Si-Ni-San alleviates intestinal and liver damage in ulcerative colitis mice by regulating cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS), a traditional Chinese medicinal formula derived from Treatise on Febrile Diseases, is considered effective in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice. However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation. AIM OF THE STUDY: This study aimed to evaluate the effect, explore the bioactive ingredients and the underlying mechanisms of SNS in ameliorating ulcerative colitis (UC) and associated liver injury in dextran sodium sulphate (DSS)-induced mouse colitis models. MATERIALS AND METHODS: The effect of SNS (1.5, 3, 6 g/kg) on 3% DSS-induced acute murine colitis was evaluated by disease activity index (DAI), colon length, inflammatory cytokines, hematoxylin-eosin (H&E) staining, tight junction proteins expression, ALT, AST, and oxidative stress indicators. HPLC-ESI-IT/TOF MS was used to analyze the chemical components of SNS and the main xenobiotics in the colon of UC mice after oral administration of SNS. Network pharmacological study was then conducted based on the main xenobiotics. Flow cytometry and immunohistochemistry techniques were used to demonstrate the inhibitory effect of SNS on Th17 cells differentiation and the amelioration of Th17/Treg cell imbalance. LC-MS/MS, Real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting techniques were performed to investigate the oxysterol-Liver X receptor (LXRs) signaling activity in colon. Targeted bile acids metabolomics was conducted to reveal the change of the two major pathways of bile acid synthesis in the liver, and the expression of key metabolic enzymes of bile acids synthesis was characterized by RT-qPCR and western blotting techniques. RESULTS: SNS (1.5, 3, 6 g/kg) decreased the DAI scores, protected intestinal mucosa barrier, suppressed the production of pro-inflammatory cytokines, improved hepatic and splenic enlargement and alleviated liver injury in a dose-dependent manner. A total of 22 components were identified in the colon of SNS (6 g/kg) treated colitis mice, and the top 10 components ranked by relative content were regarded as the potential effective chemical components of SNS, and used to conduct network pharmacology research. The efficacy of SNS was mediated by a reduction of Th17 cell differentiation, restoration of Th17/Treg cell homeostasis in the colon and spleen, and the experimental results were consistent with our hypothesis and the biological mechanism predicted by network pharmacology. Mechanistically, SNS regulated the concentration of 25-OHC and 27-OHC by up-regulated CH25H, CYP27A1 protein expression in colon, thus affected the expression and activity of LXR, ultimately impacted Th17 differentiation and Th17/Treg balance. It was also found that SNS repressed the increase of hepatic cholesterol and reversed the shift of BA synthesis to the acidic pathway in UC mice, which decreased the proportion of non-12-OH BAs in total bile acids (TBAs) and further ameliorated colitis and concomitant liver injury. CONCLUSIONS: This study set the stage for considering SNS as a multi-organ benefited anti-colitis prescription based on the significant effect of ameliorating intestinal and liver damage, and revealed that derivatives of cholesterol, namely oxysterols and bile acids, were closely involved in the mechanism of SNS anti-colitis effect.

Visualization of Unconventional Rashba Bands and Vortex Zero Mode in the Topological Superconductor Candidate AuSn4.

The noble metal alloy AuSn4 has recently been identified as an intrinsic surface topological superconductor, promisingly hosting the Majorana zero mode (MZM) for topological quantum computing. However, the atomic visualization of its nontrivial surface states and MZM remains elusive. Here, we report the direct observation of unconventional surface states and vortex zero mode in AuSn4 by scanning tunneling microscopy/spectroscopy. Unlike the trivial metallic bulk states of Sn-terminated surfaces, the Au-terminated surfaces exhibit pronounced surface states near the Fermi level, arising from unconventional Rashba bands characterized by shared helical spin textures. In the superconducting state, the Sn-terminated surfaces exhibit conventional Caroli-de Gennes-Matricon bound states, while the Au-terminated surfaces display sharp zero-energy core states resembling MZMs in a nonquantum-limit condition. This distinction may result from the dominant contribution of unconventional Rashba bands on the Au-terminated surface. Our results provide a new platform for studying termination-dependent topological surface states and MZM in noble-metal-based superconductors.

Optimized Ginkgo leaf biochar: An efficient adsorbent for 2,4-D herbicide removal from wastewater.

This research exploited biochar, sourced from Ginkgo leaves (GLs), to facilitate the adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) in aqueous environments. The results reveal that GL biochar, activated with ZnCl2 at a temperature of 500°C (500-ZGBC), demonstrated the greatest specific surface area (SBET) of 536.0 m2 g-1 for 2,4-D adsorption. The biochar's properties, including specific surface area, morphology, structure, thermal stability, and functional groups, were analyzed. Additionally, studies of kinetic and isotherm profiles were conducted, yielding the highest recorded adsorption capacity of 281.8 mg g-1. Pore filling, hydrogen bonding, π-π interactions, surface complexation with Zn groups, and electrostatic interactions contribute significantly to the adsorption performance of 500-ZGBC for 2,4-D. Optimal adsorption was determined to occur at pH 2.117, with a dose of 0.4230 g L-1 of 500-ZGBC, and an initial concentration of 2,4-D at 294.7 mg L-1, as evidenced by the application of the response surface method (RSM). PRACTITIONER POINTS: Premium pharmaceutical-grade biochar, derived from Ginkgo leaves, boasting a SBET of 536.0 m2 g-1 was produced. An absorption capacity reaching 281.8 mg g-1 was observed in Ginkgo leaf biochar for 2,4-dichlorophenoxyacetic acid (2,4-D) adsorption. The adsorption procedure was refined through the employment of response surface methodology.

Design and Modelling of Continuum Robot for Endoscopic Submucosal Dissection Surgery With Lifting Force Estimation.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early-stage gastrointestinal cancers. However, traditional surgical instruments lack accuracy and force-sensing. METHODS: A new type of continuum robot for ESD is designed. An accurate static model of the proposed continuum robot is established, considering cases where the robot bends into C-shapes and S-shapes. A force estimation method based on an accurate static model is proposed. Then, the accuracy of the static model and force estimation is verified through experiments. Finally, an ex-organ experiment is carried out. RESULTS: The average position error of the proposed static model is 0.72 mm, accounting for 2.57% of the total robot length. The average error of force estimation is 19.53 mN. By gripping and cutting ex-porcine gastric mucosa, the robot's functionality is validated. CONCLUSION: This paper contributes to precise control and safe interaction of continuum robots.

Factors related to the intention of choosing shared E-scooters for metro transfer: A survey study integrating weather perception into satisfaction evaluation from Changsha.

Shared E-scooter (SE) travel is a low-carbon transportation method that can be further enhanced by integrating with metro systems. This study aims to quantify the impact of the built environment, attitude preferences, weather perception, and other factors on the evaluation and intention to use the "SE-metro transfer" travel mode, as well as how to efficiently and concisely measure and model these effects. Empirical analysis was conducted using questionnaire data from Changsha, China, with 683 participants surveyed. Three satisfaction models were established and compared based on the Technology Acceptance Model (TAM), and an optimal M2 model was expanded to incorporate users' subjective perceptions of weather, proposing a method to simplify questionnaire length. The study found that well-designed vehicles and infrastructure, along with necessary supporting facilities, play important roles in enhancing SE usage. However, there are still many areas for optimization in Changsha's SE policies. Despite the advantages of SE in terrain and physical fitness, which have significantly expanded and changed their user base compared to traditional shared bicycles, there is still much potential to adapt to the middle-aged and older user groups. The results of this study can provide valuable insights for professionals and government officials in designing systems, constructing infrastructure, and formulating policies.

QTL mapping and omics analysis to identify genes controlling kernel dehydration in maize.

KEY MESSAGE: This study mapped and screened three candidate genes related to kernel dehydration in maize. The slow development rate of maize kernels during later stages leads to high kernel moisture content at harvest, posing a challenge for mechanized maize harvesting in China. This study utilized a recombinant inbred line population derived from Zheng 58 (slow dehydration) and PH6WC (fast dehydration) as parents. After four years of trait investigation and analysis, 25 quantitative trait loci (QTLs) associated with kernel dehydration rate and moisture content were identified, with six QTLs showing a significant contribution value exceeding 10% in the phenotype. Furthermore, a comparison was made between the QTLs identified in this study and those from previous research on maize kernel moisture content and dehydration rate, followed by screening through the omics analysis of the parental lines. Three candidate genes related to kernel dehydration rate were identified, primarily involving carbohydrate metabolism, energy metabolism processes (Zm00001d014030 and Zm00001d006476), and stimulus resistance (Zm00001d040113). These findings provide valuable insights to assist and guide future breeding efforts for mechanical harvesting of maize.

Diagnostic model for spontaneous bacterial peritonitis in cirrhotic patients with ascites: a multicenter cohort study.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a potentially life-threatening complication of cirrhotic ascites. Early diagnosis and treatment of SBP are essential to improve the survival rates and prognosis of patients. We aimed to identify the predictors of SBP to establish a new noninvasive early diagnostic tool. METHODS: We screened 1618 patients who underwent paracentesis due to cirrhotic ascites between January 2017 and December 2018 in three hospitals. We evaluated the symptomatic, clinical, and laboratory parameters to identify the predictors of SBP. The primary diagnostic model was displayed as a nomogram. RESULTS: The model included abdominal pain, diarrhea, white blood cell count, neutrophil percentage, procalcitonin, C-reactive protein, lactate dehydrogenase, glucose, and Model for End-stage Liver Disease score. The model's diagnostic performance was good, with an AUC of 0.84 [95% confidence interval (CI), 0.81-0.87] in the training cohort. In the validation cohort, the diagnostic ability was also good, with AUCs of 0.87 (95% CI, 0.83-0.91) and 0.90 (95% CI, 0.87-0.94) for inner and outer validation queues, respectively. Moreover, the decision curve analysis confirmed the clinical utility of the nomogram model. In addition, we developed a Microsoft Excel calculation model to allow convenient adoption of the model in clinical practice. CONCLUSION: We developed good performing diagnostic models for SBP.

The neural circuit of Superior colliculus to ventral tegmental area modulates visual cue associated with rewarding behavior in optical intracranial Self-Stimulation in mice.

Visual system is the most important system of animal to cognize the information in outside world, and reward-related visual cues are the key factors in the consolidation and retrieval of reward memory. However, the neural circuit mechanism is still unclear. Superior Colliculus (SC) receive direct input from the retina and belong to the earliest stages of visual processing. Recent studies identified a specific pathway from SC to ventral tegmental area (VTA) that underlie specific innate behaviors, eg. flight or freezing, approach behaviors and so on. In present research, we investigated that inhibition of SC to VTA circuit with chemogenetics suppressed light cue-associated reward-seeking behaviors, while activation of the SC-VTA circuit with chemogenetic technology triggered the reward-seeking behaviors in optical intracranial self-stimulation for VTA DA neurons (oICSS) in mice. These findings suggest that neural circuit of SC-VTA mediates the retrieval of reward memory associated with visual cues, which will provide a new field for revealing the neural mechanism of pathological memory such as addiction.

DNA-Based Complexes and Composites: A Review of Fabrication Methods, Properties, and Applications.

Deoxyribonucleic acid (DNA), a macromolecule that stores genetic information in organisms, has recently been gradually developed into a building block for new materials due to its stable chemical structure and excellent biocompatibility. The efficient preparation and functional integration of various molecular complexes and composite materials based on nucleic acid skeletons have been successfully achieved. These versatile materials possess excellent physical and chemical properties inherent to certain inorganic or organic molecules but are endowed with specific physiological functions by nucleic acids, demonstrating unique advantages and potential applications in materials science, nanotechnology, and biomedical engineering in recent years. However, issues such as the production cost, biological stability, and potential immunogenicity of DNA have presented some unprecedented challenges to the application of these materials in the field. This review summarizes the cutting-edge manufacturing techniques and unique properties of DNA-based complexes and composites and discusses the trends, challenges, and opportunities for the future development of nucleic acid-based materials.

SWFormer: Stochastic Windows Convolutional Transformer for Hybrid Modality Hyperspectral Classification.

Joint classification of hyperspectral images with hybrid modality can significantly enhance interpretation potentials, particularly when elevation information from the LiDAR sensor is integrated for outstanding performance. Recently, the transformer architecture was introduced to the HSI and LiDAR classification task, which has been verified as highly efficient. However, the existing naive transformer architectures suffer from two main drawbacks: 1) Inadequacy extraction for local spatial information and multi-scale information from HSI simultaneously. 2) The matrix calculation in the transformer consumes vast amounts of computing power. In this paper, we propose a novel Stochastic Window Transformer (SWFormer) framework to resolve these issues. First, the effective spatial and spectral feature projection networks are built independently based on hybrid-modal heterogeneous data composition using parallel feature extraction, which is conducive to excavating the perceptual features more representative along different dimensions. Furthermore, to construct local-global nonlinear feature maps more flexibly, we implement multi-scale strip convolution coupled with a transformer strategy. Moreover, in an innovative random window transformer structure, features are randomly masked to achieve sparse window pruning, alleviating the problem of information density redundancy, and reducing the parameters required for intensive attention. Finally, we designed a plug-and-play feature aggregation module that adapts domain offset between modal features adaptively to minimize semantic gaps between them and enhance the representational ability of the fusion feature. Three fiducial datasets demonstrate the effectiveness of the SWFormer in determining classification results.

Deltamethrin increased susceptibility to Aeromonas hydrophila in crucian carp through compromising gill barrier.

Pyrethroids serve as a significant method for managing and preventing parasitic diseases in fish. Among these, deltamethrin (DEL) is used extensively in aquatic environments. Our previous work has been confirmed that DEL exposure can induce oxidative stress and immunosuppression on the gill mucosal barrier of crucian carp (Carassius auratus). However, it is not clear whether DEL affects the susceptibility of farmed fish to bacterial infection. In this study, fish was pre-exposed to different DEL concentration (0, 0.3 and 0.6 µg L-1) and then challenged by immersion with Aeromonas hydrophila (1.0 × 10^8 CFU mL-1). After immersion challenge, fish pre-exposed to DEL developed prominent lipopolysaccharides level in gill and serum and had a significantly lower survival rate compared to the control group. In DEL pre-exposure fish after immersion, the gill apoptosis levels were significantly higher and disrupted the tight junction barrier by downregulating the zo1 and claudin12. Furthermore, fish pre-exposed to DEL exhibited increased activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malonaldehyde (MDA) levels in the early stage after immersion but experiencing decreased activities of glutathione peroxidase (GPx) and lysozyme (LZM) in the later stage after immersion. And this process was regulated by the NRF2 pathway. Additionally, fish pre-exposed to DEL after immersion had significantly lower mRNA levels of immune-related genes tlr4, myd88, tnfα, and il-1ß. Overall, these findings indicate that DEL damaged the gill barrier, weakened the immune response, raised LPS levels, and heightened vulnerability to A. hydrophila infection in crucian carp, resulting in mortality. Thus, this work will help social groups and aquaculture workers to understand the potential risk of DEL exposure for bacterial secondary infection in cultured fish.

SARS-CoV-2 reactivates fungal-associated Hemophagocytic lymphohistiocytosis: Case report and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease characterized by the uncontrolled activation of the immune system, resulting in a high clinical mortality rate. A 56-year-old Chinese female presented at the emergency room with symptoms including fever, fatigue, nausea, vomiting, cough, shortness of breath, and chest tightness. Laboratory investigations demonstrated decreased levels of white blood cells, hemoglobin, and platelets while interleukin-6 and ferritin exhibited significant elevations. She was subsequently admitted to the hematology department, where she was diagnosed with HLH caused by a Candida infection. Following treatment with antifungal agents, glucocorticoids, antiemetics, diuretics, and hepatoprotective therapy, the patient's condition has shown improvement. However, after being infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the patient experienced a reactivation of HLH, resulting in a more severe clinical presentation and complications compared to the initial onset. Although the patient's condition improved after the administration of antiviral drugs, etoposide, glucocorticoids, cyclosporin, and intravenous immunoglobulin, this case highlights the possibility of disease reactivation during the recovery phase of HLH. This should raise the attention of medical professionals.

Clinical evaluation of the convolutional neural network­based automatic delineation tool in determining the clinical target volume and organs at risk in rectal cancer radiotherapy.

Delineating the clinical target volume (CTV) and organs at risk (OARs) is crucial in rectal cancer radiotherapy. However, the accuracy of manual delineation (MD) is variable and the process is time consuming. Automatic delineation (AD) may be a solution to produce quicker and more accurate contours. In the present study, a convolutional neural network (CNN)-based AD tool was clinically evaluated to analyze its accuracy and efficiency in rectal cancer. CT images were collected from 148 supine patients in whom tumor stage and type of surgery were not differentiated. The rectal cancer contours consisted of CTV and OARs, where the OARs included the bladder, left and right femoral head, left and right kidney, spinal cord and bowel bag. The MD contours reviewed and modified together by a senior radiation oncologist committee were set as the reference values. The Dice similarity coefficient (DSC), Jaccard coefficient (JAC) and Hausdorff distance (HD) were used to evaluate the AD accuracy. The correlation between CT slice number and AD accuracy was analyzed, and the AD accuracy for different contour numbers was compared. The time recorded in the present study included the MD time, AD time for different CT slice and contour numbers and the editing time for AD contours. The Pearson correlation coefficient, paired-sample t-test and unpaired-sample t-test were used for statistical analyses. The results of the present study indicated that the DSC, JAC and HD for CTV using AD were 0.80±0.06, 0.67±0.08 and 6.96±2.45 mm, respectively. Among the OARs, the highest DSC and JAC using AD were found for the right and left kidney, with 0.91±0.06 and 0.93±0.04, and 0.84±0.09 and 0.88±0.07, respectively, and HD was lowest for the spinal cord with 2.26±0.82 mm. The lowest accuracy was found for the bowel bag. The more CT slice numbers, the higher the accuracy of the spinal cord analysis. However, the contour number had no effect on AD accuracy. To obtain qualified contours, the AD time plus editing time was 662.97±195.57 sec, while the MD time was 3294.29±824.70 sec. In conclusion, the results of the present study indicate that AD can significantly improve efficiency and a higher number of CT slices and contours can reduce AD efficiency. The AD tool provides acceptable CTV and OARs for rectal cancer and improves efficiency for delineation.

MicroRNAs and therapeutic potentials in acute and chronic cardiac disease.

microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.

Catalytic Asymmetric Reductive Amination for Axially Chiral Aryl Aldehydes via Desymmetrization/Kinetic Resolution Cascade.

Herein we present an efficient chiral phosphoric-acid-catalyzed atropoenantioselective asymmetric reductive amination of biaryl dialdehydes. The process involves desymmetrization and the following kinetic resolution, with a wide range of axially chiral aryl aldehydes obtained with high optical purities.

Clinical characteristics of COVID-19 clusters in three schools in Beijing, China: A retrospective study.

Background: This retrospective analysis aims to investigate the clinical characteristics of students infected with the SARS-CoV-2 Omicron variant in three Beijing schools. Additionally, we explore the dynamic trends of nucleic acid cycle threshold values (Ct values) and serum antibody titers throughout the disease course. Methods: Demographic, clinical, nucleic acid Ct values, and antibody titer data were collected from cases in a COVID-19 cluster in Beijing Ditan Hospital, Capital Medical University, spanning from September 6 to October 1, 2022. Results: A total of 107 students infected with Omicron (BA.5.2 and BA.2.76) were identified across three schools. Primary clinical manifestations included fever and upper respiratory symptoms (85/107, 79.4 %), with the majority being classified as mild cases (96/107, 89.7 %). Notably, middle school students in the second school exhibited a higher peak body temperature compared to college students in the first and third schools (39.5 °C vs. 38.4 °C, adjusted P = 0.005; 39.5 °C vs. 38.6 °C, adjusted P = 0.002). Analysis of dynamic changes in Ct values revealed the lowest median Ct value in nasopharyngeal swabs on the third day of illness, reaching 35 after 9-11 days. Oropharyngeal swab nucleic acid median Ct value reached 35 approximately 3-5 days post-onset. Serum antibody detection showed continuous negativity of IgM antibody titers from days 1-10, while IgG antibody titers were positive on the first day and increased rapidly after one week. Conclusions: The three COVID-19 cluster school outbreaks primarily resulted from Omicron infections, with no severe or fatal cases observed. Clinically, the selection of different types of SARS-CoV-2 nucleic acid swabs for virus detection can be tailored based on the infection's course.

Causality between Sarcopenia and Depression: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Numerous observational studies have suggested a correlation between sarcopenia and depression, but the nature of this relationship requires further investigation. METHODS: This study employed bidirectional Mendelian randomization to explore this connection. Data from genome-wide association studies were used, encompassing measures of sarcopenia and mental factors, including depression and emotional states. The initial analysis concentrated on the impact of depression on sarcopenia, and then it examined the reverse relationship. The same methodology was applied to emotional data for validation. RESULTS: The results indicated a reciprocal causation between sarcopenia and depression, even when emotional state data were considered. Various emotions can impact sarcopenia, and in turn, sarcopenia can affect emotions, except subjective well-being. These findings highlight a cyclic deterioration between sarcopenia and depression, with a link to negative emotions and a partially ameliorative effect of subjective well-being on sarcopenia. CONCLUSIONS: In summary, this study sheds light on the interplay between psychiatric factors and sarcopenia, offering insights into intervention and prevention strategies.

Effects of Hypericum attenuatum Choisy extract on the immunologic function and intestinal microflora of broilers under oxidative stress.

This study investigated the impact of Hypericum attenuatum Choisy extract (HYG) on immunological function and the cecum microflora in broilers. A total of 240 one-day-old AA broilers were randomly divided into 5 groups with 6 replicates of 8 broilers each: 1) the CN group, in which broilers were injected with saline and fed a basal diet; 2) the PC group, in which broilers were injected with lipolyaccharide (LPS) and fed a basal diet; 3) the HYG1 group, in which broilers were injected with LPS and fed a 400 mg/kg HYG-supplemented diet; 4) the HYG2 group, in which broilers were injected with LPS and fed a 800 mg/kg HYG-supplemented diet; 5) the HYG3 group, in which broilers were injected with LPS and fed a 1,200 mg/kg HYG-supplemented diet. Broilers were injected with 1 mg/kg LPS or the same amount saline 12 hours before sampling on d 21 and 42. The results revealed that dietary 400 mg/kg HYG supplementation alleviated spleen index and thymus index abnormalities, balanced the disturbance of serum immunoglobulin (Ig)M and IgA levels, and regulated the cytokine balance in the serum, liver, spleen and jejunum tissues included induced by LPS. Dietary supplementation with 400 mg/kg HYG also downregulated the relative expression of the inhibitor of kappa B kinase alpha (IKKα) and interleukin (IL)-6 mRNAs in the liver and upregulated the relative expression of the inhibitor kappa B alpha (IκBα) and IL-10 mRNAs in the spleen. Dietary HYG improved the cecal microflora balance at 42 d by increasing the relative abundance of beneficial bacteria, such as Alistipes and Phascolarctobacterium, while reducing the relative abundance of harmful bacteria, such as Helicobacter and Colidextribacter. Spearman correlation analysis revealed a negative correlation between activation of the NF-κB inhibitory pathway in the liver and the presence of Phascolarctobacterium, Erysipelatoclostridium, Subdoligranulum and Parabacteroides. Conclusions: The incorporation of 400 mg/kg HYG into the diet was optimal in improving broiler immunological function.

Psychosocial Clusters and Their Associations with Depression, Anxiety and Stress Among Older Adults in Shanghai Communities: Results from a Longitudinal Study.

Purpose: Psychosocial factors have been found to profoundly impact mental health of older adults, but the main focus in the current literature has been on one particular aspect of these factors. This study aimed to identify latent classes of older adults based on four psychosocial factors (loneliness, social isolation, perceived social support, and social capital) and the transition of classes over 6 months. We also sought to assess the predictive role of changes in these classes in relation to depression, anxiety, and stress at 18-month follow-up. Methods: We analyzed longitudinal data from 581 community-dwelling older adults in Shanghai, China. The data were collected at baseline (T0), 6-month follow-up (T1) and 18-month follow-up (T2) between March 2021 and April 2023. Using latent class analysis, we identified three underlying classes (Social Connectors, Subjective Social Isolates, and Social Isolates) of the sample. We also established five transition categories from T0 to T1 (Social Connectors T0-T1, Subjective Social Isolates T0-T1, Social Isolates T0-T1, Good Transition, and Bad Transition) using latent transition analysis. Logistic regression was employed to examine the temporal relationships between these transition categories and subsequent symptoms of depression, anxiety and stress, adjusting for age, sex, education, marital status, family income level, sleep quality, health status and outcome variables at T0. Results: Multivariable associations revealed that compared to older adults with persistent good social environment (Social Connectors T0-T1), those with persistent high levels of loneliness and social isolation and low levels of perceived social support and social capital (Social Isolates T0-T1), and those who shifted towards a poorer social environment (Bad Transition) were more likely to experience depression, anxiety and stress at T2. Sustained subjective social isolation (Subjective Social Isolates T0-T1) was associated with more severe depressive symptoms at T2. Conclusion: Our study indicated that adverse psychosocial environment worsened mental health in older adults. These findings highlight the importance of early identification of older individuals at long-term psychosocial risk and development of tailored interventions to improve their social environment and mental health.

Coffee, Phosphoinositide 3-Kinase Signaling Pathway, and Prostate Cancer: A Prospective Study in the Health Professionals Follow-Up Study.

BACKGROUND: Higher coffee intake has been associated with reduced risk of prostate cancer, particularly aggressive forms. The activation of the phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in prostate carcinogenesis. OBJECTIVE: To evaluate associations between prediagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-Up Study, a prospective cohort study conducted in the United States. DESIGN: A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every 4 years thereafter until prostate cancer diagnosis. PARTICIPANTS SETTING: Study participants comprised 1242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens. MAIN OUTCOME MEASURES: The outcomes include the PI3K activation score; expression of insulin receptor and insulin-like growth factor 1 receptor; angiogenesis markers; and presence of the tumor suppressor phosphatase and tensin homolog, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia. STATISTICAL ANALYSES PERFORMED: Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence. RESULTS: Among coffee drinkers (86.6% of the population), median (25th, 75th percentile) coffee intake was 2 c/day (1, 3 c/day). The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 c/day coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for phosphatase and tensin homolog loss, insulin-like growth factor 1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and postatrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58. CONCLUSIONS: Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association.