Preoperative prediction of lymphovascular invasion and T-staging of rectal cancer via a dual-energy computed tomography iodine map: a feasibility study.

PURPOSE: To investigate the value of dual-energy computed tomography (DECT) in predicting lymphovascular invasion (LVI) and the accuracy of preoperative T-staging of rectal cancer (RC). METHODS: Forty-nine patients with RC who had not received radiotherapy were enrolled to undergo a DECT scan. All patients underwent surgical tumor resection within 3-5 days after the DECT scan. Preoperative T-staging of RC based on images was performed by experienced radiologists. The normalized iodine concentrations (NIC) of the tumor and the perirectal adipose tissue (PAT) from the arterial phase (AP) and venous phase (VP) were measured using DECT. The tumor LVI and T-staging confirmed by pathology were used as the gold standard for grouping (group A, LVI-; group B, LVI+; group C, T1-2; and group D, T3-4a). The NIC values between two groups were compared using the Mann-Whitney U test, with P < 0.05 indicating a statistically significant difference. The accuracy of NIC in predicting LVI and distinguishing T1-2 RC from T3-4a RC were determined via receiver operating characteristic curve analysis, and the optimal cut-off of NIC was determined using the area under the curve. RESULTS: The tumor NIC values were significantly higher in the LV+ group than in the LVI- group in the VP (0.728 ± 0.031 vs. 0.669 ± 0.034, P < 0.001). The NIC values of PAT were significantly higher in the T3-4a group than in the T1-2 group in both the AP (4.034 ± 0.991 vs. 3.115 ± 0.581, P < 0.05) and the VP (5.481 ± 1.054 vs. 3.450 ± 0.980, P < 0.001). The accuracy of using NIC values to distinguish between the LVI+ group and the LVI- group and to diagnose the T3-4a group were 85.7% and 89.8%, respectively. However, there was no statistically significant difference between the NIC value in the LVI+ group and in the LVI- group in the AP. There was also no statistical difference in the tumor NIC value between the T1-2 group and the T3-4a group. CONCLUSION: The tumor and PAT NIC are valuable indicators in RC that can preoperatively predict LVI and improve the accuracy of preoperative RC T-staging. CLINICAL SIGNIFICANCE: The use of DECT improves the T-staging and LVI prediction of RC, which is helpful in guiding the clinical selection of appropriate treatment modalities and improving prognostic outcomes.

A comprehensive review on novel synthetic foods: Potential risk factors, detection strategies, and processing technologies.

Nowadays, the food industry is facing challenges due to the simultaneous rise in global warming, population, and food consumption. As the integration of synthetic biology and food science, novel synthetic foods have obtained high attention to address these issues. However, these novel foods may cause potential risks related to human health. Four types of novel synthetic foods, including plant-based foods, cultured meat, fermented foods, and microalgae-based foods, were reviewed in the study. The original food sources, consumer acceptance, advantages and disadvantages of these foods were discussed. Furthermore, potential risk factors, such as nutritional, biological, and chemical risk factors, associated with these foods were described and analyzed. Additionally, the current detection methods (e.g., enzyme-linked immunosorbent assay, biosensors, chromatography, polymerase chain reaction, isothermal amplification, and microfluidic technology) and processing technologies (e.g., microwave treatment, ohmic heating, steam explosion, high hydrostatic pressure, ultrasound, cold plasma, and supercritical carbon dioxide) were reviewed and discussed critically. Nonetheless, it is crucial to continue innovating and developing new detection and processing technologies to effectively evaluate these novel synthetic foods and ensure their safety. Finally, approaches to enhance the quality of these foods were briefly presented. It will provide insights into the development and management of novel synthetic foods for food industry.

Visual analysis of trustworthiness studies: based on the Web of Science database.

Trustworthiness is the most significant predictor of trust and has a significant impact on people's levels of trust. Most trustworthiness-related research is empirical, and while it has a long history, it is challenging for academics to get insights that are applicable to their fields of study and to successfully transfer fragmented results into practice. In order to grasp their dynamic development processes through the mapping of network knowledge graphs, this paper is based on the Web of Science database and uses CiteSpace (6.2.R4) software to compile and visualize the 1,463 publications on trustworthy studies over the past 10 years. This paper aims to provide valuable references to theoretical research and the practice of Trustworthiness. The findings demonstrate that: over the past 10 years, trustworthiness-related research has generally increased in volume; trustworthiness research is concentrated in industrialized Europe and America, with American research findings having a bigger global impact; The University of California System, Harvard University, and Yale University are among the high-production institutions; the leading figures are represented by Alexander Todorov, Marco Brambilla, Bastian Jaeger, and others; the core authors are distinguished university scholars; however, the level of cooperation of the core author needs to be improved. The primary journal for publishing research on trustworthiness is the Journal of Personality and Social Psychology and Biology Letters. In addition, the study focuses on three distinct domains, involving social perception, facial clues, and artificial intelligence.

G272V and P301L mutations induce isoform specific tau mislocalization to dendritic spines and synaptic dysfunctions in cellular models of 3R and 4R tau frontotemporal dementia.

Tau pathologies are detected in the brains of some of the most common neurodegenerative diseases including Alzheimer's disease (AD), Lewy body dementia (LBD), chronic traumatic encephalopathy (CTE), and frontotemporal dementia (FTD). Tau proteins are expressed in six isoforms with either three or four microtubule-binding repeats (3R tau or 4R tau) due to alternative RNA splicing. AD, LBD, and CTE brains contain pathological deposits of both 3R and 4R tau. FTD patients can exhibit either 4R tau pathologies in most cases, or 3R tau pathologies less commonly in Pick's disease, which is a subfamily of FTD. Here, we report the isoform-specific roles of tau in FTD. The P301L mutation, linked to familial 4R tau FTD, induces mislocalization of 4R tau to dendritic spines in primary hippocampal cultures that were prepared from neonatal rat pups of both sexes. Contrastingly, the G272V mutation, linked to familial Pick's disease, induces phosphorylation-dependent mislocalization of 3R tau but not 4R tau proteins to dendritic spines. The overexpression of G272V 3R tau but not 4R tau proteins leads to the reduction of dendritic spine density and suppression of miniature excitatory synaptic currents (mEPSCs) in 5-week-old primary rat hippocampal cultures. The decrease in mEPSC amplitude caused by G272V 3R tau is dynamin dependent whereas that caused by P301L 4R tau is dynamin independent, indicating that the two tau isoforms activate different signaling pathways responsible for excitatory synaptic dysfunction. Our 3R and 4R tau studies here will shed new light on diverse mechanisms underlying FTD, AD, LBD, and CTE.Significance statement Frontotemporal dementia is the third most common form of dementia caused by neurodegeneration with diverse clinical presentations. Here, we report distinct cellular mechanisms that may explain some of the similarities and differences between diverse forms of frontotemporal dementia. Tau proteins are composed of six isoforms. We found that although all isoforms can cause neural deficits, each isoform may impair the structures and functions of neurons with different temporal dynamics or through different mechanisms. The mechanistic studies of isoform-specific tau-mediated synaptic impairments reported here will add valuable information to the current molecular and cellular framework, by which diverse tau isoforms cause brain deficits in frontotemporal dementia and other neurodegenerative diseases including Alzheimer's diseases, Lewy body dementia, and chronic traumatic encephalopathy.

Developmental toxicity assay of xanthatin in zebrafish embryos.

Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, Xanthium strumarium L, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity in vivo. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes nrf2 was inhibited, while oxidative stress-related genes (keap1 and nqo1) and apoptotic genes (caspase3, caspase9 and p53) were increased after xanthatin exposure. Mitophagy related genes pink1 and parkin, and wnt pathway (ß-catenin, wnt8a and wnt11) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.

Pd(II)/N,N'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Synthesis of Cyclic Quaternary Centers and Mechanistic Investigations.

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

Fast and eco-friendly synthesis of carbon dots from pinecone for highly effective detection of 2,4,6-trinitrophenol in environmental samples.

2,4,6-Trinitrophenol (TNP) has high explosive risks and biological toxicity, and there has been considerable concern over the determination of TNP. In the present work, fluorescent carbon dots (CDs) stemmed from a green carbon source of pinecone by the facile hydrothermal approach. A novel environment- friendly fluorescent probe was developed to efficiently detect TNP by using the obtained CDs with remarkable fluorescence stability. The fluorescent CDs exhibited obvious excitation dependence with the highest peaks for excitation and emission occurring at 321 and 411 nm, respectively. The fluorescence intensity is significantly reduced by TNP owing to the inner filter effect with the CDs. The probe exhibited good linearity with TNP concentrations in the range of 0.025-20 µg mL-1, and the limit of detection was as low as 8.5 ng mL-1. Additionally, the probe proved successful in sensing TNP quantitatively in actual environmental samples with satisfied recoveries of 95.6-99.6%. The developed fluorescent probe offered an environment-friendly, efficient, rapid, and reliable platform for detecting trace TNP in the environmental field.HighlightsNovel carbon dots were synthesised from green precursors of pineal powder.The highly effective quenching process was put down to the inner filter effect.The as-constructed fluorescent probe was successfully utilised for sensing 2,4,6-trinitrophenol in environmental samples.The proposed method was simple, rapid, efficient, economical, and eco-friendly.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio and wide clinical application are needed. Based on public data sets, the Chemotherapy Cohort and the Immunotherapy Cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, single-sample gene set enrichment analysis (ssGSEA), stemness index calculation, immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful to predict the prognosis of GC patients, the degree of chemotherapy resistance and the efficacy of immunotherapy.

LINC02257 regulates colorectal cancer liver metastases through JNK pathway.

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Distinct glutamatergic projections of the posteroventral medial amygdala play different roles in arousal and anxiety.

Sleep disturbance usually accompanies anxiety disorders and exacerbates their incidence rates. The precise circuit mechanisms remain poorly understood. Here, we found that glutamatergic neurons in the posteroventral medial amygdala (MePVGlu) are involved in arousal and anxiety-like behaviors. Excitation of MePVGlu neurons not only promoted wakefulness but also increased anxiety-like behaviors. Different projections of MePVGlu neurons played various roles in regulating anxiety-like behaviors and sleep-wakefulness. MePVGlu neurons promoted wakefulness through the MePVGlu-posteromedial cortical amygdaloid area (PMCo) pathway and the MePVGlu-bed nucleus of the stria terminals (BNST) pathway. In contrast, MePVGlu neurons increased anxiety-like behaviors through the MePVGlu-ventromedial hypothalamus (VMH) pathway. Chronic sleep disturbance increased anxiety levels and reduced reparative sleep, accompanied by the enhanced excitability of MePVGlu-PMCo and MePVGlu-VMH circuits but suppressed responses of glutamatergic neurons in the BNST. Inhibition of the MePVGlu neurons could rescue chronic sleep deprivation-induced phenotypes. Our findings provide important circuit mechanisms for chronic sleep disturbance-induced hyperarousal response and obsessive anxiety-like behavior, and are expected to provide a promising strategy for treating sleep-related psychiatric disorders and insomnia.

Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).

Impact of pre-existing frailty on survival outcomes in solid-organ transplant candidates and recipients: A meta-analysis.

BACKGROUND: There is controversy surrounding the association between preexisting frailty and increased mortality in candidates and recipients of solid-organ transplants. This meta-analysis aimed to evaluate the impact of preexisting frailty on survival outcomes in solid-organ transplant candidates and recipients. METHODS: A systematic search was conducted in the PubMed, Web of Sciences, and Embase databases until October 2, 2023. Two reviewers independently selected the eligible studies according to the PECOS criteria: Participants (candidates and recipients of solid-organ transplants), Exposure (frailty), Comparison (no-frailty), Outcomes (waitlist or posttransplant mortality), and Study design (retrospective or prospective cohort studies). The pooled effects were summarized by pooling the adjusted hazard ratio (HR) with 95 % confidence intervals (CI) for the frail patients than those without frailty. RESULTS: Sixteen studies with 10091 patients met the eligibility criteria. Depending on the frailty tools used, the prevalence of frailty in solid-organ transplant candidates/recipients ranged from 4.6 % to 45.1 %. Frailty was significantly associated with an increased risk of waitlist mortality (HR 2.44; 95 % CI 1.84-3.24) and posttransplant mortality (HR 2.23; 95 % CI 1.61-3.09) in solid-organ transplant candidates and recipients, respectively. Subgroup analyses showed that the association of preexisting frailty with waitlist mortality and posttransplant mortality appeared to stronger in kidney transplant candidates (HR 2.70; 95 % CI 1.93-3.78) and lung transplantation recipients (HR 2.52; 95 % CI 1.23-5.15). CONCLUSION: Frailty is a significant predictor of reduced survival in solid-organ transplant candidates and recipients. Assessment of frailty has the potential to identify patients who are suitable for transplantation.

Specific feature recognition on group specific networks (SFR-GSN): a biomarker identification model for cancer stages.

Background and Objective: Accurate identification of cancer stages is challenging due to the complexity and heterogeneity of the disease. Current clinical diagnosis methods primarily rely on phenotypic observations, which may not capture early molecular-level changes accurately. Methods: In this study, a novel biomarker recognition method was proposed tailored for cancer stages by considering the change of gene expression relationships. Utilizing the sample-specific information and protein-protein interaction networks, the group specific networks were constructed to address the limited specificity of potential biomarkers. Then, a specific feature recognition method was proposed based on these group specific networks, which employed the random forest algorithm for initial screening followed by a recursive feature elimination process to identify the optimal biomarker subset. During exploring optimal results, a strategy termed the Cost-Benefit Ratio, was devised to facilitate the identification of stage-specific biomarkers. Results: Comparative experiments were conducted on lung adenocarcinoma and breast cancer datasets to validate the method's efficacy and generalizability. The results showed that the identified biomarkers were highly stage-specific, and the F1 scores for predicting cancer stages were significantly improved. For the lung adenocarcinoma dataset, the F1 score reached 97.68%, and for the breast cancer dataset, it achieved 96.87%. These results significantly surpassed those of three conventional methods in terms of F1 scores. Moreover, from the perspective of biological functions, the biomarkers were proved playing an important role in cancer stage-evolution. Conclusion: The proposed method demonstrated its effectiveness in identifying stage-related biomarkers. By using these biomarkers as features, accurate prediction of cancer stages was achieved. Furthermore, the method exhibited potential for biomarker identification in subtype analyses, offering novel perspectives for cancer prognosis.

Volumetric Ultrasound Imaging for the Whole Soft Tissue: Toward Enhanced Thyroid Disease Examination.

OBJECTIVES: Ultrasound imaging (USI) is the gold standard in the clinical diagnosis of thyroid diseases. Compared with two-dimensional (2D) USI, three-dimensional (3D) USI could provide more structural information. However, the unstable pressure generated by the hand-hold ultrasound probe scanning can cause tissue deformation, especially in soft tissues such as the thyroid. The deformation is manifested as tissue structure being compressed in 2D USI, which results in structural discontinuity in 3D USI. Furthermore, multiple scans apply pressure in different directions to the tissue, which will cause relative displacement between the 3D images obtained from multiple thyroid scans. METHODS: In this work, we proposed a framework to minimize the influence of the variation of pressure in thyroid 3D USI. To correct pressure artifacts in a single scanning sequence, an adaptive method to smooth the position of the 2D ultrasound (US) image sequence is adopted before performing volumetric reconstruction. To build a whole 3D US image including both sides of the thyroid gland, an iterative closest point (ICP) based registration pipeline is adopted to eliminate the relative displacement caused by different pressure directions. RESULTS: Our proposed method was validated by in vivo experiments, including healthy volunteers and volunteers with thyroid nodules at different grading levels. CONCLUSIONS: The thyroid gland and nodule are rendered intelligently in the whole scanning region to facilitate the observation of 3D USI results by the doctor. This work might make a positive contribution to the clinical diagnosis of diseases of the thyroid or other soft tissues.

Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence.

Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria.

Examining the association of family environment and children emotional/behavioral difficulties in the relationship between parental anxiety and internet addiction in youth.

Introduction: Associations between parental anxiety and adolescent internet addiction have been documented in the literature; however, few studies have analyzed the role of the family environment in this relationship. This study aims to explore the relationship between parental anxiety and adolescent internet addiction while also investigating the indirect relationships involving multiple dimensions of the family environment and child emotional behavior issues. Methods: Surveys were conducted among 6,296 parent-child pairs. We administered SDQ, CIAS-R, and FES-CV to assess adolescents' issues and internet addiction, and evaluate family environment. Additionally, parents completed GAD-7 to assess parental anxiety levels.Results: Correlation analysis revealed that the family environment and adolescent emotional behavior issues played an indirect relationship in the link between parental anxiety and internet addiction. Discussion: The findings emphasize the importance of addressing parental anxiety and fostering a positive family environment as effective measures to alleviate adolescent emotional behavior problems and reduce the risk of internet addiction.

Distance-related functional reorganization predicts motor outcome in stroke patients.

BACKGROUND: Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. METHODS: In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. RESULTS: Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. CONCLUSIONS: The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. TRIAL REGISTRATION: All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

AI-2 quorum sensing-induced galactose metabolism activation in Streptococcus suis enhances capsular polysaccharide-associated virulence.

Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.

The temporal variation in the effects of extreme temperature on respiratory mortality: Evidence from 136 cities in China, 2006-2019.

BACKGROUND: In the context of climate change and urbanization, the temporal variation of the adverse health effect of extreme temperature has attracted increasing attention. METHODS: The meteorological data and the daily death records of mortality from respiratory diseases of 136 Chinese cities were from 2006 to 2019. Heat wave and cold spell were selected as the indicator events of extreme high temperature and extreme low temperature, respectively. The generalized linear model and time-varying distributed lag model were used to perform a two-stage time-series analysis to evaluate the temporal variation of the mortality risk associated with extreme temperature in the total population, sub-populations (sex- and age- specific) and different regions (climatic zone and relative humidity level). RESULTS: During the study period, relative risk (RR) of respiratory mortality associated with heat wave decreased from 1.22 (95 %CI: 1.07-1.39) to 1.13 (95 %CI: 1.01-1.26) in the total population, and RR of respiratory mortality associated with cold spell decreased from 1.30 (95 %CI: 1.14-1.49) to 1.17 (95 %CI: 1.08-1.26). The impact of heat wave reduced in the males (P = 0.044) and in the females as with cold spell (P < 0.001). The respiratory mortality risk of people over 65 associated with cold spell decreased (P = 0.040 for people aged 65-74 and P < 0.001 for people over 75). The effect of cold spell reduced in cities from tropical or arid zone (P = 0.035). The effects of both heat wave and cold spell decreased in cities with the relative humidity in the first quartile (P = 0.046 and 0.010, respectively). CONCLUSION: The impact of heat wave on mortality of respiratory diseases decreased mainly in males and cities with the lowest relative humidity, while the impact of cold spell reduced in females, people over 65 and tropical and arid zone, suggesting adaptation to extreme temperature of Chinese residents to some extent.

Formation and Analysis of Biofilms in Vivo.

Establishing a biofilm infection model in vivo allows a better understanding of the underlying infection mechanisms of bacteria. Here we describe a method for constructing an in vivo biofilm model of Streptococcus suis. The animal modeled is a piglet, which is the natural reservoir of S. suis, and the mode of clinical infection is simulated by intranasal inoculation of S. suis. This model is in line with clinical practice, easy to operate, and has good repeated stability.