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To inhibit microbial spoilage in fresh and wet vermicelli and explore green and efficient preservatives, this study systematically investigated the antibacterial mechanism of hydrogen peroxide (H2O2), a green preservative, against the predominant spoilage bacteria in fresh and wet vermicelli. Firstly, the predominant spoilage bacteria in fresh and wet vermicelli were identified as Bacillus aryabhattai through high-throughput sequencing. Then, the influence of H2O2 on the inhibition zone diameter (IZD), the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC) and the growth curve of B. aryabhattai were analyzed through antibacterial activity assays. Simultaneously, the mechanism of antibacterial action experiments was conducted to observe the effects of H2O2 on the disruption of cell membrane and cell wall of B. aryabhattai, as well as the leakage of intracellular functional components. The results showed that increasing the concentration of H2O2 from 250 μg/mL to 1000 μg/mL resulted in an 8 mm increased IZD. Additionally, MIC and MBC of H2O2 were both 250 μg/mL. The growth curve analysis revealed that bacterial growth was completely inhibited within 24 hours when the concentration of H2O2 was higher than 250 μg/mL. The mechanism of antibacterial action experiments indicated that increasing concentrations of H2O2 significantly raised the concentrations of nucleic acids and proteins in the supernatant of the bacterial liquid (P

Abstract Efficient and reliable utilization of renewable energy at the user's end is the key to achieving a low‐carbon life. This paper proposed a new distributed energy system around the comprehensive utilization of solar energy by integrating solid oxide fuel cell (SOFC), energy storage equipment, photovoltaic thermal (PVT) collector, and heat pump. By integrating the use of SOFC and PVT, we can further minimize reliance on fossil fuels, while employing the coupling of PVT and heat pump effectively mitigates the inherent challenges of solar energy's variability and intermittency, all while enhancing overall system efficiency. On this basis, we apply the heat current method to construct a cross‐scale heat current model of the components and the system by considering the energy transfer, conversion, and storage characteristics of the system. By employing this model, we simulate the system's operation throughout an entire typical day, assess the COP enhancement of the PVT‐coupled heat pump system, analyze the influence of diverse operating conditions on daily system performance, and evaluate the economy of the energy storage devices in the system.

Abstract Background Ailanthone (Ail) extracted from medicinal plants has played an anticancer role in multiple cancers, while there is no research about Ail in renal cell carcinoma (RCC). Methods In the present study, we performed CCK-8 and flow cytometry to assess the effect of Ail on cell viability, apoptosis and cycle. We also performed tandem mass tags (TMT)-labeled quantitative proteomic technology and bioinformatic analysis to identify the functional pathway and proteins of Ail in RCC. Results The results showed Ail could inhibit cell viability and induce cell apoptosis. Proteomic profiling identified 1732 differentially expressed proteins in cells treated with Ail, compared to the negative control group. Gene ontology function annotation and Gene Set Enrichment Analysis (GSEA) were performed to identified the involved biological processes, molecular function and pathway. Results of GSEA proved the enrichment of Deps in EZH2 targets. The comparison between Deps and EZH2 co-expressed genes revealed 44 overlapped genes and we identified 4 hub genes (CDC20, CEP55, TOP2A, and UBE2C) associated with RCC progression. The molecular docking study revealed a moderate to tight binding potential of Ail and EZH2, and western blotting showed EZH2 was suppressed after cells treated with Ail. Conclusion Altogether, we identified the anticancer role of Ail in RCC, including inhibition of cell proliferation and induction of apoptosis. The results also screened the key proteins mediate the function of Ail, which have laid a theoretical foundation for elucidating the applications of Ail in clinical research.

Abstract Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system. Graphical Abstract

Abstract Background Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. Methods A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. Results Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. Conclusion The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Uncontrolled activation of c-Kit is closely related to the pathogenesis and progression of leukemia, gastrointestinal cancer, and other malignant diseases. Although there are several inhibitors available, due to the limitation of selectivity and the unfavorable side effects, designing and discovering highly selective inhibitors targeting c-Kit kinase, especially the gain of function mutation (for example c-Kit D816V), is still necessary. To identify novel c-Kit inhibitors, a metastable state-based virtual screening approach, which was successfully implemented in other kinase inhibitors, was employed in the current study. The results from our current study demonstrated the residues adjacent to the DFG motif within the activation loop could fold into short α-helices aside from the random coil, which was commonly found in the crystal structure. By expanding the conformation pool of the activation loop via PyRosetta-based ab initio folding protocol, we constructed a series of structural models of the c-Kit kinase intermediate between the inactive and active states. After evaluation of the thermal stability of the metastable state with molecular dynamics simulation, one structural model showed higher stability of α-helix, and the activation loop was retained. Considering the wild-type and D816V mutated KIT kinase shared similar metastable states during the kinase activation process, we developed a hypothesis that the identified intermediate might hold the potential to identify inhibitors targeting D816V mutations from the compound database. As expected, the intermediate structure showed higher selectivity to KIT D816V selective inhibitors, such as bezuclastinib, avapritinib, BLU-263, and elenestinib, than imatinib or masitinib. The virtual screening of the available KIT kinase inhibitor database further identified vorolanib, semaxanib, henatinib, and pexmetinib may possess potential inhibitory effects against wild type, as well as the mutated c-Kit kinase. The results from our current study not only proposed a novel structural model that could be used for the identification of selective c-Kit D816V inhibitors but also identified several potential inhibitors from available kinase inhibitors, which might shed new light on the design of new therapeutic approaches for c-Kit mutation-driven malignant diseases.

This paper introduces a novel carbon emission prediction method based on tracking control, leveraging historical CO2 emission prediction errors and feed-forward integration of electricity consumption data to enhance forecasting accuracy and minimize lag. Comparative analysis with pre-trained models such as LSTM and ARDL using Python showcases the proposed method's substantial reduction in prediction errors compared to singular reliance on electricity data, while also significantly reducing computational time in contrast to LSTM models. The findings establish a valuable reference for policymakers and researchers in refining carbon emission prediction methodologies and formulating effective carbon reduction policies.

Abstract Background Acer is a taxonomically intractable and speciose genus that contains over 150 species. It is challenging to distinguish Acer species only by morphological method due to their abundant variations. Plastome and nuclear ribosomal DNA (nrDNA) sequences are recommended as powerful next-generation DNA barcodes for species discrimination. However, their efficacies were still poorly studied. The current study will evaluate the application of plastome and nrDNA in species identification and perform phylogenetic analyses for Acer. Result Based on a collection of 83 individuals representing 55 species (c. 55% of Chinese species) from 13 sections, our barcoding analyses demonstrated that plastomes exhibited the highest (90.47%) species discriminatory power among all plastid DNA markers, such as the standard plastid barcodes matK + rbcL + trnH-psbA (61.90%) and ycf1 (76.19%). And the nrDNA (80.95%) revealed higher species resolution than ITS (71.43%). Acer plastomes show abundant interspecific variations, however, species identification failure may be due to the incomplete lineage sorting (ILS) and chloroplast capture resulting from hybridization. We found that the usage of nrDNA contributed to identifying those species that were unidentified by plastomes, implying its capability to some extent to mitigate the impact of hybridization and ILS on species discrimination. However, combining plastome and nrDNA is not recommended given the cytonuclear conflict caused by potential hybridization. Our phylogenetic analysis covering 19 sections (95% sections of Acer) and 128 species (over 80% species of this genus) revealed pervasive inter- and intra-section cytonuclear discordances, hinting that hybridization has played an important role in the evolution of Acer. Conclusion Plastomes and nrDNA can significantly improve the species resolution in Acer. Our phylogenetic analysis uncovered the scope and depth of cytonuclear conflict in Acer, providing important insights into its evolution.

Abstract Background Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. Methods We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. Results The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. Conclusions The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

Abstract Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication – a necessary step for precise medicine.

The residue generated during the production process of alumina, known as red mud, is a type of solid waste. The engineering properties of red mud can be significantly enhanced through the modification and solidification using inorganic materials. This study primarily utilized red mud as the raw material, supplemented with fly ash, lime, and clay, to conduct a solidification experiment of red mud. Orthogonal tests with three factors of two ash ratio (ratio of lime to fly ash), two ash content (total lime and fly ash), and red mud types were designed to study the changes of different ratios and maintenance conditions, etc., on the engineering properties of red mud. In addition, the micro-mechanisms of modified red mud were investigated by means of XRF, XRD, SEM and EDX. The results show that for optimum moisture content, red mud types are the most important influencing factor and for maximum dry density, two ash content is the most important influencing factor. For strength characteristics, the optimum two ash ratio was 1.5:1, the optimum two ash content was 50%, and the optimum red mud types were 70% CRM (red mud made of Chalco Shandong Co., Ltd) mixed with 30% clay. The addition of lime, fly ash, and clay improves the temperature shrinkage coefficient of the red mud. Through the analysis of microscopic composition and structure, it can be seen that goethite (α-FeO(OH)) and magnetite (γ-Fe2O3) in the red mud reacted with the modified materials to generate crystalline aluminosilicate and amorphous hydrated silicate gel, and these products together with the original calcium carbonate (CaCO3), tricalcium aluminate (Ca3Al2O6) and garnet (Ca3TiFeSi3O12) in the red mud which have certain strengths enhance the structural strength of the modified red mud. The optimum ratio obtained from the combined test results was lime: fly ash: CRM = 30:20:50. Therefore, using lime, fly ash and clay as modified materials can greatly enhance the engineering properties of red mud and realise the resourceful use of red mud.

IntroductionCognitive impairment is a frequent clinical symptom of non-communicating hydrocephalus (NCH) involving multiple domains, including executive function, working memory, visual-spatial function, language, and attention. Functional magnetic resonance imaging (fMRI) can be used to obtain information on functional activity in local brain areas and functional connectivity (FC) across multiple brain regions. However, studies on the associated cognitive impairment are limited; further, the pathophysiological mechanisms of NCH with cognitive impairment remain unclear. Here, we aimed to explore alterations in regional neural activity and FC, as well as the mechanisms of cognitive impairment, in patients with NCH.MethodsOverall, 16 patients with NCH and 25 demographically matched healthy controls (HCs) were assessed using the Mini-Mental State Examination (MMSE) and fMRI. Changes in regional homogeneity (ReHo), degree centrality (DC), and region of interest-based FC were analyzed in both groups. The relationship between fMRI metrics (ReHo, DC, and FC) and MMSE scores in patients with NCH was also investigated.Results and discussionCompared with the HC group, the NCH group exhibited significantly lower ReHo values in the left precentral and postcentral gyri, and significantly higher ReHo values in the left medial prefrontal cortex (MPFC). The NCH group also showed significantly higher DC values in the bilateral MPFC compared with the HC group. Regarding seed-based FC, the MPFC showed reduced FC values in the right superior parietal and postcentral gyrus in the NCH group compared with those in the HC group. Moreover, within the NCH group, MMSE scores were significantly negatively correlated with the ReHo value in the left MPFC and the DC value in the bilateral MPFC, whereas MMSE scores were significantly positively correlated with FC values. To conclude, regional neural activity and FC are altered in patients with NCH and are correlated with cognitive impairment. These results advance our understanding of the pathophysiological mechanisms underlying the association between NCH and cognitive impairment.

Sawdust, a solid waste generated during stone processing, poses a serious threat to the environment with its untreated accumulation. This paper first analyzes the chemical composition and physical properties of sawdust, and discusses its mechanism of action in cement mortar. By systematically optimizing the blending ratio and modification method of sawdust, the sawdust-modified cement mortar with excellent performance was prepared. This study evaluates the key performance indicators of sawdust-modified cement mortar, such as compressive strength, flexural strength, and durability, through a series of experiments. The experimental results indicate that the incorporation of an appropriate amount of sawdust significantly enhances the mechanical properties of cement mortar, while also improving its durability, particularly in terms of freeze-thaw resistance. Microstructural analysis reveals the mechanism by which sawdust improves the pore structure of cement mortar; the active components in the sawdust react with the hydration products of cement, resulting in the formation of crystalline structures with higher strength.Therefore, the use of sawdust as a modifier in cement mortar can improve its mechanical properties and durability, while simultaneously reducing the accumulation of solid waste and promoting the sustainable development of building materials.

IntroductioncGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear.MethodsTo investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed.ResultsThe results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette–Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment.ConclusionThe present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

A novel BHEs is proposed that can overcome the problems associated with the low heat-transfer efficiency of borehole heat exchangers (BHEs) that are connected in series (BHEs-S) and the low heat-transfer temperature differences of BHEs that are connected in parallel (BHEs-P). The new BHE uses a combined series and parallel connection (BHEs-CSP), which can further be classified into individual in-series and in-parallel zones. A numerical model of the new BHEs-CSP is then developed to optimize the key design parameters such as borehole spacing, number of series stages, and heat-extraction methods. The results show that, with the optimal configuration, the average soil temperature with a BHEs-CSP is 6.70°C higher than for a BHE that is connected in parallel. Furthermore, the heat-transfer efficiency can be improved by 4.1% compared to BHEs that are connected in series. It is recommended that the distance between buried pipes in the series area and parallel area should be 5.25 m, and the series number of buried pipe groups should be 4. To study the overall performance of the solar-assisted ground-source heat-pump with a BHEs-CSP (SAGSHP-CSP), a TRNSYS model is developed. The results show that the optimal area- and heat-storage-ratios (for in-series zone to in-parallel zone), using SAGSHP-CSP, are 1:4 and 3:2, respectively. Under these conditions, the system coefficient of performance (SCOP) is over 5.2 and the COP and SCOP is improved by 9.8% and 13.0% compared to GSHP systems with BHEs-P. Furthermore, an improvement by 18.4% and 18.2%, compared to the GSHP system with BHEs-S, is reported.

Objective: Hyperglycemia in individuals with diabetes is associated with chronic kidney disease (CKD); however, little is known about its association with those without diabetes. Our goal was to investigate the association between glycemic indicators and CKD in individuals without diabetes. Methods: This cross-sectional study included 9610 participants without diabetes who participated in the Health and Nutrition Examination Survey between 2005 and 2016. Exposures included postprandial glucose dip (PGD), fasting blood glucose (FBG), oral glucose tolerance test two-hour blood glucose (OGTT-2HBG), and glycated hemoglobin (HbA1C) levels. Moreover, CKD was defined as an estimated glomerular filtration rate below 60 mL/min per 1.73 m2 or a urinary albumin-creatinine ratio of ≥ 30 mg/g. Two multivariate models were constructed. Interaction effects were also explored. Results: The mean age of the participants was 46.0 years, with 50.3 % being females. The prevalence of CKD was 12.6 %. In the final multivariable models, the odds ratios (ORs) for CKD were 1.51 (95 % confidence interval [CI]: 1.22,1.88, p

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.

Objectives Hip fractures in elderly patients are associated with a high mortality rate. Most deaths associated with hip fracture result from complications after surgery. Recent studies suggest that some inflammation biomarkers may be useful to estimate excess mortality. This study aimed to investigate the prognostic value of admission inflammation biomarkers in elderly patients with hip fracture. Methods We reports on a retrospective study of elderly hip fracture patients admitted to a hospital in China between January 2015 and December 2019. A total of 1085 patients were included in the study, and their demographic and pre‐operative characteristics were analyzed. The inflammation biomarkers included monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), and C‐reactive protein (CRP) to albumin ratio (CAR). The predictive performance of NLR, MLR and CAR was assessed by receiver operating characteristics (ROC) curve analysis and the association between admission inflammation markers and mortality was evaluated by Cox proportional regression. Results The 30‐day, 1‐year, 2‐year, and 4‐year mortality were 1.6%, 11.5%, 21.4% and 48.9%, respectively. The optimal cut‐off values of admission NLR, MLR and CAR for 1‐year mortality were 7.28, 0.76, and 1.36. After adjusting the covariates, preoperative NLR ≥ 7.28 (HR = 1.419, 95% CI: 1.080–1.864, p = 0.012) were found to be only independent risk factors with 4‐year all‐cause mortality, the preoperative CAR ≥ 1.36 was independently associated with 1‐year (HR = 1.700, 95% CI: 1.173–2.465, p = 0.005), 2 year (HR = 1.464, 95% CI: 1.107–1.936, p = 0.008), and 4‐year (HR = 1.341, 95% CI: 1.057–1.700, p = 0.016) all‐cause mortality, While age, CCI score, and low hemoglobin at admission were also risk factors for postoperative all‐cause mortality. Conclusion Admission CAR and NLR may be useful indicators for predicting the long‐term mortality of elderly patients undergoing hip fracture surgery, and that more research is needed to validate these findings.

Abstract This study aimed to evaluate the association between polymyxin B (PMB) exposure and acute kidney injury (AKI) and analyze the risk factors for PMB‐induced AKI in critically ill patients. Plasma concentrations of PMB were determined using an ultraperformance liquid chromatography–tandem mass spectrometer in intensive care unit patients who were administered PMB. Univariate and multivariate analyses were conducted to identify risk factors. A receiver operating characteristic curve was constructed to assess the discriminant power of the factors and to identify the cutoff value for AKI. The white blood cell count and estimated area under the concentration–time curve (AUC) of patients administered PMB were independent risk factors for PMB‐induced AKI, where AUC were calculated using a first‐order pharmacokinetic equation based on the mid‐dosing interval concentration (C1/2t) and peak concentration. The area under the receiver operating characteristic curve of the final model was 0.805 (95% confidence interval, 0.690–0.921). The cutoff value for the combined predictor was 0.57. Alternatively, when using C1/2t, which was strongly correlated with AUC, as the only independent risk factor, the analysis showed that the 3.47 μg/ml threshold provides favorable differentiation between the AKI and non‐AKI groups. These results provide insightful information for therapeutic drug monitoring–guiding PMB dosing in clinical practice.

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds.

Introduction: Biapenem is a carbapenem antibiotic widely used in Asia, can be used for the treatment of adults and children with infections due to susceptible bacteria. Although biapenem is utilized in the treatment of a diverse range of bacterial infections, current pharmacokinetic data in the context of septic populations remain limited. Consequently, our research aims to evaluate the pharmacokinetics and efficacy of biapenem within a septic population to optimize biapenem therapy.Methods: In this study, we characterized the pharmacokinetics of biapenem in septic patients using a population pharmacokinetic (PPK) approach. The clinical PK data to develop the PPK model were obtained from 317 septic patients admitted to Nanjing Drum Tower Hospital between 2018 and 2022. All patients were randomized to the modeling and validation cohorts at a 3:1 ratio, with PPK modeling and validation performed utilizing the NONMEM software.Results: The model found to best describe the available data was a two-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V2), and intercompartmental clearance (Q). A covariate analysis identified that creatinine clearance (CLCR) was a significant covariate influencing biapenem CL, while blood urea nitrogen (BUN) was a significant covariate influencing biapenem Q. Accoding to the clinical outcome analyses, 70% of the time that the free antimicrobial drug concentration exceeds the MIC (fT>MIC) is associated with favourable clinical outcomes. The PPK model was then used to perform Monte Carlo simulations to evaluate the probability of attaining 70% fT>MIC.Conclusions: A final PPK model of biapenem was established for patients with sepsis. The current daily dosage regimen of 1.2 g may insufficient to achieve 70% fT>MIC in septic patients. The dosage regimen of 600 mg every 6 h appears to be the optimal choice.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice.A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of “Tislelizumab combined with Sunitinib”. Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good.Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

Objective The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE.Methods Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study.Results (1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p

Abstract The application of DNA barcoding has been significantly limited by the scarcity of reliable specimens and inadequate coverage and replication across all species. The deficiency of DNA barcode reference coverage is particularly striking for highly biodiverse subtropical and tropical regions. In this study, we present a comprehensive barcode library for woody plants in tropical and subtropical China. Our dataset includes a standard barcode library comprising the four most widely used barcodes (rbcL, matK, ITS, and ITS2) for 2,520 species from 4,654 samples across 49 orders, 144 families, and 693 genera, along with 79 samples identified at the genus level. This dataset also provides a super-barcode library consisting of 1,239 samples from 1,139 species, 411 genera, 113 families, and 40 orders. This newly developed library will serve as a valuable resource for DNA barcoding research in tropical and subtropical China and bordering countries, enable more accurate species identification, and contribute to the conservation and management of tropical and subtropical forests.

Abstract Irinotecan (Ir) is commonly employed as a first-line chemotherapeutic treatment for colorectal cancer (CRC). However, tremendous impediments remain to be addressed to surmount drug resistance and ameliorate adverse events. Poly-ADP-Ribose Polymerase (PARP) participates in the maintenance of genome stability and the repair of DNA damage, thus playing a critical role in chemotherapy resistance. In this work, we introduce a novel curative strategy that utilizes nanoparticles (NPs) prepared by dynamic supramolecular co-assembly of Ir and a PARP inhibitor (PARPi) niraparib (Nir) through π-π stacking and hydrogen bond interactions. The Ir and Nir self-assembled Nano-Twin-Drug of (Nir-Ir NPs) could enhance the therapeutic effect on CRC by synergistically inhibiting the DNA damage repair pathway and activating the tumor cell apoptosis process without obvious toxicity. In addition, the Nir-Ir NPs could effectively reverse irinotecan-resistance by inhibiting the expression of multiple resistance protein-1 (MRP-1). Overall, our study underscores the distinctive advantages and potential of Nir-Ir NPs as a complementary strategy to chemotherapy by simultaneously overcoming the Ir resistance and improving the anti-tumor efficacy against CRC.

Abstract Purpose This study aimed to assess the impact of perioperative care based on the Roy Adaptation Model (RAM) on psychological well-being, postoperative pain, and health-related quality of life (HRQoL) in elderly patients with benign prostatic hyperplasia (BPH) undergoing transurethral resection of the prostate (TURP). Methods A total of 160 elderly patients diagnosed with BPH between June 2021 and June 2022 and scheduled for TURP were randomly assigned to either the routine care group (n = 80) or the RAM group (n = 80). The RAM group received standard care supplemented with interventions based on the RAM model. Negative emotions measured by the Hospital Anxiety and Depression Scale (HADS), pain intensity by the Visual Analog Scale (VAS), and HRQoL by the 36-Item Short Form Health Survey (SF-36) were measured at the preoperative visit (T0), at 30 days (T1), and at 3 months of (T2) follow‑up. Results Repeated measures ANOVA revealed significant differences in psychological well-being, postoperative pain intensity, and HRQoL within both the routine care and RAM groups across the three time points. Holm-Sidak’s multiple comparisons test confirmed significant differences between each time point for both groups. The RAM intervention led to significant reductions in anxiety and depression levels, alleviation of postoperative pain intensity, and improvements in various domains of HRQoL at T1 and T2 compared to routine care. Conclusion Incorporating the RAM model into perioperative care for elderly patients undergoing TURP for BPH has shown promising results in improving psychological well-being, reducing postoperative pain intensity, and enhancing HRQoL.

In deep coal mining, the combinations of high temperature, high ground pressure, high karst water pressure and stress disturbance lead to a discontinuous deformation and complex rupture behavior of the surrounding rocks. Reproduction of the rock failure process using the numerical approaches becomes an important way to study the rock rupture phenomena and to reveal associated failure mechanisms. With a strict mathematical foundation in contact representation, numerical integration, and convergence examination, the improved DDA method with block subdivision strategy and bond representations can effectively simulate the failure process of fractured rock masses from continuous elastic deformation stage to progressive failure stage, and the complete breakage stage. Based on the idea of piecewise characterization of the edge-edge bonding effect, a segmented edge-edge bond model is proposed, where the linear and nonlinear bonding constitutive relationships are equivalently characterized by paired penalty springs at the center of each segment. The segmented edge-edge bond models are embedded into the conventional framework of the discontinuous deformation analysis with a triangular segmentation for the optimized simulation of rock fracturing process. By the deformation and stress analysis of the simulation results in the center compression test of the simple support beam, the uniaxial compression and the Brazilian splitting test of rock specimen, the accuracy of the proposed model is verified. The reasonable values or ranges of the segmentation number, bonding stiffness ratio, tangential-to-normal stiffness ratio and other associated parameters of the segmented edge-edge bond are obtained. In the numerical simulation of uniaxial compression test for complete and cavitated sandstone specimens, the assignment methods of the deformation associated parameters (e.g., block elastic modulus, block Poisson ratio) and the strength associated parameters (e.g., bond tensile strength, bond cohesion, and bond friction angle) are clarified. Also, the accuracy of the proposed model in reproducing the stress-strain curve and initial cracking position is verified. In the numerical investigation of the Brazilian splitting test of sandstone with single or combined flaws, the feasibility of the proposed model in reproducing crack initiation, propagation and intersection is verified. In summary, the proposed segmented edge-edge bond model can be applied for investigating the failure phenomena and mechanisms of rock masses with complex fracture networks.

Although considerable laboratory and modeling activities were performed to investigate the enhanced oil recovery (EOR) mechanisms and potential in unconventional reservoirs, only limited research has been reported to investigate actual EOR implementations and their surveillance in fields. Eleven EOR pilot tests that used CO2, rich gas, surfactant, water, etc., have been conducted in the Bakken unconventional play since 2008. Gas injection was involved in eight of these pilots with huff ‘n’ puff, flooding, and injectivity operations. Surveillance data, including daily production/injection rates, bottomhole injection pressure, gas composition, well logs, and tracer testing, were collected from these tests to generate time-series plots or analytics that can inform operators of downhole conditions. A technical review showed that pressure buildup, conformance issues, and timely gas breakthrough detection were some of the main challenges because of the interconnected fractures between injection and offset wells. The latest operation of co-injecting gas, water, and surfactant through the same injection well showed that these challenges could be mitigated by careful EOR design and continuous reservoir monitoring. Reservoir simulation and machine learning were then conducted for operators to rapidly predict EOR performance and take control actions to improve EOR outcomes in unconventional reservoirs.

The impact of frequent water deficits on dominant tree species in boreal forests has received increased attention, particularly towards addressing the global climate change scenarios. However, the impacts of coupled light intensity and water deficit in the regeneration and growth of Larix gmelinii seedlings, a dominant species in China’s boreal forests, are still unclear. We conducted a dual-factor controlled experiment with four light intensities (natural sunlight, 50% shading, 75% shading, and 90% shading) and three soil water conditions (80%, 60%, and 40% soil saturated water content). The results showed that the coupling of light and water has a significant effect on the growth and development of Larix gmelinii seedlings. In 40% of the saturated soil moisture content, net photosynthetic rate, transpiration rate, chlorophyll a, and total phenol—leaf were significantly lower than the same light conditions under 80% soil saturated water content. Under the coupling treatment of 60% soil saturated water content and 50% shading treatment, the plant height increment, net photosynthetic rate, stomatal conductance, transpiration rate, chlorophyll a, and phenolic compound content were significantly higher than those of other coupling treatments; however, more than 75% shading inhibited photosynthetic parameters, chlorophyll a, total flavonoid—leaf, and total flavonoid—branch. Our results have important implications for forest management practices; they provide a scientific reference for the early growth of Larix gmelinii seedlings under the coupling of light and water and promote the survival and growth of seedlings.

The strong alkalinity of red mud and the heavy metals it contains pose a serious threat to the environment. This study investigated the possibility of applying red mud as a solid waste material in road construction to mitigate the problem of red mud accumulation. Red mud was modified using titanium gypsum and phosphogypsum as curing agents. The effects of varying gypsum types and mixing ratios on the mechanical properties and heavy metal leaching of the resulting red mud-based materials were assessed using percussion tests, unconfined compressive strength measurements, scanning electron microscopy (SEM), and continuous heavy metal leaching tests. The results showed that the optimal moisture content for titanium gypsum–cement-stabilized red mud (RTC) exceeds that of phosphogypsum–cement-stabilized red mud (RPC), with RTC exhibiting a lower maximum dry density compared to RPC. When the gypsum admixture was within 10%, the strength of the RPC was higher than that of the RTC at the same and curing time. The reticulation in RPC-10 was denser. The cumulative heavy metal releases from both RTC and RPC were within the permissible limits for Class III groundwater discharge standards. Based on the comprehensive test results, RPC is identified as the superior modified red mud material, with an optimal mix ratio of red mud/phosphogypsum/cement of 87:5:8.

Utilization of red mud in road projects is an effective way to consume large amounts of red mud on a large scale. In order to meet the requirements for road performance, a modified material, Heinchem, has been developed on the basis of extensive experiments, and the long-term environmental risks of red mud modified by this material have been investigated. By collecting and modifying original red mud samples, a series of continuous leaching tank experiments are carried out based on the exposure scenario analysis. According to the leaching content of pollution in the original and modified red mud, the characteristic pollutants are identified. The release mechanism of these characteristic pollutants in the modified red mud is revealed, and the long-term release amount is predicted. Furthermore, in light of the actual road use scenario of the modified red mud, a risk assessment model is established and used to simulate the release, migration, and transformation of characteristic pollutants during the use of modified red mud as roadbed material. The groundwater environmental risk is then assessed. Finally, an acute toxicity test of earthworms and a seed germination test are conducted to investigate the impact of the modified red mud on the farmlands. The results showed that the proposed red mud modified materials have obvious curing effects on V, As, Se, Mo, and F. When the leaching contents of V, Cr6+, Cr3+, As3+, Se4+, Se6+, Mo, and F in the modified red mud were lower than 0.15 mg/L, 0.1 mg/L, 0.2 mg/L, 0.012 mg/L, 0.012 mg/L, 0.012 mg/L, 0.075 mg/L, and 1.2 mg/L, respectively, the environmental risk of modified red mud during long-term road use is acceptable. This study provides a new way for the resource utilization of red mud.

Flexible air conditioning energy use, leveraging building thermal inertia and thermal energy storage, can effectively reduce building carbon emissions. The carbon reduction potential of flexible energy use in air conditioning is influenced by uncertainties, such as dynamic electricity carbon emission factors. To accurately quantify this potential, a methodology for calculating the carbon reduction achievable through flexible energy use in air conditioning, considering these uncertainties, is proposed. First, the sources of uncertainty in air conditioning energy use are identified and mathematically described. Next, the relationship between uncertainty, load, and carbon emissions is analyzed. Subsequently, the carbon reduction mechanisms of various flexible air conditioning energy use methods, based on building thermal inertia and energy storage, are, respectively, explained, and corresponding mathematical models are established. Finally, a case study is conducted to verify the feasibility of the method and reveal the characteristics of the carbon reduction potential of various flexible energy use methods, considering uncertainty.

Oleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.

The integrated energy system at the park level, renowned for its diverse energy complementarity and environmentally friendly attributes, serves as a crucial platform for incorporating novel energy consumption methods. Nevertheless, distributed energy generation, characterized by randomness, fluctuations, and intermittency, is significantly influenced by the surrounding environment. Within the park, the output of multiple devices frequently diverges significantly from the actual demand, potentially resulting in energy waste phenomena, such as the curtailment of wind and solar power. To tackle the dual challenges of balancing energy supply and demand while reducing carbon emissions in the industrial park, this paper introduces a low-carbon integrated energy system that incorporates distributed renewable and clean energy sources. Mathematical models are formulated for the source–grid–load–storage components of this low-carbon integrated energy system. Furthermore, various operational scenarios for the park-level integrated energy system are analyzed. The ultimate goal is to devise an economically viable, low-carbon, and efficient operational strategy for the integrated energy system, aiming to satisfy the diverse objectives of various stakeholders.

The support stiffness of the turbopump rotor system with angular contact ball bearing varies with the rotational speed, which leads to the inaccurate prediction of the dynamics of the turbopump rotor system. The model of the rotor bearing system was constructed based on the theoretical model of angular contact ball bearing stiffness, and the dynamics characteristics of the turbopump system were calculated. To verify the accuracy of the stiffness and the dynamics model, a test system of the turbopump rotor with angular contact ball bearings was designed. Since the bearing stiffness cannot be measured directly, a stiffness identification model was introduced, and an unbalanced response test was conducted to verify the dynamics model. It was found that the turbopump bearing stiffness increased dynamically with speed and reduced the unbalance response of the rotor. The results show that the angular contact ball bearing stiffness model and the dynamics model of the rotor support system are accurate and provide support for the dynamics design of the turbopump rotor system with angular contact ball bearings.

Objective Establish an animal model of preeclampsia in goats, collect data on various physiological indicators and maternal biological characteristics of the disease model to compare with clinical feature of the disease in humans, provide reference for the prevention and treatment of preeclampsia in humans. Methods Twenty-three goats bred in Chongming district were divided into three groups: Control group, no surgical procedure was performed on animals of this group; sham group, ewes in this group underwent the sham operation on the 100±5th day of gestation, and only the uterine artery was exposed and dissociated; surgical group, a silver vascular clamp was clipped on one side of the uterine body artery of the ewe to narrow the inner diameter of the artery at the same gestation period (100±5) days. Heart rate and hindlimb blood pressure were continuously monitored in control and surgical ewes from 100 to 140 d of gestation, and blood flow data within the lateral branches of the uterine arteries of ewes in the sham group were collected using a hemodynamometer in combination with a hemodynamic probe and an animal physiological signal collector, as well as changes in blood flow within the uterine arteries in the lateral branches of the uterine arteries of the surgical group before and after placement of vascular clips in the surgical ewes. At the expected date of delivery, jugular vein blood was taken from ewes for routine blood test, creatinine, urea nitrogen, and blood ion analysis; urine was also collected from ewes in each group for analysis of urinary protein and urinary creatinine. All experimental groups were subjected to cesarean section on the 140±5th day of gestation in ewes, and then liver, kidney, uterus and placenta tissues were taken from ewes in each group and stained with HE for pathological observation.Results After 15 minutes of preeclampsia modeling surgery, blood flow volume remained stable in the vessel stenosis segment and the volume differential was relatively reduced in comparison to the control group and sham group (P＜0.05，P＜0.01). Compared with the control group, the ewes in the surgical group showed prenatal changes such as increased serum osmolality, decreased hemoglobin, increased blood glucose and urea nitrogen values, as well as increased levels of calcium, sodium, and chloride ions (all P

Abstract Sphingosine kinases (SphK), including SphK1 and SphK2, are important enzymes promoting progression of prostate cancer. SKI-178 is a novel and highly potent SphK1/2 dual inhibitor. We here tested the potential anti-prostate cancer cell activity of SKI-178. Bioinformatics analyses and results from local tissues demonstrated that that both SphK1 and SphK2 are upregulated in human prostate cancer tissues. Ectopic overexpression of SphK1 and SphK2, by lentiviral constructs, promoted primary prostate cancer cell proliferation and migration. In primary human prostate cancer cells and immortalized cell lines, SKI-178 potently inhibited cell viability, proliferation, cell cycle progression and cell migration, causing robust cell death and apoptosis. SKI-178 impaired mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production and ATP depletion.SKI-178 potently inhibited SphK activity and induced ceramide production, without affecting SphK1/2 expression in prostate cancer cells. Further, SKI-178 inhibited Akt-mTOR activation and induced JNK activation in prostate cancer cells. Contrarily, a constitutively-active Akt1 construct or the pharmacological JNK inhibitors attenuated SKI-178-induced cytotoxicity in prostate cancer cells. In vivo, daily intraperitoneal injection of a single dose of SKI-178 potently inhibited PC-3 xenograft growth in nude mice. SphK inhibition, ceramide production, ATP depletion and lipid peroxidation as well as Akt-mTOR inactivation and JNK activation were detected in PC-3 xenograft tissues with SKI-178 administration. Together, targeting SphK1/2 by SKI-178 potently inhibited prostate cancer cell growth in vitro and in vivo.

Abstract Background Patellofemoral pain syndrome (PFPS) is a chronic disease. Its early symptoms are mild and can be relieved by rest after the pain. If there is no effective rehabilitation, it may develop into patellofemoral arthritis. Physiotherapy and appropriate exercise intervention can improve PFPS and postural control during exercise. Tan Tui (TT) is an effective means to improve postural control. Whether combined kinesio taping (KT) can be used as an effective treatment for PFPS patients’ recovery has not yet been confirmed. Methods/design Seventy-two eligible patients with early-stage PFPS will be recruited and randomized into 4 groups: TT + KT group (n = 18), TT + KTp group (n = 18), KT group (n = 18), and CON group (n = 18). The TT + KT group was treated with TT combined with KT intervention; the TT + KTp group was treated with TT and KT placebo technical intervention; the KT group was treated with KT intervention alone; the CON group was treated with routine activities. All 4 groups received 30 min, three times a week, for a total of 6 weeks of intervention training. Measurements will be performed at baseline, mid-intervention (4 weeks), and post-intervention (6 weeks) with visual analog scale/score, (VAS), Knee joint Lysholm function score (Lysholm), UniPedal Stance Test (UST), Star Excursion Balance Test ( SEBT), Relative Peak Torque, (RPT), and Knee joint Position PercePtion (KJPP), to check the maintenance of the effect of any intervention. Discussion For the first time in this trial, the impact will be evaluated. If the results are the same as expected, they will provide evidence that TT combined with KT sticking intervention can promote the posture control of patients with early PFPS. Trial registration Chinese Clinical Trial Registry ChiCTR2100051166. Registered on 15 September 2021.

Abstract Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway.

Improving the reproducibility of biomedical research results remains a major challenge. Transparent and accurate reporting of progress can help readers evaluate the reliability of research results and further explore an experiment by repeating or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is the second part of the Chinese translation of the complete interpretation of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (original text can be found at https://arriveguidelines.org) and based on the best practices for following the ARRIVE 2.0 guidelines in international journals. This part includes Items 4-7 of "ARRIVE Essential 10" in the ARRIVE 2.0 guidelines: "Randomization", "Blinding", "Outcome Measurement", and "Statistical Methods". Our Chinese translated version aims to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhancing the standardization of experimental animal research and reporting, and promoting the high-quality development of experimental animal technology and comparative medicine research in China.

Abstract To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime‐avibactam (CAZ‐AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ‐AVI between August 2020 and May 2023 was conducted. Patients whose 12‐h creatinine clearance prior to CAZ‐AVI treatment and steady‐state concentration (Css) of CAZ‐AVI were both monitored were enrolled. The free fraction (fCss) of CAZ‐AVI was calculated from Css. The joint PK/PD targets of CAZ‐AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ‐AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ‐AVI. Optimal drug dose adjustment of CAZ‐AVI in ARC patients requires dynamic drug concentration monitoring.

Abstract Background Rice (Oryza sativa) straw is a common waste product that represents a considerable amount of bound energy. This energy can be used for biogas production, but the rate and level of methane produced from rice straw is still low. To investigate the potential for an increased biogas production from rice straw, we have here utilized WRINKLED1 (WRI1), a plant AP2/ERF transcription factor, to increase triacylglycerol (TAG) biosynthesis in rice plants. Two forms of Arabidopsis thaliana WRI1 were evaluated by transient expression and stable transformation of rice plants, and transgenic plants were analyzed both for TAG levels and biogas production from straw. Results Both full-length AtWRI1, and a truncated form lacking the initial 141 amino acids (including the N-terminal AP2 domain), increased fatty acid and TAG levels in vegetative and reproductive tissues of Indica rice. The stimulatory effect of the truncated AtWRI1 was significantly lower than that of the full-length protein, suggesting a role for the deleted AP2 domain in WRI1 activity. Full-length AtWRI1 increased TAG levels also in Japonica rice, indicating a conserved effect of WRI1 in rice lipid biosynthesis. The bio-methane production from rice straw was 20% higher in transformants than in the wild type. Moreover, a higher producing rate and final yield of methane was obtained for rice straw compared with rice husks, suggesting positive links between methane production and a high amount of fatty acids. Conclusions Our results suggest that heterologous WRI1 expression in transgenic plants can be used to improve the metabolic potential for bioenergy purposes, in particular methane production.

Improving the reproducibility of biomedical research results is a major challenge. Researchers reporting their research process transparently and accurately can help readers evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. this article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org). The first part of the article includes the preface and the "Key 10" section, which covers "study design" "sample size" and "inclusion and exclusion criteria". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China.

Objective Bioinformatics method was used to screen the key genes of ovarian cancer (OV) and analyze their correlation with immune cell infiltration. Methods We retrieved and downloaded three OV datasets from GEO, and screened DEGs in OV tissues by the GEO2R online analysis tool, then performed gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on DEGs using the Metascape database; after analyzing the PPI network of DEGs using the STRING database, the results were imported into Cytoscape software, and the MCC algorithm provided by the CytoHubba plugin was used to obtain the top 10 key genes; then we used the Kaplan-Meier Plotter database and GEPIA to perform survival analysis and co-expression analysis of key genes to derive the most highly correlated group of genes before doing their mRNA and protein expression; finally, the TISIDB database was used to explore the association between key genes and OV immune infiltration cell. Results A total of 161 DEGs were obtained in this study, and their GO functions were mainly related to the response of cells to TGF- β stimulation, P53-mediated DNA damage, cell cycle arrest and protein kinase binding caused by signal transduction, etc. KEGG pathway is mainly concentrated in cancer pathway, P53 signaling pathway, complement and coagulation cascade and PI3K-Akt signaling pathway. Among the 10 key genes screened by Cytoscape, only CCNB1, HMMR, KIAA0101, AURKA, CEP55, ECT2 and TOP2A have significant effects on the prognosis of OV patients, among which CCNB1 and AURKA have the highest expression correlation in OV, and their mRNA and protein are highly expressed, which is not conducive to the prognosis of patients. The expression of CCNB1 and AURKA was positively correlated with the abundance of Th2 cells and Act-CD4 cells, but negatively correlated with eosinophils. Conclusion CCNB1 and AURKA are the key genes of OV, which are related to immune cells in OV microenvironment, and can be used as biomarkers for early diagnosis and treatment of OV.

Two unreported heteropolysaccharides, denoted as YCJP–1 and YCJP–2, were isolated from the herbs of Chloranthus japonicus. YCJP–1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475–228,443 Da range. YCJP–2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects of C. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP–1 and YCJP–2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP–1, and YCJP–2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP–1, and YCJP–2. Moreover, YCJP–2 demonstrated superior anti-gastric cancer effects compared to YCJP–1. This could potentially be attributed to YCJP–2’s higher glucose content and narrower molecular weight distribution.

Pyroptosis, an innate immune response, plays a crucial role in the pathological process of inflammatory diseases. Although pyroptosis blockade is considered a potential therapeutic strategy, no ideal candidate drug has been identified. The natural product Chojaponilactone B (CJB) has demonstrated anti-inflammatory effects, but its role in macrophage pyroptosis has not been studied. This study aimed to investigate the effect and mechanism of CJB in inhibiting macrophage pyroptosis. Using an LPS/ATP-induced THP-1 macrophage pyroptosis model, we found that CJB significantly inhibited pyroptosis and reduced the levels of NLRP3, caspase 1, N-GSDMD, and inflammatory cytokines IL-1β and IL-18. RNA sequencing analysis revealed that CJB interfered with LPS/ATP-induced THP-1 macrophage gene expression, suggesting involvement in anti-inflammatory and anti-pyroptotic signaling pathways. Additionally, CJB suppressed LPS/ATP-induced elevations in TLRs, MyD88, pro-IL-1β, and NF-κB and blocked NF-κB p65 nuclear translocation. In summary, CJB inhibits NLRP3 activation and macrophage pyroptosis through the TLR/MyD88/NF-κB pathway, providing important evidence for its development as a potential drug for treating pyroptosis-related inflammatory diseases.

Objectives We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).Methods PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.Results A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV1 and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=−4.62, 95% CI −8.90 to −0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.Conclusion ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.PROSPERO registration number CRD42022356816.

ObjectiveTo investigate the clinical and pathological factors associated with preoperative hypothalamus invasion and postoperative outcomes of adamantinomatous craniopharyngiomas (ACPs) after the expanded endonasal approach (EEA) resection.MethodsNinety-three specimens of ACPs, consisting of 71 primary and 22 recurrent tumors, were investigated for the expression of TGF-β1, SMAD2, SMAD3, and β-catenin by immunohistochemistry staining. The clinical information of relevant patients, including the extent of resection, hypothalamus invasion, endocrinopathy, complications, and prognosis, was reviewed. The relationships between the expression of these immunopathological markers and clinical factors were analyzed.ResultsEndocrinological dysfunctions were more common in recurrent patients and primary patients with hypothalamus invasion in the comparisons. For recurrent patients, the rate of gross total resection (GTR) was significantly lower than for primary patients (63.6% vs. 90.1%, P = 0.007). According to radiological and intraoperative findings, invasive ACPs (IACPs) included 48 (67.6%) cases in primary tumors. The expression of TGF-β1 and β-catenin was significantly higher in recurrent tumors (P = 0.021 and P = 0.018, respectively) and IACPs (P = 0.008 and P = 0.004, respectively). The expression level of TGF-β1 was associated with hypothalamus involvement (Puget grade, P = 0.05; Vile grade, P = 0.002), postoperative endocrinopathy (P = 0.01), and pituitary stalk preservation (P = 0.008) in primary patients. In addition, the extent of resection, treatment history, hypothalamic invasion, and level of TGF-β1 expression had significant influences on tumor recurrence/progression after surgery separately.ConclusionOur study demonstrated the potential role of TGF-β1 in the regulation of hypothalamus invasion in ACPs and the prediction of prognosis after EEA surgery. The TGF-β signaling pathway may represent a crucial mechanism in the aggressive behavior and progression of ACPs.

Chronic wounds and scar formation are widespread due to limited suitable remedies. The macrophage is a crucial regulator in wound healing, controlling the onset and termination of inflammation and regulating other processes related to wound healing. The current breakthroughs in developing new medications and drug delivery methods have enabled the accurate targeting of macrophages in oncology and rheumatic disease therapies through clinical trials. These successes have cleared the way to utilize drugs targeting macrophages in various disorders. This review thus summarizes macrophage involvement in normal and pathologic wound healing. It further details the targets available for macrophage intervention and therapeutic strategies for targeting the behavior of macrophages in tissue repair and regeneration.

During 6–10 January 2021, a recorded strong cold surge took place in China, with over 800 observational stations reaching their historical extremes. Unlike previous studies that focused on the response of either the power load or generation separately, this study quantitatively revealed the impacts on the balance between the demand and supply sides of the grid. On the demand side, the sensitivity of power load was found to increase substantially higher in southern China (0.533 GW °C−1) than in the northern region (0.139 GW °C−1) due to the limited municipal heating system. On the supply side, the hourly wind power generation dropped from the highest of 110 GW on 6 January to the lowest of 54 GW on 9 January due to the reduction in wind speed. In addition, a reduction in solar power generation was observed during 8–10 January. Thus, the balance of the power system was influenced by this cold event. As an effective adaptation measure, results further showed that early warning by three weeks ahead can be obtained by an operational climate model. The sensitivity of China's power system to such cold surge events may increase remarkably due to the expected increase in the proportion of wind and solar power generation in future new-type power systems. Thus, close cooperation between climate scientists and power engineers is needed to build the resilience of the power system to the cold extremes.