Prevalence of sarcopenia and association with HIV infection in China elderly: An observational study.

This article aims to analyze the prevalence of sarcopenia among the elderly in Guizhou Province, China, and its association with human immunodeficiency virus (HIV) infection. This cross-sectional study included 377 patients aged 60 and above in Guiyang Public Health Treatment Center from December 2022 to October 2023, including 231 patients in the community clinic and 146 HIV-infected individuals. According to the Asian Working Group for Sarcopenia 2019 Consensus to diagnose sarcopenia. Logistic regression was used to explore association between sarcopenia and HIV, and stratified by sex and age group. The prevalence of sarcopenia in the non-HIV infection elderly in Guizhou Province was 7.8% (21.3% in males and 5.5% in females), and the prevalence of sarcopenia in HIV-infected individuals was 29.5% (33.3% in males and 13.2% in females), with a statistically significant difference between HIV groups (χ2 = 30.946, P < .001). After control of gender, age, body mass index, body fat percentage, hypertension, diabetes, taking statins, smoking status, medium to high-intensity physical activity, whether childhood poverty, and parents died young, HIV infection was significantly associated with sarcopenia in the elderly (odds ratio = 4.635, 95% confidence interval  = 1.920-11.188, P = .001). The results of stratified regression were similar to the main results. The prevalence of sarcopenia in the elderly population in China was severe. HIV infection was a risk factor for sarcopenia. It is urgent to establish a prevention and treatment system for sarcopenia in the elderly population, especially for elderly HIV-infected male.

Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Eubacterium rectale is a potential marker of altered gut microbiota in psoriasis and psoriatic arthritis.

Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.

SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors.

Despite the tremendous progress of chimeric antigen receptor T (CAR-T) cell therapy in hematological malignancies, their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment (TME) and systemic toxicity caused by excessive cytokine release. As a key regulator of the immunosuppressive TME, TGF-ß promotes cytokine synthesis via the NF-κB pathway. Here, we coexpressed SMAD7, a suppressor of TGF-ß signaling, with a HER2-targeted CAR in engineered T cells. These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-ß-triggered exhaustion, which enabled sustained tumoricidal capacity after continuous antigen exposure. Moreover, SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells. Mechanistically, SMAD7 downregulated TGF-ß receptor I and abrogated the interplay between the TGF-ß and NF-κB pathways in CAR-T cells. As a result, these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-ß. SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids. Therefore, our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.

Comparison of the effect of capsular bend on the rotational stability between 2 toric intraocular lenses.

PURPOSE: To compare the effect of capsular bend on the rotational stability between 2 toric intraocular lenses (IOLs). SETTING: Eye Hospital of Wenzhou Medical University, Hangzhou, Zhejiang Province, China. DESIGN: Prospective study. METHODS: Patients with preexisting astigmatism received AcrySof IQ (SN6AT) or TECNIS (ZCT/ZMT) toric IOL during cataract surgery. CASIA2 was used to record the toric IOL axial orientation and capsular bend index (CBI) at the 1-day, 1-week, 1-month, and 3-month interval postoperatively. The postoperative rotational stability and CBI of both models were compared. RESULTS: A total of 58 eyes from 58 patients were enrolled in this study. The total misalignment of the TECNIS (ZCT/ZMT) group (6.96 ± 5.10 degrees, 7.41 ± 5.19 degrees, 6.93 ± 5.29 degrees, and 6.86 ± 5. 27 degrees) was significantly higher than that of the AcrySof IQ (SN6AT) group (3.55 ± 2.21 degrees, 4.00 ± 2.74 degrees, 3.72 ± 2.72 degrees, and 3.52 ± 2.50 degrees) at all follow-up intervals ( P < .05). The mean rotation of the TECNIS (ZCT/ZMT) group (2.66 ± 2.18 degrees) was significantly greater than that of the AcrySof IQ (SN6AT) group (1.65 ± 1.47 degrees) from 1 day to 1 week postoperatively ( P < .05). The capsular bend formation in the TECNIS (ZCT/ZMT) group was delayed compared with the AcrySof IQ (SN6AT) group ( P < .05, at the 1-week, 1-month, and 3-month interval). The TECNIS (ZCT/ZMT) group showed fibrosis in the peripheral anterior capsule, leading to its stretching away from the IOL surface, while the AcrySof IQ (SN6AT) group exhibited gentle adherence of the anterior capsule to the IOL surface. CONCLUSIONS: The AcrySof IQ toric IOL (SN6AT) exhibited greater rotational stability than the TECNIS toric IOL (ZCT/ZMT), which may partially result from the delay in capsular bend formation of TECNIS at the 1-day to 1-week follow-up postoperatively.

Ultrasound-based detection of inflammatory changes for early diagnosis and risk model construction of psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavorable health outcomes. The application of ultrasound enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed ultrasound models to aid early diagnosis of PsA. METHODS: This is a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018-April 2021). All participants underwent thorough ultrasound examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45) and over 45 group (age > 45) and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were performed for model verification. RESULTS: A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and sixteen independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95%CI: 0.78-0.87) and 0.83 (95%CI: 0.78-0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models. CONCLUSION: The implementation of the ultrasound models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy.

Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.

Palmoplantar pustulosis with psoriatic arthritis ineffective to interleukin-17 inhibitors: two patients successfully treated with upadacitinib.

Palmoplantar pustulosis (PPP) is a rare chronic pustular disease. Psoriatic arthritis (PsA) is one of the common manifestations of arthritis in PPP associated with a high burden of disease. The treatment of PPP is difficult and still in the exploratory stage. Only a few cases show that PPP complicated with arthritis have been successfully treated with janus kinase inhibition, interleukin (IL)-6 inhibitors, IL-12/23 inhibitors and tumor necrosis factor inhibitors. Here we reported that two patients were diagnosed as PPP with PsA and initially treated with IL-17 inhibitors. One case was only partially relieved, and the other case had severe paradoxical reaction in the trunk. The joint and skin condition of two patients had been significantly improved without reported adverse reactions after 18 weeks treatment with upadacitinib, which support upadacitinib may be a potential option for patients with PPP combined PsA.

Functional polymorphisms in Benzo(a)Pyrene-induced toxicity pathways associated with the risk on laryngeal squamous cell carcinoma.

Benzo(a)Pyrene (BaP) is a well-known environmental carcinogen that poses a significant risk to human health. The pivotal genes and toxicity pathways have been identified as key events to construct the mode of action (MOA) of BaP. In this study, we focused on evaluating the association between genetic variants in BaP-disturbed toxicity pathways and the susceptibility of laryngeal squamous cell carcinoma (LSCC), based on the data of our previous genome-wide association analysis (GWAS). In addition, we investigated the biological roles of these significant polymorphisms by integrating bioinformatic annotation and experimental validation. Our findings revealed that 15 functional polymorphisms in AHR signaling, p53 signaling, NRF2 signaling, TGF-ß signaling, STAT3 signaling, and IL-8 signaling pathways were significantly associated with susceptibility to LSCC. Our study provides a novel approach for identifying novel risk genetic loci utilizing GWAS data, and suggests potential targets for early detection of LSCC in the future.

Humanized single-domain antibody targeting HER2 enhances function of chimeric antigen receptor T cells.

Introduction: Chimeric antigen receptors (CARs) can redirect T cells against antigen-expressing tumors, and each component plays an important role in the function and anti-tumor efficacy. It has been reported that using human sequences or a low affinity of CAR single-chain variable fragments (scFvs) in the CAR binding domains is a potential way to enhance the function of CAR-T cells. However, it remains largely unknown how a lower affinity of CARs using humanized scFvs affects the function of CAR-T cells until recently. Methods: We used different humanized anti-HER2 antibodies as the extracellular domain of CARs and further constructed a series of the CAR-T cells with different affinity. Results: We have observed that moderately reducing the affinity of CARs (light chain variable domain (VL)-based CAR-T) could maintain the anti-tumor efficacy, and improved the safety of CAR therapy both in vitro and in vivo compared with high-affinity CAR-T cells. Moreover, T cells expressing the VL domain only antibody exhibited long-lasting tumor elimination capability after multiple challenges in vitro, longer persistence and lower cytokine levels in vivo. Discussion: Our findings provide an alternative option for CAR-T optimization with the potential to widen the use of CAR T cells.

Ångstrom-scale silver particles ameliorate collagen-induced and K/BxN-transfer arthritis in mice via the suppression of inflammation and osteoclastogenesis.

OBJECTIVE: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. METHODS: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. RESULTS: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. CONCLUSIONS: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.

The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells.

Type 1 conventional dendritic cells (cDC1) are the most efficient cross-presenting cells that induce protective cytotoxic T cell response. However, the regulation of their homeostasis and function is incompletely understood. Here we observe a selective reduction of splenic cDC1 accompanied by excessive cell death in mice with Zeb1 deficiency in dendritic cells, rendering the mice more resistant to Listeria infection. Additionally, cDC1 from other sources of Zeb1-deficient mice display impaired cross-presentation of exogenous antigens, compromising antitumor CD8+ T cell responses. Mechanistically, Zeb1 represses the expression of microRNA-96/182 that target Cybb mRNA of NADPH oxidase Nox2, and consequently facilitates reactive-oxygen-species-dependent rupture of phagosomal membrane to allow antigen export to the cytosol. Cybb re-expression in Zeb1-deficient cDC1 fully restores the defective cross-presentation while microRNA-96/182 overexpression in Zeb1-sufficient cDC1 inhibits cross-presentation. Therefore, our results identify a Zeb1-microRNA-96/182-Cybb pathway that controls cross-presentation in cDC1 and uncover an essential role of Zeb1 in cDC1 homeostasis.

Celastrol alleviated acute kidney injury by inhibition of ferroptosis through Nrf2/GPX4 pathway.

Ferroptosis is an important pathological process in acute kidney injury (AKI) which could lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). As an active ingredient of Chinese medicine Tripterygium wilfordii, celastrol has been reported to alleviate inflammation and preclinical studies have confirmed its anticancer effect. In the present study, we investigated the renal protective effects of celastrol against cisplatin induced AKI. Mice were administrated cisplatin by intraperitoneal injection and we found that celastrol reduced serum levels of BUN and creatinine, inhibited renal dysfunction, inflammation and oxidative stress. In addition, renal iron accumulation and ferroptosis were significantly reduced by celastrol treatment. Further mechanistic analyses suggested that Nrf2 is essential for celastrol upregulated GPX4 to alleviate ferroptosis and reduction of LDH release, intracellular iron accumulation and lipid peroxidation. These findings expand the potential uses of celastrol for treatment of various kinds of AKI associated with ferroptosis.

The application of mesoporous silica nanoparticles as a drug delivery vehicle in oral disease treatment.

Mesoporous silica nanoparticles (MSNs) hold promise as safer and more effective medication delivery vehicles for treating oral disorders. As the drug's delivery system, MSNs adapt to effectively combine with a variety of medications to get over systemic toxicity and low solubility issues. MSNs, which operate as a common nanoplatform for the co-delivery of several compounds, increase therapy effectiveness and show promise in the fight against antibiotic resistance. MSNs offer a noninvasive and biocompatible platform for delivery that produces long-acting release by responding to minute stimuli in the cellular environmen. MSN-based drug delivery systems for the treatment of periodontitis, cancer, dentin hypersensitivity, and dental cavities have recently been developed as a result of recent unparalleled advancements. The applications of MSNs to be embellished by oral therapeutic agents in stomatology are discussed in this paper.

The Clinical Characteristics of Psoriatic Arthritis: A Cross-Sectional Study Based on the Psoriatic Arthritis Cohort of West China Hospital.

INTRODUCTION: This study aims to describe the demographic, clinical, laboratory, and ultrasonic characteristics of patients with psoriatic arthritis (PsA) in the Psoriatic Arthritis cohort of West China Hospital. METHODS: In this cross-sectional study, we included patients diagnosed with PsA according to the Classification Criteria for Psoriatic Arthritis, collected their demographic information, medical histories, and treatments, evaluated all domains (skin and nail lesions, tenderness, swelling, enthesitis, dactylitis, and axial arthritis) related to PsA, and then performed descriptive statistical analyses of all data. RESULTS: A total of 275 patients with PsA were included in this study. The ratio of male to female patients was 2.16:1. Skin lesions preceded arthritis in 86.5% of these patients with PsA with a mean interval of 10.1 years. The metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints of fingers, and sacroiliac joints are the most commonly involved sites of tenderness, swelling, and the spine, respectively. Among all comorbidities, fatty liver has the highest incidence with 33.1%. Finally, we noted that the mean disease duration of PsA was 4.2 years, suggesting a delay in the diagnosis of PsA. CONCLUSION: Our study proposes that the prevalent population of PsA are male patients with psoriasis over 40 years of age who have a long disease course. For patients with PsA, MCP, PIP joints of fingers, and sacroiliac joints are the most frequently affected anatomical sites. With respect to comorbidities, the association between PsA and fatty liver and the underlying molecular mechanisms are worthy of further exploration.

Smoke Exposure Reduces the Protective Effect of Physical Activity on Hypertension: Evidence from the National Health and Nutrition Examination Survey (NHANES) 2013-2018.

The joint effects between smoke exposure (SE) and physical activity (PA) on hypertension are still unclear, and the effect of SE is still debated. To explore associations and joint effects of SE and PA on hypertension, the data of 14,456 selected participants from the NHANES (2013-2018) were used for analyses. SE status was divided by serum cotinine concentrations. Moderate-to-vigorous intensity PA (MVPA) and insufficient or no PA (INPA) were divided by the Global Physical Activity Questionnaire. Hypertension was assessed by blood pressure and questionnaires. Survey logistic multivariable regression models were conducted for data analyses. In fully adjusted models, hypertension risk among SE participants increased (OR = 1.175, 95% CI: 1.036-1.332), especially those who were <40 years or female. However, the risk among MVPA participants decreased (OR = 0.747, 95% CI: 0.663-0.841), especially those who were ≥40 years. Additionally, the OR for MVPA participants without SE when compared with INPA ones without SE was 0.740 (95% CI: 0.654-0.837), especially those who were <60 years. However, the OR for MVPA participants with SE was 0.880 (95% CI: 0.747-1.037). For INPA participants, we did not observe significant ORs for SE compared with non-SE participants (p > 0.150). In conclusion, SE increased the risk of hypertension and MVPA reduced it, but SE could reduce such protective effect.

Nanosized copper particles induced mesangial cell toxicity via the autophagy pathway.

Nanosized copper particles (nano Cu) have been incorporated into products in multiple industries, although studies have demonstrated that these particles are nephrotoxic. We investigated the cytotoxicity of nanosized copper particles on rat mesangial cells and measured rates of apoptosis, the expression of caspase-3, and generation of reactive oxygen species. We also measured autophagy through the acridine orange (AO) staining and expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62 to screen the underlying mechanism of toxicity. Nanosized copper particles inhibited mesangial cell viability, up-regulated the activity of caspase-3, and increased the rates of apoptosis and the generation of reactive oxygen species in a concentration-dependent manner. Exposure to nano Cu increased the formation of acidic vesicular organelles and the expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62, and treatment with an autophagy inhibitor reduced nephrotoxicity. This indicated that the autophagy pathway is involved in the toxicity induced by nanosized copper particles to mesangial cells. This finding can contribute to the development of safety guidelines for the evaluation of nanomaterials in the future.

High cerebrospinal fluid lactate concentration at 48 h of hospital admission predicts poor outcomes in patients with tuberculous meningitis: A multicenter retrospective cohort study.

Objective: This study aimed to analyze the cerebrospinal fluid (CSF) parameters affecting the outcomes of patients with tuberculous meningitis (TBM). Methods: This is a multi-center, retrospective, cohort study involving 81 patients who were diagnosed with TBM and treated in Haihe Clinical College of Tianjin Medical University, Tianjin Medical University General Hospital, and General Hospital of Air Force PLA from January 2016 to December 2019. Baseline data, Glasgow Coma Scale (GCS) score, and clinical presentations of all patients were collected at admission. CSF samples were collected at 48 h, 1, 2, and 3 weeks after admission. CSF lactate, adenosine deaminase, chloride, protein, glucose levels and intracranial pressure were measured. After a follow-up of 16.14 ± 3.03 months, all patients were assessed using the modified Rankin Scale (mRS) and divided into good (mRS scores of 0-2 points) and poor outcome groups (mRS scores of 3-6 points). The differences in patients' baseline data, GCS score, clinical presentations, and levels of CSF parameters detected at 48 h, 1, 2, and 3 weeks after admission between two groups were compared. Statistically significant variables were added to the binary logistic regression model to identify the factors impacting the outcomes of patients with TBM. Receiver operating characteristic (ROC) curve was used to assess the predictive ability of the model. Results: The CSF lactate level exhibited a decreasing trend within 3 weeks of admission in the two groups. For the within-group comparison, statistically significant differences in the lactate level was found in both groups between four different time points. A binary logistic regression model revealed that CSF lactate level at 48 h after admission, age, and GSC score on admission were independently associated with the outcomes of patients with TBM. ROC curve analysis showed that the area under the ROC curve (AUC) was 0.786 for the CSF lactate level (48 h), 0.814 for GCS score, and 0.764 for age. Conclusion: High CSF lactate level at 48 h after admission is one of the important factors for poor outcomes in patients with TBM.

Ångstrom-scale silver particles potently combat SARS-CoV-2 infection by suppressing the ACE2 expression and inflammatory responses.

The SARS-CoV-2 pandemic has become a severe global public health event, and the development of protective and therapeutic strategies is urgently needed. Downregulation of angiotensin converting enzyme 2 (ACE2; one of the important SARS-CoV-2 entry receptors) and aberrant inflammatory responses (cytokine storm) are the main targets to inhibit and control COVID-19 invasion. Silver nanomaterials have well-known pharmaceutical properties, including antiviral, antibacterial, and anticancer properties. Here, based on a self-established metal evaporation-condensation-size graded collection system, smaller silver particles reaching the Ångstrom scale (AgÅPs) were fabricated and coated with fructose to obtain a stabilized AgÅP solution (F-AgÅPs). F-AgÅPs potently inactivated SARS-CoV-2 and prevented viral infection. Considering the application of anti-SARS-CoV-2, a sterilized F-AgÅP solution was produced via spray formulation. In our model, the F-AgÅP spray downregulated ACE2 expression and attenuated proinflammatory factors. Moreover, F-AgÅPs were found to be rapidly eliminated to avoid respiratory and systemic toxicity in this study as well as our previous studies. This work presents a safe and potent anti-SARS-CoV-2 agent using an F-AgÅP spray.