Search

Societal Impact Statement The invasive species S. alterniflora and P. australis are fast growing coastal wetland plants sequestering large amounts of carbon in the soil and protect coastlines against erosion and storm surges. In this global analysis, we found that Spartina and Phragmites increase methane but not nitrous oxide emissions, with Phragmites having a lesser effect. The impact of the invasive species on emissions differed greatly among different types of native plant groups, providing valuable information to managers and policymakers during coastal wetland planning and restoration efforts. Further, our estimated net emissions per wetland plant group facilitate regional and national blue carbon estimates. Summary Globally, Spartina alterniflora and Phragmites australis are among the most pervasive invasive plants in coastal wetland ecosystems. Both species sequester large amounts of atmospheric carbon dioxide (CO2) and biogenic carbon in soils but also support production and emission of methane (CH4). In this study, we investigated the magnitude of their net greenhouse gas (GHG) release from invaded and non‐invaded habitats. We conducted a meta‐analysis of GHG fluxes associated with these two species and related soil carbon content and plant biomass in invaded coastal wetlands. Our results show that both invasive species increase CH4 fluxes compared to uninvaded coastal wetlands, but they do not significantly affect CO2 and N2O fluxes. The magnitude of emissions from Spartina and Phragmites differs among native habitats. GHG fluxes, soil carbon and plant biomass of Spartina‐invaded habitats were highest compared to uninvaded mudflats and succulent forb‐dominated wetlands, while being lower compared to uninvaded mangroves (except for CH4). This meta‐analysis highlights the important role of individual plant traits as drivers of change by invasive species on plant‐mediated carbon cycles.

Abstract Background/Aims Chemotherapy resistance in liver cancer is a major clinical issue, with CD147 playing a vital role in this process. However, the specific mechanisms underlying these processes remain largely unknown. This study investigates how CD147 internalization leads to cytoprotective autophagy, contributing to chemotherapy resistance in hepatocellular carcinoma (HCC). Methods Utilizing bioinformatics methods for KEGG pathways enrichment and screening key molecules associated with chemotherapy resistance through analyses of GEO and TCGA databases. An overexpression/knockdown system was used to study how CD147 internalization leads to autophagy in vitro and in vivo. The process was observed using microscopes, and molecular interactions and autophagy flux were analyzed. Analyzing the internalization of CD147 intracellular domains and the interaction with G3BP1 in clinical chemotherapy recurrence HCC tissues by immunohistochemistry, tissue immunofluorescence, and mass spectrometry. A tumor xenograft mice model was used to study cytoprotective autophagy induced by CD147 and test the effectiveness of combining cisplatin with an autophagy inhibitor in nude mice models. Results In our study, we identified the tumor-associated membrane protein CD147, which implicated in chemoresistance lysosome pathways, by evaluating its protein degree value and betweenness centrality using Cytoscape. Our findings revealed that CD147 undergoes internalization and interacts with G3BP1 following treatment with cisplatin and methyl-β-cyclodextrin, forming a complex that is transported to lysosomes via Rab7A. Notably, higher doses of cisplatin enhanced CD147-mediated lysosomal transport while concurrently inhibiting SG assembly. The CD147-G3BP1 complex additionally inhibits mTOR activity, promoting autophagy and augmenting chemoresistance in hepatoma cells. In vivo studies investigations and analyses of clinical samples revealed that elevated internalization of CD147 is associated with chemotherapy recurrence in liver cancer and the maintenance of stem cells. Mice experiments found that the combined administration of cisplatin and hydroxychloroquine enhanced the efficacy of treatment. Conclusions This study reveals that CD147 internalization and CD147-G3BP1 complex translocation to lysosomes induce cytoprotective autophagy, reducing chemotherapy sensitivity by suppressing mTOR activity. It is also shown that chemotherapy drugs combined with autophagy inhibitors can improve the therapeutic effect of cancer, providing new insights into potential targeted therapeutic approaches in treating HCC.

Abstract Background Both lipid metabolism and cyclic RNAs (circRNAs) have been found to be involved in pancreatic adenocarcinoma (PAAD) progression, but the relationship between lipid metabolism and circRNAs remains unclear. Methods The expression levels of miR-223-3p, circ_0124346, and acyl-CoA synthetase long chain family member 3 (ACSL3) were determined through qRT-PCR and Western blot analysis. Cell proliferation was evaluated using the CCK-8 and EdU incorporation assays. Cholesterol (CH) and triglyceride (TG) levels were quantified using relevant kits. The relationships between miR-223-3p and circ_0124346 or ACSL3 mRNA were examined by bioinformatics analysis, luciferase reporter, RNA-RNA pull-down, and RIP assays. Results We observed a significant elevation in circ_0124346 expression in both pancreatic adenocarcinoma (PAAD) tissues and cell lines, and its expression level was shown to be correlated with tumor size. Circ_0124346 stimulated cell proliferation and facilitated lipid synthesis in PAAD cells. Additionally, we found that circ_0124346 functioned as a sponge for miR-223-3p, preventing miR-223-3p’s binding to the 3'-UTR of ACSL3 mRNA, which subsequently led to an elevation in ACSL3 expression and promoted lipid synthesis. Accordingly, circ_0124346 knockdown resulted in a significant decrease in lipid synthesis and cell proliferation in PAAD cells, with partial reversal of these effects achieved via inhibiting miR-223-3p or overexpressing ACSL3. Conclusion Our study demonstrated that circ_0124346 regulates lipid metabolism in PAAD cells via the miR-223-3p/ACSL3 axis, suggesting that targeting circ_0124346 may serve as a potential strategy for treating PAAD and assisting in its diagnosis.

Background/Aims Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Abstract Background Laboratory rats, as model animals, have been extensively used in the fields of life science and medicine. It is crucial to routinely monitor the genetic background of laboratory rats. The conventional approach relies on gel electrophoresis and capillary electrophoresis (CE) technologies. However, the experimental and data analysis procedures for both of these methods are time consuming and costly. Results We established a single-nucleotide polymorphism (SNP) typing scheme using multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) to address the genetic background ambiguity in laboratory rats. This methodology involved three rounds of PCR and two rounds of magnetic bead selection to improve the quality of the sequencing data. We simultaneously analysed 100 laboratory rats (including rats of 5 inbred strains and 2 in-house closed colonies), and the sequencing depth varied from an average of 108.25 to 5189.89, with sample uniformity ranging from 82.5 to 97.5%. A total of 98.9% of the amplicons were successfully genotyped (≥ 30 reads). Genetic background analysis revealed that all 38 experimental rats from the 5 inbred strains were successfully identified (without a heterozygous allele). For the 2 in-house closed colonies, the average heterozygosity (0.162 and 0.169) deviated from the typical range of 0.5–0.7, indicating a departure from the ideal heterozygosity level. Additionally, we employed multiplex PCR-CE to validate the NGS-based method, which yielded consistent results for all the rat strains. These results demonstrated that this approach significantly improves efficiency, saves time, reduces costs and ensures accuracy. Conclusion By utilizing NGS technology, our developed method leverages SNP genotyping for genetic background identification in laboratory rats, demonstrating advantages in terms of labour efficiency and cost-effectiveness, thereby rendering it well suited for projects involving extensive sample cohorts.

Abstract Purpose Analyzing the correlation between patients’ basic information, three-dimensional parameters after calcaneal fractures, and the prognosis of calcaneal fractures. Methods A retrospective analysis was conducted on 43 patients with calcaneal fractures who underwent surgical treatment in the Foot and Ankle Surgery, Xi’an Honghui Hospital, from September 2019 to August 2022. Patient demographics including gender and age were collected, as well as the preoperative posterior articular surface collapse area, number of fracture fragments, length, width, height, and volume of the calcaneus obtained from preoperative three-dimensional imaging. Patients were followed up for VAS, AOFAS, and SF-36 scores. Correlation analysis was performed on the obtained data. Results All 43 included patients received complete follow-up, including 40 males and 3 females, with an average follow-up time of 35.37 ± 10.73 months, and an average age of 43.98 ± 12.08 years. All patients’ VAS, AOFAS, and SF-36 scores at the last follow-up showed no correlation with patient age, gender, or the area of posterior articular collapse, number of fracture fragments, length, width, height, or volume of the calcaneus. Conclusions The prognosis of calcaneal fractures is unrelated to three-dimensional factors such as patient age, gender, length, width, height, volume of the calcaneus, area of the posterior joint, and number of fracture fragments.

Introduction: The objective of this study was to examine the interplay of polygenic risk and individual lifestyle factors (and a composite score of lifestyle) as antecedents of CHD in a large multiethnic cohort. Methods: We used Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort participants free of CHD at baseline (n = 60,568; 67 % female; 18 % non-European). The individual and joint associations of smoking, Mediterranean diet pattern, level of physical activity and polygenic risk with incident CHD were assessed using Cox regression adjusting for genetic ancestry and non-mediating risk factors. Hazard ratios (HRs) and number needed to treat (NNT) were estimated according to these lifestyle factors and polygenic risk categories. Strengths included large sample size, long-follow-up, ethnic diversity, a clinically-validated polygenic risk score (PRS), and rich phenotype information. Results: After 14 years of follow-up, there were 3159 incident CHD events. We observed no statistically significant interactions between individual lifestyle factors and polygenic risk (all p > 0.23). For individuals with a high genetic risk, moving from the worse lifestyle combination (no favorable lifestyle factors) to the best lifestyle combination (all three) is associated with 52 % lower rate of CHD. The NNT was highest in the low polygenic risk group (34), lowest in the high polygenic risk group [19] and in-between (Jin et al., 2011) [24] in the intermediate polygenic risk group. Conclusions: Lifestyle and polygenic risk together influence the risk of incident CHD. Our results support consideration of polygenic risk in lifestyle interventions because those with high polygenic risk are likely to derive the most benefit.

Abstract Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing understanding of the basis of neuronal functions. However, the rapid millisecond‐scale fluctuations in neuronal activity and the subtle sub‐diffraction resolution changes of synaptic morphology pose significant challenges to this endeavor. Here, specially designed graphene microelectrode arrays (G‐MEAs) are used, which are compatible with high spatial resolution imaging across various scales as well as permit high temporal resolution electrophysiological recordings to address these challenges. Furthermore, alongside G‐MEAs, an easy‐to‐implement machine learning algorithm is developed to efficiently process the large datasets collected from MEA recordings. It is demonstrated that the combined use of G‐MEAs, machine learning (ML) spike analysis, and 4D structured illumination microscopy (SIM) enables monitoring the impact of disease progression on hippocampal neurons which are treated with an intracellular cholesterol transport inhibitor mimicking Niemann–Pick disease type C (NPC), and show that synaptic boutons, compared to untreated controls, significantly increase in size, leading to a loss in neuronal signaling capacity.

Abstract Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.

Milk is an excellent medium for the growth of microorganisms, which is easily contaminated by microorganisms from the environment. Psychrophilic bacteria are the most common microorganisms in cold-stored raw milk. Moreover, psychrophilic bacteria produce heat-resistant proteases and lipases in low-temperature environments, which remain active even after heat treatment, and decompose proteins and fats in liquid milk during storage, thereby affecting the quality of milk. The counting method for psychrophilic bacteria in milk specified by the agricultural industry standard of China takes 10 days to culture samples at 6.5 ℃ for 10 days, which is time-consuming and has low application value in actual production. Therefore, the development of detection technologies for psychrophilic bacteria and their heat-resistant enzymes is very important for ensuring the quality of milk and dairy products. This article reviews a variety of methods for the identification and analysis of psychrophilic bacteria in milk, including polymerase chain reaction (PCR), sequencing, fluorescence in situ hybridization, and loop-mediated isothermal amplification. It provides a reference for the development of new detection technologies for psychrophilic bacteria in milk.

Abstract Body weight is related to both diabetes and cognitive impairment; however, the associations between body mass index (BMI) and cognitive impairment have been reported less frequently among diabetes patients. A total of 1355 patients with type 2 diabetes aged ≥ 60 years were included in this study. The Montreal Cognitive Assessment (MoCA) was administered to assess participants’ cognitive status. We collected self-reported body weight, weight loss and appetite loss data using questionnaires. Associations between body weight status (in childhood, midlife age, and late life), weight loss, appetite changes and cognitive impairment were explored using logistic regression. Among the participants, 41.7% exhibited cognitive impairment. Overweight in childhood and late life was associated with cognitive impairment among diabetes patients (OR 2.63, 95% CI 1.52–4.55; OR 1.32, 95% CI 1.03–1.69). Diabetes patients with cognitive impairment were more likely to report a body weight decline and appetite reduction in the past three months (OR 4.18, 95% CI 2.61–6.71; OR 4.41, 95% CI 2.67–7.29). Higher BMI, weight loss, and appetite reduction were positively correlated with cognitive impairment. Given the risk of cognitive impairment, we suggest that body weight and BMI decline should be monitored in patients with diabetes.

Background: Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model. Methods: C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3β (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed. Results: SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors. Conclusions: Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway.

Metagenomic time-course studies provide valuable insights into the dynamics of microbial systems and have become increasingly popular alongside the reduction in costs of next-generation sequencing technologies. Normalization is a common but critical preprocessing step before proceeding with downstream analysis. To the best of our knowledge, currently there is no reported method to appropriately normalize microbial time-series data. We propose TimeNorm, a novel normalization method that considers the compositional property and time dependency in time-course microbiome data. It is the first method designed for normalizing time-series data within the same time point (intra-time normalization) and across time points (bridge normalization), separately. Intra-time normalization normalizes microbial samples under the same condition based on common dominant features. Bridge normalization detects and utilizes a group of most stable features across two adjacent time points for normalization. Through comprehensive simulation studies and application to a real study, we demonstrate that TimeNorm outperforms existing normalization methods and boosts the power of downstream differential abundance analysis.

Abstract Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs‐mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal‐regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin‐11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin‐11 pathways, which are associated with NCK1. The anti‐platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases.

Abstract It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

We present a genome assembly from an individual Geum urbanum the (wood avens; Streptophyta; Magnoliopsida; Rosales; Rosaceae). The genome sequence is 1,304.9 megabases in span. Most of the assembly is scaffolded into 21 chromosomal pseudomolecules. The mitochondrial and plastid genomes have also been assembled and are 335.5 and 156.1 kilobases in length respectively. Gene annotation of this assembly on Ensembl identified 50,336 protein-coding genes.

Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14–1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49–1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9–3.8) for the entire cohort and 9.7 (7.5–12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

Abstract Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan.

Understanding whether a droplet adheres to or detaches from a flexible filament upon axial impact is of significant interest, particularly in the context of raindrop impact on natural surfaces. This process involves dynamic buckling followed by mode coarsening, dissipating the initial droplet kinetic energy and converting the remaining into elastic energy of the filament. To elucidate this phenomenon, we construct two phase diagrams, one while fixing the filament height and the other the droplet diameter. Notably, we observe that the energy conversion rate is inversely proportional to a Cauchy number, defining the transition between attached and detached droplet in the filament length–falling height diagram. This enables us to derive an expression for the critical falling height as a function of the filament parameters, accounting for the energy conversion rate, which emerges as a key factor for droplet detachment.

Background and Purpose: Emerging researches have regarded serum chloride as a capable predictor of mortality in liver cirrhosis. We aim to investigate the clinical role of admission chloride in cirrhotic patients with esophagogastric varices receiving transjugular intrahepatic portosystemic shunt (TIPS), which is unclear. Methods: We retrospectively analyzed data of cirrhotic patients with esophagogastric varices undergoing TIPS in Zhongnan Hospital of Wuhan University. Mortality outcome was obtained by following up for 1-year after TIPS. Univariate and multivariate Cox regression were used to identify independent predictors of 1-year mortality post-TIPS. The receiver operating characteristic (ROC) curves were adopted to assess the predictive ability of the predictors. In addition, log-rank test and Kaplan–Meier (KM) analyses were employed to evaluate the prognostic value of predictors in the survival probability. Results: A total of 182 patients were included ultimately. Age, fever symptom, platelet-to lymphocyte-ratio (PLR), lymphocyte-to-monocyte ratio (LMR), total bilirubin, serum sodium, chloride, and Child-Pugh score were related to 1-year follow-up mortality. In multivariate Cox regression analysis, serum chloride (HR = 0.823, 95%CI = 0.757–0.894, p

Abstract Background The mechanism of hepatitis B virus (HBV)‐induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV‐related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan‐mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development. Methods An HBV‐transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real‐time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues. Results We found sustained activation of ER stress in the HBV‐transgenic mouse model of hepatitis‐fibrosis‐HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues. Conclusions This study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV‐related carcinogenesis.

Abstract Aim To evaluate the efficacy and safety of vonoprazan–amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). Methods The PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach. Results Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07–1.23, p

Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of proinflammatory factors in macrophages stimulated by lipopolysaccharide (LPS). Multiplex proteomic profiling identified the immunoproteasome, which is a specific isoform of the 20s constitutive proteasome, as a substrate that is degraded by selective autophagy. SQSTM1/p62 was found to be a selective autophagy-related receptor that mediated this degradation. Autophagy deficiency or p62 knockdown blocked the effects of LY2874455, leading to the accumulation of immunoproteasomes and increases in inflammatory reactions. Expression of proinflammatory factors in autophagy-deficient macrophages could be reversed by immunoproteasome inhibitors, confirming the pivotal role of immunoproteasome turnover in the autophagy-mediated suppression on the expression of proinflammatory factors. In mice, LY2874455 protected against LPS-induced acute lung injury and dextran sulfate sodium (DSS)-induced colitis and caused low levels of proinflammatory cytokines and immunoproteasomes. These findings suggested that selective autophagy of the immunoproteasome was a key regulator of signaling via the innate immune system.

Abstract Background To evaluate the quantity and quality of bone in the newly formed edentulous area produced by the orthodontic implant site-switching technique. Methods The bilateral maxillary first premolars of five beagle dogs were extracted and bone defects were created. The right and left sides of the maxilla were randomly divided into control and experimental sides. On the experimental side, the maxillary second premolar was mesially moved into the position of the missing first premolar. On the control side, the second maxillary premolar was extracted. Six months later, the beagles were euthanized. Microcomputer tomography was used to analyze bone microstructure parameters, alveolar bone height and alveolar bone width of the regenerated bone. Histological analysis was performed by staining tissue sections with toluidine blue. Results Median BV/TV values in the experimental group (81.78%) were significantly larger than those in the control group (35.67%; p = 0.04). Median Tb.Sp values in the experimental group (0.14 mm) were significantly lower than those in the control group (0.54 mm; p = 0.04). Median Tb.Th values in the experimental group (0.48 mm) were significantly higher than those in the control group (0.21 mm; p = 0.04). Median Tb.Pf values in the experimental group (0.65/mm) were significantly lower than those in the control group (3.15/mm; p = 0.04). There was no significant difference in the trabecular number (Tb.N) between the two groups (p = 0.23). The median alveolar bone height values in the experimental group (-0.81 mm) were significantly higher than those in the control group (-2.11 mm; p = 0.04) at a distance 5 mm from the mesial CEJ of the third premolar. The median alveolar bone height values in the experimental group (0.45 mm) were significantly higher than those in the control group (-1.70 mm; p = 0.04) at a distance 6 mm from the mesial CEJ of the third premolar. There was no significant difference in alveolar bone width when compared between the two groups (p > 0.05). Conclusions The newly formed edentulous area created by orthodontic treatment had more compact and thicker trabeculae than the extraction socket. Furthermore, the newly formed edentulous area had a greater alveolar bone height available for the placement of implants.

Interest in searches for Charged Lepton Flavor Violation (CLFV) has continued in the past few decades since the observation of CLFV would indicate a new physics Beyond the Standard Model (BSM). As several future lepton colliders with high luminosity have been proposed, the search for CLFV will reach an unprecedented level of precision. Many BSM models allow CLFV processes at the tree level, such as the R-parity-violating (RPV) Minimal Supersymmetric Standard Model (MSSM), which is a good choice for benchmarking. In this paper, we perform a detailed fast Monte Carlo simulation study on RPV-induced CLFV processes at future lepton colliders, including a 240 GeV circular electron positron collider (CEPC) and a 6 or 14 TeV Muon Collider. As a result, we found that the upper limits on the τ-related RPV couplings will be significantly improved, while several new limits on RPV couplings can be set, which are inaccessible by low-energy experiments.

Research related to hydrological big data has been a focal point and core issue in the field of hydrology in recent years.It is also an important component for improving the efficiency of hydrological affairs processing and enhancing the authenticity and credibility of hydrological patterns.This study utilized a sample dataset comprising 264 papers collected from China Knowledge Infrastructure (CNKI) and 219 papers collected from Web of Science (WOS).Using CiteSpace software,this paper analyzed the researchers,institutions, and research hotspots and explored the development trend of research in this field in depth.The findings indicate that,overall,both Chinese and international publications show an increasing trend.Regarding researchers and research institutions,there is a phenomenon of “large scattering and small gathering” among Chinese scholars and institutions.Examining research hotspots reveals that keywords such as “intelligent hydrology,”“early warning system,”“big data testing” signify that the focus of research in this field is gradually shifting towards technological and digital directions.Whether domestically or internationally,modern hydrological monitoring technologies and hydrological methods,in comparison to traditional technologies and methods,demonstrate higher accuracy and stability.They can more fully meet the practical application requirements,and the combination of hydrology and big data has gradually become a research trend in this field.

Extracellular vesicles (EVs) carry DNA, RNA, protein, and other substances involved in intercellular crosstalk and can be used for the targeted delivery of drugs. Triple-negative breast cancer (TNBC) is rich in recurrent and metastatic disease and lacks therapeutic targets. Studies have proved the role of EVs in the different stages of the genesis and development of TNBC. Cancer cells actively secrete various biomolecules, which play a significant part establishing the tumor microenvironment via EVs. In this article, we describe the roles of EVs in the tumor immune microenvironment, metabolic microenvironment, and vascular remodeling, and summarize the application of EVs for objective delivery of chemotherapeutic drugs, immune antigens, and cancer vaccine adjuvants. EVs-based therapy may represent the next-generation tool for targeted drug delivery for the cure of a variety of diseases lacking effective drug treatment.

Breast cancer is the leading cause of cancer-related deaths in females worldwide, and the liver is one of the most common sites of distant metastases in breast cancer patients. Patients with breast cancer liver metastases face limited treatment options, and drug resistance is highly prevalent, leading to a poor prognosis and a short survival. Liver metastases respond extremely poorly to immunotherapy and have shown resistance to treatments such as chemotherapy and targeted therapies. Therefore, to develop and to optimize treatment strategies as well as to explore potential therapeutic approaches, it is crucial to understand the mechanisms of drug resistance in breast cancer liver metastases patients. In this review, we summarize recent advances in the research of drug resistance mechanisms in breast cancer liver metastases and discuss their therapeutic potential for improving patient prognoses and outcomes.

Abstract Charged lepton flavor violation (CLFV) represents a transition between charged leptons of different generations that violates lepton flavor conservation, which is a clear signature of possible new physics beyond the standard model. By exploiting a typical example model of extra Z′ gauge boson, we perform a detailed comparative study on CLFV searches at several future lepton colliders, including a 240 GeV electron-positron collider and a TeV scale muon collider. Based on detailed signal and background Monte-Carlo studies with fast detector simulations, we derive the potentials in searching for Z′ mediated CLFV couplings with eμ, eτ and μτ of different future colliders. The results are compared with the current and prospect limits set by either low-energy experiments or the high-energy LHC experiments. The sensitivity of the τ related CLFV coupling strength at future lepton colliders will be significantly improved in comparison to the current best constraints and the prospect constraints for the μτ channel.

Covalent organic frameworks (COFs) are an emerging type of crystalline and porous photocatalysts for hydrogen evolution. Here, the authors report a β-ketoamine COF by systematically engineering N-sites, architecture, and morphology for improved water splitting activity.

Zinc (Zn) is an essential trace mineral that is required for plant growth and development. A number of protein transporters, which are involved in Zn uptake, translocation and distribution, are finely regulated to maintain Zn homeostasis in plant. In this study, we functionally characterized an ATP-binding cassette (ABC) transporter gene, OsPDR7, which is involved in Zn homeostasis. OsPDR7 encodes a plasma membrane-localized protein that is expressed mainly in the exodermis and xylem in the rice root. ospdr7 mutants resulted in higher Zn accumulation compared with the wild type. Heterogeneous expression of OsPDR7 in a yeast mutant rescued the Zn-deficiency phenotype, implying transport activity of OsPDR7 to Zn in yeast. However, no ZIP genes except for OsZIP9 showed change in expression profile in the ospdr7 mutants, which suggested that OsPDR7 maintains cellular Zn homeostasis through regulating OsZIP9 expression. RNA-Seq analysis further revealed a set of differentially expressed genes between the wild type and ospdr7 mutants that allowed us to propose a possible OsPDR7-associated signaling network involving transporters, hormone responsive genes, and transcription factors. Our results revealed a novel transporter involved in the regulation of Zn homeostasis and will pave the way toward a better understanding of the fine-tuning of gene expression in the network of transporter genes.

Structured Illumination Microscopy allows for the visualization of biological structures at resolutions below the diffraction limit, but this imaging modality is still hampered by high experimental complexity. Here, the authors present a combination of interferometry and machine learning to construct a structured illumination microscope for super resolution imaging of dynamic sub-cellular biological structures in multiple colors.

Abstract Background Immunotherapy has been proved to have a large effect on extensive‐stage small cell lung cancer, but the role of immunotherapy in limited‐stage small‐cell lung cancer (LS‐SCLC) is still unknown. Methods A retrospective study of six patients with LS‐SCLC who were treated with neoadjuvant chemoimmunotherapy (durvalumab plus etoposide combined with cisplatin) was performed. Patients were evaluated by the safety, feasibility and pathologic responses of neoadjuvant chemoimmunotherapy. Results Neoadjuvant durvalumab combined chemotherapy was associated with few immediate adverse events and did not delay planned surgery. All patients achieved partial pathologic response (pPR) instead of major pathologic response, or pathologic complete response. No association was observed between programmed death‐ligand 1 expression in tumor specimens and the pathologic response. However, tumors with high expression of immune cells such as CD4+ T cells, CD8+ T cells and FoxP3+ Tregs tended to have better pathologic responses than tumors with low expression of immune cells. Conclusions Neoadjuvant durvalumab combined chemotherapy could induce pPR with few side effects in resectable LS‐SCLC. The immune cells in the tumor microenvironment might play an important role in neoadjuvant chemoimmunotherapy in resectable LS‐SCLC.

We present a genome assembly from a Linaria vulgaris specimen (the common toadflax; Streptophyta; Magnoliopsida; Lamiales; Plantaginaceae). The genome sequence is 760.5 megabases in span. Most of the assembly is scaffolded into six chromosomal pseudomolecules. Two mitochondrial genomes were assembled, which were 330.8 and 144.0 kilobases long. The plastid genome was also assembled and is 156.7 kilobases in length.

The green and efficient remediation of soil cadmium (Cd) is an urgent task, and plant-microbial joint remediation has become a research hotspot due to its advantages. High-throughput sequencing and metabolomics have technical advantages in analyzing the microbiological mechanism of plant growth-promoting bacteria in improving phytoremediation of soil heavy metal pollution. In this experiment, a pot trial was conducted to investigate the effects of inoculating the plant growth-promoting bacterium Enterobacter sp. VY on the growth and Cd remediation efficiency of the energy plant Hybrid pennisetum. The test strain VY-1 was analyzed using high-throughput sequencing and metabolomics to assess its effects on microbial community composition and metabolic function. The results demonstrated that Enterobacter sp. VY-1 effectively mitigated Cd stress on Hybrid pennisetum, resulting in increased plant biomass, Cd accumulation, and translocation factor, thereby enhancing phytoremediation efficiency. Analysis of soil physical-chemical properties revealed that strain VY-1 could increase soil total nitrogen, total phosphorus, available phosphorus, and available potassium content. Principal coordinate analysis (PCoA) indicated that strain VY-1 significantly influenced bacterial community composition, with Proteobacteria, Firmicutes, Chloroflexi, among others, being the main differential taxa. Redundancy analysis (RDA) revealed that available phosphorus, available potassium, and pH were the primary factors affecting bacterial communities. Partial Least Squares Discriminant Analysis (PLS-DA) demonstrated that strain VY-1 modulated the metabolite profile of Hybrid pennisetum rhizosphere soil, with 27 differential metabolites showing significant differences, including 19 up-regulated and eight down-regulated expressions. These differentially expressed metabolites were primarily involved in metabolism and environmental information processing, encompassing pathways such as glutamine and glutamate metabolism, α-linolenic acid metabolism, pyrimidine metabolism, and purine metabolism. This study utilized 16S rRNA high-throughput sequencing and metabolomics technology to investigate the impact of the plant growth-promoting bacterium Enterobacter sp. VY-1 on the growth and Cd enrichment of Hybrid pennisetum, providing insights into the regulatory role of plant growth-promoting bacteria in microbial community structure and metabolic function, thereby improving the microbiological mechanisms of phytoremediation.

Biomass allocation in plants is fundamental for understanding and predicting terrestrial carbon storage. Here, the authors conduct a meta-analysis showing that warming effect on plant root:shoot is influenced by precipitation and the type of mycorrhizal fungi associated.

Abstract Background Evaluation of vestibular graviceptive pathway (VGP) in patients with unilateral peripheral vestibular dysfunction (UPVD) has received increasing attention from researchers. The study aimed to investigate the value of VGP evaluation in the diagnosis of UPVD. Methods Ninety‐five UPVD patients were divided into attack and remission phase groups. VGP evaluation‐related indicators, including subjective visual vertical (SVV), subjective visual horizontal (SVH), head tilt, ocular torsion (OT), and skew deviation (SD), were measured, and their correlations with cochleovestibular function test results were analyzed. The possible etiologies of contralesional VGP (c‐VGP) were analyzed. Results Positive rates of SVV, SVH, OT, and SD were significantly higher, and the degrees of SVV, SVH, and OT were significantly greater in the attack phase group than the remission phase group. The sides with abnormal VGP evaluation results were correlated with the sides with hearing loss, abnormal caloric, and video head impulse test (vHIT) results. A total of 14 patients showed c‐VGP, and possible etiologies included contralateral benign paroxysmal positional vertigo (n = 4), bilateral hearing loss (n = 8), bilateral vHIT gain reduction (n = 1), autoimmune diseases (n = 6), vascular risk factors (n = 6), lacunar infarction (n = 3), and endolymphatic hydrops (n = 3). Conclusions Alterations in SVV, SVH, OT, and SD were noted in UPVD patients in different phases, which are presumed to be related to dynamic vestibular compensation; correlations between VGP evaluation results and cochleovestibular function test results indicate that VGP evaluation may be helpful for the diagnosis of the side affected in UPVD; the presence of c‐VGP may be related to bilateral labyrinth lesions or endolymphatic hydrops on the affected side; and the involvement of autoimmune mechanisms also deserves attention.

Herein, a wavelength‐selective pyroelectric sensor based on a graphene field‐effect transistor (gFET) with a plasmon‐enhanced pyroelectric gate (PG) is reported. The PG gFET (PG‐gFET) uses a poly(vinylidene fluoride‐co‐trifluoroethylene) or PVDF‐TrFE membrane doped with plasmonic nanoparticles as the gate. Gold nanorods (AuNRs) or silver nanoparticles (AgNPs) are incorporated into the PVDF‐TrFE membrane to enhance the photothermal conversion efficiency of PVDF‐TrFE in a specific narrowband wavelength range. The wavelength‐selective photothermal effect can optically modulate the gate potential of the PG‐gFET; this, in turn, leads to a change in current through the graphene film of the transistor. The PG‐gFET with AuNRs exhibits a maximum responsivity of 0.79 μA mW−1 at the wavelength of 660 nm. Replacing AuNRs with AgNPs in the PVDF‐TrFE membrane results in tuning the plasmonic response of the transistor to 488 nm with a maximum responsivity of 0.68 μA mW−1. When plasmonic nanoparticles are absent from the PVDF‐TrFE membrane, the maximum response wavelength of the transistor is shifted to a midinfrared regime at 3125 nm, which is associated with the CC absorption of PVDF‐TrFE. The ability of the PG‐gFET to selectively respond to different light wavelengths will benefit many fields, including pyroelectric sensors, spectroscopy, and imaging.

Electrocatalytic CO2 reduction (ECR) to high value-added chemicals by using renewable electricity presents a promising strategy to realize “carbon neutrality”. However, the ECR system is still limited by its low current density and poor CO2 utilization efficiency. Herein, by using the confinement effect of covalent organic frameworks (COFs) to confine the in-situ growth of metal nanoclusters (NCs), we develop a series of Cu NCs encapsulated on COF catalysts (Cu-NC@COF) for ECR. Among them, Cu-NC@CuPc-COF as a gas diffusion electrode (GDE) achieves a maximum CO2-to-CH4 Faradaic efficiency of 74 ​± ​3% (at −1.0 ​V vs. Reversible Hydrogen Electrode (RHE)) with a current density of 538 ​± ​31 ​mA ​cm−2 (at −1.2 ​V vs. RHE) in a flow cell, making it one of the best among reported materials. More importantly, the current density is much higher than the relevant industrial current density (200 ​mA ​cm−2), indicating the potential for industrial application. This work opens up new possibilities for the design of ECR catalysts that utilize synergistic strategy.

We present photometric and spectroscopic observations and analysis of the Type IIb supernova (SN) SN 2019tua, which exhibits multiple bumps in its declining light curves between 40 and 65 days after discovery. SN 2019tua shows a time to peak of about 25 days, similar to other Type IIb SNe. Our observations indicate a decrease in its brightness of about 1 mag in the 60 days after the peak. At about days 50 and 60, its multiband light curves exhibit bumpy behavior. The complex luminosity evolution of SN 2019tua could not be well modeled with a single currently popular energy source model, e.g., radioactive decay of ^56 Ni, magnetar, interaction between the ejecta and a circumstellar shell. Even though the magnetar model has a smaller χ ^2 /dof value, the complex changes in SN 2019tua’s brightness suggest that more than one physical process might be involved. We propose a hybrid circumstellar medium (CSM) interaction plus ^56 Ni model to explain the bolometric light curve of SN 2019tua. The fitting results show that the ejecta mass M _ej ≈ 2.4 M _⊙ , the total CSM mass M _CSM ≈ 1.0 M _⊙ , and the ^56 Ni mass M _Ni ≈ 0.4 M _⊙ . The total kinetic energy of the ejecta is E _k ≈ 0.5 × 10 ^51 erg. Preexisting multiple shells suggest that the progenitor of SN 2019tua experienced mass ejections within approximately ∼6–44 yr prior to the explosion.

M-type stars are the ones that flare most frequently, but how big their maximum flare energy can reach is still unknown. We present 163 flares from 162 individual M2 through L1-type stars that triggered the GWAC, with flare energies ranging from 10 ^32.2 to 10 ^36.4 erg. The flare amplitudes range from △ G = 0.84 to ∼10 mag. Flare energy increases with stellar surface temperature ( T _eff ) but both △ G and equivalent duration ${\mathrm{log}}_{10}(\mathrm{ED})$ seem to be independent of T _eff . Combining periods detected from light curves of TESS and K2, spectra from LAMOST, the Sloan Digital Sky Survey, the 2.16 m telescope, and the Gaia DR3 data, we found that these GWAC flare stars are young. For the stars that have spectra, we found that these stars are in or very near the saturation region, and ${\mathrm{log}}_{10}({L}_{{\rm{H}}\alpha }/{L}_{\mathrm{bol}})$ is lower for M7–L1 stars than for M2–M6 stars. We also studied the relation between GWAC flare bolometric energy E _bol and stellar hemispherical area S , and found that ${\mathrm{log}}_{10}{E}_{\mathrm{bol}}$ (in erg) increases with increasing S (in square centimeters), and the maximum flare energy ${\mathrm{log}}_{10}{E}_{\mathrm{bol},\ \max }\geqslant {\mathrm{log}}_{10}S+14.25$ . For M7–L1 stars, there seem to be other factors limiting their maximum flare energies in addition to the stellar hemispherical area.

Abstract Background Synapses can adapt to changes in the intracerebral microenvironment by regulation of presynaptic neurotransmitter release and postsynaptic neurotransmitter receptor expression following hypoxic ischemia (HI) injury. The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) exerts a protective effect on neurons after HI and may be involved in maintaining the function of synaptic networks. In this study, we investigated the changes in the expression of NAAG, glutamic acid (Glu) and metabotropic glutamate receptors (mGluRs), as well as the dynamic regulation of neurotransmitters in the brain after HI, and assessed their effects on synaptic plasticity of the cerebral cortex. Methods Thirty-six Yorkshire newborn pigs (3-day-old, males, 1.0–1.5 kg) were selected and randomly divided into normal saline (NS) group (n = 18) and glutamate carboxypeptidase II inhibition group (n = 18), both groups were divided into control group, 0–6 h, 6–12 h, 12–24 h, 24–48 h and 48–72 h groups (all n = 3) according to different post-HI time. The content of Glu and NAAG after HI injury were detected by 1H-MRS scanning, immunofluorescence staining of mGluRs, synaptophysin (syph) along with postsynaptic density protein-95 (PSD95) and transmission electron microscopy were performed. ANOVA, Tukey and LSD test were used to compare the differences in metabolite and protein expression levels among subgroups. Correlation analysis was performed using Pearson analysis with a significance level of α = 0.05. Results We observed that the NAAG and mGluR3 expression levels in the brain increased and then decreased after HI and was significantly higher in the 12–24 h (P

Objective: To explore the mechanism underlying Kaixin-San (KXS) regulation of postsynaptic AMPA receptor (AMPAR) expression to mitigate toxic effects of the amyloid-β protein (Aβ).Methods: An animal model was established via intracerebroventricular injection of Aβ1–42. The Morris water maze test was conducted to evaluate learning and memory, while electrophysiological recording was conducted to assess the hippocampal long-term potentiation (LTP). Western blotting was used to detect expression levels of the hippocampal postsynaptic AMPAR and its accessory proteins.Results: The time spent to find the platform was significantly prolonged, the number of mice crossing the target site was significantly reduced, and the maintenance of LTP was inhibited in the Aβ group than in the control group. In the Aβ/KXS group, the time taken to find the platform was significantly shortened and the number of mice crossing the target site was significantly increased than in the Aβ group; furthermore, the inhibition of LTP induced by Aβ was reversed. The expression of GluR1, GluR2, ABP, GRIP1, NSF, and pGluR1–Ser845 was upregulated, while that of pGluR2–Ser880 and PKC δ was downregulated in the Aβ/KXS group.Conclusion: The increased expression of ABP, GRIP1, NSF, and pGluR1–Ser845 and the decreased expression of pGluR2–Ser880 and PKC δ under the influence of KXS, followed by the upregulation of postsynaptic GluR1 and GluR2, alleviated the inhibition of LTP induced by Aβ. Ultimately, the memory function of model animals was improved by KXS. Our study provides novel insights into the mechanism underlying KXS mitigation of Aβ-induced synaptic plasticity inhibition and memory impairment by altering the levels of accessory proteins associated with AMPAR expression.

Abstract The LHCb Collaboration recently gave an update on testing lepton flavour universality with B + → K +ℓ+ℓ − , in which a 3.1 standard deviations from the standard model prediction was observed. The g-2 experiment also reports a 3.3 standard deviations from the standard model on muon anomalous magnetic moment measurement. These deviations could be explained by introducing new particles including leptoquarks. In this paper, we show the possibility to search for heavy spin-1 leptoquarks at a future TeV scale muon collider by performing studies from three channels: 1) same flavour final states with either two bottom or two light quarks, 2) different flavour quark final states, and 3) a so-called “VXS” process representing the scattering between a vector boson and a leptoquark to probe the coupling between leptoquark and tau lepton. We conclude that a 3 TeV muon collider with 3 ab −1 of integrated luminosity is already sufficient to cover the leptoquark parameter space in order to explain the LHCb lepton flavour universality anomaly.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1β, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

(1) Background: Solanum nigrum L. is a plant of the genus Solanum in the family Solanaceae and is commonly used to treat tumors. Solasonin (SS) is a steroidal alkaloid extracted from Solanum nigrum L. that has anti-colorectal cancer (CRC) activity. (2) Methods: Column chromatography, semi-preparative HPLC and cellular activity screening were used to isolate potential anti-CRC active compounds in Solanum nigrum L., and structure identification using 1H-NMR and 13C-NMR techniques. Expression levels of HDAC in CRC were mined in the UALCAN database. The in vitro effects of SS on SW620 cell line and its mechanism were examined via Western blot, EdU staining, flow cytometry and immunofluorescence. CRC xenograft model and IHC staining were mainly used to evaluate the role of SS in vivo. (3) Results: The results showed that SS was the most potent anti-CRC component in Solanum nigrum L., which induced apoptosis and cell cycle arrest in the SW620 cell line. HDAC was highly expressed in CRC. The treatment of SW620 cell line with SS resulted in a significant downregulation of HDAC, an increase in the level of P53 acetylation and a subsequent increase in the level of P21. The in vivo validation results showed that SS could effectively inhibit CRC growth, which was associated with the downregulation of HDAC. (4) Conclusions: SS treatment for CRC mainly works through the induction of apoptosis and cycle arrest, and its mechanism of action is mainly related to HDAC-induced P53 acetylation, and the HDAC/P53 signaling pathway may be a potential pathway for the treatment of CRC.

Abstract This study aimed to compare the therapeutic effects of biplane skin dilator implantation with those of conventional skin dilator implantation in auricular reconstruction. A total of 137 patients with microtia who met the inclusion criteria from January 2020 to April 2021 were retrospectively selected. Sixty-three patients comprised the control group and were implanted with a skin expander using the conventional method. Seventy-four patients comprised the experimental group and were implanted with a skin expander using the biplane method. Non-parametric tests were used to compare the down-moving distance of the skin dilator between the experimental group and the control group. There was a statistically significant difference in the down-moving distance of the skin dilator between the experimental group and the control group (P 0.05). Moreover, there was no significant difference in the satisfaction rate of patients and their families between the experimental group and the control group (P > 0.05). In this study, the treatment effect of biplane skin dilator implantation was better than that of conventional skin dilator implantation.

Abstract Influenza viruses are major respiratory pathogens known to infect human and a variety of animals and are widely prevalent worldwide. Genome structure of influenza D virus (IDV) is identical to that of influenza C virus (ICV), and phylogenetic analyses suggest that IDV and ICV share a common ancestry and high homology. To date, the prevalence of ICV and IDV in China is unclear, but these viruses represent a potential threat to public health due to cross-species transmission and zoonotic potential. To efficiently monitor ICV and IDV, it is necessary to establish a dual detection method to understand their prevalence and conduct in-depth research. A duplex real-time PCR method for the simultaneous detection of ICV and IDV was developed. TaqMan fluorescent probes and specific primers targeting NP gene of ICV and PB1 gene of IDV were designed. This method exhibited good specificity and sensitivity, and the detection limit reached 1 × 101 copies/μL of plasmid standards of each pathogen. Thirty-one clinical swine samples and 10 clinical cattle samples were analyzed using this method. One positive sample of IDV was detected, and the accuracy of clinical test results was verified by conventional PCR and DNA sequencing. The duplex real-time PCR detection method represents a sensitive and specific tool to detect ICV and IDV. It provides technical support for virus research and clinical diagnosis of ICV and IDV. This information will benefit animal and human health.

Meniscal injuries caused by trauma, degeneration, osteoarthritis, or other diseases always result in severe joint pain and motor dysfunction. Due to the unique anatomy of the human meniscus, the damaged meniscus lacks the ability to repair itself. Moreover, current clinical treatments for meniscal injuries, including meniscal suturing or resection, have significant limitations and drawbacks. With developments in tissue engineering, biopolymer scaffolds have shown promise in meniscal injury repair. They act as templates for tissue repair and regeneration, interacting with surrounding cells and providing structural support for newly formed meniscal tissue. Biomaterials offer tremendous advantages in terms of biocompatibility, bioactivity, and modifiable mechanical and degradation kinetics. In this study, the preparation and composition of meniscal biopolymer scaffolds, as well as their properties, are summarized. The current status of research and future research prospects for meniscal biopolymer scaffolds are reviewed in terms of collagen, silk, hyaluronic acid, chitosan, and extracellular matrix (ECM) materials. Overall, such a comprehensive summary provides constructive suggestions for the development of meniscal biopolymer scaffolds in tissue engineering.

MicroRNAs are small non-coding RNAs that play important roles in gene regulation by influencing the translation and longevity of various target mRNAs and the expression of various target genes as well as by modifying histones and DNA methylation of promoter sites. Consequently, when dysregulated, microRNAs are involved in the development and progression of a variety of diseases, including cancer, by affecting cell growth, proliferation, differentiation, migration, and apoptosis. Preparations from the dried root and rhizome of Salvia miltiorrhiza Bge (Lamiaceae), also known as red sage or danshen, are widely used for treating cardiovascular diseases. Accumulating data suggest that certain bioactive constituents of this plant, particularly tanshinones, have broad antitumor effects by interfering with microRNAs and epigenetic enzymes. This paper reviews the evidence for the antineoplastic activities of S. miltiorrhiza constituents by causing or promoting cell cycle arrest, apoptosis, autophagy, epithelial-mesenchymal transition, angiogenesis, and epigenetic changes to provide an outlook on their future roles in the treatment of cancer, both alone and in combination with other modalities.