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Objective: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations. Methods: Patients with ROHHAD syndrome reported before and after 2019 were divided into groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups. Results: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among groups 1–3, the rates of cardiovascular manifestations were NA vs 12.8% vs 81.2%; gastrointestinal disturbances were 11.4% vs 8.5% vs 62.5%; strabismus was 25.7% vs 12.8% vs 62.5%; sleep disturbance was NA vs 6.4% vs 50.0%; and abnormal pain threshold was NA vs 10.6% vs 25.0% (all P < 0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (P < 0.01). Conclusion: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

Abstract Background In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. Methods This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. Results After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P

Abstract Cutaneous squamous cell carcinoma (CSCC) is common among the elderly, typically treated with surgery. However, for surgery-ineligible patients or those with non-healing wounds progressing to malignant ulcers, non-surgical local treatments are viable. This case details an 80-year-old with recurrent back CSCC and intractable malignant ulcers post-radiotherapy and chemotherapy. Treatment involved Hematoporphyrin Derivative (HpD) Photodynamic Therapy (PDT) with low-dose cindilimab immunotherapy (intravenous and intralesional). Two cycles achieved lesion remission, altering peripheral immune cell counts. HpD-PDT combined with immunotherapy is promising for treating CSCC, particularly with malignant ulcers.

Abiotic and biotic stressors adversely affect plant survival, biomass generation, and crop yields. As the global availability of arable land declines and the impacts of global warming intensify, such stressors may have increasingly pronounced effects on agricultural productivity. Currently, researchers face the overarching challenge of comprehensively enhancing plant resilience to abiotic and biotic stressors. The secondary cell wall plays a crucial role in bolstering the stress resistance of plants. To increase plant resistance to stress through genetic manipulation of the secondary cell wall, we cloned a cell wall protein designated glycine-rich protein-like (GhGRPL) from cotton fibers, and found that it is specifically expressed during the period of secondary cell wall biosynthesis. Notably, this protein differs from its Arabidopsis homolog, AtGRP, since its glycine-rich domain is deficient in glycine residues. GhGRPL is involved in secondary cell wall deposition. Upregulation of GhGRPL enhances lignin accumulation and, consequently, the thickness of the secondary cell walls, thereby increasing the plant's resistance to abiotic stressors, such as drought and salinity, and biotic threats, including Verticillium dahliae infection. Conversely, interference with GhGRPL expression in cotton reduces lignin accumulation and compromises that resistance. Taken together, our findings elucidate the role of GhGRPL in regulating secondary cell wall development through its influence on lignin deposition, which, in turn, reinforces cell wall robustness and impermeability. These findings highlight the promising near-future prospect of adopting GhGRPL as a viable, effective approach for enhancing plant resilience to abiotic and biotic stress factors.

Wampee (Clausena lansium) is an important evergreen fruit tree native to southern China that has a long history of use for medicinal purposes. Here, a chromosome-level genome of C. lansium was constructed with a genome size of 282.9 Mb and scaffold N50 of 30.75 Mb. The assembled genome contains 48.70% repetitive elements and 24,381 protein-coding genes. Comparative genomic analysis showed that C. lansium diverged from Aurantioideae 15.91–24.95 million years ago. Additionally, some expansive and specific gene families related to methyltransferase activity and S-adenosylmethionine-dependent methyltransferase activity were also identified. Further analysis indicated that N-methyltransferase (NMT) is mainly involved in alkaloid biosynthesis and O-methyltransferase (OMT) participates in the regulation of coumarin accumulation in wampee. This suggested that wampee's richness in alkaloids and coumarins might be due to the gene expansions of NMT and OMT. The tandem repeat event was one of the major reasons for the NMT expansion. Hence, the reference genome of C. lansium will facilitate the identification of some useful medicinal compounds from wampee resources and reveal their biosynthetic pathways.

Electricity-driven water splitting to produce hydrogen is one of the most efficient ways to alleviate energy crisis and environmental pollution problems, in which the anodic oxygen evolution reaction (OER) is the key half-reaction of performance-limiting in water splitting. Given the complicated reaction process and surface reconstruction of the involved catalysts under actual working conditions, unraveling the real active sites, probing multiple reaction intermediates and clarifying catalytic pathways through in-situ characterization techniques and theoretical calculations are essential. In this review, we summarize the recent advancements in understanding the catalytic process, unlocking the water oxidation active phase and elucidating catalytic mechanism of water oxidation by various in-situ characterization techniques. Firstly, we introduce conventionally proposed traditional catalytic mechanisms and novel evolutionary mechanisms of OER, and highlight the significance of optimal catalytic pathways and intrinsic stability. Next, we provide a comprehensive overview of the fundamental working principles, different detection modes, applicable scenarios, and limitations associated with the in-situ characterization techniques. Further, we exemplified the in-situ studies and discussed phase transition detection, visualization of speciation evolution, electronic structure tracking, observation of reaction active intermediates, and monitoring of catalytic products, as well as establishing catalytic structure–activity relationships and catalytic mechanism. Finally, the key challenges and future perspectives for demystifying the water oxidation process are briefly proposed.

The climate crisis necessitates the development of non-fossil energy sources. Harnessing solar energy for fuel production shows promise and offers the potential to utilize existing energy infrastructure. However, solar fuel production is in its early stages of development, constrained by low conversion efficiency and challenges in scaling up production. Concentrated solar energy (CSE) technology has matured alongside the rapid growth of solar thermal power plants. This review provides an overview of current CSE methods and solar fuel production, analyzes their integration compatibility, and delves into the theoretical mechanisms by which CSE impacts solar energy conversion efficiency and product selectivity in the context of photo-electrochemistry, thermochemistry, and photo-thermal co-catalysis for solar fuel production. The review also summarizes approaches to studying the photoelectric and photothermal effects of CSE. Lastly, it explores emerging novel CSE technology methods in the field of solar fuel production.

Peach gum polysaccharides have multiple biological functions, such as anti-oxidation, blood lipids reduction, and immune protection. However, their impact on the gut microbiota was still unclear. Here, high throughput sequencing was used to study the regulatory effects of peach gum polysaccharide on gut microbiota using an in vitro fermentation model of human gut microbiota. The results showed that gut microbiota species increased significantly and α-diversity index (Sobs, Ace, Chao1, Shannon) decreased significantly after polysaccharide fermentation compared with control group (distilled water). At phylum level, the relative abundance of Firmicutes and Actinomyces increased (61.76% vs. 56.64%, 28.24% vs. 23.11%). In contrast, relative abundance of Bacteroides decreased significantly (8.10% vs. 19.21%). At genus level, the relative abundance of Bifidobacteria, Colinella and Parazobacteria increased significantly (21.43% vs. 19.08%, 6.32% vs. 3.73%, 6.37% vs. 0.00%), while the relative abundance of Bacteroides and Prevotella decreased significantly (3.83% vs. 5.52%, 3.49% vs. 12.15%). Precisely, peach gum polysaccharide can effectively regulate the structure of gut microbiota and has potential probiotic effects including anti-obesity, anti-inflammatory, maintenance of gut epithelial barrier and so on.

A well-designed spray system, which is located near the source of high-temperature smoke, can improve the capture efficiency of traditional local exhaust ventilation (LEV). However, there is currently no comprehensive evaluation index that clearly reflects the performance of spray-local exhaust ventilation (SLEV), making it challenging to optimize the spray arrangement. The two-phase flow fields in the SLEV and LEV were compared to evaluate the impact of spray on smoke control. The effects of spray arrangement parameters, such as spray position, spacing, initial droplet size, and angle, on the performance of the SLEV system were further evaluated using current evaluation indicators. Based on this, we developed a comprehensive evaluation model for SLEV using the AHP-entropy combination weighting method. The results revealed that the decrease in smoke control with an increase in rolling speed is primarily caused by a reduction in spray control in the central region of the smoke. When the spray flow rate is 0.0028 kg/s and the velocity is 30 m/s, the primary factor that improves ventilation performance is the downward drag force exerted by the spray on smoke, rather than the cooling effect. The comprehensive model was developed using weights of 0.45, 0.34, and 0.21 for the three evaluation indicators: capture efficiency, high-quality concentration field ratio, and spatial droplet size. The model showed good reliability based on the results of the smoke concentration analysis. The results of this study are expected to guide the design, implementation, and evaluation of SLEV systems.

Self-supervised learning guided by masked image modeling, such as masked autoencoder (MAE), has attracted wide attention for pretraining vision transformers in remote sensing. However, MAE tends to excessively focus on pixel details, limiting the model's capacity for semantic understanding, particularly for noisy synthetic aperture radar (SAR) images. In this article, we explore spectral and spatial remote sensing image features as improved MAE-reconstruction targets. We first conduct a study on reconstructing various image features, all performing comparably well or better than raw pixels. Based on such observations, we propose feature guided MAE (FG-MAE): reconstructing a combination of histograms of oriented gradients (HOG) and normalized difference indices (NDI) for multispectral images, and reconstructing HOG for SAR images. Experimental results on three downstream tasks illustrate the effectiveness of FG-MAE with a particular boost for SAR imagery (e.g., up to 5% better than MAE on EuroSAT-SAR). Furthermore, we demonstrate the well-inherited scalability of FG-MAE and release a first series of pretrained vision transformers for medium-resolution SAR and multispectral images.

Abstract Maintaining freshness and quality is crucial in the meat industry, as lipid oxidation can lead to undesirable odors, flavors, and potential health risks. Traditional methods for assessing meat freshness often involve time‐consuming and destructive techniques, highlighting the need for rapid, noninvasive approaches. Recent advancements in spectroscopic and chromogenic sensor array technologies have opened up new avenues for monitoring meat quality parameters, offering the potential for real‐time, accurate, and cost‐effective solutions. As thiobarbituric acid reactive substances (TBARS) value is a classic indicator of meat lipid oxidation, this study investigated the data fusion of near‐infrared spectroscopy (NIR) and paper chromogenic array (PCA) for monitoring ground beef TBARS. A standardized PCA was fabricated by photolithography with nine chemoresponsive dyes. Changes in ground beef volatile organic compounds during storage were captured in the shifts of PCA color patterns. Nippy, an open‐source Python module, was used for automated NIR spectra preprocessing. The optimal preprocessing pipeline was found by 10‐fold cross‐validation in machine learning model development. Among optimized models, partial least square regression showed the best performance in coefficient of determination (R2) of .9477, root mean squared error of prediction of 0.0545 mg malondialdehyde/kg meat, and residual prediction deviation of 4.3717. The promising result of this study indicated the potential for NIR and PCA combinations to monitor TBARS values for ground beef freshness assessment.

The large-diameter and long-distance drilling in coal mines can serve as a transportation channel to replace traditional underground tunnels. Compared with conventional large-diameter drilling, the main differences and difficulties lie in “point-to-point” precise drilling, efficient and rapid reaming of large-diameter and long-distance classification, and full hole section casing laying and grouting for pipe fixation. This article introduces the key technology for drilling holes through large-diameter and long-distance boreholes in coal mines. We will conduct in-depth research on five aspects, including RMRS obstacle avoidance and docking technology, graded hole reaming technology, slag removal process technology, full hole section casing laying technology, and grouting and pipe fixing technology, in order to achieve efficient drilling of large-diameter and long-distance through holes. In the guide straight holes drilled at multiple key points of the drilling design direction track, RMRS technology is used for advanced guidance to achieve directional obstacle avoidance and precise point-to-point penetration; reasonably optimize the drilling sequence and adopt the back pull drilling process to improve the efficiency of drilling; utilizing the combined slag removal process of “intra hole circulation + mechanical assistance” to improve the slag removal efficiency of borehole drilling; optional ball centralizer, using a combination of “forward pull + backward push” to achieve long-distance full hole section casing laying; adopting the “annular pressure grouting method” to ensure the quality of grouting and pipe fixation. Based on the above key technologies, a large-diameter long-distance water transmission pipeline was constructed between Daliuta Well and Huojitu Well, with a total length of 1 932 m, a final borehole diameter of 330 mm, and a water transmission casing size for the entire borehole section ϕ219 mm×8.94 mm; the pilot hole successfully passed diagonally and safely between two bridge piers. The horizontal projection displacement deviation between the actual penetration point Bs and the design penetration point B was 0.4 m, the vertical profile displacement deviation was 0.25 m, and the spatial displacement deviation was 0.47 m, basically achieving point-to-point connectivity; the qualification rate of acoustic amplitude logging for grouting pipes is 95%, and the actual water delivery capacity of the pipeline exceeds 150 m3/h.

Abstract By analyzing e + e − annihilation data corresponding to an integrated luminosity of 2.93 fb −1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the semileptonic decays D 0 → K S 0 π − π 0 e + ν e $$ {D}^0\to {K}_S^0{\pi}^{-}{\pi}^0{e}^{+}{\nu}_e $$ and D + → K S 0 π + π − e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^{+}{\pi}^{-}{e}^{+}{\nu}_e $$ is reported. In the hypothesis that all events correspond to K 1(1270) decays, the branching fractions are measured to be B D 0 → K 1 1270 − → K S 0 π − π 0 e + ν e = 1.69 − 0.46 + 0.53 ± 0.15 × 10 − 4 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}\left(\to {K}_S^0{\pi}^{-}{\pi}^0\right){e}^{+}{\nu}_e\right)=\left({1.69}_{-0.46}^{+0.53}\pm 0.15\right)\times {10}^{-4} $$ and B D + → K ¯ 1 1270 0 → K S 0 π + π − e + ν e = 1.47 − 0.40 + 0.45 ± 0.14 × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0\left(\to {K}_S^0{\pi}^{+}{\pi}^{-}\right){e}^{+}{\nu}^e\right)=\left({1.47}_{-0.40}^{+0.45}\pm 0.14\right)\times {10}^{-4} $$ with statistical significance of 5.4σ and 5.6σ, respectively. When combined with measurements of the K 1(1270) → K + π − π decays, the absolute branching fractions are determined to be B D 0 → K 1 1270 − e + ν e = 1.08 − 0.13 − 0.10 + 0.14 + 0.08 ± 0.21 × 10 − 3 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}{e}^{+}{\nu}_e\right)=\left({1.08}_{-0.13-0.10}^{+0.14+0.08}\pm 0.21\right)\times {10}^{-3} $$ and B D + → K ¯ 1 1270 0 e + ν e = 1.70 − 0.23 + 0.26 ± 0.13 ± 0.35 × 10 − 3 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0{e}^{+}{\nu}_e\right)=\left({1.70}_{-0.23}^{+0.26}\pm 0.13\pm 0.35\right)\times {10}^{-3} $$ . The first and second uncertainties are statistical and systematic, respectively, and the third uncertainties originate from the assumed branching fractions of the K 1(1270) → Kππ decays.

ABSTRACT Importance Digital technology is now widely available for the interventions of autism, but its validity and feasibility remain to be proved. Objective This study aimed to investigate the effectiveness of digital health interventions (DHIs) in improving core symptoms or intelligence quotient in patients with autism spectrum disorder (ASD). Methods Three databases including PubMed, Cochrane, and Scopus, were searched on November 15, 2022. Randomized clinical trials that enrolled patients with ASD who received DHIs and a control group without DHI treatment were included. Cochrane risk of bias tool (RoB 2) was applied to assess the risk of bias. Results A total of 33 studies, involving 1285 participants (658 [51.2%] in DHI groups and 627 [48.8%] in control groups), were analyzed to investigate the differences between DHI groups and control groups. Significantly greater improvements in the overall performance of ASD were observed in the DHI groups compared to the control groups (including active, waitlist, treatment‐as‐usual, and no treatment) with an effect size of 1.89 (Cohen's d 95% confidence interval [CI]: 1.26–2.52). Studies with treatment‐as‐usual, waitlist, and no treatment control demonstrated large effect sizes of Cohen's d 3.41 (95% CI: 0.84–5.97), Cohen's d 4.27 (95% CI: 1.95–6.59), and Cohen's d 4.52 (95% CI: 2.98–6.06) respectively. In contrast, studies with active control revealed insignificant effect sizes (Cohen's d 0.73, 95% CI: 0.12–1.33). Interpretation This meta‐analysis found significantly greater improvements in core symptoms or intelligence quotient in ASD patients receiving DHIs compared to those in control conditions. ASD patients may benefit from the DHIs and reduce the economic burden.

This study investigates the impact of various molecular weights (MWs) of fulvic acid (FA) on maize growth, grain yield, and nutrient uptake under different nitrogen levels (NLs). A 2 × 3 balanced design was employed, with high (0.2 g N/kg) and low (0.05 g N/kg) NLs, and three FA MW ranges (W1 ≤ 3 000 D, 3 000 < W2 ≤ 10 000 D, W3 > 10 000 D) were applied at 25 mg/kg in soil. Significant interactions between NLs and FA MWs were observed in chlorophyll a/b ratio, nitrate reductase and glutamate dehydrogenase activities, nitrogen content, and nitrogen uptake efficiency. Overall, under different NLs, FA application reduced chlorophyll a/b ratio, increased nitrogen metabolism enzyme activities, promoted maize growth, and thereby improved grain yield and nitrogen fertiliser uptake efficiency. Additionally, the promotion effect of low MW FA on these indicators outweighed that of high MW FA, yet the latter exhibited a more pronounced effect on increasing grain nitrogen concentration. Structural equation model analysis revealed direct effects of chlorophyll content, nitrogen accumulation, nitrogen uptake efficiency, NLs and FA MWs on maize grain yield, with FA MWs negatively impacting yield.

Abstract Background Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. Methods The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. Results We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. Conclusion These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis. Graphical Abstract

Abstract Background Parasitic diseases remain a serious public health problem in China. Health education aimed at disseminating health-related knowledge and promoting healthy behaviours, plays a crucial role in the prevention and control of parasitic diseases. This study aims to develop a tool to measure the parasitic disease health literacy of residents in China. Methods Scale development was based on qualitative and quantitative methods. Qualitative method included focus group discussions and Delphi consultations. A methodological design with multistage sampling and a pilot study was used to evaluate the questionnaire. The scale’s reliability was tested using Cronbach’s α and split-half reliability, while its construct validity was assessed using confirmatory factor analysis. The scale’s passing score was determined using the receiver operating characteristic curve. A cross-sectional survey was conducted in six districts of the prefecture of Jiangsu and residents aged 14–69 years in the participating townships were randomly selected based on their location. Results The health literacy indicator system for parasitic diseases included 3 first-level, 9 s-level and 23 third-level indicators. The 23-item questionnaire demonstrated good internal consistency (Cronbach’s alpha = 0.774) and split-half reliability (Spearman-Brown coefficient = 0.778). The questionnaire’s passing score was 60. A total of 990 valid questionnaires were collected from participants in three cities. The percentage of participants with health literacy regarding parasitic diseases was 15.8%. Their scores were influenced by age, income, employment, and educational level. Conclusions Health literacy of parasitic diseases is an integrated indicator rather than just knowledge or behavior information. The correlation between knowledge and behavior is weak. The capacity for healthy behavior of parasitic disease is associated with the location and culture of the city. For neglected diseases, it is important for people to talk positively about their behaviors with a doctor.

Abstract Background CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. Method We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P

Abstract Introduction In 2016, the Chinese government officially scaled up family doctor contracted services (FDCS) scheme to guide patients’ health seeking behavior from tertiary hospitals to primary health facilities. Methods This study evaluated the overall gate-keeping effects of this scheme on healthcare utilization of rural residents by using a difference-in-differences (DiD) design. The analysis was based on Shandong Rural Elderly Health Cohort 2019 and 2020. Participants who contracted FDCS in second round and were not contracted with a family doctor in the first round were regarded as treatment group. In total, 310 respondents who have used medical care were incorporated for final study. Results Participants who contracted FDCS (treatment group) experienced a significant decline in the mean level of first-contact health-care facilities, decreasing from 2.204 to 1.981. In contrast, participants who did not contract FDCS (control group), showed an increasing trend in the mean level of first-contact health-care facilities, rising from 2.128 to 2.445. Our results showed that contracting FDCS is associated with approximately 0.54 extra lower mean level of first-contact health-care facilities (P = 0.03, 95% CI: -1.03 to 0.05), which suggests an approximately 24.5% reduction in the mean first-contact health-care facility level for participants compared with contracted FDCS than those who did not. Conclusions The study suggested primary healthcare quality should be strengthened and restrictive first point of contact policy should be enacted to establish ordered healthcare seeking behavior among rural residents.

Abstract Using e + e − annihilation data sets corresponding to an integrated luminosity of 4.5 fb −1, collected with the BESIII detector at center-of-mass energies between 4.600 and 4.699 GeV, we report the first measurements of the absolute branching fractions B Λ c + → p K L 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0\right) $$ = (1.67 ± 0.06 ± 0.04)%, B Λ c + → p K L 0 π + π − $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^{+}{\pi}^{-}\right) $$ = (1.69 ± 0.10 ± 0.05)%, and B Λ c + → p K L 0 π 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^0\right) $$ = (2.02 ± 0.13 ± 0.05)%, where the first uncertainties are statistical and the second systematic. Combining with the known branching fractions of Λ c + → p K S 0 $$ {\Lambda}_c^{+}\to p{K}_S^0 $$ , Λ c + → p K S 0 π + π − $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^{+}{\pi}^{-} $$ , and Λ c + → p K S 0 π 0 $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^0 $$ , we present the first measurements of the K S 0 $$ {K}_S^0 $$ - K L 0 $$ {K}_L^0 $$ asymmetries R Λ c + K S , L 0 X = B Λ c + → K S 0 X − B Λ c + → K L 0 X B Λ c + → K S 0 X + B Λ c + → K L 0 X $$ R\left({\Lambda}_c^{+},{K}_{S,L}^0X\right)=\frac{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)-\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)}{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)+\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)} $$ in charmed baryon decays: R Λ c + p K S , L 0 = − 0.025 ± 0.031 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0\right)=-0.025\pm 0.031 $$ , R Λ c + p K S , L 0 π + π − = − 0.027 ± 0.048 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^{+}{\pi}^{-}\right)=-0.027\pm 0.048 $$ and R Λ c + p K S , L 0 π 0 = − 0.015 ± 0.046 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^0\right)=-0.015\pm 0.046 $$ . No significant asymmetries with statistical significance are observed.

Abstract Persistent subretinal fluid (PSF) after scleral bucking of rhegmatogenous retinal detachment may delay recovery and affect the final visual quality, but with no effective treatment. This study firstly investigated the safety and efficacy of 577 nm yellow subthreshold micropulse laser (SML) on PSF after scleral bucking surgery. This double-masked randomized clinical trial was conducted from December 2020 to October 2022 at Chongqing Aier Eye Hospital. Participants with PSF last for 1 month after scleral bucking surgery with break closed and retina reattachment were recruitment. These participants were treated by 577 nm yellow SML or sham treatment. Funduscopy, optical coherence tomography (OCT) volume change, best corrected vision acuity (BCVA) and visual field test were evaluated for six mouths follow-up. A total of 24 participants were randomized into SML group or Sham group equally. Compared with Sham group, the OCT volume within 6 mm of macular fovea was significantly less in SML group 6 months after therapy (P = 0.048). There were no statistically significant differences of OCT volume at 1, 2 and 3 months from baseline between groups. BCVA of ETDRS letters had no statistically significant difference. Pattern Standard Deviation amelioration (P = 0.039) had statistically significance in SML group compared with Sham group. There were no complications in the 2 groups. These preliminary findings suggest that 577 nm yellow SML therapy could accelerate PSF absorption after scleral bucking surgery. Trial registration: Chinese Clinical Trial Registry No. ChiCTR2000037838, 02/09/2020, https://www.chictr.org.cn/showproj.html?proj=51885 .

Abstract Background This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. Methods From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. Results The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P

Background: DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Nevertheless, the precise role of DNA methylation in chemotherapeutic drug-induced alopecia remains unclear. This study examined the role and novel processes of DNA methylation in regulating of chemotherapeutic drug-induced alopecia. Methods: A mouse model of cyclophosphamide (CTX)-induced alopecia was established. Hematoxylin-eosin staining and immunohistochemical staining for the Ki67 proportion and a mitochondrial membrane potential assay (JC-1) were performed to assess the structural integrity and proliferative efficiency of the hair follicle stem cells (HFSCs). Immunofluorescence staining and real-time fluorescence quantitative PCR (RT-qPCR) were performed to determine the expression levels of key HFSC markers, namely Lgr5, CD49f, Sox9, CD200, and FZD10. Differential DNA methylation levels between the normal and CTX-induced model groups were determined through simple methylation sequencing and analyzed using bioinformatics tools. The expression levels of miR-365-1, apoptosis markers, and DAP3 were detected through RT-qPCR and western blotting. In parallel, primary mouse HFSCs were extracted and used as a cell model, which was constructed using 4-hydroperoxycyclophosphamide. The luciferase reporter gene assay was conducted to confirm miR-365-1 binding to DAP3. To measure the expression of relevant indicators, superoxide dismutase (SOD) and malondialdehyde (MDA) kits were used. Methylation-specific PCR (MS-PCR) was performed to determine DNA methylation levels. The regulatory relationship within HFSCs was confirmed through plasmid overexpression of miR-365-1 and DAP3. Result: In the alopecia areata model, a substantial number of apoptotic cells were observed within the hair follicles on the mouse backs. Immunofluorescence staining revealed that the expression of HFSC markers significantly reduced in the CTX group. Both RT-qPCR and western blotting demonstrated a noteworthy difference in DNA methyltransferase expression. Simple methylation sequencing unveiled that DNA methylation substantially increased within the dorsal skin of the CTX group. Subsequent screening identified miR-365-1 as the most differentially expressed miRNA. miR-365-1 was predicted and confirmed to bind to the target gene DAP3. In the CTX group, SOD and ATP expression markedly reduced, whereas MDA levels were significantly elevated. Cellular investigations revealed 4-HC-induced cell cycle arrest and decreased expression of HFSC markers. MS-PCR indicated hypermethylation modification of miR-365-1 in the 4-HC-induced HFSCs. The luciferase reporter gene experiment confirmed the binding of miR-365-1 to the DAP3 promoter region. miR-365-1 overexpression dramatically reduced apoptotic protein expression in the HFSCs. However, this effect was slightly reversed after DAP3 overexpression in lentivirus. Conclusion: This study explored the occurrence of miR-365-1 DNA methylation in chemotherapeutic drug-induced alopecia. The results unveiled that miR-365-1 reduces cell apoptosis by targeting DAP3 in HFSCs, thereby revealing the role of DNA methylation of the miR-365-1 promoter in chemotherapeutic drug-induced alopecia.

Abstract The processes h c → γP (P = η′, η, π 0) are studied with a sample of (27.12 ± 0.14) × 108 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The decay h c → γη is observed for the first time with the significance of 9.0 σ, and the branching fraction is determined to be (3.77 ± 0.55 ± 0.13 ± 0.26) × 10 −4, while B $$ \mathcal{B} $$ (h c → γη′) is measured to be (1.40 ± 0.11 ± 0.04 ± 0.10) × 10 −3, where the first uncertainties are statistical, the second systematic, and the third from the branching fraction of ψ(3686) → π 0 h c . The combination of these results allows for a precise determination of R h c = B h c → γη B h c → γ η ′ , $$ {R}_{h_c}=\frac{\mathcal{B}\left({h}_c\to {\pi}^0\gamma \eta \right)}{\mathcal{B}\left({h}_c\to {\pi}^0\gamma {\eta}^{\prime}\right)}, $$ which is calculated to be (27.0 ± 4.4 ± 1.0)%. The results are valuable for gaining a deeper understanding of η − η′ mixing, and its manifestation within quantum chromodynamics. No significant signal is found for the decay h c → γπ 0, and an upper limit is placed on its branching fraction of B $$ \mathcal{B} $$ (h c → γπ 0) < 5.0 × 10 −5, at the 90% confidence level.

Abstract Background Reflux esophagitis (RE) is a disease in which inflammation of the esophageal mucosa owing to the reflux of gastric contents into the esophagus results in cytokine damage. Britannilactone 1-O-acetate (Brt) has anti-inflammatory effects, significantly inhibiting the activation of the NLRP3 inflammasome, leading to a decrease in inflammatory factors including IL-1 β, IL-6, and TNF-α. However, the mechanism underlying its protective effect against RE-induced esophageal injury remains unclear. In the present study, we investigated the protective mechanism of TRIM31 against NLRP3 ubiquitination-induced RE both in vivo and in vitro. Methods A model of RE was established in vivo in rats by the method of “4.2 mm pyloric clamp + 2/3 fundoplication”. In vitro, the mod was constructed by using HET-1A (esophageal epithelial cells) and exposing the cells to acid, bile salts, and acidic bile salts. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to screen the concentration of administered drugs, and the viability of HET-1A cells in each group. HE staining was used to assess the degree of pathological damage in esophageal tissues. Toluidine blue staining was used to detect whether the protective function of the esophageal epithelial barrier was damaged and restored. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-1 β, IL-6, and TNF-α factors in serum. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3 in esophageal tissues. The molecular docking and Co-immunoprecipitation assay (Co-IP assay) were used to detect the TRIM31 interacts with NLRP3. Western blotting detected the Claudin-4, Claudin-5, The G-protein-coupled receptor calcium-sensitive receptor (CaSR), NLRP3, TRIM31, ASC, C-Caspase1, and Caspase1 protein expression levels. Results Brt could alleviate RE inflammatory responses by modulating serum levels of IL-1 β, IL-6, and TNF-α. It also activated the expression of NLRP3, ASC, Caspase 1, and C-Caspase-1 in HET-1A cells. Brt also attenuated TRIM31/NLRP3-induced pathological injury in rats with RE through a molecular mechanism consistent with the in vitro results. Conclusions Brt promotes the ubiquitination of NLRP3 through TRIM31 and attenuates esophageal epithelial damage induced by RE caused by acidic bile salt exposure. This study provides valuable insights into the mechanism of action of Brt in the treatment of RE and highlights its promising application in the prevention of NLRP3 inflammatory vesicle-associated inflammatory pathological injury. Graphical Abstract

Abstract The joint utilization of the Fifth Generation Communications Technology (5G) and the Global Navigation Satellite System (GNSS) serves as a promising solution to address the challenges associated with insufficient visible satellites and lower observation quality in urban environments. 5G allows for the angle and distance measurements, augmenting the performance of Real-Time Kinematic (RTK) positioning. To quantify the improvement of 5G observations on RTK positioning, this paper proposes a float solution gain factor and the Ambiguity Dilution of Precision (ADOP) gain factor. Based on these gain factors, the theoretical analysis and simulation are performed. This study designs an extended Kalman filter for 5G-assisted BeiDou Navigation Satellite System (BDS) RTK positioning, employing both the Full Ambiguity Resolution (FAR) and Partial Ambiguity Resolution (PAR) modes. Our experiment verified the effectiveness of 5G-assisted BDS RTK positioning in mitigating outlier occurrences and improving the ambiguity fixing rate as well as the positioning accuracy. In the FAR and PAR modes, the Three-Dimensional (3D) spatial accuracy increased by 48% and 18.8%, respectively, and the results are consistent with theoretical analysis based on gain factors. The fixing rate of RTK increased from 11.11% to 13.93%, while it increased from 32.58% to 44.43% for the PAR mode. The assistance of 5G observations reduced the median error for the FAR mode from over 1.3m to 0.9 m, and the third quartile from 2.1m to 1.05 m. For the PAR mode, the median error decreased from 0.5m to 0.12 m, and the third and fourth quartiles decreased from 0.65m to 0.38 m.

Abstract This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

Abstract Existing strategies use bifunctional chimaeras to mediate extracellular protein degradation. However, these strategies rely on specific lysosome-trafficking receptors to facilitate lysosomal delivery, which may raise resistance concerns due to intrinsic cell-to-cell variation in receptor expression and mutations or downregulation of the receptors. Another challenge is establishing a universal platform applicable in multiple scenarios. Here, we develop MONOTAB (MOdified NanOparticle with TArgeting Binders), a plug-and-play monofunctional degradation platform that can drag extracellular targets into lysosomes for degradation. MONOTAB harnesses the inherent lysosome-targeting ability of certain nanoparticles to obviate specific receptor dependency and the hook effect. To achieve high modularity and programmable target specificity, we utilize the streptavidin-biotin interaction to immobilize antibodies or other targeting molecules on nanoparticles, through an antibody mounting approach or by direct binding. Our study reveals that MONOTAB can induce efficient degradation of diverse therapeutic targets, including membrane proteins, secreted proteins, and even extracellular vesicles.

Abstract Background An increasing number of clinical trials for new therapeutic strategies are underway or being considered for dystrophinopathy. Having detailed data on the natural progression of this condition is crucial for assessing the effectiveness of new drugs. However, there’s a lack of data regarding the long-term data on the natural course and how it’s managed in China. In this study, we offer a comprehensive overview of clinical and molecular findings, as well as treatment outcomes in the Chinese population. Methods Institutional data on all patients with dystrophinopathy from August 2011 to August 2021 were retrospectively reviewed. The data included geographic distribution, age at diagnosis, molecular findings, and treatment options, such as corticosteroids, cardiac interventions, and clinical outcomes. Results In total, 2097 patients with dystrophinopathy, including 1703 cases of Duchenne muscular dystrophy (DMD), 311 cases of Becker muscular dystrophy (BMD), 46 cases of intermediate muscular dystrophy (IMD), and 37 cases categorized as “pending” (individuals with an undetermined phenotype), were registered in the Children’s Hospital of Fudan University database for dystrophinopathy from August 2011 to August 2021. The spectrum of identified variants included exonic deletions (66.6%), exonic duplications (10.7%), nonsense variants (10.3%), splice-site variants (4.5%), small deletions (3.5%), small insertions/duplications (1.8%), and missense variants (0.9%). Four deep intronic variants and two inversion variants were identified. Regarding treatment, glucocorticoids were administered to 54.4% of DMD patients and 39.1% of IMD patients. The median age at loss of ambulation was 2.5 years later in DMD patients who received glucocorticoid treatment. Overall, one cardiac medicine at least was prescribed to 7.4% of DMD patients, 8.3% of IMD patients, and 2.6% of BMD patients. Additionally, ventilator support was required by four DMD patients. Eligibility for exon skipping therapy was found in 55.3% of DMD patients, with 12.9%, 10%, and 9.6% of these patients being eligible for skipping exons 51, 53, and 45, respectively. Conclusions This is one of the largest studies to have evaluated the natural history of dystrophinopathy in China, which is particularly conducive to the recruitment of eligible patients for clinical trials and the provision of real-world data to support drug development.

Abstract Polyploidization presents an unusual challenge for species with sex chromosomes, as it can lead to complex combinations of sex chromosomes that disrupt reproductive development. This is particularly true for allopolyploidization between species with different sex chromosome systems. Here, we assemble haplotype-resolved chromosome-level genomes of a female allotetraploid weeping willow (Salix babylonica) and a male diploid S. dunnii. We show that weeping willow arose from crosses between a female ancestor from the Salix-clade, which has XY sex chromosomes on chromosome 7, and a male ancestor from the Vetrix-clade, which has ancestral XY sex chromosomes on chromosome 15. We find that weeping willow has one pair of sex chromosomes, ZW on chromosome 15, that derived from the ancestral XY sex chromosomes in the male ancestor of the Vetrix-clade. Moreover, the ancestral 7X chromosomes from the female ancestor of the Salix-clade have reverted to autosomal inheritance. Duplicated intact ARR17-like genes on the four homologous chromosomes 19 likely have contributed to the maintenance of dioecy during polyploidization and sex chromosome turnover. Taken together, our results suggest the rapid evolution and reversion of sex chromosomes following allopolyploidization in weeping willow.

Abstract Background Negative energy balance (NEB) typically occurs in dairy cows after delivery. Cows with a high yield are more likely to experience significant NEB. This type of metabolic imbalance could cause ketosis, which is often accompanied by a decline in reproductive performance. However, the molecular mechanisms underlying NEB have yet to be fully elucidated. During excessive NEB, the body fat is extensively broken down, resulting in the abnormal accumulation of non-esterified fatty acids (NEFAs), represented by palmitic acid (PA), within the uterus. Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells (BEECs), while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs remains poorly understood. Melatonin (MT) is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species (mitoROS). However, little is known as to whether MT could ameliorate the damage incurred by BEECs in response to PA and the molecular mechanism involved. Results Analysis showed that 0.2 mmol/L PA stress increased the level of cellular and mitochondrial oxidative stress, as indicated by increased reactive oxygen species (ROS) level. In addition, we observed mitochondrial dysfunction, including abnormal mitochondrial structure and respiratory function, along with a reduction in mitochondrial membrane potential and mitochondrial copy number, and the induction of apoptosis. Notably, we also observed the upregulation of autophagy proteins (PINK, Parkin, LC3B and Ubiquitin), however, the P62 protein was also increased. As we expected, 100 μmol/L of MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function. Meanwhile, MT pretreatment reversed the upregulation of P62 induced by PA and activated the AMPK-mTOR-Beclin-1 pathway, contributing to an increase of autophagy and decline apoptosis. Conclusions Our findings indicate that PA can induce mitochondrial dysfunction and enhance autophagy in BEECs. In addition, MT is proved to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria by upregulating autophagy pathways, thereby safeguarding the mitochondrial pool and promoting cellular viability. Our study provides a better understanding of the molecular mechanisms underlying the effect of an excess of NEB on the fertility outcomes of high yielding dairy cows.

Abstract Objective Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment. Methods Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)‐induced mouse seizure model. Results DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti‐seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low‐frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti‐seizure and EEG‐modulating effects of septal DBS, suggesting the seizure‐alleviating effect of DBS was dependent on local cholinergic neurons. Significance DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons‐augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS. Plain Language Summary The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons‐augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.

Abstract Background Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. Methods This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan–Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). Results We included 132 patients in this study, divided into RDI

To explore the quality and material basis of Shoumei white tea from different varieties of tea trees, in this study, Shoumei white tea made from the raw materials of Fu'an Da Bai (FA), Fuding Da Hao (FD), Meizhan (MZ) and Fengqing Da Ye Zhong (FQ) were analyzed for their quality using sensory evaluation, high performance liquid chromatography (HPLC), headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) and its permutation test were used to distinguish the differences among the samples, and variables were selected based on the variable importance in projection (VIP) values and P-values. The results indicated that there were differences in both sensory evaluation and physicochemical properties among the white teas processed from the four varieties of tea trees. Each of the Shoumei white teas from the four varieties of tea trees exhibited good sensory qualities and distinct characteristics. The water extract content of the different Shoumei white teas ranged from 45.48% to 46.89%, the tea polyphenol content ranged from 16.79% to 19.96%, the caffeine content ranged from 41.34 to 56.61 mg/g, the total theaflavin content ranged from 3.31 to 8.22 mg/g, the total catechin content ranged from 143.90 to 165.62 mg/g, the non-esterified catechin content ranged from 21.55 to 36.01 mg/g, the esterified catechin content ranged from 114.14 to 134.16 mg/g, and the total free amino acid content ranged from 30.35 to 38.31 mg/g. Furthermore, differences in the content of non-volatile compounds were observed among the different tea samples. A total of 57 volatile compounds were detected in the four tea samples, with a total concentration ranging from 121.63 to 203.43 μg/g. Among them, alcohols and aldehydes accounted for the majority. Significant differences were observed among the tea samples in terms of the aroma profile, types, and concentrations of volatile compounds. OPLS-DA based on 93 compounds from the four tea samples was employed to effectively differentiate between the tea samples and identify 56 differentiating compounds (VIP>1 and P

Objective Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤−1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.

Infectious diseases are a global public health problem, with emerging and re-emerging infectious diseases on the rise worldwide. Therefore, their prevention and treatment are still major challenges. Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids, glucose, and energy. Bile acids have historically been utilized as first-line, valuable therapeutic agents for related metabolic and hepatobiliary diseases. Notably, bile acids are the major active ingredients of cow bezoar and bear bile, which are commonly used traditional Chinese medicines (TCMs) with the therapeutic effects of clearing heat, detoxification, and relieving wind and spasm. In recent years, the promising performance of bile acids against infectious diseases has attracted attention from the scientific community. This paper reviews for the first time the biological activities, possible mechanisms, production routes, and potential applications of bile acids in the treatment and prevention of infectious diseases. Compared with previous reviews, we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality. In addition, to ensure a stable supply of bile acids at affordable prices, it is necessary to clarify the biosynthesis of bile acids in vivo, which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis, biosynthesis, and chemoenzymatic synthesis. Finally, we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids. The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Abstract Background Osteoclast hyperactivation due to the pathological overproduction of reactive oxygen species (ROS) stimulated by glucocorticoids (GCs) is one of the key drivers behind glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). The insulin degrading enzyme (IDE), a conserved Zn2+ metallo-endopeptidase, facilitates the DNA binding of glucocorticoid receptor and plays a substantial role in steroid hormone-related signaling pathways. However, the potential role of IDE in the pathogenesis of GIONFH is yet undefined. Methods In this study, we employed network pharmacology and bioinformatics analysis to explore the impact of IDE inhibition on GIONFH with 6bK as an inhibitory agent. Further evidence was collected through in vitro osteoclastogenesis experiments and in vivo evaluations involving methylprednisolone (MPS)-induced GIONFH mouse model. Results Enrichment analysis indicated a potential role of 6bK in redox regulation amid GIONFH development. In vitro findings revealed that 6bK could attenuate GCs-stimulated overactivation of osteoclast differentiation by interfering with the transcription and expression of key osteoclastic genes (Traf6, Nfatc1, and Ctsk). The use of an H2DCFDA probe and subsequent WB assays introduced the inhibitory effects of 6bK on osteoclastogenesis, linked with the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2)-mediated antioxidant system. Furthermore, Micro-CT scans validated that 6bK could alleviate GIONFH in MPS-induced mouse models. Conclusions Our findings suggest that 6bK suppresses osteoclast hyperactivity in GCs-rich environment. This is achieved by reducing the accumulation of intracellular ROS via promoting the Nrf2-mediated antioxidant system, thus implying that IDE could be a promising therapeutic target for GIONFH.

Abstract Small extracellular vesicles (sEV) derived from diverse natural killer (NK) cell lines have proven their exceptional antitumor activities. However, sEV from human primary NK cells, especially memory-like NK cells, are rarely utilized for cancer treatment. In this study, we obtained sEV from IL-12, IL-15 and IL-18 cultured human memory-like NK cells (mNK-sEV) that showed strong cytokine-secretory ability. It was uncovered that mNK-sEV entered cancer cells via macropinocytosis and induced cell apoptosis via caspase-dependent pathway. Compared to sEV from conventionally cultured NK cells (conNK-sEV), mNK-sEV inhibited tumor growth to a greater extent. Concomitantly, pharmacokinetics and biodistribution results validated a higher accumulation of mNK-sEV than conNK-sEV in tumors of xenografted murine models. Notably, elevated containment of granulysin (GNLY) within mNK-sEV, at least in part, may contribute to the enhanced therapeutic effect. Herein our results present that mNK-sEV can be a novel class of therapeutic reagent for effective cancer treatment. Graphical Abstract

According to the engineering geological characteristics and production technology level of Qianyingzi Coal Mine, the stability control technology of surrounding rock of the cutting roof and pressure relief roadway is proposed. For the advanced section, lagging section and stable section of the mining roadway, technical measures of advanced reinforcement support, side wall protection and lagging temporary support were proposed. Through the real-time monitoring system, the stress of anchor cable and surrounding rock deformation of goaf roadway are monitored, the deformation characteristics of roadway and stope surrounding rock are studied, and the law of mine pressure development in self-formed roadway without coal pillar is revealed by the comparison and analysis with the existing goaf roadway. The results show that the deformation rate of surrounding rock reaches the maximum at the position of 170 m away from the working face, and the deformation of surrounding rock is the most intense at this stage, and then tends to be gentle, and the deformation of surrounding rock reaches the stable stage when the working face lags 220 m. The application effect of the pre-cracking blasting cutting roof for gob-side entry retaining in the W3233 working face of Qianyingzi Coal Mine has reached the expected goal.

Abstract Using e + e − collision data collected with the BESIII detector at the BEPCII collider at center-of-mass energies between 3.510 and 4.914 GeV, corresponding to an integrated luminosity of 25 fb −1, we measure the Born cross sections for the process e + e − → K − Ξ ¯ + Λ / Σ 0 $$ {e}^{+}{e}^{-}\to {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ at thirty-five energy points with a partial-reconstruction strategy. By fitting the dressed cross sections of e + e − → K − Ξ ¯ + Λ / Σ 0 $$ {e}^{+}{e}^{-}\to {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ , evidence for ψ 4160 → K − Ξ ¯ + Λ $$ \psi (4160)\to {K}^{-}{\overline{\Xi}}^{+}\Lambda $$ is found for the first time with a significance of 4.4σ, including systematic uncertainties. No evidence for other possible resonances is found. In addition, the products of electronic partial width and branching fraction for all assumed resonances decaying into K − Ξ ¯ + Λ / Σ 0 $$ {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ are determined.

Abstract Lipid metabolism reprogramming involves in epithelial-mesenchymal transition (EMT), cancer stemness and immune checkpoints (ICs), which influence the metastasis of cancer. This study aimed to generate lipid metabolism-based signatures to predict prognosis, immunotherapy and chemotherapy response for colorectal adenocarcinoma (COAD). Transcriptome data and clinical information of COAD patients were collected from the cancer genome atlas (TCGA) database. The expression of EMT-, stem cell-, and IC-related genes were assessed between COAD and control samples. Modules and genes correlated EMT, ICs and stemness signatures were identified through weighted gene co-expression network analysis (WGCNA). Prognostic signatures were generated and then the distribution of risk genes was evaluated using single-cell RNA sequencing (scRNA-seq) data from GSE132465 dataset. COAD patients exhibited increased EMT score and stemness along with decreased ICs. Next, 12 hub genes (PIK3CG, ALOX5AP, PIK3R5, TNFAIP8L2, DPEP2, PIK3CD, PIK3R6, GGT5, ELOVL4, PTGIS, CYP7B1 and PRKD1) were found within green and yellow modules correlated with EMT, stemness and ICs. Lipid metabolism-based prognostic signatures were generated based on PIK3CG, GGT5 and PTGIS. Patients with high-risk group had poor prognosis, elevated ESTIMATEScore and StromalScore, 100% mutation rate and higher TIDE score. Samples in low-risk group had more immunogenicity on ICIs. Notably, PIK3CG was expressed in B cells, while GGT5 and PTGIS were expressed in stromal cells. This study generates lipid metabolism-based signatures correlated with EMT, stemness and ICs for predicting prognosis of COAD, and provides potential therapeutic targets for immunotherapy in COAD.

Abstract Solar-driven evaporation offers a sustainable solution for water purification, but efficiency losses due to heat dissipation and fouling limit its scalability. Herein, we present a bilayer-structured solar evaporator (SDWE) with dynamic fluidic flow mechanism, designed to ensure a thin water supply and self-cleaning capability. The porous polydopamine (PDA) layer on a nickel skeleton provides photothermal functionality and water microchannels, while the thermo-responsive sporopollenin layer on the bottom acts as a switchable water gate. Using confocal laser microscopy and micro-CT, we demonstrate that this unique structure ensures a steady supply of thin water layers, enhancing evaporation by minimizing latent heat at high temperatures. Additionally, the system initiates a self-cleaning process through bulk water convection when temperature drops due to salt accumulation, thus maintaining increased evaporation efficiency. Therefore, the optimized p-SDWE sample achieved a high evaporation rate of 3.58 kg m−2 h−1 using 93.9% solar energy from 1 sun irradiation, and produces 18–22 liters of purified water per square meter of SDWE per day from brine water. This dynamic water transport mechanism surpasses traditional day-night cycles, offering inherent thermal adaptability for continuous, high-efficiency evaporation.

Abstract Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy. Graphical Abstract

Abstract Background Spinal muscular atrophy (SMA) is a progressive neurodegenerative disorder that can be treated with intrathecal nusinersen, an antisense oligonucleotide. In addition to efficacy, safety is a determining factor in the success of any therapy. Here, we aim to assess the safety of nusinersen therapy in paediatric patients with SMA. Methods Laboratory data of paediatric patients with SMA who received nusinersen between October 2019 and May 2022 were retrospectively analysed. Results During the observation period, 46 infants and children aged 2.9 months to 13.6 years received a total of 213 nusinersen doses without safety concerns. Inflammatory markers were stable throughout the study. International normalized ratio was increased by 0.09 per injection. Urea levels were increased by 0.108 mmol/L, and cystatin C decreased by 0.029 mg/L per injection. There were no significant changes in platelet count, activated partial thrombin time, creatinine levels or liver enzyme levels during treatment. The cerebrospinal fluid (CSF) leukocyte count remained stable, and total protein increased by 24.038 mg/L per injection. Conclusion Our data showed that nusinersen therapy is generally safe in children with SMA. Laboratory monitoring did not identify any persistent or significantly abnormal findings. CSF protein should be monitored to gain more insights.

Abstract Background Cardiometabolic multimorbidity (CM) is emerging as a global health challenge. This study investigated the potential impact of muscle strength on the risk of CM in middle-aged and older Chinese adults. Methods In total, 7610 participants were identified from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was measured by absolute, relative grip strength (normalized for body mass index) and chair-rising time which were classified into three categories according to tertiles stratified by gender. Cox proportional hazards models were adopted to evaluate the effect of muscle strength on CM. Results During follow-up, 235(3.76%) participants from none cardiometabolic diseases (CMD), 140 (19.23%) from diabetes, 119 (21.17%) from heart disease, and 22 (30.56%) from stroke progressed to CM. In participants who had low relative grip strength, CM was more likely to occur in individuals with heart disease at baseline (HR: 1.89, 95%CIs: 1.10 to 3.23). Those with high chair-rising time had a higher risk of CM than those with low chair-rising time in the individuals with diabetes (HR: 1.85, 95%CIs:1.20 to 2.86) and with heart disease (HR: 1.67, 95%CIs:1.04 to 2.70). However, we did not observe an association between muscle strength and CM in participants without CMD or with stroke at baseline. Conclusions In Chinese middle-aged and older adults, low relative grip strength was associated with a higher risk of CM in individuals with heart disease, while high chair-rising time was associated with a higher risk of CM in individuals with diabetes or heart disease.

Abstract With a sample of (10087 ± 44) × 106 J/ψ events accumulated with the BESIII detector, we analyze the decays η′ → π + π − l + l − (l = e, μ) via the process J/ψ → γη′. The branching fractions are measured to be B $$ \mathcal{B} $$ (η′ → π + π − e + e − ) = (2.45 ± 0.02(stat.) ± 0.08(syst.)) × 10 −3 and B $$ \mathcal{B} $$ (η′ → π + π − μ + μ − ) = (2.16 ± 0.12(stat.) ± 0.06(syst.)) × 10 −5, and the ratio is B η ′ → π + π − e + e − B η ′ → π + π − μ + μ − = 113.4 ± 0.9 stat . ± 3.7 syst . $$ \frac{\mathcal{B}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{e}^{+}{e}^{-}\right)}{\mathcal{B}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{\mu}^{+}{\mu}^{-}\right)}=113.4\pm 0.9\left(\textrm{stat}.\right)\pm 3.7\left(\textrm{syst}.\right) $$ . In addition, by combining the η′ → π + π − e + e − and η′ → π + π − μ + μ − decays, the slope parameter of the electromagnetic transition form factor is measured to be b η′ = 1.30 ± 0.19 (GeV/c 2) −2, which is consistent with previous measurements from BESIII and theoretical predictions from the VMD model. The asymmetry in the angle between the π + π − and l + l − decay planes, which has the potential to reveal the CP-violation originating from an unconventional electric dipole transition, is also investigated. The asymmetry parameters are determined to be A CP η ′ → π + π − e + e − = − 0.21 ± 0.73 stat . ± 0.01 syst . % $$ {\mathcal{A}}_{CP}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{e}^{+}{e}^{-}\right)=\left(-0.21\pm 0.73\left(\textrm{stat}.\right)\pm 0.01\left(\textrm{syst}.\right)\right)\% $$ and A CP η ′ → π + π − μ + μ − = 0.62 ± 4.71 stat . ± 0.08 syst . % $$ {\mathcal{A}}_{CP}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{\mu}^{+}{\mu}^{-}\right)=\left(0.62\pm 4.71\left(\textrm{stat}.\right)\pm 0.08\left(\textrm{syst}.\right)\right)\% $$ , implying that no evidence of CP-violation is observed at the present statistics. Finally, an axion-like particle is searched for via the decay η′ → π + π − a, a → e + e − , and upper limits of the branching fractions are presented for the mass assumptions of the axion-like particle in the range of 0 − 500 MeV/c 2.

Abstract Aquilaria yunnanensis is an endangered agarwood-producing tree currently listed on the IUCN Red List of Threatened Species. The agarwood it produces has important medicinal and economic value, but its population has sharply declined due to human destruction and habitat reduction. Therefore, obtaining genomic information on A. yunnanensis is beneficial for its protection work. We assembled a chromosome-level reference genome of A. yunnanensis by using BGI short reads, PacBio HiFi long reads, coupled with Hi-C technology. The final genome assembly of A. yunnanensis is 847.04 Mb, with N50 size of 99.68 Mb, in which 805.49 Mb of the bases were anchored on eight pseudo-chromosomes. Two gapless pseudo-chromosomes were detected in the assembly. A total of 27,955 protein-coding genes as well as 74.65% repetitive elements were annotated. These findings may provide valuable resources in conservation, functional genomics, and molecular breeding of A. yunnanensis, as well as the molecular phylogenetics and evolutionary patterns in Aquilaria.

Abstract Alkylamine structures represent one of the most functional and widely used in organic synthesis and drug design. However, the general methods for the functionalization of the shielded and deshielded alkyl radicals remain elusive. Here, we report a general deoxygenative amination protocol using alcohol-derived carbazates and nitrobenzene under electrochemical conditions. A range of primary, secondary, and tertiary alkylamines are obtained. This practical procedure can be scaled up through electrochemical continuous flow technique.