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Diabetes is one of the most common metabolic diseases worldwide, leading to complications, mortality, and significant healthcare expenditures, which impose a substantial social and financial burden globally. A diabetic environment can induce metabolic changes, negatively affecting tendon homeostasis, leading to alterations in biomechanical properties and histopathology. Numerous studies have investigated the mechanisms through which diabetes exerts pathological effects on tendons, including increased free radical production, oxidative stress, inflammatory responses, deposition of advanced glycation end products (AGEs), and microvascular changes. These metabolic changes damages tendon structure, biomechanics, and tendon repair processes. The proliferation of tendon stem cells decreases, apoptosis increases, and abnormal differentiation, along with abnormal expression of myofibroblasts, ultimately lead to insufficient tendon repair, fibrosis, and remodeling. Although researches unveiling the effects of diabetes on tendinopathy, fibrosis or contracture, and tendon injury healing are growing, systematic understanding is still lacking. Therefore, this review summarizes the current research status and provides a comprehensive overview, offering theoretical guidance for future in-depth exploration of the impact of diabetes on tendons and the development of treatments for diabetes-related tendon diseases.

Objective: This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism. Methods: A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed. Results: Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers. Conclusion: These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

Abstract Objective Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. Methods The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. Results Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. Conclusion This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.

Abstract Suicide is prevalent among young adults, and epidemiological studies indicate that insomnia, nightmares, and depression are significantly associated with a high incidence of suicidal ideation (SI). However, the causal relationship between these factors and SI remains unclear. Therefore, the purpose of this study was to examine the association between nightmares and depression and insomnia and SI in young adults, as well as to develop a mediation model to investigate the causal relationship between insomnia, nightmare, depression, and SI. We assessed insomnia, nightmares, depression, and SI in 546 young adults using the Insomnia Severity Scale (ISI), Disturbing Dream and Nightmare Severity Scale (DDNSI), Depression Study Scale (CESD-20), and Columbia-Suicide Severity Rating Scale (C-SSRS). Using the Bootstrap method, the mediation effects of nightmares and depression between insomnia and SI were calculated. The results demonstrated that nightmares and depression fully mediated the relationship between insomnia and SI, including the chain-mediation of insomnia and SI between nightmare and depression with an effect value of 0.02, 95% CI 0.01–0.04, and depression as a mediator between insomnia and SI with an effect value of 0.22, 95% CI 0.15–0.29. This study found that depression and nightmares may be risk and predictive factors between insomnia and SI, which implies that the assessment and treatment of depression and the simple or linked effect of nightmares play crucial roles in preventing SI in young adults.

Background: Identifying the factors influencing mental health of mothers at critical stages of childrearing is significant for the implementation of effective promotion policies and counselling activities. Objective: This study aimed to investigate the relationships between children's feeding difficulties, marital quality, parenting quality and maternal mental health risks amidst Chinese mothers with high and low social support using a multi-group structural equation modelling approach. Participants: A cross-sectional study was conducted in Wenzhou, China and a total of 772 mothers with children aged 0–3 were surveyed by using purposive sampling. Findings: Results showed that of the 772 participants, 23.6 % reported anxiety, 50.1 % reported depression, 91.2 % reported insomnia, and 24 % reported feeding difficulties. The joint occurrence of multiple forms of mental problems is the most commonly reported features of mental health risks among mothers. The positive association between feeding difficulties of children and mental health risks of mothers was mediated by marital quality and parenting quality. In addition, feeding difficulties were not related to mental health risks in high social support group but all the relationships were significant in low social support group. Conclusions: These findings highlight the importance of the specific interventions to enhance social support, marital quality and parenting quality for improving mental health of mothers of children with feeding difficulties.

BackgroundUnderstanding the interplay between psychopathology of alcohol withdrawal syndrome (AWS) in alcohol use disorder (AUD) patients may improve the effectiveness of relapse interventions for AUD. Network theory of mental disorders assumes that mental disorders persist not of a common functional disorder, but from a sustained feedback loop between symptoms, thereby explaining the persistence of AWS and the high relapse rate of AUD. The current study aims to establish a network of AWS, identify its core symptoms and find the bridges between the symptoms which are intervention target to relieve the AWS and break the self-maintaining cycle of AUD.MethodsGraphical lasso network were constructed using psychological symptoms of 553 AUD patients. Global network structure, centrality indices, cluster coefficient, and bridge symptom were used to identify the core symptoms of the AWS network and the transmission pathways between different symptom clusters.ResultsThe results revealed that: (1) AWS constitutes a stable symptom network with a stability coefficient (CS) of 0.21-0.75. (2) Anger (Strength = 1.52) and hostility (Strength = 0.84) emerged as the core symptom in the AWS network with the highest centrality and low clustering coefficient. (3) Hostility mediates aggression and anxiety; anger mediates aggression and impulsivity in AWS network respectively.ConclusionsAnger and hostility may be considered the best intervention targets for researching and treating AWS. Hostility and anxiety, anger and impulsiveness are independent but related dimensions, suggesting that different neurobiological bases may be involved in withdrawal symptoms, which play a similar role in withdrawal syndrome.

Microwave heating has the characteristics of simple control and high efficiency, in which electromagnetic force plays an important role. Using the UDF function and energy equation in FLUENT software, the electromagnetic force model in the tube is established. The mixing process of cerium chloride solution under different heating modes, the mixing effect of Lorentz force and the preparation process of cerium oxide under different inlet material velocities were numerically simulated. CFD-Post and MATLAB software are used to post-process the data of the whole fluid area. Through the above analysis, the best process conditions of numerical simulation and experiment are finally determined. The results show that microwave heating has better mixing effect and lower material loss compared with conventional heating, in which electromagnetic force plays a promoting role; Under the condition of microwave heating, the product conversion rate is high, and the concentration of cerium oxide is high and distributed evenly. The more appropriate mixing method of cerium chloride and preparation method of cerium oxide are microwave heating, and the more appropriate inlet velocity of materials is 0.15 m/s.

Sweet cherry has a short shelf life due to the occurrence of senescence and fungal infection after harvest. This study aimed to study the effects of high-voltage electrostatic field (HVEF) on the physicochemical properties and fungal composition of sweet cherry during cold storage. The experiments were conducted at 4 °C for 28 days and the quality indicators were determined every 7 days during the period of storage. The fungal composition on sweet cherry was determined using high-throughput sequencing. The results showed that HVEF could better maintain the total soluble solids and inhibit the respiration of cherries. The decay incidence in sweet cherries was decreased by HVEF during cold storage. High-throughput sequencing revealed that HVEF could alter the fungal community and increase the fungal diversity on sweet cherries. Compared with the control group, HVEF decreased the abundance of Alternaria and Cladosporium on sweet cherries, while Aureobasidium, as a nonpathogenic fungus, increased and became the dominant strain at the end of the storage period. In summary, HVEF can improve the physicochemical properties of sweet cherry by inhibiting respiration and can reduce decay incidence by inhibiting specific pathogenic fungi. HVEF is expected to become an efficient and promising technology for the preservation of fruit.

ObjectivePrevious research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1.MethodsThis case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders.ResultsActive smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance.ConclusionWe provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

IntroductionPatients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD.MethodsWe recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data.ResultsThe T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness.Conclusion and significanceThe combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

Objective: Preventing adverse events due to unstable oxygen saturation (SpO2) at night in pregnant women is of utmost importance. Poor sleep has been demonstrated to impact SpO2 levels. Nowadays, many gravida have a habit of prolonged exposure to light before sleep, which can disrupt their sleep. Therefore, this study aimed at investigate the relationship between lights-out time, sleep parameters and SpO2, exploring the underlying mechanisms. Methods: The data of 2881 eligible subjects from the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be and Sleep Disordered Breathing (nuMOM2b-SDB) database were analyzed. Multiple linear regression models were used to investigate the relationship between lights-out time and SpO2. In addition, restricted cubic splines (RCS) were employed to fit the nonlinear correlation between the two variables. The smoothing curve method was further utilized to depict the relationship between lights-out time and SpO2 based on various subgroup variables. Results: All participants were categorized according to race/ethnicity. A negative correlation was observed between nighttime lights-out time and average value of SpO2 (Avg-SpO2) (β = −0.05, p = 0.010). RCS revealed a U-shaped relationship between lights-out time and Avg-SpO2, with the turning point at 22:00. The subcomponent stratification results indicated that the Avg-SpO2 and minimum value of SpO2(Min-SpO2) of advanced maternal age decreased as the lights-out time was delayed. Furthermore, overweight and obese gravida showed lower Avg-SpO2 and Min-SpO2 levels than normal weight. Conclusions: A U-shaped relationship was identified between lights-out time and nocturnal Avg-SpO2 during early pregnancy, with the inflection at 22:00. Notably, later lights-out times are associated with lower levels of Min-SpO2 for advanced maternal age. The findings suggest that appropriately adjusting the duration of light exposure before sleep and maintaining a relatively restful state may be more beneficial for the stability of SpO2 in pregnant women. Conversely, deviations from these practices could potentially lead to pathological alterations in SpO2 levels.

BackgroundThe importance of healthy aging is growing in China as it has the largest number of older adults in the world and is one of the fastest-aging countries. This study aimed to examine the predictive value of regular physical exercise in relation to the physical, emotional, and cognitive health among samples of adults aged ≥60 years in China during an 8-year period.MethodsA total of 10,691 older adults were extracted from two waves of national data from the China Family Panel Studies in 2010 and 2018. To minimize the impact of selection bias on the findings, a longitudinal propensity score matching (LPSM) method was used to examine the relationships between regular physical exercise and emotional health (depression), between regular physical exercise and physical health (instrumental activities of daily living), and between regular physical exercise and cognitive health (cognitive ability) of older adults. After LPSM, 856 older adults were included in the study. In the regular physical exercise group, the average age of participants at baseline year was 65.67 years, with an average age of 65.90 years for 238 men and 65.45 years for 190 women, and in the non-physical exercise group, their average age at baseline year was 65.70 years, with an average age of 65.45 years for 253 men and 65.98 years for 175 women.ResultsLPSM indicated that regular physical exercise has been found to be effective in improving physical function and reducing depressive symptoms in old adults, even after controlling for background differences. However, the sensitivity analysis suggests that the positive association between regular physical exercise and cognitive function may not be sufficiently valid.ConclusionThe findings of this study indicate that engaging in long-term structured and repetitive physical exercise can have a significant positive effect on reducing depressive symptoms and improving the physical function of older adults. As a result, incorporating regular physical exercise into the lifestyle of older adults is recognized as an effective strategy for promoting healthy aging and reducing the strain on public health resources.

IntroductionSorghum plant color is the leaf sheath/leaf color and is associated with seed color, tannin and phenol content, head blight disease incidence, and phytoalexin production.ResultsIn this study, we evaluated plant color of the sorghum mini core collection by scoring leaf sheath/leaf color at maturity as tan, red, or purple across three testing environments and performed genome-wide association mapping (GWAS) with 6,094,317 SNPs markers.Results and DiscussionEight loci, one each on chromosomes 1, 2, 4, and 6 and two on chromosomes 5 and 9, were mapped. All loci contained one to three candidate genes. In qPC5-1, Sobic.005G165632 and Sobic.005G165700 were located in the same linkage disequilibrium (LD) block. In qPC6, Sobic.006G149650 and Sobic.006G149700 were located in the different LD block. The single peak in qPC6 covered one gene, Sobic.006G149700, which was a senescence regulator. We found a loose correlation between the degree of linkage and tissue/organ expression of the underlying genes possibly related to the plant color phenotype. Allele analysis indicated that none of the linked SNPs can differentiate between red and purple accessions whereas all linked SNPs can differentiate tan from red/purple accessions. The candidate genes and SNP markers may facilitate the elucidation of plant color development as well as molecular plant breeding.

The field of epigenetics pertains to alterations in gene function that are inherited without changes in the DNA sequence, including histone modifications, post-translational modifications of amino acids, and covalent modifications of DNA bases. These alteration pathways modulate the transformation of genotypes into specific phenotypes. Epigenetics plays major roles in cell growth, development, and differentiation by dynamically regulating gene transcription and ensuring genomic stability. This regulation is performed by three key players: writers, readers, and erasers. In recent years, epigenetic proteins have been found to have crucial roles in epigenetic regulation, and have become important targets in drug research and development. Although targeted therapy is an essential treatment strategy, the effectiveness of targeted drugs is often limited by drug resistance, thus posing a major dilemma in clinical practice. Targeted protein degradation technologies, including proteolysis-targeting chimeras (PROTACs), have great potential in overcoming drug resistance and targeting undruggable targets. PROTACs are gaining increasing attention in the treatment of various epigenetic diseases. In this review, we summarize recently developed degraders targeting epigenetic readers, writers, and erasers. Additionally, we outline new applications for epigenetic protein degraders. Finally, we address several unresolved challenges in the PROTAC field, and suggest potential solutions from our perspective. As the field continues to advance, the integration of these innovative methods holds great promise in addressing the challenges associated with PROTAC development.

Appropriate reference genes must be selected for accurate qRT-PCR data to conduct a thorough gene expression analysis in the sorghum aphid (Melanaphis sacchari, Hemiptera, Aphididae). This approach will establish a foundation for gene expression analysis and determines the efficacy of RNA interference in the sorghum aphid. Nine potential reference genes, including Actin, 18S, GAPDH, RPL7, EF-1α, EF-1β, 28S, HSP70, and TATA, were assessed under various experimental conditions to gauge their suitability based on qRT-PCR Ct values. The stability of these candidate reference genes in diverse experimental setups was analyzed employing several techniques, including the ΔCt comparative method, geNorm, Normfinder, BestKeeper, and RefFinder. The findings revealed that the quantity of ideal reference genes ascertained by the geNorm method for diverse experimental conditions remained consistent. For the developmental stages of the sorghum aphid, RPL7 and 18S proved to be the most dependable reference genes, whereas GAPDH and EF-1β were recommended as the most stable reference genes for different tissues. In experiments involving wing dimorphism, EF-1α and GAPDH were identified as the optimal reference gene pair. Under varying temperatures, EF-1α and EF-1β were found to be the most dependable gene pair. For studies focusing on insecticide susceptibility, 18S and TATA emerged as the most stable candidate reference genes. Across all experimental conditions, EF-1α and EF-1β was the optimal combination of reference genes in the sorghum aphid. This research has pinpointed stable reference genes that can be utilized across various treatments, thereby enhancing gene expression studies and functional genomics research on the sorghum aphid.

Abstract The traditional identification methods of direct current‐to‐direct current (DC–DC) converters usually consider the common situation where the training and testing sets have the same input voltage. In real‐world applications, the actual input voltage may fluctuate beyond its original value, thus negatively affecting the parameter identification accuracy. Therefore, this paper presents a parameter identification method under fluctuating input voltages. Firstly, to increase the identification accuracy, the paper proposes the coefficient of variation method to extract key features from all time‐ and frequency‐domain features as training data. Then, for fluctuating input voltages, the paper adds the input voltages into the training data to build the parameter identification network based on Dendrite Net. When using the established network to identify component parameters in practical applications, the actual input voltage may change to an unknown value because of irregular fluctuation. Hence, the actual input voltage needs to be identified before identifying the component parameters of a DC–DC converter. Finally, the paper builds the input voltage identification network. By combining the identification results of the actual input voltage, the parameter identification under fluctuating input voltages can be completed. The simulation and hardware experiments results validate the practicability and effectiveness of the proposed method.

Abstract Background Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility. Methods A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses. Results Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging. Conclusions De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.

Abstract Introduction Cigarette smoking increases both the risk for insulin resistance and amyloid‐β (Aβ) aggregation, and impaired brain insulin/insulin‐like growth factor 1 (IGF1) signaling might increase risk factors for Alzheimer's disease (AD). We aimed to investigate the association among cerebrospinal fluid (CSF) insulin sensitivity/IGF1, glucose/lactate, and Aβ42 and further explore whether insulin sensitivity contributed to the risk for AD in active smokers. Methods In this cross‐sectional study, levels of insulin, IGF1, and lactate/glucose of 75 active smokers and 78 nonsmokers in CSF were measured. Three polymorphisms regulating IGF1 were genotyped. Analysis of variance was used to compare differences of variables between groups. Partial correlation was performed to test the relationship between CSF biomarkers and smoking status. General linear models were applied to test the interaction of the effect of single nucleotide polymorphisms and cigarette smoking on CSF IGF1 levels. Results In the CSF from active smokers, IGF1 and lactate levels were significantly lower (p = .016 and p = .010, respectively), whereas Aβ42 (derived from our earlier research) and insulin levels were significantly higher (p

ObjectiveProlonged sleep onset latency (PSOL) and age have been linked to ischemic stroke (IS) severity and the production of chemokines and inflammation, both of which contribute to IS development. This study aimed to explore the relationship between chemokines, inflammation, and the interplay between sleep onset latency (SOL) and age in influencing stroke severity.MethodsA cohort of 281 participants with mild to moderate IS was enrolled. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and SOL was recorded. Serum levels of macrophage inflammatory protein-1alpha (MIP-1α), macrophage inflammatory protein-1beta (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured.ResultsNIHSS scores of middle-aged participants with PSOL were significantly higher than those with normal sleep onset latency (NSOL) (p = 0.046). This difference was also observed when compared to both the elderly with NSOL (p = 0.022), and PSOL (p

The Monocyte chemoattractant protein-1 (MCP-1), also referred to as chemokine ligand 2 (CCL2), belongs to the extensive chemokine family and serves as a crucial mediator of innate immunity and tissue inflammation. It has a notable impact on inflammatory conditions affecting the kidneys. Upon binding to its receptor, MCP-1 can induce lymphocytes and NK cells’ homing, migration, activation, differentiation, and development while promoting monocytes’ and macrophages’ infiltration, thereby facilitating kidney disease-related inflammation. As a biomarker for kidney disease, MCP-1 has made notable advancements in primary kidney diseases such as crescentic glomerulonephritis, chronic glomerulonephritis, primary glomerulopathy, idiopathic proteinuria glomerulopathy, acute kidney injury; secondary kidney diseases like diabetic nephropathy and lupus nephritis; hereditary kidney diseases including autosomal dominant polycystic kidney disease and sickle cell kidney disease. MCP-1 not only predicts the occurrence, progression, prognosis of the disease but is also closely associated with the severity and stage of nephropathy. When renal tissue is stimulated or experiences significant damage, the expression of MCP-1 increases, demonstrating a direct correlation with the severity of renal injury.

Summary: Background: The use of artificial intelligence (AI) in detecting colorectal neoplasia during colonoscopy holds the potential to enhance adenoma detection rates (ADRs) and reduce adenoma miss rates (AMRs). However, varied outcomes have been observed across studies. Thus, this study aimed to evaluate the potential advantages and disadvantages of employing AI-aided systems during colonoscopy. Methods: Using Medical Subject Headings (MeSH) terms and keywords, a comprehensive electronic literature search was performed of the Embase, Medline, and the Cochrane Library databases from the inception of each database until October 04, 2023, in order to identify randomized controlled trials (RCTs) comparing AI-assisted with standard colonoscopy for detecting colorectal neoplasia. Primary outcomes included AMR, ADR, and adenomas detected per colonoscopy (APC). Secondary outcomes comprised the poly missed detection rate (PMR), poly detection rate (PDR), and poly detected per colonoscopy (PPC). We utilized random-effects meta-analyses with Hartung-Knapp adjustment to consolidate results. The prediction interval (PI) and I2 statistics were utilized to quantify between-study heterogeneity. Moreover, meta-regression and subgroup analyses were performed to investigate the potential sources of heterogeneity. This systematic review and meta-analysis is registered with PROSPERO (CRD42023428658). Findings: This study encompassed 33 trials involving 27,404 patients. Those undergoing AI-aided colonoscopy experienced a significant decrease in PMR (RR, 0.475; 95% CI, 0.294–0.768; I2 = 87.49%) and AMR (RR, 0.495; 95% CI, 0.390–0.627; I2 = 48.76%). Additionally, a significant increase in PDR (RR, 1.238; 95% CI, 1.158–1.323; I2 = 81.67%) and ADR (RR, 1.242; 95% CI, 1.159–1.332; I2 = 78.87%), along with a significant increase in the rates of PPC (IRR, 1.388; 95% CI, 1.270–1.517; I2 = 91.99%) and APC (IRR, 1.390; 95% CI, 1.277–1.513; I2 = 86.24%), was observed. This resulted in 0.271 more PPCs (95% CI, 0.144–0.259; I2 = 65.61%) and 0.202 more APCs (95% CI, 0.144–0.259; I2 = 68.15%). Interpretation: AI-aided colonoscopy significantly enhanced the detection of colorectal neoplasia detection, likely by reducing the miss rate. However, future studies should focus on evaluating the cost-effectiveness and long-term benefits of AI-aided colonoscopy in reducing cancer incidence. Funding: This work was supported by the Heilongjiang Provincial Natural Science Foundation of China (LH2023H096), the Postdoctoral research project in Heilongjiang Province (LBH-Z22210), the National Natural Science Foundation of China’s General Program (82072640) and the Outstanding Youth Project of Heilongjiang Natural Science Foundation (YQ2021H023).

In order to integrate the concept of intangible cultural heritage (ICH) protection into the construction of smart cities, realize the organic integration of smart cities and cultural heritage, and improve the cultural experience of urban residents and tourists, this study explores an interactive design scheme of smart cities application interface applied to ICH protection to meet the needs of protection and inheritance. Firstly, the ICH of Chongqing is sorted out and classified. The ICH-related APP interfaces in the market are analyzed through investigation. Secondly, an image recognition algorithm of ICH based on deep learning (DL) technology is proposed and applied in APP to realize automatic recognition and introduction of ICH. Finally, a set of APP interface interaction design schemes is designed based on user habits and visual feelings to enhance user experience. The experimental results reveal: (1) The model for recognizing ICH images using the convolutional neural network (CNN) has higher recognition accuracy, recall, and F1 value than the model without CNNs; (2) After incorporating transfer learning (TL) into the model, the recognition accuracy, recall, and F1 value of the model have further improved; (3) The survey results show that the Chongqing ICH APP interface system based on DL technology, user habits, and visual perception performs better in terms of user experience, usability, and other aspects. This study aims to design an APP interface system for the Chongqing ICH based on DL technology, user habits, and visual perception, to improve user experience and usability. Future research directions can further optimize image recognition algorithms to improve ICH's recognition accuracy and efficiency. Meanwhile, new technologies, such as virtual reality, are combined to enhance users' interactive experience and immersion.

The spray pyrolysis method has the disadvantage of nozzle plugging, and the conventional heating model causes a large temperature gradient, which leads to unevenly heated reactants. This study used cerium chloride heptahydrate and Venturi reactor as raw material and core equipment. The technology of microwave heating was combined to prepare single-phase sphere-like cerium oxide. The mean size of the particles was near 80nm. The product was characterized via XRD, SEM, and EDS technologies. The purity, morphology, and energy consumption were compared with the conventional spray pyrolysis. Fluent software coupled with HFSS was employed to simulate the effects of different process conditions on products’ purity and temperature field in the reactor. There was good correspondence between experimental and simulated results. The results showed that as gas velocity Vg increased, the tendency of the temperature field distribution did not change. The lowest mass fraction of chlorine element reached 0.13% when the gas inlet velocity reached 1.7 m/s. When the material inlet velocity was 0.05 m/s, the mass fraction of the chlorine element was below 0.1%, which indicated that the reactants had a complete reaction. It has been calculated that the heating cost, energy consumption, and CO2 emission decreased sharply compared with the spray pyrolysis method.

Abstract Melilotus officinalis is an important legume crop with forage and Chinese medicinal value. The unknown genome of M. officinalis restricted the domestication and utilization of the species and its germplasm resource diversity. A chromosome‐scale assembly of the M. officinalis genome was assembled and analysed. The 976.27 Mb of genome was divided into eight chromosomes covering 99.16% of the whole genome. A total of 50022 genes were predicted in the genome. M. officinalis and Melilotus albus shared a common ancestor 0.5–5.65 million years ago (MYA). A genome‐wide doubling event occurred 68.93 MYA according to the synonymous nucleotide‐substitution values. A total of 552102 tandem repeats were predicted, and 46004 SSR primers of TRs with 10 or more base pairs were developed and designed. The elucidation of the M. officinalis genome provides a compelling model system for studying the genetic, evolutionary and biosynthesis of this legume.

ObjectiveAlcohol use disorder (AUD) is the second most prevalent mental disorder and might be related to depression. Major vault protein (MVP) is a cytoplasmic protein related to vesicle transport. The present study aimed to investigate the interaction between a genetic variant (MVP rs4788186) and depression in adult male Han Chinese with AUD during withdrawal.MethodsAll participants (N = 435) were diagnosed with AUD. Alcohol dependence level was measured using the Michigan Alcoholism Screening Test, and depression was measured using the self-rating depression scale. Genomic DNA was extracted from peripheral blood and genotyped.ResultsHierarchical regression analysis identified an interaction between MVP rs4788186 and alcohol dependence level for depression (β = −0.17, p

BackgroundSystemic inflammation is associated with the prognosis of colorectal cancer (CRC). The current study aimed to construct a comprehensively inflammatory prognostic scoring system named risk score (RS) based on eosinophil- and basophil-related markers and assess its prognostic value in patients with stage II and stage III CRC.Patients and methodsA total of 3,986 patients were enrolled from January 2007 to December 2013. The last follow-up time was January 2019. They were randomly assigned to the training set and testing set in a 3:2 split ratio. Least absolute shrinkage and selection operator (LASSO)–Cox regression analysis was performed to select the optimal prognostic factors in the construction of RS. The Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC), and Cox analysis were used to evaluate the association between RS and overall survival (OS).ResultsIn the training set, all inflammatory markers showed certain prognostic values. Based on LASSO-Cox analysis, nine markers were integrated to construct RS. The Kaplan–Meier curve showed that a higher RS (RS > 0) had a significantly worse prognosis (log-rank p< 0.0001). RS (>0) remained an independent prognostic factor for OS (hazard ratio (HR): 1.70, 95% confidence interval (CI), 1.43–2.03, p< 0.001). The prognostic value of RS was validated in the entire cohort. Time-dependent ROC analysis showed that RS had a stable prognostic effect throughout the follow-up times and could enhance the prognostic ability of the stage by combination. Nomogram was established based on RS and clinicopathological factors for predicting OS in the training set and validated in the testing set. The area under the curve (AUC) values of the 3-year OS in the training and testing sets were 0.748 and 0.720, respectively. The nomogram had a satisfactory predictive accuracy and had better clinical application value than the tumor stage alone.ConclusionsRS might be an independent prognostic factor for OS in patients with stage II and III CRC, which is helpful for risk stratification of patients. Additionally, the nomogram might be used for personalized prediction and might contribute to formulating a better clinical treatment plan.

ObjectiveAlcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promising candidate for treating alcohol withdrawal symptoms. Previous studies indicated that people with different genotypes of OXTR rs2254298 were reported to suffer from more significant depressive or heightened anxiety symptoms when experiencing early adversity. The present study aims to explore the modulatory role of the polymorphism OXTR rs2254298 on mood disorders during alcohol withdrawal and to help researchers better understand and develop effective relapse prevention and interventions for alcohol use disorders.MethodsWe recruited 265 adult Chinese Han men with AUD. Anxiety and depressive symptoms were measured using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Alcohol dependence levels were measured using Michigan Alcoholism Screening Test. Genomic DNA extraction and genotyping from participants’ peripheral blood samples.ResultFirst, a multiple linear regression was used to set the alcohol dependence level, OXTR.rs2254298, interaction terms as the primary predictor variable, and depression or anxiety as an outcome; age and educational years were covariates. There was a significant interaction between OXTR rs2254298 and alcohol dependence level on anxiety (B = 0.23, 95% confidence interval [CI]: 0.01–0.45) but not on depression (B = −0.06, 95% CI: −0.30 – 0.18). The significance region test showed that alcohol-dependent men who are GG homozygous were more likely to experience anxiety symptoms than subjects with the A allele (A allele: β = 0.27, p

BackgroundTo comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.MethodsThe association between IGF2 methylation in PBLs and CRC risk was initially evaluated in a case-control study and then validated in a nested case-control study and a twins’ case-control study, respectively. Meanwhile, an initial CRC patient cohort was used to assess the effect of IGF2 methylation on CRC prognosis and then the finding was validated in the EPIC-Italy CRC cohort and TCGA datasets. A propensity score (PS) analysis was performed to control for confounders, and extensive sensitivity analyses were performed to assess the robustness of our findings.ResultsPBL IGF2 hypermethylation was associated with an increased risk of CRC in the initial study (ORPS-adjusted, 2.57, 95% CI: 1.65 to 4.03, P

Abstract Adenovirus belongs to the family of Adenoviridae. As a vaccine carrier, it has high safety and stimulates the body to produce cellular immunity and humoral immunity. This study prepared an adenoviral vector-specific single-domain antibody for use in adenovirus identification and purification. We successfully constructed a single domain antibody phage display library with a capacity of 1.8 × 109 by immunizing and cloning the VHH gene from Bactrian camel. After the second round of biopanning, clones specific for adenovirus were screened using phage ELISA. Twenty-two positive clones were obtained, and two clones with the highest binding affinity from ELISA were selected and named sdAb 5 and sdAb 31 for further application. The recombinant single-domain antibody was solublely expressed in E. coli and specifically bound to adenoviruses rAd26, ChAd63 and HAd5 in ELISA and live cell immunofluorescence assays. We established an effective method for immunoaffinity purification of adenovirus by immobilizing the single domain antibody to Sepharose beads, and it may be used to selectively capture adenoviruses from cell culture medium. The preparation of the adenovirus-specific single-domain antibody lays a foundation for the one-step immunoaffinity purification and identification of adenoviruses.

Adaptive sampling of the marine environment may improve the accuracy of marine numerical prediction models. This study considered adaptive sampling path optimization for a three-dimensional (3D) marine observation platform, leading to a path-planning strategy based on evolutionary deep reinforcement learning. The low sampling efficiency of the reinforcement learning algorithm is improved by evolutionary learning. The combination of these two components as a new algorithm has become a current research trend. We first combined the evolutionary algorithm with different reinforcement learning algorithms to verify the effectiveness of the combination of algorithms with different strategies. Experimental results indicate that the fusion of the two algorithms based on a maximum-entropy strategy is more effective for adaptive sampling using a 3D marine observation platform. Data assimilation experiments indicate that adaptive sampling data from a 3D mobile observation platform based on evolutionary deep reinforcement learning improves the accuracy of marine environment numerical prediction systems.

Background Tannins are the main bottlenecks restricting the transformation efficiency of plants. Hongyingzi is a special tannin-containing sorghum cultivar used in brewing. Methods In this study, a highly efficient microprojectile transformation system for tannin-containing sorghum was successfully exploited using immature embryos (IEs) of Hongyingzi as explants. Results Hongyingzi presented two types of calli. Type II calli were found to be the most suitable and effective explants for transformation. After optimization of the geneticin (G418) concentration and tissue culture medium, an average transformation frequency of 27% was achieved. Molecular analyzis showed that all transgenic plants were positive and showed transgenes expression. The inheritance analyzis confirmed that the transgenes could be inherited into the next generation. Thus, we successfully established an efficient transformation system for tannin-containing sorghum and demonstrated the possibility of breaking the restriction imposed by tannins in plants.

ObjectiveInternet gaming disorder (IGD) can seriously impair an individual’s physical and mental health. However, unlike the majority of those suffering from substance addiction, individuals with IGD may recover without any professional intervention. Understanding the brain mechanisms of natural recovery from IGD may provide new insight into how to prevent addiction and implement more targeted interventions.MethodsSixty individuals with IGD were scanned by using a resting-state fMRI to assess brain region changes associated with IGD. After 1 year, 19 individuals with IGD no longer met the IGD criteria and were considered recovered (RE-IGD), 23 individuals still met the IGD criteria (PER-IGD), and 18 individuals left the study. The brain activity in resting state between 19 RE-IGD individuals and 23 PER-IGD individuals was compared by using regional homogeneity (ReHo). Additionally, brain structure and cue-craving functional MRIs were collected to further support the results in the resting-state.ResultsThe resting-state fMRI results revealed that activity in brain regions responsible for reward and inhibitory control [including the orbitofrontal cortex (OFC), the precuneus and the dorsolateral prefrontal cortex (DLPFC)] was decreased in the PER-IGD individuals compared to RE-IGD individuals. In addition, significant positive correlations were found between mean ReHo values in the precuneus and self-reported craving scores for gaming, whether among the PER-IGD individuals or the RE-IGD individuals. Furthermore, we found similar results in that brain structure and cue-craving differences exist between the PER-IGD individuals and RE-IGD individuals, specifically in the brain regions associated with reward processing and inhibitory control (including the DLPFC, anterior cingulate gyrus, insula, OFC, precuneus, and superior frontal gyrus).ConclusionThese findings indicate that the brain regions responsible for reward processing and inhibitory control are different in PER-IGD individuals, which may have consequences on natural recovery. Our present study provides neuroimaging evidence that spontaneous brain activity may influence natural recovery from IGD.

Abstract Background Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. However, no biomarker of impulsivity available so far. This study explored the association between cerebrospinal fluid (CSF) fibroblast growth factor 21 (FGF21), a key hormonal mediator of the stress response, and impulsivity in healthy subjects. Methods A total of 126 healthy persons subjected to surgery of anterior cruciate ligament were recruited in the present study. The impulsiveness of the subjects was evaluated by the Chinese version of the Barratt Impulsiveness Scale (BIS)-11 before surgery. CSF and blood samples of the subjects were collected before spinal anesthesia for surgery. The levels of FGF21, serotonin and dopamine in CSF and the level of FGF21 in blood of the subjects were measured by ELISA using commercial kits. Results Negative correlations were found between BIS-11 total score and either FGF21, serotonin or dopamine in CSF. However, BIS-11 total score was not correlated with FGF21 in blood. In addition, FGF21 was positively correlated with serotonin and dopamine in CSF, respectively. Multivariable linear regression models indicated that the decrease of FGF21 level associating with the decrease of serotonin and dopamine level in CSF contributed to the higher impulsivity. Furthermore, receiver operating characteristic curve (ROC) analysis indicated an important role of CSF FGF21 predicting high impulsivity. Conclusions FGF21, serotonin and dopamine in CSF associate with impulsivity in opposite directions. The decrease of CSF FGF21 is related to higher impulsivity, and indicate that CSF FGF21 may predict impulsivity in healthy subjects.

Multi-microgrid collaborative scheduling can promote the local consumption of renewable energy in the smart grid and reduce the operating costs of the power grid park. At the same time, the access of the distributed energy storage (ES) system provides an opportunity to further enhance the park’s peak shaving and valley filling capacity, thereby reducing costs. However, the uncertainty of photovoltaic (PV) power generation and load demand seriously affects the profit maximization of the microgrid in the park. To address this challenge, this paper proposes a stochastic optimal scheduling strategy for industrial park smart microgrids with multiple transformers based on the information gap decision theory (IGDT). We first introduce a revenue maximization model for industrial parks, incorporating a two-part tariff system and distributed ES. Subsequently, we employ an envelope constraint model to accurately represent the uncertainty associated with PV generation and load demand. By integrating these components, we establish the IGDT stochastic optimization scheduling model for industrial parks with multiple transformers. Finally, we simulate and analyze the performance of the proposed IGDT model under various cost deviation factors during typical spring and summer days. The simulation results demonstrate the effectiveness of the proposed control strategy in mitigating the impact of PV generation and load uncertainty on industrial parks. The IGDT-based scheduling approach provides an efficient solution for maximizing revenue and enhancing the operational stability of industrial park microgrids.

Although approved as an alcohol-abuse drug, disulfiram (DSF) exhibited potential anticancer activity when chelated with copper (Cu). However, the low level of intrinsic Cu, toxicity originated from exogenous Cu supplementation, and poor stability of DSF in vivo severely limited its application in cancer treatment. Herein, we proposed an in situ DSF antitumor efficacy triggered system, taking advantages of Cu-based metal-organic framework (MOF). In detail, DSF was encapsulated into Cu-MOF nanoparticles (NPs) during its formation, and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility. Notably, DSF loaded Cu-MOF NPs maintained stability and integrity without Cu2+ leakage in blood circulation, thus showing excellent biosafety. Once accumulating at tumor site, NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu2+ simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment. This profile lead to in situ chelation reaction between DSF and Cu2+, generating toxic DSF/Cu complex against tumor cells. Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs, which facilitated the tumor-specific chemotherapeutic effects of DSF. This system provided a promising strategy for the application of DSF in tumor therapy.

BackgroundPrevious studies suggest that alcohol dependence is associated with depression, however, the effect of alcohol dependence varies from individual to individual, which may be due to different genetic backgrounds. The interactions between alcohol dependence and different gene polymorphisms may finally shape the onset of depression. Neuropeptide Y (NPY), which can maintain homeostasis from high-stress stimulation, may protect individuals from the onset of depression. Here, we explored whether the NPY rs16147:T>C has an association with depression in individuals with alcohol dependence during the period of alcohol dependence withdrawal.MethodsA total of 455 males with alcohol dependence were recruited. The scale of Michigan Alcoholism Screening Test (MAST) and Self-Depression Scale (SDS) were respectively used to analyze the condition of alcohol dependence and depression. Genomic DNA was extracted from each blood sample and NPY polymorphisms were genotyped. The interaction between NPY rs16147:T>C and alcohol dependence on depression was first analyzed. Then, region of significance analysis was used to confirm which model provided the best fit for the interaction (diathesis-stress or differential susceptibility). Finally, by using internal replication analyses, the accuracy and robustness of the interaction results were improved.ResultsAlcohol dependence was positively correlated with depression. CC homozygotes of NPY rs16147:T>C exhibited less depression when exposed to low alcohol dependence, but more depression when exposed to high alcohol dependence. Individuals with the T allele showed the opposite result.ConclusionNPY rs16147:T>C might be correlated with susceptibility for depression in males during alcohol dependence withdrawal. The findings support the differential susceptibility model.

BackgroundLong-term alcohol exposure is associated with oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation, which may impair cognitive function. Probiotics supplements can significantly improve cognitive function in neurodegenerative diseases such as Alzheimer’s disease. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (LP-cs) on alcohol-induced cognitive dysfunction remains unclear.MethodsA mouse model of cognitive dysfunction was established by intraperitoneal injection of alcohol (2 g/kg body weight) for 28 days. Mice were pre-treated with LP-cs, and cognitive function was evaluated using the Morris water maze test. Hippocampal tissues were collected for biochemical and molecular analysis.ResultsLP-cs significantly ameliorated alcohol-induced decline in learning and memory function and hippocampal morphology changes, neuronal apoptosis, and synaptic dysfunction. A mechanistic study showed that alcohol activated protein kinase R-like endoplasmic reticulum kinase (PERK) signaling and suppressed brain derived neurotrophic factor (BDNF) levels via ER stress in the hippocampus, which LP-cs reversed. Alcohol activated oxidative stress and inflammation responses in the hippocampus, which LP-cs reversed.ConclusionLP-cs significantly ameliorated alcohol-induced cognitive dysfunction and cellular stress. LP-cs might serve as an effective treatment for alcohol-induced cognitive dysfunction.

Shewanella baltica is the dominant bacterium that causes spoilage of seafood. RpoS is an alternative sigma factor regulating stress adaptation in many bacteria. However, the detailed regulatory mechanism of RpoS in S. baltica remains unclear. This study aims to investigate the regulatory function of RpoS on spoilage activity and adhesion ability in S. baltica. Results revealed that RpoS had no effect on the growth of S. baltica, but positively regulated the spoilage potential of S. baltica accompanied by a slower decline of total volatile basic nitrogen, lightness, and the sensory score of fish fillets inoculated with rpoS mutant. RpoS negatively regulated the adhesion ability, which was manifested in that the bacterial number of rpoS mutant adhered to stainless steel coupon was higher than that of the S. baltica in the early stage, and the biofilm formed on glass slide by rpoS mutant was thicker and tighter compared with S. baltica. Transcriptomic analysis showed that a total of 397 differentially expressed genes were regulated by RpoS. These genes were mainly enrichment in flagellar assembly, fatty acid metabolism/degradation, and RNA degradation pathways, which were associated with motility, biofilm formation and cold adaptation. This study demonstrated that RpoS is a primary regulator involved in flagellar assembly mediated biofilm formation and cold adaptation-related spoilage activity of S. baltica. Our research will provide significant insights into the control of microbiological spoilage in seafood.

Colorectal cancer (CRC) remains one of the most common malignancies worldwide and its mechanism is unclear. Polymeric immunoglobulin receptor (PIGR) which plays an important role in mucosal immunity is widely expressed in the mucosal epithelium and is dysregulated in different tumors. However, the role and underlying mechanisms of PIGR in CRC remain unclear. Here, we demonstrated that PIGR was hypermethylated and downregulated in our cohort (N = 272), and these features were associated with reduced overall survival in patients (HRmethylation 1.61, 95% CI [1.11-2.33]). These findings were validated by external TCGA and GEO data. Moreover, PIGR overexpression inhibits CRC cell malignant phenotypes in vitro and impedes CRC cells growth in male BALB/c nude mice. Mechanistically, PIGR physically associates with RE1 silencing transcription factor (REST) and blocks the transcription of laminin subunit beta 3 (LAMB3). Subsequently, the AKT-FOXO3/4 axis was suppressed by downregulated LAMB3. In the drug sensitive assay, PIGR-overexpressing cells were more sensitive to cisplatin and gemcitabine. Together, PIGR may serve as a powerful prognostic biomarker and putative tumor suppressor by suppressing the AKT-FOXO3/4 axis by downregulating LAMB3 in CRC. Our study may offer a novel therapeutic strategy for treating CRC patients who highly express PIGR with cisplatin and gemcitabine.

Early and specific detection of cancer provides an opportunity for appropriate treatment. Although studies have suggested that QKI is a tumor suppressor gene, no studies have evaluated the diagnostic utility of QKI methylation in colorectal cancer (CRC). Here, we evaluated the methylation status of QKI by integrating the methylation data of tissues and cell lines of multiple cancer types. The diagnostic performance of QKI was analyzed in the discovery dataset from the TCGA CRC 450K array (n = 440) and tested in the test sets (n = 845) from the GEO. The methylation level of QKI was further validated in our independent dataset (n = 388) using targeted bisulfite sequencing. All detected CpG sites in the QKI promoter showed CRC-specific hypermethylation in 31 types of tumor tissues. In the discovery dataset, six consecutive CpG sites achieved high diagnostic performances, with AUCs ranging from 0.821 to 0.930. In the test set, a region (chr6: 163,834,452–163,834,924) including four consecutive CpG sites had robust diagnostic ability in distinguishing CRC and adenoma from normal samples. In the validation dataset, similar robust results were observed in both early- and advanced-stage CRC patients. In addition, QKI exhibited hypermethylation in the cfDNA of patients with CRC (n = 14). Collectively, the QKI promoter is a CRC-specific methylation biomarker and holds great promise for improving the diagnosis using minimally invasive biopsy.

Bisphenol A (BPA) is a high-production-volume industrial chemical. Despite recent research conducted on its carcinogenicity, its role in the development of colon cancer (CC) has been rarely studied. This study aims to evaluate the effects of BPA on the migration and invasion of CC cells. First, we clinically verified that patients with CC exhibit higher serum BPA level than healthy donors. Subsequently, different CC cell lines were exposed to a series of BPA concentrations, and the migration and invasion of cells were detected by the wound healing test and transwell assay. Finally, N-acetyl-L-cysteine (NAC) and siHIF-1α intervention was used to explore the effects of ROS and HIF-1α on cell migration and invasion, respectively. The results demonstrated that the occurrence of BPA-induced migration and invasion were dependent on the dose and time and was most pronounced in DLD1 cells. ROS production was jointly driven by NADPH oxidase (NOX) and mitochondrial electron-transport chain (ETC). Furthermore, the intervention of NAC and siHIF-1α blocked the HIF-1α/VEGF/PI3K/AKT axis and inhibited cell migration and invasion. In conclusion, our results suggest that BPA exposure promotes the excessive production of ROS induced by NOX and ETC, which in turn activates the HIF-1α/VEGF/PI3K/AKT axis to promote the migration and invasion of CC cells. This study provides new insights into the carcinogenic effects of BPA on CC and warns people to pay attention to environmental pollution and the harm caused to human health by low-dose BPA.

PurposeTo investigate the association between fatigue and sleep habits of pregnant women to further explore the effect of sleep duration and bedtime on fatigue during the third trimester.Materials and MethodsA total of 465 Chinese Han pregnant women in the third trimester (after 28 weeks) with a singleton gestation were recruited. Sleep habits (such as bedtime, sleep onset latency, and night sleep duration) and the 14-item Fatigue Scale scores (FS-14, used to assess fatigue) were collected.ResultsThe effects of sleep duration and bedtime on FS-14 physical and total scores were significant. FS-14 physical scores and total scores of the participants in the group of sleep before 23 o’clock (SBC) of short sleep duration (

Cancer is a worldwide problem that threatens human health. Radiotherapy plays an important role in a variety of cancer treatment methods. The administration of radiotherapy can alter the differentiation pathways and functions of T cells, which in turn improves the immune response of T cells. Radiotherapy can also induce up-regulation of PD-L1 expression, which means that it has great potential for enhancing the therapeutic effect of anti-PD-1/PD-L1 inhibitors and reducing the risk of drug resistance toward them. At present, the combination of radiotherapy and anti-PD-1/PD-L1 inhibitors has shown significant therapeutic effects in clinical tumor research. This review focuses on the mechanism of radiotherapy on T cells reported in recent years, as well as related research progress in the application of PD-1/PD-L1 blockers. It will provide a theoretical basis for the rational clinical application of radiotherapy combined with PD-1/PD-L1 inhibitors.

The outbreak of COVID-19 epidemic has increased work demands for medical staff and has a certain impact on their mental health. The present study aimed to examine the role of perceived stress and social support in explaining the association between the occupational stressors and three mental health symptoms (i.e., anxiety, depression, and insomnia) of frontline medical staff. Five hundred twenty five frontline medical staff were investigated online after the outbreak of the COVID-19 (16 February, 2020–2 March, 2020) in China. The results found that the prevalence of anxiety, depression, and insomnia among frontline medical staff were 39.8, 29.9, and 37.9%, respectively. Occupational stressors were associated with anxiety, depression, and insomnia symptoms. Perceived stress significantly mediated this link. Social support moderated the second half of the indirect effect of occupational stressors on anxiety and depression symptoms. Under the epidemic situation of COVID-19, for frontline medical staff, high perceived stress and low social support may increase vulnerability for mental health symptoms triggered by occupational stressors. Thus, improving the social support and promoting the cognitive reappraisal of perceived stress may help to maintain mental health among medical staff.

ObjectiveAlcohol dependence can increase the level of anxiety. A growing body of research has identified a link between anxiety symptoms of problem drinkers and their genetic or environment factors, respectively. However, to date few studies have directly examined gene-environment (G × E) interaction on their anxiety symptoms during the acute alcohol withdrawal. The present study aims to examine the interaction between the proopiomelanocortin (POMC) rs2071345 polymorphism and alcohol dependence on anxiety symptoms of male problem drinkers, and further test the exact form of interaction on two competing models: the diathesis-stress model vs. the differential susceptibility model.MethodsA total of 440 male problem drinkers (Mage = 44.5 years, SD = 9.45) were recruited from nine main psychiatric hospitals of northern China during acute alcohol withdrawal. Blood samples were collected for genotyping, self-reported anxiety symptoms, and levels of alcohol dependence were assessed.ResultsResults indicated that the POMC rs2071345 polymorphism significantly moderated anxiety symptoms associated with alcohol dependence. A region of significance (RoS) test showed that male problem drinkers with T allele were more likely to experience more anxiety symptoms than those with CC homozygote when the standardized score of concurrent alcohol dependence was above 0.31. Confirmatory model evaluation indicated that the interaction effect involving POMC gene polymorphism conformed to the diathesis-stress model rather than differential-susceptibility model of person × environment interaction.ConclusionsThis study suggested that the SNP in POMC rs2071345 was associated with alcohol dependence in anxiety symptoms of male problem drinkers and further provided evidence in support of the diathesis-stress hypothesis of alcohol dependence in terms of anxiety symptoms.

BackgroundPrevious researches have shown that the aberrant expression of Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in tumour tissues may serve as a biomarker for colorectal cancer (CRC) prognosis. However, these previous studies have small sample sizes and lacked validation from independent external populations. We therefore aimed to clarify the prognostic value of MALAT1 expression status in CRC patients using a large cohort and validate the findings with another large external cohort.MethodsThe prognostic association between MALAT1 expression status and CRC outcomes was evaluated initially in a prospective cohort in China (n=164) and then validated in an external TCGA population (n=596). In the initial cohort, MALAT1 expression levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Propensity score (PS) adjustment method was used to control potential confounding biases. The prognostic significance was reported as PS-adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI).ResultsThere was no statistically significant association between MALAT1 expression status and CRC patient overall survival (OS) or disease free survival (DFS) in both initial cohort and external validation cohort populations. When combining these populations together, the results did not change materially. The summarized HRPS-adjusted were 1.010 (95% CI, 0.752-1.355, P=0.950) and 1.170 (95% CI, 0.910-1.502, P=0.220) for OS and DFS, respectively.ConclusionsMALAT1 expression status is not associated with prognostic outcomes of CRC patients. However, additional larger population studies are needed to further validate these findings.

Background: Colon cancer is one of the most common cancer types, although it has certain unique genetic features. This study aimed to develop a unique score for assessing prognosis and immunotherapy efficacy using integrated multi-omics analysis.Methods: Isobaric tagging for relative and absolute quantification (iTRAQ) based proteomic analysis was used to screen differentially expressed proteins (DEP) between tumor and normal samples. DEP mRNA obtained from TCGA were clustered into different categories to show landscape-related prognosis and function. Following that, DEG was extracted from DEP mRNA, and the DEP-related score (DEPRS) was constructed to investigate the difference in immunotherapy prognosis and sensitivity. Finally, WCGNA, random forest, and artificial neural networks were used to screen for key genes. The prognostic value and protein level of these genes were validated.Results: A total of 243 DEPs were identified through iTRAQ analysis, and the corresponding DEP mRNA was clustered into three. Following a series of tests, 1,577 DEGs were identified from overlapped DEP mRNA clusters and were classified into three gene clusters. The two types of clusters described above shared comparable characteristics in terms of prognosis and function. Then, it was established that a high DEPRS indicated a poor prognosis and DEPRS had significant associations with TMB, MSI status, and immunotherapeutic response. Finally, the key genes HART3 and FBLN2 were identified and were found to be implicated in immunotherapy and prognosis.Conclusion: The development of a DEPRS based on multi-omics analysis will aid in improving our understanding of colon cancer and guiding a more effective immunotherapy strategy. DEPRS and key genes are used as biomarkers in the clinical evaluation of patients.

Trichogramma chilonis Ishii is an important natural enemy of several lepidopterous pests on crops. In this study, we sequenced the complete mitochondrial genome of T. chilonis (GenBank accession number MW789210). The length of the complete mitochondrial genome was 16,147 bp, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a non-coding control region. The overall base composition of the genome in descending order was 44.8% T, 41.8% A, 9.0% G and 4.5% C, with a significant AT bias of 86.6%. Phylogenetic analysis indicated that T. chilonis had a close relationship with Trichogramma ostriniae.