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IntroductionAlcoholic liver disease (ALD) is a pathological state of the liver caused by longterm alcohol consumption. Recent studies have shown that the modulation of the gut microbiota and its metabolic products, specifically the short-chain fatty acids (SCFAs), exert a critical role in the evolution and progression of ALD. The Liuweizhiji Gegen-Sangshen beverage (LGS), as a functional beverage in China, is derived from a traditional Chinese herbal formula and has been clinically applied for ALD treatment, demonstrating significant efficacy. However, the underlying mechanisms of LGS for alleviating ALD involving gut microbiota regulation remain unknown.MethodsIn this study, an ALD murine model based on the National Institute on Alcohol Abuse and Alcoholism (NIAAA) method was established.ResultsThe results showed that oral LGS treatment dose-dependently alleviated alcoholinduced liver injury and inflammation in mice through decreasing levels of ALT, AST and proinflammatory cytokines (TNF-α, IL-6, IL-1β). LGS significantly improved liver steatosis, enhanced activities of alcohol metabolizing enzymes (ALDH and ADH), and reduced the CYP2E1 activity. Notably, regarding most detected indices, the effect of LGS (particularly at medium and high dose) was comparable to the positive drug MTDX. Moreover, LGS had a favorable effect on maintaining intestinal barrier function through reducing epithelial injury and increasing expression of occludin. 16S rRNA sequencing results showed that LGS remarkably modulated gut microbiota structure in ALD mice via recovering alcohol-induced microbial changes and specifically mediating enrichment of several bacterial genera (Alloprevotella, Monoglobus, Erysipelatoclostridium Parasutterella, Harryflintia and unclassified_c_Clostridia). Further study revealed that LGS increased production of SCFAs of hexanoic acid in cecum, promoted alcohol-mediated reduction of GRP43 expression in ileum, and increased serum GLP-1 level.DiscussionOverall, LGS exerts a remarkable protective effect on ALD mice through the gut microbiota mediated specific hexanoic acid production and GPR43/GLP-1 pathway.

Blueberry anthocyanins (ACNs) have been widely applied in the food industry and medicine due to their numerous beneficial properties. However, the stability of ACNs is extremely poor. This study aimed to develop a delivery system for ACNs using nanocomplexes prepared from gellan gum (GG) and whey protein isolate (WPI) via Maillard reaction. The effects of the GG-WPI nanocomplexes on the stability, antioxidant capacity, and bioavailability of ACNs were investigated. FTIR, fluorescence spectroscopy, and UV–vis absorption spectroscopy revealed covalent bonding between the GG and WPI in the nanocomplexes. The nanocomplex demonstrated a good loading efficiency for ACNs (60.34 %), with a particle size of 368.42 nm. It also showed better stability and bioaccessibility than free ACNs, and their DPPH radical scavenging capacity reached a maximum of 63.11 %. Our research is significant for developing novel multifunctional foods and constructing high-performance food delivery systems.

Microstructure engineering serves as a potent approach to counteract the mechanical deterioration of Ni-rich layered cathodes, stemming from anisotropic strain during Li+ (de)intercalation. However, a pressing challenge persists in devising a direct method for fabricating radially aligned cathodes utilizing oriented hydroxide precursors. In this study, we synthesized LiNi0.92Co0.04Mn0.04O2 oxides boasting superior radially aligned, size-refined primary particles through a combination of strategic precipitation regulation and lithiation tuning. Elongated primary particles, achieved by stepwise control of ammonia concentration and pH during particle growth, facilitate the formation of radially aligned hydroxide precursor particles. Leveraging the size-refined and radially aligned primary particles, our prepared LiNi0.92Co0.04Mn0.04O2 cathode exhibits a high discharge capacity of 229 ​mAh ​g−1 ​at 0.05 C, alongside excellent cycle stability, retaining 93.3% capacity after 200 cycles at 0.5 C (30 ​°C) in a half cell, and 86.4% capacity after 1000 cycles at 1 C (30 ​°C) in a full cell. Revisiting the regulation from precursor to oxide underscores the significance of controlling primary particles to maximize size perpendicular to [001] and attain suitable size along [001] during precursor precipitation and high-temperature calcination, offering valuable insights for synthesizing high-performance Ni-rich cathodes.

In the retail industry, effective management of memberships is crucial, particularly within the pharmaceutical sector, as it fosters customer loyalty and drives sales growth. However, pharmacies often face challenges related to membership attrition and inactive members, which restrict the full potential of their membership programs. This research aims to address these challenges by optimizing pharmacy membership management systems through the utilization of big data technology. By leveraging the power of big data and employing machine learning algorithms, this study examines member data from multiple prominent pharmacy chains. The findings demonstrate the effectiveness of this approach in significantly increasing the level of activity among inactive memberships. Furthermore, this research unveils significant behavioral patterns among pharmacy members, shedding light on their preferences, purchasing habits, and interaction patterns. In this study, an artificial neural network (ANN) is employed to predict reactivation success rates, membership activity, and sales revenue based on website/app usage and member engagement. Two input factors, namely the frequency of website/app usage and member engagement score, are evaluated alongside three output factors: reactivation success rate, increase in membership activity levels, and increase in overall sales and revenue. Tailoring strategies based on member profiles and preferences enables pharmacies to re-engage customers and cultivate renewed loyalty. Importantly, these efforts yield positive impacts beyond membership activity, influencing overall sales and revenue generation for pharmacies. The ANN analysis reveals significant correlations and acceptable prediction errors. The insights gained from this study offer valuable information for enhancing membership management strategies and adjusting marketing efforts to cater to the specific needs and expectations of diverse customer segments. The practical, data-driven approach presented in this study equips pharmacies with the means to activate and re-engage dormant members. By harnessing the potential of big data technology and leveraging machine learning algorithms, pharmacies can optimize their membership management systems, enhance customer engagement, and improve their overall retail operations. This research underscores the significance of leveraging data-driven insights in the retail industry and showcases the transformative capabilities of big data technology in enhancing customer relationship management practices.

The confined aquifer dewatering for long-deep excavations usually encounters challenges due to complicated geotechnical conditions, large excavation sizes, and high hydraulic pressures. To propose the most efficient scheme of confined aquifer dewatering for long-deep excavations, dewatering optimizations were performed using the simulation–optimization method. An open cut tunnel of the Jiangyin-Jingjiang Yangtze River Tunnel Project was taken as an example. The methods of finite element and linear programming (LP) were combined to optimize the dewatering process. A three-dimensional finite element model was developed. After simulating the pumping tests, hydraulic conductivity was inverted. Then, necessary parameters in the LP method were determined by simulating dewatering with each pumping well, and various LP models were developed based on some important influence factors such as dewatering sequence, considered pumping wells, and pumping rate limitation. Finally, the optimal pumping rates were solved and applied to the numerical model, with induced drawdown and ground settlement computed for comparison. The results indicate that the optimization can significantly reduce the required wells in the original design. Dewatering in the deepest zone exhibits the highest efficiency for long-deep excavations with gradually varying depths. For the dewatering sequence from the shallowest to the deepest zone, more pumping wells are required but less energy is consumed. Higher quantity and more advantageous locations of pumping wells in the LP model usually result in lower total pumping rate, drawdown, and ground settlement. If more pumping wells are considered in the deepest zone, pumping rate limitation of single well will only slightly increase the total pumping rate, number of required pumping wells, drawdown, and ground settlement.

ABSTRACT Aims Very few cohort studies are available about the relation between remnant cholesterol (RC) and diabetes. Based on a prospective cohort survey, this research aimed at investigating if high RC was related to a future diabetes risk in the Chinese population, as well as to compare the association between RC, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), triglycerides (TG), TG/HDL‐C, LDL‐C/HDL‐C, TC/HDL‐C, and non‐high‐density lipoprotein cholesterol (non‐HDL‐C), and future diabetes risk. Materials and Methods 6,700 baseline normoglycemic participants of the REACTION study's Beijing center were recruited in 2011–2012 and followed up in 2015. Multivariate Cox regression analyses were performed to explore the relationship of RC, HDL‐C, LDL‐C, TC, TG, LDL‐C/HDL‐C, TG/HDL‐C, TC/HDL‐C, and non‐HDL‐C and a future diabetes risk. Results After potential confounders were adjusted for, only RC (HR 1.134, 95% CI 1.016–1.267, P = 0.025) was positively related to a future diabetes risk, and only HDL‐C (HR 0.728, 95% CI 0.578–0.918, P = 0.007) was negatively related to a future diabetes risk. The rest of the lipid parameters were not related to a future risk of diabetes. Sensitivity and stratification analyses revealed that the relation between RC and future diabetes risk was stable. RC and future diabetes risk were still positively correlated even when the HDL‐C was ≥1.04 mmol/L (HR 1.167, 95% CI 1.050–1.297, P = 0.004). Conclusions It was RC, but not other lipid parameters, that was independently and positively related to a future risk of diabetes among the Chinese general population. Moreover, the relationship between RC and diabetes risk was stable, even with appropriate levels of HDL‐C.

To examine how different harvesting periods affect the storage quality of 'Satsuma' plum fruits, this study analyzed 13 quality and physiological metrics post-harvest and utilized principal component analysis (PCA) and mathematical models to assess (0±0.5)℃ low temperature storage quality across three different harvesting periods (100 d after flowering, 103 d after flowering, 106 d after flowering). The results showed that harvesting at 103 days after full bloom led to the best preservation effect. Additionally, the hardness and total acidity of plum fruit decreased by 37.37% and 27.06% respectively until the end of the storage period, which was the slowest. Furthermore, changes in relative conductivity, anthocyanins, total soluble solids, malondialdehyde, total phenols, and flavonoids were relatively smooth. The activity of polyphenol oxidase was low, while peroxidase, superoxide dismutase, and catalase activities were high, specifically catalase activities. After conducting PCA analysis, it was determined that PC1, PC2, and PC3 accurately capture 87.472% of the relevant information. These results suggested that varying harvesting periods would have significant impacts on all indicators. The mathematical model analysis revealed that the plum fruits harvested at 100, 103, and 106 days after bloom, and stored for 56 days, had comprehensive scores of 1.06, 0.99, and 2.69, respectively. Lower comprehensive scores indicated better quality, so the order of preservation effect was as follows: 103 days after bloom>100 days after bloom>106 days after bloom. The study provides a theoretical framework for evaluating postharvest preservation and quality of plum fruits, along with technical parameters to enable timely harvesting.

Abstract Nanocrystalline metallic materials have the merit of high strength but usually suffer from poor ductility and rapid grain coarsening, limiting their practical application. Here, we introduce a core-shell nanostructure in a multicomponent alloy to address these challenges simultaneously, achieving a high tensile strength of 2.65 GPa, a large uniform elongation of 17%, and a high thermal stability of 1173 K. Our strategy relies on an ordered superlattice structure that excels in dislocation accumulation, encased by a ≈3 nm disordered face-centered-cubic nanolayer acting as dislocation sources. The ordered superlattice with high anti-phase boundary energy retards dislocation motions, promoting their interaction and storage within the nanograins. The disordered interfacial nanolayer promotes dislocation emission and effectively accommodates the plastic strain at grain boundaries, preventing intergranular cracking. Consequently, the order-disorder core-shell nanostructure exhibits enhanced work-hardening capability and large ductility. Moreover, such core-shell nanostructure exhibits high coarsening resistance at elevated temperatures, enabling it high thermal stability. Such a design strategy holds promise for developing high-performance materials.

Abstract There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs’ long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.

Abstract Objective In the surgery-focused field of obstetrics and gynecology (OB-GYN), the development of residents’ skills is paramount. This study aims to evaluate the impact of an enhanced Peyton Four-Step Teaching Model on the foundational skill training of first-year OB-GYN residents. Methods Utilizing a cohort study design, we assessed 116 first-year residents from the OB-GYN residency program at Shengjing Hospital of China Medical University from June 2021 to June 2023. The 57 residents beginning their training in 2022 were part of the Refined Peyton (RP) group, introduced to the RP method; the 59 residents from 2021 served as the Traditional Teaching-mode (TTM) group, receiving conventional simulation-based instruction. Teaching effectiveness was assessed by comparing theoretical knowledge and skill performance assessments, National Medical Licensing Examination (NMLE) pass rates, direct observation of procedural skills (DOPS) one year post-training, and survey feedback. Results The theoretical knowledge scores for both groups were comparable at 78.78 ± 4.08 and 78.70 ± 3.83, with no significant difference (P = 0.76). However, the experimental group demonstrated superior performance in skill operation assessments, first-time NMLE pass rates, and DOPS evaluations one year after training [(77.05 ± 5.39) vs. (84.60 ± 5.65), 100.0% (57/57) vs. 86.4% (51/59), and (75.22 ± 3.56) vs. (82.54 ± 3.43)], as well as higher teaching satisfaction scores [(4.63 ± 0.46) vs. (3.92 ± 0.62)], with all differences being statistically significant (P

Abstract The honeybee gut microbiome is crucial for degrading diverse pollen glycans. Yet it is unclear how this process shapes the interactions among bacteria. Here, we demonstrate a conditional mutualistic interaction between strains of two honeybee gut bacteria Bifidobacterium asteroides and Gilliamella apicola. When co-occurring in vitro and in vivo, Bifidobacterium provides complementary demethylation service to promote Gilliamella growth on methylated homogalacturonan, an enriched polysaccharide of pectin. In exchange, Gilliamella shares digestive products with Bifidobacterium, through which a positive interaction is established. This positive interaction vanishes when Bifidobacterium is not required on a non-methylated diet. Results from biochemical and gene expression analyses combined with model simulation further suggest that the ratio change of the two major homogalacturonan breakdown products, galacturonic acid (GalA) and di-GalA, determines the bacterial interaction. This study unravels how glycan metabolism may shape the interactions between honeybee gut bacteria.

Abstract Objective The current research aims to evaluate the efficacy and safety of anlotinib, an orally administered small-molecular tyrosine kinase inhibitor (TKI), in the treatment of recurrent epithelial ovarian cancer (EOC). Methods Patients with recurrent EOC subjected to treatment with anlotinib in Fourth Hospital of Hebei Medical University from 2020 to 2022 were included. The evaluation involved a thorough review of medical records, focusing on parameters such as the objective response rate (ORR), disease control rate (DCR), survival outcomes, and safety profile. Results This study recorded 51 patients, with 26 patients undergoing anlotinib monotherapy. The median progression-free survival (PFS) was 4.0 months, whereas the median overall survival (OS) was not reached. Seven cases underwent a combined treatment of anlotinib with chemotherapy. Among them, two patients achieved partial response (PR), two were categorized as stable disease (SD), and three were identified as having progressive disease (PD). The ORR and DCR were 28.5% (2/7) and 57.1% (4/7), respectively. Additionally, 18 cases received anlotinib maintenance therapy, and the median PFS and the median OS were 7.0 months and 25.5 months, respectively. The most prevalent adverse effects included fatigue (38.6%), hypertension (27.3%), nausea and vomiting (25.0%) and hand-foot syndrome (25.0%). Conclusion Anlotinib demonstrated mild efficacy in the treatment of recurrent EOC, whether employed as monotherapy, chemotherapy-combined therapy, or maintenance therapy. The safety profile was proven manageable and well-tolerated, suggesting that anlotinib may emerge as a viable and novel treatment option for recurrent EOC.

Abstract Background Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients. Methods Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed. Results Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P

Background/Aims: As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Materials and Methods: Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Results: Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Conclusion: Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Abstract Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.

Abstract Phage therapy holds promise as an alternative to antibiotics for combating multidrug-resistant bacteria. However, host bacteria can quickly produce progeny that are resistant to phage infection. In this study, we investigated the mechanisms of bacterial resistance to phage infection. We found that Rsm1, a mutant strain of Salmonella enteritidis (S. enteritidis) sm140, exhibited resistance to phage Psm140, which was originally capable of lysing its host at sm140. Whole genome sequencing analysis revealed a single nucleotide mutation at position 520 (C → T) in the rfbD gene of Rsm1, resulting in broken lipopolysaccharides (LPS), which is caused by the replacement of CAG coding glutamine with a stop codon TAG. The knockout of rfbD in the sm140ΔrfbD strain caused a subsequent loss of sensitivity toward phages. Furthermore, the reintroduction of rfbD in Rsm1 restored phage sensitivity. Moreover, polymerase chain reaction (PCR) amplification of rfbD in 25 resistant strains revealed a high percentage mutation rate of 64% within the rfbD locus. We assessed the fitness of four bacteria strains and found that the acquisition of phage resistance resulted in slower bacterial growth, faster sedimentation velocity, and increased environmental sensitivity (pH, temperature, and antibiotic sensitivity). In short, bacteria mutants lose some of their abilities while gaining resistance to phage infection, which may be a general survival strategy of bacteria against phages. This study is the first to report phage resistance caused by rfbD mutation, providing a new perspective for the research on phage therapy and drug-resistant mechanisms.

Abstract Background Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. Results The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 ℃, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. Conclusion In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.

Abstract Background Human umbilical cord mesenchymal stem cells-derived extracellular vesicles (hUCMSC-EVs) have potent immunomodulatory properties similar to parent cells. This study investigated the therapeutic effects and immunomodulatory mechanisms of hUCMSC-EVs in an experimental lupus nephritis model. Methods The hUCMSC-EVs were isolated by using differential ultracentrifugation. In vivo, the therapeutic effects of hUCMSC-EVs in lupus-prone MRL/lpr mice were investigated, and the mechanisms of treatment were explored according to the abnormal T and B cell responses among both the spleen and kidney. Results MRL/lpr mice treated with hUCMSC-EVs reduced proteinuria extent, serum creatinine and renal pathological damage; decreased splenic index and serum anti-dsDNA IgG level; and improved survival rate. hUCMSC-EVs lowered the percentage of T helper (Th)1 cells, double-negative T (DNT) cells, and plasma cells among splenocytes; inhibited the infiltration of Th17 cells but promoted regulatory T (Treg) cells in the kidney, followed by a reduction in pro-inflammatory cytokine levels(IFN-γ, IL-2, IL-6, IL-21, and IL-17 A). In addition, hUCMSC-EVs inhibited the activation of STAT3 and down-regulated IL-17 A protein levels in the kidney. Conclusion The results of this study demonstrated that hUCMSC-EVs had therapeutic effects on experimental lupus nephritis (LN) by regulating Th1/Th17/Treg imbalance and inhibiting DNT and plasma cells. Additionally, hUCMSC-EVs inhibited Th17 cell differentiation in kidney by regulating the IL-6/STAT3/IL-17 signal pathway, which might be an important mechanism for alleviating renal injury. Taken together, we demonstrated that hUCMSC-EVs regulating T and B cell immune responses might represent a novel mechanism of hUCMSCs in treating LN, thus providing a new strategy for treating LN.

Three mole percent yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) ceramics are exemplary materials for dental restoration due to their high mechanical strength, fracture toughness, chemical endurance, and biocompatibility. Nevertheless, 3Y-TZP ceramics are opaque and their CAD/CAM manufacturing process may cause micro-cracks in conventional clinical practice. In this study, 3Y-TZP ceramic samples were prepared using vat photopolymerization, pre-sintering, external staining, and final high-temperature sintering. The microstructures, mechanical properties, optical properties, and cytotoxicity of the 3Y-TZP ceramic samples were investigated. The results indicate that with increasing Fe3+ concentration of staining solution from 0.1 mol/L to 0.3 mol/L and increasing staining time from 5 s to 30 min, the 3Y-TZP ceramic samples showed a tetragonal crystal structure of zirconia with densely packed grains and a slight increase in grain size. The flexural strength, Vickers hardness, and fracture toughness of 3Y-TZP ceramic samples stained in 0.1–0.3 mol/L Fe3+ solution for 5 s to 3 min were all greater than 665 MPa, 11.9 GPa, and 5 MPa m1/2, respectively, meeting the mechanical requirements for clinical application. Colorimetric analysis revealed a decrease in L* (black-white index) from 90.4 to 81.3, an increase in a* (green-red index) from −1.5 to 3.2, and an increase in b* (blue-yellow index) from 11.6 to 20.3, approximating the commercial VITA 3D-Master Shade Guide chromaticity. Furthermore, the 3Y-TZP ceramic samples exhibited a cell viability of 90% or higher toward L929 cells.

Abstract Background Evidence on the association between serum vitamin C (sVC) levels and obesity is limited. This study aimed to explore the relationship between sVC and body mass index (BMI) in adolescents aged 12 to 19 years. Methods We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006, with 3952 participants. sVC and BMI were independent variables and dependent variables, respectively. The associations of sVC with BMI were examined using multivariable linear regression models. Age, sex, and race/ethnicity were analyzed as subgroups. Then, we devised smooth curve fittings and saturation threshold analysis to address the nonlinear relationship. Results sVC had a negative correlation with BMI after adjusting for all covariates (β: -1.020, 95% CI: -1.359, -0.680). In the subgroup analysis by age, sex, and race/ethnicity, there was still a negative correlation between sVC and BMI (p

Abstract Chronic heart failure is one of the most common reasons for hospitalization. Current risk stratification is based on ejection fraction, whereas many arrhythmic events occur in patients with relatively preserved ejection fraction. We aim to investigate the mechanistic link between proarrhythmic abnormalities, reduced contractility and diastolic dysfunction in heart failure, using electromechanical modelling and simulations of human failing cardiomyocytes. We constructed, calibrated and validated populations of human electromechanical models of failing cardiomyocytes, that were able to reproduce the prolonged action potential, reduced contractility and diastolic dysfunction as observed in human data, as well as increased propensity to proarrhythmic incidents such as early afterdepolarization and beat-to-beat alternans. Our simulation data reveal that proarrhythmic incidents tend to occur in failing myocytes with lower diastolic tension, rather than with lower contractility, due to the relative preserved SERCA and sodium calcium exchanger current. These results support the inclusion of end-diastolic volume to be potentially beneficial in the risk stratifications of heart failure patients.

Abstract During the drilling process, the issue of drilling fluid loss can lead to changes in the mechanical properties of the formation, thereby altering the stress environment of nearby faults. In order to assess the risk of fault activation during drilling operations, the Ordos M area shale was selected as the research object. Mechanical experiments were conducted on rock samples immersed in water-based drilling fluid with a pressure differential of 2 MPa and a temperature of 50 °C. The changes in the mechanical properties of the shale before and after immersion in drilling fluid were determined. Based on the experimental results, combined with the spring combination model and fault activation theory, a quantitative evaluation of fault activation risk was conducted. The findings revealed that the shale in this region has a high clay content, demonstrating a certain level of water sensitivity. The presence of micro-pores and micro-fractures is well-developed, increasing the interaction probability between drilling fluids and clay minerals. After immersion in drilling fluid, there was a varied decline in all mechanical strengths of the shale. The elastic modulus is positively correlated with the shear strength and Coulomb stress of the fault plane. The Poisson’s ratio is positively correlated with the shear strength and negatively correlated with the Coulomb stress. The greater the internal friction and cohesion, the higher the shear strength of the fault plane, and the larger the friction coefficient, the smaller the Coulomb stress, resulting in a more stable fault.

Objective The most common causes of plantar and heel pain are plantar fasciitis and calcaneal spurs, and they often co‐exist. Surgery is a recognized treatment for refractory plantar fasciitis. However, few studies have proposed treatment options for patients with metatarsophalangeal fasciitis with bone spurs. Accordingly, this study's purpose was to propose a four‐step surgical regimen, and to improve the surgical outcome of plantar fasciitis with osteophytes and to establish a procedure for surgical treatment. Methods Retrospective analysis of 45 patients suffering from plantar fasciitis with bone spurs from 2020 to 2023. All patients underwent a four‐step procedure, including plantar fascia release, calcaneal spur grinding, inflammatory tissue removal, and calcaneal burr decompression. The imaging parameters and functional scores were recorded before and after the operation. The objective evaluation included the measurement of calcaneal spur length on radiographs. Clinical evaluation included the American Orthopaedic Foot and Ankle Society (AOFAS), the Visual Analog Scale (VAS), and the Foot and Ankle Outcome Scale (FAOS). Measurement data that conformed to normal distribution were expressed as (x2 ± s), and pre‐and postoperative AOFAS, FAOS, and VAS scores were compared using repeated‐measures ANOVA, and preoperative and postoperative spur lengths were compared using paired t‐tests. Results The 45 patients were followed up for 3 to 30 months, (17.72 ± 8.53) months, at final follow‐up, the patient's AOFAS score improved from preoperative (74.93 ± 5.56) to (94.78 ± 3.98), FAOS score increased from preoperative (76.42 ± 3.37) to (96.16 ± 2.74), the VAS score decreased from (3.18 ± 0.54) to (1.07 ± 1.20) (p

Abstract In recent years, deep learning has been widely used in vulnerability detection with remarkable results. These studies often apply natural language processing (NLP) technologies due to the natural similarity between code and language. Since NLP usually consumes a lot of computing resources, its combination with quantum computing is becoming a valuable research direction. In this paper, we present a Recurrent Quantum Embedding Neural Network (RQENN) for vulnerability detection. It aims to reduce the memory consumption of classical models for vulnerability detection tasks and improve the performance of quantum natural language processing (QNLP) methods. We show that the performance of RQENN achieves the above goals. Compared with the classic model, the space complexity of each stage of its execution is exponentially reduced, and the number of parameters used and the number of bits consumed are significantly reduced. Compared with other QNLP methods, RQENN uses fewer qubit resources and achieves a 15.7% higher accuracy in vulnerability detection.

Abstract Abnormalities in the extracellular matrix (ECM) play important roles in the regulation and progression of clear cell renal cell carcinoma (ccRCC). The cysteine cathepsin is one of the major proteases involved in ECM remodeling and has been shown to be aberrantly expressed in multiple cancer types. However, the clinical significance and biological function of distinct cysteine cathepsins in ccRCC remain poorly understood. In this study, several bioinformatics databases, including UALCAN, TIMER, GEPIA and the Human Protein Atlas datasets, were used to analyze the expression and prognostic value of different cysteine cathepsin family members in ccRCC. We found that the expression level of CTSF was downregulated in tumor tissues and closely related to the poor survival of ccRCC patients. Further in vitro experiments suggested that CTSF overexpression suppressed the proliferation and migration of ccRCC cells. Moreover, the expression of CTSF was shown to be associated with several immune-infiltrating cells and immunomodulators in ccRCC. These results indicated that CTSF might be a promising diagnostic and prognostic marker in ccRCC.

Abstract Background Chronic inflammation may contribute to increased mortality risk in individuals with osteoarthritis (OA), but research on the prognostic value of inflammatory biomarkers is limited. We aimed to evaluate the associations of the systemic immune–inflammation index (SII) and systemic inflammation response index (SIRI) with all-cause and cardiovascular mortality among US adults with OA. Methods This cohort study included 3545 adults with OA aged ≥ 20 years from the National Health and Nutrition Examination Survey 1999–2020. The SII and SIRI were calculated using complete blood cell count data. Participants were categorized as having a higher or lower SII and SIRI using cutoff points derived by the maximally selected rank statistics method. Cox proportional hazards models, Fine–Gray competing risk regression models and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the associations between the SII/SIRI and mortality in OA patients. Results Over a median follow-up of 5.08 (3.42–9.92) years, 636 (17.94%) deaths occurred, including 149 (4.20%) cardiovascular deaths. According to multivariable-adjusted models involving demographic, socioeconomic, and health factors, OA patients with a higher SII had a twofold greater risk of all-cause mortality than patients with a lower SII (HR 2.01; 95% CI: 1.50–2.68). Similarly, a higher SIRI was associated with an 86% increased risk of all-cause mortality relative to a lower SIRI (HR 1.86; 95% CI: 1.46–2.38). Similar to the trend found with all-cause mortality, patients with an elevated SII and SIRI had a 88% and 67% increased risk of cardiovascular mortality, respectively, compared to patients with a lower SII (HR 1.88; 95% CI: 1.16–3.03) and SIRI (HR 1.67; 95% CI: 1.14–2.44). Time-dependent ROC curves showed that both the SII and SIRI have moderate and valid performance in predicting short- and long-term mortality in patients with OA. Conclusions Higher SII and SIRI values were associated with greater all-cause and cardiovascular mortality among US adults with OA.

Abstract Traditional herbs have a history of clinical use in anti-fatigue. However, several adverse effects of herbs have been identified. Pityriasis rosea-like eruption (PR-LE) is a rare cutaneous complication of herbs. To the best of our knowledge, there have been few reports of PR-LE following herbs. Here, we described a case of PR-LE that developed 6 days after taking anti-fatigue herbs. After the 17 days of stopping Aconitum carmichaelii Debx and Panax Ginseng, it notably faded. So, when anti-fatigue herbs being authorized for fatigue use, monitoring for potential adverse effects is necessary.

Soil freeze–thaw (F/T) processes are a typical physical phenomenon on the Qinghai-Tibetan Plateau (QTP), significantly impacting regional climate change and the hydrological cycle. This study presents a Seasonal-Trend Decomposition using Loess and Long Short-Term Memory (STL-LSTM) method to detect spatiotemporal variations in soil F/T on the QTP using time series data from the Cyclone Global Navigation Satellite System (CYGNSS). The model was validated against ERA5 soil temperature data (0–7 cm) and independent in-situ observations, demonstrating good consistency. The SHapley Additive exPlanations (SHAP) model was integrated into the STL-LSTM framework to quantitatively evaluate the contributions of input features to F/T retrieval, revealing that time features contributes the most to retrieval results, followed by surface reflectivity. Moreover, spatiotemporal analysis of QTP F/T dynamics shows prominent seasonal patterns, with topography-induced shielding delaying thawing in central QTP regions and freezing trends extending from low (28°N) to high latitudes (36°N). The proposed method offers a new pathway for monitoring freeze–thaw transitions in high-latitude regions and holds potential for expansion into future high-frequency and multi-polarization GNSS-R missions.

The current study was conducted to investigate the influences of dietary compound acidifier (CA, Formic acid (45 %), malic acid (0.3 %), Fumaric acid (0.6 %) and Succinic acid (0.6 %), Biomin Feed Additives (Shanghai) Ltd) on the growth, anti-oxidation, immunity, and intestinal health of channel catfish (Ictalurus punctatus). Six experimental diets (about 36 % crude protein and 5 % crude lipid) were prepared with graded levels of dietary CA (0 (control), 0.05 %, 0.10 %, 0.20 %, 0.40 %, and 0.80 %). A total of 648 fish with similar initial body weight (143.77 ± 0.73 g) were randomly placed into 18 tanks, with 36 fish in each tank. Fish were hand-fed to apparent satiation thrice daily for 72 days (water temperature was 25–27℃). The results showed that the WGR (weight giant rate) and SGR (specific growth rate) of channel catfish in the 0.10 % group were significantly increased compared with the control group (P

BackgroundObesity is a significant part of the factors affecting lung function, and the assessment of obesity using the Metabolic Score for Visceral Fat (METS-VF) is more precise than other indicators like waist circumference and body mass index. This study investigated the relationship between lung function and METS-VF in The National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2012.MethodThe data utilized in this study was obtained from National Health and Nutrition Examination Survey spanning the years 2007 to 2012. A multivariate linear regression analysis was employed to investigate the association between METS-VF and lung function, followed by subgroup analysis to identify populations that may exhibit heightened sensitivity. Nonlinear correlations were assessed by fitting a restricted cubic spline, with validation of results conducted via threshold effect analysis.ResultIn a study involving 4,356 participants, a weighted multiple linear regression model revealed a significant negative association between the METS-VF and forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). However, no association was observed with peak expiratory flow rate (PEF). When dividing the METS-VF into thirds, participants in the highest third exhibited significantly decreased levels of FEV1 (β: −342, 95%CI: −440, −245, p 6.426 (β = −314.548, 95%CI: −387.326, −241.770). For FVC, a negative association was observed when the METS-VF 6.401, METS VF and lung function show a significant negative correlation (β = −399.288, 95%CI: −486.187, −312.388). FEV1/FVC showed a negative correlation only before the inflection point (METS-VF 6.263), no correlation was found, but there was no statistical significance (β = 0.000; 95%CI: −0.006, 0.007), and METS-VF had a linear negative correlation with FEF25-75%. Subgroup analysis showed that the association was consistent across a variety of demographic factors, including age, sex, race, hypertension, and coronary heart disease. In addition, we found a stronger association between men under 40 and lung function.ConclusionMETS-VF showed a linear negative correlation with FEF25-75%, and a nonlinear negative correlation with FEV1, FVC, FEV1/FVC, and FEF25-75%, but was not associated with PEF, particularly among males under the age of 40. These findings offer valuable insights into managing lung function by controlling visceral fat.

ObjectiveBaduanjin, a traditional Chinese exercise for health enhancement and chronic disease prevention, has been practiced for millennia. However, studies on the exercise intensity of Baduanjin are limited. Most existing studies focus on its general health benefits rather than quantifying its specific intensity levels. This study aims to measure and compare the exercise intensity indices of long-term Baduanjin practitioners and beginners, providing insights into its mechanisms for disease prevention and treatment and supporting the scientific formulation of clinical exercise prescriptions.MethodsTwenty healthy adults aged 35–45 years old and the mean BMI was 24.45 were recruited and divided into a beginner group (A group, no prior practice, 10 participants) and a skilled group (B group, practice duration ≥3 years, 10 participants). The Italian Cosmed/K5 wireless portable cardiopulmonary testing system was used to measure indicators during the practice.ResultsWithin-group analysis revealed statistically significant differences in oxygen consumption (VO2), oxygen consumption per kilogram of body weight (VO2/kg), metabolic equivalent (METs), heart rate (HR), oxygen pulse (VO2/HR), respiratory rate (RR), and minute ventilation (VE) between exercise and resting states in both the B and A groups (P

As a subset of mononuclear phagocytes in the central nervous system, microglia play a crucial role in immune defense and homeostasis maintenance. Microglia can regulate their states in response to specific signals of health and pathology. Microglia-mediated neuroinflammation is a pathological hallmark of neurodegenerative diseases, neurological damage and neurological tumors, underscoring its key immunoregulatory role in these conditions. Intriguingly, a substantial body of research has indicated that extracellular vesicles can mediate intercellular communication by transporting cargoes from parental cells, a property that is also reflected in microenvironmental signaling networks involving microglia. Based on the microglial characteristics, we briefly outline the biological features of extracellular vesicles and focus on summarizing the integrative role played by microglia in the maintenance of nervous system homeostasis and progression of different neurological diseases. Extracellular vesicles may engage in the homeostasis maintenance and pathological process as a medium of intercellular communication. Here, we aim to provide new insights for further exploration of neurological disease pathogenesis, which may provide theoretical foundations for cell-free therapies.

PurposePrevious observational studies about the link between dietary factors and diabetic microvascular complications (DMCs) is controversial. Thus, we systemically assessed the potential causal relationship between diet and DMCs risk using Mendelian randomization (MR) methods.MethodsWe used genome-wide association studies (GWAS) statistics to estimate the causal effects of 17 dietary patterns on three common DMCs in European. Summary statistics on dietary intakes were obtained from the UK biobank, and data on DMCs [diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic neuropathy (DNP)] were obtained from the FinnGen Consortium. A two-sample MR (TSMR) was conducted to explore the causal relationships of dietary habits with DMCs. In addition, multivariable MR analysis (MVMR) was performed to adjust for traditional risk factors for eating habits, and evaluated the direct or indirect effects of diet on DMCs.ResultsTSMR analysis revealed that salad/raw vegetable intake (odd ratio [OR]: 2.830; 95% confidence interval [CI]: 1.102–7.267; p = 0.0306) and fresh fruit intake (OR: 2.735; 95% CI: 1.622–4.611; p = 0.0002; false discovery rate [FDR] = 0.0082) increased the risk of DR, whereas cheese intake (OR: 0.742; 95% CI: 0.563–0.978; p = 0.0339) and cereal intake (OR: 0.658; 95% CI: 0.444–0.976; p = 0.0374) decreased the risk of DR. Salad/raw vegetable (OR: 6.540; 95% CI: 1.061–40.300; p = 0.0430) and fresh fruit consumption (OR: 3.573; 95% CI: 1.263–10.107; p = 0.0164) are risk factors for DN, while cereal consumption (OR: 0.380; 95% CI: 0.174–0.833; p = 0.0156) is the opposite. And genetically predicted higher pork intake increased the risk of DNP (OR: 160.971; 95% CI: 8.832–2933.974; p = 0.0006; FDR = 0.0153). The MVMR analysis revealed that cheese intake may act as an independent protective factor for DR development. Moreover, fresh fruit intake, salad/raw vegetable intake and pork intake may be independent risk factors for DR, DN and DNP, respectively. Other causal associations between dietary habits and DMCs risk may be mediated by intermediate factors.ConclusionThis causal relationship study supports that specific dietary interventions may reduce the risk of DMCs.

The island mining face in coal mines often encounters stress concentration and significant air leakage, elevating the risk of rock burst and spontaneous combustion of residual coal in the goaf. This study centers on the investigation of the 9305 island mining face within a mine situated in Shandong Province, China. Leveraging the features of coal spontaneous combustion and data from microseismic and gas monitoring throughout the mining process, a novel method for calculating safe mining speeds under compound disasters is introduced. The safe mining speed of the 9305 island mining face is stratified, and a prevention and control technology integrating long distance directional drilling for impact-spontaneous combustion compound disasters is proposed. Findings suggest that to mitigate spontaneous combustion of residual coal, considering the seam's spontaneous combustion tendency, the safe mining speed should exceed 3.7 m per day. Accounting for the distribution of microseismic events during coal seam extraction, the safe mining speed is maintained below 4.8 m per day in the unprotected mining area and capped at 8 m per day in the protected zone. Through a comprehensive analysis considering coal seam spontaneous combustion tendency, impact tendency, and time to coal seam oxidation to critical temperature, the safe mining speed for the island mining face ranges from 3.7 m per day to 4.8 m per day in the unprotected area and from 5.14 m per day to 8 m per day in the protected area. The proposed long distance directional drilling 'one hole, multiple purposes' scheme enables an integrated approach encompassing pressure relief before coal seam extraction, water injection during mining, and grouting post-mining. This method effectively prevents and controls the compound disasters of rock burst and coal spontaneous combustion, presenting innovative technical solutions for the safe extraction of coal resources.

BackgroundConstipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation.MethodsFecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis.ResultsThe alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p

Nickel/iron-layered double hydroxide (NiFe-LDH) tends to undergo an electrochemically induced surface reconstruction during the water oxidation in alkaline, which will consume excess electric energy to overcome the reconstruction thermodynamic barrier. In the present work, a novel ultrasonic wave-assisted Fenton reaction strategy is employed to synthesize the surface reconstructed NiFe-LDH nanosheets cultivated directly on Ni foam (NiFe-LDH/NF-W). Morphological and structural characterizations reveal that the low-spin states of Ni2+ (t2g6eg2) and Fe2+ (t2g4eg2) on the NiFe-LDH surface partially transform into high-spin states of Ni3+ (t2g6eg1) and Fe3+ (t2g3eg2) and formation of the highly active species of NiFeOOH. A lower surface reconstruction thermodynamic barrier advantages the electrochemical process and enables the NiFe-LDH/NF-W electrode to exhibit superior electrocatalytic water oxidation activity, which delivers 10 mA cm−2 merely needing an overpotential of 235 mV. Besides, surface reconstruction endows NiFe-LDH/NF-W with outstanding electrooxidation activities for organic molecules of methanol, ethanol, glycerol, ethylene glycol, glucose, and urea. Ultrasonic-assisted Fenton reaction inducing surface reconstruction strategy will further advance the utilization of NiFe-LDH catalyst in water and organics electrooxidation.

Summary: As an important way of maximizing land productivity by growing more than one crop type in the same field, mixed cropping has been an effective option for sustaining population growth under different climatic conditions since prehistoric period. We used a combination of archaeological data and an improved prehistoric land use model (PLUM) to quantitatively reconstruct spatiotemporal changes in cropland types and areas in the Huai River Valley of China, a core region of mixed cropping during the Holocene. The total cropland area increased more than 25 times during 8–2 ka BP, with northward expansion of rice-dominated cultivation during 5–4 ka BP and southward expansion of dry-dominated cultivation after 4 ka BP. Temperature and precipitation determined cropland types distribution, while that of cropland area was controlled by cultural development. The interplay between past climate, culture, and cultivation potentially provides useful insights into mitigating future population pressures with climate change.

Nickel oxide (NiOx) serves as one of the most promising hole transport materials for perovskite light‐emitting diodes (PeLEDs). However, only moderate PeLED performances have been reported on the pristine NiOx layer due to insufficient hole injection, interfacial exciton quenching, and poor perovskite quality. Herein, a multifunctional molecule of 3‐mercapto‐1‐propanesulfonate (MPS) is demonstrated to successfully tailor the NiOx–perovskite heterogenous interface by addressing the above issues. In detail, the large binding energy between mercapto sulfur and nickel induces preferential self‐assembly of the mercapto group on the NiOx surface, which simultaneously enlarges the NiOx work function by the formation of interfacial dipole and suppresses the trap‐assisted exciton quenching by the passivation of the oxygen vacancies. Meanwhile, the self‐assembled MPS on NiOx also favors high‐quality perovskite films with good morphology, high crystallinity, and reduced defects for efficient carrier radiative recombination. As a result, blue PeLEDs show a remarkable efficiency of 10.4%, representing one of the highest efficiencies for NiOx‐based blue PeLEDs, as well as a very low turn‐on voltage of 2.8 V. Consequently, this work contributes to an efficient approach to tailor the NiOx–perovskite interface for highly efficient blue PeLEDs.

BackgroundOvarian cancer is the most mortality malignancy in gynecology. N7-methylguanosine (m7G) is one of the most prevalent RNA modifications in the development and progression of cancer. The aim of this study is to investigate the effect of m7G-related lncRNA on ovarian cancer in terms of instruction prognosis and immunotherapy.MethodsAfter integrating and processing the RNA expression profiles with the clinical sample information in the TCGA database, we initially screened to the m7G-related lncRNAs by Spearman correlation analysis, and subsequently obtained a prognostic model constructed by five m7G-related lncRNAs with Univariate Cox analysis, LASSO regression analysis, and Multivariate Cox regression analysis, after which we further evaluated and validated the prognostic value of the model using Kaplan-Meier survival analysis, Principal component analysis, Nomogram, and ROC curve. In addition, based on this risk model, we explored the differentially enriched pathways and functions of the high and low risk groups, and characterized the immune cells, immune functions, gene mutations, and drug sensitivity between the two groups.ResultsAfter a series of rigorous filtering, we finally attained a prognostic risk model consisting of KRT7-AS, USP30-AS1, ZFHX4-AS1, ACAP2-IT1, and TWSG1-DT which is excellent in predicting the prognostic survival of ovarian cancer patients as well as existing as an independent prognostic factor. Moreover, the model has certain relevance in the immune cells and functions between high and low risk groups, and simultaneously, the signature has the role of guiding the option of immunotherapy and chemotherapeutic drugs.ConclusionAltogether, our study established a tight connection between m7G-associated lncRNAs and ovarian cancer, with potential that the prognostic patterns contribute to steering the prognosis of ovarian cancer patients, measuring the efficacy of immunotherapeutic approaches, and detecting effective chemotherapeutic agents.

BackgroundLarge soft tissue defects of the lower limb and foot are common occurrence in clinical practice and a considerable number of flaps have been used to treat them. However, there have been few reports using the superficial inferior epigastric artery (SIEA) flap. This review aims to present the experience of using the SIEA flaps for the repair of large soft tissue defects of the lower limb and foot.MethodsA retrospective review of data from 11 patients who underwent coverage of lower limb and foot defects exceeding 120 cm2 (15 × 9 cm) using SIEA flaps from March 2018 to July 2022 were retrospectively reviewed. The average size of the defects was 18 × 11 cm2 (range 15 × 9 cm2–32 × 16 cm2). Flap survival rates, surgical complications and overall long-term outcomes were recorded.ResultsAll 11 flaps survived. One flap was partially necrotic at the edge and healed after several changes of dressing. Additionally, one flap presented with mild venous congestion. The mean follow-up period was 18 months (ranging from 12 to 30 months). The mean size of the flaps was 20 × 12 cm2 (range 17 × 9 cm2–34 × 18 cm2). The flaps were observed to be aesthetically pleasing and exhibited a well-defined texture. The donor wounds were successfully closed primarily, with only linear scarring remaining.ConclusionsThe SIEA flap is characterised by concealed donor area, superficial vascular location, easy access and primary closure, which results in favourable aesthetic outcomes. It is an appropriate choice for the repair of large soft tissue defects of the lower limb and foot.

Background: Early childhood obesity poses a significant global public health challenge, necessitating the identification of treatable causes, particularly congenital leptin deficiencies. Serum leptin level measurement aids in diagnosing these rare contributors, guiding effective management. Methods: A Chinese family with early-onset obesity underwent LEP mutational screening via direct sequencing. mRNA expression and protein stability patterns of LEP were separately analyzed using qPCR and bioinformatics. Results: We present a case of a 12.5-year-old girl born to non-obese, non-consanguineous Chinese parents, exhibiting low leptin levels. Leptin gene sequencing revealed novel compound heterozygous mutations in exon 3. RT-PCR analysis showed the mutation didn't affect leptin production. Bioinformatics analysis indicated the variant rendered the leptin protein unstable. Conclusion: Loss-of-function mutations in LEP underlies early-onset obesity in the patient.

BackgroundHIV notification and testing integrated into partner service (PS) practices among HIV-positive individuals have been proven to be an efficient approach for case finding, although it remains a weak link in China. Although nonmarital sexual activities accounted for a large proportion of newly diagnosed HIV-positive cases in China, little is known about PS uptake and associated factors within nonmarital partnerships. ObjectiveThis study aimed to describe HIV PS utilization and its associated factors among HIV-positive individuals with nonmarital sexual partners. MethodsWe recruited newly diagnosed HIV-positive individuals who had nonmarital sexual partners in 2022 in Zhejiang Province and offered them PS. We described the PS uptake cascade within sexual partner categories and analyzed the associated factors with 3 primary outcomes from the participants’ perspective: nonmarital partner enumeration, HIV testing, and HIV positivity. ResultsIn this study, 3509 HIV-positive individuals were recruited as participants, and they enumerated 2507 nonmarital sex partners (2507/14,556, 17.2% of all nonmarital sex partners) with contact information. Among these, 43.1% (1090/2507) underwent an HIV test, with an HIV-positive rate of 28.3% (309/1090). Heterosexual commercial partners were the least likely of being enumerated (441/4292, 10.3%) and had the highest HIV-positive rate (40/107, 37.4%). At the participant level, 48.1% (1688/3509) of the participants enumerated at least one nonmarital sex partner with contact information, 52.7% (890/1688) had a sex partner tested for HIV, and 31% (276/890) had at least one nonmarital sex partner who tested positive. Multivariate analysis indicated that gender and transmission route were associated with both nonmarital sex partner enumeration and HIV testing. Age and occupation were associated with nonmarital sex partner enumeration and HIV positivity. Compared with participants who had no regular nonmarital sex partner, those who had a regular nonmarital sex partner were more likely to enumerate nonmarital sex partners (adjusted odds ratio [aOR] 3.017, 95% CI 2.560-3.554), have them get tested for HIV (aOR 1.725, 95% CI 1.403-2.122), and have an HIV-positive nonmarital sex partner (aOR 1.962, 95% CI 1.454-2.647). ConclusionsThe percentage of partner enumeration was low, and HIV testing rate was moderate among nonmarital partnerships of HIV-positive individuals. More efforts should be made to improve PS practices among HIV-positive individuals and address the gap in partner enumeration, especially for heterosexual commercial nonmarital partnerships. Additionally, enhancing PS operational skills among health care personnel could increase the overall efficiency of PS uptake in China.

Citrus aurantium L., sometimes known as “sour orange,” is an important Chinese herb with young, immature fruits, or “zhishi,” that are high in synephrine. Synephrine is a commonly utilized natural chemical with promising applications in effectively increasing metabolism, heat expenditure, energy level, oxidative fat, and weight loss. However, little is known about the genes and pathways involved in synephrine production during the critical developmental stages of C. aurantium L., which limits the development of the industry. According to this study, the concentration of synephrine gradually decreased as the fruit developed. Transcriptome sequencing was used to examine the DEGs associated with synephrine connections and served as the foundation for creating synephrine-rich C. aurantium L. Comparisons conducted between different developmental stages to obtain DEGs, and the number of DEGs varied from 690 to 3,019. Tyrosine and tryptophan biosynthesis, glycolysis/gluconeogenesis, pentose phosphate pathway, phenylalanine, and tyrosine metabolism were the main KEGG pathways that were substantially enriched. The results showed that 25 genes among these KEGG pathways may be related to synephrine synthesis. The WGCNA and one-way ANOVA analysis adoption variance across the groups suggested that 11 genes might play a crucial role in synephrine synthesis and should therefore be further analyzed. We also selected six DEGs at random and analyzed their expression levels by RT-qPCR, and high repeatability and reliability were demonstrated by our finished RNA-seq study results. These results may be useful in selecting or modifying genes to increase the quantity of synephrine in sour oranges.

IntroductionCytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague.MethodsUsing spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed.ResultsThis study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1β, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB–dependent transcription of CRS-related inflammatory cytokines.DiscussionTargeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.

Immunity is a critical self-defense mechanism of the human body, wherein immune cells and immune molecules play a crucial role. Extracellular vesicles (EVs), derived from immune cells or other cells, play a significant role in tumors, autoimmune diseases and other immune-related disorders by serving as carriers and facilitating intercellular communication through the transfer of cargoes. Numerous studies have revealed that EVs can exacerbate disease development by modulating immune responses. Therefore, this paper focuses on the effects of EVs on the number, activity and function of different types of immune cells and the release of immune molecules (such as cytokines, antigens, antibodies, etc) in various diseases, as well as the roles of EVs associated with different types of immune cells in various diseases. We aim to provide a comprehensive review of the negative effects that EVs play in the immune system to provide more ideas and strategies for the management of clinical immune diseases.

Abstract The high‐speed impact‐resistanct materials are of great significance while their development is hindered by the intrinsic tradeoff between mechanical strength and energy dissipation capability. Herein, the new chemical system of molecular granular material (MGM) is developed for the design of impact‐resistant materials from the supramolecular complexation of sub‐nm molecular clusters (MCs) and hyper‐branched polyelectrolytes. Their hierarchical aggregation provides the origin of the decoupling of mechanical strengths and structural relaxation dynamics. The MCs’ intrinsic fast dynamics afford excellent high‐speed impact‐resistance, up to 5600 s−1 impact in a typical split‐Hopkinson pressure bar test while only tiny boundary cracks can be observed even under 7200 s−1 impact. The high loadings of MCs and their hierarchical aggregates provide high‐density sacrificial bonding for the effective dissipation of the impact energy, enabling the protection of fragile devices from the direct impact of over 200 m s−1 bullet. Moreover, the MGMs can be conveniently processed into protective coatings or films with promising recyclability due to the supramolecular interaction feature. The research not only reveals the unique relaxation dynamics and mechanical properties of MGMs in comparison with polymers and colloids, but also develops new chemical systems for the fabrication of high‐speed impact‐resistant materials.