Single-Atom Iridium Nanozyme-Based Persistent Luminescence Nanoparticles for Multimodal Imaging-Guided Combination Tumor Therapy.

Persistent luminescence nanoparticles (PLNPs) can achieve autofluorescence-free afterglow imaging, while near-infrared (NIR) emission realizes deep tissue imaging. Nanozymes integrate the merits of nanomaterials and enzyme-mimicking activities with simple preparation. Here PLNPs are prepared of Zn1.2Ga1.6Ge0.2O4:Cr0.0075 with NIR emission at 700 nm. The PLNPs are then incubated with IrCl3 solution, and the nanoparticles are collected and annealed at 750 °C to obtain iridium@PLNPs. Iridium is observed on the PLNPs at the atomic level as a single-atom nanozyme with peroxidase-like catalytic activity, photothermal conversion, and computed tomography (CT) contrast capability. After coating with exosome membrane (EM), the Ir@PLNPs@EM composite exhibits long-lasting NIR luminescence, peroxidase-like catalytic activity, photothermal conversion, and CT contrast capability, with the targeting capability and biocompatibility from EM. Thus, NIR afterglow/photothermal/CT trimodal imaging-guided photothermal-chemodynamic combination therapy is realized as validated with the in vitro and in vivo inhibition of tumor growth, while toxicity and side effects are avoided as drug-free treatment. This work offers a promising avenue for advanced single-atom nanozyme@PLNPs to promote the development of nanozymes and PLNPs for clinical applications.

The association of psychological and trauma-related factors with biological and facial aging acceleration: evidence from the UK Biobank.

BACKGROUND: Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking. METHODS: Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models. RESULTS: We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the "Absence of trauma and psychopathology" cluster, the "adverse childhood experiences (ACEs) with psychopathology" cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 - 1.23] for biological and 1.52 [1.18 - 1.95] for facial aging acceleration), while no such association was observed for the "ACEs without psychopathology" cluster (1.04 [0.99 - 1.09] and 1.02 [0.84 - 1.24]. CONCLUSIONS: Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals' psychological resilience to prevent aging acceleration.

Fabrication, digestion behavior and ß-carotene bioaccessibility of emulsion-filled double-network gel: Effect of corn fiber gum/soy protein isolate ratio and surfactant types.

Emulsion fortified with ß-carotene was added to corn fiber gum (CFG)/soy protein isolate (SPI) double network gel matrix to obtain emulsion-filled gels (EFG) via dual induction of laccase and glucono-δ-lactone. Protein digestion was accompanied by the release of ß-carotene from gel matrix during in vitro digestion. The surfactant types and corn fiber gum/soy protein isolate ratio affected the ß-carotene bioaccessibility via changing oil-water interfacial composition and emulsion particle size during in vitro digestion. As compared with Tween-20 EFGs, emulsion droplets released from SPI EFGs was more susceptible to flocculation, followed with coalescence due to proteolysis of interfacial SPI during gastric digestion. The resulting oil droplets with large particle size exhibited lower lipase adsorption, thus reducing the free fatty acid content and ß-carotene bioaccessibility. The confocal laser scanning microscope (CLSM) observation confirmed that protein hydrolysate from gel matrix were adsorbed onto the oil-water interface competing with Tween-20 during intestinal digestion. For EFGs with higher CFG content, steric hindrance of CFG molecules and less emulsion release could inhibit droplet flocculation, thus enhancing ß-carotene bioaccessibility.

Structure-dependent destructive adsorption of organophosphate flame retardants on lipid membranes.

The widespread use of organophosphate flame retardants (OPFRs), a serious type of pervasive environmental contaminants, has led to a global concern regarding their diverse toxicities to living beings. Using a combination of experimental and theoretical approaches, we systematically studied the adsorption, accumulation, and influence of a series of OPFRs on the lipid membranes of bacteria and cells. Our results revealed that OPFRs can aggregate in lipid membranes, leading to the destruction of membrane integrity. During this process, the molecular structure of the OPFRs is a dominant factor that significantly influences the strength of their interaction with the lipid membrane, resulting in varying degrees of biotoxicity. Triphenyl phosphate (TPHP), owing to its large molecular size and strong hydrophobicity, causes severe membrane disruption through the formation of nanoclusters. The corresponding severe toxicity originates from the phase transitions of the lipid membranes. In contrast, smaller OPFRs such as triethyl phosphate (TEP) and tris(2-chloroethyl) phosphate (TCEP) have weaker hydrophobicity and induce minimal membrane disturbance and ineffective damage. In vivo, gavage of TPHP induced more severe barrier damage and inflammatory infiltration in mice than TEP or TCEP, confirming the higher toxicity of TPHP. Overall, our study elucidates the structure-dependent adsorption of OPFRs onto lipid membranes, highlighting their destructive interactions with membranes as the origin of OPFR toxicity.

Application of combined anesthesia with spontaneous breathing in the surgery of intertrochanteric fracture of femur in elderly patients.

OBJECTIVES: This study aims to investigate the feasibility and safety of combined anesthesia with spontaneous breathing in the operation of intertrochanteric fracture of femur in the elderly. PATIENTS AND METHODS: Between January 2020 and January 2023, a total of 141 elderly patients (45 males, 96 females; mean age: 72.5±6.8 years; range, 65 to 87 years) who underwent proximal femoral nail anti-rotation (PFNA) surgery for intertrochanteric fracture of femur were included in this single-blind, prospective, randomized-controlled study. The patients were randomly divided into three groups. Group A (experimental group) was a general anesthesia with laryngeal mask airway (LMA) group preserving spontaneous breathing, Group B (control group 1) was a general anesthesia with LMA group for mechanical ventilation, and Group C (control group 2) was a tracheal intubation anesthesia group for mechanical ventilation. The differences of related indexes among the three groups were compared. RESULTS: The mean onset time of anesthesia (6.23±1.45 vs. 12.78±2.78 vs. 13.73±2.43 min), postoperative recovery time of consciousness (8.13±0.83 vs. 11.34±0.89 vs. 12.45±0.86 min), and postoperative complete awakening time (10.45±2.34 vs. 18.87±2.56 vs. 19.62±2.93 min) were significantly shorter in Group A than in Groups B and C (p<0.05). The duration of analgesic effect was longer in Group A than in Groups B and C (p<0.05). After anesthesia, the Ramsay Sedation Scale and Visual Analog Scale (VAS) scores were significantly lower in Group A than the other groups (p<0.05). The mean Mini-Mental State Examination (MMS) scores were significantly higher in Group A than in Groups B and C (p<0.05). Hemodynamic parameters showed that blood pressure, heart rate, cardiac output, and cardiac index (CI) levels were significantly higher in Group A than the other groups (p<0.05). CONCLUSION: Our study results indicate that combined anesthesia preserving spontaneous breathing is safe and feasible in the operation of intertrochanteric fracture of femur in the elderly, with faster anesthesia recovery than the mechanical ventilation group.

[Effects of Questionnaire-Based Psychological Survey Methods on the Evaluation Results in a Patient Cohort].

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.

Cardiovascular Disease, Genetic Susceptibility, and Risk of Psychiatric Disorders and Suicide Attempt: A Community-Based Matched Cohort Study Based on the UK Biobank.

BACKGROUND: The associations between cardiovascular disease (CVD) and multiple psychiatric disorders and suicide attempt, and whether different genetic susceptibilities affect such links, have not been investigated clearly. METHODS AND RESULTS: Based on the UK Biobank, we conducted a matched cohort study involving 63 923 patients who were first hospitalized with a CVD diagnosis between 1997 and 2020, and their 127 845 matched unexposed individuals. Cox models were used to examine the subsequent risk of psychiatric disorders and suicide attempt (ie, anxiety, depression, stress-related disorder, substance misuse, psychotic disorder, and suicide behaviors) following CVD. We further performed stratified analyses by polygenic risk score for each studied psychiatric condition to detect the possible effects of genetic susceptibility on the observed associations. We found an increased risk of any psychiatric disorders and suicide attempt among CVD patients, compared with matched unexposed individuals, particularly within 1 year following the CVD (fully adjusted hazard ratio [HR] within 1 year, 1.83 [95% CI, 1.58-2.12]; HR after 1 year, 1.24 [95% CI, 1.16-1.32]). By subtype, the risk elevations existed for any psychiatric disorders and suicide attempt following most categories of CVDs. Analyses stratified by polygenic risk score revealed little impact of genetic predisposition to studied psychiatric conditions on these observed links. CONCLUSIONS: Patients hospitalized for CVD were at increased subsequent risk of multiple types of psychiatric disorders and suicide attempt, especially in the first year after hospitalization, irrespective of their genetic susceptibilities to studied psychiatric conditions, and these findings underscore the necessity of developing timely psychological interventions for this vulnerable population.

Association Between Body Composition Patterns, Cardiovascular Disease, and Risk of Neurodegenerative Disease in the UK Biobank.

BACKGROUND AND OBJECTIVES: Accumulating evidence connects diverse components of body composition (e.g., fat, muscle, and bone) to neurodegenerative disease risk, yet their interplay remains underexplored. This study examines the associations between patterns of body composition and the risk of neurodegenerative diseases, exploring the mediating role of cardiovascular diseases (CVDs). METHODS: This retrospective analysis used data from the UK Biobank, a prospective community-based cohort study. We included participants free of neurodegenerative diseases and with requisite body composition measurements at recruitment, who were followed from 5 years after recruitment until April 1, 2023, to identify incident neurodegenerative diseases. We assessed the associations between different components and major patterns of body composition (identified by principal component analysis) with the risk of neurodegenerative diseases, using multivariable Cox models. Analyses were stratified by disease susceptibility, indexed by polygenetic risk scores for Alzheimer and Parkinson diseases, APOE genotype, and family history of neurodegenerative diseases. Furthermore, we performed mediation analysis to estimate the contribution of CVDs to these associations. In addition, in a subcohort of 40,790 participants, we examined the relationship between body composition patterns and brain aging biomarkers (i.e., brain atrophy and cerebral small vessel disease). RESULTS: Among 412,691 participants (mean age 56.0 years, 55.1% female), 8,224 new cases of neurodegenerative diseases were identified over an average follow-up of 9.1 years. Patterns identified as "fat-to-lean mass," "muscle strength," "bone density," and "leg-dominant fat distribution" were associated with a lower rate of neurodegenerative diseases (hazard ratio [HR] = 0.74-0.94) while "central obesity" and "arm-dominant fat distribution" patterns were associated with a higher rate (HR = 1.13-1.18). Stratification analysis yielded comparable risk estimates across different susceptibility groups. Notably, 10.7%-35.3% of the observed associations were mediated by CVDs, particularly cerebrovascular diseases. The subcohort analysis of brain aging biomarkers corroborated the findings for "central obesity," "muscle strength," and "arm-dominant fat distribution" patterns. DISCUSSION: Our analyses demonstrated robust associations of body composition patterns featured by "central obesity," "muscle strength," and "arm-dominant fat distribution" with both neurodegenerative diseases and brain aging, which were partially mediated by CVDs. These findings underscore the potential of improving body composition and early CVD management in mitigating risk of neurodegenerative diseases.

Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine.

Chronic Fatigue Syndrome (CFS) is a complex and perplexing medical disorder primarily characterized by persistent and debilitating fatigue, often accompanied by a constellation of symptoms, including weakness, dyspnea, arthromyalgia, sore throat, and disrupted sleep patterns. CFS is defined by its persistent or recurrent manifestation for a minimum duration of six months, marked by an enduring and unrelenting fatigue that remains refractory to rest. In recent decades, this condition has garnered significant attention within the medical community. While the precise etiology of CFS remains elusive, it is postulated to be multifactorial. CFS is potentially associated with various contributory factors such as infections, chronic stress, genetic predisposition, immune dysregulation, and psychosocial influences. The pathophysiological underpinnings of CFS encompass viral infections, immune system dysregulation, neuroendocrine aberrations, heightened oxidative stress, and perturbations in gut microbiota. Presently, clinical management predominantly relies on pharmaceutical interventions or singular therapeutic modalities, offering alleviation of specific symptoms but exhibiting inherent limitations. Traditional Chinese Medicine (TCM) interventions have emerged as a promising paradigm, demonstrating notable efficacy through their multimodal, multi-target, multi-pathway approach, and holistic regulatory mechanisms. These interventions effectively address the lacunae in contemporary medical interventions. This comprehensive review synthesizes recent advancements in the understanding of the etiological factors, pathophysiological mechanisms, and interventional strategies for CFS, drawing from a corpus of domestic and international literature. Its aim is to furnish valuable insights for clinicians actively involved in diagnosing and treating CFS, as well as for pharmaceutical researchers delving into innovative drug development pathways. Moreover, it seeks to address the intricate challenges confronted by clinical practitioners in managing this incapacitating condition.

Effect of electroacupuncture on expression of protein phosphorylation in hippocampus tissues of rats with chronic fatigue syndrome. / ç”µé’ˆå¹²é¢„å¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ æµ·é©¬ç»„ç»‡è›‹ç™½è´¨ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on behavior and hippocampal protein phosphorylation in rats with chronic fatigue syndrome (CFS), so as to explore its mechanisms underlying improvement of CFS. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The CFS model was established by chronic multifactor combined with stress stimulation (treadmill training + restraint stress + sleep disturbance + crowded environment). For rats of the EA group, EA (1 mA, frequency of 10 Hz) was applied to "Shenting" (GV24) (with an acupuncture needle penetrated from GV24 to "Baihui" ï¼»GV20ï¼½) and "Dazhui" (GV14) for 15 min, once daily for 28 days. After treatment, the body weight, food intake and water intake of rats in each group were observed. The fatigue degree of rats was evaluated by Semi-quantitative score observation table of the general condition of experimental rats.The open field test (OFT) was used to assess the rats'anxiety severity by detecting the total number of grid-crossing and the times of the central area entered in 5 min, and Morris water maze test was employed to assess the rats' learning-memory ability by detecting the escape latency in 1 min, and the times of the original platform quadrant crossing in 1 min. The hippocampaus was taken for phosphorylated Label-free quantitative proteomics analysis by using Maxquant technology based on full scan mode to calculate the integral of each peptide signal of liquid chromatography-mass spectrometry(LC-MS). The differentially-expressed proteins (>1.5 folds for up-regulation or <0.67 folds for down-regulation) were evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Compared with the control group, the body weight, food intake, and the times of original-platform quadrant crossing of spatial exploring of Morris water maze test were significantly decreased (P<0.01, P<0.05) , and the score of general conditions, times of grid-crossing and center area-entering of OFT, and the escape latency of navigation task were apparently increased (P<0.01) in rats of the model group. After EA intervention, the decreased original-platform quadrant crossing, and the increased score of general conditions, times of grid-crossing and the escape latency of navigation task were all reversed (P<0.01, P<0.05). Outcomes of proteomics analysis indicated that compared with the model group, there were 297 differentially expressed peptide (48 up-regulated and 249 down-regulated) segments in the control group, and there were 245 differentially expressed peptide (185 up-regulated and 60 down-regulated) segments in the EA group, in which, 25 overlapping peptide segments were reversed after EA treatment, corresponding to 24 proteins, mainly involving cytoskeletal structure. GO function annotation analysis showed that the top three differentially expressed phosphorylated proteins involved in the effect of EA intervention were the actin filament polymerization, protein depolymerization and cytoskeletal tissue in the biological process, the actin binding, structural molecular activity and cytoskeletal protein binding in the molecular function, and the cytoskeleton, dendrites and dendritic trees in the cellular component, respectively. The KEGG pathway annotation analysis for differentially expressed phosphorylated proteins showed that theinsulin secretion, axon guidance, phosphatidylinositol signaling system and lysine biosynthesis, etc. were involved in the effect of EA intervention. CONCLUSIONS: EA of GV24-GV20 and GV14 can improve the general state, anxiety and learning-memory ability of CFS model rats, which may be related to its functions in regulating the hippocampal protein phosphorylation level, and repairing the structure and function of synapses in hippocampus.

Atorvastatin ameliorates diabetic nephropathy through inhibiting oxidative stress and ferroptosis signaling.

Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The present study investigated the effects of atorvastatin on diabetes renal injury and ferroptosis signaling. A mouse model of diabetes was established by the intraperitoneal injection of streptozotocin (50 mg/kg/day) plus a high fat diet with or without atorvastatin treatment. Diabetes mice manifested increased plasma glucose and lipid profile, proteinuria, renal injury and fibrosis, atorvastatin significantly lowered plasma lipid profile, proteinuria, renal injury in diabetes mice. Atorvastatin reduced renal reactive oxygen species (ROS), iron accumulation and renal expression of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), transferrin receptor 1 (TFR1), and increased renal expression of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2) and ferritin heavy chain (FTH) in diabetes mice. Consistent with the findings in vivo, atorvastatin prevented high glucose-induced ROS formation and Fe2+ accumulation, an increase in the expression of 4-HNE, MDA and TFR1, and a decrease in cell viability and the expression of NRF2, GPX4 and FTH in HK2 cells. Atorvastatin also reversed ferroptosis inducer erastin-induced ROS production, intracellular Fe2+ accumulation and the changes in the expression of above-mentioned ferroptosis signaling molecules in HK2 cells. In addition, atorvastatin alleviated high glucose- or erastin-induced mitochondria injury. Ferroptosis inhibitor ferrostatin-1 and antioxidant N-acetylcysteine (NAC) equally reversed the expression of high glucose-induced ferroptosis signaling molecules. Our data support the notion that statins can inhibit diabetes-induced renal oxidative stress and ferroptosis, which may contribute to statins protection of diabetic nephropathy.

Calcium-sensing receptor-mediated macrophage polarization improves myocardial remodeling in spontaneously hypertensive rats.

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.

Association of pre-existing depression and anxiety with Omicron variant infection.

Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January 2023 and April 2023. Participants with a self-reported history or self-rated symptoms of depression or anxiety before the Omicron pandemic were considered the exposed group, whereas the others were considered unexposed. We employed multivariate logistic regression models to examine the association of pre-existing depression or anxiety with the risk of any or severe Omicron infection indexed by medical interventions or severe symptoms. Further, we stratified the analyses by polygenic risk scores (PRSs) for COVID-19 and repeated the analyses using the UK Biobank data. We included 10,802 individuals from the Chinese cohorts (mean age = 51.1 years, 45.6% male), among whom 7841 (72.6%) were identified as cases of Omicron infection. No association was found between any pre-existing depression or anxiety and the overall risk of Omicron infection (odds ratio [OR] =1.04, 95% confidence interval [CI] 0.95-1.14). However, positive associations were noted for severe Omicron infection, either as infections requiring medical interventions (1.26, 1.02-1.54) or with severe symptoms (≥3: 1.73, 1.51-1.97). We obtained comparable estimates when stratified by COVID-19 PRS level. Additionally, using clustering method, we identified eight distinct symptom patterns and found associations between pre-existing depression or anxiety and the patterns characterized by multiple or complex severe symptoms including cough and taste and smell decline (ORs = 1.42-2.35). The results of the UK Biobank analyses corroborated findings of the Chinese cohorts. In conclusion, pre-existing depression and anxiety was not associated with the risk of Omicron infection overall but an elevated risk of severe Omicron infection, supporting the continued efforts on monitoring and possible early intervention in this high-risk population during Omicron prevalence.

Organic-Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme.

Plasmonic nanozymes bring enticing prospects for catalytic sterilization by leveraging plasmon-engendered hot electrons. However, the interface between plasmons and nanozymes as the mandatory path of hot electrons receives little attention, and the mechanisms of plasmonic nanozymes still remain to be elucidated. Herein, a plasmonic carbon-dot nanozyme (FeCG) is developed by electrostatically assembling catalytic iron-doped carbon dots (Fe-CDs) with plasmonic gold nanorods. The energy harvesting and hot-electron migration are remarkably expedited by a spontaneous organic-inorganic heterointerface holding a Fermi level-induced interfacial electric field. The accumulated hot electrons are then fully utilized by conductive Fe-CDs to boost enzymatic catalysis toward overproduced reactive oxygen species. By synergizing with localized heating from hot-electron decay, FeCG achieves rapid and potent disinfection with an antibacterial efficiency of 99.6% on Escherichia coli within 5 min and is also effective (94.2%) against Staphylococcus aureus. Our work presents crucial insights into the organic-inorganic heterointerface in advanced plasmonic biocidal nanozymes.

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome. / ç”µé’ˆå¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ è¡Œä¸ºå­¦åŠæµ·é©¬ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.

An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase.

The main proteinase (Mpro) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of Mpro has both scientific and practical significance. In this study, we explored the binding characteristics and inhibiting process of Mpro activity by two recently reported allosteric inhibitors, pelitinib and AT7519 which were obtained by the X-ray screening experiments, to probe the allosteric mechanism via molecular dynamic (MD) simulations. We found that pelitinib and AT7519 can stably bind to Mpro far from the active site. The binding affinity is estimated to be -24.37 ± 4.14 and - 26.96 ± 4.05 kcal/mol for pelitinib and AT7519, respectively, which is considerably stable compared with orthosteric drugs. Furthermore, the strong binding caused clear changes in the catalytic site of Mpro, thus decreasing the substrate accessibility. The community network analysis also validated that pelitinib and AT7519 strengthened intra- and inter-domain communication of Mpro dimer, resulting in a rigid Mpro, which could negatively impact substrate binding. In summary, our findings provide the detailed working mechanism for the two experimentally observed allosteric sites of Mpro. These allosteric sites greatly enhance the 'druggability' of Mpro and represent attractive targets for the development of new Mpro inhibitors.

Childhood maltreatment and risk of endocrine diseases: an exploration of mediating pathways using sequential mediation analysis.

BACKGROUND: Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking. METHODS: Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (< 2 and ≥ 2) variable, with any and specific endocrine diseases, adjusted for multiple covariates. We further examined the risk of having multiple endocrine diseases using Linear or Logistic Regression models. Then, sequential mediation analyses were performed to assess the contribution of four possible mechanisms (i.e., suboptimal socioeconomic status (SES), psychological adversities, unfavorable lifestyle, and biological alterations) on the observed associations. RESULTS: During an average follow-up of 30.8 years, 20,885 participants received a diagnosis of endocrine diseases. We observed an association between the cumulative number of experienced childhood maltreatment and increased risk of being diagnosed with any endocrine disease (adjusted hazard ratio (HR) = 1.10, 95% confidence interval 1.09-1.12). The HR was 1.26 (1.22-1.30) when comparing individuals ≥ 2 with those with < 2 experienced childhood maltreatment. We further noted the most pronounced associations for type 2 diabetes (1.40 (1.33-1.48)) and hypothalamic-pituitary-adrenal (HPA)-axis-related endocrine diseases (1.38 (1.17-1.62)), and the association was stronger for having multiple endocrine diseases, compared to having one (odds ratio (95% CI) = 1.24 (1.19-1.30), 1.35 (1.27-1.44), and 1.52 (1.52-1.53) for 1, 2, and ≥ 3, respectively). Sequential mediation analyses showed that the association between childhood maltreatment and endocrine diseases was consistently and most distinctly mediated by psychological adversities (15.38 ~ 44.97%), while unfavorable lifestyle (10.86 ~ 25.32%) was additionally noted for type 2 diabetes whereas suboptimal SES (14.42 ~ 39.33%) for HPA-axis-related endocrine diseases. CONCLUSIONS: Our study demonstrates that adverse psychological sequel of childhood maltreatment constitutes the main pathway to multiple endocrine diseases, particularly type 2 diabetes and HPA-axis-related endocrine diseases. Therefore, increased access to evidence-based mental health services may also be pivotal in reducing the risk of endocrine diseases among childhood maltreatment-exposed individuals.

Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants.

Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Development of sorghum arabinoxylan-soy protein isolate composite nanoparticles for delivery of curcumin: Effect of polysaccharide content on stability and in vitro digestibility.

The purpose of this study was to fabricate composite nanoparticles using soy protein isolate (SPI) and sorghum bran arabinoxylan (AX) for the delivery of curcumin (Cur). The influences of AX concentrations on the physicochemical characteristic, stability and bioaccessibility of curcumin were investigated. The findings showed that the encapsulation efficiency of curcumin obviously increased upon incorporating AX in comparison to SPI-Cur particles. Hydrogen bonds and hydrophobic interactions were the primary driving forces for the formation of SPI-Cur-AX nanoparticles (SCA). SCA nanoparticles with 1.00 % AX exhibited a uniform size with orderly distribution, suggesting its remarkable physical stability due to the strengthened electrostatic repulsion. However, excessive AX led to aggregation of particles, a noticeable increase in size, and subsequently, a reduction in stability. Due to the heightened free radical scavenging capacity of sorghum AX, SCA nanoparticles exhibited superior antioxidant capabilities. Compared to free curcumin, encapsulation within composite particles significantly enhanced the retention rate and bioaccessibility of curcumin. This improvement was attributed to the potent emulsification ability of AX, which coordinated with bile salt to promote the transfer of curcumin into micelles. The research provides an effective strategy for developing food-grade delivery carriers aimed at enhancing dispersibility, stability and bioaccessibility of the fat-soluble bioactives.

Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank.

PURPOSE: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. METHODS: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. RESULTS: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. CONCLUSION: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.