Associations between adverse childhood experiences and pain in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress.

Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.

Role of mitochondria-associated membranes in the hippocampus in the pathogenesis of depression.

BACKGROUND: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. LIMITATION: The cellular specificity of MAMs related protein changes in CSDS mice was not explored. CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses.

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Stability analysis of nonlinear localized modes in the coupled Gross-Pitaevskii equations with [Formula: see text] -symmetric Scarf-II potential.

We study the nonlinear localized modes in two-component Bose-Einstein condensates with parity-time-symmetric Scarf-II potential, which can be described by the coupled Gross-Pitaevskii equations. Firstly, we investigate the linear stability of the nonlinear modes in the focusing and defocusing cases, and get the stable and unstable domains of nonlinear localized modes. Then we validate the results by evolving them with 5% perturbations as an initial condition. Finally, we get stable solitons by considering excitations of the soliton via adiabatical change of system parameters. These findings of nonlinear modes can be potentially applied to physical experiments of matter waves in Bose-Einstein condensates.

Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines.

Under the catalysis of Rh2(OAc)4 (10 mol%) and binapbisphosphine ligand (±)-L3 (20 mol%) in DCE at 80 °C, the cascade cyclization of diazoimides with alkylidenepyrazolones underwent stereoselectively (dr > 20:1), affording pyrazole-fused oxa-bridged oxazocines in reasonable chemical yields. The chemical structure and relative configuration of title products were firmly identified by X-ray diffraction analysis.

Novel results on asymptotic stability and synchronization of fractional-order memristive neural networks with time delays: The 0<뫲1 case.

This paper investigates the asymptotic stability and synchronization of fractional-order (FO) memristive neural networks with time delays. Based on the FO comparison principle and inverse Laplace transform method, the novel sufficient conditions for the asymptotic stability of a FO nonlinear system are given. Then, based on the above conclusions, the sufficient conditions for the asymptotic stability and synchronization of FO memristive neural networks with time delays are investigated. The results in this paper have a wider coverage of situations and are more practical than the previous related results. Finally, the validity of the results is checked by two examples.

Bullatine A has an antidepressant effect in chronic social defeat stress mice; Implication of microglial inflammasome.

Inflammatory microglia and P2X7R are involved in the development of stress-induced depression. Endoplasmic reticulum (ER) stress and mitochondrial damage play an important role in depression and microglial activation. Bullatine A (BLA) has anti-inflammatory and anti-rheumatic effects, and can be used as a P2X7R antagonist. We found that Bullatine A can effectively inhibit the calcium overload of mitochondria and the increase of ER and mitochondrial colocalization caused by eATP (extracellular ATP) in BV2-cells. Bullatine A can also inhibit the activation of PERK-elF-2α unfolded protein response (UPR), lysosome production and the increase of NLRP3 inflammasome protein expression in BV2-cells Both intragastric administration and intra-hippocampal microinjection of Bullatine A can significantly improve the despair behavior but not anhedonia of Chronic chronic social defeat stress (CSDS) mice. Bullatine A may have a beneficial therapeutic effect in treating diseases related to stress stimulation, such as depression.

Synergic chitin degradation by Streptomyces sp. SCUT-3 chitinases and their applications in chitinous waste recycling and pathogenic fungi biocontrol.

The genus Streptomyces comprises the most important chitin decomposers in soil and revealing their chitinolytic machinery is beneficial for the conversion of chitinous wastes. Streptomyces sp. SCUT-3, a chitin-hydrolyzing and a robust feather-degrading bacterium, was isolated previously. The potential chitin-degrading enzymes produced by SCUT-3 were analyzed in the present study. Among these enzymes, three chitinases were successfully expressed in Pichia pastoris at comparatively high yields of 4.8 U/mL (SsExoChi18A), 11.2 U/mL (SsExoChi18B), and 17.8 U/mL (SsEndoChi19). Conserved motifs and constructive 3D structures of these three exo- and endochitinases were also analyzed. These chitinases hydrolyzed colloidal chitin to chitin oligomers. SsExoChi18A showed apparent synergic effects with SsEndoChi19 in colloidal chitin and shrimp shell hydrolysis, with an improvement of 29.3 % and 124.9 %, respectively. Compared with SsExoChi18B and SsEndoChi19, SsExoChi18A exhibited the strongest antifungal effects against four plant pathogens by inhibiting mycelial growth and spore germination. This study provided good candidates for chitinous waste-processing enzymes and antifungal biocontrol agents. These synergic chitin-degrading enzymes of SCUT-3 are good targets for its further genetical modification to construct super chitinous waste-degrading bacteria with strong abilities to hydrolyze both protein and chitin, thereby providing a direction for the future path of the chitinous waste recycling industry.

Event-related potential response to drivers' facial expressions in an online car-hailing scene.

Recognizing facial expressions is crucial for adaptive social interaction. Prior empirical research on facial expression processing has primarily focused on isolated faces; however, facial expressions appear embedded in surrounding scenes in everyday life. In this study, we attempted to demonstrate how the online car-hailing scene affects the processing of facial expression. This study examined the processing of drivers' facial expressions in scenes by recording event-related potentials, in which neutral or happy faces embedded in online car-hailing orders were constructed (with type of vehicle, driver rating, driver surname, and level of reputation controlled). A total of 35 female volunteers participated in this experiment and were asked to judge which facial expressions that emerged in scenes of online car-hailing were more trustworthy. The results revealed an interaction between facial expression scenes, brain areas, and electrode sites in the late positive potential, which indicated that happy faces elicited larger amplitudes than did neutral ones in the parietal areas and that scenes with happy facial expressions had shorter latencies than did those with neutral ones. As expected, the late positive potential evoked by happy facial expressions in a scene was larger than that evoked by neutral ones, which reflected motivated attention and motivational response processes. This study highlights the importance of scenes as context in the study of facial expression processing.

Sinudenoids A-E, C19-Norcembranoid Diterpenes with Unusual Scaffolds from the Soft Coral Sinularia densa.

Five new furanobutenolide-derived C19-norcembranoid diterpenes, sinudenoids A-E (1-5, respectively), were isolated from the soft coral Sinularia densa. Sinudenoid A (1) possesses an uncommon 5/5/11-fused tricyclic ring system. Sinudenoids B-D (2-4, respectively) share the same tetracyclic 5/5/6/6 ring system but represent two kinds of new skeletons. Sinudenoid E (5) is the second compound with the rare 8/8 bicyclic carbon core. A plausible biosynthesis pathway for compounds 1-6 is proposed. Compound 5 exhibits strong anti-inflammatory activity in the zebrafish model.

Heterogeneous self-healing assembly of MXene and graphene oxide enables producing free-standing and self-reparable soft electronics and robots.

Self-healing materials (SHMs) with unique mechanical and electronic properties are promising for self-reparable electronics and robots. However, the self-healing ability of emerging two-dimensional (2D) materials, for instance, MXenes, has not been systematically investigated, which limits their applications in self-healing electronics. Herein, we report the homogeneous self-healing assembly (homo-SHA) of MXene and the heterogeneous self-healing assembly (hetero-SHA) of MXene and graphene oxide (GO) under moisture treatments. The self-healing mechanism has been attributed to the hydration induced interlayer swelling of MXene and GO and the recombination of hydrogen bond networks after water desorption. The multiform hetero-SHA of MXene and GO not only enables facile fabrication of free-standing soft electronics and robots, but also endows the resultant devices with damage-healing properties. As proof-of-concept demonstrations, free-standing soft electronic devices including a generator, a humidity sensor, a pressure sensor, and several robotic devices have been fabricated. The hetero-SHA of MXene and GO is simple yet effective, and it may pioneer a new avenue to develop miniature soft electronics and robots based on 2D materials.

Minocycline alleviates abnormal microglial phagocytosis of synapses in a mouse model of depression.

BACKGROUND: As antidepressants commonly used in the clinic have proved to be problematic, it is urgent to gain an updated understanding of the pathogenesis of depression and find potential therapeutic targets. Since both functional brain imaging studies and autopsy reports indicated that there is indeed a loss of synapses in depressed patients, it is necessary to explore the mechanism of this process. METHODS: We firstly investigated the effect of chronic social defeat stress (CSDS), a mouse model of depression, on behaviors, synapses, microglia, and microglial phagocytosis of synapses in mice. Then, as it is unclear whether microglial phagocytosis leads to synaptic loss, or synaptic loss induces the microglial clearance in CSDS mice, we used minocycline, a microglial activation inhibitor, to inhibit the microglial phagocytosis of synapses and study its effect on synapses and behaviors in CSDS mice. RESULTS: Our results showed that the expression levels of PSD-95 in the hippocampal dentate gyrus (DG) of CSDS mice were significantly reduced, while the microglia were significantly activated and the Iba1+CD68+ cell (phagocytic microglia) density was increased. We co-labeled the synaptic protein PSD-95 with the microglia marker Iba1 and found that the microglia in the hippocampal DG of CSDS mice contained significantly more PSD-95 engulfed puncta, which revealed that microglia in CSDS mice abnormally phagocytized synapses. Moreover, our results indicated that minocycline treatment dampened microglial activation, decreased the phagocytic microglia density, reduced abnormal microglial phagocytosis of synapses, reversed synaptic loss, and alleviated behavioral impairment in CSDS mice. CONCLUSIONS: Under depressive pathological conditions, the activated microglia may abnormally engulf neuronal synapses causing synaptic loss and behavioral impairments. Thus, microglial phagocytosis may be a novel therapeutic target for the treatment of depression.

Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer.

IgGFc-binding protein (FCGBP) is a mucin first detected in the intestinal epithelium. It plays an important role in innate mucosal epithelial defense, tumor metastasis, and tumor immunity. FCGBP forms disulfide-linked heterodimers with mucin-2 and members of the trefoil factor family. These formed complexes inhibit bacterial attachment to mucosal surfaces, affect the motility of pathogens, and support their clearance. Altered FCGBP expression levels may be important in the pathologic processes of Crohn's disease and ulcerative colitis. FCGBP is also involved in regulating the infiltration of immune cells into tumor microenvironments. Thus, the molecule is a valuable marker of tumor prognosis. This review summarizes the functional relevance and role of FCGBP in immune responses and disease development, and highlights the potential role in diagnosis and predicting tumor prognosis.

Multicoating Nanoarchitectonics for Facile Preparation of Multi-Responsive Paper Actuators.

Stimuli-responsive actuators (SRAs) that can harvest environmental energies and convert them to mechanical works without additional energy-supplying systems have revealed great potential for robotic applications. However, at present, the practical usage of SRAs is significantly limited due to the problems with respect to solo responsiveness, simple deformation, and the difficulties for large-scale and cost-effective production. In this paper, multi-responsive paper actuators with multicoating nanoarchitectonics that enable complex deformation have been fabricated through a very simple painting process on common papers. The resultant paper actuator permits large-scale and low-cost production (A4 size: ∼0.5 dollar). The paper actuators that consist of a paper/graphite/polydimethylsiloxane sandwich structure can be actuated by multi-form stimuli, including moisture, temperature, light, and volatile organic compounds. More importantly, the bending deformation of the paper actuators can be further programmed by controlling the pencil drawing orientation, providing the feasibility of performing more complex deformations. Several multi-responsive paper actuators, including organic compound-responsive smart devices working in the liquid environment, moisture-enabled terrestrial crawling actuator, and a light-responsive attitude-control actuator integrated with an airplane model, have been demonstrated. The development of multi-responsive yet cost-effective paper actuators may hold great promise for a wide range of practical applications, for instance, soft micro-electromechanical systems, lab-on-a-chip systems, smart homes, and robotics.

Oxidation-reduction potential affects medium-chain fatty acid ethyl ester production during wine alcohol fermentation.

The medium-chain fatty acid ethyl esters (MCFAEEs) are a group of important aroma compounds generated during wine production. Wine alcohol fermentation involves several redox processes, which are affected by the oxidation-reduction potential (ORP). However, the mechanism via which ORP regulates MCFAEE production remains unclear. To investigate the effect of ORP on MCFAEE production, wine alcohol fermentation was performed using Saccharomyces cerevisiae under different ORPs. The results demonstrated that the ORPs studied (except for 90 mV) did not significantly affect cell growth, sugar consumption, and ethanol production, while the MCFAEE concentration in the simulated wines can be manipulated by ORP operation. MCFAEE levels increased till 96 h, and then decreased. The maximum MCFAEE level of 1222.97 µg/L was obtained after 96 h at 0 mV, which was 45.32% higher than that of the control. During the increase, higher relative expression of ACC1, FAS1, FAA2 and EEB1, elevated external citric acid flux, and moderate intracellular NADP+/NADPH ratio were observed at 0 mV compared to that at other ORPs. During the decrease, lowest relative expression of POX1 was detected at 0 mV. We showed for the first time the relationship between ORP operation and MCFAEE production in winemaking, which will improve the aroma quality of wine.

Coagulants put phosphate-accumulating organisms at a competitive disadvantage with glycogen-accumulating organisms in enhanced biological phosphorus removal system.

Enhanced biological phosphorus removal (EBPR) process is susceptible to the changed operation condition, which results in an unstable treatment performance. In this work, long-term effect of coagulants addition, aluminum salt for the reactor R1 and iron salt for the reactor R2, on EBPR systems was comprehensively evaluated. Results showed that during the initial 30 days' coagulant addition, effluent chemical oxygen demand and phosphorus can be reduced below 25 and 0.5 mg·L-1, respectively. Further supply of metal salts would stimulate microbial extracellular polymeric substance excretion and induce reactive oxygen species accumulation, which destroyed the cell membrane integrity and deteriorated the phosphorus removal performance. Moreover, coagulants would decrease the relative abundance of Candidatus Accumulibacter while increase the relative abundance of Candidatus Competibacter, leading phosphors accumulating organisms in a disadvantage position. The results of this work might be valuable for the operation of chemical assisted biological phosphorus removal bioreactor.

Natural ingredients from Chinese materia medica for pulmonary hypertension.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Effects of Primary Decompressive Craniectomy on the Outcomes of Serious Traumatic Brain Injury with Mass Lesions, and Independent Predictors of Operation Decision.

BACKGROUND: Although operative indications for traumatic brain injury (TBI) are known, neurosurgeons are unsure whether to remove the bone flap after mass lesion extraction, and an efficient scoring system for predicting which patients should undergo decompressive craniectomy (DC) does not exist. METHODS: Nine parameters were assessed. In total, 245 patients with severe TBI were retrospectively assessed from June 2015 to May 2019, who underwent DC or craniotomy to remove mass lesions. The 6-month mortality and Extended Glasgow Outcome Scale scores were compared between the DC and craniotomy groups. Using univariable and multivariable logistic regression equations, receiver operating characteristic curves were obtained for predicting the decision for DC. RESULTS: The overall 6-month mortality in the entire cohort was 11.43% (28/245). Patients undergoing DC had lower mean preoperative Glasgow Coma Scale scores (P = 0.01), and higher amounts of individuals with a Glasgow Coma Scale score of 6 (P = 0.007), unresponsive pupillary light reflex (P < 0.001), closed basal cisterns (P < 0.001), and diffuse injury (P = 0.025), compared with the craniotomy group. Because of high disease severity, individuals administered primary DC showed increased 6-month mortality compared with the craniotomy group. However, in surviving patients, favorable Extended Glasgow Outcome Scale rates were similar in both groups. Pupillary light reflex and basal cisterns were independent predictors of the DC decision. Based on receiver operating characteristic curves, the model had sensitivity and specificity of 81.6% and 84.9%, respectively, in predicting the probability of DC. CONCLUSIONS: These preliminary data showed that primary DC may benefit some patients with severe TBI with mass lesions. In addition, unresponsive preoperative pupil reaction and closed basal cistern could predict the DC decision.

The antidepressant and anxiolytic effect of GPER on translocator protein (TSPO) via protein kinase a (PKA) signaling in menopausal female rats.

Postmenopausal depression is mainly caused by the deprivation of ovarian hormones during menopausal transition, it is of great importance to study on the treatment that could effectively relieve symptoms of menopausal depression with fewer side effects. Activation of G-protein-coupled estrogen receptor (GPER) has long been reported to facilitate neuronal plasticity and improve cognition in animals. Meanwhile, it could participate in regulation of intracellular signaling pathways through the characteristic of GPER, ameliorate intracellular mitochondrial function and oxidative stress. However, the impact of GPER on regulating estrogen deprived-depressant and anxious behaviors is still largely unknown. Here we used the ovariectomized female rats to imitate the condition of menopause. Owing to the lateral ventricle administration of G-1 which specifically react with GPER receptor intracerebrally, Ovariectomized (OVX) female rats showed depressive- or anxiety-like phenotypes with attenuated mitochondrial function. In addition, G-1 facilitated PKA activation, which further accelerated TSPO phosphorylation and alleviated menopausal depression- and anxiety-like behaviors. Moreover, PKA inhibitor PKI could partially antagonized the anti-anxiety and anti-depression effects of G-1. Taken together, we concluded that GPER activation might exhibit antidepressant and anxiolytic effect by elevating TSPO phosphorylation via protein kinase A signaling and rescuing the redox status in menopausal female rats.