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Abstract This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.

Abstract Purpose The objective of this study was to evaluate the clinical efficacy of a 4D digital strabismus and amblyopia visual function correction system (4D-DSAAVFCS) in combination with conventional modalities compared with conventional modalities alone in children with anisometropic amblyopia. Methods This nonrandomized controlled study collected data on best-corrected visual acuity (BCVA), simultaneous vision, fusion vision, near stereoscopic vision, the amplitude of P100 wave (graphic evoked visual potentials), and the latency of P100 wave from both eyes at the beginning of the treatment and one year later. The Mann‒Whitney U test was used to compare BCVA contrasts in different subgroups, and the independent samples t test was used to compare the amplitude and latency of P100 wave contrasts in different subgroups. The basic cure rate, simultaneous vision recovery rate, fusion vision recovery rate, and near stereoscopic vision recovery rate contrasts in different subgroups were compared via the chi-square test. Results This study included 393 children (217 boys and 176 girls) aged 3 to 12 years with anisometropic amblyopia who were treated at the Aier Eye Hospital of Wuhan University from January 2020 to December 2022. The children were divided into two groups, the 4D group (263 cases) and the traditional group (130 cases), on the basis of the treatment modality. The children in the traditional group received treatment through the conventional method of occlusion and regular training. Meanwhile, the children in the 4D group received treatment through the traditional method and the 4D-DSAAVFCS. The 4D group was divided into two age groups: 3 ~ 6 years (161 cases) and 6 ~ 12 years (102 cases). The basic cure rate of the 4D group was significantly better than that of the traditional group (χ2 = 4.318, P 0.05 ). After one year of treatment, a statistically significant difference was observed between the 4D group and the conventional group in terms of BCVA, the latency of P100 wave, and the amplitude of P100 wave (U=-1.243, t=-0.853, t=-1.546, all P

Abstract The association between tobacco smoke exposure and sleep has been widely discussed, but the correlation between serum cotinine levels and sleep health outcomes in adolescents has not been well described. This study aimed to further evaluate the association between serum cotinine levels and sleep health outcomes in adolescents using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. This cross-sectional study included participants aged 16–19 years from the NHANES 2005–2018. A weighted multivariate logistic regression model was used for the primary analysis. A restricted cubic spline (RCS) model was employed to investigate the non-linear association between serum cotinine levels and trouble sleeping. Subgroup analyses based on population characteristics were also conducted. In total, 2630 participants were included, which are representative of the 11.5 million US adolescents. Higher serum cotinine levels (≥ 3 ng/ml) were significantly associated with trouble sleeping in the fully adjusted model (odds ratio [OR] 1.817). The RCS model revealed a non-linear relationship between serum cotinine levels and trouble sleeping. Subgroup analyses indicated that this relationship was consistent and stable across various population characteristics. Serum cotinine levels are associated with sleep health outcomes in adolescents, with high serum cotinine levels being linked to increased trouble sleeping and longer or shorter sleep duration.

Abstract Rice grown in cadmium (Cd)-contaminated soil, is a potential threat to human health, but exogenous selenium (Se) application on rice can mitigate Cd toxicity. However, the mechanisms underlying Se mitigation of Cd stress in ratoon rice (RR) are still poorly understood. We conducted a pot experiment with moderate Cd-contaminated yellow–brown paddy soil on two rice varieties ‘Taoyouxiangzhan’ (TX) and ‘Liangyou 6326’(LY). For all treatments, 1.0 mg kg−1 sodium selenite solution was added to soil. Treatment T1 was sodium selenite only, and in the other treatments 100 mg L−1 Se solution was sprayed on the leaves at seedling stage (T2), at tillering stage (T3), and in early anthesis stage (T4). Se treatments decreased Cd accumulation in rice grains and herbage. Under foliar spraying 100 mg L−1 Se at the seedling + 1.0 mg kg−1 Se in soil (T2), leaf Cd content decreased 16.95% in the current season and grains content decreased 46.67% in the subsequent season. Furthermore, grain Se content increased 0.94 mg kg−1 for the TX variety combined with the analysis of Cd bio-accumulation factor in grains, and Se treatments effectively decreased Cd grain concentrations due to reduced Cd translocation from roots to grains. TX variety rice showed a more pronounced response to Se treatments than LY.

Abstract The emergence of spatial multi-omics has helped address the limitations of single-cell sequencing, which often leads to the loss of spatial context among cell populations. Integrated analysis of the genome, transcriptome, proteome, metabolome, and epigenome has enhanced our understanding of cell biology and the molecular basis of human diseases. Moreover, this approach offers profound insights into the interactions between intracellular and intercellular molecular mechanisms involved in the development, physiology, and pathogenesis of human diseases. In this comprehensive review, we examine current advancements in multi-omics technologies, focusing on their evolution and refinement over the past decade, including improvements in throughput and resolution, modality integration, and accuracy. We also discuss the pivotal contributions of spatial multi-omics in revealing spatial heterogeneity, constructing detailed spatial atlases, deciphering spatial crosstalk in tumor immunology, and advancing translational research and cancer therapy through precise spatial mapping.

In order to investigate the distribution and accumulation characteristics of metabolites and mineral elements in different parts of Peganum harmala L. (P. harmala), and the synergistic or antagonistic effects between them. In this study, nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and inductively coupled plasma optical emission spectrometer (ICP-OES) were used to determine the contents of metabolites (proline, phosphorylcholine, choline, lysine, 4-hydroxyisoleucine, asparagine, acetic acid, sucrose, harmaline and vasicine) and mineral elements (Ca, Mg, K, P, Na, Cr, Cu, Fe, Zn, Mn, Ni, C, N) in five parts of P. harmala, including root, seed, testa, stem and leaf, and to analyze the relationship among the contents of metabolites and mineral elements. The results showed that the contents of acetic acid, proline, lysine, sucrose and Fe in the root were higher than those in other parts, and the contents of harmaline, phosphorylcholine, P, C, N and Zn in the seeds were the highest. The leaves were rich in vasicine, Na, K, Ca, Mg and Mn. The principal component analysis (PCA) showed that the cumulative variance contribution of the first two principal components was 69.00 %, and the loading values of K, Cu and sucrose were higher, which was consistent with the results of biplot and cluster analysis(HCA). Correlation analysis (CA) results showed that there was a strong overall correlation between the different components of seeds and leaves, and the correlation was greater than that of other parts. The results of this study are helpful to understand the correlation of functional traits among different parts of plants, and determine the internal mechanism of controlling functional traits and the proportional relationship between traits, so as to provide a reference for the resource utilization of plants.

Stroke episodes represent a significant subset of cerebrovascular diseases globally, often resulting in diverse neurological impairments such as hemiparesis, spasticity, dysphagia, sensory dysfunction, cognitive impairment, depression, aphasia, and other sequelae. These dysfunctions markedly diminish patients' quality of life and impose substantial burdens on their families and society. Consequently, the restoration of neurological function post-stroke remains a primary objective of clinical treatment. Acupuncture, a traditional Chinese medicine technique, is endorsed by the World Health Organization (WHO) for stroke treatment due to its distinct advantages in managing cerebrovascular diseases, including ischemic stroke. Numerous clinical studies have substantiated the efficacy of acupuncture in ameliorating neurological dysfunctions following stroke. This review systematically examines the improvements in post-stroke neurological dysfunction attributable to acupuncture treatment and elucidates potential mechanisms of action proposed in recent years. Additionally, this article aims to present novel therapeutic concepts and strategies for the clinical management of post-stroke neurological dysfunction.

Abstract Nucleolar protein 12 (NOL12), one of the nucleolar proteins which are primarily expressed in the nucleolus and play key roles in RNA metabolism, cell proliferation, cell cycle, and cell survival, is widely expressed in various species and multiple organs. Although it has been reported that the mRNA of Drosophila NOL12 homolog viriato is expressed in the eyes of Drosophila, the protein expression of NOL12 in mammalian eyes remains to be elucidated. In this study, we showed through immunohistochemistry that NOL12 was present in the rat retina, with predominant distribution in the cytoplasm of the retinal neuronal cells. In the human retinoblastoma cell line WERI-Rb1, we found that altering NOL12 expression led to a change in WERI-Rb1 cell viability. Knocking down NOL12 expression decreased cell viability. In contrast, overexpressing NOL12 increased cell viability. Furthermore, increasing NOL12 expression inhibited ultraviolet (UV)-induced apoptosis. These findings demonstrated that NOL12 may play an important protective role in retinal cells. In the WERI-Rb1 cells exposed to UV irradiation, we detected that NOL12 was degraded, but this degradation could be attenuated by a pan-Caspase inhibitor. Notably, the inhibitory effect of NOL12 against UV-induced apoptosis could be restrained by increasing the expression of ATR serine/threonine kinase (ATR), a kinase that, when activated by severe DNA damage, can result in apoptosis. We also found that upregulating NOL12 inhibited the activation of ATR caused by UV irradiation. Additionally, inhibiting ATR activity reduced apoptosis resulting from both silencing NOL12 expression and UV exposure. Thus, NOL12 may protect against UV irradiation-induced retinal damage by inhibiting ATR activity.

Renal fibrosis, a critical factor in the development of chronic kidney disease (CKD), is predominantly initiated by acute kidney injury (AKI) and subsequent maladaptive repair resulting from pharmacological or pathological stimuli. Phosphatase and tensin homolog (PTEN), also known as phosphatase and tensin-associated phosphatase, plays a pivotal role in regulating the physiological behavior of renal tubular epithelial cells, glomeruli, and renal interstitial cells, thereby preserving the homeostasis of renal structure and function. It significantly impacts cell proliferation, apoptosis, fibrosis, and mitochondrial energy metabolism during AKI-to-CKD transition. Despite gradual elucidation of PTEN’s involvement in various kidney injuries, its specific role in AKI and maladaptive repair after injury remains unclear. This review endeavors to delineate the multifaceted role of PTEN in renal pathology during AKI and CKD progression along with its underlying mechanisms, emphasizing its influence on oxidative stress, autophagy, non-coding RNA-mediated recruitment and activation of immune cells as well as renal fibrosis. Furthermore, we summarize prospective therapeutic targeting strategies for AKI and CKD-treatment related diseases through modulation of PTEN.

Cordyceps militaris, also called as bei-chong-cao, is an insect-pathogenic fungus from the Ascomycota phylum and the Clavicipitaceae family. It is a valuable filamentous fungus with medicinal and edible properties that has been utilized in traditional Chinese medicine (TCM) and as a nutritious food. Cordycepin is the bioactive compound firstly isolated from C. militaris and has a variety of nutraceutical and health-promoting properties, making it widely employed in nutraceutical and pharmaceutical fields. Due to the low composition and paucity of wild resources, its availability from natural sources is limited. With the elucidation of the cordycepin biosynthetic pathway and the advent of synthetic biology, a green cordycepin biosynthesis in Saccharomyces cerevisiae and Metarhizium robertsii has been developed, indicating a potential sustainable production method of cordycepin. Given that, this review primarily focused on the metabolic engineering and heterologous biosynthesis strategies of cordycepin.

Abstract Background Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery. Methods This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale. Discussion We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine. Trial registration ClinicalTrials.gov NCT05479006 . Registered on 26 July 2022.

Abstract WRKY transcription factors are pivotal regulators in various aspects of plant biology, including growth, development, secondary metabolic biosynthesis, and responses to both biotic and abiotic stresses. The legume plant Grona styracifolia is widely utilized for its medicinal properties in treating urinary calculi and combating SARS-CoV-2, owing to its bioactive component schaftoside. However, the regulatory function of GsWRKYs in schaftoside biosynthesis within G. styracifolia remains elusive. In the G. styracifolia genome, we identified a total of 102 GsWRKYs, classified phylogenetically into Group I (18), II (68), and III (16). Genomic analysis revealed an uneven distribution of GsWRKYs on chromosomes (Chr), with prevalence on Chr 1, followed by Chr 2, 3, 5, and 6. Among the 82 duplicated GsWRKYs, comprising 12, 54, and 16 members in Group I, II, and III respectively, 11 GsWRKYs were tandemly duplicated genes located across Chr 2 (2), Chr 5 (7), and Chr 9 (2). Weighted gene co-expression network analysis unveiled that 2 Group I (GsWRKY44 and GsWRKY95) and 14 Group II GsWRKYs, including two pairs of segmentally duplicated Group II GsWRKYs associated with thermomorphogenesis, exhibited coexpression with Grona styracifolia C-glycosyltransferases (GsCGT), a gene encoding a C-glucosyltransferase involved in schaftoside biosynthesis. Furthermore, GsWRKY95 demonstrated coexpression with other schaftoside biosynthetic genes. Dual-luciferase and yeast one-hybrid assays provided additional evidence that GsWRKY95 binds to the W-box of GsCGT, activating its expression. In addition, GsWRKY95- and GsCGT-coexpressing G r o na styracifolia chalcone synthase (GsCHSs), along with 11 pairs of segmentally duplicated Group II GsWRKYs, responded to both abiotic and biotic stresses. Notably, certain GsWRKYs were identified as regulators specific to schaftoside biosynthesis in stems, roots, and leaves. These findings suggest that duplication events, particularly in segmentally duplicated Group II GsWRKYs, play a pivotal role in orchestrating the hierarchical regulation of schaftoside biosynthesis. Overall, our results establish a foundation for genetically enhancing G. styracifolia to abundantly produce schaftoside, thereby contributing to its medicinal efficacy.

Rural household energy transition from biomass energy to modern energy is essential for poverty alleviation and sustainable development. Existing studies have explored the determinants of rural household energy transition, but few of them consider household energy availability for modern energy, which is crucial for rural household energy consumption especially in energy poverty areas such as the Tibetan Plateau. This study establishes an analytical framework for exploring the determinants of rural household energy transition by considering household energy availability and household characteristics. By employing the Tobit model, the empirical analysis of Pumqu River Basin (PRB) of the Tibetan Plateau is conducted. The results show that (1) biomass energy is still the dominant energy source in the PRB, with 99.27% of users and 90.77% of rural household energy consumption. (2) The limited energy accessibility in the PRB plays a significant negative role in accelerating rural household energy transition. (3) Educational level of householder, per capita living space, the number of rural household appliances, and community organizations are the drivers for rural household energy transition, whereas per capita livestock number and per capita grassland areas are the constraints. The findings of this study can help decision makers formulate effective measures to promote rural household energy transition in energy poverty area. The framework introduced can be extended for application to examine the determinants of rural household energy transition in other regions.

In this study, diatomite was used as an effective carrier for carvacrol to prepare an antibacterial complex, which was further incorporated into gelatin solution to obtain active composite films. The effect of the addition of the complex on the physical properties and antibacterial activity of gelatin based composite films was investigated. The results of scanning electron microscopy (SEM) and infrared spectroscopy showed that carvacrol was successfully adsorbed to the pores and surface of diatomite. With increasing content of the complex, the thickness, elongation at break, water vapor permeability, oxygen permeability, antioxidant activity and antibacterial activity increased, whereas the light transmission, moisture content, water solubility and tensile strength of the films decreased. Overall, the film with the complex added at 20% showed good performance, whose tensile strength and elongation at break were 15.13 MPa and 67.43%, respectively. The film scavenged 56.33% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, and the inhibition zone diameter of the film against Staphylococcus aureus and Escherichia coli was 39.4 and 23.7 mm, respectively. More importantly, the gelatin film containing diatomite/carvacrol complex exhibited a much slower release rate of carvacrol and longer-acting antibacterial activity than the film containing the same content of carvacrol. These experimental results provide theoretical guidance and an experimental reference for using diatomite to carry carvacrol in developing antibacterial gelatin films with sustained release properties.

Allium wallichii Kunth is a herb species with potentially extensive applications because of its edible, ornamental, and pharmaceutical values. The structural characteristics and phylogenetic relationships of its chloroplast genome were determined here for the first time. The complete cp genome was found to be 152,496 bp long, with a GC content of 37.04%. It consists of four distinct regions: a large single copy (LSC) region of 82,510 bp, a small single copy (SSC) region of 17,460 bp, and two inverted repeat (IR) regions of 26,263 bp each. The genome encodes 129 genes, including 86 protein-coding genes, 37 tRNA genes, and six rRNA genes. Our phylogenetic analysis revealed that A. wallichii was closely related to Allium wallichii var. platyphyllum, which are included in the section Bromatorrhiza, subgenus Amerallium Traub of the genus Allium. Our report provides valuable information on the genetic diversity of Allium species.

Abstract Traffic prediction is an important part of intelligent transportation system. Recently, graph convolution network (GCN) is introduced for traffic flow forecasting and achieves good performance due to its superiority of representing the graph traffic road structure network. Moreover, the dynamic GCN is put forward to model the temporal property of the traffic flow. Although great progress has been made, most GCN based traffic flow forecasting methods utilize a single graph for convolution, which is considered not enough to reveal the inherent property of traffic graph as it is influenced by many factors, for example weather, season and traffic accidents etc. In this paper, an exotic graph transformer based dynamic multiple graph convolution networks (GTDMGCN) is conceived for traffic flow forecasting. Instead of the single graph, multiple graphs are constructed to modulate the complex traffic network by the proposed graph transformer network. Additionally, a temporal gate convolution is proposed to get the temporal property of traffic flow. The proposed GTDMGCN model is evaluated on four real traffic datasets of PEMS03, PEMS04, PEMS07, PEMS08, and there are average increments of 9.78%, 7.80%, 5.96% under MAE, RMSE, and MAPE metrics compared with the current results.

Licorice (Glycyrrhiza uralensis Fisch), a significant traditional Chinese herbal medicine, has been extensively utilized in China to treat various ailments. Natural bioactive coumarins, glycycoumarin, glycyrin, and 3-O-methylglycyrol, were isolated from licorice, and they exhibited various pharmacological properties. In this report, we have accomplished the total synthesis of glycycoumarin, glycyrin, and 3-O-methylglycyrol in 5–7 linear steps from commercially available 2,4,6-trihydroxybenzaldehyde with yields of 12.3–21.2%. Additionally, their anti-inflammatory activities were studied and compared. Glycycoumarin, glycyrin, and 3-O-methylglycyrol exhibited different levels of anti-inflammatory activities, with glycyrin being the most potent. Mechanistic studies indicated that glycyrin exerted its anti-inflammatory properties by inhibiting the activation of TNF-α, IL-6, and IL-1β, making it a potential anti-inflammatory lead compound for further optimization and discovery of new agents.

Abstract Background Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration Chictr.org.cn identifier: ChiCTR-SOC-17010976.

BackgroundNonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM.MethodsThis 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed.DiscussionThis double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM.Trial registrationThis study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

People unfamiliar with the law may not know what kind of behavior is considered criminal behavior or the lengths of sentences tied to those behaviors. This study used criminal judgments from the district court in Taiwan to predict the type of crime and sentence length that would be determined. This study pioneers using Taiwanese criminal judgments as a dataset and proposes improvements based on Bidirectional Encoder Representations from Transformers (BERT). This study is divided into two parts: criminal charges prediction and sentence prediction. Injury and public endangerment judgments were used as training data to predict sentences. This study also proposes an effective solution to BERT’s 512-token limit. The results show that using the BERT model to train Taiwanese criminal judgments is feasible. Accuracy reached 98.95% in predicting criminal charges and 72.37% in predicting the sentence in injury trials, and 80.93% in predicting the sentence in public endangerment trials.

Toxic epidermal necrolysis (TEN) is a rare severe cutaneous adverse reaction that involves more than 30% of the body surface area. TEN can be accompanied by a series of systemic symptoms and has a high risk of death. Tumor necrosis factor (TNF)-α inhibitors such as adalimumab and etanercept have been shown to be safe and effective for the treatment of TEN in some cases. However, clinical data on the use of TNF-α inhibitors to treat TEN with severe systemic infection are scarce. In the present study, three adult patients who developed TEN with serious active infection were successfully treated with etanercept. One of the three patients had active open pulmonary tuberculosis, and the other two had septicemia and/or fungal sepsis. All patients’ skin lesions significantly improved after several days, and none of the patients developed emerging or re-emerging infectious diseases, adverse reactions, or a similar rash during follow-up. TNF-α inhibitors may be an effective treatment choice for TEN with severe systemic infection. However, further studies with large samples are still required for validation because clinical experience is limited.

A microwave-induced thermoacoustic imaging (MITAT) system is a non-destructive physical medical imaging method that combines the advantages of the high contrast of microwave imaging and the high resolution of ultrasound imaging. It uses the microwave as the excitation source and ultrasound as the information carrier. When different kinds of biological tissue absorb electromagnetic energy, it results in localized temperature rises. The thermal expansion will induce ultrasonic signals (i.e., thermoacoustic signals) known as the thermoacoustic effect. The microwave absorption image of the sample can be reconstructed by algorithm processing. The MITAT contrast depends on different dielectric parameters of different kinds of tissue. We introduce the developed system and its application. In addition, the challenges and prospects of MITAT for further development are discussed.

Abstract Background Salicylic Acid (SA) is a pivotal phytohormone in plant innate immunity enhancement of triggered by various pathogens, such as Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). WRKY is a plant specific transcription factor (TF) family, which plays crucial roles in plant response to biotic stresses. So far, the evolutionary history, functions, and expression patterns under SA treatment and CLas infection of WRKY family are poorly understood in Citrus, despite the release of the genome of several Citrus species. A comprehensive genomic and expressional analysis is worth to conduct for this family. Results Here, a genome-wide identification of WRKY TFs was performed in two Citrus species: Citrus sinensis (HLB-sensitive) and Poncirus trifoliata (HLB-tolerant). In total, 52 CsWRKYs and 51 PtrWRKYs were identified, whose physical and chemical properties, chromosome locations, phylogenetic relationships and structural characteristics were comparatively analyzed. Especially, expression patterns of these WRKY genes before and after SA treatment and CLas infection were compared. Based on this result, seven pairs of orthologous WRKY genes showing opposite expression patterns in two Citrus species were screened out. Moreover, two pairs of orthologous WRKY genes with significant differences in the number or type of stress-responsive cis-elements in the promoter regions were discovered. Subcellular localization and transcriptional activation activity assays revealed that these two pairs of orthologous genes are classic WRKY TFs localize in the nucleus and could function as transcriptional activators. Conclusion In this study, we systematically analyzed the genomic characterization of WRKY family in two Citrus species, together with the analyses of expression patterns under SA signaling and CLas infection. Our study laid a foundation for further study on the function of WRKY TFs in HLB response and SA signaling of Citrus.

Abstract Background Plant cells usually sustain a stable membrane potential due to influx and/or efflux of charged ions across plasma membrane. With the growth and development of plants, different tissues and cells undergo systemic or local programmed decline. Whether the membrane potential of plasma membrane could report senescence signal of plant tissues and cells is unclear. Results We applied a maneuverable transmembrane potential (TMP) detection method with patch-clamp setup to examine the senescence signal of leaf tissue cells in situ over the whole life cycle in Arabidopsis thaliana. The data showed that the TMPs of plant tissues and cells were varied at different growth stages, and the change of TMP was higher at the vegetative growth stage than at the reproductive stage of plant growth. The distinct change of TMP was detectable between the normal and the senescent tissues and cells in several plant species. Moreover, diverse abiotic stimuli, such as heat stress, hyperpolarized the TMP in a short time, followed by depolarized membrane potential with the senescence occurring. We further examined the TMP of plant chloroplasts, which also indicates the senescence signal in organelles. Conclusions This convenient TMP detection method can report the senescence signal of plant tissues and cells, and can also indicate the potential of plant tolerance to environmental stress.

Abstract The basal forebrain is a group of nerve nuclei on the ventral side of the ventral ganglion, composed of γ‐aminobutyric acid neurons, glutamatergic neurons, cholinergic neurons, and orexigenic neurons. Previous studies have focused on the involvement of the basal forebrain in regulating reward, learning, movement, sleep–awakening, and other neurobiological behaviors, but its role in the regulation of general anesthesia has not been systematically elucidated. Therefore, the different neuronal subtypes in the basal forebrain and projection pathways in general anesthesia will be discussed in this paper. In this paper, we aim to determine and elaborate on the role of the basal forebrain in general anesthesia and the development of theoretical research and provide a new theory.

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.

Cinnamomum camphora seed kernel protein isolate (CPI) has attracted increasing attention due to its sustainability and potential applications. This study aimed to investigate the effects of freeze-drying (FD), vacuum-drying (VD), and spray-drying (SD) on the physicochemical and functional properties of CPI. The morphology observation results showed that the SD-CPI, SD-CPI, and VD-CPI were spherical, lamellar, and massive, respectively. Compared to FD and SD, VD had more impact on the color, surface hydrophobicity, intermolecular disulfide bonds, intrinsic fluorescence, and thermal stability of CPI. Fourier transform infrared spectroscopy (FTIR) analyses showed that among three CPI samples, VD-CPI had the highest content of β-sheet but the lowest contents of α-helix and β-turn. At different pH values, the solubility, emulsification, and foaming properties of VD-CPI were inferior to those of FD-CPI and SD-CPI. These results provide useful information on the changes in the physicochemical and functional properties of CPI subjected to different drying methods, and offer theoretical guidance for the production and use of CPI in the food industry.

Summary: Background: Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of tumor and immune microenvironment remains elusive. Methods: Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC and three CAde samples, and systematically outlined their specific transcriptome atlas. Findings: We found CD8+ T cells in CSCC were more cytotoxic but lower exhausted compared to those in CAde, and phagocytic MRC1+ macrophages were specifically enriched in CSCC. Interestingly, we discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) and cancer-associated vascular-fibroblasts (vCAFs) were more abundant in CSCC, and further verified their pro-metastatic roles in vitro. Furthermore, we also identified some specific chemotherapy drugs for CSCC (Dasatinib and Doramapimod) and CAde (Pyrimethamine and Lapatinib) by revealing their heterogeneity in transcriptomic profiles of malignant epithelial cells, and further verified their specific sensitivity in cell lines and constructed CC-derived organoids. Cell–cell communication networks revealed that the pathways of NRG1-ERBB2, and FN1-ITAG3 were specific for CAde and CSCC, respectively, which may partly explain the specificities of identified chemotherapy drugs. Interpretation: Our study described the immune heterogeneity and specific cellular interactions between CSCC and CAde, which could provide insights for uncovering pathogenesis and designing personalized treatment. Fundings: National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China (82072895, 82141106, 82103134, 81903114).

Background The present study aims to use structural equation modelling (SEM) with multiple regression pathways to examine direct and indirect links from diet and metabolic traits to microvascular endothelial dysfunction (ED) among middle-aged Chinese males.Methods The study was conducted in middle-aged Chinese males, who underwent a health check-up between 2018 and 2019. Data on lifestyle behaviour factors (physical activity, diet pattern, sleep quality and diet data underwent factor analysis in advance) and metabolic risk factors referring to metabolic traits were introduced into the SEM to examine inter-relationship among these factors and their association with ED, as evaluated by the reactive hyperaemia index (RHI).Results Both exploratory factor analysis and confirmatory factor analysis identified two major dietary patterns: ‘prudent pattern’ and ‘western pattern’. The univariate test suggested that only triglycerides (TGs) and prudent dietary pattern were directly associated with RHI. Furthermore, prudent dietary pattern had an indirect association with RHI via TG (prudent diet→TG: β=−0.15, p

In the “boat at the dock” theory, pelvic organ prolapse (POP) may happen when the ropes (uterine supportive ligaments) break and/or the water level drops (pelvic floor muscles). Thus, it causes the boat (uterus and other pelvic organs) to slip from normal position and protrude out of the vagina. Surgical intervention with or without hysterectomy (hystero-preservation) is the most effective treatment for POP. Both hysterectomy and hystero-preservation for POP had a high anatomic and clinical cure rate. There is an increasing trend of hystero-preservation for POP during the past decades. The choices of either hysterectomy or hystero-preservation depend on the surgical factors, psychosocial factors, self-esteem and sexuality factors, and surgeon factors. Pelvic reconstructive surgery, either hysterectomy or hystero-preservation, can be performed via different approaches, including abdominal, laparoscopic, and vaginal routes, with native tissue or with mesh. This review will elucidate their related pros and cons, with further discussion and comparison of hystero-preservation via different routes.

Here the authors developed a nucleolus Hi-C technique (nHi-C) for enriching nucleolus-associated interactions, and revealed specific heterochromatin interaction patterns within and around nucleoli in human cells at high resolution.

Firms that extend their e-commerce platforms into customer decision-making to build relationships need to understand the customer journey or build e-relationships through a lens that the customer uses to assess the value created and fulfilled. By contrasting the value cycles that customers and firms use, four different activities are identified for firms with shorter and longer value cycles. By enabling customers to support value creation, fulfilling the value created by enlisting partners and expanding services, and engaging the customers during value-in-use, three organizations discussed in the published literature appear to have developed e-relationship strategies to create and sustain value both before and during COVID-19. This analysis led us to develop three different insights: customer empowerment, collaborative competency, and intelligent digital platform for organizational capability. These insights were used to analyze two different organizations interviewed during the 2020period, as they faced many COVID-19 challenges, and assess the generalizability of these capabilities. We provide three recommendations for IS leaders for building e-relationships through a customer lens, by drawing on five case studies of companies to remain agile. Keywords: Value creation, value fulfillment, e-relationship, intelligent digital platform, organizational capability, sustain value, INTRODUCTION Businesses have used the primary and support activities of their business value chain to transform inputs into outputs and fulfill value propositions made to their customers, with the expectation [...]

Abstract Background Severe neonatal thrombocytopenia is a rare disease with multiple etiologies. Severe thrombocytopenia with bleeding is life-threatening and has attracted significant attention from clinicians. However, only a few studies have focused on the association between severe thrombocytopenia and bleeding. Thus, this study aimed to describe the neonates’ postnatal age at which severe thrombocytopenia was first recognized, clinical characteristics, bleeding patterns, and outcomes and to evaluate the association between minimum platelet count and bleeding. Methods A single-center retrospective cohort study for neonates with severe thrombocytopenia (platelet count ≤ 50 × 109/L) was conducted. Neonates who were admitted to our neonatal intensive care unit between October 2016 and February 2021 and developed severe thrombocytopenia were analyzed. Data were collected retrospectively until the patients were referred to other hospitals, discharged, or deceased. Results Among the 5819 neonatal inpatients, 170 with severe thrombocytopenia were included in this study. More than 30% of the patients had severe thrombocytopenia in the first 3 days of life. Among the 118 neonates with bleeding, 47 had more than one type of pathological bleeding. Neonates with very severe thrombocytopenia (point estimate: 53.7%, 95% confidence interval [CI]: 44.2%–63.1%) had a higher incidence rate of cutaneous bleeding than those with severe thrombocytopenia (point estimate: 23.4%, 95% CI: 12.3%–34.4%). The gestational age (median: 36.2 [interquartile range [IQR]: 31.4–39.0] weeks) and birth weight (median: 2310 [IQR: 1213–3210] g) of the major bleeding group were the lowest among no bleeding, minor bleeding, and major bleeding groups. Regression analysis controlled for confounders and confirmed that a lower platelet count (odds ratio [OR]: 2.504 [95% CI: 1.180–5.314], P = 0.017) was associated with a significant increase in the rate of bleeding. Very severe thrombocytopenia (point estimate: 49.1%, 95% CI: 39.6%–58.6%) had a higher rate of platelet transfusion than severe thrombocytopenia (point estimate: 5.7%, 95% CI: 0.7%–10.7%). The mortality rate was higher in neonates with bleeding than in those without bleeding (point estimates with 95% CI: 33.1% [24.4%–41.7%] vs. 7.7% [0.2%–15.2%]). Conclusions These findings describe the incidence of severe thrombocytopenia and demonstrate that a lower platelet count is associated with an increased bleeding rate in patients with severe thrombocytopenia.

Abstract Introduction Although aerobic physical exercise may improve osteoporosis during ageing, the underlying mechanism of the favorable effects remains unclear. The aim of this study was to examine the localized and generalized proinflammatory indicators and the adaptive skeletal responses to treadmill training in aged rats to explore the potential mechanisms by which treadmill training impacts bone deterioration in a natural aged rat model. Materials and methods A total of 24 Sprague Dawley (SD) rats were included in this study. Sixteen of all these animals were twenty-four months natural aged male SD rats, which were distributed into two groups (n = 8/group): AC group with sham treadmill training, and AT group with 8 weeks treadmill training. The remaining 8 were six months male SD rats matched subline and supplier, which were used as the adult control group with sham treadmill training (YC group, n = 8). The serum, bone marrow, fresh femur, tibia, and lumbar spine were harvested for molecular biological analysis, bone mineral density (BMD) testing, and micro-CT analysis after 8 weeks of treadmill training. Results After 8 weeks of intervention, the results showed that treadmill training increased BMD and inhibited deterioration of bone microarchitecture of hind limb bones. Further analysis showed that treadmill training increased serum P1CP concentration and decreased serum CTX-1level. Interestingly, treadmill training down-regulated the protein expressions of proinflammatory indicators, including NLRP3, proCaspase1, cleaved Caspase1, IL-1β, and GSDMD-N, and the mRNA levels of NLRP3, Caspase1, and IL-1β of the bone marrow. In addition, treadmill training also inhibited serum TNF-α and IL-1β concentration. However, 8 weeks of treadmill training did not increase BMD and bone microarchitecture in the lumbar spine. Conclusion Treadmill training mitigates the ageing-induced bone loss and reverses the deterioration of bone microarchitecture in hind limbs probably through inhibiting NLRP3/Caspase1/IL-1β signaling to attenuate low-grade inflammation and improve the inflammatory bone microenvironment.