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Abstract Utilizing Generative Adversarial Networks (GANs) to generate 3D representations of the Terracotta Warriors offers a novel approach for the preservation and restoration of cultural heritage. Through GAN technology, we can produce complete 3D models of the Terracotta Warriors’ faces, aiding in the repair of damaged or partially destroyed figures. This paper proposes a distillation model, DIGAN, for generating 3D Terracotta Warrior faces. By extracting knowledge from StyleGAN2, we train an innovative 3D generative network. G2D, the primary component of the generative network, produces detailed and realistic 2D images. The 3D generator modularly decomposes the generation process, covering texture, shape, lighting, and pose, ultimately rendering 2D images of the Terracotta Warriors’ faces. The model enhances the learning of 3D shapes through symmetry constraints and multi-view data, resulting in high-quality 2D images that closely resemble real faces. Experimental results demonstrate that our method outperforms existing GAN-based generation methods.

Highlights Negative charged acidic polarity (NCAP) has been unveiled as the guideline for selecting additives to regulate electric double layer (EDL) for Zn-ion batteries. NCAP glutamate has been verified to regulate EDL structure with synergetic effects, including preferential adsorption on Zn anode and reconstruction of hydrated Zn-ion clusters. Adding NCAP additives, Zn|Cu half-cell achieves a high Coulombic efficiency of 99.83% for 2000 cycles, and NH4V4O10|Zn full cell realizes a high-capacity retention of 82.1% for 3000 cycles.

Abstract Background Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear. Methods We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018. Results We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo. Conclusions Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.

Abstract Traditional Chinese settlements (TCSs) embody millennia of human and cultural history, with the core culture serving as their essence. However, any damage incurred by these TCSs can result in the loss of core culture. In the era of China’s digital transformation, there has recently been a significant push toward digital reforms within TCSs. Thus, this paper introduces a traditional settlement digitalization (TSD) framework with a specific focus on enhancing the preservation of TCS landscape gene through the perspective of landscape gene information chain theory. This research uses the Nanxun traditional settlement (TS), Huzhou, Zhejiang, China, the first TS listed as a World Cultural Heritage Site in China, as a case study, extracting and identifying the area landscape gene and digital visualization status. This article identifies the landscape gene information chain of the Nanxun TS and redesigns its digital visualization and application scheme under the TSD framework. This study reveals the notion of a digital landscape gene characterized by four key attributes: identical, interactive, immersive, and intelligent. The results of this study will help guide the sustainable protection, application and planning of the Nanxun TS and promote the study of other sections of landscape gene theory. This research not only contributes to the development of landscape gene information chain theory but also provides guidance for the digital transformation of other TCSs and cultural heritage sites.

Abstract Background Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15–39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). Result In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. Conclusion ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Research have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of MSCs in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.

Abstract The integrity of shale gas wells is crucial in ensuring safety and efficiency throughout the development process. Such integrity spans the entire process of drilling and fracturing horizontal wells and is an essential indicator for ensuring safe and stable production throughout the lifespan of the well. This study investigates methods for assessing the integrity of shale gas wells by employing the analytic hierarchy process combined with experimental data to establish evaluation criteria and weights. The assessment is carried out specifically on shale gas wells in Changning Block. Results indicate that the integrity of these shale gas wells is influenced by various factors, such as drilling and fracturing processes. Moreover, the integrity assessment of indicators such as oil layer casing/technical casing, liquid carrying capacity, and tube column deformation is relatively low, indicating a need for enhanced monitoring and management. The comprehensive evaluation results indicate that, overall, the integrity rating of shale gas wells is generally considered “common,” but some potential safety hazards still remain that require timely attention and resolution. Case analysis reveals varying levels of integrity risks in shale gas wells. Case 1’s score of 93.51 warrants attention but is still deemed generally safe. However, Case 2’s score of 73.89 indicates a disaster level, emphasizing urgent intervention needs. Critical factors such as pressure, cementation quality, and corrosion demand proactive management for safe, sustainable operations.

Agarwood is a traditional medicinal material and natural fragrance in the world, with long history of application. At present, Aquilaria Lam. is the main species in agarwood production. The development of and market demand of agarwood industry has led to excessive exploitation and depletion of Aquilaria tree species in the wild, posing a threat to their germplasm diversity and sustainable development. To better utilize and protect the agarwood resources, this paper analyzed the development status of the agarwood industry based on the reference materials related to genetic diversity and molecular identification of Aquilaria, combined with the market research at home and abroad. And we conducted a systematic investigation into the development and utilization of the germplasm resources of Aquilaria in Guangdong, Hainan, Guangxi, Fujian and other domestic provinces as well as in overseas countries, such as Malaysia and Vietnam. We summarized and outlined the genetic diversity and molecular identification studies of Aquilaria plants at home and abroad. We explored the research progress of genetic diversity in Aquilaria from four aspects, including phenotypic traits, DNA molecular markers, DNA fingerprinting technology and nuclear genome level, and the current research status of molecular identification of Aquilaria from three major aspects, including DNA fingerprinting, DNA barcoding of nucleoplasmic gene fragments, and put forward the problems and trends of Aquilaria in molecular genetics, with a view to providing references for the researches of germplasm resources of Aquilaria.

Abstract Background Soybean (Glycine max), a vital grain and oilseed crop, serves as a primary source of plant protein and oil. Soil salinization poses a significant threat to soybean planting, highlighting the urgency to improve soybean resilience and adaptability to saline stress. Melatonin, recently identified as a key plant growth regulator, plays crucial roles in plant growth, development, and responses to environmental stress. However, the potential of melatonin to mitigate alkali stress in soybeans and the underlying mechanisms remain unclear. Results This study investigated the effects of exogenous melatonin on the soybean cultivar Zhonghuang 13 under alkaline stress. We employed physiological, biochemical, transcriptomic, and metabolomic analyses throughout both vegetative and pod-filling growth stages. Our findings demonstrate that melatonin significantly counteracts the detrimental effects of alkaline stress on soybean plants, promoting plant growth, photosynthesis, and antioxidant capacity. Transcriptomic analysis during both growth stages under alkaline stress, with and without melatonin treatment, identified 2,834 and 549 differentially expressed genes, respectively. These genes may play a vital role in regulating plant adaptation to abiotic stress. Notably, analysis of phytohormone biosynthesis pathways revealed altered expression of key genes, particularly in the ARF (auxin response factor), AUX/IAA (auxin/indole-3-acetic acid), and GH3 (Gretchen Hagen 3) families, during the early stress response. Metabolomic analysis during the pod-filling stage identified highly expressed metabolites responding to melatonin application, such as uteolin-7-O-(2''-O-rhamnosyl)rutinoside and Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside, which helped alleviate the damage caused by alkali stress. Furthermore, we identified 183 differentially expressed transcription factors, potentially playing a critical role in regulating plant adaptation to abiotic stress. Among these, the gene SoyZH13_04G073701 is particularly noteworthy as it regulates the key differentially expressed metabolite, the terpene metabolite Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. WGCNA analysis identified this gene (SoyZH13_04G073701) as a hub gene, positively regulating the crucial differentially expressed metabolite of terpenoids, Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. Our findings provide novel insights into how exogenous melatonin alleviates alkali stress in soybeans at different reproductive stages. Conclusions Integrating transcriptomic and metabolomic approaches, our study elucidates the mechanisms by which exogenous melatonin ameliorates the inhibitory effects of alkaline stress on soybean growth and development. This occurs through modulation of biosynthesis pathways for key compounds, including terpenes, flavonoids, and phenolics. Our findings provide initial mechanistic insights into how melatonin mitigates alkaline stress in soybeans, offering a foundation for molecular breeding strategies to enhance salt-alkali tolerance in this crop.

Abstract The image classification task of porcelain fragments is of great significance for the digital preservation of cultural heritage. However, common issues are encountered in the image processing of porcelain fragments, including the low computation speed, decreased accuracy due to the uneven distribution of sample categories, and model instability. This study proposes a novel Capsule Network model, referred to as LBCapsNet, which is suitable for the extraction of features from images of porcelain artifacts fragments. A bottleneck-like channel transformation module denoted by ChannelTrans, which resides between the convolutional layer and the PrimaryCaps layer, was first designed. This module is used to reduce the computational complexity and enhance the processing speed when dealing with intricate porcelain images. The MF-R loss function was then proposed by incorporating focal loss into the original loss function. This allows to address the issue of imbalanced distribution of ceramic shard samples and reduce the classification errors, which leads to faster convergence with smoother trend. Finally, an adaptive dynamic routing mechanism is designed with a dynamic learning rate to enhance the overall stability of the classification process. The experimental results obtained on public datasets, such as MNIST, Fashion- MNIST, CIFAR10, FMD and DTD as well as porcelain fragments dataset, demonstrate that LBCapsNet achieves high classification accuracy with faster and more stable computation compared with existing methods. Furthermore, the ability of LBCapsNet to process special textures can provide technical support for the digital preservation and restoration of cultural heritage.

Soil and water conservation measures (SWCM) have wide-ranging effects on vegetation and soil, and their effects on the ecosystem are multifaceted, with complex mechanisms. While numerous studies have focused on the impact of such measures on soil, the improvement of plant functional traits is a major factor in the ecological recovery of the Loess Plateau. This survey extensively investigated no measure plots, vegetation measure plots, and engineering measure plots in the Loess Plateau. The impact of SWCM on plant functional traits was investigated using structural equation modeling. We examined six plant functional traits—leaf dry weight (LD), specific leaf area (SLA), leaf tissue density (LTD), leaf total phosphorus (LTP), leaf total nitrogen (LTN), and leaf volume (LV)—correlated with resource acquisition and allocation. In 122 plots, we explored the effects of measures, soil, diversity, and community structure on the weighted average of plant functional traits. The findings showed substantial positive correlations between LD and SLA, LD and LV, SLA and LV, SLA and LTP, and LTP and LTN. LTD has a substantial negative correlation with LD, LTD with SLA, and LTD with LV. SWCM limits diversity, and the mechanisms by which it affects plant functional traits vary. In the structural equation model (SEM) of vegetation measures, improving community structure enhances plant functional traits, but soil factors have the greatest influence on plant functional traits in SEM engineering measures. Plant functional trait differences on the Loess Plateau result are due to differential plant responses to diverse soil properties and community structure. Vegetation measures enhance the chemical properties of plant functional traits, while engineering measures improve physical properties. The study provides a theoretical foundation for vegetation restoration and management following the implementation of diverse SWCM.

Objective: The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema. Methods: A mice model of middle cerebral artery occlusion and reperfusion was used. A fluorescence tracer was injected into the cortex and evaluated glymphatic clearance. To investigate the role of DP71 in maintaining AQP4 polarization, an adeno-associated virus with the astrocyte promoter was used to overexpress Dp71. The expression and distribution of DP71 and AQP4 were analyzed using immunoblotting, immunofluorescence, and co-immunoprecipitation techniques. The behavior ability of mice was evaluated by open field test. Open-access transcriptome sequencing data were used to analyze the functional changes of astrocytes after cerebral ischemia. MG132 was used to inhibit the ubiquitin-proteasome system. The ubiquitination of DP71 was detected by immunoblotting and co-immunoprecipitation. Results: During the vasogenic edema stage following cerebral ischemia, a decline in the efflux of interstitial fluid tracer was observed. DP71 and AQP4 were co-localized and interacted with each other in the perivascular astrocyte endfeet. After cerebral ischemia, there was a notable reduction in DP71 protein expression, accompanied by AQP4 depolarization and proliferation of reactive astrocytes. Increased DP71 expression restored glymphatic drainage and reduced brain edema. AQP4 depolarization, reactive astrocyte proliferation, and the behavior of mice were improved. After cerebral ischemia, DP71 was degraded by ubiquitination, and MG132 inhibited the decrease of DP71 protein level. Conclusion: AQP4 depolarization after cerebral ischemia leads to glymphatic clearance disorder and aggravates cerebral edema. DP71 plays a pivotal role in regulating AQP4 polarization and consequently influences glymphatic function. Changes in DP71 expression are associated with the ubiquitin-proteasome system. This study offers a novel perspective on the pathogenesis of brain edema following cerebral ischemia.

Abstract Sulfide solid‐state electrolytes (SSEs) with superior ionic conductivity and processability are highly promising candidates for constructing all‐solid‐state lithium metal batteries (ASSLMBs). However, their practical applications are limited by their intrinsic air instability and serious interfacial incompatibility. Herein, a novel glass‐ceramic electrolyte Li3.12P0.94Bi0.06S3.91I0.18 was synthesized by co‐doping Li3PS4 with Bi and I for high‐performance ASSLMBs. Owing to the strong Bi‒S bonds that are thermodynamically stable to water, increased unit cell volume and Li+ concentration caused by P5+ substitution with Bi3+, and the in situ formed robust solid electrolyte interphase layer LiI at lithium surface, the as‐prepared Li3.12P0.94Bi0.06S3.91I0.18 SSE achieved excellent air stability with a H2S concentration of only 0.205 cm3 g−1 (after 300 min of air exposure), outperforming Li3PS4 (0.632 cm3 g−1) and the most reported sulfide SSEs, together with high ionic conductivity of 4.05 mS cm−1. Furthermore, the Li3.12P0.94Bi0.06S3.91I0.18 effectively improved lithium metal stability. With this SSE, an ultralong cyclability of 700 h at 0.1 mA cm−2 was realized in a lithium symmetrical cell. Moreover, the Li3.12P0.94Bi0.06S3.91I0.18‐based ASSLMBs with LiNi0.8Mn0.1Co0.1O2 cathode achieved ultrastable capacity retention rate of 95.8% after 300 cycles at 0.1 C. This work provides reliable strategy for designing advanced sulfide SSEs for commercial applications in ASSLMBs.

Aim: To explore the mechanisms of IRF9 in the progression of rheumatoid arthritis(RA), and the effects of IRF9 on M1/M2 polarization. Methods: RA dataset (GSE55457) was downloaded from GEO. Correlation analysis between IRF9 and its downstream target protein PSMA5 was performed using bioinformatics analysis. The M1/M2 cell ratio of peripheral blood mononuclear cells which from 20 healthy specimen and 40 RA patients was determined. The expression of IRF9 and PSMA5 was detected using qPCR and Western blot. Then, knockdown IRF9 in RAW264.7 cell line (sh-IRF9 RAW264.7) was constructed. The effect of sh-IRF9 RAW264.7 on RA was explored by constructing a CIA mouse model. Results: IRF9 is upregulated in RA and is of good early screening effect. The results of pathway analysis showed that IRF9 targets and regulates the PSMA5 signaling pathway. IRF9 and PSMA5 were significantly elevated in RA patients, M1/M2 ratio was also increased. The effects of IRF9 on RAW264.7 macrophages were deeply explored in vitro, revealing that knockdown of IRF9 suppressed PSMA5, M1/M2 ratio and the secretion of pro-inflammatory factor in RAW264.7. In mouse in vivo experiments, sh-IRF9 RAW264.7 cells were found to modulate RA by downregulating PSMA5, modulating the M1/M2 ratio through enhancing the anti-inflammatory factor, and suppressing the pro-inflammatory factor. Conclusion: IRF9 promoted the progression of RA via regulating macrophage polarization through PSMA5.

Agarwood is a valuable traditional medicine and fragrance. The production process is a typical injury-induced defense response. Currently, there are approximately 22 known species in the genus Aquilaria Lam., all of which can produce agarwood, whereas there are only two legal species of traditional Chinese medicinal agarwood, Aquilaria sinensis (Lour.) Spreng. and Aquilaria agallocha (Lour.) Roxb. The Taiwan herbal Pharmacopoeia of China stipulates that the medicinal agarwood species are A. sinensis and its relatives in the same genus. Moreover, there are five species of agarwood available for clinical medicinal use in Japan, including A. agallocha and A. sinensis, which are often confused with each other or used in a mixed way in the trade process. Therefore, accurate identification of traditional Chinese medicinal agarwood species is important to ensure the authenticity of traditional medicines and to guide the safety of clinical medication. In this study, 59 specific single-nucleotide polymorphism loci were screened and obtained from the chloroplast genomes of 12 species of the genus Aquilaria Lam. We established an identification method for traditional Chinese medicinal agarwood using mini-barcoding combined with high-resolution melting (HRM) and designed and validated 10 pairs of primers from the psbM-trnD, psbA, rps16, petN, ndhE-psaC, rps4, atpE, ycf1, rps15-trnN, and matK regions. The amplification products were all less than 200 bp, with a high success rate of amplification. The method was applied to successfully identify traditional Chinese medicinal agarwood species from commercial agarwood samples. Overall, the sensitivity of this method was sufficient to detect 1% of adulterants in medicinal agarwood products, proving that mini-barcoding HRM is a powerful and flexible tool. This method can be used as a fast and effective high-throughput method for authenticity testing of traditional Chinese medicinal agarwood and its raw materials containing agarwood-containing proprietary Chinese medicines and is recommended for industrial applications.

AimThe prevalence of obesity (Ob), overweight (Ow) and central obesity (CO) in children and adolescents has increased dramatically over the past decades globally. Flavanones have been recently studied as adjuvants for the treatment of obesity. This study was aimed at evaluating the association between intake of flavanones and its subclasses and the Ow/Ob and CO in children and adolescents.MethodsThis cross-sectional study extracted the data of children and adolescents with Ow/Ob and CO from the National Health and Nutrition Examination Survey (NHANES) database for 2007–2010 and 2017–2018. Ow and Ob were defined as a body mass index (BMI) ≥ 85th percentile. CO was defined as a waist circumference (WC) ≥ 90th percentile. The association between intake of flavanones and its subclasses and the Ow/Ob and CO in children and adolescents was determined by weighted univariate and multivariate Logistic regression models adjusted for potential covariates, and odds ratios (ORs) with 95% confidence intervals (CIs) was calculated. To further explore association between intake of flavanones and its subclasses and the Ow/Ob and CO in children and adolescents, subgroup analyses stratified by age, and gender.ResultsOf the total 5,970 children and adolescents, 2,463 (41.2%) developed Ow/Ob and 1,294 (21.7%) patients developed CO. High intake of flavanones, eriodictyol, hesperetin, and naringenin were associated with lower odds of Ow/Ob in children and adolescents. (OR: 0.75, 95%CI: 0.62–0.92, OR: 0.69, 95%CI: 0.55–0.87, OR: 0.69, 95%CI: 0.55–0.87, and OR: 0.76, 95%CI: 0.63–0.92, respectively). In addition, high intake of flavanones, eriodictyol, and naringenin were associated with lower odds of CO in children and adolescents (OR: 0.71, 95%CI: 0.57–0.88, OR: 0.67, 95%CI: 0.51–0.86, and OR: 0.69, 95%CI: 0.55–0.86, respectively). Subgroup analyses showed that among all the different subgroups, high intake of flavanones was associated with lower odds of Ow/Ob and CO in children and adolescents.ConclusionA diet loaded with high flavanones were associated with lower odds of Ow/Ob and CO in children and adolescents, and children and adolescents should be encouraged to increase their intake of flavanones.

Obtained from Aquilaria Lam. and Gyrinops Gaertn., agarwood is a prestigious perfume and medicinal material in the world. Its primary chemical constituents and indicators of agarwood's development are 2-(2-phenylethyl)chromones (PECs). However, how PECs affect its quality, accumulation, and transformation pattern is still unclear. The present study investigated this issue by monitoring resin filling in agarwood generated by the whole-tree agarwood-inducing technique over a span of a year, observing the ethanol extract concentration at different sampling times, and statistically examining PECs in agarwood from each sampling period. In agarwood, the resin accumulated over time, except during the 4th–6th month due to the creation of a barrier layer. The relative content of total PECs demonstrated an overall increase throughout the year but a decrease from the 4th month to the 6th month, and the relative content of 19 PECs that persisted throughout the year was positively correlated with the content of ethanol extracts. In addition, the process of chromone accumulation was accompanied by the production and transformation of different types of chromones, with flindersia type 2-(2-phenylethyl)chromones, epoxy-2-(2-phenylethyl)chromones, and diepoxy-2-(2-phenylethyl)chromones being the major chromone components; in addition, the content of 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones kept increasing after 6 months of agarwood formation. Three main trends were identified from 58 analogs of PECs, each with notable variation. The first type had the highest content at the beginning of resin formation. The second type had the highest content at 6 months and then started to decrease, and the third type had a slowly increasing content. As a whole, this study systematically investigated the accumulation of PECs during injury-induced agarwood production in A. sinensis, which is of scientific significance in resolving the transformation of PECs and revealing the secret of agarwood formation.

Abstract Pleckstrin homology domain-containing family M member 2 (PLEKHM2) is an essential adaptor for lysosomal trafficking and its homozygous truncation have been reported to cause early onset dilated cardiomyopathy (DCM). However, the molecular mechanism of PLEKHM2 deficiency in DCM pathogenesis and progression is poorly understood. Here, we generated an in vitro model of PLEKHM2 knockout (KO) induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the potential pathogenic mechanism of PLEKHM2-deficient cardiomyopathy. PLEKHM2-KO hiPSC-CMs developed disease phenotypes with reduced contractility and impaired calcium handling. Subsequent RNA sequencing (RNA-seq) analysis revealed altered expression of genes involved in mitochondrial function, autophagy and apoptosis in PLEKHM2-KO hiPSC-CMs. Further molecular experiments confirmed PLEKHM2 deficiency impaired autophagy and resulted in accumulation of damaged mitochondria, which triggered increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential (Δψm). Importantly, the elevated ROS levels caused oxidative stress-induced damage to nearby healthy mitochondria, resulting in extensive Δψm destabilization, and ultimately leading to impaired mitochondrial function and myocardial contractility. Moreover, ROS inhibition attenuated oxidative stress-induced mitochondrial damage, thereby partially rescued PLEKHM2 deficiency-induced disease phenotypes. Remarkably, PLEKHM2-WT overexpression restored autophagic flux and rescued mitochondrial function and myocardial contractility in PLEKHM2-KO hiPSC-CMs. Taken together, these results suggested that impaired mitochondrial clearance and increased ROS levels play important roles in PLEKHM2-deficient cardiomyopathy, and PLEKHM2-WT overexpression can improve mitochondrial function and rescue PLEKHM2-deficient cardiomyopathy.

Abstract Background Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. Methods A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. Results Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. Conclusions These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Abstract Background Square dancing is a kind of aerobic fitness exercise without environmental restrictions that yields many benefits for physical and mental health; this exercise is popular among middle-aged and elderly people in China and in these populations in other countries. This study aimed to evaluate the effects of square dance exercise on the overall cognitive function of elderly individuals with mild cognitive impairment (MCI) and to research its mechanisms. Methods A total of 60 elderly people with MCI (60–69 years old) without square dance experience were selected and randomly divided into an experimental group (n = 30) and a control group (n = 30). The experimental group participated in square dance exercise for 12 weeks, while the control group maintained their original lifestyle habits. One week before and after the intervention period, the overall cognitive function, physical fitness, and executive function of both groups were measured. Results According to the results, square dance exercise directly improved the overall cognitive function of elderly individuals with MCI and indirectly affected overall cognitive function through the mediating effects of balance ability and executive function. Conclusions Square dance exercise represents a nonpharmacological intervention for the prevention and treatment of MCI. Importantly, it is best to combine this exercise with other forms of physical exercise and comprehensive treatment programs such as cognitive training, social interaction, and psychological intervention to realize its maximum effect.

Some haplotypes of the sucrose synthase gene TaSus1 are associated with thousand-grain weight (TGW) in wheat (Triticum aestivum L.). However, no mutations have been identified within the gene to test this association. The effects of TaSus1 on grain number per spike (GNS) also are largely unknown. Our previous genome-wide association study identified TaSus-A1 as a candidate gene controlling fertile spikelet number per spike (FSN). In the present study, we generated two independent mutants for the three TaSus1 homoeologs by CRISPR/Cas9-mediated genome editing. The triple mutants displayed lower FSN, GNS, grain number per spikelet (GNST), and TGW than wild-type plants. In 306 hexaploid wheat accessions, two single-nucleotide polymorphisms in TaSus-A1 contributed differently to GNS. Introgression of the two alleles into a wheat genetic background confirmed their effects. The alleles differed in geographical distribution among the accessions.

Highlights A fluorinated zincophilic covalent organic framework (COF-S-F) with sulfonic acid group (-SO3H) is prepared on the surface of Zn anode, which promotes the desolvation of hydrated Zn ions and inhibits the side reactions. The highly electronegative -F group in COF-S-F promotes fast and uniform transport of Zn ions along the interconnected channels, which contributes to the uniform electrodeposition process of Zn metal. Zn@COF-S-F symmetric cell achieves a superior stability of 1,000 h and Zn@COF-S-F|MnO2 cell delivers high specific capacity of 206.8 mAh g−1 at current density of 1.2 A g−1.

In this work, the explicit boundary-condition-enforced immersed boundary method (EIBM) and the lattice Boltzmann flux solver (LBFS) are integrated into OpenFOAM to efficiently solve incompressible flows with complex geometries and moving boundaries. The EIBM applies the explicit technique to greatly improve the computational efficiency of the original boundary-condition-enforced immersed boundary method. In addition, the improved EIBM inherits the accurate interpretation of the no-slip boundary condition and the simple implementation from the original one. The LBFS uses the finite volume method to discretize the recovered macroscopic governing equations from the lattice Boltzmann equation. It enjoys the explicit relationship between the pressure and density, which avoids solving the pressure Poisson equation and thus saves much computational cost. Another attractive feature of the LBFS lies in its simultaneous evaluation of the inviscid and viscous fluxes. OpenFOAM, as an open-source CFD platform, has drawn increasing attention from the CFD community and has been proven to be a powerful tool for various problems. Thus, implementing the EIBM and LBFS into such a popular platform can advance the practical application of these two methods and may provide an effective alternative for complicated incompressible flow problems. The performance of the integrated solver in OpenFOAM is comprehensively assessed by comparing it with the widely used numerical solver in OpenFOAM, namely, the Pressure-Implicit with Splitting of Operators (PISO) algorithm with the IBM. A series of representative test cases with stationary and moving boundaries are simulated. Numerical results confirm that the present method does not have any streamline penetration and achieves the second-order accuracy in space. Therefore, the present method implemented in the open-source platform OpenFOAM may have good potential and can serve as a powerful tool for practical engineering problems.

Endometrial cancer is one of the three major malignant tumors of the reproductive system that threaten women’s lives and health. The incidence of this disease is on the rise globally. Most cases of endometrial cancer comprise endometrioid adenocarcinomas, whose treatment is challenged by factors such as their high recurrence rate and the need to preserve fertility among young patients. Thus, oral endocrine therapy has become the main treatment modality. The main drugs used in oral endocrine therapy are progestins, selective estrogen receptor antagonists, and aromatase inhibitors. However, their clinical use is hindered by their low solubility and low oral utilization. The rapid development of nanotechnology allows the combination of these drugs with oral nano-formulations to create a good carrier. Such nanocarriers, including nanospheres, nanocapsules, and micelles can protect the drug against clearance and increase the site specificity of drug delivery. This paper reviews the pathogenesis of endometrioid endometrial cancer (EEC) and oral nano-formulations for endocrine therapy.

Orchidaceae stands as one of the “flagship” groups in global biodiversity conservation, attracting significant attention from researchers in China. Previous studies have focused on taxonomic diversity, neglecting the integration of phylogeny and functional aspects. Here, we have leveraged a large dataset of distributions, evolutionary relationships, and functional traits of orchids in China to analyze geographic patterns of species richness (SR), weighted endemism (WE), phylogenetic diversity (PD), phylogenetic endemism (PE), functional diversity (FD), and functional endemism (FE). Furthermore, we analyzed the deviations between PD (or FD) and SR (PDdev, and FDdev), as well as between PE (or FE) and WE (PEdev, and FEdev), taking into account climatic and environmental variables. We also delineated the priority protection and survey areas of orchid plants in China. Our results revealed that the geographic patterns of SR, WE, PD, PE, FD, and FE for orchids generally exhibited similar trends. However, there were notable inconsistencies in the geographical patterns of PDdev, FDdev, PEdev, and FEdev, which might be related to the different environmental responses of these four diversity deviation metrics. We have pinpointed six priority conservation areas for orchids in China, i.e., southeasterrn Xizang, western Yunnan, central Yunan, the Karst area at the border of Guizhou and Guangxi, the border of Guangdong and Guangxi, and Taiwan Island. In addition, we have also identified certain priority survey areas for orchids, encompassing southeastern Xizang and other crucial locales. These findings will guide future conservation and research efforts aimed at safeguarding the rich biodiversity of orchids in China.

The growing use of nanomaterials has sparked significant interest in assessing the insect toxicities of nanoparticles. The silkworm, as an economically important insect, serves as a promising model for studying how insects respond to harmful substances. Here, we conducted a comprehensive investigation on the impact of graphene oxide (GO) on silkworms using a combination of physiological and transcriptome analyses. GO can enter the midguts and posterior silk glands of silkworms. High GO concentrations (> 25 mg/L) significantly (P < 0.01) inhibited larval growth. Additionally, GO (> 5 mg/L) significantly reduced the cocooning rate, and GO (> 15 mg/L) hindered oviduct development and egg laying in silkworms. GO increased the reactive oxygen species content and regulated catalase activity, suggesting that it may affect insect growth by regulating reactive oxygen detoxification. The transcriptome data analysis showed that 35 metabolism-related genes and 20 ribosome biogenesis-related genes were differentially expressed in response to GO, and their expression levels were highly correlated. Finally, we propose that a Ribosome biogenesis–Metabolic signaling network is involved in responses to GO. The research provides a new perspective on the molecular responses of insects to GO.

BackgroundThe HIV-1 molecular network is an innovative tool, using gene sequences to understand transmission attributes and complementing social and sexual network studies. While previous research focused on static network characteristics, recent studies’ emphasis on dynamic features enhances our understanding of real-time changes, offering insights for targeted interventions and efficient allocation of public health resources. ObjectiveThis study aims to identify the dynamic changes occurring in HIV-1 molecular transmission networks and analyze the primary influencing factors driving the dynamics of HIV-1 molecular networks. MethodsWe analyzed and compared the dynamic changes in the molecular network over a specific time period between the baseline and observed end point. The primary factors influencing the dynamic changes in the HIV-1 molecular network were identified through univariate analysis and multivariate analysis. ResultsA total of 955 HIV-1 polymerase fragments were successfully amplified from 1013 specimens; CRF01_AE and CRF07_BC were the predominant subtypes, accounting for 40.8% (n=390) and 33.6% (n=321) of the specimens, respectively. Through the analysis and comparison of the basic and terminal molecular networks, it was discovered that 144 sequences constituted static molecular networks, and 487 sequences contributed to the formation of dynamic molecular networks. The findings of the multivariate analysis indicated that the factors occupation as a student, floating population, Han ethnicity, engagement in occasional or multiple sexual partnerships, participation in anal sex, and being single were independent risk factors for the dynamic changes observed in the HIV-1 molecular network, and the odds ratio (OR; 95% CIs) values were 2.63 (1.54-4.47), 1.83 (1.17-2.84), 2.91 (1.09-7.79), 1.75 (1.06-2.90), 4.12 (2.48-6.87), 5.58 (2.43-12.80), and 2.10 (1.25-3.54), respectively. Heterosexuality and homosexuality seem to exhibit protective effects when compared to bisexuality, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. Additionally, the National Eight-Item score and sex education experience were also identified as protective factors against dynamic changes in the HIV-1 molecular network, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. ConclusionsThe HIV-1 molecular network analysis showed 144 sequences in static networks and 487 in dynamic networks. Multivariate analysis revealed that occupation as a student, floating population, Han ethnicity, and risky sexual behavior were independent risk factors for dynamic changes, while heterosexuality and homosexuality were protective compared to bisexuality. A higher National Eight-Item score and sex education experience were also protective factors. The identification of HIV dynamic molecular networks has provided valuable insights into the characteristics of individuals undergoing dynamic alterations. These findings contribute to a better understanding of HIV-1 transmission dynamics and could inform targeted prevention strategies.

Areca nut (AN), the fruit or seed of Areca catechu Linn, has many uses, including chewing and medicinal purposes. It has sparked worries about health due to the presence of alkaloids. Chewing AN may have a variety of negative consequences; however, the medicinal use of AN has no notable adverse effects. To completely understand and effectively use AN, researchers have investigated its chemical makeup or biological activity, analyzed the variations between different AN species and different periods, and improved extraction and processing procedures. Today, an increasing number of researchers are exploring the underlying reasons for AN variations, as well as the molecular mechanisms of biosynthesis of chemical components, to comprehend and change AN at the genetic level. This review presents an overview of the clinical study, pharmacology, and detection of the main bioactive components in AN, and the main factors influencing their content, delving into the omics applications in AN research. On the basis of the discussions and summaries, this review identifies current research gaps and proposes future directions for investigation.

BackgroundAgarwood moxibustion is a folk therapy developed by individuals of the Li nationality in China. There is evidence that agarwood moxa smoke (AMS) generated during agarwood moxibustion therapy can treat sleep disorders via traditional Chinese medicines’ multiple target and pathway characteristics. However, the specific components and mechanisms involved have yet to be explored.ObjectiveGC–MS (Gas Chromatography–Mass Spectrometry) and network pharmacology were used to investigate AMS’s molecular basis and mechanism in treating sleep deprivation.MethodGC–MS was used to determine the chemical composition of AMS; component target information was collected from TCMSP (Traditional Chinese Medicine Systems Pharmacology), PubChem (Public Chemical Database), GeneCards (Human Gene Database), and DisGeNet (Database of Genes and Diseases) were used to identify disease targets, and JVenn (Joint Venn) was used to identify the common targets of AMS and sleep disorders. STRING was used to construct a protein interaction network, Cytoscape 3.9.1 was used to build a multilevel network diagram of the “core components-efficacy targets-action pathways,” the targets were imported into Metascape and DAVID for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and Autodock was used for molecular docking. This research used a network pharmacology methodology to investigate the therapeutic potential of Agarwood Moxa Smoke (AMS) in treating sleep problems. Examining the target genes and chemical constituents of AMS offers insights into the molecular processes and targets of the disease.ResultNine active ingredients comprising anti-inflammatory substances and antioxidants, such as caryophyllene and p-cymene, found seven sleep-regulating signaling pathways and eight targets linked to sleep disorders. GC–MS was used to identify the 94 active ingredients in AMS, and the active ingredients had strong binding with the key targets. Key findings included active components with known medicinal properties, such as p-cymene, eucalyptol, and caryophyllene. An investigation of network pharmacology revealed seven signaling pathways for sleep regulation and eight targets linked to sleep disorders, shedding light on AMS’s effectiveness in enhancing sleep quality.ConclusionAMS may alleviate sleep disorders by modulating cellular and synaptic signaling, controlling hormone and neurotransmitter pathways, etc. Understanding AMS’s material basis and mechanism of action provides a foundation for future research on treating sleep disorders with AMS. According to the study, Agarwood Moxa Smoke (AMS) may improve sleep quality by modifying cellular and synaptic signaling pathways for those who suffer from sleep problems. This might lead to the development of innovative therapies with fewer side effects.

Introduction: Agarwood is a traditional aromatic southern medicine. It has a long history of being used in traditional Chinese aromatherapy to treat insomnia, anxiety and depression. Due to the scarcity of wild resources, people have planted trees successfully and begun to explore various agarwood-inducing techniques. This study comparative analysis of volatile metabolites in agarwood produced by various inducing techniques and its potential sleep-promoting, anti-anxiety and anti-depressant network pharmacological activities. Methods: A total of 23 batches of two types of agarwood were collected, one of which was produced by artificial techniques, including 6 batches of TongTi (TT) agarwood produced by “Agar-Wit” and 6 batches of HuoLao (HL) agarwood produced by “burning, chisel and drilling”, while the other was collected from the wild, including 6 batches of BanTou (BT) agarwood with trunks broken due to natural or man-made factors and 5 batches of ChongLou (CL) agarwood with trunks damaged by moth worms. The study employed metabolomics combined with network analysis to compare the differences in volatile metabolites of agarwood produced by four commonly used inducing techniques, and explored their potential roles and possible action targets in promoting sleep, reducing anxiety, and alleviating depression. Results: A total of 147 volatile metabolites were detected in agarwood samples, mainly including small aromatic hydrocarbons, sesquiterpenes and 2-(2-phenylethyl) chromone and their pyrolysis products. The results showed composition of metabolites was minimally influenced by the agarwood induction method. However, their concentrations exhibited significant variations, with 17 metabolites showing major differences. The two most distinct metabolites were 6-methoxy-2-(2-phenylethyl) chromone and 6,7-dimethoxy-2-(2-phenylethyl) chromone. Among the volatile metabolites, 142 showed promising potential in treating insomnia, anxiety, and depression, implicating various biological and signaling pathways, predominantly ALB and TNF targets. The top three active metabolites identified were 2-(2-phenylethyl) chromone, 1,5-diphenylpent-1-en-3-one, and 6-methoxy-2-[2-(4'-methoxyphenyl) ethyl] chromone, with their relative content in the four types of agarwood being TT>HL>CL>BT. Conclusion: The differences in the content of 2-(2-phenylethyl) chromones suggest that they may be responsible for the varying therapeutic activities observed in different types of agarwood aromatherapy. This study offers theoretical support for the selection of agarwood in aromatherapy practices.

Background The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well‐tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin‐induced heart failure. Methods and Results Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin‐induced cardiotoxicity. Conclusions Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Quantifying the impacts of climate change, vegetation greening and human activities (CVH) on evapotranspiration (ET), surface drought intensity (ET divided by precipitation, SDI), and vegetation available water (precipitation minus ET, VAW) would improve our understanding of water cycle processes. The Yellow River Basin (YRB) is a significant climate-sensitive region in China, resulting in an obvious spatiotemporal heterogeneity of ET, SDI, and VAW in response to driving variables. In this study, we analysed the spatiotemporal variation characteristics of ET, SDI, and VAW in the YRB from 1984 to 2018. We also quantified the direct and indirect contributions of the CVH to the changes in ET, SDI, and VAW, and revealed the influence mechanism of each link. Finally, water resource risks were assessed from a probabilistic perspective. The results indicated that vegetation greening was the primary driver of ET with an increase rate of 1.60 mm/a, which was also the most important influencing factor of SDI increase and VAW decrease. Leaf area index (LAI) and relative humidity (RH) jointly dominated the ET changes in 66 % of the YRB, temperature (Temp) dominated the SDI changes in nearly half of the basin, precipitation (Pre) and LAI jointly dominated the VAW changes in 66 % of the YRB. Temp indirectly influenced ET primarily through LAI, whereas LAI primarily influenced ET directly. Temp had a significant direct impact on SDI, while LAI mainly influenced SDI through RH and wind speed (WS). Temp exhibited the most substantial negative influence on VAW. LAI was identified as the primary factor contributing to water resource risks, with a probability reaching 0.8, while the probabilities associated with other factors inducing such risks were similar at the basin level, but disparities existed among different land use types. The findings of the study significantly enhanced our understanding of the role that the CVH played in hydrological processes, serving as a crucial foundation for achieving a balance between ecological restoration and socio-economic development in the YRB.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

Abstract The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.

Objective Geological storage of CO2 is an important technology for reducing CO2 emissions, and the assessment of CO2 leakage risk is the key to its implementation. Research on natural CO2 leakage is an important means to obtain key information for leakage assessment. Methods The source of CO2, the characteristics of CO2 leakage, and the relevant response of shallow aquifers to the CO2 leakage have been analysed through field investigations, on-site measurements, and sampling and testing of water, gas and rock. Results A number of natural CO2 leakages have been discovered in the southern Xining Basin, including CO2-rich springs, CO2-driven cold-water geysers from abandoned wells, and CO2 blowouts, as well as large-scale travertine associated with them. CO2 is the dominant component in the gas phase, and the abundance of carbon isotope of CO2 is between -2.5‰ and -0.4‰, indicating that the leaked CO2 comes from a deep inorganic origin, leaks into shallow confined aquifers through deep faults, and flows and discharges with the groundwater or accumulates secondarily in shallow formations. The concentration of soil 222Rn in areas of CO2 leakage is abnormal (over 9 000 Bq/m3), which can be used as an important method of identifying hidden leakage channels. The groundwater has a pronounced response to CO2 leakage, including a unique phenomenon of intermittent eruptions (eruption for 200 s and incubation for 130 s), changes in groundwater hydrochemical characteristics (e.g., a decrease in pH, an increase in conductance and HCO3- and Ca2+ concentrations, and a drift in oxygen isotopes), and travertine composed mainly of calcite with a bubble structure at the surface. The natural CO2 leakage characteristics at this site are highly similar to those in Utah, USA. Conclusion The results of this study not only provide knowledge of natural analogous for leakage risk assessment of CO2 geological storage, but also contribute to the understanding of geological activity in the deep earth.

Abstract Atomic-level coordination engineering is an efficient strategy for tuning the catalytic performance of single-atom catalysts (SACs). However, their rational design has so far been plagued by the lack of a universal correlation between the coordination symmetry and catalytic properties. Herein, we synthesised planar-symmetry-broken CuN3 (PSB-CuN3) SACs through microwave heating for electrocatalytic CO2 reduction. Remarkably, the as-prepared catalysts exhibited a selectivity of 94.3% towards formate at −0.73 V vs. RHE, surpassing the symmetrical CuN4 catalyst (72.4% at −0.93 V vs. RHE). In a flow cell equipped with a PSB-CuN3 electrode, over 90% formate selectivity was maintained at an average current density of 94.4 mA cm−2 during 100 h operation. By combining definitive structural identification with operando X-ray spectroscopy and theoretical calculations, we revealed that the intrinsic local symmetry breaking from planar D 4h configuration induces an unconventional dsp hybridisation, and thus a strong correlation between the catalytic activity and microenvironment of metal centre (i.e., coordination number and distortion), with high preference for formate production in CuN3 moiety. The finding opens an avenue for designing efficient SACs with specific local symmetries for selective electrocatalysis.

Abstract This study investigated the effects of Tai Chi exercise on subjective well-being in the aged. The participants were randomly assigned to an experimental group or a control group. The experimental group received 12-week Tai Chi exercise while the control group maintain their original living habits. The participants’ subjective well-being, physical fitness, self-control, and executive function were measured at baseline and after 12 weeks of Tai Chi exercise. Results: (1) Tai Chi exercise can positively affect the subjective well-being of the aged (F(1,78) = 37.699, p

The interest in edible insects’ mass rearing has grown considerably in recent years, thereby highlighting the challenges of domesticating new animal species. Insects are being considered for use in the management of organic by-products from the agro-industry, synthetic by-products from the plastics industry including particular detoxification processes. The processes depend on the insect’s digestive system which is based on two components: an enzymatic intrinsic cargo to the insect species and another extrinsic cargo provided by the microbial community colonizing—associated with the insect host. Advances have been made in the identification of the origin of the digestive functions observed in the midgut. It is now evident that the community of microorganisms can adapt, improve, and extend the insect’s ability to digest and detoxify its food. Nevertheless, edible insect species such as Hermetia illucens and Tenebrio molitor are surprisingly autonomous, and no obligatory symbiosis with a microorganism has yet been uncovered for digestion. Conversely, the intestinal microbiota of a given species can take on different forms, which are largely influenced by the host’s environment and diet. This flexibility offers the potential for the development of novel associations between insects and microorganisms, which could result in the creation of synergies that would optimize or expand value chains for agro-industrial by-products, as well as for contaminants.

BackgroundHypertension is one of the most prevalent chronic diseases among the older adult population in China and older adults with hypertension are more susceptible to mental health problems. This study aimed to explore the network structure of depression and anxiety, and their association with life satisfaction (LS) in older adults with hypertension.MethodsA total of 4,993 hypertensive individuals aged 60 and above were selected from the Chinese Longitudinal Healthy Longevity Survey (CLHLS 2017–2018). The design of the CLHLS study was approved by the Campus Institutional Review Board of Duke University (Pro00062871) and the Biomedical Ethics Committee of Peking University (IRB00001052-13,074). The Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and the Generalized Anxiety Disorder Scale-7 (GAD-7) were used to assess depressive and anxiety symptoms. Central and bridge symptoms were identified via “Expected Influence” and “Bridge Expected Influence”, respectively. Network stability was assessed using the case-dropping bootstrap technique.ResultsNetwork analysis identified CESD3 (Feeling blue/depressed), GAD4 (Trouble relaxing), and GAD2 (Uncontrollable worry) as the most influential central symptoms in the network of depression and anxiety. Concurrently, GAD1 (Nervousness or anxiety), CESD10 (Sleep disturbances), and CESD1 (Feeling bothered) stand as critical bridge symptoms between depression and anxiety disorders. Moreover, CESD7 (Lack of happiness) exhibited the strongest negative correlation with LS in Chinese hypertensive older adults.ConclusionThis exploratory study represents the first investigation to examine the mutual relationship between depressive and anxiety symptoms among Chinese hypertensive older adults. Interventions addressing targeting bridge symptoms have the potential to alleviate depressive and anxiety symptoms. Furthermore, improving happiness, hope, and sleep quality in this population may mitigate the adverse effects of depression and anxiety on LS.

A two-stage robust planning method for energy storage in distribution networks based on load prediction is proposed to address the uncertainty of active load in energy storage planning. First, considering the uncertainty of active load, a short-term load forecasting model combining the mutual information method and BiLSTM is established based on k-means++ clustering. Second, based on the results of load forecasting, a comprehensive norm-constrained uncertainty set is constructed, and a two-stage robust model for distribution network energy storage planning is established. The first stage aims to minimize the annual investment cost of the energy storage system, while the second stage aims to minimize the daily operating cost of the distribution network. At the same time, a second-order cone relaxation transformation model with non-convex constraints is introduced to ultimately achieve the optimal economy of the distribution network in energy storage planning. Finally, the effectiveness of the proposed method and model is validated on the IEEE 33-node distribution network model using the MATLAB platform.

Endometriosis is a disease characterized by the ectopic growth of endometrial tissue (glands and stroma) outside the confines of the uterus and often involves vital organs such as the intestines and urinary system. Endometriosis is considered a refractory disease owing to its enigmatic etiology, propensity for recurrence following conservative or surgical interventions, and the absence of radical treatment and long-term management. In recent years, the incidence of endometriosis has gradually increased, rendering it a pressing concern among women of childbearing age. A more profound understanding of its pathogenesis can significantly improve prognosis. Recent research endeavors have spotlighted the molecular mechanisms by which microRNAs (miRNAs) regulate the occurrence and progression of endometriosis. Many miRNAs have been reported to be aberrantly expressed in the affected tissues of both patients and animal models. These miRNAs actively participate in the regulation of inflammatory reactions, cellular proliferation, angiogenesis, and tissue remodeling. Their capacity to modulate crucial signaling pathways, such as the Wnt/β-catenin signaling pathway, reinforces their potential utility as diagnostic markers or therapeutic agents for endometriosis. In this review, we provide the latest insights into the role of miRNAs that interact with the Wnt/β-catenin pathway to regulate the biological behaviors of endometriosis cells and disease-related symptoms, such as pain and infertility. We hope that this review will provide novel insights and promising targets for innovative therapies addressing endometriosis.

Deer products from sika deer (Cervus nippon) and red deer (C. elaphus) are considered genuine and used for Traditional Chinese Medicine (TCM) materials in China. Deer has a very high economic and ornamental value, resulting in the formation of a characteristic deer industry in the prescription preparation of traditional Chinese medicine, health food, cosmetics, and other areas of development and utilization. Due to the high demand for deer products, the products are expensive and have limited production, but the legal use of deer is limited to only two species of sika deer and red deer; other wild deer are prohibited from hunting, so there are numerous cases of mixing and adulteration of counterfeit products and so on. There have been many reports that other animal (pig, cow, sheep, etc.) tissues or organs are often used for adulteration and confusion, resulting in poor efficacy of deer traditional medicine and trade fraud in deer products. To authenticate the deer products in a rapid and effective manner, the analysis used 22 deer products (antler, meat, bone, fetus, penis, tail, skin, and wool) that were in the form of blind samples. Total DNA extraction using a modified protocol successfully yielded DNA from the blind samples that was useful for PCR. Three candidate DNA barcoding loci, cox1, Cyt b, and rrn12, were evaluated for their discrimination strength through BLAST and phylogenetic clustering analyses. For the BLAST analysis, the 22 blind samples obtained 100% match identity across the three gene loci tested. It was revealed that 12 blind samples were correctly labeled for their species of origin, while three blind samples that were thought to originate from red deer were identified as C. nippon, and seven blind samples that were thought to originate from sika deer were identified as C. elaphus, Dama dama, and Rangifer tarandus. DNA barcoding analysis showed that all three gene loci were able to distinguish the two Cervus species and to identify the presence of adulterant species. The DNA barcoding technique was able to provide a useful and sensitive approach in identifying the species of origin in deer products.

Endocytosis constitutes a cellular process in which cells selectively encapsulate surface substances into endocytic vesicles, also known as endosomes, thereby modulating their interaction with the environment. Platelets, as pivotal hematologic elements, play a crucial role not only in regulating coagulation and thrombus formation but also in facilitating tumor invasion and metastasis. Functioning as critical components in the circulatory system, platelets can internalize various endosomal compartments, such as surface receptors, extracellular proteins, small molecules, and pathogens, from the extracellular environment through diverse endocytic pathways, including pinocytosis, phagocytosis, and receptor-mediated endocytosis. We summarize recent advancements in platelet endocytosis, encompassing the catalog of cargoes, regulatory mechanisms, and internal trafficking routes. Furthermore, we describe the influence of endocytosis on platelet regulatory functions and related physiological and pathological processes, aiming to offer foundational insights for future research into platelet endocytosis.

Currently, prostate cancer (PCa) poses a global risk to the well-being of males. Over the past few years, the utilization of prostate-specific antigen (PSA) screening has become prevalent in the identification and management of PCa, which has promoted a large number of patients with advanced PCa to receive timely treatment and reduce the mortality. Nevertheless, the utilization of PSA in PCa screening has sparked debate, and certain research has validated the potential for overdiagnosis and overtreatment associated with PSA screening. Hence, in order to decrease the mortality rate of PCa patients and prevent unnecessary diagnosis and treatment, it is crucial to carefully choose the suitable population and strategy for PSA screening in PCa. In this systematic review, the clinical studies on PSA screening for the diagnosis and treatment of PCa were thoroughly examined. The review also delved into the effects and mechanisms of PSA screening on the prognosis of PCa patients, examined the factors contributing to overdiagnosis and overtreatment, and put forth strategies for optimization. The objective of this research is to offer valuable recommendations regarding the utilization of PSA screening for the detection and management of PCa.

Abstract Background Physical inactivity is a significant public health concern globally, associated with an increased risk of chronic diseases and detrimental effects on both physical and mental health. Technologically based interventions have emerged as a potential solution to promote physical activity engagement and improve mental health outcomes. However, understanding the effectiveness of these interventions and the role of gender in their outcomes is essential for developing tailored strategies. Objective This study aims to examine the effectiveness of technologically based interventions in promoting physical activity and improving mental health outcomes, with a specific focus on gender differences. Methodology This study employed a three-phase mixed methods research design. Phase one was an experimental phase where 300 participants were randomly assigned to intervention or control groups. The intervention group received a technologically based physical activity intervention, while the control group did not. Physical activity levels and mental health outcomes were assessed before and after the intervention. Phase two involved qualitative interviews with a subset of participants (n = 20) from the intervention group. These interviews explored motivations and barriers to physical activity, aiming to uncover personal factors influencing engagement. Thematic analysis was used to identify recurring themes. Phase three utilized a quantitative survey to compare motivations and barriers between males and females. The survey, administered to a larger sample, included participants from both intervention and control groups. It assessed various factors and allowed for a quantitative comparison of gender differences. Findings findings indicated that the intervention improved the mental health and physical activities level of the intervention groups. Findings also there are 8 motivations for and barriers to using technology in physical activities. Male and females’ scores on some of the motivations and barriers were statistically significant. Conclusion technology plays an important role in improving the mental health and physical activities of adults. Findings can be used by health care centers, digital psychologists, and physical trainers.

Abstract Background Large-scale genotype–phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments. Results We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection. Conclusion Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.

Abstract Background Sepsis poses a serious threat to human life and health, with limited options for current clinical treatments. Acupuncture plays an active role in treating sepsis. However, previous studies have focused on the neuromodulatory effect of acupuncture, neglecting its network modulatory effect. Exosomes, as a new way of intercellular communication, may play an important role in transmitting acupuncture information. This paper explores the possibility of electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs as a potential treatment for sepsis. Methods The sepsis mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS) (12 mg/kg, 24 mg/kg), and EA (continuous wave, 10 Hz, intensity 5) or intraperitoneal injection of Acupuncture Exosomes (Acu-exo) were performed before the model establishment. The therapeutic effect was evaluated by survival rate, ELISA, H&E staining and lung wet/dry weight ration (W/D). In vivo imaging of small animals was used to observe the accumulation of Acu-exo in various organs of sepsis mice. LPS was used to induce macrophages in cell experiments, and the effect of Acu-exo on macrophage inflammatory cytokines was observed. In addition, The miRNA sequencing method was further used to detect the serum exosomes of normal and EA-treated mice, and combined with network biology analysis methods to screen possible key targets. Results EA and Acu-exo reduced the W/D and lung tissue damage in sepsis mice, down-regulated the expression of serum inflammatory cytokines TNF-α and IL-6, and increased the survival rate of sepsis mice. In vivo imaging of small animals found that Acu-exo were accumulated in the lungs of sepsis mice. Cell experiments proved that Acu-exo down-regulated the expression of inflammatory cytokines TNF-α, IL-6 and IL-1β to alleviate the inflammatory response induced by LPS in macrophages. MiRNA sequencing revealed 53 differentially expressed miRNAs, and network biology analysis revealed the key targets of Acu-exo in sepsis treatment. Conclusion Electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs may be a potential treatment for sepsis.

A multi-strain yeast-based paraprobiotic (MsYbP) comprising inactive cells and polysaccharides (β-glucan, mannan oligosaccharides, and oligosaccharides) derived from Saccharomyces cerevisiae and Cyberlindnera jadinii could ensure optimal growth and health in farmed fish. This study assessed the impact of an MsYbP on the growth, immune responses, antioxidant capacities, and liver health of largemouth bass (Micropterus salmoides) through lab-scale (65 days) and pilot-scale (15 weeks) experiments. Two groups of fish were monitored: one fed a control diet without the MsYbP and another fed 0.08% and 0.1% MsYbP in the lab-scale and pilot-scale studies, respectively (referred to as YANG). In the lab-scale study, four replicates were conducted, with 20 fish per replicate (average initial body weight = 31.0 ± 0.8 g), while the pilot-scale study involved three replicates with approximately 1500 fish per replicate (average initial body weight = 80.0 ± 2.2 g). The results indicate that the MsYbP-fed fish exhibited a significant increase in growth in both studies (p < 0.05). Additionally, the dietary MsYbP led to a noteworthy reduction in the liver function parameters (p < 0.05), such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP), and hepatic nuclear density, indicating improved liver health. Furthermore, the dietary MsYbP elevated the antioxidative capacity of the fish by reducing their malondialdehyde levels and increasing their levels and gene expressions related to antioxidative markers, such as total antioxidant ca-pacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), nuclear factor erythroid 2-related factor 2 (nrf2) and kelch-1ike ech-associated protein (keap1) in both studies (p < 0.05). In terms of hepatic immune responses, the lab-scale study showed an increase in inflammation-related gene expressions, such as interleukin-1β (il-1β) and transforming growth factor β1 (tgf-β1), while the pilot-scale study significantly suppressed the expressions of genes related to inflammatory responses, such as tumor necrosis factor α (tnfα) and interleukin-10 (il-10) (p < 0.05). In summary, our findings underscore the role of dietary multi-strain yeast-based paraprobiotics in enhancing the growth and liver health of largemouth bass, potentially through increased antioxidative capacity and the modulation of immune responses, emphasizing the significance of employing yeast-based paraprobiotics in commercial conditions.

Uncovering the trade-offs and synergy relationship of multiple ecosystem services (ESs) is important for scientific ecosystem management and the improvement of ecological service functions. In this study, we investigated the spatiotemporal changes of four typical ES types (i.e., water yield (WY), carbon storage (CS), soil conservation (SC), and habitat quality (HQ)) from 2001 to 2020 in the Han River Basin (HRB). Meanwhile, the trade-offs and synergies between paired ESs and the socioecological drivers of these ESs were further explored. The results showed that grassland, cropland, and bare land decreased by 12,141.3 km2, 624.09 km2, and 22.1 km2 during the study period, respectively, which can be attributed to their conversion to forests in the HRB. Temporally, the WY, CS, and SC all showed a continuously increasing trend. Spatially, WY and HQ exhibited bipolar clustering characteristics, with WY exhibiting low-value clustering in the upstream and high-value clustering in the downstream, while CS showed the clustering characteristics of a scattered distribution of cold and hot spots from 2001 to 2020. The spatial patterns of aggregation locations in CS and HQ were relatively similar, with clusters of higher ES values mainly distributed in the western and central regions and clusters of lower ES values mainly located in the eastern and southeastern regions, while the aggregation of WY was spatially concentrated. Overall, the CS showed a significant positive correlation with HQ, but a significant negative correlation with WY. Spatially, WY and HQ, CS, and SC showed a substantial trade-off relationship in the northwest and southeast parts of the study area, while HQ, CS, and SC mainly exhibited a synergistic relationship in most parts of the study area. Slope and temperature had high influencing factor coefficients on multiple ESs; the mixed effect of terrain and natural factors was significantly greater than the impact of a single factor on ESs, and terrain factors played an essential role in the changes in ESs. The findings can provide technical and theoretical support for integrated scientific ecosystem management and sustainable development at the local scale.

Abstract Background Based on the results of existing observational studies, it can be found that the association between serum vitamin D levels and the risk of Sjogren’s syndrome (SS) in humans is still controversial. Based on this situation, this study aimed to assess the causal relationship between serum vitamin D levels and SS by using the Mendelian randomization (MR) approach. Methods In this study, genome-wide association studies (GWAS) summary statistics on serum vitamin D levels [sample size = 417,580 (UK Biobank)] and SS [sample size = 416,757 (cases = 2495, controls = 414,262) (FinnGen)] were used. The bi-directional MR analysis was then used to assess possible causal relationships. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger and the weighted median approaches. In addition, sensitivity analyses were used to ensure the stability of the results, including Cochran’s Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. Results The MR suggested that no significant causal effects of serum 25(OH)D levels on SS risks were observed [odds ratio (OR) = 0.9824; 95% confidence interval (CI) = 0.7130 to 1.3538; P = 0.9137]. Similarly, no evidence supported the causal effects of SS on serum vitamin D levels (β: 0.0076, 95% CI: − 0.0031 to 0.0183; P = 0.1640). Conclusion This study found no obvious evidence that serum vitamin D level is causally associated with SS risks or vice versa. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.