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Abstract Background Amomum tsao-ko is an important aromatic crop used in medicines and food. It can be categorized into three main types based on the fruit shape: long (L), oval (O), and round (R). However, limited information is available on the volatile substances present in differently shaped A. tsao-ko fruits. This study investigated the characteristics and biosynthesis of volatile organic compounds (VOCs) in fresh and dried A. tsao-ko fruits of different shapes using widely targeted volatilomics and transcriptome analyses. Results In total, 978 VOCs, primarily terpenoids, esters, and heterocyclic compounds, were detected. The number of differentially accumulated volatile organic compounds (DAVOCs) in dried fruits of various shapes was significantly higher than that in fresh fruits, with terpenoids, esters, and heterocyclic compounds accounting for approximately 50% of the total DAVOCs. Notably, α-phellandrene, identified as a shared differential accumulated terpenoid across various fruit shapes, was detected in both fresh and dried fruits. Through transcriptome analysis, 40 candidate genes implicated in the terpenoid biosynthesis pathway were screened. An integrated analysis of the metabolome and transcriptome revealed that the structural genes HMGR-2, TPS7, TPS5-10, TPS21-3, TPS21-5, TPS21-6, TPS21-7, and TPS21-9, along with 81 transcription factors (including 17 NACs, 16 MYBs, 16 AP2/ERFs, 13 WRKYs, 13 bHLHs, and 6 bZIPs), co-regulate the biosynthesis of volatile terpenoids. Conclusions This study expands our understanding of the volatile metabolism profile of A. tsao-ko and provides a solid foundation for future investigations of the mechanisms governing fruit quality.

Abstract In the past decade, the exploration of genetic resources in rice has significantly enhanced the efficacy of rice breeding. However, the exploration of genetic resources is hindered by the identification of candidate genes. To expedite the identification of candidate genes, this study examined tapetum programmed cell death-related genes OsiWAK1, OsPDT1, EAT1, TDR, and TIP2 to assess the efficacy of the Dual-Luciferase (Dual-LUC) assay in rapidly determining gene relationships. The study found that, in the Dual-LUC assay, OsiWAK1 and its various recombinant proteins exhibit comparable activation abilities on the EAT1 promoter, potentially indicating a false positive. However, the Dual-LUC assay can reveal that OsiWAK1 impacts both the function of its upstream regulatory factor OsPDT1 and the TDR/TIP2 transcription complex. By rapidly studying the relationship between diverse candidate genes and regulatory genes in a well-known trait via the Dual-LUC assay, this study provides a novel approach to expedite the determination of candidate genes such as genome-wide association study.

Abstract Background The purpose of this study was to investigate the relationships between generalized, abdominal, and visceral fat obesity and the prevalence of gout in patients with type 2 diabetes mellitus (T2DM). Methods Data were obtained from the electronic medical databases of the National Metabolic Management Center (MMC) of Yuhuan Second People’s Hospital and Taizhou Central Hospital (Taizhou University Hospital) between September 2017 and June 2023. Four obesity indicators were analyzed: waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and visceral fat area (VFA). The relationships between these parameters and gout prevalence were analyzed using multivariate logistic regression and restricted cubic spline (RCS) analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of the four parameters for gout. Results This cross-sectional study enrolled 10,535 participants (600 cases and 9,935 controls). Obesity was more common in patients with gout, and the obesity indicators were markedly higher in this group. After adjustment for confounders, obesity, as defined by BMI, WC, WHR, and VFA, was found to be associated with greater gout prevalence, with odds ratios (OR) of 1.775, 1.691, 1.858, and 1.578, respectively (P

Abstract Background Although China has a long history of using insects as food and medicine and has developed numerous associated knowledge and practices, especially in its rural and mountainous areas, systematic surveys concerning this subject are limited. In-depth ethnobiological research is needed to compile a comprehensive database of edible and medicinal insects and record the associated knowledge of these food and medicinal resources. Methods Data on edible and medicinal insects and associated knowledge about them were collected by interviewing 216 local villagers in a mountainous territory in southeast Guangxi Zhuang Autonomous Region, China. Results Local villagers used at least 16 edible and 9 medicinal insects, of which 4 wasp species were used in both entomophagy and medicinal practices. Parapolybia varia, Polistes olivaceus, and Anomala chamaeleon were newly recorded edible insects in China. The wasps, Euconocephalus sp., Gryllotalpa orientalis, and Cyrtotrachelus longimanus, were preferred and culturally important edible insects. Populations of Euconocephalus sp. and G. orientalis were reported to have substantially decreased in recent years. Wasps and a bamboo bee were used to treat rheumatism, while cockroaches and antlions were used to treat common cold symptoms in infants. Insect-related knowledge was positively correlated with the interviewees’ age. Conclusions Villagers have accumulated considerable local and traditional knowledge of entomophagy and entomo-therapeutic practices. However, this knowledge is in danger of being lost, which highlights the urgent need to document this information. Edible insects enrich local diets, and a more sustainable supply (such as through insect farming) could maintain local entomophagy practices. Medicinal insects are a part of local folk medicine, and pharmacological and chemical techniques could be applied to identify various biologically active substances in these insects.

Study region: Luanhe River Basin in North China Study focus: Global warming exacerbates hydrological cycles, leading to increased intensity and frequency of floods. Regional studies on the impacts of climate change and land cover changes on flood events in recent decades are particularly important for flood prevention and risk assessment. In this study, the Peak Over Threshold- Generalized Pareto Distribution (POT-GPD) method is used to fit extreme runoff values in the Luanhe River Basin from 1961 to 2018 to identify floods with different return periods. Six flood behavior indicators are adopted to analyze the flood characteristics and extreme climate indices are also used for breakpoint testing and trend analysis. Various scenarios are established as the input of the SWAT model to study the impacts of climate change and land-use change on the flood events. New hydrological insights for the region: The results indicate that the 2-year and 20-year return period floods are primarily rapid-rise single-peak floods, dominated by short-duration intense precipitation. The 5-year and 10-year return period floods are mainly multi-peak floods, primarily caused by long-duration precipitation. Floods in the Luanhe River Basin are primarily influenced by climate change, however, flood events do not directly correspond to the return periods of precipitation events. Forest is the most effective land-use type for flood retention. It could reduce flood magnitudes, especially for the 20-year return period floods. However, increasing forest cover does not effectively reduce the occurrence of the 5-year or 10-year floods, i.e. multi-peak floods. With more extreme rainfall events triggered by future climate change, particular attention should be paid to long-duration precipitation events, which may result in more severe disasters and economic losses.

Herbivores rely heavily on liver enzymes to deal with plant secondary metabolites (PSMs) due to their consumption on plant-based diets, but only a small amount of enzymes have been described based on the genomic level. It is suggested that a multigene subfamily, cytochrome P450 2B (CYP2B), involved in PSMs processing. However, CYP2B subfamily genes of only several rodent species have been characterized, and the copies of CYP2B gene have been compared between the specialist and generalist. Here we investigated the phylogeny of CYP2B subfamily genes in primates with known genome sequences, and related the number of gene to the diet. Furthermore, we compared the CYP2B subfamily genes in two closely related species, Macaca assamensis and Ma. mulatta, which can be viewed as specialist (mainly feeds on Bonia saxatilis) and generalist, respectively, to examine whether the difference of gene number or sequence diversity exists between these two species. The result showed that, most primates have only one CYP2B subfamily gene, although several herbivores have two copies; and both Ma. assamensis and Ma. mulatta have one CYP2B subfamily gene, each with 8 SNPs in them, which is mainly because that multiple SNPs can lead to higher diversity, and further can help deal with various toxins. Physicochemical property prediction indicated that some of these SNPs may cause radical variations between the gene functions. This study is a comprehensive exploration on the evolution of a detoxification enzyme gene subfamily in the primate group, and provides an initial genetic foundation to explore how the closely related species respond to diet from the perspective of P450.

Abstract Background Accumulating evidence suggests that thyroid dysfunction may be related to the risk of dementia. However, previous studies evaluating the association between subclinical hyperthyroidism and the risk of dementia showed inconsistent results. This systematic review and meta‐analysis were performed to evaluate the relationship between subclinical hyperthyroidism and the incidence of dementia in the general population. Methods Cohort studies relevant were retrieved by searching the electronic databases including PubMed, Web of Science, and Embase. A random‐effects model was used to combine the data by incorporating the influence of between‐study heterogeneity. Subgroup and meta‐regression analyses were performed to investigate the source of heterogeneity. Results Nine cohort studies including 49,218 community‐derived participants were included. Among them, 3177 (6.5%) had subclinical hyperthyroidism at baseline. During a mean follow‐up of 10.2 years, 4044 participants developed dementia. The pooled results showed that compared to the participants with euthyroidism, those with subclinical hyperthyroidism had a higher incidence of dementia (risk ratio: 1.38, 95% confidence interval: 1.09 to 1.74, p = .006; I2 = 47%). Subgroup analyses according to study design, age of the participants, methods for diagnosis of dementia, or analytic model did not significantly change the results. The univariate meta‐regression showed that the cutoff of thyroid‐stimulating hormone for defining subclinical hyperthyroidism negatively affected the association between subclinical hyperthyroidism and dementia (coefficient: –1.44, p = .009), which completely explained the heterogeneity (residual I2 = 0%). Conclusion Subjects with subclinical hyperthyroidism may have a higher risk of dementia compared to those with euthyroidism.

Objective This study harnesses the power of text mining to quantitatively investigate the causative factors of falls in adult inpatients, offering valuable references and guidance for fall prevention measures within hospitals.Methods Employing KH Coder 3.0, a cutting-edge text mining software, we performed co-occurrence network analysis and text clustering on fall incident reports of 2,772 adult patients from a nursing quality control platform in a particular city in Jiangsu Province, spanning January 2017 to December 2022.Results Among the 2,772 patients who fell, 80.23% were aged above 60, and 73.27% exhibited physical frailty. Text clustering yielded 16 distinct categories, with four clusters implicating patient factors, four linking falls to toileting processes, four highlighting dynamic interplays between patients, the environment, and objects, and another four clusters revealing the influence of patient-caregiver interactions in causing falls.Conclusion This study highlights the complex, multifactorial nature of falls in adult inpatients. Effective prevention requires a collaborative effort among healthcare staff, patients, and caregivers, focusing on patient vulnerabilities, environmental factors, and improved care coordination. By strengthening these aspects, hospitals can significantly reduce fall risks and promote patient safety.

Abstract Background It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. Methods We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009–2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. Results Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019–1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052–1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p 0.05). Conclusion A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.

Abstract Background Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood. Methods Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3. Results The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells. Conclusions Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.

As the eLoran signal propagates, its strength gradually diminishes with increasing distance, making subsequent signal capture and terminal development challenging. To address this phenomenon, this paper proposes an improved method based on wavelet hard thresholding. This method applies hierarchical processing to the coefficients obtained after wavelet decomposition, based on the signal’s center frequency. It effectively addresses issues like the disappearance of trailing edges and the presence of the noise with large coefficients. Simulation results show that the improved method has the largest output signal-to-noise ratio and effectively improves the problem of tailing vanishing and eliminates the noise with large coefficients. In analog source signal testing, the results show that the method can extract signals of 30 dBμv/m and above well. In actual signal testing, the improved method can extract eLoran signals transmitted over a distance of approximately 1000 km. Based on the results, it can be deduced that the input signal-to-noise ratio is −28.8 dB. Therefore, this method is a suitable and effective solution for extracting weak eLoran signals, providing strong support for signal monitoring in areas at the coverage boundaries of eLoran signals.

Considering the sensitivity and vulnerability of vegetation to precipitation changes, exploring the response of vegetation to standardized precipitation index (SPI) is essential for ecosystem stability. Based on observed data from 624 stations and Moderate Resolution Imaging Spectroradiometer (MODIS) dataset from 2000 to 2018, Spearman's rank correlation coefficient (rs) of SPI and vegetation condition index (VCI) in Chinese mainland was analysed, response time of vegetation to SPI was investigated, and random forest models were constructed to explore the drivers of vegetation response. The results revealed that: (1) SPI and VCI exhibit a loop distribution. The correlation between VCI and 1-month SPI is mostly positive, accounting for 77.58% of the total; rs shows an increasing-decreasing distribution pattern, and the response time of VCI to 1-month SPI indicates an overall decreasing-increasing-decreasing trend. (2) Precipitation, temperature, altitude, vegetation, land use, landform and soil types all have influence on the correlation between 1-month SPI and VCI. Under various factors, rs is concentrated in the range of -0.1 ∼ 0.2, and the response time of VCI to SPI under various factors primarily falls into the ranges of 0 ∼ 1 month and 6 ∼ 9 months. Meanwhile, rs generally decreases with the increasing latitude, ranging between -0.1 and 0.2, whereas the mean response time increases with latitude, within a 0 ∼ 6 months range. (3) Precipitation, temperature and altitude are the top three important factors that affect both maximum rs of VCI and 1-month SPI and response time of VCI to 1-month SPI. The rs is positive in areas with low precipitation, high temperature and low altitude, whereas response time is generally long in areas with low precipitation, low temperature and high altitude. This study is significant for better understanding the interactions between vegetation and SPI changes, and provides reference for vegetation irrigation and vegetation management.

Abstract Emerging evidence indicates that DNA methylation plays an important role in the initiation and progression of nasopharyngeal carcinoma (NPC). DNAJA4 is hypermethylated in NPC, while its role in regulating NPC progression remains unclear. Here, we revealed that the promoter of DNAJA4 was hypermethylated and its expression was downregulated in NPC tissues and cells. Overexpression of DNAJA4 significantly suppressed NPC cell migration, invasion, and EMT in vitro, and markedly inhibited the inguinal lymph node metastasis and lung metastatic colonization in vivo, while it did not affect NPC cell viability and proliferation capability. Mechanistically, DNAJA4 facilitated MYH9 protein degradation via the ubiquitin-proteasome pathway by recruiting PSMD2. Furthermore, the suppressive effects of DNAJA4 on NPC cell migration, invasion, and EMT were reversed by overexpression of MYH9 in NPC cells. Clinically, a low level of DNAJA4 indicated poor prognosis and an increased probability of distant metastasis in NPC patients. Collectively, DNAJA4 serves as a crucial driver for NPC invasion and metastasis, and the DNAJA4-PSMD2-MYH9 axis might contain potential targets for NPC treatments.

Abstract Objective To investigate the incidence of suicide attempts among adolescents with HIV/AIDS in Liangshan Prefecture, Sichuan Province, as well as the correlation between negative life events, sleep, exercise, drug therapy and suicide attempts. Methods A total of 180 Yi adolescents aged 11–19 years with HIV/AIDS in a county of Liangshan Prefecture, Sichuan Province, China, were investigated by census. The main outcome indicators included the incidence of suicide attempts and whether negative life events, sleep, exercise, drug therapy and other factors were related to suicide attempts. Results We found that the incidence rate of suicide attempts among Yi adolescents with HIV/AIDS in Liangshan Prefecture was 13.9%. Negative life events were a risk factor for suicide attempts (OR = 1.047, p

Entity alignment aims to match entities with the same semantics from different knowledge graphs. Most existing studies use neural networks to combine graph-structure information and additional entity information (such as names, descriptions, images, and attributes) to achieve entity alignment. However, due to the heterogeneity of knowledge graphs, aligned entities often do not have the same neighbors, which makes it difficult to utilize the structural information from knowledge graphs and results in a decrease in alignment accuracy. Therefore, in this paper, we propose an interaction model that exploits only the additional information on entities. Our model utilizes names, attributes, and neighbors of entities for interaction and introduces attention interaction to extract features to further evaluate the matching scores between entities. Our model is applicable to Chinese datasets, and experimental results show that it has achieved good results on the Chinese medical datasets denoted MED-BBK-9K.

IntroductionAtherosclerosis is the primary pathological basis of ischemic stroke, and dyslipidemia is one of its major etiological factors. Acute ischemic stroke patients exhibit imbalances in lymphocyte subpopulations, yet the correlation between these dynamic changes in lymphocyte subpopulations and lipid metabolism disorders, as well as carotid atherosclerosis in stroke patients remains poorly understood.MethodsWe retrospectively analyzed the demographic data, risk factors of cerebrovascular disease, laboratory examination (lymphocyte subsets, lipid indexes, etc.), clinical features and c;/]-sity from December 2017 to September 2019 and non-stroke patients with dizziness/vertigo during the same period.ResultsThe results showed that peripheral B lymphocyte proportions are elevated in acute ischemic stroke patients compared with those of the control group (13.6 ± 5.3 vs. 11.7 ± 4.4%, p = 0.006). Higher B lymphocyte proportions are associated with concurrent dyslipidemia, increased levels of vascular risk factors including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), as well as decreased levels of the protective factor high-density lipoprotein cholesterol (HDL-C). Elevated B lymphocyte proportions are independently correlated with carotid atherosclerosis in stroke patients.DiscussionWe found CD19 positive B Lymphocytes increase after ischemic stroke and correlate with Carotid Atherosclerosis. Lymphocyte subpopulations should be highlighted in stroke patients.

ABSTRACTObjective: To explore the feasibility, safety and cost effectiveness of the use of peripherally inserted central catheter (PICC) in children with hemophilia A and inhibitors who underwent ITI treatment.Method: This retrospective cohort study evaluated the effect of PICC placement and ITI on bleeding rates, costs, and parents’ satisfaction before and within 6 months after PICC placement in children with hemophilia A and inhibitors.Results: A total of 20 children with hemophilia A and high-titer inhibitors were included, with a success rate for PICC placement of 100%, at a cost of ¥6730.50. Parents’ satisfaction with PICC was 100%, and the total length of catheter indwelling was 6055 days. In terms of curative effect, the success rate of ITI treatment was 75%, and the annualized bleeding rate was decreased from 10.90 ± 12.16 times before placement to 2.10 ± 3.32 times (p

Abstract Background Leaf morphology is an important component of the idea plant architecture that extensively influences photosynthesis, transpiration, and ultimately grain yield in crops. However, the genetic and molecular mechanisms regulating this morphology remain largely unclear. Results In this study, a mutant showing a narrow and stripe leaf phonotype, designated nsl2, was obtained. Histological analysis revealed defects in the vascular system and reduced epidermal cell number in the nsl2, while the cell size remained unchanged. Map-based cloning and genetic complementation experiments revealed that NSL2, which encodes a small subunit of ribonucleotide reductases (RNRs), is a null allelic with ST1 and SDL. The NSL2 was expressed in variety of tissues, with the highest levels detected in leaves, and its protein was localized in the nucleus and cytoplasm. The dNTPs level was altered in the nsl2 mutant, and thereby affecting the dNTPs pool balance. In addition, flow cytometric analysis and the altered transcript level of genes related to cell cycle indicated that NSL2 affects cell cycle progression. Conclusions Our findings here suggest that NSL2 function in the synthesis of dNTP, the deficient of which leads to DNA synthesis block and in turn affects cell cycle progression, and ultimately decreased cell number and narrow leaf in the nsl2 plant.

A considerable amount of research on link prediction has recently been driven by missing relationships between knowledge graph entities and the problem of the incompleteness of knowledge graphs. Some recent studies have shown that convolutional neural networks based on knowledge embeddings are highly expressive and have good performance in link prediction. However, we found that the convolutional neural network (CNN)-based models do not handle the link between relations and entities well. For this reason, this paper proposes a link prediction model (LPM) based on feature mapping and bi-directional convolution. For the modeling of the task, an encoding layer–mapping layer–decoding layer structure is used. Among these layers, the encoding layer adopts a graph attention network to encode multi-hop triad information and obtains richer encoding of entities and relationships. The mapping layer can realize the mapping transformation between entities and relations and project the entity encoding in the space of relation encoding to capture the subtle connection between entities and relations. The decoding layer adopts bidirectional convolution to merge and decode the triples in a sequential inverse order, which makes the decoding layer model more advantageous in prediction. In addition, the decoding layer also adopts the r-drop training method to effectively reduce the distribution error generated by training between models and enhance the robustness of the model. Our experiments demonstrated the effectiveness of mapping relations, bidirectional convolution, and r-drop, and the accuracy of the proposed model showed significant improvements for each evaluation metric on two datasets, WN18RR and FB15k-237.

Joint relational triple extraction is a crucial step in constructing a knowledge graph from unstructured text. Recently, multiple methods have been proposed for extracting relationship triplets. Notably, end-to-end table-filling methods have garnered significant research interest due to their efficient extraction capabilities. However, existing approaches usually generate separate tables for each relationship, which neglects the global correlation between relationships and context, producing a large number of useless blank tables. This problem results in issues of redundant information and sample imbalance. To address these challenges, we propose a novel framework for joint entity and relation extraction based on a single-table filling method. This method incorporates all relationships as prompts within the text sequence and associates entity span information with relationship labels. This approach reduces the generation of redundant information and enhances the extraction capability for overlapping triplets. We utilize the internal and external multi-head tensor fusion approach to generate two sets of table feature vectors. These vectors are subsequently merged to capture a wider range of global information. Experimental results on the NYT and WebNLG datasets demonstrate the effectiveness of our proposed model, which maintains excellent performance, even in complex scenarios involving overlapping triplets.

Abstract Bitter taste perception plays an important role in preventing animals from digesting poisonous and harmful substances. In primates, especially the Cercopithecidae species, most species feed on plants; thus, it is reasonable to speculate that most of the bitter taste receptor genes (T2Rs) of primates are under purifying selection to maintain the functional stability of bitter taste perception. Gene duplication has happened in T2Rs frequently, and what will be the fate of T2Rs copies is another question we are concerned about. To answer these questions, we selected the T2Rs of primates reported in another study and conducted corresponding selective pressure analyses to determine what kind of selective pressure was acting on them. Further, we carried out selective pressure analyses on gene copies and their corresponding ancestors by considering several possible situations. The results showed that among the 25 gene groups examined here, 15 groups are subject to purifying selection and others are under relaxed selection, with many positively selected sites detected. Gene copies existed in several groups, but only some groups (clade1_a1‐b2, clade1_c‐c2, clade1_d1‐d3, clade1_f1‐f2, T2R10, T2R13, and T2R42) have positively selected sites, inferring that they may have some relation to functional divergence. Taken together, T2Rs in primates are under diverse selective pressures, and most gene copies are subject to the same selective pressures. In such cases, the copies may be just to keep the function conservative, and more copies can increase the quantity of the bitter taste receptor, raise the efficiency of bitter substance recognition, and finally enhance the fitness of feeding during the evolutionary course of primates. This study can improve our understanding of T2Rs evolution in primates.

Peritoneal fibrosis (PF) is the main reason leading to declining efficiency and ultrafiltration failure of peritoneum, which restricts the application of peritoneal dialysis (PD). We aimed to investigate the effects and mechanisms of miR-122-5p on the PF. Sprague-Dawley (SD) rats were infused with glucose-based standard PD fluid to establish PF model. HE staining was performed to evaluate the extent of PF. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were performed to measure the expression level of miR-122-5p. Western blot was used to test the expression of transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-A, Fibronectin 1 (FN1), extracellular matrix protein 1 (ECM1), Smad5, α-smooth muscle actin (SMA), collagen type 1(COL-1), Vimentin, E-Cadherin, Wnt1, β-catenin, p-β-catenin, c-Myc, c-Jun, and Cyclin D1. Immunohistochemistry (IHC) staining was used to detect type I collagen alpha 1 (Col1α1), α-SMA, and E-Cadherin expression. We found PF was glucose concentration-dependently enhanced in peritoneum of PD rat. The PD rats showed increased miR-122-5p and decreased Smad5 expression. MiR-122-5p silencing improved PF and epithelial–mesenchymal transition (EMT) process in PD rats. MiR-122-5p silencing attenuated the activity of the Wnt/β-catenin signaling pathway. Importantly, dual-luciferase reporter assay showed Smad5 was a target gene of miR-122-5p. Smad5 overexpression significantly reversed the increases of PF and EMT progression induced by miR-122-5p overexpression. Moreover, miR-122-5p mimic activated Wnt/β-catenin activity, which was blocked by Smad5 overexpression. Overall, present results demonstrated that miR-122-5p overexpression showed a deterioration effect on PD-related PF by targeting Smad5 to activate Wnt/β-catenin pathway.

Thrombocytopenia or platelet dysfunction is a risk factor for severe infection. Staphylococcus aureus (S. aureus) releases a variety of virulence factors especially toxic shock syndrome toxin 1 (TSST-1), which may cause toxic shock syndrome. S. aureus, when carrying the tst gene, is more prone to cause toxic shock syndrome and is responsible for an especially high rate of mortality. However, the effect of TSST-1 protein on platelets is unknown. Patients with the tst gene positive S. aureus bacteremia showed more serious infection, higher mortality and lower platelet count. The tst gene positive S. aureus strains induce more platelet apoptosis and activation and corresponding up-regulation of Bak and down-regulation of Bcl-XL in addition to the activation of Caspase-3. C57BL/6 mice infected with the tst gene positive strains resulted in both a decrease in platelet count and an increase in platelet apoptosis and/or activation events and mortality. Moreover, TSST-1 protein, encoded by tst gene, caused the decrease of platelet count, the increase of platelet apoptosis and activation events and the level of inflammatory cytokines in vivo. However, TSST-1 protein was unable to induce traditional activation and apoptosis on human platelets in vitro. These results suggested that TSST-1 protein may exert indirect effects on platelet activation and apoptosis in vivo.

Abstract Background Cancer diagnoses and deaths among the elderly (65 +) are expected to increase significantly over the next decade. Immune checkpoint inhibitors specifically target ICI genes and enhance immune system function. However, poor outcomes may be associated with aging. Methods We downloaded the Genomic Data Commons from the Cancer Genome Atlas (TCGA) and collected gene expression data from malignant melanoma (MM) tissues, the third level as the primary site. The CKTTD ICI genes database were applied and validated using the GEO database and lab experiments. Results In 414 patients, 13 ICI genes were obtained as risk gene signature by univariate and multivariate Cox hazard models and were associated with poor survival in the older group. At 1, 3, and 5 years (79%, 76%, and 76%, respectively), we investigate TNFRFS4 gene and age prediction using novel nomogram-associated aging (HR = 1.79, P 0.001, CI = 1.32–2.45) with higher sensitivity testing.TNFRSF4 gene expression was significantly high in younger (15 years interval) MM patients (P

The purpose of this paper is to address the extraction of entities and relationships from unstructured Chinese text, with a particular emphasis on the challenges of Named Entity Recognition (NER) and Relation Extraction (RE). This will be achieved by integrating external lexical information and utilizing the abundant semantic information available in Chinese. We utilize a pipeline model that is applied separately to NER and RE by introducing an innovative NER model that integrates Chinese pinyin, characters, and words to enhance recognition capabilities. Simultaneously, we incorporate information such as entity distance, sentence length, and part-of-speech to improve the performance of relation extraction. We also delve into the interactions among data, models, and inference algorithms to improve learning efficiency in addressing this challenge. In comparison to existing methods, our model has achieved significant results.

Relation extraction tasks aim to predict the type of relationship between two entities from a given text. However, many existing methods fail to fully utilize the semantic information and the probability distribution of the output of pre-trained language models, and existing data augmentation approaches for natural language processing (NLP) may introduce errors. To address this issue, we propose a method that introduces prompt information and Top-K prediction sets and utilizes ChatGPT for data augmentation to improve relational classification model performance. First, we add prompt information before each sample and encode the modified samples by pre-training the language model RoBERTa and using these feature vectors to obtain the Top-K prediction set. We add a multi-attention mechanism to link the Top-K prediction set with the prompt information. We then reduce the possibility of introducing noise by bootstrapping ChatGPT so that it can better perform the data augmentation task and reduce subsequent unnecessary operations. Finally, we investigate the predefined relationship categories in the SemEval 2010 Task 8 dataset and the prediction results of the model and propose an entity location prediction task designed to assist the model in accurately determining the relative locations between entities. Experimental results indicate that our model achieves high results on the SemEval 2010 Task 8 dataset.

Owing to messenger RNA's unique biological advantages, it has received increasing attention to be used as a therapeutic, known as mRNA-based gene therapy. It is critical to have an ideal strategy of mRNA gene therapy for glioma, which grows in a special environment. In the present study, we screened out a safe and efficient transfection reagent for intracranial delivery of synthetic mRNA in mouse brain. First, in order to analyze the effect of different transfection reagents on the intracranial delivery of mRNA, the synthetic luciferase mRNA was wrapped with two different transfection reagents and microinjected into the brain at the fixed point. The expression status of delivered mRNA was monitored by a small animal imaging system. The possible reagent-induced biological toxicity was evaluated by behavioral and blood biochemical measurements. Then, to test the therapeutic effect of our intracranial delivery mRNA model on glioma, synthetic modified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA was used as an example of therapeutic application. This model demonstrated that synthetic mRNA could be successfully delivered into the brain using commercially available transfection reagents, and TransIT-mRNA showed better results than in vivo-jetPEI kit. This model can be applied in precise targeting and personalized gene therapy of glioma.

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

Background. With the decreasing age of type 2 diabetes mellitus (T2DM) onset, the incidence of diabetic complications is gradually increasing. We evaluated the independent effect of age at diabetes onset on diabetic retinopathy (DR) development. Methods. A total of 7472 patients with T2DM were enrolled in the National Metabolic Management Center from September 2017 to May 2022. Anthropometry data, laboratory reports, and medical history were collected. The independent association of DR with age at diabetes onset was analyzed using multivariable logistic regression models. In addition, a stratified analysis was performed to determine the effect of confounding variables. Results. Of the 7472 patients recruited, 1642 (21.98%) had DR. Patients with DR had considerably younger ages of diabetes onset than those without DR (45 (38–53) years vs. 50 (43–57) years, P

The Omicron wave of the COVID-19 pandemic significantly affected Shanghai, China, from March to June 2022. Numbers of Fangcang Shelter Hospitals (FSHs) were conversed from stadiums and exhibition centers to tackle the pandemic. This study aimed to identify the stress load profiles of nurses working in FSHs and explore the characteristics and factors influencing stress load profiles. Totally, 609 out of 700 FSH nurses (with an effective response rate of 87%) participated in an online survey investigating their socio-demographic information, work-related stressors, and stress load. Results of the latent profile analysis identified four classes of stress load, which were labeled as the low (Class 1), mild (Class 2), moderate (Class 3), and high (Class 4) stress load class. Maternity status and self-perceived health condition were significantly different between the four stress load classes by comparisons using the Chi-square test and the Kruskal–Wallis test. The contributors to the stress load profiles were determined by the multinomial logistic regression analysis, including age, education, maternity status, self-perceived health condition, working time in FSHs, and the four dimensions of work-related stressors. Participants who were less healthy (OR = 0.045, 95% CI:0.012,0.171), worked longer time in FSHs (OR = 40.483, 95% CI: 12.103,135.410), faced with more workload (OR = 3.664, 95% CI: 1.047,12.815), and worse working environment (OR = 12.274, 95% CI: 3.029,49.729) were more likely to be classified to the high stress load class. The task arrangement and working environment for FSH nurses should be optimized, and psychological training should be conducted routinely.

Booking decision is a typical decision-making behavior in hospitality, while the neural processing of it is still unclear. To address this issue, with the help of event-related potential (ERP), this work uncovered the neural mechanism of the influence of two extrinsic cues, namely, brand familiarity (familiar vs. unfamiliar) and online reviews (positive vs. negative) on online hotel booking decisions. Behavioral results indicated that the booking rate under the condition of positive reviews was higher than that of negative reviews. In addition, the response time in the case of familiar brands was longer than that of unfamiliar brands. ERP results showed that the P200 amplitude of familiar brands was smaller than that of unfamiliar brands, while for the late positive potential amplitude, the opposite was the case. It is suggested that in the early stage of cognitive processing, unfamiliar brands evoke more automatic and unconscious attention while in the later stage, familiar brands attract more conscious attention. This study also found that the N400 amplitude of negative online reviews was larger than that of positive online reviews, indicating that negative stimuli can result in a larger emotional conflicts than that of positive stimuli. This study provides new insights into the neural mechanism of online booking decisions in the hospitality.

BackgroundGeneralized anxiety disorder (GAD) is a chronic disorder characterized by excessive, pervasive, persistent worrying that is difficult to control. Jiuwei Zhenxin granules may be safer and more effective than non-benzodiazepine anti-anxiety drugs for treating GAD. This study aimed to assess the efficacy and safety of Jiuwei Zhenxin granules alone or in combination with the benzodiazepine alprazolam.Materials and methodsA total of 710 patients were recruited from outpatient clinics and were randomly divided into two groups to receive Jiuwei Zhenxin granules (single drug group) or Jiuwei Zhenxin granules and alprazolam (combination group). The primary outcome was the response rate, which was defined as a ≥ 50% reduction from the baseline total score on the Hamilton Anxiety Scale (HAMA). Secondary outcome measures included mean changes in HAMA total score, psychological and somatic factors, Hamilton Depression Rating Scale total score, and SF-36 health survey score.ResultsAt 4 weeks after treatment, the single and combination treatment groups showed significant improvement in the HAMA total score and they did not differ significantly in response rate (77.58 vs. 79.17%) or rate of adverse drug reactions (16.22 vs. 16.07%).ConclusionJiuwei Zhenxin granules are an effective, safe, and well-tolerated treatment against GAD. Combining them with alprazolam may not significantly improve efficacy.Clinical trial registration[www.ClinicalTrials.gov], identifier [CHICTR1800020095].

Abstract. Background:. Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. Methods:. Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. Results:. At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. Conclusions:. This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. Trial Registration:. Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.

Abstract Bitter taste perception is important in food choice of animals, and it is mediated by bitter taste receptor (T2R) containing three regions: extracellular regions (ECs), transmembrane regions (TMs), and intracellular regions (ICs). It is hypothesized that ECs, TMs, and ICs are under different selective pressures, with ECs being unstable while TMs and ICs being constrained. To test this hypothesis, we examined the selective pressures on one of the bitter taste receptor genes‐T2R1 and its different areas from 35 primates and found that T2R1 was under neutral evolution but with some positively selected sites in it. Further analyses suggested that TMs, ICs, and the concatenated transmembrane region TM1237 were under purifying selection; in contrast, extracellular regions, the first and second extracellular loop (EL1, EL2), were subject to positive selection with several positively selected sites in them. Therefore, this study supported the above‐mentioned hypothesis. The reason why EL1 and EL2 of T2R1 have positively selected sites is probably due to their participation in forming the cap‐like structure involved in ligand binding. Positive selection acts as a driving force of the T2R1 functional differentiation and confers the ability to discern various bitter substances for primates, which could help them to adapt to the changing environment during the evolutionary course.

Fiscal and taxation policy tools play an important role in promoting green and low-carbon development. Based on classical tax theory, including the Potter hypothesis and the environmental Kuznets curve, this paper explores the impact of environmental tax regulation on economic growth and carbon emission reduction. We find that resource tax reform could promote green total factor productivity; however, the ad valorem reform of resource tax does not significantly raise the level of low carbon development. This effect varies among different regions as well as different tax cuts and fee reductions. Fiscal revenue decentralization has a reverse adjustment effect on the impact of resource taxes on green total factor productivity. We conclude that it is necessary to deepen the reform of the fiscal and taxation system to achieve the carbon neutrality and emission peak goal.

Summary: Background: Distant metastasis remains the leading cause of treatment failure in patients with nasopharyngeal carcinoma (NPC), making it critical to identify efficient therapeutic targets for metastatic NPC. Previous studies have demonstrated that deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) is associated with the development of various types of cancer. However, its role and mechanism in NPC have not been explored. Methods: RNA-seq profiling was performed for three pairs of NPC and normal nasopharynx tissues. DNTTIP1 expression in NPC specimens was detected by immunohistochemistry. In vitro and in vivo assays were used to investigate the function of DNTTIP1. The molecular mechanism was determined using RT-qPCR, western blotting, RNA-seq, luciferase reporter assays, ChIP assays, and co-IP assays. Findings: DNTTIP1 was found to be significantly upregulated in NPC tissues. Furthermore, DNTTIP1 promoted NPC growth and metastasis in vitro and in vivo. Upregulation of DNTTIP1 in NPC indicated poor clinical outcomes. Mechanistically, DNTTIP1 suppressed DUSP2 gene expression via recruiting HDAC1 to its promoter and maintaining a deacetylated state of histone H3K27. The downregulation of DUSP2 resulted in aberrant activation of the ERK signaling and elevated MMP2 levels, promoting NPC metastasis. Chidamide, an HDAC inhibitor, was shown to suppress NPC metastasis by regulating the DNTTIP1/HDAC1-DUSP2 axis. Interpretation: Our findings demonstrate that DNTTIP1 not only regulates NPC metastasis but also independently predicts NPC prognosis. Furthermore, targeting DNTTIP1/HDAC1 by Chidamide may benefit NPC patients with metastasis. Funding: This work was supported by the National Natural Science Foundation of China (No. 81872464, 82073243).

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

The existing studies have analyzed the advertising effects of metaphorical advertisements and straightforward adverts in traditional advertising media. However, their advertising effects on social media are still unclear. To address this issue, this study uses eye-tracking and questionnaires to examine two types of social media tourism advertising—metaphorical and straightforward in posts with both high and low popularity. This within-subject (n = 55) experiment was designed to examine the effects of social media tourism advertising types on visual attention and tourism intention and to identify the moderating role of post popularity based on the elaboration likelihood model (ELM). We found that advertising types had no significant effect on visual attention, but metaphorical advertisements increased tourism intention compared with straightforward adverts. Furthermore, we found that the level of post popularity moderated the effect of advertising types on visual attention. Specifically, metaphorical adverts in highly popular posts attracted more visual attention in the advertising text area and in the whole advert. Straightforward adverts in posts with low popularity attracted more visual attention in the advertising text area. This research advances the current literature by exploring the effects of social media tourism advertising types and has implications for managers deciding on strategies for social media tourism marketing.

Context Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. Objective To observe the clinical safety and tolerability of CALAS. Materials and methods Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Results Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). Discussion and conclusions CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

Abstract The relevance of pregestational body mass index (BMI) on adverse pregnancy outcomes remained unclear in Southwest China. This study aimed to investigate the overall and age-category specific association between pre-gestational BMI and gestational diabetes mellitus (GDM), preeclampsia, cesarean delivery, preterm delivery, stillbirth, macrosomia, and small-for-gestational age (SGA) or large-for-gestational age (LGA) neonates in Southwest China. Furthermore, it explores the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. 51,125 Chinese singleton pregnant women were recruited as study subjects. Multiple logistic regression models were used to examine the influence of pre-pregnancy BMI on adverse pregnancy outcomes. Gradient boosting machine was used to evaluate the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. It is found that women who were overweight or obese before pregnancy are at higher risk of adverse pregnancy outcomes except for SGA neonates, while pre-pregnancy underweight is a protective factor for GDM, preeclampsia, cesarean delivery, macrosomia and LGA, but not SGA. Younger mothers are more susceptible to GDM and macrosomia neonates, while older mothers are more prone to preeclampsia. Pre-pregnancy BMI has more influence on various pregnancy outcomes than maternal age. To improve pregnancy outcomes, normal BMI weight as well as relatively young maternal ages are recommended for women in child-bearing age.

Abstract Background Enteral nutrition (EN) therapy is widely used in clinical practice to provide artificial nutrition to patients, while the incidence of adverse events are relatively highly. In the clinical setting, the occurrence of adverse events is associated with the nurse’s risk perception. Thus, using tool to evaluate nurse’s risk perception of enteral nutrition is necessary. Methods The draft questionnaire with 37-items was formed by comprehensive literature reviews and semi-structured in-depth interviews with 11 nurses. Two iterations of expert consultations were used to evaluate the content validity, and 4 items were deleted in this phrase. A 33-items questionnaire was used to survey 352 nurses from five tertiary hospitals in China from May to July 2019 with convenience sampling. Content validity, construct validity and known-groups validity were evaluated by content validity index (CVI), exploratory factor analysis, and the comparisons of the different EN risk perception levels of nurses at different working departments and different educational backgrounds, respectively. Reliability was tested by internal consistency, test-retest reliability, and split-half reliability. Results After the exploratory factor analysis, four items were excluded. Finally, the newly developed questionnaire included 29 items explaining 71.356% of the total variance. It consisted of three factors: Risks of operation (15 items); Risks of EN-related adverse events (11 items), and Risks of EN solution selection (3 items). The CVI of the questionnaire was 0.95 and the CVI of items ranged from 0.875–1.0. The results of known-groups validity showed that the nurses with different educational backgrounds had a statistically significant difference of EN risk perception (z = − 3.024, p = 0.002), whereas there was not significantly different between EN risk perception of nurses working in different departments (z = − 1.644, p = 0.100). The Cronbach’s α, test-retest reliability, and split-half reliability of the questionnaire were 0.967, 0.818, and 0.815, respectively. Conclusions The newly developed questionnaire for assessing nurse’s EN risk perception showed good reliability and validity. It can be used as a tool for nursing managers to assess Chinese nurses’ EN risk perception ability, so as to help to reduce the occurrence of adverse events during EN implementation.

Abstract Background Mitochondria are vital regulators of plant growth and development, constitute the predominant source of ATP, and participate in multiple anabolic and catabolic metabolic pathways. But the mechanism by which dysfunctional mitochondria affect plant growth remains unknown, and more mitochondria-defective mutants need to be identified. Results A mitochondria-defective mutant decreased vascular bundle 1 (dvb1) was isolated from rice mutant library mutagenized by EMS (ethylmethane sulfonate), which shows dwarfism, narrow leaves, short branches, few vascular bundles, and low fertility. Map-based cloning, genetic complementation, and phylogenetic analysis revealed that DVB1 encodes a structural protein classified in the Mic10 family and is required for the formation of cristae in mitochondria, and was primarily expressed in vascular bundles. The DVB1 protein is partially localized in the mitochondria and capable of forming dimers and polymers. Comparing with the wild type, disruption of amino acid metabolism and increased auxin synthesis were observed in dvb1 mutant which also showed increased sensitivity to the mitochondrial electron transport inhibitors. Conclusions DVB1 belongs to Mic10 family and DVB1 is partially localized in the mitochondria. Further studies indicated that DVB1 is important for mitochondrial and plant development in rice.

Abstract Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng’ score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p 90% for 3-month mortality, while PALS score of 6–9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3–5 who received 3–5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1–2 sessions (32.8% vs. 59.2%, p

Drought is an important factor that limits economic and social development due to its frequent occurrence and profound influence. Therefore, it is of great significance to make accurate predictions of drought for early warning and disaster alleviation. In this paper, SPEI-1 was confirmed to classify drought grades in the Guanzhong Area, and the autoregressive integrated moving average (ARIMA), random forest (RF) and support vector machine (SVM) model were established. Meteorological data and remote sensing data were used to derive the prediction models. The results showed the following. (1) The SVM model performed the best when the models were developed using meteorological data, remote sensing data and a combination of meteorological and remote sensing data, but the model's corresponding kernel functions are different and include linear, polynomial and Gaussian radial basis kernel functions, respectively. (2) The RF model driven by the remote sensing data and the SVM model driven by the combined meteorological and remote sensing data were found to perform better than the model driven by the corresponding other data in the Guanzhong Area. It is difficult to accurately measure drought with the single meteorological data. Only by considering the combined factors can we more accurately monitor and predict drought. This study can provide an important scientific basis for regional drought warnings and predictions. HIGHLIGHTS SPEI-1 was used to analyze the temporal distribution characteristics of drought and the main driving factors in Guanzhong Area, China.; Drought grades were selected as the dependent variable, and the meteorological, geographical and vegetative factors were selected as the independent variables to establish an autoregressive integrated moving average (ARIMA) model, random forest (RF) model and support vector machine model.; Meteorological data and remote sensing data were used as independent variables to derive prediction models, respectively.; Comparing the models driven by remote sensing data only and the combination of meteorological and remote sensing data, the RF model driven by the remote sensing data and the SVM model driven by the combined meteorological and remote sensing data were found to perform better than the model driven by the corresponding other data in Guanzhong Area.; This study can provide an important scientific basis for regional drought warning and prediction.;

Flood scaling theory is important for flood predictions in data-scarce regions but is often applied to quantile-based floods that have no physical mechanisms. In this study, we propose a framework for flood prediction in data-scarce regions by event-based flood scaling. After analyzing the factors controlling the flood scaling, flood events are first simulated by a hydrological model with different areally averaged rainfall events and curve number (CN) values as inputs, and the peak discharge of each subcatchment is obtained. Then, the flood scaling is analyzed according to the simulated peak discharge and subcatchment area. Accordingly, the relationship curves between the scaling exponent and the two explanatory factors (rainfall intensity and CN) can be drawn. Assuming that the flood and the corresponding rainfall event have the same frequency, the scaling exponent with a specific flood frequency can be interpolated from these curves. HIGHLIGHTS Hydrological modeling was used to conduct flood scaling analysis.; Rainfall intensity and curve number were identified to be the two main factors affecting flood scaling.; A framework of flood prediction by event-based flood scaling in data-scarce regions was proposed.;

Context Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods The effects of CEP (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific probe actions and probe substrates. In addition, the enzyme kinetic parameters were calculated. Results The results showed that the activity of CYP3A4, CYP2E1 and CYP2C9 was inhibited by CEP, with IC50 values of 16.29, 25.62 and 24.57 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that CEP was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 8.12, 11.78 and 13.06 μM, respectively. Additionally, CEP is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.84/0.058 min/μM. Discussion and conclusions The in vitro studies of CEP with CYP isoforms indicate that CEP has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further clinical studies are needed to evaluate the significance of this interaction.

Abstract Background Zebra leaf mutants are an important resource for studying leaf colour in rice. In most such mutants, the zebra leaf phenotype results from defective chloroplast biogenesis. The molecular mechanism by which zebra leaves develop remains unclear, so additional zebra-leaf mutants need to be identified. Results We isolated a novel rice zebra-leaf mutant, named zebra leaf 15 (z15), which showed transversely striped leaves with yellow-green or white-green sectors, in which chloroplast structure was disturbed. Transmission electron microscopy revealed that the structure of various organelles was impaired in yellow/white sectors. Z15, a single-copy gene in the rice genome, encodes a receptor-like protein kinase. Subcellular localization analysis indicates that Z15 and z15 are localized on the plasma membrane. The expression of Z15 is induced by moderate low temperature (18 °C). The mutation of Z15 influenced the expression of two downstream genes, OsWRKY71 and OsMYB4, that were responsive to moderate low temperature. The results show that Z15 plays a crucial role in the early stages of the response to moderate low temperature in rice. Conclusions We identified a novel zebra-leaf mutant (z15) that impaired chloroplast structure in rice, LOC_Os05g12680, encoding a receptor-like protein kinase. Further study indiceted that Z15 plays a crucial role in the early stages of the response to moderate low temperature in rice.

Abstract Background This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins. Methods A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1–8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9–11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events. Results No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools. Conclusions DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools.