Phylogenomic analyses sheds new light on the phylogeny and diversification of Corydalis DC. in Himalaya-Hengduan Mountains and adjacent regions.

The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

[Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months]. / æ—©äº§å°äºŽèƒŽé¾„å„¿æ ¡æ­£0~24æœˆé¾„è¿½èµ¶ç”Ÿé•¿çš„çºµå‘ç ”ç©¶.

OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

Influencing factors analysis of adaptability of cancer patients to return-to-work.

OBJECTIVES: To clarify the adaptability of cancer patients to return to work and explore its influencing factors. DESIGN: A cross-sectional study. SETTINGS/PARTICIPANTS: From March to October 2021, 283 cancer patients in the follow-up period were recruited from the oncology departments of four secondary and above hospitals and cancer friendship associations in Nantong city using self-developed scale of adaptability to return to work for cancer patients by convenience sampling method. METHODS: The contents included general sociodemographic data, disease-related data, cancer patients' readability to work Scale, Medical Coping Style Questionnaire, Social Support Rating Scale, Family Closeness and Readability Scale, General self-efficacy Scale and Social impact Scale. Paper questionnaires were used for face-to-face data collection, and SPSS17.0 was used for statistical analysis. Univariable analyses and multiple linear regression analysis were conducted. RESULTS: The overall score of cancer patients' adaptability to return to work was (87.05±20.255), (22.54±4.234) for the dimension of focused rehabilitation, (32.02±9.013) for the dimension of reconstruction effectiveness, and (32.49±9.023) for the dimension of adjustment planning. Multiple linear regression analysis showed that the current return to full-time work (ß =0.226, P 0.05), the current return to non-full-time work (ß =0.184, P 0.05), yield response (ß = -0.132, P 0.05), and general self-efficacy (ß =0.226, P 0.05) could affect their return to work adaptation. CONCLUSION: The results of status quo and influencing factors showed that the adaptability of cancer patients to return to work was generally higher in this study. Cancer patients who had participated in work, had lower yield coping scores and stigma scores, and higher self-efficacy scores and family adjustment and intimacy scores had better adaptability to return to work again. ETHICAL APPROVAL: It has been approved by the Human Research Ethics Committee of the Affiliated Hospital of Nantong University (Project No.202065).

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus.

Mounting evidence indicates that immune dysfunction may contribute to the neurobiology of major depressive disorder (MDD). Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) were recently reckoned pivotally to regulate NOD-like receptor protein 3 (NLRP3) in microglia. Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been studied in various animal models of human disease with anti-inflammatory and antioxidant activities. Herein, we investigated the potential antineuroinflammatory effects of pinocembrin on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. Male C57BL/6J mice were subjected to CUMS for 4 weeks, treatment group was injected with pinocembrin at a dose of 20 mg/kg. After the stress procedure, behavioral tests, including sucrose preference tests (SPTs) and tail suspension tests (TSTs) were performed to evaluate depressive-like phenotype. Subsequently, the expression of cytokines and microglia-related inflammatory biomarkers were assessed. In the study, we found that pinocembrin significantly blocked the declination of SPT percentage and the extension of TST immobility durations in the depression mouse model. Also, we observed that pinocembrin significantly suppressed microglial activation in the hippocampus. Additionally, pinocembrin downregulated hippocampal NLRP3 through P2X7/TLR4 pathway, and also regulated the CUMS-induced imbalance of pro-inflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha and interleukin-6. In conclusion, pinocembrin ameliorates CUMS-induced depressive-like behaviors possibly through downregulating P2X7/TLR4 pathway, providing the mechanism of antidepressant treatment.

Integration of Motion and Form Cues for the Perception of Self-Motion in the Human Brain.

When moving around in the world, the human visual system uses both motion and form information to estimate the direction of self-motion (i.e., heading). However, little is known about cortical areas in charge of this task. This brain-imaging study addressed this question by using visual stimuli consisting of randomly distributed dot pairs oriented toward a locus on a screen (the form-defined focus of expansion [FoE]) but moved away from a different locus (the motion-defined FoE) to simulate observer translation. We first fixed the motion-defined FoE location and shifted the form-defined FoE location. We then made the locations of the motion- and the form-defined FoEs either congruent (at the same location in the display) or incongruent (on the opposite sides of the display). The motion- or the form-defined FoE shift was the same in the two types of stimuli, but the perceived heading direction shifted for the congruent, but not for the incongruent stimuli. Participants (both sexes) made a task-irrelevant (contrast discrimination) judgment during scanning. Searchlight and ROI-based multivoxel pattern analysis revealed that early visual areas V1, V2, and V3 responded to either the motion- or the form-defined FoE shift. After V3, only the dorsal areas V3a and V3B/KO responded to such shifts. Furthermore, area V3B/KO shows a significantly higher decoding accuracy for the congruent than the incongruent stimuli. Our results provide direct evidence showing that area V3B/KO does not simply respond to motion and form cues but integrates these two cues for the perception of heading.SIGNIFICANCE STATEMENT Human survival relies on accurate perception of self-motion. The visual system uses both motion (optic flow) and form cues for the perception of the direction of self-motion (heading). Although human brain areas for processing optic flow and form structure are well identified, the areas responsible for integrating these two cues for the perception of self-motion remain unknown. We conducted fMRI experiments and used multivoxel pattern analysis technique to find human brain areas that can decode the shift in heading specified by each cue alone and the two cues combined. We found that motion and form cues are first processed in the early visual areas and then are likely integrated in the higher dorsal area V3B/KO for the final estimation of heading.

COVID-19 pandemic related long-term chronic stress on the prevalence of depression and anxiety in the general population.

BACKGROUND: The COVID-19 pandemic has lasted for more than 1 year, causing far-reaching and unprecedented changes in almost all aspects of society. This study aimed to evaluate the long-term consequences of the COVID-19 pandemic on depression and anxiety, and explore the factors associated with it. METHODS: A cross-sectional study using an online survey was conducted to assess mental health problems from February 2 to February 9, 2021 by using patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). The insomnia severity index (ISI), demographic data and COVID-19 related variables were measured by a self-designed questionnaire. The factors associated with depressive and anxiety symptoms were identified by Pearson chi-square test and binary logistic regression analysis. RESULTS: In the study that 1171 participants enrolled, the overall prevalence of depressive and anxiety symptoms among general people was 22.6 and 21.4% respectively in the present study. Living alone was a potential risk factor for depressive symptoms, while regular exercises was a potential protective factor. The prevalence of depressive and anxiety symptoms was significantly associated with the severity of insomnia symptoms and the negative feelings about pandemic. CONCLUSION: COVID-19 pandemic- related chronic stress has brought about profound impacts on long-term mental health in the general population. The level of insomnia and a negative attitude towards the pandemic are significantly correlated with unfavorable mental health. However, we failed to found a significant association of age and gender with the mental health symptoms, although they were recognized as well-established risk factors during the outbreak by some other studies. This discrepancy may be because the acute and chronic effects of the pandemic are influenced by different factors, which reminds that more attention should be paid to the intrinsic psychological factors and physical reactions towards COVID-19.

Exploration of interventions to enhance return-to-work for cancer patients: A scoping review.

OBJECTIVE: With the increasing incidence and earlier onset of cancer, more and more cancer patients are facing the problems of return-to-work. This review is to explore the types, contents, and results of return-to-work interventions for cancer patients. METHODS: This scoping review followed Arksey and O'Malley's framework and PRISMA-ScR List. Three Chinese databases and five English databases were searched from the establishment of databases to 31 March, 2021. Article selection and data extraction were conducted by two researchers. RESULTS: Thirty-two studies and 1916 cancer patients with mainly breast and gastrointestinal cancer were included. According to the contents, interventions could be divided into four types: (1) physical interventions (n = 6), including high-intensity exercise, low-to-moderate intensity exercise, yoga, and upper limb functional training, (2) psychological interventions (n = 2), including early active individualized psychosocial support and mindfulness-based recovery, (3) vocational interventions (n = 14), including making work plans, educational leaflets, vocational consultations, electronic health intervention, and interventions targeting at employers, (4) multidisciplinary interventions (n = 10), including any combination of above interventions. Physical exercises, making working plans, vocational consultations, educational leaflets, two combinations of vocational and physical interventions were validated to have positive results in enhancing cancer patients' return-to-work. CONCLUSIONS: Return-to-work interventions for cancer patients are diversified and can be divided into physical, psychological, vocational, and multidisciplinary interventions. Medical staffs can utilize physical exercises, making working plans, vocational consultation, educational leaflets, combinations of vocational and physical interventions to enhance cancer patients' return-to-work. Other interventions still need to be developed and validated.

Genome-wide analysis and prediction of genes involved in the biosynthesis of polysaccharides and bioactive secondary metabolites in high-temperature-tolerant wild Flammulina filiformis.

BACKGROUND: Flammulina filiformis (previously known as Asian F. velutipes) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicted its biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis. RESULTS: We found that the genome of the F. filiformis was 35.01 Mb in length and harbored 10,396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain. CONCLUSIONS: F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.

Minocycline prevents the depressive-like behavior through inhibiting the release of HMGB1 from microglia and neurons.

BACKGROUND: Our previous study reports the causal role of high mobility group box 1 (HMGB1) in the development of depression; and we find glycyrrhizic acid (GZA) can be a potential treatment for major depressive disorder (MDD) considering its inhibition of HMGB1 activity. This study aims to further explore the exact cell types that release HMGB1 in the hippocampus. METHODS: We detected the effects of microglia conditioned medium on primary astrocytes and neurons. The effects of minocycline on depressive-like behaviors were tested in BABLB/c mice after four weeks of chronic unpredictable mild stress (CUMS) exposure. Furthermore, the immunofluorescence (IF) assays, hematoxylin-eosin (HE) and TUNEL staining were used to observe hippocampal slices to evaluate the release of HMGB1. The cytoplasmic translocations of HMGB1 protein were assayed by western-blot. RESULTS: Exposure to CUMS caused an active release of HMGB1 from microglia and neurons in the hippocampus. After minocycline administration for inhibiting the activation of microglia, both microglia and neurons reduced the release of HMGB1 and the protein level of central and peripheral HMGB1 recovered accordingly. Along with blocking the release of HMGB1, behavioral and cognitive deficits induced by CUMS were improved significantly by minocycline. In addition, the supernatant of primary microglia stimulated the secretion of HMGB1 in primary neurons, not in astrocytes, at 24 h after 4 h-LPS treatment. CONCLUSION: All the evidence supported our hypotheses that microglia and neurons are the main cell sources of HMGB1 release under CUMS condition, and that the release of HMGB1 by microglia may play an important role in the development of depressive-like behavior.

Synthesis of gem-difluoroalkenes via nickel-catalyzed allylic defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides.

A nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides has been developed. Various substituted trifluoromethyl alkenes and epoxides were found to be suitable reaction substrates. This reaction enabled C(sp3)-C(sp3) bond construction through allylic defluorinative cross-coupling of trifluoromethyl alkenes under mild reaction conditions. This methodology was highly compatible with various sensitive functional groups, providing access to a diverse array of functionalized gem-difluoroalkene-containing alcohol compounds.

Sex differences in depressive-like behaviour may relate to imbalance of microglia activation in the hippocampus.

As is reported, the incidence and prevalence of depression are higher in women than in men, but the cause of this sex difference remains elusive. Although recent studies implicated that over-activated microglia played a crucial role in depression, whether hippocampal microglia associates with the sex difference of depressive-like behaviours is intriguing. In the present study, both male and female mice were subjected to chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioural tests were performed to evaluate depressive-like phenotypes, while several microglia-related biomarkers and neurotrophic factor in hippocampi were detected to analyse sex difference. As a result, CUMS interfered with the body weight gain, sucrose preference and spontaneous activity in mice of both sexes. However, this effect tended to be more impressive in females. Generally, hippocampal microglia were activated regardless of sex, but the expressions of pro- and anti-inflammatory factors induced by CUMS were sex-specific. Chronic stress increased hippocampal iNOS and IL-1ß mRNA levels only in male mice, while upregulated TNF-α mRNA just in females. Meanwhile, the expressions of hippocampal IL-10, Arg-1 and IL-1ra were all downregulated in CUMS females rather than males. In addition, though the ratios of the pro- vs. anti-inflammatory cytokines elevated after the stress paradigm in both sexes, we noticed more remarkable trends in female mice regarding TNF-α/IL-10 and iNOS/Arg-1. This discovery suggested that females were inclined to be more pro-inflammatory after stress. Afterwards, we observed that the expressions of BDNF and its receptor TrkB in hippocampus decreased greater in female compared to male mice when facing stress stimulations. Furthermore, the depressive-like behaviours were correlated to BDNF mRNA quantities in both sex mice, and there was also a sex-specific relationship between BDNF and hippocampal microglia-related inflammatory biomarkers. Collectively, our study speculated that the imbalance of microglial pro- and anti-inflammatory states as well as the BDNF-TrkB-dependent pathway in hippocampus is involved in the depressive-like behaviours. The "microglia-neuroinflammation-BDNF" interconnection may be a fundamental mechanism for sex differences in depression.

Chemical Composition and Antioxidant Activity of Tuber indicum from Different Geographical Regions of China.

Tuber indicum, an endemic truffle species in eastern Asian, is an edible mushroom that is both an important export and widely distributed across China. Many existing studies on truffles focus on analyzing their taxonomy, population genetics, volatile organic compounds and artificial cultivation of the truffles, while little information is available about their nutrient composition and pharmacological activity, especially the relationship between chemical composition in ascocarps and their geographic distributions. This study presents a comprehensive investigation of the chemical composition of T. indicum, including free sugars, fatty acids, organic acids, phenolic acids, flavonoids, and polysaccharides, and tracks the antioxidant activity of T. indicum ascocarps collected from five geographical regions of four provinces in P. R. China: Hebei, Tibet, Yunnan, and Liaoning province. Our results showed that T. indicum collected from Qujing, Yunnan province, possessed the highest amount of free sugars (23.67 mg/g dw), total flavonoids (2.31 mg/g dw), total phenolics (4.46 mg/g dw) and the highest DPPH and ABTS radical-scavenging activities. The amount of water-soluble polysaccharides was the highest (115.24 mg/g dw) in ascocarps from Tibet, the total organic acids was the highest (22.073 mg/g dw) in ascocarps from Gongshan, and polyunsaturated fatty acids were most abundant in those from Hebei province. This study reveals that the quantity of chemical compounds in T. indicum varies by geographical origin. Detecting differences in chemical composition may provide important data for understanding the relationship between environmental factors and truffle formation, as well as quality evaluation of the commercial species T. indicum throughout China.

Peer Supporters' Experience of Supporting Cancer Patients: A Meta-synthesis.

BACKGROUND: With the widespread use of peer support in the cancer field, more and more cancer survivors are becoming supporters. However, they may bear a huge psychological burden in the peer support project. There has been little effort to analyze supporters' experiences from a meta-perspective. OBJECTIVE: The aims of this study were to review the literature on the experience of patients serving as peer supporters, integrate qualitative data to explore the experiences of supporters participating in peer support programs, and provide suggestions for future researchers. INTERVENTIONS/METHODS: China Knowledge Network, Wanfang Database, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, CINAHL, and PsycINFO were searched. Titles, abstracts, and full texts were screened. Included articles (n = 10) underwent data extraction, the Joanna Briggs Institute Critical Appraisal Tool for qualitative researches (2016) quality evaluation, and thematic synthesis. RESULTS: The literature ultimately included 10 studies from which 29 themes were distilled and grouped into 2 main categories: benefits and challenges of peer support for supporters. CONCLUSIONS: Peer supporters will not only gain social support, growth, and recovery but also experience various challenges when providing peer support. Both supporters' and patients' experiences of participating in peer support programs deserve the attention of researchers. Researchers need to be rigorous in controlling the implementation of peer support programs to help supporters gain and overcome challenges. IMPLICATIONS FOR PRACTICE: Future researchers can use study findings to better develop peer support programs. More peer support projects are needed to explore a standardized peer support training guide.

Microglial NLRP3 inflammasome activation mediates diabetes-induced depression-like behavior via triggering neuroinflammation.

BACKGROUND: Abundant evidence suggests that the prevalence and risk of depression in people with diabetes is high. However, the pathogenesis of diabetes-related depression remains unclear. Since neuroinflammation is associated with the pathophysiology of diabetic complications and depression, this study aims to elucidate the neuroimmune mechanism of diabetes-related depression. METHODS: Male C57BL/6 mice were injected with streptozotocin to establish a diabetes model. After screening, diabetic mice were treated with the NLRP3 inhibitor MCC950. Then, metabolic indicators and depression-like behaviors were evaluated in these mice, as well as their central and peripheral inflammation. To explore the mechanism of high glucose-induced microglial NLRP3 inflammasome activation, we performed in vitro studies focusing on its canonical upstream signal I (TLR4/MyD88/NF-κB) and signal II (ROS/PKR/P2X7R/TXNIP). RESULTS: Diabetic mice exhibited depression-like behaviors and activation of NLRP3 inflammasome in hippocampus. In vitro high-glucose (50 mM) environment primed microglial NLRP3 inflammasome by promoting NF-κB phosphorylation in a TLR4/MyD88-independent manner. Subsequently, high glucose activated the NLRP3 inflammasome via enhancing intracellular ROS accumulation, upregulating P2X7R, as well as promoting PKR phosphorylation and TXNIP expression, thereby facilitating the production and secretion of IL-1ß. Inhibition of NLRP3 with MCC950 significantly restored hyperglycemia-induced depression-like behavior and reversed the increase in IL-1ß levels in the hippocampus and serum. CONCLUSION: The activation of NLRP3 inflammasome, probably mainly in hippocampal microglia, mediates the development of depression-like behaviors in STZ-induced diabetic mice. Targeting the microglial inflammasome is a feasible strategy for the treatment of diabetes-related depression.

Colorectal cancer survivors' experiences of return-to-work: A meta-synthesis of qualitative studies.

INTRODUCTION: This review is to explore the relevant experience of colorectal cancer survivors' return-to-work, reintegrating and analyzing the promoting factors and obstacles of colorectal cancer survivors' return-to-work. METHODS: This review followed PRISMA List. Databases including the Cochrane Library, PubMed, Web of Science, EM base, CINAHL, APA PsycInfo, Wangfang Database, CNKI and CBM from inception to October 2022 were searched to collect qualitative studies in the experience of colorectal cancer survivors' return-to-work. Article selection and data extraction were conducted by two researchers used the Joanna Briggs Institute Critical Appraisal Tool for qualitative researches (2016) in Australia. RESULTS: Seven studies were included, the thirty-four themes distilled from the literature were grouped into eleven new categories and summed into two integrated findings: (1) facilitators to return-to-work for colorectal cancer survivors: desire and expectation for return-to-work and social dedication, economic needs, support and tolerance from employers and colleagues, work suggestions provided by professionals, health insurance policy of the workplace. (2) obstacles to return-to-work for colorectal cancer survivors: physical problems, psychological barriers, lack of family support, negative attitudes of employers and colleagues, limited information and resources available from professionals, Imperfection of related policies. CONCLUSION: This study shows that colorectal cancer survivors' return-to-work is influenced by many factors. We should pay attention to and avoid obstacles, help colorectal cancer survivors recover their physical functions and maintain a positive psychological state, improve the social support for colorectal cancer survivors to return-to-work, so as to achieve comprehensive rehabilitation as soon as possible.

Development and validation of Adaptability to Return-to-Work Scale (ARTWS) for cancer patients.

Introduction: The research on cancer patients returning to work in China is still in its infancy, and there is no research and discussion on the adaptability to return-to-work for cancer patients. It is critical to develop the Adaptability to Return-to-Work Scale (ARTWS) for cancer patients and evaluate its psychometric properties. Methods: The items of the initial scale were compiled based on the theoretical model and literature review results. Through two rounds of Delphi expert consultation (N = 15) and a pilot survey (N = 40), the initial scale was further checked and revised. Conduct a large sample survey (N = 376) and the construct validity and reliability of the ARTWS were assessed by confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Results: The final ARTWS consisted of 24 items. "Focusing on rehabilitation," "Rebuilding Self-efficiency," and "Adjusting plans" as common factors in determining adaptability to return to work for cancer patients, and the cumulative variance contribution rate for these three factors was 66.6%. The S-CVI of the total scale was 0.979. The Cronbach's α coefficient was 0.937 and the 2-week test-retest reliability was 0.814. Discussion: ARTWS has good correlation validity and can be used as a tool to measure the adaptability of cancer patients' return to work. The presentation of the manuscript in Research Square (https://doi.org/10.21203/rs.3.rs-2323264/v1).