Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis.

Background: Observational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive. Methods: In this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness. Results: The IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061-1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059-1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791-0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839-0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods. Conclusion: This study establishes a causal relationship between the gut microbiota and SP, shedding light on the "gut-spine" axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.

Puerarin Delays Mammary Gland Aging by Regulating Gut Microbiota and Inhibiting the p38MAPK Signaling Pathway.

Mammary gland aging is one of the most important problems faced by humans and animals. How to delay mammary gland aging is particularly important. Puerarin is a kind of isoflavone substance extracted from Pueraria lobata, which has anti-inflammatory, antioxidant, and other pharmacological effects. However, the role of puerarin in delaying lipopolysaccharide (LPS)-induced mammary gland aging and its underlying mechanism remains unclear. On the one hand, we found that puerarin could significantly downregulate the expression of senescence-associated secretory phenotype (SASP) and age-related indicators (SA-ß-gal, p53, p21, p16) in mammary glands of mice. In addition, puerarin mainly inhibited the p38MAPK signaling pathway to repair mitochondrial damage and delay mammary gland aging. On the other hand, puerarin could also delay the cellular senescence of mice mammary epithelial cells (mMECs) by targeting gut microbiota and promoting the secretion of gut microbiota metabolites. In conclusion, puerarin could not only directly act on the mMECs but also regulate the gut microbiota, thus, playing a role in delaying the aging of the mammary gland. Based on the above findings, we have discovered a new pathway for puerarin to delay mammary gland aging.

Phase-Transition-Promoted Thermoelectric Textiles Based on Twin Surface-Modified CNT Fibers.

With the fast development of new science and technology, wearable devices are in great demand in modern human daily life. However, the energy problem is a long-lasting issue to achieve real smart, wearable, and portable devices. Flexible thermoelectric generators (TEGs) based on thermoelectric conversion systems can convert body waste heat into electricity with excellent flexibility and wearability, which shows a new direction to solving this issue. Here in this work, polyethylenimine (PEI) and gold nanoparticles (Au NPs) twin surface-modified carbon nanotube fibers (CNTFs) were designed and prepared to fabricate thermoelectric textiles (TET) with high performance, good air stability, and high-efficiency power generation. To better utilize the heat emitted by the human body, microencapsulated phase change materials (MPCM) were coated on the hot end of the TET to achieve the phase-transition-promoted TET. MPCM-coated TET device could generate 25.7% more energy than the untreated control device, which indicates the great potential of the phase-transition-promoted TET.

PELE scores: pelvic X-ray landmark detection with pelvis extraction and enhancement.

PURPOSE: Pelvic X-ray (PXR) is widely utilized in clinical decision-making associated with the pelvis, the lower part of the trunk that supports and balances the trunk. In particular, PXR-based landmark detection facilitates downstream analysis and computer-assisted diagnosis and treatment of pelvic diseases. Although PXR has the advantages of low radiation and reduced cost compared to computed tomography (CT), it characterizes the 2D pelvis-tissue superposition of 3D structures, which may affect the accuracy of landmark detection in some cases. However, the superposition nature of PXR is implicitly handled by existing deep learning-based landmark detection methods, which mainly design the deep network structures for better detection performances. Explicit handling of the superposition nature of PXR is rarely done. METHODS: In this paper, we explicitly focus on the superposition of X-ray images. Specifically, we propose a pelvis extraction (PELE) module that consists of a decomposition network, a domain adaptation network, and an enhancement module, which utilizes 3D prior anatomical knowledge in CT to guide and well isolate the pelvis from PXR, thereby eliminating the influence of soft tissue for landmark detection. The extracted pelvis image, after enhancement, is then used for landmark detection. RESULTS: We conduct an extensive evaluation based on two public and one private dataset, totaling 850 PXRs. The experimental results show that the proposed PELE module significantly improves the accuracy of PXRs landmark detection and achieves state-of-the-art performances in several benchmark metrics. CONCLUSION: The design of PELE module can improve the accuracy of different pelvic landmark detection baselines, which we believe is obviously conducive to the positioning and inspection of clinical landmarks and critical structures, thus better serving downstream tasks. Our project has been open-sourced at https://github.com/ECNUACRush/PELEscores .

Gene association analysis to determine the causal relationship between immune cells and juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date. The objective of our study is to approach this inquiry from a genetic perspective, employing a method of genetic association analysis to ascertain the causal relationship between immune phenotypes and the onset of JIA. METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was used to select single nucleotide polymorphisms (SNPs) significantly associated with immune cells as instrumental variables to analyze the bidirectional causal relationship between 731 immune cells and JIA. There were four types of immune features (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)). Finally, the heterogeneity and horizontal reproducibility of the results were verified by sensitivity analysis, which ensured more robust results. RESULTS: We found that CD3 on CM CD8br was causally associated with JIA at the level of 0.05 significant difference (95% CI = 0.630 ~ 0.847, P = 3.33 × 10-5, PFDR = 0.024). At the significance level of 0.20, two immunophenotypes were causally associated with JIA, namely: HLA DR on CD14+ CD16- monocyte (95% CI = 0.633 ~ 0.884, P = 6.83 × 10-4, PFDR = 0.16) and HLA DR on CD14+ monocyte (95% CI = 0.627 ~ 0.882, P = 6.9 × 10-4, PFDR = 0.16). CONCLUSION: Our study assessed the causal effect of immune cells on JIA from a genetic perspective. These findings emphasize the complex and important role of immune cells in the pathogenesis of JIA and lay a foundation for further study of the pathogenesis of JIA.

Silent information regulator 2 deficiency exacerbates chronic cold exposure-induced colonic injury and p65 activation in mice.

Cold is a common stressor that threatens colonic health by affecting internal homeostasis. From the literature, Silent information regulator 2 (SIRT2) may have important roles during cold stress, but this conjecture requires investigation. To address this knowledge gap, we investigated the effects of SIRT2 on colonic injury in chronically cold-exposure mice. In a previous study, we showed that SIRT2 regulated p65 activation after cold exposure. In the current study, mice were exposed to 4 °C for 3 h/day for 3 weeks to simulate a chronic cold exposure environment. Chronic cold exposure shortened colon length, disrupted tight junctions in colonic epithelial tissue, and disordered colonic flora. Chronic cold exposure also increased p65 acetylation levels, promoted nuclear factor (NF)-κB activation, and increased the expression of its downstream pro-inflammatory factors, while SIRT2 knockdown aggravated the consequences of tissue structure disruption and increased inflammatory factors brought about by chronic cold exposure to some extent, but could alleviate the downregulation of colonic tight junction-related proteins to some extent. We also observed direct SIRT2 regulatory effects toward p65, and in Caco-2 cells treated with lipopolysaccharide (LPS), SIRT2 knockdown increased p65 acetylation levels and pro-inflammatory factor expression, while SIRT2 overexpression reversed these phenomena. Therefore, SIRT2 deletion exacerbated chronic cold exposure-induced colonic injury and p65 activation in mice. Mechanistically, p65 modification by SIRT2 via deacetylation may affect NF-κB signaling. These findings suggest that SIRT2 is a key target of colonic health maintenance under chronic cold exposure conditions.

A mixed-dimensional quasi-1D BiSeI nanowire-2D GaSe nanosheet p-n heterojunction for fast response optoelectronic devices.

Due to the unique combination configuration and the formation of a built-in electric field, mixed-dimensional heterojunctions present fruitful possibilities for improving the optoelectronic performances of low-dimensional optoelectronic devices. However, the response times of most photodetectors built from mixed-dimensional heterojunctions are within the millisecond range, limiting their applications in fast response optoelectronic devices. Herein, a mixed-dimensional BiSeI/GaSe van der Waals heterostructure is designed, which exhibits visible light detection ability and competitive photoresponsivity of 750 A W-1 and specific detectivity of 2.25 × 1012 Jones under 520 nm laser excitation. Excitingly, the device displays a very fast response time, e.g., the rise time and decay time under 520 nm laser excitation are 65 µs and 190 µs, respectively. Our findings provide a prospective approach to mixed-dimensional heterojunction photodetection devices with rapid switching capabilities.

Homogenizing out-of-plane cation composition in perovskite solar cells.

Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.

Research on Resistance to Water Intoxication of LaCoO3 Doped with Fe at B Sites.

In this paper, the methods of spin polarization density functional theory and vasp software package are used to simulate the adsorption of H2O molecules on the surface of LaCoO3 and La2CoFeO6(001). It was found that when Fe was doped at B-sites, the adsorption energy changed from -3.7493 eV at CoO2 to -2.5397 eV at CoFeO4, which decreased by about 1/3. Meanwhile, the change of electric charge and the amount of electron transfer decreased overall. The results indicated that Fe doping could inhibit the adsorption of H2O by perovskites and thus hinder the next toxic reaction. Therefore, this paper will lay a certain theoretical foundation for the study of perovskite anti-poisoning mechanism and provide a meaningful reference for further experimental research.

Manual Therapy for a Chronic Non-Specific Low Back Pain Rat Model.

Chronic low back pain (CLBP) is a highly prevalent condition worldwide and a major cause of disability. The majority of patients with CLBP are diagnosed with chronic non-specific low back pain (CNLBP) due to an unknown pathological cause. Manual therapy (MT) is an integral aspect of traditional Chinese medicine and is recognized as Tuina in China. It involves techniques like bone-setting and muscle relaxation manipulation. Despite its clinical efficacy in treating CNLBP, the underlying mechanisms of MT remain unclear. In animal experiments aimed at investigating these mechanisms, one of the main challenges is achieving normative MT on CNLBP model rats. Improving the stability of finger strength is a key issue in MT. To address this technical limitation, a standardized procedure for MT on CNLBP model rats is presented in this study. This procedure significantly enhances the stability of MT with the hands and alleviates common problems associated with immobilizing rats during MT. The findings of this study are of reference value for future experimental investigations of MT.

Lever positioning manipulation alters real-time brain activity in patients with lumbar disc herniation: An amplitude of low-frequency fluctuation and regional homogeneity study.

INTRODUCTION: Lumbar disk herniation (LDH) is the preeminent disease of lever positioning manipulation (LPM), a complex disorder involving alterations in brain function. Resting-state functional magnetic resonance imaging (rs-fMRI) has the advantages of non-trauma, zero radiation, and high spatial resolution, which has become an effective means to study brain science in contemporary physical therapy. Furthermore, it can better elucidate the response characteristics of the brain region of LPM intervention in LDH. We utilized two data analysis methods, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of rs-fMRI, to assess the effects of LPM on real-time brain activity in patients with LDH. METHODS: Patients with LDH (Group 1, n = 21) and age-, gender- and education-matched healthy controls without LDH (Group 2, n = 21) were prospectively enrolled. Brain fMRI was performed for Group 1 at two-time points (TPs): before LPM (TP1) and after one LPM session (TP2). The healthy controls (Group 2) did not receive LPM and underwent only one fMRI scan. Participants in Group 1 completed clinical questionnaires assessing pain and functional disorders using a Visual Analog Scale and the Japanese Orthopaedic Association (JOA), respectively. Furthermore, we employed MNL90 (Montreal Neurological Institute) as a brain-specific template. RESULTS: Compared to the healthy controls (Group 2), the patients with LDH (Group 1) had significant variation in ALFF and ReHo values in brain activity. After the LPM session (TP2), Group 1 at TP1 also showed significant variation in ALFF and ReHo values in brain activity. In addition, the latter (TP2 vs TP1) showed more significant changes in brain regions than the former (Group 1 vs Group 2). The ALFF values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The Reho values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The ALFF values were increased in the Precuneus_R and decreased in the Frontal_Mid_Orb_L in Group 1 compared with Group 2. Only three brain areas with significant activity in Group 1 compared with Group 2: Frontal_Mid_Orb_L, Frontal_Sup_Orb_L, and Frontal_Mid_R. ALFF value in the Frontal_Mid_R at TP2 correlated positively with the change rates of JOA scores between TP1 and TP2 (P = 0.04, r = 0.319, R2 = 0.102). DISCUSSION: Patients with LDH showed abnormal brain ALFF and ReHo values, which were altered after LPM. The default mode network, prefrontal cortex, and primary somatosensory cortex regions could predict real-time brain activity for sensory and emotional pain management in patients with LDH after LPM.

Role of SIRT2 in intestinal barrier under cold exposure.

Prolonged cold exposure causes body stress and damages health. The intestinal environment is complex and variable, and direct contact with the external environment can easily cause stress, damage and even lead to diseases such as diarrhea. AIMS: This study aimed to reveal the role of cold exposure on ileum damage and the role of SIRT2 in this process. MAIN METHODS: C57BL6 mice and SIRT2 knockout mice were used to construct a chronic cold exposure model (21 days, random 4 °C exposure for 3 h per day), which was tested by various methods, including intestinal permeability assays, morphological assays, ultrastructural assays, western blotting, and fluorescence staining. In vitro assays were performed on the mouse small intestinal epithelial cell line MODE-K to investigate the role of endoplasmic reticulum stress, SIRT2 knockout, and autophagy on tight junctions. KEY FINDINGS: The results showed that chronic cold exposure damaged the ileal epithelial barrier, with endoplasmic reticulum stress. Knockout of SIRT2 alleviates ileal injury via enhanced autophagy under cold exposure. And autophagy can restore the expression of ZO-1 under stress. SIGNIFICANCE: This study can provide potential target and basic data for the treatment of IBD and other disorders of the intestinal barrier. Autophagy may be an important means of restoring damage to the intestinal barrier.

Three-dimensional topography of eye-specific domains in the lateral geniculate nucleus of pigmented and albino rats.

We previously revealed the presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of pigmented rats. On the other hand, previous studies have shown that the ipsilateral-eye domains of the dorsal lateral geniculate nucleus (dLGN) are segregated into a handful of patches in pigmented rats. To investigate the three-dimensional (3D) topography of the eye-specific patches of the dLGN and its relationship with ODCs, we injected different tracers into the right and left eyes and examined strain difference, development, and plasticity of the patches. Furthermore, we applied the tissue clearing technique to reveal the 3D morphology of the LGN and were able to observe entire retinotopic map of the rat dLGN at a certain angle. Our results show that the ipsilateral domains of the dLGN appear mesh-like at any angle and are developed at around time of eye-opening. Their development was moderately affected by abnormal visual experience, but the patch formation was not disrupted. In albino Wistar rats, ipsilateral patches were observed in the dLGN, but they were much fewer, especially near the central visual field. These results provide insights into how ipsilateral patches of the dLGN arise, and how the geniculo-cortical arrangement is different between rodents and primates.

Bibliometric Analysis of Functional Magnetic Resonance Imaging Studies on Manual Therapy Analgesia from 2002-2022.

Background: Research on the brain mechanisms underlying manual therapy (MT)-induced analgesia has been conducted worldwide. However, no bibliometric analysis has been performed on functional magnetic resonance imaging (fMRI) studies of MT analgesia. To provide a theoretical foundation for the practical application of MT analgesia, this study examined the current incarnation, hotspots, and frontiers of fMRI-based MT analgesia research over the previous 20 years. Methods: All publications were obtained from the Science Citation Index-Expanded (SCI-E) of Web of Science Core Collection (WOSCC). We used CiteSpace 6.1.R3 to analyze publications, authors, cited authors, countries, institutions, cited journals, references, and keywords. We also evaluated keyword co-occurrences and timelines, and citation bursts. The search was conducted from 2002-2022 and was completed within one day on October 7, 2022. Results: In total, 261 articles were retrieved. The total number of annual publications showed a fluctuating but overall increasing trend. Author B. Humphreys had the highest number of publications (eight articles) and J. E. Bialosky had the highest centrality (0.45). The United States of America (USA) was the country with the most publications (84 articles), accounting for 32.18% of all publications. Output institutions were mainly the University of Zurich, University of Switzerland, and the National University of Health Sciences of the USA. The Spine (118) and the Journal of Manipulative and Physiological Therapeutics (80) were most frequently cited. The four hot topics in fMRI studies on MT analgesia were "low back pain", "magnetic resonance imaging", "spinal manipulation", and "manual therapy." The frontier topics were "clinical impacts of pain disorders" and "cutting-edge technical capabilities offered by magnetic resonance imaging". Conclusion: fMRI studies of MT analgesia have potential applications. fMRI studies of MT analgesia have linked several brain areas, with the default mode network (DMN) garnering the most attention. Future research should include international collaboration and RCTs on this topic.

Leveraging single-cell Raman spectroscopy and single-cell sorting for the detection and identification of yeast infections.

Invasive fungal infection serves as a great threat to human health. Discrimination between fungal and bacterial infections at the earliest stage is vital for effective clinic practice; however, traditional culture-dependent microscopic diagnosis of fungal infection usually requires several days, meanwhile, culture-independent immunological and molecular methods are limited by the detectable type of pathogens and the issues with high false-positive rates. In this study, we proposed a novel culture-independent phenotyping method based on single-cell Raman spectroscopy for the rapid discrimination between fungal and bacterial infections. Three Raman biomarkers, including cytochrome c, peptidoglycan, and nucleic acid, were identified through hierarchical clustering analysis of Raman spectra across 12 types of most common yeast and bacterial pathogens. Compared to those of bacterial pathogens, the single cells of yeast pathogens demonstrated significantly stronger Raman peaks for cytochrome c, but weaker signals for peptidoglycan and nucleic acid. A two-step protocol combining the three biomarkers was established and able to differentiate fungal infections from bacterial infections with an overall accuracy of 94.9%. Our approach was also used to detect ten raw urinary tract infection samples. Successful identification of fungi was achieved within half an hour after sample obtainment. We further demonstrated the accurate fungal species taxonomy achieved with Raman-assisted cell ejection. Our findings demonstrate that Raman-based fungal identification is a novel, facile, reliable, and with a breadth of coverage approach, that has a great potential to be adopted in routine clinical practice to reduce the turn-around time of invasive fungal disease (IFD) diagnostics.

Effectiveness and safety of acupuncture and moxibustion for chronic prostatitis: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Chronic prostatitis (CP) refers to a disease characterized by local pain and discomfort, urination discomfort, and quality of life. Acupuncture (ACU) and moxibustion are widely used in the treatment of CP, and the curative effect is satisfactory. Several systematic reviews (SRs) and meta-analyzes have reported the effectiveness of ACU and moxibustion in treating patients with CP. However, the evidence is not systematically integrated. This overview aims to integrate and evaluate the reliability of these SRs and the evidence generated from the ACU and moxibustion for CP meta-analysis. METHODS: We will make a comprehensive retrieval in seven databases as following: Embase, Cochrane Library, Pubmed, Chinese databases SinoMed (previously called the Chinese Biomedical Database), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Data (WF). The time is limited from the construction of the library to May 2021. We will use the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool to evaluate methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) will be used in the report checklist to assess the quality of reports in the study. The GRADE will be used to evaluate the included SRs and meta-analysis. Our reviewers will conduct SRs, qualification evaluation, data extraction, methodological quality and evidence quality screening in pairs. The outcomes of interest include: NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), effective rate, other CP symptom scales, EPS-WBC, and adverse events. Evidence will be combined based on patient subgroups and results where appropriate. RESULTS: The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: INPLASY202150018. CONCLUSION: This overview will provide comprehensive evidence of ACU and moxibustion for patients with CP.

Stain-free Gram staining classification of pathogens via single-cell Raman spectroscopy combined with machine learning.

Gram staining (GS) is one of the routine microbiological operations to classify bacteria based on the cell wall structure. Accurate GS classification of pathogens is of great significance since it helps correct administration of antimicrobial treatment. The laborious procedure and low sensitivity results related to conventional GS have resulted in reluctance among clinicians. In this study, we integrate confocal Raman spectroscopy and machine learning techniques to distinguish Gram-negative (GN) or Gram-positive (GP) bacteria. A single-cell Raman database including seven most common clinical pathogens (three GP strains and four GN strains) was constructed. Machine learning algorithms including the support-vector machine (SVM), k-nearest neighbors' algorithm (k-NN), gradient boosting machine (GBM), linear discriminant analysis (LDA), and t-distributed stochastic neighbor embedding (t-SNE) were trained to achieve the binary classification for GS. With such a relatively small database, the SVM model achieved the highest accuracy of 98.1%. The molecular signatures of GN and GP embedded in their Raman fingerprints were identified with hierarchical cluster analysis (HCA). The results indicated that Raman peaks for peptidoglycan and teichoic acid were the most significant factors that contributed to accurate classification. The Raman machine learning approach could greatly enhance the diagnosis of pathogenic infections.

Cold exposure-induced endoplasmic reticulum stress regulates autophagy through the SIRT2/FoxO1 signaling pathway.

Cold is a factor affecting health in humans and animals. The liver, a major metabolic center, is highly susceptible to ambient air temperature. Recent studies have shown that endoplasmic reticulum (ER) stress is associated with the liver, and regulates the occurrence and development of liver injury and autophagy. However, the mechanism underlying the relationship between cold exposure and ER stress in the liver is not well understood. In this study, we investigated the effect of ER stress on liver autophagy and its mechanism under cold exposure. AML12 cells were treated with Tg to construct an ER stress model, and the level of autophagy increased. To further explore the mechanism through which ER stress regulates autophagy, we knocked down SIRT2 with shRNA in Tg-treated AML12 cells. Knockdown of SIRT2 significantly increased ER stress and autophagy, increased FoxO1 acetylation, and promoted its entry into the nucleus. To further verify the results of in vitro experiments, we exposed mice to 4°C for 3 h per day for 3 weeks to exacerbate the burden on the liver after cold exposure. Cold exposure damaged the structure and function of the liver and promoted the inflammatory response. It also activated ER stress and promoted autophagy. In addition, cold exposure inhibited the expression of SIRT2, promoted FoxO1 acetylation, and enhanced the interaction with autophagy. Our findings indicated that cold exposure induces liver damage, ER stress, and autophagy through the SIRT2/FoxO1 pathway. These findings suggest that SIRT2 may be a potential target for regulating health under cold exposure.

Depression and Cognition Mediate the Effect of Self-Perceptions of Aging Over Frailty Among Older Adults Living in the Community in China.

Objectives: The aims of the study were first to investigate the association between self-perceptions of aging and frailty and second to determine whether self-perceptions of aging affects frailty via depressive symptoms and cognitive status among older adults living in the community in China. Methods: Among 850 older adults who participated in this cross-sectional study, 822 older adults made valid responses to Tilburg Frailty Indicator, Brief Aging Perceptions Questionnaire, UCLA loneliness scale-8, Mini-Mental State Examination, and Patient Health Questionnaire-9 between March to December 2019. The possible pathways of self-perceptions of aging affecting frailty were analyzed based on the structural equation modeling analysis. Results: A total of 21.53% of older adults reported frailty. Correlation analyses showed that higher degrees of frailty were related to greater loneliness, more depressive symptoms, more negative self-perceptions of aging, worse locomotive function, and cognitive status (r = 0.267, r = 0.440, r = 0.481, r = 0.451, r = -0.337; p < 0.001). Multiple regression analysis showed that loneliness, depressive symptoms, self-perceptions of aging, locomotive function, and cognitive status were the five factors to be entered the regression equation, and the variance of joint explanation was 46.60%. SPA had a direct effect on frailty (ß = 0.306 and p < 0.001), and SPA indirectly affects frailty by independently affecting depressive symptoms (ß = 0.391, 95% CI [0.027, 0.061], and p < 0.001) or cognitive status (ß = 0.148, 95% CI [0.009, 0.024], and p < 0.001) of older adults. Conclusion: These findings help explain the potential psychological mechanisms through which SPA impacts frailty and may aid community healthcare providers in China in identifying individuals at high risk of frailty. The results suggest that health staff should help older adults improve their perspectives on aging, alleviate or prevent depressive symptoms, and improve cognitive status to delay the progress of frailty and promote healthy aging.

Cold Exposure Induces Intestinal Barrier Damage and Endoplasmic Reticulum Stress in the Colon via the SIRT1/Nrf2 Signaling Pathway.

Ambient air temperature is a key factor affecting human health. Long-term exposure to a cold environment can cause various diseases, while the impact on the intestine, the organ which has the largest contact area with the external environment, cannot be ignored. In this study, we investigated the effect of chronic cold exposure on the colon and its preliminary mechanism of action. Mice were exposed to 4°C for 3 hours a day for 10 days. We found that cold exposure damaged the morphology and structure of the colon, destroyed the tight junctions of the colonic epithelial tissue, and promoted inflammation of the colon. At the same time, cold exposure also activated the unfolded protein response (UPR) in the colon and promoted apoptosis in intestinal epithelial cells. Chronic cold exposure induced oxidative stress in vivo, but also significantly enhanced the response of the Nrf2 pathway that promotes an anti-oxidant effect. Furthermore, we demonstrated that chronic cold exposure promoted p65 acetylation to aggravate the inflammatory response by inhibiting SIRT1. Similar results were observed following SIRT1 knock-down by shRNA in Caco-2 cells treated with Thapsigargin (Tg). Knock-down of SIRT1 promoted nuclear localization of Nrf2, and increased the level of Nrf2 acetylation. Taken together, our study indicates that cold exposure may aggravate endoplasmic reticulum stress and damage epithelial tight junctions in the colon by inhibiting SIRT1, which promotes nuclear localization of Nrf2 and induces an anti-oxidant response to maintain intestinal homeostasis. These findings suggest that SIRT1 is a potential target for regulating intestinal health under cold exposure conditions.