Ten New Guidelines" to optimize the coronavirus disease 2019 (COVID-19) prevention policies further. This signaled a broader shift from "dynamic clearing" to "coexisting with the virus" nationwide. OBJECTIVE: This study aims to examine the experiences and perspectives of interdisciplinary nurses during the COVID-19 outbreak in China after the implementation of the "Ten New Guidelines". The goal is to understand the challenges faced by this unique nursing group and inform organizational support to bolster their well-being and resilience. METHODS: Two tertiary hospitals in southeastern Zhejiang Province were selected, with interdisciplinary nurses chosen as subjects. A constructivist qualitative research approach was employed, using semi-structured face-to-face interviews. Research data were collected through interviews and analyzed using content analysis. RESULTS: Fifteen interdisciplinary nurses were included in this study. The analysis revealed four main themes and nine sub-themes. The main themes were: (1) ineffective organizational support (inadequate organizational care, poor PPE, excessive workload), (2) physiological distress after contracting COVID-19 (extreme physical fatigue, leakage of urine due to severe coughing), (3) fear of being wrong (fear of being reprimanded in public, psychological anxiety), and (4) family responsibility anxiety (difficulty of loyalty and filial piety, obligations to their children). CONCLUSION: We provide new evidence that organizations must proactively address the support, training, and communication needs of staff, particularly interdisciplinary nurses, to supplement epidemic containment. This is also essential in helping mitigate the work-family conflicts such roles can create.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Krüppel-like factor 4 (KLF4) facilitates lipid production in immortalized human sebocytes via regulating the expression of SREBP1.

BACKGROUND: Acne is associated with the excessive production of sebum, a complex mixture of lipids, in the sebaceous glands. The transcription factor Krüppel-like factor 4 (KLF4) plays an important role in skin morphogenesis, but its role in sebum production by sebocytes is not well known. PURPOSE: In this study, we investigated the possible action mechanism of KLF4 during calcium-induced lipogenesis in immortalized human sebocytes. METHODS: Sebocytes were treated with calcium, and lipid production was confirmed by thin-layer chromatography (TLC) and Oil Red O staining. To investigate the effect of KLF4, sebocytes were transduced with the KLF4-overexpressing adenovirus, and then lipid production was evaluated. RESULTS: Calcium treatment resulted in increased sebum production in terms of squalene synthesis in sebocytes. In addition, calcium increased the expression of lipogenic regulators such as sterol-regulatory element binding protein 1 (SREBP1), sterol-regulatory element binding protein 2 (SREBP2), and stearoyl-CoA desaturase (SCD). Similarly, the expression of KLF4 was increased by calcium in sebocytes. To investigate the effect of KLF4, we overexpressed KLF4 in sebocytes using recombinant adenovirus. As a result, KLF4 overexpression increased the expression of SREBP1, SREBP2, and SCD. Parallel to this result, lipid production was also increased by KLF4 overexpression. Chromatin immunoprecipitation revealed the binding of KLF4 to the SREBP1 promoter, indicating that KLF4 may directly regulate the expression of lipogenic regulators. CONCLUSION: These results suggest that KLF4 is a novel regulator of lipid production in sebocytes.

Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice.

Protein arginine methyltransferase 1 (PRMT1) has been reported to be involved in various diseases. The expression of PRMT1 was increased in cirrhotic livers from human patients. However, the role of PRMT1 in hepatic fibrogenesis remains largely unexplored. In this study, we investigated the effect of PRMT1 on hepatic fibrogenesis and its underlying mechanism. We found that PRMT1 expression was significantly higher in fibrotic livers of the mice treated with thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Immunofluorescence staining revealed that PRMT1 expression was augmented in both hepatocytes and hepatic stellate cells (HSCs) in the fibrotic livers. Applying a selective inhibitor of PRMT1, PT1001B, significantly suppressed PRMT1 activity and mitigated liver fibrosis in mice. Hepatocyte-specific Prmt1 knockout did not affect liver fibrosis in mice. PRMT1 overexpression promoted the expression of fibrotic genes in the LX-2 cells, whereas knockdown of PRMT1 or treatment with PT1001B exhibited reversal effects, suggesting that PRMT1 plays an important role in HSC activation. Additionally, HSC-specific Prmt1 knockout attenuated HSC activation and liver fibrosis in TAA-induced fibrotic model. RNA-seq analysis revealed that Prmt1 knockout in HSCs significantly suppressed pro-inflammatory NF-κB and pro-fibrotic TGF-ß signals, and also downregulated the expression of pro-fibrotic mediators in mouse livers. Moreover, treatment with PT1001B consistently inhibited hepatic inflammatory response in fibrotic model. In conclusion, PRMT1 plays a vital role in HSC activation. Inhibition of PRMT1 mitigates hepatic fibrosis by attenuating HSC activation in mice. Therefore, targeting PRMT1 could be a feasible therapeutic strategy for liver fibrosis.

MXene-sensitized electrochemiluminescence sensor for thrombin activity detection and inhibitor screening.

Thrombin, a crucial enzyme involved in blood coagulation and associated diseases, requires accurate detection of its activity and screening of inhibitors for clinical diagnosis and drug discovery. To address this, an electrochemiluminescence (ECL) method was developed to detect thrombin activity based on the sensitization of Ti3C2Tx MXene, which could sensitize the Ru(bpy)32+ ECL system greatly. The thrombin-cleavable substrate bio-S-G-R-P-V-L-G-C was used as recognizer to evaluate the activity of thrombin. Under the optimal conditions, the limit of detection for thrombin in serum was 83 pU/mL (S/N = 3) with a linear range from 0.1 nU/mL to 1 µU/mL. Moreover, the developed ECL biosensor was employed to screen for thrombin inhibitors from Artemisiae argyi Folium. Four potential thrombin inhibitors (isoquercitrin, nepetin, L-camphor, L-borneol) were screened out with inhibition rates beyond 50%, among which isoquercitrin had the best inhibition rate of 90.26%. Isoquercitrin and nepetin were found to be competitive inhibitors of thrombin, with [Formula: see text] values of 0.91 µM and 2.18 µM, respectively. Molecular docking results showed that these compounds could interact with the active sites of thrombin through hydrogen bonds including ASP189, SER195, GLY216, and GLY219. The electrochemical biosensor constructed provides a new idea for the detection of thrombin activity and screening of its inhibitors.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Liver regeneration: Cellular origin and molecular mechanisms.

The liver is known as an organ with high proliferation potential. Clarifying the cellular origin and deepening the understanding of liver regeneration mechanisms will help provide new directions for the treatment of liver disease. With the development and application of lineage tracing technology, the specific distribution and dynamic changes of hepatocyte subpopulations in homeostasis and liver injury have been illustrated. Self-replication of hepatocytes is responsible for the maintenance of liver function and mass under homeostasis. The compensatory proliferation of remaining hepatocytes is the main mechanism of liver regeneration following acute and chronic liver injury. Transdifferentiation between hepatocytes and cholangiocytes has been recognized upon severe chronic liver injury. Wnt/ß-catenin, Hippo/YAP and Notch signalling play essential roles in the maintenance of homeostatic liver and hepatocyte-to-cholangiocyte conversion under liver injury. In this review, we summarized the recent studies on cell origin of newly generated hepatocytes and the underlying mechanisms of liver regeneration in homeostasis and liver injury.

Deletion of Sox9 in the liver leads to hepatic cystogenesis in mice by transcriptionally downregulating Sec63.

Hepatic cysts are found in heterogeneous disorders with different pathogeneses, of which simple hepatic cysts and polycystic liver diseases are two major types. The process of hepatic cytogenesis for these two diseases is caused by defects in remodelling of the ductal plate during biliary tract development, which is called ductal plate malformation. SOX9 is a transcription factor participating in the process of bile duct development, and thus, its dysregulation may play important roles in hepatic cystogenesis. SEC63 encodes an endoplasmic reticulum membrane protein that is mutated in human autosomal dominant polycystic liver disease. However, the transcriptional regulation of SEC63 is largely unknown. In the present study, a liver-specific Sox9 knockout (Sox9LKO ) mouse was generated to investigate the roles and underlying mechanism of SOX9 in hepatic cystogenesis. We found that hepatic cysts began to be observed in Sox9LKO mice at 6 months of age. The number and size of cysts increased with age in Sox9LKO mice. In addition, the characteristics of hepatic cytogenesis, including the activation of proliferation, absence of primary cilium, and disorder of polarity in biliary epithelial cells, were detected in the livers of Sox9LKO mice. RNAi silencing of SOX9 in human intrahepatic biliary epithelial cells (HIBEpic) resulted in increased proliferation and reduced formation of the primary cilium. Moreover, Sec63 was downregulated in primary biliary epithelial cells from Sox9LKO mice and SEC63 in HIBEpic transfected with siSOX9. Chromatin immunoprecipitation assays and luciferase reporter assays further demonstrated that SOX9 transcriptionally regulated the expression of SEC63 in biliary epithelial cells. Importantly, the overexpression of SEC63 in HIBEpic partially reversed the effects of SOX9 depletion on the formation of primary cilia and cell proliferation. These findings highlight the biological significance of SOX9 in hepatic cytogenesis and elucidate a novel molecular mechanism underlying hepatic cytogenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The effectiveness of acupressure for managing postoperative pain in patients with thoracoscopic surgery: A randomized control trial.

PURPOSE: More than 86% patients experience moderate to severe pain after thoracoscopic surgery. A combination of diverse nonpharmacological pain relief methods is a developing trend for pain management. The purpose of this study was to explore the effect of acupressure in reducing pain after thoracoscopic surgery. DESIGN: A Randomized controlled study with purpose sampling was used for this study. Patients who underwent thoracoscopic surgery at a medical center in central Taiwan were enrolled. Study data was collected from September 2020 to April 2021 after the approval of the institutional review board. A total of 100 participants were randomized into two groups (49 and 51 in the experimental and control groups, respectively). METHODS: Participants in the experimental group received acupressure at the Neiguan (PC6) and Shenmen (HT7) acupoints thrice a day for 2 days, whereas those in the control group received routine treatment and did not receive acupressure. The measurement included questionnaires for the collection of general information, physiological information, and disease rating scale. The Visual Analogue Scale-Pain (VAS-P) was used to measure the severity of pain. SPSS statistical software was used for data analysis. Independent sample t-test and chi-squared test were used for descriptive statistics, and paired t-test and linear mixed model were used to examine the effect of acupressure in alleviating pain. FINDINGS: After acupressure intervention, the pain score of the experimental group was lower than that of the control group, and this difference was significant ß = 17.76, p < 0.001 on day 1 after intervention; ß = 19.80, p < 0.001 on day 2 after intervention. The postoperative pain score in the experimental group on day 2 after intervention was significantly lower than that in the control group (t = 2.039, p = 0.044). After the subjects received acupressure, pain index significantly decreased after considering the interaction between time and group (p < 0.001). Regardless of the type of surgery, there were significant differences in pain index when the interaction between time and group was considered (p < 0.001). CONCLUSIONS: This study provided an experimental basis that acupressure can help in pain management in patients after thoracoscopic surgery, and the pain relief results become more significant as the duration of intervention increases. CLINICAL RELEVANCE: Acupressure is effective in relieving postoperative pain in any type of thoracoscopic surgery. Nurses can use acupressure to help control pain in patients after thoracoscopic surgery.

Transcutaneous Electrical Acustimulation Ameliorates Motion Sickness Induced by Rotary Chair in Healthy Subjects: A Prospective Randomized Crossover Study.

OBJECTIVES: Motion sickness (MS) is a common physiological response to real or virtual motion. The purpose of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on MS and the underlying mechanisms in healthy subjects. MATERIALS AND METHODS: A total of 50 healthy participants were recruited and randomly assigned into two groups to complete two separate sessions in a crossover study. A Coriolis rotary chair was used as a model to provoke severe MS. The total tolerable rotation time and Graybiel scoring scale were recorded. Gastric slow waves were detected by electrogastrogram. The autonomic nervous function, including the vagal activity, was evaluated by the analysis of heart rate variability derived from the electrocardiogram recording. The serum levels of arginine vasopressin (AVP) and norepinephrine (NE) were examined. RESULTS: Of note, 22 participants in TEA and only 11 participants in the sham-TEA session completed the entire five-rotation MS stimuli (p = 0.019). TEA significantly prolonged the total tolerable rotation time of MS stimuli (220.4 ± 11.59 vs 173.6 ± 12.3 seconds, p < 0.001) and lowered MS symptom scores (12.56 ± 2.03 vs 22.06 ± 3.0, p < 0.001). TEA improved the percentage of normal gastric slow waves, compared with sham-TEA (56.0 ± 2.1% vs 51.6 ± 2.0%, p = 0.033). TEA also significantly enhanced vagal activity compared with sham-TEA (0.41 ± 0.02 vs 0.31 ± 0.02, p < 0.001). In addition, the increased serum levels of AVP and NE on MS stimulation were markedly suppressed by TEA treatment, compared with sham-TEA (AVP, 56.791 ± 4.057 vs 79.312 ± 10.036 ng/mL, p = 0.033; NE, 0.388 ± 0.037 vs 0.501 ± 0.055 ng/mL, p = 0.021). CONCLUSIONS: Needleless TEA is a potent therapeutic approach for severe MS, as it increases participants' tolerance and ameliorates MS symptoms, which may be attributed to the integrative effects of TEA on autonomic functions and neuroendocrine balance.

Use of a purified ß-glucosidase from coral-associated microorganisms to enhance wine aroma.

BACKGROUND: ß-Glucosidases (3.2.1.21) play essential roles in the removal of nonreducing terminal glucosyl residues from saccharides and glycosides. However, the full potential and different applications of recombinant high-yield microbial ß-glucosidase-producing systems remain to be tackled. RESULTS: A ß-glucosidase gene designated as Mg132 was isolated from a coral microorganism by high-throughput sequencing and functional screening. The deduced amino acid sequences of Mg132 showed a highest identity of 97% with ß-glucosidase predicted in the GenBank database. This gene was cloned and overexpressed in Escherichia coli BL21 (DE3) for the first time. The optimal pH and temperature of purified recombinant Mg132 were 8.0 and 50 °C respectively. It exhibited a high level of stability at high concentration of glucose and ethanol, and glucose concentrations below 300 mmol L-1 distinctly stimulated p-nitrophenyl-ß-d-glucopyranoside hydrolysis, reaching 200% at 15% ethanol. The Km and Vmax values were 0.293 mmol L-1 and 320 µmol min-1  mg-1 respectively while using p-nitrophenyl-ß-d-glucopyranoside as a substrate. Wine treated with Mg132 had an obvious positive catalytic specificity for glycosides, which give a pleasant flavor of temperate fruity and floral aromas. The total concentration of fermentative volatiles was 201.42 ± 10.22 µg L-1 following Mg132 treatment and 99.21 ± 7.72 µg L-1 in control samples. CONCLUSION: Good tolerance of winemaking and aroma fermentative properties suggest that Mg132 has potential application in aroma enhancement in wine and warrants further study. © 2021 Society of Chemical Industry.