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The liquid-like feature of thermoelectric superionic conductors is a double-edged sword: the long-range migration of ions hinders the phonon transport, but their directional segregation greatly impairs the service stability. We report the synergetic enhancement in figure of merit (ZT) and stability in Cu1.99Se-based superionic conductors enabled by ion confinement effects. Guided by density functional theory and nudged elastic band simulations, we elevated the activation energy to restrict ion migrations through a cation-anion co-doping strategy. We reduced the carrier concentration without sacrificing the low thermal conductivity, obtaining a ZT of â¼3.0 at 1,050 K. Notably, the fabricated device module maintained a high conversion efficiency of up to â¼13.4% for a temperature difference of 518 K without obvious degradation after 120 cycles. Our work could be generalized to develop electrically and thermally robust functional materials with ionic migration characteristics.
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BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.
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Circuncisão Masculina , Infecções por HIV , Homossexualidade Masculina , Humanos , Masculino , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , China/epidemiologia , Incidência , Comportamento Sexual , Análise de Intenção de TratamentoRESUMO
One-dimensional molecular crystal waveguide (MCW) can transmit self-generated electrochemiluminescence (ECL), but heavy optical loss occurs because of the small difference in the refractive index between the crystal and its surroundings. Herein, we report a micropipette electrode-supported MCW (MPE/MCW) for precisely controlling the far-field transmission of ECL in air with a low optical loss. ECL is generated from one terminal of the MCW positioned inside the MPE, which is transmitted along the MCW to the other terminal in air. In comparison with conventional waveguides on solid substrates or in solutions, the MPE/MCW is propitious to the total internal reflection of light at the MCW/air interface, thus confining the ECL efficiently in MCW and improving the waveguide performance with an extremely low-loss coefficient of 4.49 × 10-3 dB µm-1. Moreover, by regulation of the gas atmosphere, active and passive waveguides can be resolved simultaneously inside MPE and in air. This MPE/MCW offers a unique advantage of spatially controlling and separating ECL signal readout from its generation, thus holding great promise in biosensing without or with less electrical/chemical disturbance.
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Nucleic acid detection of pathogens in a point-of-need (PON) manner is of great significance yet remains challenging for sensitive and accurate visual discrimination. Here, we report a CRISPR-Cas12a-mediated lateral flow assay for PON detection of Salmonella typhimurium (S.ty) that is a prevailing pathogen disseminated through tainted food. The variation of the fluorescence color of the test line is exploited to interpret the results, enabling the discrimination between positive and negative samples on the basis of a hue-recognition mechanism. By leveraging the cleavage activity of Cas12a and hue-recognition readout, the assay facilitated by recombinase polymerase amplification can yield a visual detection limit of 1 copy µL-1 for S.ty genomic DNA within 1 h. The assay also displays a high specificity toward S.ty in fresh chicken samples, as well as a sensitivity 10-fold better than that of the commercial test strip. Moreover, a semiquantitative detection of S.ty ranging from 0 to 4 × 103 CFU/mL by the naked eye is made possible, thanks to the easily discernible color change of the test line. This approach provides an easy, rapid, accurate, and user-friendly solution for the PON detection of Salmonella and other pathogens.
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Sistemas CRISPR-Cas , Salmonella typhimurium , Animais , Sistemas CRISPR-Cas/genética , Salmonella typhimurium/genética , Bioensaio , Galinhas , Alimentos , Técnicas de Amplificação de Ácido NucleicoRESUMO
Paper-based lateral flow immunoassays (LFIAs) are cost-effective, portable, and simple methods for detection of diverse analytes, which however only provide qualitative or semiquantitative results and lack sufficient sensitivity. A combination of LFIA and electrochemical detection, namely, electrochemical lateral flow immunoassay (eLFIA), enables quantitative detection of analytes with high sensitivity, but the integration of external electrodes makes the system relatively expensive and unstable. Herein, the working, counter, and reference electrodes were prepared directly on the nitrocellulose membrane using screen printing, which remarkably simplified the structure of eLFIA and decreased the cost. Moreover, a horseradish peroxidase (HRP)-based electrochemical signal amplification strategy was used for further increasing the analytical sensitivity. HRP captured on the working electrode can catalyze the oxidation of tetramethylbenzidine (TMB) to form the TMB-TMBox precipitate on the electrode surface, which as an electrochemically active product can output an amplified current for quantification. We demonstrated that the eLFIA could detect low-abundant inflammatory biomarkers in human plasma samples with limits of detection of 0.17 and 0.54 pg mL-1 for interleukin-6 and C-reactive protein, respectively. Finally, a fully portable system was fabricated by integrating eLFIA with a flexible and wireless electrochemical workstation, realizing the point-of-care detection of interleukin-6.
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Biomarcadores , Proteína C-Reativa , Técnicas Eletroquímicas , Eletrodos , Interleucina-6 , Humanos , Imunoensaio/métodos , Imunoensaio/instrumentação , Técnicas Eletroquímicas/instrumentação , Biomarcadores/sangue , Biomarcadores/análise , Interleucina-6/sangue , Interleucina-6/análise , Proteína C-Reativa/análise , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Limite de Detecção , Inflamação/sangue , Inflamação/diagnóstico , BenzidinasRESUMO
Telomerase reverse transcriptase (TERT) not only upholds telomeric equilibrium but also plays a pivotal role in multiple non-canonical cellular mechanisms, particularly in the context of aging, cancer, and genomic stability. Though depletion of SIRT1 in mouse embryonic fibroblasts has demonstrated telomere shortening, the impact of SIRT1 on enabling TERT to regulate telomeric homeostasis remains enigmatic. Here, we reveal that SIRT1 directly interacts with TERT, and promotes the nuclear localization and stability of TERT. Reverse transcriptase (RT) domain of TERT and N-terminus of SIRT1 mainly participated in their direct interaction. TERT, concomitantly expressed with intact SIRT1, exhibits nuclear localization, whereas TERT co-expressed with N-terminal-deleted SIRT1 remains in the cytosol. Furthermore, overexpression of SIRT1 enhances the nuclear localization and protein stability of TERT, akin to overexpression of deacetylase-inactive SIRT1, whereas N-terminal-deleted SIRT1 has no effect on TERT. These findings suggest a novel regulatory role of SIRT1 for TERT through direct interaction. This interaction provides new insights into the fields of aging, cancer, and genome stability governed by TERT and SIRT1.
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Sirtuína 1 , Telomerase , Animais , Humanos , Camundongos , Núcleo Celular/metabolismo , Estabilidade Enzimática , Células HEK293 , Ligação Proteica , Estabilidade Proteica , Sirtuína 1/metabolismo , Sirtuína 1/genética , Telomerase/metabolismo , Telomerase/genéticaRESUMO
MXenes, with their remarkable attributes, stand at the forefront of diverse applications. However, the challenge remains in sustaining their performance, especially concerning Ti3C2Tx MXene electrodes. Current self-healing techniques, although promising, often rely heavily on adjacent organic materials. This study illuminates a pioneering water-initiated self-healing mechanism tailored specifically for standalone MXene electrodes. Here, both water and select organic solvents seamlessly mend impaired regions. Comprehensive evaluations around solvent types, thermal conditions, and substrate nuances underline water's unmatched healing efficacy, attributed to its innate ability to forge enduring hydrogen bonds with MXenes. Optimal healing environments range from ambient conditions to a modest 50 °C. Notably, on substrates rich in hydroxyl groups, the healing efficiency remains consistently high. The proposed healing mechanism encompasses hydrogen bonding formation, capillary action-induced expansion of interlayer spacing, solvent lubrication, Gibbs free energy minimizing MXene nanosheet rearrangement, and solvent evaporation-triggered MXene layer recombination. MXenes' resilience is further showcased by their electrical revival from profound damages, culminating in the crafting of Joule-heated circuits and heaters.
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Electrochemiluminescence (ECL) is one of the most powerful techniques that meet the needs of analysis and detection in a variety of scenarios, because of its highly analytical sensitivity and excellent spatiotemporal controllability. ECL combined with microscopy (ECLM) offers a promising approach for quantifying and mapping a wide range of analytes. To date, ECLM has been widely used to image biological entities and processes, such as cells, subcellular structures, proteins and membrane transport properties. In this review, we first introduced the mechanisms of several classic ECL systems, then highlighted the progress of visual biosensing and bioimaging by ECLM in the last decade. Finally, the characteristics of ECLM were summarized, as well as some of the current challenges. The future research interests and potential directions for the application of ECLM were also outlooked.
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People living with HIV (PLWH) are particularly vulnerable to SARS-CoV-2. This multicentre prospective cohort study evaluated the long-term immunogenicity and safety of a third homologous dose of Sinovac CoronaVac in PLWH in China. A total of 228 PLWH and 127 HIV-negative controls were finally included and followed up for 6 months. Fewer participants reported mild or moderate adverse reactions, and no serious adverse events were observed. The median levels of neutralizing antibodies (nAbs) and immunoglobulin G against the receptor-binding domain of the spike protein (S-IgG) in PLWH (655.92 IU/mL, IQR: 175.76-1663.55; 206.83 IU/mL, IQR: 85.20-397.82) were comparable to those in control group (1067.16 IU/mL, IQR: 239.85-1670.83; 261.70 IU/mL, IQR: 77.13-400.75), and reached their peak at 4 weeks, exhibiting a delayed peak pattern compared to the 2-week peak in control group. After then, the immune titres gradually decreased over time, but most participants still maintained positive seroconversion at the 6-month mark. Multivariable generalized estimating equation analysis indicated that CD4+T cell count, HIV viral load, and antiretroviral therapy (ART) were independent factors strongly associated with immune response (each p < 0.05). We suggested that PLWH should maintain well-controlled HIV status through ART and receive timely administration of the second booster dose for optimal protection.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , Vacinas de Produtos Inativados , Humanos , Estudos Prospectivos , China , Contagem de Linfócito CD4 , Imunogenicidade da VacinaRESUMO
Herein, we report an electroosmotic pump (EOP) based on a multilayer track-etched polycarbonate (PC) membrane. A remarkable increase of maximum backpressure (198.2-2400 mmH2 O) of a fundamental pump unit was obtained at 0.8 mA, when the number of PC membranes was increased from 1 to 10. Meanwhile, the corresponding flow rate was increased from 80.3 to 111.7 µL/min. Furthermore, multiple pump units were assembled in series to obtain a multistage EOP. For a three-stage EOP (EOP-3), the operating voltage and power can be decreased significantly by 52%-72% under different driving currents, with a minimum power of 26.7 µW. Thus, EOP-3 can run stably over 35 h at a pulse current of 0.1 mA without the generation of gas bubbles. The pump was further integrated into a miniature device, which was successfully used to decrease the blood glucose level of diabetic rats by subcutaneous delivery of fast-acting insulin. This work brings a facile and efficient strategy to enhance the backpressure and lower the operating voltage and power of EOPs, which may find promising applications in drug delivery.
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Diabetes Mellitus Experimental , Animais , Ratos , Eletro-OsmoseRESUMO
Cathodic electrochemiluminescence (ECL) of a luminol (or its analogues)-dissolved oxygen (O2) system is an ideal alternative to ECL of the traditional luminol-hydrogen peroxide (H2O2) system, which can efficiently avoid the self-decomposition of H2O2 at room temperature. However, the mechanism for the generation of cathodic ECL by the luminol (or its analogues)-O2 system is still ambiguous. Herein, we report the study of cathodic ECL generation by the L012-O2 system at a glassy carbon electrode (GCE). The types of reactive oxygen species (ROS) involved generated during ECL reactions were verified. A possible reaction mechanism for the system was proposed and the rate constants of related reactions were estimated. Furthermore, several intermediates of L012 involved in the proposed pathways were validated by electrochemistry-coupled mass spectrometry. Finally, the cathodic ECL system was successfully used for measuring the antioxidant capacity of commercial juice with Trolox as a standard.
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Antioxidantes , Técnicas Biossensoriais , Luminol/química , Peróxido de Hidrogênio/química , Medições Luminescentes/métodos , Eletrodos , Oxigênio/química , Técnicas Eletroquímicas , Limite de DetecçãoRESUMO
Despite significant improvements in vaccines and chemotherapeutic drugs, pathogenic RNA viruses continue to have a profound impact on the global economy and pose a serious threat to animal and human health through emerging and re-emerging outbreaks of diseases. To overcome the challenge of viral adaptation and evolution, increased vigilance is required. Particularly, antiviral drugs derived from new, natural sources provide an attractive strategy for controlling problematic viral diseases. In this antiviral study, we discovered a previously unknown bacterium, Mameliella sp. M20D2D8, by conducting an antiviral screening of marine microorganisms. An extract from M20D2D8 exhibited antiviral activity with low cytotoxicity and was found to be effective in vitro against multiple influenza virus strains: A/PR8 (IC50 = 2.93 µg/mL, SI = 294.85), A/Phil82 (IC50 = 1.42 µg/mL, SI = 608.38), and B/Yamagata (IC50 = 1.59 µg/mL, SI = 543.33). The antiviral action was found to occur in the post-entry stages of viral replication and to suppress viral replication by inducing apoptosis in infected cells. Moreover, it efficiently suppressed viral genome replication, protein synthesis, and infectivity in MDCK and A549 cells. Our findings highlight the antiviral capabilities of a novel marine bacterium, which could potentially be useful in the development of drugs for controlling viral diseases.
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Herpesvirus Cercopitecino 1 , Influenza Humana , Viroses , Animais , Humanos , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Replicação ViralRESUMO
BACKGROUND: Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated. METHODS: There were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis. RESULTS: Of the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result. CONCLUSION: This study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.
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Infecções por HIV , Centros de Atenção Terciária , Carga Viral , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Masculino , Feminino , Adulto , Pequim , Pessoa de Meia-Idade , HIV-1/genética , HIV-1/isolamento & purificação , RNA Viral/sangue , Anticorpos Anti-HIV/sangue , Adulto Jovem , China/epidemiologia , Diagnóstico Precoce , AdolescenteRESUMO
In previous studies, we developed anti-trypanosome tubulin inhibitors with promising in vitro selectivity and activity against Human African Trypanosomiasis (HAT). However, for such agents, oral activity is crucial. This study focused on further optimizing these compounds to enhance their ligand efficiency, aiming to reduce bulkiness and hydrophobicity, which should improve solubility and, consequently, oral bioavailability. Using Trypanosoma brucei brucei cells as the parasite model and human normal kidney cells and mouse macrophage cells as the host model, we evaluated 30 new analogs synthesized through combinatorial chemistry. These analogs have fewer aromatic moieties and lower molecular weights than their predecessors. Several new analogs demonstrated IC50s in the low micromolar range, effectively inhibiting trypanosome cell growth without harming mammalian cells at the same concentration. We conducted a detailed structure-activity relationship (SAR) analysis and a docking study to assess the compounds' binding affinity to trypanosome tubulin homolog. The results revealed a correlation between binding energy and anti-Trypanosoma activity. Importantly, compound 7 displayed significant oral activity, effectively inhibiting trypanosome cell proliferation in mice.
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Tripanossomicidas , Trypanosoma brucei brucei , Animais , Trypanosoma brucei brucei/efeitos dos fármacos , Tripanossomicidas/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/química , Relação Estrutura-Atividade , Camundongos , Humanos , Administração Oral , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Simulação de Acoplamento Molecular , Tubulina (Proteína)/metabolismo , Testes de Sensibilidade Parasitária , Relação Dose-Resposta a Droga , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Tripanossomíase Africana/tratamento farmacológicoRESUMO
Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.
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Doenças do Cão , Neoplasias Mamárias Animais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Cães , Feminino , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Doenças do Cão/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transdução de Sinais , Inibidores de Fosfoinositídeo-3 Quinase/farmacologiaRESUMO
Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.
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Regeneração Óssea , Diferenciação Celular , Osteogênese , Animais , Camundongos , Engenharia Tecidual/métodos , Células-Tronco Mesenquimais/citologia , HumanosRESUMO
BACKGROUND: Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. METHODS: We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. RESULTS: The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6-25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3-54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. CONCLUSIONS: Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. TRIAL REGISTRATION: PROSPERO; No: CRD42022338586.
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Infecções por HIV , Tuberculose Meníngea , Humanos , Tuberculose Meníngea/epidemiologia , Tuberculose Meníngea/mortalidade , Tuberculose Meníngea/complicações , Incidência , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Prevalência , AdultoRESUMO
OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810ï½0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018ï½12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131ï½2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.
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PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.
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Exoesqueleto Energizado , Extremidade Inferior , Equilíbrio Postural , Robótica , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/instrumentação , Reabilitação do Acidente Vascular Cerebral/métodos , Masculino , Projetos Piloto , Feminino , Pessoa de Meia-Idade , Extremidade Inferior/fisiopatologia , Equilíbrio Postural/fisiologia , Método Simples-Cego , Robótica/instrumentação , Idoso , Adulto , Acidente Vascular Cerebral/fisiopatologia , Eletromiografia , Resultado do Tratamento , Recuperação de Função FisiológicaRESUMO
Urban Particulate Matter (UPM) induces skin aging and inflammatory responses by regulating skin cells through the transient receptor potential vanilloid 1 (TRPV1). Although oleic acid, an unsaturated free fatty acid (FFA), has some functional activities, its effect on UPM-induced skin damage has not been elucidated. Here, we investigated signaling pathways on how oleic acid is involved in attenuating UPM induced cell damage. UPM treatment increased XRE-promoter luciferase activity and increased translocation of AhR to the nucleus, resulting in the upregulation of CYP1A1 gene. However, oleic acid treatment attenuated the UPM effects on AhR signaling. Furthermore, while UPM induced activation of TRPV1 and MAPKs signaling which activated the downstream molecules NFκB and AP-1, these effects were reduced by cotreatment with oleic acid. UPM-dependent generation of reactive oxygen species (ROS) and reduction of cellular proliferation were also attenuated by the treatment of oleic acid. These data reveal that cell damage induced by UPM treatment occurs through AhR signaling and TRPV1 activation which in turn activates ERK and JNK, ultimately inducing NFκB and AP-1 activation. These effects were reduced by the cotreatment of oleic acid on HaCaT cells. These suggest that oleic acid reduces UPM-induced cell damage through inhibiting both the AhR signaling and activation of TRPV1 and its downstream molecules, leading to a reduction of pro-inflammatory cytokine and recovery of cell proliferation.