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Organic-inorganic hybrid metal halide perovskite solar cells have been considered as one of the most promising next-generation photovoltaic technologies. Nevertheless, perovskite defects and Li+ ionic migration will seriously affect the power conversion efficiency and stability of the formal device. Herein, we designed two crown ether derivatives (PC12 and PC15) with different cavity diameters, which selectively bind to different metal cations. It is found that PC15 in perovskite precursor solution can actively regulate the nucleation and crystallization processes and passivate the uncoordinated Pb2+ ions, while PC12 at the interface between the perovskite layer and hole-transporting layer can effectively inhibit the migration of Li+ ions and reduce nonradiative recombination losses. Therefore, PC12 and PC15 can act as "lubricant" and defect passivators, as well as inhibitors of ion migration, when they are synergistically applied at the surface and bulk of perovskite layer. Consequently, the optimized device achieved a champion efficiency of 24.8% with significantly improved humidity, thermal, and light stability.
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External ventricular drainage (EVD) is a common procedure in neurosurgical practice. Presently, the three methods used most often include direct EVD (dEVD), long-tunneled external ventricular drains (LTEVDs), and EVD via the Ommaya reservoir (EVDvOR). But they possess drawbacks such as limited duration of retention, vulnerability to iatrogenic secondary infections, and challenges in regulating drainage flow. This study aimed to explore the use of a modified ventriculoperitoneal shunt (mVPS)-the abdominal end of the VPS device was placed externally-as a means of temporary EVD to address the aforementioned limitations. This retrospective cohort study, included 120 cases requiring EVD. dEVD was performed for 31 cases, EVDvOR for 54 cases (including 8 cases with previously performed dEVD), and mVPS for 35 cases (including 6 cases with previously performed EVDvOR). The one-time success rate (no need for further other EVD intervention) for dEVD, EVDvOR, and mVPS were 70.97%, 88.89%, and 91.42%, dEVD vs EVDvOR (P < 0.05), dEVD vs mVPS (P < 0.05), EVDvOR vs mVPS (P > 0.05). Puncture needle displacement or detachment was observed in nearly all cases of EVDvOR, while no such complications have been observed with mVPS. Apart from this complication, the incidence of postoperative complications was 35.48%, 14.81%, and 8.5%, dEVD vs EVDvOR (P < 0.05), dEVD vs mVPS (P < 0.05), EVDvOR vs mVPS (P > 0.05). Mean postoperative retention for EVD was 14.68 ± 9.50 days, 25.96 ± 15.14 days, and 82.43 ± 64.45 days, respectively (P < 0.001). In conclusion, mVPS significantly extends the duration of EVD, which is particularly beneficial for patients requiring long-term EVD.
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Drenagem , Derivação Ventriculoperitoneal , Humanos , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Drenagem/métodos , Adulto , Idoso , Hidrocefalia/cirurgia , Adolescente , Criança , Adulto Jovem , Resultado do Tratamento , Pré-EscolarRESUMO
Urban last-mile express delivery in China encounters several challenges. This paper presents the establishment of a sharing logistics center aimed at enhancing the overall efficiency of urban last-mile express delivery while optimizing the utilization of essential resources. The successful implementation of shared delivery within sharing logistics center necessitates the creation of a robust collaborative mechanism. Recognizing that cooperative benefit allocation is dynamically influenced by factors such as resource input, operational efficiency, risk management, and other cost-related considerations, this study introduces a multi-weight H-Shapley value method for benefit allocation. By conducting empirical analyses of urban last-mile express delivery in Beijing within a sharing logistics service framework, our findings reveal that the revised benefit allocation model better aligns with the interests of participating entities and positively correlates with their contributions. Analyzing the impact of delivery volume and express operational costs changes, it is found that when the delivery volume and express operational costs of the sharing logistics center change, the benefits of participating enterprises move in the same direction. The benefit allocation model established in this study enriches the existing body of research in the field of shared delivery and offers valuable insights for benefit allocation issues that necessitate consideration of the dynamic effects of multiple parameter variations.
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Alocação de Recursos , Humanos , China , Modelos Teóricos , PequimRESUMO
The chemical kinetic studies of hydrogen atom (H-atom) abstraction reactions by hydroperoxyl (HȮ2) radicals from five branched pentanol isomers, including 3-methyl-1-butanol, 2-methyl-1-butanol, 1,1-dimethyl-1-propanol, 1,2-dimethyl-1-propanol, and 2,2-dimethyl-1-propanol were investigated systematically through high-level ab initio calculations. Geometry optimization, frequency analysis, and zero-point energy (ZPE) corrections were performed for six reactants, twenty-three transition states (TSs), and twenty-four products at the M06-2X/6-311++G(d,p) level of theory. The intrinsic reaction coordinate calculation was performed at the same level of theory to confirm the transition state connection. The one-dimensional hindered rotor treatment for low-frequency torsional modes was also treated at the M06-2X/6-311++G(d,p) level of theory. The QCISD(T)/CBS level of theory was used to calculate the single-point energies for the species whose T1 diagnostic value was lower than 0.035. At the same time, the CASPT2/CBS level of theory was used to calculate the single-point energies for the channel in which the T1 diagnostic value of transition states was greater than 0.035. Rate constants for the H-atom abstraction reactions from the five branched pentanol isomers by HȮ2 radicals were calculated by using conventional transition state theory with asymmetric Eckart tunneling corrections in the temperature range of 500-2000 K. Rate constants and branching ratios for the title reactions and the rate rules for ten different H-atom abstraction types were investigated. Temperature-dependent thermochemistry properties for all reactants and products were calculated by the composite methods of G3/G4/CBS-QB3/CBS-APNO, which were in good agreement with the data available in the literature. Rate constants for the H-atom abstraction reactions by HȮ2 radical from branched pentanol isomers were investigated in this work as part I, and those for linear pentanol isomers will be analyzed in part II. All the calculated kinetics and thermochemistry data can be utilized in the model development for branched pentanol isomers oxidation.
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Background and Aims: The aim of this study was to investigate the association between serum phosphate levels and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods and Results: The study sample consisted of 1657 T2DM patients hospitalized between 2017 and 2019. Patients were categorized into quartiles based on their serum phosphate levels (Q1-Q4). An increasing trend in the prevalence of DR was observed across these quartiles. Subsequently, logistic regression analysis was employed to adjust for potential confounders, such as gender, age, BMI, and duration of diabetes, and to evaluate the odds ratios (ORs) associated with these quartiles. The prevalence of DR showed an increasing trend with elevated serum phosphate levels. Logistic regression further confirmed that serum phosphate levels remain an independent risk factor for DR. Conclusion: Elevated serum phosphate levels are closely associated with the prevalence of DR in hospitalized T2DM patients. Further studies are needed to establish causality. This trial is registered with chiCTR2000032374.
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Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.
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Infecções por Paramyxoviridae , Paramyxovirinae , Paramyxovirinae/genética , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/veterinária , Mamíferos , China , Filogenia , Genoma Viral , Especificidade de HospedeiroRESUMO
High-level ab initio calculations are conducted for studying the kinetics of three linear pentanol radicals generated through H-atom abstraction reactions. The species involved are optimized using the M06-2X/6-311++G(d,p) level of theory, while a relaxed scan at the M06-2X/6-31g level of theory with 10° increments is used for the hindrance potential for low-frequency torsional modes. Single-point energies for all stationary points are obtained through the QCISD(T) and MP2 methods in combination with cc-pVDZ, cc-pVTZ, and cc-pVQZ basis sets, which can be extrapolated to the complete basis set (CBS) limit. The rate constants and branching ratios for isomerization and decomposition reactions are computed over a temperature range of 250-2000 K and a pressure range of 0.01-100 atm. Isomerization reactions are dominant at low temperatures, while decomposition reactions are more dominant at high temperatures. The branching ratio of the isomerization reaction exhibits a slight decrease with increasing pressure, while the trend for decomposition reactions depends on the type of the breaking bond. Based on the calculations for five branched pentanol radicals in part I, kinetics of linear and branched pentanol radicals are compared in this work and the results reveal that, for the same kind of ß-scission reaction at similar positions of linear and branched pentanol radicals, the rate constants of branched ones are faster than those of linear ones at low temperatures. The hydroxyl group adjacent to the breaking bond can increase the ß-scission reaction rate constants, while the effect can be ignored when the hydroxyl group is not adjacent to the breaking bond. Moreover, compared to when the hydroxyl group is located in the middle of the carbon chain, its positioning at the chain's end yields a more noticeable impact on the products and rate constants of C-O bond and O-H bond ß-scission reactions. Besides, when incorporating calculated rate constants into the CRECK model, the updated mechanism shows a better performance for ignition delay times of 1-pentanol in the NTC range but exhibits lower reactivity at higher temperatures. The simulation of speciation profiles also shows better agreement with the experimental data obtained using a flow reactor.
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The genus Hepacivirus comprises a diverse range of genetically distinct viruses that infect both mammalian and non-mammalian hosts, with some posing significant risks to human and animal health. Members of the genus Hepacivirus are typically classified into fourteen species (Hepacivirus A-N), with ongoing discoveries of novel hepaciviruses like Hepacivirus P and Hepacivirus Q. In this study, a novel Hepacivirus was identified in duck liver samples collected from live poultry markets in Hunan province, China, using unbiased high-throughput sequencing and meta-transcriptomic analysis. Through sequence comparison and phylogenetic analysis, it was determined that this newly discovered Hepacivirus belongs to a new subspecies of Hepacivirus Q. Moreover, molecular screening revealed the widespread circulation of this novel virus among duck populations in various regions of Hunan province, with an overall prevalence of 13.3%. These findings significantly enhence our understanding of the genetic diversity and evolution of hepaciviruses, emphasizing the presence of genetically diverse hepaciviruses duck populations in China. Given the broad geographical distribution and relatively high positive rate, further investigations are essential to explore any potential associations between Hepacivirus Q and duck-related diseases.
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BACKGROUND: It is imperative for public health to identify the factors that contribute to the progression of sarcopenia among middle-aged and older adults. Our study aimed to investigate the association between pain characteristics and the progression to sarcopenia and its subcomponents among middle-aged and older adults in China. METHODS: We included 5 568 participants from the China Health and Retirement Longitudinal Study. All participants completed assessments for pain characteristics and sarcopenia. Pain assessment included pain status (baseline pain, incident pain, and pain persistence) and pain distribution (single-site pain and multisite pain) using a self-report questionnaire. Diagnosis of sarcopenia followed The Asian Working Group for Sarcopenia 2019 consensus. The odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by logical regression analysis. RESULTS: Participants who reported baseline pain, multisite pain, pain persistence, or multisite pain persistence were more likely to progress to sarcopenia than those without pain, with ORs of 1.33 (95% CI: 1.08-1.65), 1.44 (95% CI: 1.15-1.80), 1.63 (95% CI: 1.23-2.14), and 1.59 (95% CI: 1.19-2.11), respectively. Even after adjusting for other covariates such as gender, age, residential area, education level, marital status, smoking, alcohol consumption, comorbidities, and falls, these associations remained significant. Additionally, pain persistence and multisite pain persistence were significantly associated with low grip strength and clinically meaningful Short Physical Performance Battery decline, but not with low muscle mass. CONCLUSIONS: Our study showed that pain, especially pain persistence, was closely correlated to the increased risk of progression to sarcopenia in Chinese middle-aged and older adults.
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Sarcopenia , Humanos , Pessoa de Meia-Idade , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/complicações , Estudos Longitudinais , Força da Mão/fisiologia , Dor/complicações , FumarRESUMO
To address the challenges faced in the prediction of rolling bearing life, where temporal signals are affected by noise, making fault feature extraction difficult and resulting in low prediction accuracy, a method based on optimal time-frequency spectra and the DenseNet-ALSTM network is proposed. Firstly, a signal reconstruction method is introduced to enhance vibration signals. This involves using the CEEMDAN deconvolution method combined with the Teager energy operator for signal reconstruction, aiming to denoise the signals and highlight fault impacts. Subsequently, a method based on the snake optimizer (SO) is proposed to optimize the generalized S-transform (GST) time-frequency spectra of the enhanced signals, obtaining the optimal time-frequency spectra. Finally, all sample data are transformed into the optimal time-frequency spectrum set and input into the DenseNet-ALSTM network for life prediction. The comparison experiment and ablation experiment show that the proposed method has high prediction accuracy and ideal prediction performance. The optimization terms used in different contexts in this paper are due to different optimization methods, specifically the CEEMDAN method.
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OBJECTIVES: The respiratory tract is the portal of entry for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a variety of respiratory pathogens other than SARS-CoV-2 have been associated with severe cases of COVID-19 disease, the dynamics of the upper respiratory microbiota during disease the course of disease, and how they impact disease manifestation, remain uncertain. METHODS: We collected 349 longitudinal upper respiratory samples from a cohort of 65 COVID-19 patients (cohort 1), 28 samples from 28 recovered COVID-19 patients (cohort 2), and 59 samples from 59 healthy controls (cohort 3). All COVID-19 patients originated from the earliest stage of the epidemic in Wuhan. Based on a modified clinical scale, the disease course was divided into five clinical disease phases (pseudotimes): "Healthy" (pseudotime 0), "Incremental" (pseudotime 1), "Critical" (pseudotime 2), "Complicated" (pseudotime 3), "Convalescent" (pseudotime 4), and "Long-term follow-up" (pseudotime 5). Using meta-transcriptomics, we investigated the features and dynamics of transcriptionally active microbes in the upper respiratory tract (URT) over the course of COVID-19 disease, as well as its association with disease progression and clinical outcomes. RESULTS: Our results revealed that the URT microbiome exhibits substantial heterogeneity during disease course. Two clusters of microbial communities characterized by low alpha diversity and enrichment for multiple pathogens or potential pathobionts (including Acinetobacter and Candida) were associated with disease progression and a worse clinical outcome. We also identified a series of microbial indicators that classified disease progression into more severe stages. Longitudinal analysis revealed that although the microbiome exhibited complex and changing patterns during COVID-19, a restoration of URT microbiomes from early dysbiosis toward more diverse status in later disease stages was observed in most patients. In addition, a group of potential pathobionts were strongly associated with the concentration of inflammatory indicators and mortality. CONCLUSION: This study revealed strong links between URT microbiome dynamics and disease progression and clinical outcomes in COVID-19, implying that the treatment of severe disease should consider the full spectrum of microbial pathogens present.
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COVID-19 , Microbiota , Humanos , SARS-CoV-2 , Nariz , Progressão da DoençaRESUMO
BACKGROUND: Ferroptosis, a distinct iron-dependent form of regulated cell death, is induced by severe lipid peroxidation due to reactive oxygen species (ROS) generation. Breast cancer patient survival is correlated with the tumor-suppressing properties of Rho guanosine triphosphatase hydrolase enzyme (GTPase)-activating protein 6 (ARHGAP6). This study investigates the impact and mechanisms of ARHGAP6 on ferroptosis in breast cancer. METHODS: Using quantitative RT-PCR, Western blotting, and immunofluorescence staining, ARHGAP6 expression was detected in a gene expression dataset, cancer tissue samples, and cells. ARHGAP6 was overexpressed or silenced in breast cancer cell lines. Cell proliferation was measured using 5-ethynyl-2-deoxyuridine (EdU) assay, and cell death rate was determined using LDH cytotoxicity assay. As indicators of ferroptosis, Fe2+ ion content, lipid ROS, glutathione peroxidase 4 (GPX4), ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), prostaglandin-endoperoxide synthase 2 (PTGS2), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were evaluated. RESULTS: ARHGAP6 was obviously downregulated in cancer tissues and cells. ARHGAP6 overexpression decreased cell proliferation, elevated cell death and lipid ROS, decreased GPX4 and SLC7A11, increased PTGS2, ACSL4, and CHAC1, and inhibited RhoA/ROCK1 and p38 MAPK signaling in cancer cells. ARHGAP6 knockdown exerted opposite effects to those of ARHGAP6 overexpression. p38 signaling suppression reversed the effect of ARHGAP6 knockdown on ferroptosis, while RhoA/ROCK1 signaling inhibition compromised the effect of ARHGAP6 on p38 MAPK signaling. In mice models, ARHGAP6 together with the ferroptosis inducer RSL3 cooperatively enhanced ferroptosis and inhibited tumor growth of cancer cells. ARHGAP6 mRNA level was positively correlated with that of ferroptosis indicators in tumor tissues. CONCLUSIONS: This study revealed that ARHGAP6 inhibited tumor growth of breast cancer by inducing ferroptosis via RhoA/ROCK1/p38 MAPK signaling. Integrating ARHGAP6 with ferroptosis-inducing agents may be a promising therapeutic strategy for breast cancer treatment.
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Neoplasias da Mama , Ferroptose , Proteínas Ativadoras de GTPase , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/genética , Ciclo-Oxigenase 2 , Ferroptose/genética , Proteínas Ativadoras de GTPase/genética , Lipídeos , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Espécies Reativas de Oxigênio , Quinases Associadas a rho/genéticaRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is a pathological subtype with a high mortality, and the development of inhibitors in the ubiquitin-proteasome system (UPS) component could be a novel therapeutic tool. METHODS: Triple-negative breast cancer data were obtained from The Cancer Genome Atlas (TCGA), and subtype analysis was performed by consistent clustering analysis to identify molecular subtypes of TNBC according to UPS characteristics. Differential analysis, COX and least absolute shrinkage and selection operator (LASSO) COX regression analyses were performed to select genes associated with overall survival in TNBC. The final prognostic model (UPS score) was determined using the LASSO COX model. The model performance was assessed using receiver operating characteristic (ROC) curves and survival curves. In addition, the results of the UPS score on analyzing the abundance of immune cell infiltration and immunotherapy were explored. Finally, we developed a nomogram for TNBC survival prediction. RESULTS: Two UPS subtypes (UPSMS1 and UPSMS2) showing significant survival differences were classified. COX regression analysis on differentially expressed genes in UPSMS1 and UPSMS2 filtered five genes that affected overall survival. Based on the regression coefficients and expression data of the five genes, we built a prognostic assessment system (UPS score). The UPS score showed consistent prognostic and therapeutic guidance values. Finally, the ROC curve of the nomogram and UPS score showed the highest predictive efficacy compared with traditional clinical prognostic indicators. CONCLUSION: The UPS score represented a promising prognostic tool to predict overall survival and immune status and guide personalized treatment selection in TNBC patients, and this study may provide a more practical alternative for clinical monitoring and management of TNBC.
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Complexo de Endopeptidases do Proteassoma , Neoplasias de Mama Triplo Negativas , Humanos , Complexo de Endopeptidases do Proteassoma/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Citoplasma , Imunoterapia , UbiquitinasRESUMO
Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains.
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Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Vírus de RNA , Animais , Humanos , Febre Hemorrágica com Síndrome Renal/epidemiologia , Filogenia , Orthohantavírus/genética , Roedores , China/epidemiologiaRESUMO
We propose a scheme to achieve controllable nonreciprocal behavior in asymmetric graphene metasurfaces composed of a continuous graphene sheet and a poly crystalline silicon slab with periodic grooves of varying depths on each side. The proposed structure exhibits completely asymmetric reflection in opposite directions in the near-infrared range, which is attributed to the pronounced structural asymmetry and its accompanying nonlinear effects. The obtained nonreciprocal reflection ratio, reaching an impressive value of 21.27â dB, combined with a minimal insertion loss of just -0.76â dB, highlights the remarkable level of nonreciprocal efficiency achieved by this design compared to others in its category. More importantly, the proposed design can achieve dynamic tunability by controlling the incident field intensity and the graphene Fermi level. Our design highlights a potential means for creating miniaturized and integratable nonreciprocal optical components in reflection mode, which can promote the development of the integrated isolators, optical logic circuits, and bias-free nonreciprocal photonics.
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Objective: Sarcopenia and chronic pain are prevalent among older adults, and despite numerous studies, the potential epidemiological link between the two conditions remains a topic of controversy. Therefore, we performed a comprehensive systematic review and meta-analysis to assess the relationship between chronic pain and sarcopenia in the elderly. Methods: EMBASE, Web of Science, PubMed, and the Cochrane Library were searched through 22 March 2023 with additional manual searches of reference lists of included studies and relevant reviews. We used a random effects model to conduct the meta-analysis and evaluated heterogeneity across studies with Cochran's Q statistic and I2. Subgroup analyses were conducted based on income level, diagnostic criteria for sarcopenia, and pain site. Results: 17 observational studies (33,600 participants, 49% female) were included, of which 6 articles were retrieved for narrative review. The pooled prevalence of sarcopenia and the pooled odds ratios (OR) between chronic pain and sarcopenia were extracted from the remaining 11 studies. The pooled prevalence of sarcopenia among older adults suffering from chronic pain was 0.11 (95% CI, 0.08-0.18). Our analysis revealed a statistically significant positive association between chronic pain and an increased risk of sarcopenia, yielding a pooled OR of 1.52 (95% CI, 1.31-1.76). Furthermore, our subgroup analysis demonstrated that the low-income countries group showed a stronger association (OR, 1.73; 95% CI, 1.54-1.95) between chronic pain and sarcopenia than the high-income countries group (OR, 1.38; 95% CI, 1.20-1.60). Conclusion: Older adults with chronic pain have a significantly higher prevalence of sarcopenia and risk of developing sarcopenia compared to those without pain. These findings highlight the importance of prioritizing the assessment and early detection of chronic pain in older people, as well as implementing proactive intervention measures in clinical practice. In addition, our results suggest that older people with chronic pain should be actively screened for sarcopenia. Prospero Registration Number: CRD42021239807.
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Sarcopenia involves in the loss of muscle mass associated with aging, which is the major cause of progressive muscle weakness and deterioration in older adults. Muscle atrophy is a direct presentation of sarcopenia, and it greatly contributes to the decline in quality of life among older adults. Neuromuscular junction (NMJ) stability is the key link to maintain muscle function. Besides, the degenerative change of NMJ promotes the process of muscle atrophy in the elderly. Based on previous transcriptome sequencing and bioinformatics analyses of aged muscle, this study used the 18-month-old aged mouse model and the 6-month-old young mouse model to deliberate the role and underlying mechanisms of Cullin-3 (Cul3) in age-related muscle atrophy. The results of reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting analysis showed that the expression of CUL3 increased in aged muscle tissue, while the expression level of postsynaptic membrane nicotinic acetylcholine receptors (nAChRs) decreased significantly, which manfested a negative correlation. Meanwhile, immunofluorescence demonstrated that Cul3 was highly expressed in senile muscle NMJ. The results of ubiquitin indicated that the ubiquitin level of aged muscle nAChRs was evidently increased. Co-immunoprecipitation furtherly verified the correlation between Cul3 and nAChRs. Taken together, Cul3 may mediate the ubiquitination degradation of nAChRs protein at the NMJ site in aged mice, leading to NMJ degeneration and accelerated atrophy of fast-twitch muscle fibers in aged muscle. As a prominent element to maintain the stability of NMJ, Cul3 is supposed to be one of candidate intervention targets in sarcopenia.
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Receptores Nicotínicos , Sarcopenia , Animais , Camundongos , Proteínas Culina/genética , Proteínas Culina/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Junção Neuromuscular/fisiologia , Qualidade de Vida , Receptores Nicotínicos/metabolismo , Sarcopenia/patologia , Ubiquitinação , Ubiquitinas/metabolismoRESUMO
Fluorescent point-of-care (POC) sensors have found great utility in fields like clinical diagnosis, food testing, and environmental monitoring. Herein, we developed a highly stable POC sensor that enabled the visual detection of tetracycline (TC) in a distinct fluorescent-traffic-light manner. In the sensor, a composite material of copper nanoclusters and metal-organic framework (CuNCs@MOF-5) prepared with a facile one-pot synthetic strategy was employed as the core element for target recognition and signal transduction. As evidenced by experiments, the as-prepared CuNCs@MOF-5 exhibited significantly improved fluorescence properties in terms of emission enhancement (about 28-fold) and stability improvement (over 110 days) compared to the CuNCs without confining and protection by MOF-5. More importantly, it was found that TC could uniquely interact with Zn(II) to trigger the disassembly of CuNCs@MOF-5, resulting in green fluorescence emission from the TC-Zn(II) complex and red fluorescence weakening of CuNCs. On the basis of this finding, a simple and stable sensor was proposed for POC detection of TC, which demonstrated high sensitivity, selectivity, and reproducibility. In addition to homogeneous visual detection in a 96-well plate, a CuNCs@MOF-5-contained agarose gel array was easily fabricated to achieve direct detection of TC in milk without any pretreatment, thanks to the size-sieving effect of the gel. Moreover, a test paper array was also put forward for low-cost TC detection, which indicates the extensibility and practicability of this sensing strategy.
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Antibacterianos , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos Testes , Tetraciclina , Corantes Fluorescentes , CobreRESUMO
Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic ß-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.
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Complicações do Diabetes , Diabetes Mellitus , Animais , Humanos , Peptídeo C , Qualidade de Vida , Diabetes Mellitus/tratamento farmacológicoRESUMO
Diabetic nephropathy (DN) affects around 40% of people with diabetes, the final outcome of which is end-stage renal disease. The deficiency of autophagy and excessive oxidative stress have been found to participate in the pathogenesis of DN. Sinensetin (SIN) has been proven to have strong antioxidant capability. However, the effect of SIN on DN has not been studied. We examined the effect of SIN on cell viability and autophagy in the podocyte cell line, MPC5 cells, treated with high glucose (HG). For in vivo studies, DN mice models were established by intraperitoneal injected with streptozotocin (40 mg/kg) for 5 consecutive days and fed with a 60% high-fat diet, and SIN was given (10, 20, and 40 mg/kg) for 8 weeks via intraperitoneal injection. The results showed that SIN could protect MPC5 cells against HG-induced damage and significantly improve the renal function of DN mice. Moreover, SIN remarkably restored the autophagy activity of MPC5 cells which was inhibited under HG conditions. Consistent with this, SIN efficiently improved autophagy in the kidney tissue of DN mice. In brief, our findings demonstrated the protective effect of SIN on DN via restoring the autophagic function, which might provide a basis for drug development.