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The growth of industry has resulted in increased global air pollution, necessitating the urgent development of highly sensitive gas detectors. In this work, the adsorption of the Janus ZrSSe monolayer for CO, CO2, NH3, NO, NO2, and O2 was studied by first-principles calculations. First, the stability of the ZrSSe monolayer is confirmed through calculations of cohesive energy and AIMD simulations. Furthermore, the calculations indicate that the Se layer exhibits higher selectivity and sensitivity toward gas molecules compared to the S layer. Specifically, among the gases adsorbed on the Se layer, NO has the shortest adsorption distance (1.804 Å), the lowest adsorption energy (-0.424 eV), and the greatest electron transfer (0.098 e). Additionally, density of states analysis reveals that adsorption of NO, NO2, and O2 on the Janus ZrSSe monolayer can induce a transition from a nonmagnetic to a magnetic state. The adsorption of NO not only alters the magnetic state but also induces a transition from a semiconductor to metal, which is highly advantageous for gas sensing applications. There results suggest that the Janus ZrSSe monolayer has the potential to serve as a highly sensitive detector for NO gas.
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Human appendix is critical for the maintenance of intestinal homeostasis. Appendicectomy has been the optimal treatment of acute appendicitis, yet the cancer incidence after appendix removal remains unclear. In this territory-wide retrospective cohort study, adult participants who underwent appendicectomy from 2000 to 2018 were retrieved from a population database (n = 43,983), while matched reference participants were retrieved as controls (n = 85,853). After appendicectomy, the overall cancer risk was significantly increased (subdistribution hazard ratio (SHR) = 1.124) compared to the non-appendicectomy group. Appendicectomy-treated males had higher cancer risk than males without appendicectomy (SHR = 1.197), while such difference was not observed in female participants. Significant increase in cancer risk was also observed in elder participants (age >60) with appendicectomy (SHR = 1.390). Appendicectomy was positively correlated with the risk of digestive tract and respiratory cancers including colon (SHR = 1.440), pancreas (SHR = 1.930), and trachea, bronchus, and lung (SHR = 1.394). In contrast, the risk of liver cancer was markedly decreased after appendicectomy (SHR = 0.713). In conclusion, we reported the association of appendicectomy with subsequent cancer incidence. These findings highlight the potential complication after appendix removal and the necessity of post-operative management to monitor and prevent long-term adverse events.
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Lifetime productivity is a trait of great importance to dairy cattle populations as it combines information from production and longevity variables. Therefore, we investigated the genetic background of lifetime productivity in high-producing dairy cattle by integrating genomics and transcriptomics data sets. A total of 3,365,612 test-day milk yield records from 134,029 Chinese Holstein cows were used to define 6 lifetime productivity traits, including lifetime milk yield covering full lifespan and 5 cumulative milk yield traits covering partial lifespan. Genetic parameters were estimated based on univariate and bivariate linear animal models and the Restricted Maximum Likelihood (REML) method. Genome-wide association studies (GWAS) and weighted gene co-expression network analyses (WGCNA) were performed to identify candidate genes associated with lifetime productivity based on genomic data from 3,424 cows and peripheral blood RNA-seq data from 23 cows, respectively. Lifetime milk yield averaged 24,800.8 ± 14,396.6 kg (mean ± SD) across an average of 2.4 parities in Chinese Holstein population. The heritability estimates for lifetime productivity traits ranged from 0.05 (±0.01 for SE) to 0.10 (±0.02 for SE). The estimate of genetic correlation between lifetime milk yield and productive life is 0.88 (±0.3 for SE) while the genetic correlation with 305d milk yield in the first lactation was 0.49 (±0.08 for SE). Absolute values for most genetic correlation estimates between lifetime productivity and type traits were lower than 0.30. Moderate genetic correlations were found between udder related traits and lifetime productivity, such as with udder depth (0.33), rear udder attachment height (0.33), and udder system (0.34). Some single nucleotide polymorphisms and gene co-expression modules significantly associated with lifetime milk yield were identified based on GWAS and WGCNA analyses, respectively. Functional enrichment analyses of the candidate genes identified revealed important pathways related to immune system, longevity, energy utilization and metabolism, and FoxO signaling. The genes NTMT1, FNBP1, and S1PR1 were considered to be the most important candidate genes influencing lifetime productivity in Holstein cows. Overall, our findings indicate that lifetime productivity is heritable in Chinese Holstein cattle and important candidate genes were identified by integrating genomic and transcriptomic data sets.
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Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer (CRC). Cisplatin (DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair. Among the elements that lead to DDP resistance, O 6-methylguanine (O 6-MG)-DNA-methyltransferase (MGMT), a DNA-repair enzyme, performs a quintessential role. In this study, we clarify the significant involvement of MGMT in conferring DDP resistance in CRC, elucidating the underlying mechanism of the regulatory actions of MGMT. A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study, and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo. Conversely, in cancer cells, MGMT overexpression abolishes their sensitivity to DDP treatment. Mechanistically, the interaction between MGMT and cyclin dependent kinase 1 (CDK1) inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1. Meanwhile, to achieve nonhomologous end joining, MGMT interacts with XRCC6 to resist chemotherapy drugs. Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation, and several Wnt inhibitors can repress drug-resistant cells. In summary, our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.
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OBJECTIVES: The preferred endovascular therapy (EVT) for large-vessel occlusion in intracranial atherosclerosis (ICAS) is unknown. We compared the efficacy of preferred stent thrombectomy and preferred angioplasty in patients with acute large-vessel occlusion in ICAS. METHODS: Data from consecutive EVT patients (May 2020 to September 2023) with acute middle cerebral artery occlusion in ICAS were retrospectively analyzed. Preferred angioplasty was performed if there was a preoperative "microcatheter first-pass effect;" otherwise, preferred stent thrombectomy was performed. Analyses were grouped according to the two EVT treatments. Clinical data of all patients, including the time from puncture to recanalization, rate of successful reperfusion, early neurological improvement, intracranial hemorrhage, and modified Rankin Scale score at 90 days, were recorded and analyzed. RESULTS: Six-two patients were enrolled in this study (mean age was 60.66±13.21 y, 22.6% female). The preferred angioplasty group had a higher first-pass recanalization rate than the preferred stent thrombectomy group (61.3% vs. 21.9%, P<0.001) and a higher proportion of patients who were functionally independent (defined as a modified Rankin Scale score of 0 to 3) at 90 days [odds ratio,3.681; 95% confidence interval (CI):1.009 to 13.428; P=0.048]. There was no significant difference between the groups in the time from puncture to recanalization, the frequency of successful reperfusion, and early neurological improvement, or intracranial hemorrhage (P>0.05). CONCLUSIONS: This study suggests that for acute middle cerebral artery occlusion in ICAS, preferred angioplasty may be a safe and effective procedure.
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The denitrifying sulfur (S) conversion-associated enhanced biological phosphorus removal (DS-EBPR) process for treating saline wastewater is characterized by its unique microbial ecology that integrates carbon (C), nitrogen (N), phosphorus (P), and S biotransformation. However, operational instability arises due to the numerous parameters and intricates bacterial interactions. This study introduces a two-stage interpretable machine learning approach to predict S conversion-driven P removal efficiency and optimize DS-EBPR process. Stage one utilized the XGBoost regression model, achieving an R2 value of 0.948 for predicting sulfate reduction (SR) intensity from anaerobic parameters with feature engineering. Stage two involved the CatBoost classification and regression model integrating anoxic parameters with the predicted SR values for predicting P removal, reaching an accuracy of 94% and an R2 value of 0.93, respectively. This study identified key environmental factors, including SR intensity (20-45 mg S/L), influent P concentration (<9.0 mg P/L), mixed liquor volatile suspended solids (MLVSS)/mixed liquor suspended solids (MLSS) ratio (0.55-0.72), influent C/S ratio (0.5-1.0), anoxic reaction time (5-6 h), and MLSS concentration (>6.50 g/L). A user-friendly graphic interface was developed to facilitate easier optimization and control. This approach streamlines the determination of optimal conditions for enhancing P removal in the DS-EBPR process.
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Carbono , Aprendizado de Máquina , Nitrogênio , Fósforo , Enxofre , Águas Residuárias , Fósforo/metabolismo , Nitrogênio/metabolismo , Enxofre/metabolismo , Águas Residuárias/química , Carbono/metabolismo , Biotransformação , Ecossistema , Eliminação de Resíduos Líquidos/métodos , DesnitrificaçãoRESUMO
Background: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa. Methods: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis. Results: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (ß=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (ß=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (ß=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (ß=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%). Conclusions: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.
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Estudo de Associação Genômica Ampla , Lipídeos , Análise da Randomização Mendeliana , Humanos , Lipídeos/sangue , LDL-Colesterol/sangue , Triglicerídeos/sangue , Telômero/genética , HDL-Colesterol/sangue , Polimorfismo de Nucleotídeo Único , Homeostase do Telômero , Apolipoproteína A-I/sangue , Apolipoproteína A-I/genéticaRESUMO
Direct nose-to-brain drug delivery, a promising approach for treating neurological disorders, faces challenges due to anatomical variations between adults and children. This study aims to investigate the spatial particle deposition of micron-sized particles in the nasal cavity among adult and pediatric subjects. This study focuses on the olfactory region considering the effect of intrasubject parameters and particle properties. Two child and two adult nose models were developed based on computed tomography (CT) images, in which the olfactory region of the four nasal cavity models comprises 7% to 10% of the total nasal cavity area. Computational Fluid Dynamics (CFD) coupled with a discrete phase model (DPM) was implemented to simulate the particle transport and deposition. To study the deposition of micrometer-sized drugs in the human nasal cavity during a seated posture, particles with diameters ranging from 1 to 100 µm were considered under a flow rate of 15 LPM. The nasal cavity area of adults is approximately 1.2 to 2 times larger than that of children. The results show that the regional deposition fraction of the olfactory region in all subjects was meager for 1-100 µm particles, with the highest deposition fraction of 5.7%. The deposition fraction of the whole nasal cavity increased with the increasing particle size. Crucially, we identified a correlation between regional deposition distribution and nasal cavity geometry, offering valuable insights for optimizing intranasal drug delivery.
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Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and ß-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.
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Electrochemical pretreatment (EPT) has shown to be superior in improving acidogenic co-fermentation (Co-AF) of waste activated sludge (WAS) and food waste (FW) for volatile fatty acids (VFAs). However, the influence of EPT electrode materials on the production of electrogenerated oxidants (such as singlet oxygen (1O2) and reactive chlorine species (RCS)), as well as their effects on properties of electrodes, the microbial community structure and functional enzymes remain unclear. Therefore, this study investigated the effects of various metal oxide coated electrodes (i.e., Ti/PbO2, Ti/Ta2O5-IrO2, Ti/SnO2-RuO2, and Ti/IrO2-RuO2) on EPT and subsequent Co-AF of WAS-FW. The results showed that EPT with Ti/PbO2, Ti/Ta2O5-IrO2, Ti/SnO2-RuO2 and Ti/IrO2-RuO2 electrodes generated 165.3-848.2 mg Cl2/L of RCS and 5.643 × 1011-3.311 × 1012 spins/mm3 of 1O2, which significantly enhanced the solubilization and biodegradability of WAS-FW by 106.4 %-233.6 % and 177.3 %-481.8 %, respectively. Especially with Ti/Ta2O5-IrO2 as the electrode material, an appropriate residual RCS (2.0-10.4 mg Cl2/L) remained in Co-AF step, resulted in hydrolytic and acidogenic bacteria (e.g., Prevotella_7, accounting for 78.9 %) gradually become dominant rather than methanogens (e.g., Methanolinea and Methanothrix) due to their different tolerance to residual RCS. Meanwhile, the functional gene abundances of hydrolytic and acidogenic enzymes increased, while the methanogenic enzymes deceased. Consequently, this reactor produced the highest VFAs up to 545.5 ± 36.0 mg COD/g VS, which was 101.8 % higher than that of the Control (without EPT). Finally, the economic analysis and confirmatory experiments further proved the benefits of WAS-FW Co-AF with EPT.
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Eletrodos , Ácidos Graxos Voláteis , Esgotos , Ácidos Graxos Voláteis/metabolismo , Esgotos/química , Cloro , Fermentação , Óxidos/química , Metais , Eliminação de Resíduos Líquidos/métodos , Perda e Desperdício de AlimentosRESUMO
BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.
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Equinococose Hepática , Doenças dos Ovinos , Ultrassonografia , Animais , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/diagnóstico por imagem , Ovinos , China/epidemiologia , Ultrassonografia/veterinária , Equinococose Hepática/veterinária , Equinococose Hepática/epidemiologia , Equinococose Hepática/diagnóstico por imagem , Prevalência , Cães , Praziquantel/uso terapêutico , Anti-Helmínticos/uso terapêutico , FemininoRESUMO
Major Vault Protein (MVP) has emerged as a potential prognostic and immunological biomarker in various cancer types. This pan-cancer study aimed to investigate expression of MVP and its correlation with clinical outcomes and immune infiltration across diverse cancer types. We conducted an analysis of extensive transcriptomic and clinical data from publicly available databases. Our findings unveiled a significant association between MVP expression and cancer progression, with higher expression levels predicting poorer overall survival in multiple cancer types. Importantly, MVP expression demonstrated a close relationship with immune infiltration in the tumor microenvironment, showing that higher expression levels were associated with increased immune cell infiltration. We further validated expression of MVP and function in cancer cell lines A549 and AGS. These compelling results suggest that MVP holds promise as a valuable biomarker for prognostic assessment and the development of immunotherapeutic strategies across various cancer types. Consequently, targeting MVP may offer a compelling therapeutic approach in the treatment of human cancers.
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Biomarcadores Tumorais , Neoplasias , Microambiente Tumoral , Partículas de Ribonucleoproteínas em Forma de Abóbada , Humanos , Neoplasias/imunologia , Neoplasias/mortalidade , Prognóstico , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/metabolismo , Partículas de Ribonucleoproteínas em Forma de Abóbada/genética , Partículas de Ribonucleoproteínas em Forma de Abóbada/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met-GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe3+) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
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Groundwater contamination resulting from petroleum development poses a significant threat to drinking water sources, especially in developing countries. In situ natural remediation methods, including microbiological processes, have gained popularity for the reduction of groundwater contaminants. However, assessing the stage of remediation in deep contaminated groundwater is challenging and costly due to the complexity of diverse geological conditions and unknown initial concentrations of contaminants. This research proposes that redox zonation may be a more convenient and comprehensive indicator than the concentration of contaminants for determining the stage of natural remediation in deep groundwater. The combination of sequencing microbial composition using the high-throughput 16S rRNA gene and function predicted by FAPROTAX is a useful approach to determining the redox conditions of different contaminated groundwater. The sulfate-reducing environment, represented by Desulfobacteraceae, Peptococcaceae, Desulfovibrionaceae, and Desulfohalobiaceae could be used as characteristic early stages of remediation for produced water contamination in wells with high concentrations of SO42-, benzene, and salinity. The nitrate-reducing environment, enriched with microorganisms related to denitrification, sulfur-oxidizing, and methanophilic microorganisms could be indicative of the mid stages of in situ bioremediation. The oxygen reduction environment, enriched with oligotrophic and pathogenic Sphingomonadaceae, Caulobacteraceae, Syntrophaceae, Legionellales, Moraxellaceae, and Coxiellaceae, could be indicative of the late stages of remediation. This comprehensive approach could provide valuable insights into the process of natural remediation and facilitate improved environmental management in areas of deep contaminated groundwater.
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Biodegradação Ambiental , Água Subterrânea , Oxirredução , Poluentes Químicos da Água , Água Subterrânea/química , Água Subterrânea/microbiologia , Poluentes Químicos da Água/análise , RNA Ribossômico 16S , Monitoramento Ambiental/métodos , Recuperação e Remediação Ambiental/métodos , Microbiologia da ÁguaRESUMO
INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Sirtuína 3 , Animais , Ratos , Trifosfato de Adenosina/farmacologia , Hiperalgesia , Mitofagia , Proteínas Quinases/metabolismo , Transdução de Sinais , Sirtuína 3/genética , Sirtuína 3/metabolismo , Ubiquitina-Proteína Ligases/genéticaRESUMO
INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.
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Neoplasias Pulmonares , Pulmão , Pneumonectomia , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pulmão/crescimento & desenvolvimento , Idoso , Adulto , Tamanho do Órgão , Período Pós-OperatórioRESUMO
Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in Staphylococcus aureus. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of sa00565 in resistance, we generated sa00565 gene deletion mutant (Δsa00565) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δsa00565 mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in S. aureus.IMPORTANCEIn this study, we addressed the significance of drug efflux systems in multidrug resistance of Staphylococcus aureus, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δsa00565 mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in S. aureus, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.
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Antibacterianos , Proteínas de Bactérias , Proteínas de Membrana Transportadoras , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Tetraciclina , Tetraciclina/farmacologia , Tetraciclina/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Resistência a Tetraciclina/genética , Humanos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Doxiciclina/farmacologiaRESUMO
Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.
Assuntos
Estivação , Hibernação , Humanos , Animais , Estivação/genética , Peixes/genética , Perfilação da Expressão Gênica/veterinária , Transcriptoma , Hibernação/genéticaRESUMO
Gas-insulated switchgear (GIS) equipment must be protected by detecting and eliminating the toxic SF6 partial discharge decomposition components. This study employs first-principles calculations to thoroughly investigate the interaction between a Pd-adsorbed SiN3 monolayer (Pd-SiN3) and four typical SF6 decomposition gases (H2S, SO2, SOF2, and SO2F2). The study also investigates the associated geometric, electrical, and optical characteristics along with the sensing sensitivity and desorption efficiency. The ab initio molecular dynamics (AIMD) simulations demonstrated the favorable stability of the Pd-SiN3 monolayer. Furthermore, the Pd-SiN3 monolayer exhibited strong chemisorption behavior toward H2S, SO2, SOF2, and SO2F2 gases because of the higher adsorption energies of -2.717, -2.917, -2.457, and -2.025 eV, respectively. Furthermore, significant changes occur in the electronic and optical characteristics of the Pd-SiN3 monolayer following the adsorption of these gases, resulting in remarkable sensitivity of the Pd-SiN3 monolayer in relation to electrical conductivity and optical absorption. Meanwhile, all of these gas adsorption systems exhibited extremely long recovery times. The aforementioned theoretical findings suggest that the Pd-SiN3 monolayer has the potential to be an effective gas scavenger for the storage or removal of the SF6 decomposition components. Additionally, it might function as a reliable one-time sensor for detecting these gases. The results potentially provide valuable theoretical guidance for maintaining the normal operation of the SF6 insulation devices.