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BACKGROUND: Dysbiosis of gut microbiota is frequent in liver cirrhosis (LC) patients, and splenectomy (SP) has been reported to improve LC. Herein, we report the effects of SP on gut microbiota, especially on Veillonella parvula, a Gram-negative coccus of the gastrointestinal tract, in LC mice, and the underlying mechanism. METHODS: LC mice models were induced by tail vein injection of concanavalin A (ConA), followed by SP. 16 s rRNA sequencing was conducted to analyze the effects of ConA induction and SP on mouse gut microbiota and the gene expression affected by gut microbiota. LC mice receiving SP were gavaged with Veillonella parvula. Likewise, hepatic stellate cells (HSC) and hepatocytes (HC) were induced with conditioned medium (CM) of Veillonella parvula. RESULTS: SP alleviated LC in mice by restoring gut barrier function and maintaining gut microbiota balance, with Veillonella as the key genus. The Veillonella parvula gavage on LC mice reversed the ameliorative effect of SP. The CM of Veillonella parvula promoted the activation of HSC and the release of IL-6, IL-1ß, and TNF-α. Also, the CM of Veillonella parvula induced HC pyroptosis and the release of ALT and AST. Veillonella parvula represented an imbalance in the gut microbiota, thus enhancing gut-derived endotoxins in the liver with the main target being Tlr4/Nlrp3. Inhibition of Tlr4 blocked Veillonella parvula-induced HC damage, HSC activation, and subsequent LC progression. CONCLUSION: SP-mediated gut microbiota regulation ameliorates ConA-related LC progression by inhibiting Tlr4/Nlrp3 in the liver.
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Microbioma Gastrointestinal , Veillonella , Humanos , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Esplenectomia , Receptor 4 Toll-Like/metabolismo , Cirrose Hepática/terapiaRESUMO
P2-Na2/3Ni1/3Mn2/3O2 cathode materials have garnered significant attention due to their high cationic and anionic redox capacity under high voltage. However, the challenge of structural instability caused by lattice oxygen evolution and P2-O2 phase transition during deep charging persists. A breakthrough is achieved through a simple one-step synthesis of Cr, Mg co-doped P2-NaNMCM, resulting in a bi-functional improvement effect. P2-NaNMCM-0.01 exhibits an impressive capacity retention rate of 82% after 100 cycles at 1 C. In situ X-ray diffraction analysis shows that the "pillar effect" of Mg mitigates the weakening of the electrostatic shielding and effectively suppresses the phase transition of P2-O2 during the charging and discharging process. This successfully averts serious volume expansion linked to the phase transition, as well as enhances the Na+ migration. Simultaneously, in situ Raman spectroscopy and ex situ X-ray photoelectron spectroscopy tests demonstrate that the strong oxygen affinity of Cr forms a robust TMâO bond, effectively restraining lattice oxygen evolution during deep charging. This study pioneers a novel approach to designing and optimizing layered oxide cathode materials for sodium-ion batteries, promising high operating voltage and energy density.
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LiNO3 has attracted intensive attention as a promising electrolyte additive to regulate Li deposition behavior as it can form favorable Li3N, LiNxOy species to improve the interfacial stability. However, the inferior solubility in carbonate-based electrolyte restricts its application in high-voltage Li metal batteries. Herein, an artificial composite layer (referred to as PML) composed of LiNO3 and PMMA is rationally designed on Li surface. The PML layer serves as a reservoir for LiNO3 release gradually to the electrolyte during cycling, guaranteeing the stability of SEI layer for uniform Li deposition. The PMMA matrix not only links the nitrogen-containing species for uniform ionic conductivity but also can be coordinated with Li for rapid Li ions migration, resulting in homogenous Li-ion flux and dendrite-free morphology. As a result, stable and dendrite-free plating/stripping behaviors of Li metal anodes are achieved even at an ultrahigh current density of 20 mA cm-2 (>570 h) and large areal capacity of 10 mAh cm-2 (>1200 h). Moreover, the Li||LiFePO4 full cell using PML-Li anode undergoes stable cycling for 2000 cycles with high-capacity retention of 94.8%. This facile strategy will widen the potential application of LiNO3 in carbonate-based electrolyte for practical LMBs.
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The increasing demand for graphite and the higher lithium content than environment abundance make the recycling of anode in spent lithium-ion batteries (LIBs) also become an inevitable trend. This work proposes a simple pathway to convert the retired graphite to high-performance expanded graphite (EG) under mild conditions. After the oxidation and intercalation by FeCl3 for the retired graphite, H2O2 molecules are more likely to penetrate into the extended layers. And the gas phase diffusion caused by the produced O2 from the redox reaction between FeCl3 and H2O2 further promotes lattice expansion of interlayers (0.535 nm), which is beneficial to the stripping of graphene oxide (GO) with fewer layers. The EG exhibits excellent electrochemical performances in both LIBs and sodium-ion batteries (SIBs). It delivers 331.5 mAh g-1 at 3C (1C = 372 mA g-1) in LIBs, while it achieves 176.8 mAh g-1 at 3C (1C = 120 mA g-1) in SIBs. Then the capacity retains 753.6 (LIBs) and 201.6 (SIBs) mAh g-1 after a long-term cycling of 500 times at 1C, respectively. The full cells with the EG electrodes after prelithium/presodiation also show excellent cycle stability. Thus, this work offers another referable strategy for the recycling of waste graphite in spent LIBs.
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BACKGROUND AND AIMS: Microvascular invasion (MVI) is a crucial pathological hallmark of HCC that is closely associated with poor outcomes, early recurrence, and intrahepatic metastasis following surgical resection and transplantation. However, the intricate tumor microenvironment and transcriptional programs underlying MVI in HCC remain poorly understood. APPROACH AND RESULTS: We performed single-cell RNA sequencing of 46,789 individual cells from 10 samples of MVI+ (MVI present) and MVI- (MVI absent) patients with HCC. We conducted comprehensive and comparative analyses to characterize cellular and molecular features associated with MVI and validated key findings using external bulk, single-cell, and spatial transcriptomic datasets coupled with multiplex immunofluorescence assays. The comparison identified specific subtypes of immune and stromal cells critical to the formation of the immunosuppressive and pro-metastatic microenvironment in MVI+ tumors, including cycling T cells, lysosomal associated membrane protein 3+ dendritic cells, triggering receptor expressed on myeloid cells 2+ macrophages, myofibroblasts, and arterial i endothelial cells. MVI+ malignant cells are characterized by high proliferation rates, whereas MVI- malignant cells exhibit an inflammatory milieu. Additionally, we identified the midkine-dominated interaction between triggering receptor expressed on myeloid cells 2+ macrophages and malignant cells as a contributor to MVI formation and tumor progression. Notably, we unveiled a spatially co-located multicellular community exerting a dominant role in shaping the immunosuppressive microenvironment of MVI and correlating with unfavorable prognosis. CONCLUSIONS: This study provides a comprehensive single-cell atlas of MVI in HCC, shedding light on the complex multicellular ecosystem and molecular features associated with MVI. These findings deepen our understanding of the underlying mechanisms driving MVI and provide valuable insights for improving clinical diagnosis and developing more effective treatment strategies.
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The 2022 multi-country mpox outbreak raised public concern globally. Self-isolation and informing close contacts after developing mpox-related symptoms are critical measures in controlling the outbreak. This study investigated behavioral intentions of self-isolation and informing close contacts after developing mpox-related symptoms and associated factors among young men who have sex with men (YMSM) aged 18-29 years in China. The cross-sectional study was conducted among 2493 YMSM in six provincial regions in China from September 10th to 30th, 2022. Descriptive and logistic analyses were applied, using the intentions of self-isolation and informing close contacts after developing mpox-related symptoms as binary outcomes. The mean age of the participants was 24.6 (SD = 2.9) years. The prevalence of having intentions of self-isolation and informing close contacts after developing mpox-related symptoms was 88.6% (95% CI: 87.3%-89.9%) and 84.9% (95% CI: 83.5%-86.3%). Participants who were employed (adjusted odds ratio (AOR) = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI:1.002, 1.876), had higher mpox knowledge scores (AOR = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI: 1.002-1.876), and had higher perceived threats of mpox (AOR = 1.079, 95% CI: 1.030-1.130; AOR = 1.045, 95% CI: 1.002-1.090) were more likely to intend to self-isolate and inform close contacts. Participants who had MSM in-person gatherings in the past 6 months were more likely to intend to self-isolate (AOR = 1.392, 95% CI: 1.066-1.208). Participants with higher depression scores (AOR = 0.968, 95% CI: 0.948-0.989) and self-stigma (AOR = 0.975, 95% CI: 0.954-0.997) were less likely to intend to self-isolate and inform close contacts, respectively. Self-isolation and informing close contacts when developing disease-related symptoms are acceptable measures in response to mpox in China. Strengthening targeted risk communication and self-efficacy, raising disease knowledge, providing mental support, and reducing stigma toward the affected community are warranted.
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Infecções por HIV , Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto Jovem , Adulto , Homossexualidade Masculina , Estudos Transversais , Intenção , China/epidemiologia , Infecções por HIV/epidemiologiaRESUMO
The practical application of Zn-air batteries require exploring cost-effective and durable bifunctional electrocatalysts. However, the simultaneous preparation of catalysts with bifunctional activities for oxygen reduction reaction (ORR) and oxygen precipitation reaction (OER) remains challenging. Herein, we synthesized a novel hybrid catalyst (FePc/NiCo/CNT), which couples NiCo alloy with FePc through electrostatic interaction. The interaction between FePc and NiCo alloy can enhance the intrinsic catalytic activity of the active site Fe-N4 and prevent the electrolyte corrosion of the metal alloy, ultimately improving the stability of the catalyst by the microenvironment-tailoring strategy. The resultant FePc/NiCo/CNT catalyst exhibits outstanding oxygen reduction reaction (ORR) activity with a half-wave potential of 0.88 V, which is attributed to the abundant Fe-Nx active sites. Furthermore, the electron interactions between NiCo/CNT and FePc accelerate electron transfer and enhance the activation of oxygen intermediates, consequently boosting the OER activity with an overpotential of 260 mV at 10 mA cm-2. The Zn-air batteries assembled with FePc/NiCo/CNT show a high power density of 175.1 mW cm-2 and excellent cycling stability for up to 430 h at 20 mA cm-2. The preparation of oxygen electrode catalysts for renewable clean energy devices can be made more convenient with this directly engineered strategy for ORR and OER active centers.
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BACKGROUND: The incidence of neuroendocrine neoplasms (NENs) is rising rapidly worldwide. However, there are few reports on these heterogeneous diseases in China. Our study aimed to explore the epidemiological characteristics of NENs in Beijing. METHODS: We conducted a retrospective cohort study using population-based cancer surveillance data in Beijing, China. All data were extracted from the Beijing Cancer Registry with incidence dates from 1 January 1998 to 31 December 2018; the follow-up period was through 31 December 2021. Segi's world standard population was used to estimate the age-standardized rate. Survival was estimated using the Kaplan-Meier method. RESULTS: From 1998 to 2018, the incidence of NENs in Beijing initially showed a significant increasing trend, from 1.07/100,000 to 3.53/100,000; this began to plateau after 2013. The age-specific incidence rate increased with age and peaked in the age group 70-74 years. The incidence in men was significantly higher than that in women (4.41/100,000 vs. 1.69/100,000). The most common sites of NENs were the lung (2.38/100,000) and rectum (0.14/100,000). Most NENs were diagnosed at a late stage. We found that NENs originating from the lung had worse overall survival than extrapulmonary NENs, and male patients had worse survival than female patients. CONCLUSIONS: This study retrospectively analyzed the epidemiological characteristics of NENs in Beijing from 1998 to 2018. Our findings provide a reference regarding the epidemiological statistics of NENs in Beijing to contribute to the prevention, diagnosis, and treatment of these specific tumors.
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Tumores Neuroendócrinos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Pequim/epidemiologia , Idoso , Tumores Neuroendócrinos/epidemiologia , Incidência , Adulto , Adulto Jovem , Idoso de 80 Anos ou mais , Sistema de Registros , Adolescente , CriançaRESUMO
Diabetic cataract (DC) is a major cause of blindness in diabetic patients and it is characterized by early onset and rapid progression. MiR-204-5p was previously identified as one of the top five down-regulated miRNAs in human DC lens tissues. We aimed to determine the expression of miR-204-5p in human lens epithelial cells (HLECs) and explore its effects and mechanisms in regulating the progression of DC. The expression of miR-204-5p in the anterior capsules of DC patients and HLECs was examined by RT-qPCR. Bioinformatics tools were then used to identify the potential target of miR-204-5p. The relationship between miR-204-5p and the target gene was confirmed through a dual luciferase reporter assay. Additionally, the regulatory mechanism of oxidative stress, apoptosis, and inflammation in DC was investigated by overexpressing miR-204-5p using miR-204-5p agomir. The expression of miR-204-5p was downregulated in the anterior capsules of DC patients and HLECs. Overexpression of miR-204-5p reduced ROS levels, pro-apoptosis genes (Bid, Bax, caspase-3), and IL-1ß production in HG-treated HLECs. TXNIP was the direct target of miR-204-5p by dual luciferase reporter assay. Therefore, this study demonstrated that miR-204-5p effectively reduced oxidative damage, apoptosis, and inflammation in HLECs under HG conditions by targeting TXNIP. Targeting miR-204-5p could be a promising therapeutic strategy for the potential treatment of DC.
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The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague-Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.
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PURPOSE: This retrospective study aimed to investigate whether the repair of medial meniscus posterior root tears (MMPRTs) is effective for improving clinical outcomes and return to sports rates in young patients (50 years old or younger) with medial compartment knee osteoarthritis (KOA) and MMPRTs. METHODS: Between 2016 and 2019, 153 patients with KOA and MMPRTs who underwent open-wedge high tibial osteotomy (OWHTO) were retrospectively included. The patients were divided into OWHTO combined with MMPRT repair (n = 73) and isolated OWHTO (n = 80) groups. Lysholm scores, Hospital for Special Surgery (HHS) scores, Tegner scores, flexion contracture, range of knee flexion, return to sports rates and postoperative complications were compared. Radiological outcomes, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and Kellgren-Lawrence (K-L) grade, were compared between the two groups. RESULTS: After a mean follow-up of 30.1 ± 3.0 months, the OWHTO + Repair group observed better clinical outcomes compared with the OWHTO group (Lysholm score: 86.7 ± 7.4 vs. 81.6 ± 6.9, p = 0.023. HHS score: 85.4 ± 8.20 vs. 80.5 ± 7.1, p = 0.039). The OWHTO + Repair group had higher Tegner scores and return to sports rates than the OWHTO group (Tegner score: 6 vs. 5, p = 0.020; return to sports rates: 38% vs. 15%, p = 0.001). No fracture or major complications occurred. Radiological outcomes showed no significant differences between the two groups (HKA: 181.1 ± 2.7 vs. 180.1 ± 1.5 n.s; MPTA: 90.1 ± 1.8 vs. 89.2 ± 1.4, n.s; JLCA:1.9 ± 0.7 vs. 2.1 ± 0.7, n.s). CONCLUSIONS: Additional MMPRT repair during OWHTO was associated with better clinical outcomes and higher rates of return to sports in young patients with medial compartment KOA and MMPRTs. LEVEL OF EVIDENCE: Level III.
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Osteoartrite do Joelho , Osteotomia , Volta ao Esporte , Tíbia , Lesões do Menisco Tibial , Humanos , Estudos Retrospectivos , Osteotomia/métodos , Masculino , Feminino , Osteoartrite do Joelho/cirurgia , Lesões do Menisco Tibial/cirurgia , Pessoa de Meia-Idade , Tíbia/cirurgia , Adulto , Resultado do Tratamento , Amplitude de Movimento Articular , Complicações Pós-Operatórias/epidemiologiaRESUMO
Chronic Hepatitis B virus (CHB) infection is a global health challenge, causing damage ranging from hepatitis to cirrhosis and hepatocellular carcinoma. In our study, single-cell RNA sequencing (scRNA-seq) analysis was performed in livers from mice models with chronic inflammation induced by CHB infection and we found that endothelial cells (ECs) exhibited the largest number of differentially expressed genes (DEGs) among all ten cell types. NF-κB signaling was activated in ECs to induce cell dysfunction and subsequent hepatic inflammation, which might be mediated by the interaction of macrophage-derived and cholangiocyte-derived VISFATIN/Nampt signaling. Moreover, we divided ECs into three subclusters, including periportal ECs (EC_Z1), midzonal ECs (EC_Z2), and pericentral ECs (EC_Z3) according to hepatic zonation. Functional analysis suggested that pericentral ECs and midzonal ECs, instead of periportal ECs, were more vulnerable to HBV infection, as the VISFATIN/Nampt- NF-κB axis was mainly altered in these two subpopulations. Interestingly, pericentral ECs showed increasing communication with macrophages and cholangiocytes via the Nampt-Insr and Nampt-Itga5/Itgb1 axis upon CHB infection, which contribute to angiogenesis and vascular capillarization. Additionally, ECs, especially pericentral ECs, showed a close connection with nature killer (NK) cells and T cells via the Cxcl6-Cxcr6 axis, which is involved in shaping the microenvironment in CHB mice livers. Thus, our study described the heterogeneity and functional alterations of three subclusters in ECs. We revealed the potential role of VISFATIN/Nampt signaling in modulating ECs characteristics and related hepatic inflammation, and EC-derived chemokine Cxcl16 in shaping NK and T cell recruitment, providing key insights into the multifunctionality of ECs in CHB-associated pathologies.
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Células Endoteliais , Hepatite B Crônica , Análise de Célula Única , Animais , Hepatite B Crônica/virologia , Hepatite B Crônica/genética , Hepatite B Crônica/metabolismo , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Análise de Sequência de RNA , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Transdução de Sinais , Fígado/metabolismo , Fígado/virologia , Fígado/patologia , NF-kappa B/metabolismo , Masculino , Nicotinamida Fosforribosiltransferase/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , HumanosRESUMO
OBJECTIVES: To investigate the incidence and influencing factors of allergic reactions to cephalosporins. METHODS: A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated. The influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression. RESULTS: A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67 , the highest incidences of anaphylaxis occurred in ceftizoxime (4.27), followed by ceftriaxone (3.49) and cefotaxime (2.40). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75 vs. 1.63, RR=1.07, 95%CI:0.70-1.63, P> 0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/cm2 (RR=2.43, 95%CI: 1.23-4.82, P<0.01) and history of ß-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftriaxone (RR=3.74, 95%CI: 1.64-8.50, P<0.01). CONCLUSIONS: Lower BMI and history of ß-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions, and the routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.
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The mpox outbreak since 2022 had attacked the community of men who have sex with men (MSM) heavily. This large cross-sectional study investigated the levels and associated factors of mpox risk perception among young MSM (YMSM) aged 18-29 years in six provincial regions of China in September 2022. The participants were recruited via facility-based sampling. Mpox risk perception was measured by perceived susceptibility and perceived severity of mpox. Geodetector was used to measure stratified heterogeneity of mpox risk perception. Univariate and multivariable linear regressions were used to examine the factors associated with mpox risk perception. A total of 2493 participants were included with a mean age of 24.6 years. The proportion of perceiving a susceptibility of mpox under different scenarios ranged 3.7%-17.0% and that of perceiving a severity of mpox ranged 81.6%-83.2%. Stratified heterogeneity of perceived susceptibility, perceived severity, and overall perceived risk of mpox were observed in several characteristics such as study sites, monthly income, risk behaviors, and psychosocial factors. Multivariable regression showed the level of mpox risk perception was positively associated with having in-person gathering activities (ba = 0.457, 95% CI: 0.208, 0.705), history of HIV infection (ba = 0.431, 95% CI: 0.028, 0.834), depressive symptoms (ba = 0.069, 95% CI: 0.049, 0.090), and self-stigma to MSM identity (ba = 0.047, 95% CI: 0.024, 0.071). The Chinese YMSM showed a high level of perceived severity of mpox but a low level of perceived susceptibility. It is warranted to strengthen targeted risk communication of mpox, develop comprehensive and unstigmatized health messages, and provide mental health support for YMSM.
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Infecções por HIV , Homossexualidade Masculina , Mpox , Minorias Sexuais e de Gênero , Adulto , Humanos , Masculino , Adulto Jovem , Estudos Transversais , População do Leste Asiático , Infecções por HIV/epidemiologia , Percepção , Risco , AdolescenteRESUMO
BACKGROUND: Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein. METHODS: C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-ß2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit. RESULTS: ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased. Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-ß2 treatment. These effects were reversed by ARG1 knockdown. The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes. Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-ß2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression. Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients. CONCLUSIONS: ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients.
Fibrotic cataracts can be classified as anterior subcapsular cataract or posterior capsular opacification depending on where fibrosis occurs. The mechanism of fibrotic cataracts is not fully understood. Fibrotic opacities induced by trauma, inflammation, or radiation can accumulate underneath the anterior lens capsule, causing anterior subcapsular cataract. Posterior capsular opacification is one of the most common complications of phacoemulsification with intraocular lens implantation, with a high incidence in young patients. We show for the first time that ARG1 can regulate EMT in fibrotic cataracts. TGF-ß2 is the main cause of fibrosis in LECs. The expression of ARG1 and fibronectin in LECs increased after TGF-ß2 treatment or mouse lens capsular injury. We investigated the specific molecular mechanisms by which ARG1 regulates EMT in fibrotic cataracts. The mRNA expression of enzymes of the arginase-related pathway was decreased due to knockdown of ARG1 expression in HLECs. These effects were reversed by ARG1 overexpression. Additionally, knockdown of ARG1 decreased collagen 1A1, fibronectin, and vimentin expression; superoxide levels; and cell migration and increased NO levels. These effects were reversed by ARG1 overexpression. Pharmacological blockade of the ARG1 pathway with CB-1158 reduced the proliferation of LECs and decreased fibronectin, α-SMA, collagen 1A1, and vimentin expression in mouse lenses. We believe that ARG1 promotes the production of collagen 1A1 by directly activating the arginase pathway and leads to lens fibrosis by reducing NO production and increasing superoxide levels, providing a new mechanism for the prevention and treatment of fibrotic cataracts. Video Abstract.
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Arginase , Catarata , Transição Epitelial-Mesenquimal , Animais , Humanos , Camundongos , Antígeno Ki-67 , Camundongos Endogâmicos C57BL , Superóxidos , Fator de Crescimento Transformador beta2 , VimentinaRESUMO
Electrochemical exfoliation starting with graphite powder as the raw material for graphene production shows superiority in cost effectiveness over the popular bulk graphite. However, the crucial conductive network inside the graphite powder electrode along with its formation and influence mechanisms remains blank. Here, an adjustable-pressure graphite powder electrode with a sandwich structure was designed for this. Appropriate encapsulation pressure is necessary and conducive to constructing a continuous and stable conductive network, but overloaded encapsulation pressure is detrimental to the exfoliation and graphene quality. With an initial encapsulation pressure (IEP) of 4 kPa, the graphite powders expand rapidly to a final stable expansion pressure of 49 kPa with a final graphene yield of 46.3%, where 84% of the graphene sheets are less than 4 layers with ID/IG values between 0.22 and 1.24. Increasing the IEP to 52 kPa, the expansion pressure increases to 73 kPa, but the graphene yield decreases to 39.3% with a worse graphene quality including higher layers and ID/IG values of 1.68-2.13. In addition, small-size graphite powders are not suitable for the electrochemical exfoliation. With the particle size decreasing from 50 to 325 mesh, the graphene yield decreases almost linearly from 46.3% to 5.5%. Conductive network and electrolyte migration synergize and constrain each other, codetermining the electrochemical exfoliation. Within an encapsulated structure, the electrochemical exfoliation of the graphite powder electrode proceeds from the outside to the inside. The insights revealed here will provide direction for further development of electrochemical exfoliation of graphite powder to produce graphene.
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BACKGROUND: We aimed to assess the performance of the risk assessment questionnaire and fecal immunochemical test (FIT) in a population-based colorectal cancer (CRC) screening program to provide timely evidence for tailored screening strategies in China. METHODS: This analysis was conducted using data from Beijing Cancer Screening Prospective Cohort Study (BCSPCS). A risk assessment questionnaire and FIT were selected as the primary screening methods, and participants with any positive results were referred to undergo a diagnostic colonoscopy. RESULTS: From 2015 to 2020, 148,636 Beijing residents aged 40-69 years were invited from designated communities, with 147,807 finishing the risk assessment questionnaire and 115,606 (78.2%) completing the FIT. Among the 42,969 (29.1%) high-risk CRC participants, 23,824 (55.4%) underwent colonoscopy. One year after enrollment, all subjects were linked to the Beijing Cancer Registry (BCR) database and 241 cases of CRC were confirmed. The CRC incidence rate was 58.2/100,000 for the low-risk arm and 418.9/100,000 for the high-risk arm. For participants who underwent colonoscopy, 91 CRC cases were detected, with a detection rate of 91.9% and 63.7% of them were early-stage cases. Furthermore, the sensitivities of utilizing the risk assessment questionnaire alone, FIT alone, combined risk assessment questionnaire and FIT were 75.7%, 50.1%, and 95.1%, and the specificities were 75.3%, 87.3%, and 70.7%, respectively. CONCLUSION: The Beijing CRC screening program can effectively detect early-onset CRC; however, the compliance with colonoscopy still needs to be improved.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Pequim/epidemiologia , Seguimentos , Estudos Prospectivos , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologiaRESUMO
Aiming at the problem of distributed state estimation in sensor networks, a novel optimal distributed finite-time fusion filtering method based on dynamic communication weights has been developed. To tackle the fusion errors caused by incomplete node information in distributed sensor networks, the concept of limited iterations of global information aggregation was introduced, namely, fast finite-time convergence techniques. Firstly, a local filtering algorithm architecture was constructed to achieve fusion error convergence within a limited number of iterations. The maximum number of iterations was derived to be the diameter of the communication topology graph in the sensor network. Based on this, the matrix weight fusion was used to combine the local filtering results, thereby achieving optimal estimation in terms of minimum variance. Next, by introducing the generalized information quality (GIQ) calculation method and associating it with the local fusion result bias, the relative communication weights were obtained and embedded in the fusion algorithm. Finally, the effectiveness and feasibility of the proposed algorithm were validated through numerical simulations and experimental tests.
RESUMO
This paper is concerned with the estimation of correlated noise and packet dropout for information fusion in distributed sensing networks. By studying the problem of the correlation of correlated noise in sensor network information fusion, a matrix weight fusion method with a feedback structure is proposed to deal with the interrelationship between multi-sensor measurement noise and estimation noise, and the method can achieve optimal estimation in the sense of linear minimum variance. Based on this, a method is proposed using a predictor with a feedback structure to compensate for the current state quantity to deal with packet dropout that occurs during multi-sensor information fusion, which can reduce the covariance of the fusion results. Simulation results show that the algorithm can solve the problem of information fusion noise correlation and packet dropout in sensor networks, and effectively reduce the fusion covariance with feedback.
Assuntos
Algoritmos , Retroalimentação , Simulação por ComputadorRESUMO
To assess the health of river ecosystems, it is essential to quantify the ecological risk of heavy metals in river sediments and the structure of microbial communities. As important tributaries of the Tuo River in the upper reaches of the Yangtze River, the Mianyuan River and the Shiting River, are closely related to the economic development and human daily life in the region. This study assessed the ecological risks of heavy-metal-polluted river sediments, the heavy-metal-driven bacterial communities were revealed, and the relationships between the ecological risks and the identical bacterial communities were discussed. The Cd content was significantly greater than the environmental background value, leading to a serious pollution and very high ecological risk at the confluence of the two rivers and the upper reaches of the Mianyuan River. Microbial community analysis showed that Rhodobacter, Nocardioides, Sphingomonas, and Pseudarthrobacter were the dominant bacterial genera in the sediments of the Shiting River. However, the dominant bacterial genera in the Mianyuan River were Kouleothrix, Dechloromonas, Gaiella, Pedomicrobium, and Hyphomicrobium. Mantel test results showed (r = 0.5977, P = 0.005) that the Cd, As, Zn, Pb, Cr, and Cu were important factors that influenced differences in the distribution of sediment bacterial communities Mianyuan and Shiting rivers. A correlation heatmap showed that heavy metals were negatively correlated for most bacterial communities, but some bacterial communities were tolerant and showed a positive correlation. Overall, the microbial structure of the river sediments showed a diverse spatial distribution due to the influence of heavy metals. The results will improve the understanding of rivers contaminated by heavy metals and provide theoretical support for conservation and in situ ecological restoration of river ecosystems.