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Cytokine of interferon-gamma (IFNγ) plays a vital role in the immune response against Mycobacteria tuberculosis (Mtb) infection, yet the specific function of T cells producing IFNγ in this process remains unclear. In this study, we first isolated IFNγ+CD3+ T cells induced by Mtb antigens using surface staining assays. which showed a strong ability to inhibit the growth of intracellular mycobacteria in macrophages. Peripheral blood mononuclear cells (PBMCs) from healthy individuals were then challenged with Bacillus Calmette–Guérin (BCG) or Mtb, respectively, to sort IFNγ-secreting T cells for mRNA sequencing to analyze the gene expression patterns. The results of the integrated data analysis revealed distinct patterns of gene expression between IFNγ+CD3+ T cells induced by the BCG vaccine and those induced by Mtb pathogens. Further, unlike Mtb-induced cells, BCG-induced IFNγ+CD3+ T cells expressed high levels of interleukin-2 (IL-2), which increased the frequencies of these cells and the production of effector cytokines IFNγ and IL-2. Our findings suggested that IFNγ+CD3+ T cells with high IL-2 expression presented potent effector functions to inhibit intracellular Mtb growth, while Mtb infection impaired IL-2 expression in IFNγ+CD3+ T cells.

Congenital portosystemic shunts (CPSS) are rare pediatric vascular malformations characterized by abnormal development of the portal vein, which is attributed to incomplete embryonic remodeling of the hepatic and surrounding vasculature. CPSS manifests in two main forms: intrahepatic and extrahepatic. This study details the management of a pediatric patient diagnosed with Congenital Intrahepatic Portosystemic Shunt (CIPS) who was referred to our institution. By using a computer-assisted surgical system, the right hepatectomy was successfully performed, guided by precise intraoperative navigation based on three-dimensional reconstructions of enhanced CT imagery. The patient exhibited a favorable postoperative recovery trajectory, with the absence of complications or recurrence throughout the monitoring period.

IntroductionFatty liver disease in dairy cows is a metabolic disorder that significantly affects their health and productivity, imposing a notable economic burden on the global dairy industry. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target features, has shown unique advantages in the prevention and treatment of various diseases. Guiqi Yimu Powder, a traditional TCM formula, enhances growth, boosts production efficiency, and strengthens immune function in livestock by regulating antioxidant along with anti-inflammatory pathways. However, its specific regulatory mechanisms on fatty liver in dairy cows remain unclear. This study aims to investigate the molecular-level effects and potential regulatory mechanisms of Guiqi Yimu Powder in a Trimethylamine N-oxide (TMAO) induced fatty liver cell model of dairy cows.MethodsWe employed a comprehensive analysis integrating transcriptomics, proteomics, metabolomics, and network pharmacology. An in vitro dairy cow fatty liver cell model was established using TMAO to induce lipid accumulation. Cells were treated with the optimal TMAO concentration identified through preliminary experiments, and further divided into a lipid accumulation group and Guiqi Yimu Powder treatment groups. The treatment groups received varying concentrations of Guiqi Yimu Powder (10, 20, 30, 40, or 50 g/L). High-throughput omics sequencing technologies were utilized to perform a comprehensive analysis of the treated cells. Bioinformatics methods were applied to explore the regulatory effects, aiming to elucidate the specific impacts of Guiqi Yimu Powder on lipid metabolism, liver function, and related signaling pathways, thereby providing scientific evidence for its potential application in the prevention and treatment of fatty liver in dairy cows.ResultsGuiqi Yimu Powder treatment significantly affected 1,536 genes, 152 proteins, and 259 metabolites. KEGG enrichment analysis revealed that the significantly altered molecules are involved in multiple pathways related to the pathology of fatty liver, including metabolic pathways, glutathione metabolism, hepatitis B, and AMPK signaling pathway (p

With the increasingly prominent environmental issues in China, the government and citizens alike have intensified their focus on corporate investments in green environmental protection. Nevertheless, as government regulations become more stringent, there is substantial debate over whether environmental regulatory policies can consistently encourage listed companies to increase green environmental investments. Simultaneously, independent board supervision plays a crucial role in promoting the compliance and sustainability of listed companies regarding environmental protection. This paper selected a sample of 246 Chinese listed companies from 2010 to 2019, and used a fixed effects model to examine the impact of environmental regulation on the environmental investment of listed companies in China. Moreover, we used a mediation effect model to analyze the role of independent director supervision in influencing the relationship between environmental regulation and companies’ green environmental investment. Additionally, we discuss the heterogeneous impact of environmental regulations on corporate environmental investments. Our findings are as follows: first, during the sample period, the tightening of environmental regulations significantly reduces the growth of environmental investment among the studied firms. As government environmental regulatory policies gradually intensify, the negative impact on environmental investments by listed companies becomes increasingly evident. Second, independent directors help alleviate the adverse impacts of environmental regulations on the environmental investment levels of listed companies. This suggests that the inclusion of independent directors in board governance plays a role in assessing government environmental regulatory policies and overseeing corporate decisions related to environmental investment. Lastly, the heterogeneity analysis indicates that environmental regulation significantly negatively impacts the environmental investment of listed companies in pollution-intensive industries and those located in the western regions. Furthermore, environmental regulatory policies impose greater constraints on the environmental investments of small-sized listed companies compared to their large-sized counterparts.

Melanin is an amino acid derivative produced by melanocyte through a series of enzymatic reactions using tyrosinase as substrate. Human skin and hair color is also closely related to melanin, so understanding the mechanisms and proteins that produce melanin is very important. There are many proteins involved in the process of melanin expression, For example, proteins involved in melanin formation such as p53, HNF-1α (Hepatocyte nuclear factor 1α), SOX10 (Sry-related HMg-Box gene 10) and pax3 (paired box gene 3), MC1R(Melanocortin 1 Receptor), MITF (Microphthalmia-associated transcription factor), TYR (tyrosinase), TYRP1 (tyrosinase-related protein-1), TYRP2 (tyrosinase-related protein-2), and can be regulated by changing their content to control the production rate of melanin. Others, such as OA1 (ocular albinism type 1), Par-2 (protease-activated receptor 2) and Mlph (Melanophilin), have been found to control the transfer rate of melanosomes from melanocytes to keratinocytes, and regulate the amount of human epidermal melanin to control the depth of human skin color. In addition to the above proteins, there are other protein families also involved in the process of melanin expression, such as BLOC, Rab and Rho. This article reviews the origin of melanocytes, the related proteins affecting melanin and the basic causes of related gene mutations. In addition, we also summarized the active ingredients of 5 popular whitening cosmetics and their mechanisms of action.

Nitrate (NO3−) reduction is a key process governing the nitrogen (N) dynamics of coastal wetland sediments. Although the effects of environmental factors on the NO3− reduction mechanism in coastal wetland sediments have been examined in various studies, the effects of spatial variation in potential NO3− reduction processes in coastal wetland sediments and the factors driving geographical variation in these processes have not been widely examined. Here, we conducted research on surface sediment samples from four different vegetation types at six coastal wetland sites across two regions. We characterized potential rates of NO3− reduction processes (including denitrification (DF), anammox (ANA), and dissimilatory nitrate reduction to ammonium (DNRA)) using a15N tracer method. Additionally, we assessed the abundances of functional genes, and microbial community structure using high-throughput sequencing, and metagenomic sequencing. In six wetland sites, the contribution ranges of DF, ANA, and DNRA to NO3− reduction were 38.43%–55.69%, 31.33%–45.65%, and 5.26%–17.11%, respectively, and potential NO3− reduction was mainly driven by N removal via gaseous N (DF+ANA). Significant spatial differences were observed in the structure of bacterial and fungal microbial communities, suggesting that geographical distance has a major effect on microbial community structure. Environmental factors and Functional gene abundances were significantly related to potential NO3− reduction processes, and physicochemical properties had a stronger effect on potential NO3− reduction processes than gene abundances. Factors showing significant differences across regions were the main drivers of variation in potential NO3− reduction processes. Overall, our study showed that sediment substrates and geographical environmental factors rather than the abundance of functional genes and vegetation types were the main indicators of potential NO3− reduction activities in coastal wetlands.

High sugar content in peanut seeds is one of the major breeding objectives for peanut flavor improvement. In order to explore the genetic control of sugar accumulation in peanut kernels, we constructed a recombinant inbred line population of 256 F2:6-7 lines derived from the Luhua11 × 06B16 cross. A high-resolution genetic map was constructed with 3692 bin markers through whole genome re-sequencing. The total map distance was 981.65 cM and the average bin marker distance was 0.27cM. A major stable QTL region (qSCB09/qSSCB09) was identified on linkage group (LG) B09 associated with both sucrose content (SC) and soluble sugar content (SSC) explaining 21.51-33.58% phenotypic variations. This major QTL region was consistently detected in three environments and mapped within a physical interval of 1.56 Mb on chromosome B09, and six candidate genes were identified. These results provide valuable information for further map-based cloning of favorable allele for sugar content in peanut.

BackgroundLow-intensity pulsed ultrasound (LIPUS) can accelerate tooth movement and preserve tooth and bone integrity during orthodontic treatment. However, the mechanisms by which LIPUS affects tissue remodeling during orthodontic tooth movement (OTM) remain unclear. Periodontal ligament cells (PDLCs) are pivotal in maintaining periodontal tissue equilibrium when subjected to mechanical stimuli. One notable mechano-sensitive ion channel, Piezo1, can modulate cellular function in response to mechanical cues. This study aimed to elucidate the involvement of Piezo1 in the osteogenic response of force-treated PDLCs when stimulated by LIPUS.MethodAfter establishing rat OTM models, LIPUS was used to stimulate rats locally. OTM distance and alveolar bone density were assessed using micro-computed tomography, and histological analyses included hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining and immunohistochemical staining. GsMTx4 and Yoda1 were respectively utilized for Piezo1 functional inhibition and activation experiments in rats. We isolated human PDLCs (hPDLCs) in vitro and evaluated the effects of LIPUS on the osteogenic differentiation of force-treated hPDLCs using real-time quantitative PCR, Western blot, alkaline phosphatase and alizarin red staining. Small interfering RNA and Yoda1 were employed to validate the role of Piezo1 in this process.ResultsLIPUS promoted osteoclast differentiation and accelerated OTM in rats. Furthermore, LIPUS alleviated alveolar bone resorption under pressure and enhanced osteogenesis of force-treated PDLCs both in vivo and in vitro by downregulating Piezo1 expression. Subsequent administration of GsMTx4 in rats and siPIEZO1 transfection in hPDLCs attenuated the inhibitory effect on osteogenic differentiation under pressure, whereas LIPUS efficacy was partially mitigated. Yoda1 treatment inhibited osteogenic differentiation of hPDLCs, resulting in reduced expression of Collagen Ⅰα1 and osteocalcin in the periodontal ligament. However, LIPUS administration was able to counteract these effects.ConclusionThis research unveils that LIPUS promotes the osteogenesis of force-treated PDLCs via downregulating Piezo1.

BackgroundPositive psychology is a vibrant field of study, and conceptualizations of the components of well-being have received a great deal of attention from researchers. The study of well-being literacy thus provides an innovative perspective for enhancing and sustaining individuals’ experiences of well-being.ObjectiveThis study aimed to examine the psychometric properties of the wellbeing literacy 6-item (Well-Lit 6) scale in Chinese military academy cadets.MethodsA total of 3,218 undergraduate students from five military academies in China were recruited to complete questionnaires online.Results(1) The items of the scale showed high discrimination; (2) The alpha coefficient of the scale was 0.986 and the split-half reliability was 0.981, indicating high homogeneous reliability and split-half reliability; (3) The scale model fitted well and displayed structural validity; (4) The correlation between well-being literacy and related indicators was significant, and the calibration correlation and convergent-discriminant validity of the scale were high; (5) After gradually adding demographic variables, known predictors factors and well-being literacy, the ∆R2 for subjective well-being, life satisfaction, depression, and anxiety ranged from 0.036 to 0.067, 0.184 to 0.340, and 0.009 to 0.017, respectively, showing high incremental validity; (6) the total well-being literacy scores differed significantly by gender, grade, and parenting style.ConclusionThe Chinese version of the Well-Lit 6 is reliable and valid in predicting and accessing the subjective well-being, life satisfaction, emotion regulation, and psychological resilience of Chinese military academy cadets.

Listeria monocytogenes (Lm) is associated with severe foodborne infections and ubiquitous in the nature. Identification of characteristics of Lm transmission through trading of food products is essential for rapidly tracking Lm sources and controlling dissemination of listeriosis. In this study, a total of 44 Lm strains were isolated from food products originating from 14 countries/regions during 2003-2018 at the Shanghai port. The genomes of these Lm strains were sequenced by high-throughput sequencing. Multilocus sequence typing (MLST) analysis showed that 43 isolates were divided into 17 sequence types (STs). The distribution of STs was decentralized, with the dominant ST2 accounting for only 18.18% of the strains. The LM63 strain did not match with any of the existing STs. Core-genome MLST (cgMLST) analysis based on 1748 core genes categorized the 44 strains into 30 cgMLST types (CTs), with CT10153 and CT7892 as the most predominant CTs. Notably, LM63 and LM67 shared the same CT in the cgMLST analysis. The phylogenetic analysis based on single-copy homologous genes revealed that the 44 Lm strains were primarily classified into two lineages. The SNP analysis also indicated that these strains were roughly divided into two clades, with strains in the first clade mainly collected earlier than those in the second clade, which were predominantly collected from 2010 onwards. The analysis using the virulence factor database (VFDB) indicated that the virulence gene inlJ was the most prevalent among these 44 strains. Notably, ddrA, msbA, and sugC were enriched in this dataset, requiring further clarification of their roles in Listeria through future studies. These results might provide a clue for understanding of the global epidemiology and surveillance of Lm and present insights for implementing effective measures to reduce or prevent Listeria contamination outbreaks in imported food products.

Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood.Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein.Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116-5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU.Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance.

BackgroundCognitive deficits are core characteristics of schizophrenia, presenting before the emergence of psychotic symptoms. Individuals with a clinical high-risk for psychosis (CHR) and those with genetically high-risk of psychosis (GHR) also exhibit cognitive impairments. Nonetheless, it remains uncertain in which domains of cognitive impairments in these two groups were more similar to those of schizophrenia patients. Moreover, it is unclear which domains of impairment are caused by quality factors and which are more related to the state of disease. This research initiative aimed to extensively examine the distinct cognitive impairment profiles among the CHR, GHR, and first-episode schizophrenia (FES) cohorts.MethodsWe compared the cognitive functions of the three groups and a healthy control group (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). The participants for this study were recruited from the Beijing Anding Hospital of Capital Medical University. Our sample consisted of 56 patients with FES, 42 with CHR, 26 with GHR, and 62 HCs. The participants across all groups were matched in terms of gender, age, and level of education.ResultsIndividuals with FES, GHR, and CHR showed significant impairment across the majority of MCCB domains, with the exception of visual learning, in comparison to HCs. None of the MCCB domains demonstrated a discerning ability to accurately differentiate between individuals with CHR and those with GHR. In the speed of processing and attention/vigilance domains, individuals with GHR and CHR exhibited scores between those of FES and HCs, with all group differences reaching statistical significance. This pattern of results indicates an intermediate level of cognitive function in individuals with GHR and CHR. Conversely, the levels of impairment observed in working memory and verbal learning were relatively consistent across all three groups: FES, CHR, and GHR. Notably, individuals in the CHR group exhibited performance akin to that of the HCs in the reasoning/problem-solving domain, while showing significant differences from the FES group, with the CHR individuals demonstrating better performance. Additionally, individuals with GHR displayed performance in social cognition similar to that of the HCs, while also demonstrating significant distinctions from the FES group, with the GHR individuals demonstrating better performance.ConclusionSignificant cognitive deficits exist in individuals with CHR, GHR, and FES, and these deficits vary across domains. Processing speed and attention/vigilance could potentially serve as robust biomarkers for identifying individuals at a risk of psychosis. The impairment observed in reasoning/problem-solving abilities might signify a qualitative trait, whereas deficits in social recognition could indicate a state characteristic specific to schizophrenia.

Cosmetic peptides have gained popularity in a wide range of skincare products due to their good biocompatibility, effective anti-oxidative properties, and anti-aging effects. However, low binding between peptides and the cell surface limits the efficacy of functional peptides. In this study, we designed two novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface, thereby improving their performance for skin health. To achieve this, we optimized the well-known peptide tripeptide-1 (GHK) by separately grafting the integrin αvβ3-binding motif RGD and the chondroitin sulfate (CS)-binding motif sOtx2 onto it, forming two chimeric targeting peptides, RGD-GHK and sOtx2-GHK. Comparative analysis showed that both RGD-GHK and sOtx2-GHK exhibited superior anti-oxidative and anti-apoptotic effects compared to the non-targeting peptide, GHK. Furthermore, RGD-GHK demonstrated exceptional anti-aging activity, and its potential for promoting wound healing and repairing the skin barrier was evaluated in vitro using cells and skin models. In vitro permeation and in vivo adsorption testing confirmed that RGD-GHK achieved a high local concentration in the skin layer, initiating peptide effects and facilitating in vivo wound healing, while maintaining excellent biocompatibility. The enhancement of signaling cosmetic peptides can be attributed to the specific interaction between the binding motif and cell surface components. Consequently, this targeting peptide holds promising potential as a novel functional peptide for application in cosmetics.

BackgroundHigh-producing dairy cows face varying degrees of metabolic stress and challenges during the late perinatal period, resulting in ruminal bacteria abundance and their fermentative ability occurring as a series of changes. However, the dynamic changes are still not clear.Aims/methodsTen healthy, high-producing Holstein dairy cows with similar body conditions and the same parity were selected, and ruminal fluid from the dairy cows at postpartum 0, 7, 14, and 21 d was collected before morning feeding. 16S rRNA high-throughput sequencing, GC-MS/MS targeted metabolomics, and UPLC-MS/MS untargeted metabolomics were applied in the study to investigate the dynamic changes within 21 d postpartum.ResultsThe results displayed that the structures of ruminal bacteria were significantly altered from 0 to 7 d postpartum (R = 0.486, P = 0.002), reflecting the significantly declining abundances of Euryarchaeota and Chloroflexi phyla and Christensenellaceae, Methanobrevibacter, and Flexilinea genera (P < 0.05) and the obviously ascending abundances of Ruminococcaceae, Moryella, Pseudobutyrivibrio, and Prevotellaceae genera at 7 d postpartum (P < 0.05). The structures of ruminal bacteria also varied significantly from 7 to 14 d postpartum (R = 0.125, P = 0.022), reflecting the reducing abundances of Christensenellaceae, Ruminococcaceae, and Moryella genera (P < 0.05), and the elevating abundances of Sharpea and Olsenella genera at 14 d postpartum (P < 0.05). The metabolic profiles of ruminal SCFAs were obviously varied from 0 to 7 d postpartum, resulting in higher levels of propionic acid, butyric acid, and valeric acid at 7 d postpartum (P < 0.05); the metabolic profiles of other ruminal metabolites were significantly shifted from 0 to 7 d postpartum, with 27 significantly elevated metabolites and 35 apparently reduced metabolites (P < 0.05). The correlation analysis indicated that propionic acid was positively correlated with Prevotellaceae and Ruminococcaceae (P < 0.05), negatively correlated with Methanobrevibacter (P < 0.01); butyric acid was positively associated with Prevotellaceae, Ruminococcaceae, and Pseudobutyrivibrio (P < 0.05), negatively associated with Christensenellaceae (P < 0.01); valeric acid was positively linked with Prevotellaceae and Ruminococcaceae (P < 0.05); pyridoxal was positively correlated with Flexilinea and Methanobrevibacter (P < 0.05) and negatively correlated with Ruminococcaceae (P < 0.01); tyramine was negatively linked with Ruminococcaceae (P < 0.01).ConclusionThe findings contribute to the decision of nutritional management and prevention of metabolic diseases in high-producing dairy cows during the late perinatal period.

ObjectiveThis study aimed to compare the efficacy of novel oral anticoagulants (NOACs) with traditional anticoagulants vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) post transcatheter aortic valve replacement (TAVR).MethodsStudies comparing the usage of NOACs and VKAs in AF patients with oral anticoagulant indication post-TAVR were retrieved from PubMed, EMBASE, Medline, and Cochrane databases from their building-up to Jan. 2023. The literature was screened in line of inclusion and exclusion criteria. Risk ratio (RR) or odds ratio (OR),95% confidence interval (CI) and number needed to treat (NNT) were calculated for four main indexes that composite endpoints composed mainly of any clinically relevant risk events, stroke, major bleeding, and all-cause mortality. Subsequently, a meta-analysis was performed using the RevMan5.3 and Stata 16.0 software.ResultsIn the aggregate of thirteen studies, contained 30388 post-TAVR patients with AF, were included in this meta-analysis. Our results indicated that there was no significant difference in stroke between the NOACs group and the VKAs group, and the NOACs group had a numerically but non-significantly higher number of composite endpoint events compared with the other group. Nevertheless, the incidence of major bleeding [11.29% vs. 13.89%, RR 0.82, 95%CI (0.77,0.88), P

IntroductionTicks and fleas, as blood-sucking arthropods, carry and transmit various zoonotic diseases. In the natural plague foci of China, monitoring of Yersinia pestis has been continuously conducted in Marmota himalayana and other host animals, whereas other pathogens carried by vectors are rarely concerned in the Qinghai-Tibet Plateau.MethodsIn this study, we investigated the microbiota of ticks and fleas sampling from M. himalayana in the Qinghai-Tibet Plateau, China by metataxonomics combined with metagenomic methods.ResultsBy metataxonomic approach based on full-length 16S rDNA amplicon sequencing and operational phylogenetic unit (OPU) analyses, we described the microbiota community of ticks and fleas at the species level, annotated 1,250 OPUs in ticks, including 556 known species and 492 potentially new species, accounting for 48.50% and 41.71% of the total reads in ticks, respectively. A total of 689 OPUs were detected in fleas, consisting of 277 known species (40.62% of the total reads in fleas) and 294 potentially new species (56.88%). At the dominant species categories, we detected the Anaplasma phagocytophilum (OPU 421) and potentially pathogenic new species of Wolbachia, Ehrlichia, Rickettsia, and Bartonella. Using shotgun sequencing, we obtained 10 metagenomic assembled genomes (MAGs) from vector samples, including a known species (Providencia heimbachae DFT2), and six new species affliated to four known genera, i.e., Wolbachia, Mumia, Bartonella, and Anaplasma. By the phylogenetic analyses based on full-length 16S rRNA genes and core genes, we identified that ticks harbored pathogenic A. phagocytophilum. Moreover, these potentially pathogenic novel species were more closely related to Ehrlichia muris, Ehrlichia muris subsp. eauclairensis, Bartonella rochalimae, and Rickettsia limoniae, respectively. The OPU 422 Ehrlichia sp1 was most related to Ehrlichia muris and Ehrlichia muris subsp. eauclairensis. The OPU 230 Bartonella sp1 and Bartonella spp. (DTF8 and DTF9) was clustered with Bartonella rochalimae. The OPU 427 Rickettsia sp1 was clustered with Rickettsia limoniae.DiscussionThe findings of the study have advanced our understanding of the potential pathogen groups of vectors in marmot (Marmota himalayana) in the Qinghai-Tibet Plateau.

Introduction: A growing body of evidence suggests that parental substance abuse, even prior to conception, may induce phenotypic changes in offspring. Parental opioid exposure has been shown to affect developmental processes, induce memory deficits, and lead to psycho-emotional disorders in offspring. However, how parental, especially paternal, chronic drug exposure affects offspring remains unexplored.Methods: Adult male rats were subjected to 31 days of heroin self-administration followed by mating with naïve females. Litter size and body weight of F1 offspring were recorded. Object-based attention tests, cocaine self-administration tests, and hot plate tests were used to test for potential effects of chronic paternal heroin seeking on cognition, reward, or analgesic sensitivity in the offspring.Results: Body weight and litter size of the heroin F1 generation were not altered compared to the saline F1 generation. Furthermore, paternal chronic heroin self-administration experience had no significant effect on object-based attention tests or cocaine self-administration behavior in either sex. However, in the hot plate test, although no difference in basal latency was found between the two groups in either sex, a significant increase in the analgesic effect of heroin was observed in the male heroin F1 generation.Conclusions: Taken together, these data provide evidence that paternal chronic heroin self-administration experience could sex-dimorphically increase the analgesic effect of heroin in male offspring, but had no significant effect on response to cocaine reinforcement or attentional behavior.

Most of the natural gas hydrate sources in the world are biogenic gas, but there are still many unsolved problems in the formation process of biogenic gas. The gas source of gas hydrates in the northern South China Sea is also controversial, and the evaluation of biogas source rock in hydrate development areas lacks experimental basis and quantitative data. In order to solve these problems, this paper used the sediments obtained from the GMGS2 hydrate drilling voyage to simulate the biological gas production. Through the culture experiment, the relationship between sedimentary gas production, temperature and sediment characteristics in the hydrate development area of Dongsha Sea area was comparatively studied, and the results were compared with typical biological gas fields. The results showed that CH4 and CO2 were the main gas products, and a small amount of H2 was formed. Methane yield is closely related to temperature, and the optimal temperature range in the study area is 20°C~ 40°C. At the same time, it is found that organic carbon content (TOC) has no significant correlation with methane yield, and it is not suitable to be used as an index for the evaluation of biogas source rock. Comprehensive analysis shows that the methane production rate in the study area is relatively high and the hydrocarbon generation potential is great, which meets the gas source conditions for the formation of gas hydrate ore body. The main factors affecting biomethane yield include available organic matter, bacterial community and environmental factors.

MADS-box transcription factors are crucial members of regulatory networks underlying multiple developmental pathways and abiotic stress regulatory networks in plants. Studies on stress resistance-related functions of MADS-box genes are very limited in barley. To gain insight into this gene family and elucidate their roles in salt and waterlogging stress resistance, we performed genome-wide identification, characterization and expression analysis of MADS-box genes in barley. A whole-genome survey of barley revealed 83 MADS-box genes, which were categorized into type I (Mα, Mβ and Mγ) and type II (AP1, SEP1, AGL12, STK, AGL16, SVP and MIKC*) lineages based on phylogeny, protein motif structure. Twenty conserved motifs were determined and each HvMADS contained one to six motifs. We also found tandem repeat duplication was the driven force for HvMADS gene family expansion. Additionally, the co-expression regulatory network of 10 and 14 HvMADS genes was predicted in response to salt and waterlogging stress, and we proposed HvMADS11,13 and 35 as candidate genes for further exploration of the functions in abiotic stress. The extensive annotations and transcriptome profiling reported in this study ultimately provides the basis for MADS functional characterization in genetic engineering of barley and other gramineous crops.

BackgroundMultidrug resistance in bacteria is a serious problem in organ transplantations. This study aimed to identify risk factors and establish a predictive model for screening deceased organ donors for multidrug-resistant (MDR) bacteria.MethodsA retrospective cohort study was conducted at the First Affiliated Hospital of Zhejiang University School of Medicine from July 1, 2019 to December 31, 2022. The univariate and multivariate logistic regression analysis was used to determine independent risk factors associated with MDR bacteria in organ donors. A nomogram was established based on these risk factors. A calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to estimated the model.ResultsIn 164 organ donors, the incidence of MDR bacteria in culture was 29.9%. The duration of antibiotic use ≥3 days (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.62–8.81, p=0.002), length of intensive care unit (ICU) stay per day(OR 1.06, 95% CI 1.02–1.11, p=0.005) and neurosurgery (OR 3.31, 95% CI 1.44–7.58, p=0.005) were significant independent predictive factors for MDR bacteria. The nomogram constructed using these three predictors displayed good predictive ability, with an area under the ROC curve value of 0.79. The calibration curve showed a high consistency between the probabilities and observed values. DCA also revealed the potential clinical usefulness of this nomogram.ConclusionsThe duration of antibiotic use ≥3 days, length of ICU stay and neurosurgery are independent risk factors for MDR bacteria in organ donors. The nomogram can be used to monitor MDR bacteria acquisition risk in organ donors.

The benthic foraminiferal assemblages are commonly used to indicate different oxygenation conditions. In the last few decades, pore characteristics of the benthic foraminiferal tests from the micro-perspective using high-spatial-resolution analysis have been extensively suggested to indicate redox changes. Based on the whole test of the living shallow-infaunal species Bolivina robusta using a more representative and comprehensive method, we observed a significant negative correlation between the pore density (PD) and bottom dissolved oxygen (DO) concentration, and the average PD was about 36% higher in hypoxic environments (DO3 mg/l). In terms of reproduction pattern in hypoxic environments, the species seemed to mainly choose the asexual life cycle (74.60%) to get more small generations with larger pore size (PS) (asexual 7 μm vs. sexual 4 μm) and exterior ornamentation (irregular papillae) as their survival strategy. The results provide new insight into the benthic foraminiferal ecology to reconstruct the pale-oceanography and paleo-ecology changes in the East China Sea. Moreover, this study has the potential to be applied in broad regions as an independent proxy by comparison to other widely-distributed benthic foraminiferal species.

Objective: This study aimed to identify the different associations between antiarrhythmic drugs (AADs) and arrhythmias, and to determine whether pharmacokinetic drug interactions involving AADs increase the risk of AAD-related arrhythmias compared to using AADs alone.Materials and methods: The disproportionality analysis of AAD-associated cardiac arrhythmias, including AAD monotherapies and concomitant use of pharmacokinetic interacting agents involving AADs, was conducted by using reporting odds ratio (ROR) and information component (IC) as detection of potential safety signals based on FAERS data from January 2016 to June 2022. We compared the clinical features of patients reported with AAD–associated arrhythmias between fatal and non-fatal groups, and further investigated the onset time (TTO) following different AAD regimens.Results: A total of 11754 AAD–associated cardiac arrhythmias reports were identified, which was more likely to occur in the elderly (52.17%). Significant signals were detected between cardiac arrhythmia and all AAD monotherapies, with ROR ranging from 4.86 with mexiletine to 11.07 with flecainide. Regarding four specific arrhythmias in High Level Term (HLT) level, the AAD monotherapies with the highest ROR were flecainide in cardiac conduction disorders (ROR025 = 21.18), propafenone in rate and rhythm disorders (ROR025 = 10.36), dofetilide in supraventricular arrhythmias (ROR025 = 17.61), and ibutilide in ventricular arrhythmias (ROR025 = 4.91). Dofetilide/ibutilide, ibutilide, mexiletine/ibutilide and dronedarone presented no signal in the above four specific arrhythmias respectively. Compared with amiodarone monotherapy, sofosbuvir plus amiodarone detected the most significantly increased ROR in arrhythmias.Conclusion: The investigation showed the spectrum and risk of AAD–associated cardiac arrhythmias varied among different AAD therapies. The early identification and management of AAD-associated arrhythmias are of great importance in clinical practice.

Prostate cancer (PC) is one of the major health issues of elderly men in the word. It is showed that there were approximately 1.414 million patients with PC in 2020 worldwide, with a high mortality rate in metastatic cases. In the present choices of treatment in PC, androgen deprivation therapy has long been as a backbone of them. But the clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) were not ideal because of their poor prognosis, more effective therapeutic approaches are still necessary to further improve this problem. Poly (ADP-ribose) polymerase (PARP) inhibitors lead to the single-strand DNA breaks and/or double-strand DNA breaks, and result in synthetic lethality in cancer cells with impaired homologous recombination genes. It is estimated that approximately 20~25% of patients with mCRPC have a somatic or germinal DNA damage repair gene mutation. Furthermore, in “BRCAness” cases, which has been used to describe as tumors that have not arisen from a germline BRCA1 or BRCA2 mutation, there were also a number of studies sought to extend these promising results of PARP inhibitors. It is worth noting that an interaction between androgen receptor signaling and synthetic lethality with PARP inhibitors has been proposed. In this review, we discussed the mechanism of action and clinical research of PARP inhibitors, which may benefit population from “specific” to the “all-comer” in patients with PC when combined with novel hormonal therapies.

BackgroundBurnout and depression have overlapping symptoms, but the extent of overlap remains unclear, and the complex relationship between burnout and depression in pharmacists is rarely explored.MethodsWe investigated burnout and depression in 1,322 frontline pharmacists, and explored the complex relationship between burnout and depression in those pharmacists using network analysis.ResultsNetwork analysis showed that there were 5 communities. A partial overlap was found between burnout and depressive symptoms in pharmacists. The nodes MBI-6 (I have become more callous toward work since I took this job), D18 (My life is meaningless), and D10 (I get tired for no reason) had the highest expected influence value. D1 (I feel down-hearted and blue) and D14 (I have no hope for the future) were bridge symptoms connected with emotional exhaustion and reduced professional efficacy, respectively.ConclusionA partial overlap exists between burnout and depressive symptoms in pharmacists, mainly in the connection between the emotional exhaustion and reduced professional efficacy and the depressive symptoms. Potential core targets identified in this study may inform future prevention and intervention.

IntroductionSoy isoflavone, a class of polyphenolic compounds exclusively occurred in legumes, is an important bioactive compound for both plants and human beings. The outline of isoflavones biosynthesis pathway has been drawn up basically in the previous research. However, research on the subject has been mostly restricted to investigate the static regulation of isoflavone content in soybean, rather than characterize its dynamic variation and modulation network in developing seeds.MethodsIn this study, by using eight recombinant inbred lines (RIL), the contents of six isoflavone components in the different stages of developing soybean seeds were determined to characterize the dynamic variation of isoflavones, and the isoflavones accumulation pattern at physiological level was investigated. Meanwhile, we integrated and analyzed the whole genome expression profile of four lines and 42 meta-transcriptome data, based on the multiple algorithms.ResultsThis study: 1) obtained 4 molecular modules strongly correlated with isoflavone accumulation; 2) identified 28 novel major genes that could affect the accumulation of isoflavones in developing seeds free from the limitation of environments; 3) discussed the dynamic molecular patterns regulating isoflavones accumulation in developing seed; 4) expanded the isoflavone biosynthesis pathway.DiscussionThe results not only promote the understandings on the biosynthesis and regulation of isoflavones at physiological and molecular level, but also facilitate to breed elite soybean cultivars with high isoflavone contents.

ObjectivePositive psychology is a revolution in the science of psychology as well as a new milestone in the development of human society. The purpose of the study was to use bibliometrics and visual analysis to assess the current state and trends in positive psychology research.MethodsThe Web of Science Core Collection was searched for 4,378 papers on positive psychology between 1999 and 2021. The features of positive psychology research were analyzed using Microsoft Excel 2013, VOSviewer (1.6.17), and CiteSpace (5.8.R1).ResultsThe findings demonstrate a steady growth in positive psychology publications from 1999 to 2021. The United States (1,780) and Harvard University (104), respectively, were the most productive nations and organizations in this subject. Frontiers in Psychology was the most productive journal (288), while the Journal of Personality and Social Psychology had the most co-citations (8,469). Seligman was the most influential author, with 3,350 citations and 5,020 co-citations. The top ten co-cited references, in terms of citation explosion, suggesting that these papers provide the foundation for the growth of this discipline. The systematic review, character strengths, positive psychology intervention, language pleasure, and the COVID-19 pandemic are the focal points of research and development developments in this discipline.ConclusionThese findings have helped researchers in positive psychology find new ways to collaborate with partners, hot topics, and research frontiers.

Identifying Bowel strangulation and the approach and timing of surgical intervention for pediatric SBO are still uncertain. In this study, 75 consecutive pediatric patients with surgically confirmed SBO were retrospectively reviewed. The patients were divided into group 1 (n = 48) and group 2 (n = 27) according to the presence of reversible or irreversible bowel ischemia, which was analyzed based on the degree of ischemia at the time of operation. The results demonstrated that the proportion of patients with no prior abdominopelvic surgery was higher, the serum albumin level was lower, and the proportion of patients in which ascites were detected by ultrasonography was higher in group 2 than that in group 1. The serum albumin level was negatively correlated with ultrasonographic findings of the fluid sonolucent area in group 2. There were significant differences in the choice of surgical approach between group 1 and group 2. A symptom duration of >48 h was associated with an increased bowel resection rate. The mean length of hospital stay was shorter in group 1 than that in group 2. In conclusion, immediate surgical intervention should be considered in patients with a symptom duration of >48 h or the presence of free ascites between dilated small bowel loops on ultrasonography. Laparoscopic exploration is recommended as first-line treatment in patients with stable status.

The cell wall plays an important role in plant mechanical strength. Cellulose is the major component of plant cell walls and provides the most abundant renewable biomass resource for biofuels on earth. Mutational analysis showed that cellulose synthase (CESA) genes are critical in cell wall biosynthesis in cereal crops like rice. However, their role has not been fully elucidated in barley. In this study, we isolated a brittle culm mutant brittle culm 3 (bc3) derived from Yangnongpi 5 ethyl methanesulfonate (EMS) mutagenesis in barley. The bc3 mutants exhibited reduced mechanical strength of the culms due to impaired thickening of the sclerenchyma cell wall and reduced cellulose and hemicellulose content in the culms. Genetic analysis and map-based cloning revealed that the bc3 mutant was controlled by a single recessive gene and harbored a point mutation in the HvCESA5 gene, generating a premature stop codon near the N-terminal of the protein. Quantitative real-time PCR (qRT-PCR) analysis showed that the HvCESA5 gene is predominantly expressed in the culms and co-expressed with HvCESA4 and HvCESA8, consistent with the brittle culm phenotype of the bc3 mutant. These results indicate that the truncated HvCESA5 affects cell wall biosynthesis leading to a brittle culm phenotype. Our findings provide evidence for the important role of HvCESA5 in cell wall biosynthesis pathway and could be a potential target to modify cell wall in barley.

Introduction: With the widespread application of Immune checkpoint inhibitors (ICIs), it is important to explore the association between ICIs and cardiac arrhythmias and to characterize the clinical features of ICI-associated cardiac arrhythmias in real-world studies.Objective: The purpose of this study was to characterize the main features of ICI-related cardiac arrhythmias.Methods: From January 2017 to June 2021, data in the Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved to conduct the disproportionality analysis. For the ICI-related cardiac arrhythmia detection, signals were detected by reporting odds ratio (ROR) and information component (IC), calculated using two-by-two contingency tables The clinical characteristics of patients reported with ICI-related cardiac arrhythmias were compared between fatal and non-fatal groups, and the time to onset (TTO) following different ICI regimens was further investigated. Multivariate logistic regression was used to evaluate the association between concurrent cardiotoxicities and ICI-associated arrhythmias.Results: We identified a total of 1957 ICI–associated cardiac arrhythmias reports which appeared to influence more men (64.44%) than women (30.76%), with a median age of 68 [interquartile range (IQR) 60–75] years. Cardiac arrhythmias were reported most often in patients with lung, pleura, thymus and heart cancers (38.02% of 1957 patients). Compared with the full database, ICIs were detected with pharmacovigilance of cardiac arrhythmias (ROR025 = 1.16, IC025 = 0.19). Anti-PD-1 and anti-PD-L1 monotherapies were found to be related to higher reporting of arrhythmias, corresponding to ROR025 = 1.03, IC025 = 0.06 and ROR025 = 1.27, IC025 = 0.29, respectively, with the exception of anti-CTLA-4 monotherapies (ROR025 = 0.57, IC025 = −1.21). The spectrum of arrhythmias induced by ICIs differed among therapeutic regimens. There was no significant difference in the onset time between monotherapy and combination regimen. Moreover, reports of ICI-associated arrhythmias were associated with other concurrent cardiotoxicity, including cardiac failure [ROR 2.61 (2.20–3.09)], coronary artery disorders [ROR 2.28 (1.83–2.85)], myocardial disorders [ROR 5.25 (4.44–6.22)], pericardial disorders [ROR 2.76 (2.09–3.64)] and cardiac valve disorders [ROR 3.21 (1.34–7.68)].Conclusion: ICI monotherapy and combination therapy can lead to cardiac arrhythmias that can result in serious outcomes and tend to occur early. Our findings underscore the importance of early recognition and management of ICI-related cardiac arrhythmias.

Background and objectivesInsulin resistance (IR) is closely related to non-small-cell lung cancer (NSCLC) risk. Recently, triglyceride glucose-body mass index (TyG-BMI) has been recognized as one of the simple indexes of insulin resistance (IR). However, there are limited data on the relationship between TyG-BMI and NSCLC. Here, we investigated the association of TyG-BMI with NSCLC risk in Chinese adults.MethodsThis study consisted of 477 NSCLC cases and 954 healthy subjects. All participants were enrolled from 3201 Hospital affiliated to the Medical Department of Xi’an Jiaotong University. TyG-BMI was calculated based on the values of fasting blood glucose, triglyceride, and BMI. The association of TyG-BMI with NSCLC risk was estimated by logistic regression analysis.ResultsThe mean value of TyG-BMI was statistically increased in patients with NSCLC compared to the control group (201.11 ± 28.18 vs. 174 ± 23.78, P < 0.01). There was a significant positive association between TyG-BMI and NSCLC (OR = 1.014; 95% CI 1.007–1.021; P < 0.001) after controlling for confounding factors. Moreover, the prevalence of NSCLC was significantly elevated in participants in the high TyG-BMI tertiles than those in the intermediate and low TyG-BMI tertiles (60.46% vs. 12.61% vs. 26.83%, P < 0.01). Importantly, TyG-BMI achieved a significant diagnostic accuracy for NSCLC, with an AUC (area under the curve) of 0.769 and a cutoff value of 184.87.ConclusionThe findings suggest that TyG-BMI is a useful tool for assessing NSCLC risk. Thus, it is essential to follow up on high TyG-BMI, and lifestyle modification is needed to prevent NSCLC in people with high TyG-BMI.

Oral squamous cell carcinoma (OSCC) is a common head-and-neck cancer with a deficiency of early diagnosis and poor prognosis. To identify potential diagnostic and prognostic markers of OSCC, we firstly used weighted gene co-expression network analysis (WGCNA) to build a co-expression module from GSE42743. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on specified units from selected modules utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID). Additionally, we identified and validate hub genes of these specified modules from multiple datasets like GEPIA and TCGA. In total 16 co-expression modules were built by 17,238 genes of 74 tumor samples utilizing WGCNA. Through pathway and functional enrichment analysis, the turquoise module was most firmly relevant to the cell cycle, oocyte meiosis, and p53 signaling pathway. Hub genes VRK1, NUP37, HMMR, SPC25, and RUVBL1 were identified to be related to oral cancer at both molecular level and clinical levels. The expressions of these genes differed in tumor tissues and normal tissues. Meanwhile, patients with high hub gene expression had a poor prognosis clinically. To conclude, five hub genes were identified to be relevant to oral cancer from the molecular level and the clinical level. Therefore, the detection of these genes was of great significance. They can be regarded as diagnostic and prognostic biomarkers for oral cancer. Also, they could shed light on the improvement of patients’ overall survival and prognosis, which needs further analysis in the future.

The soybean root necrosis 1 (rn1) mutation causes progressive browning of the roots soon after germination and provides increased tolerance to the soil-borne oomycete pathogen Phytophthora sojae in soybean. Toward understanding the molecular basis of the rn1 mutant phenotypes, we conducted tandem mass tag (TMT)-labeling proteomics and phosphoproteomics analyses of the root tissues of the rn1 mutant and progenitor T322 line to identify potential proteins involved in manifestation of the mutant phenotype. We identified 3,160 proteins. When the p-value was set at ≤0.05 and the fold change of protein accumulation between rn1 and T322 at ≥1.5 or ≤0.67, we detected 118 proteins that showed increased levels and 32 proteins decreased levels in rn1 as compared to that in T322. The differentially accumulated proteins (DAPs) are involved in several pathways including cellular processes for processing environmental and genetic information, metabolism and organismal systems. Five pathogenesis-related proteins were accumulated to higher levels in the mutant as compared to that in T322. Several of the DAPs are involved in hormone signaling, redox reaction, signal transduction, and cell wall modification processes activated in plant–pathogen interactions. The phosphoproteomics analysis identified 22 phosphopeptides, the levels of phosphorylation of which were significantly different between rn1 and T322 lines. The phosphorylation levels of two type II metacaspases were reduced in rn1 as compared to T322. Type II metacaspase has been shown to be a negative regulator of hypersensitive cell death. In absence of the functional Rn1 protein, two type II metacaspases exhibited reduced phosphorylation levels and failed to show negative regulatory cell death function in the soybean rn1 mutant. We hypothesize that Rn1 directly or indirectly phosphorylates type II metacaspases to negatively regulate the cell death process in soybean roots.

Aging-related retinal degeneration can manifest as decreased visual function due to damage to retinal structures and dysfunction in retinal homeostasis. Naringenin, a flavonoid, has beneficial effects in preventing cellular aging, preserving the functionality of photoreceptors, and slowing down visual function loss. However, the role and potential mechanism of naringenin in the aging mouse retina require further investigation. In this study, we evaluated the effects of naringenin on the aging eye using electroretinogram (ERG) and hematoxylin and eosin staining and explored its potential mechanism by western blotting. ERG showed that naringenin increased the amplitude of the a- and b-waves of scotopic 3.0, 10.0, and the a-wave amplitude of photopic 3.0 in the aging mouse retina. Furthermore, administration of naringenin prevented aging-induced retinal degeneration in the total retina, ganglion cell, inner plexiform layer, inner nuclear layer, and outer nuclear layer. The expression of mitochondrial fusion protein two was increased, OPA1 protein expression and the ratio of L-OPA1/S-OPA1 were unchanged, and dynamin-related protein one was decreased in the 12-month-old mice treated with naringenin compared with the 12-month-old mice treated with vehicle. Furthermore, the downregulation of age-related alterations in autophagy was significantly rescued in the aging mice by treatment with naringenin. Taken together, these results suggest that the oral administration of naringenin improves visual function, retinal structure, mitochondrial dynamics, and autophagy in the aging mouse retinas. Naringenin may be a potential dietary supplement for the prevention or treatment of aging-related retinal degeneration.

With increased global competition and the advent of the knowledge economy, developing graduate students’ ability to innovate in their research has become a core focus of graduate education. Graduate students’ perceived help and assistance from supervisors is one of the key resources for research innovation. This study explored the relationships between graduate students’ perceived supervisor support and their innovative behavior in research, and examined the mediation effect of creative self-efficacy, their confidence in abilities to generate creative ideas or produce creative outcomes. Survey data were collected from a sample of 996 Chinese graduate students. The results revealed that academic support was negatively related to idea generation and idea search; personal support was positively related to overcoming obstacles; autonomy support was positively related to all factors of innovative behavior except overcoming obstacles and innovation outputs. The mediation analysis suggested that creative self-efficacy significantly mediated the relationship between academic support and graduate students’ innovative behavior in research. The results of this study highlight the significance of both supervisor support and creative self-efficacy in developing graduate students’ research innovation. The findings have significant implications for stimulating students’ research innovation and for improving the quality of graduate education.

Background: As a malignant tumor, pancreatic cancer is difficult to detect in its early stage. Pancreatic cancer progresses rapidly and has a short survival time. Most cases have metastasized to distant organs before diagnosis. The mechanism of induction of pancreatic cancer is not fully understood.Methods: In this study, bioinformatics predicted ATP binding cassette subfamily A member 12 (ABCA12) expression in pancreatic tissues and performed survival analysis, risk assessment, and enrichment analysis. The expression of ABCA12 in 30 pairs of clinical samples was detected by immunohistochemistry and we analyzed its correlation with clinical information. Both reverse transcription polymerase chain reaction (RT–PCR) and western blot analysis were used to detect mRNA and protein expression in cell lines. Two different siRNAs and SW1990 cell line were used to construct pancreatic cancer cell models with ABCA12 knockdown. Cell viability was evaluated by cell counting kit-8 (CCK-8) and EdU proliferation assays. Wound healing assays and Transwell assays were used to measure the ability of cell migration and invasion. Flow cytometry was used to investigate the effect of ABCA12 on the proliferation cycle and apoptosis of pancreatic cancer. Western blot analysis detected changes in apoptosis, migration, and other pathway proteins in SW1990 cells after transfection.Results:ABCA12 is highly expressed in pancreatic cancer tissues and cells. After ABCA12 was knocked down, the proliferation, invasion, and migration of SW1990 cells were significantly reduced, and apoptosis was increased. The changes in pathway proteins suggested that ABCA12 may regulate the progression of pancreatic cancer through the AKT pathway.Conclusion: We found that ABCA12 is differentially expressed in pancreatic tissues and cells. ABCA12 can also affect the biological behavior of pancreatic cancer cells effectively, which may serve as a new target for pancreatic cancer diagnosis and treatment.

It is found that natural gas hydrate is not only a pore-filling material but also exists in the reservoir in the form of rock skeleton particles. Therefore, the traditional petrophysical simulation method cannot well describe the physical properties of natural gas hydrate reservoir. At the same time, the physical properties of the hydrate layer and its associated free gas layer are quite different, so it is difficult to fit the physical properties of the two media using traditional modeling methods. The two-phase modeling technology used in this paper is the equivalent medium modeling technology based on BK solid substitution theory and Gassmann fluid substitution theory, which simulates hydrate particles in rock skeleton and hydrate filling in pores, respectively. The forward simulation results show that the two-phase simulation technology of natural gas hydrate can well fit the P-wave and S-wave velocity information of the medium. At the same time, the equivalent medium model of the free gas reservoir is established by using only Gassmann fluid substitution theory. The practical application shows that the subsection modeling method can well solve the problem of the too large difference between the two sets of reservoir physical properties and make the calibration results of forward modeling synthetic records more accurate.

ObjectiveDue to the low incidence of pulmonary large cell neuroendocrine carcinoma (LCNEC), the survival analysis for comparing lobectomy and sublobar resection (SLR) for stage IA LCNEC remains scarce.MethodsPatients diagnosed with pathological stage IA LCNEC between 1998 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The oncological outcomes were cancer-specific survival (CSS) and overall survival (OS). Kaplan–Meier analysis and Cox multivariate analysis were used to identify the independent prognostic factors for OS and CSS. Furthermore, propensity score matching (PSM) was performed between SLR and lobectomy to adjust the confounding factors.ResultsA total of 308 patients with stage IA LCNEC met the inclusion criteria: 229 patients (74.4%) received lobectomy and 79 patients (25.6%) received SLR. Patients who underwent SLR were older (P < 0.001), had smaller tumor size (P = 0.010), and less lymph nodes dissection (P < 0.001). The 5-year CSS and OS rates were 56.5 and 42.9% for SLR, and 67.8 and 55.7% for lobectomy, respectively (P = 0.037 and 0.019, respectively). However, multivariate analysis did not identify any differences between the SLR group and lobectomy group in CSS (P = 0.135) and OS (P = 0.285); and the PSM also supported these results. In addition, the age at diagnosis and laterality of tumor were identified as significant predictors for CSS and OS, whereas the number of lymph nodes dissection was a significant predictor for CSS.ConclusionsAlthough SLR is not inferior to lobectomy in terms of oncological outcomes for patients with stage IA LCNEC, more lymph nodes can be dissected or sampled during lobectomy. Lobectomy should still be considered as a standard procedure for patients with early-stage LCNEC who are able to withstand lobectomy.

Sirtuin 4 (SIRT4) is one of seven mammalian sirtuins that possesses ADP-ribosyltransferase, lipoamidase and deacylase activities and plays indispensable role in metabolic regulation. However, the role of SIRT4 in the retina is not clearly understood. The purpose of this study was to explore the location and function of SIRT4 in the retina. Therefore, immunofluorescence was used to analyze the localization of SIRT4 in rat, mouse and human retinas. Western blotting was used to assess SIRT4 and glutamine synthetase (GS) protein expression at different developmental stages in C57BL/6 mice retinas. We further analyzed the retinal structure, electrophysiological function and the expression of GS protein in SIRT4-deficient mice. Excitotoxicity was caused by intravitreal injection of glutamate (50 nmol) in mice with long-term intraperitoneal injection of resveratrol (20 mg/Kg), and then retinas were subjected to Western blotting and paraffin section staining to analyze the effect of SIRT4 on excitotoxicity. We show that SIRT4 co-locates with Müller glial cell markers (GS and vimentin). The protein expression pattern of SIRT4 was similar to that of GS, and both increased with development. There were no significant retinal structure or electrophysiological function changes in 2-month SIRT4-deficient mice, while the expression of GS protein was decreased. Moreover, long-term administration of resveratrol can upregulate the expression of SIRT4 and GS while reducing the retinal injury caused by excessive glutamate. These results suggest that SIRT4 is highly expressed in retinal Müller glial cells and is relevant to the expression of GS. SIRT4 does not appear to be essential in retinal development, but resveratrol, as an activator of SIRT4, can upregulate GS protein expression and protect the retina from excitotoxicity.

First-line treatments for oral cancer typically include surgery, radiation, and in some cases, chemotherapy. Radiation and oral cancer chemotherapeutics confer cytotoxicity largely by inducing DNA damage, underscoring the importance of the cellular DNA damage repair and response pathways in cancer therapy. However, tumor recurrence and acquired resistance, following the initial response to treatment, remains as a major clinical challenge. By analyzing oral tumor cells derived from the primary and recurrent tumors of the same patient, our study revealed upregulated PARP1 expression in the recurrent tumor cells. Cisplatin and 5-fluorouracil treatment further augmented PARP1 expression in the recurrent, but not the primary, tumor cells. Post-treatment upregulation of PARP1 was dependent on the catalytic activities of PARP and CDK7. Consistent with the established function of PARP1 in DNA repair, we showed that overexpression of PARP1 rendered the primary tumor cells highly resistant to DNA damage treatment. Conversely, PARP inhibition partially reversed the treatment resistance in the recurrent tumor cells; combinatorial treatment using a PARP inhibitor and cisplatin/5-fluorouracil significantly sensitized the tumor response in vivo. Taken together, we reported here PARP1 upregulation as a clinically relevant mechanism involved in oral cancer recurrence, and suggested the clinical benefit of PARP inhibitors, currently approved for the treatment of several other types of cancer, in oral cancer.

Isoflavone, protein, and oil are the most important quality traits in soybean. Since these phenotypes are typically quantitative traits, quantitative trait locus (QTL) mapping has been an efficient way to clarify their complex and unclear genetic background. However, the low-density genetic map and the absence of QTL integration limited the accurate and efficient QTL mapping in previous researches. This paper adopted a recombinant inbred lines (RIL) population derived from ‘Zhongdou27’and ‘Hefeng25’ and a high-density linkage map based on whole-genome resequencing to map novel QTL and used meta-analysis methods to integrate the stable and consentaneous QTL. The candidate genes were obtained from gene functional annotation and expression analysis based on the public database. A total of 41 QTL with a high logarithm of odd (LOD) scores were identified through composite interval mapping (CIM), including 38 novel QTL and 2 Stable QTL. A total of 660 candidate genes were predicted according to the results of the gene annotation and public transcriptome data. A total of 212 meta-QTL containing 122 stable and consentaneous QTL were mapped based on 1,034 QTL collected from previous studies. For the first time, 70 meta-QTL associated with isoflavones were mapped in this study. Meanwhile, 69 and 73 meta-QTL, respectively, related to oil and protein were obtained as well. The results promote the understanding of the biosynthesis and regulation of isoflavones, protein, and oil at molecular levels, and facilitate the construction of molecular modular for great quality traits in soybean.

Heart failure (HF) leads to a progressive increase in morbidity and mortality rates. This study aimed to explore the transcriptional landscape during HF and identify differentially expressed transcripts (DETs) and alternative splicing events associated with HF. We generated a dog model of HF (n = 3) using right ventricular pacemaker implantation. We performed full-length transcriptome sequencing (based on nanopore platform) on the myocardial tissues and analyzed the transcripts using differential expression analysis and functional annotation methods [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses]. Additionally, we estimated the expression of the selected genes by quantitative real-time PCR (qRT-PCR) and detected the proportion of immune cells using flow cytometry. We found that increased B-type natriuretic peptide reduced ejection fraction, and apparent clinical signs were observed in the dog model of HF. We identified 67,458 transcripts using full-length transcriptome sequencing. A total of 785 DETs were obtained from the HF and control groups. These DETs were mainly enriched in the immune responses, especially Th1, Th2, and Th17 cell differentiation processes. Furthermore, flow cytometry results revealed that the proportion of Th1 and Th17 cells increased in patients with HF compared to controls, while the proportion of Th2 cells decreased. Differentially expressed genes in the HF and control groups associated with Th1, Th2, and Th17 cell differentiation were quantified using qRT-PCR. We also identified variable splicing events of sarcomere genes (e.g., MYBPC3, TNNT2, TTN, FLNC, and TTNI3). In addition, we detected 4,892 transcription factors and 406 lncRNAs associated with HF. Our analysis based on full-length transcript sequencing provided an analysis perspective in a dog model of HF, which is valuable for molecular research in an increasingly relevant large animal model of HF.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.

Active form of vitamin D (VitD) enhances human innate immunity against Mycobacterium tuberculosis (Mtb) infection. Our previous studies showed that MIR337-3p was highly expressed in lymphocytes of tuberculosis (TB) patients. Here, we identified the mechanism of MIR337-3p in the regulation of fast-acting anti-TB immunity by inhibiting VitD-dependent antimicrobial response pathways. While high-level MIR337-3p expression was induced by mycobacterial infection in cellular models and mice, TB patients exhibited significantly increased MIR337-3p in CD14+ monocytes/macrophages, innate-like Vγ2+ T cells, and CD8+ lymphocytes containing natural killer (NK)/innate lymphoid cells. MIR337-3p promoted the mycobacterial entry/infection and replication/growth in host target cells: macrophages and lung epithelial cells. Such MIR337-3p-enhanced pathogenicity coincided with the MIR337-3p depression of VitD-dependent antimicrobial response of cytochrome P450, family 27, subfamily b, polypeptide 1 (CYP27B1)/Beta-defensin 4 (DEFB4A)/ cathelicidin antimicrobial peptide CAMP pathways. Surprisingly, single MIR337-3p species could specifically target both the Toll-like receptor 4 (TLR4) and signal transducer and activator of transcription 3 (STAT3) 3′-untranslated regions (UTRs) to depress the TLR4/MYD88 and STAT3 signals and impair either of the two signals inhibiting the VitD-dependent antimicrobial pathways in macrophages. Concurrently, human peripheral blood mononuclear cells (PBMCs) expressing high-level MIR337-3p exhibited a reduced ability of innate cell populations to mount fast-acting cellular immunity against intracellular mycobacterial infection. Furthermore, a higher expression of Mir337-3p after mycobacterial infection of mice coincided with much greater colony-forming unit (CFU) counts in lungs and even the death of infected animals, whereas Mir337-3p inhibitor treatment of infected mice reduced Mir337-3p levels and reversed Mir337-3p-mediated increases in CFU counts. Thus, TB-driven single MIR337-3p species could specifically target/impair both TLR4/MYD88 and STAT3 activation signals, inhibiting VitD-dependent antimicrobial response and fast-acting anti-TB immunity, leading to enhanced pathogenicity.

Following Grandey's integrative model of emotional labor and emotion regulation, this study examined the relationships between university teachers' reported use of various emotional labor strategies and some antecedents (i. e., perceived emotional job demands and teaching support) and teaching efficacy. A sample of 643 university teachers from 50 public higher education institutions in an East China province responded to a questionnaire survey. The data analysis based on descriptive statistics and structural equation modeling showed that surface acting impeded teaching efficacy in instructional strategy and learning assessment, while deep acting and expression of naturally felt emotions enhanced teaching efficacy in course design, instructional strategy, and learning assessment. For the antecedents of university teachers' emotional labor strategies, teachers perceived that the emotional job demands of teaching facilitated their use of surface and deep acting; in contrast, teachers' perceived teaching support decreased their use of surface acting and increased their use of expression of naturally felt emotions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing acute respiratory tract infection in humans. The virus has the characteristics of rapid transmission, long incubation period and strong pathogenicity, and has spread all over the world. Therefore, it is of great significance to select appropriate animal models for antiviral drug development and therapeutic effect evaluation. Here, we review and compare the current animal models of SARS-CoV-2.

Signal transducer and activator of transcription-3 (STAT3) plays an important role in biological balance. Our and others previous studies implied that STAT3 had a great effect on fast-acting innate immunity against tuberculosis (TB). We hypothesized that stat3 SNP down-regulation of STAT3 leads to a change in susceptibility to TB in humans. To test this hypothesis, we investigated STAT3 SNPs using SNP scan™ technique in a case-control study of TB patients (n = 470) and HC subjects (n = 356), and then conducted functional studies of them using cellular models. We found that SNPs in STAT3 3`-UTR of rs1053004 TT and rs1053005 AA genotypes or T-A haplotype were associated with susceptibility to TB or TB severity. While the TT/AA genotype correlated with the low constitutive expression of stat3 and IL-17A in PBMC, the variant stat3 of rs1053004-rs1053005 T-A haplotype indeed reduced stat3 expression in reporter assays. Interestingly, host PBMC expressing the rs1053005 AA genotype and low constitutive stat3 exhibited the reduced ability to mount fast-acting innate immunity against mycobacterial infection in cellular models. Finally, mechanistic experiments showed that the STAT3 down-regulation broadly depressed STAT3 downstream anti-mycobacterial activities involving VDR-related CAMP pathway as well as IL-32, iNOS and autophagy mechanisms, leading to an enhanced mycobacterial infection. The findings of this study suggest that low constitutive stat3 derived from the TT/AA genotype/T-A haplotype acts to down-regulate STAT3, depressing multiple anti-mycobacterial pathways/mechanisms downstream, which leads to an enhanced mycobacterial infection or TB in high-risk individuals.

MicroRNAs (miRNAs) play key roles in many physiologic and pathologic processes, including autophagy. Autophagy is cellular in an emergency response mechanism of environment stress, but their complex molecular regulatory mechanism under low-temperature stress is largely unknown in shrimp, especially miRNA-mediated regulation of autophagy in low-temperature tolerance. In this article, a shrimp PvTOR and miRNA pva-miR-151 cooperation in response to low-temperature stress has been reported. Pva-miR-151 showed expression patterns opposite to target PvTOR under low-temperature stress. The pva-miR-151 targets the 3′-UTR region of PvTOR, regulate the formation of autophagosome, which contribute to the degradation and recycling of damaged organelles. In addition, the low-temperature tolerance was correlated positively with autophagy in shrimp. Silenced pva-miR-151 increased sensitivity to low-temperature stress, whereas overexpression pva-miR-151 decreased the expression of PvTOR and p-TOR and increased tolerance to low-temperature stress by improving the formation of autophagosome and total hemocyte count. In addition, the TOR activator 3BDO can partially rescue autophagy induced by overexpression of pva-miR-151; these results indicate that miR-151 was necessary for the low-temperature tolerance in shrimp. Taken together, we provide a novel strategy and mechanism for shrimp breeding to improve shrimp low-temperature tolerance.

Kolmer–Agduhr (KA) cells are a subgroup of interneurons positioned adjacent to the neurocoele with cilia on the apical surface protruding into the central canal of the spinal cord. Although KA cells were identified almost a century ago, their development and functions are only beginning to be unfolded. Recent studies have revealed the characteristics of KA cells in greater detail, including their spatial distribution, the timing of their differentiation, and their specification via extrinsic signaling and a unique combination of transcription factors in zebrafish and mouse. Cell lineage-tracing experiments have demonstrated that two subsets of KA cells, named KA’ and KA” cells, differentiate from motoneuronal progenitors and floor-plate precursors, respectively, in both zebrafish and mouse. Although KA’ and KA” cells originate from different progenitors/precursors, they each share a common set of transcription factors. Intriguingly, the combination of transcription factors that promote the acquisition of KA’ cell characteristics differs from those that promote a KA” cell identity. In addition, KA’ and KA” cells exhibit separable neuronal targets and differential responses to bending of the spinal cord. In this review, we summarize what is currently known about the genetic programs defining the identities of KA’ and KA” cell identities. We then discuss how these two subgroups of KA cells are genetically specified.

Aim: We aim to study clinically and pathologically whether narrow resection margin (1 cm) and narrow resection margin (

Background: Exosomes are cell-derived vesicles and bear a specific set of nucleic acids including DNA (exoDNA). Thus, this study is to explore whether exoDNA in malignant pleural effusions (MPEs) could be a novel DNA source for mutation detection of epidermal growth factor receptor (EGFR).Methods: In this study, 52 lung adenocarcinoma patients were enrolled, and EGFR mutation status was detected with tumor tissues as well as cell blocks and exosomes in MPEs. The sensitivity, specificity and consistency of EGFR detection using exosomes were evaluated, compared with gene detection using tumor tissues and cell blocks. And the clinical response of patients who were detected as EGFR mutation in exosomes and treated with EGFR tyrosine kinase inhibitor (EGFR-TKI) was explored.Results: Gene detection using exosomes showed sensitivity of 100%, specificity of 96.55% and coincidence rate of 98.08% (Kappa = 0.961, P < 0.001), compared with detection using tumor tissues and cell blocks. After EGFR-TKI treatment, patients detected as EGFR mutation by exosomes showed efficacy rate of 83% and disease control rate of 100%. And patients who were detected as wild type in tumor tissues or cell blocks but EGFR mutation in exosomes turned up as PR or SD.Conclusions: These results demonstrated that exoDNA in MPEs could be used as a DNA source for EGFR detection in lung adenocarcinoma.