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1.
Neurosurg Rev ; 47(1): 258, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38839660

RESUMO

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.


Assuntos
Aspirina , Hemorragia Cerebral , Inibidores da Agregação Plaquetária , Humanos , Masculino , Feminino , Aspirina/efeitos adversos , Aspirina/administração & dosagem , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Hemorragia Pós-Operatória/epidemiologia , Fatores de Risco , Adulto , Hemorragias Intracranianas/epidemiologia
2.
Data Brief ; 54: 110432, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38698798

RESUMO

Object Detection and Tracking have provided a valuable tool for many tasks, mostly time-consuming and prone-to-error jobs, including fruit counting while in the field, among others. Fruit counting can be a challenging assignment for humans due to the large quantity of fruit available, which turns it into a mentally-taxing operation. Hence, it is relevant to use technology to ease the task of farmers by implementing Object Detection and Tracking algorithms to facilitate fruit counting. However, those algorithms suffer undercounting due to occlusion, which means that the fruit is hidden behind a leaf or a branch, complicating the detection task. Consequently, gathering the datasets from multiple viewing angles is essential to boost the likelihood of recording the images and videos from the most visible point of view. Furthermore, the most critical open-source datasets do not include labels for certain fruits, such as grape bunches. This study aims to unravel the scarcity of public datasets, including labels, to train algorithms for grape bunch Detection and Tracking by considering multiple angles acquired with a UAV to overcome fruit occlusion challenges.

3.
Langmuir ; 40(21): 11251-11262, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38748644

RESUMO

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

4.
Cell Mol Biol Lett ; 29(1): 72, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745296

RESUMO

BACKGROUND: Aberrant mitochondrial fission, a critical pathological event underlying myocardial ischemia/reperfusion (MI/R) injury, has emerged as a potential therapeutic target. The long non-coding RNA (lncRNA) Oip5-as1 is increasingly recognized for its regulatory roles, particularly in MI/R injury. However, its precise mechanistic role in modulating mitochondrial dynamics remains elusive. This study aims to elucidate the mechanistic role of Oip5-as1 in regulating mitochondrial fission and evaluate its therapeutic potential against MI/R injury. METHODS: To simulate in vitro MI/R injury, HL-1 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R). Lentiviral vectors were employed to achieve overexpression or knockdown of Oip5-as1 in HL-1 cells by expressing Oip5-as1 or shRNA targeting Oip5-as1, respectively. The impact of Oip5-as1 on mitochondrial dynamics in HL-1 cells was assessed using CCK-8 assay, flow cytometry, immunofluorescence staining, and biochemical assays. MI/R injury was induced in mice by ligating the left anterior descending coronary artery. Conditional knockout mice for Oip5-as1 were generated using the CRISPR/Cas9 genome editing technology, while overexpression of Oip5-as1 in mice was achieved via intramyocardial administration of AAV9 vectors. In mice, the role of Oip5-as1 was evaluated through echocardiographic assessment, histopathological staining, and transmission electron microscopy. Furthermore, Western blotting, RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation assays were conducted to investigate Oip5-as1's underlying mechanisms. RESULTS: The expression levels of Oip5-as1 are significantly decreased in MI/R-injured HL-1 cells and myocardium. In HL-1 cells undergoing H/R injury, overexpression of Oip5-as1 attenuated excessive mitochondrial fission, preserved mitochondrial functionality, and reduced cellular apoptosis, while knockdown of Oip5-as1 exhibited the opposite effects. Furthermore, in a mouse model of MI/R injury, overexpression of Oip5-as1 diminished mitochondrial fission, myocardial infarct size and improved cardiac function. However, knockout of Oip5-as1 exacerbated myocardial injury and cardiac dysfunction, which were significantly reversed by treatment with a mitochondrial division inhibitor-1 (Mdivi-1). Mechanistically, Oip5-as1 selectively interacts with AKAP1 and CaN proteins, inhibiting CaN activation and subsequent DRP1 dephosphorylation at Ser637, thereby constraining DRP1's translocation to the mitochondria and its involvement in mitochondrial fission. CONCLUSIONS: Our study underscores the pivotal role of Oip5-as1 in mitigating excessive mitochondrial fission during MI/R injury. The findings not only enhance our comprehension of the molecular mechanisms underlying MI/R injury but also identify Oip5-as1 as a potential therapeutic target for ameliorating MI/R injury.


Assuntos
Dinaminas , Dinâmica Mitocondrial , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Dinâmica Mitocondrial/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Dinaminas/metabolismo , Dinaminas/genética , Camundongos , Fosforilação , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Linhagem Celular , Camundongos Knockout , Masculino , Camundongos Endogâmicos C57BL
5.
Sci Total Environ ; 931: 172938, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38703850

RESUMO

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.


Assuntos
Cádmio , Mitocôndrias , Piroptose , Testículo , Animais , Cádmio/toxicidade , Masculino , Camundongos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Piroptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Proteostase , Proteínas Mitocondriais/metabolismo , Exposição Ambiental/efeitos adversos , DNA Mitocondrial , Proteases Dependentes de ATP/metabolismo , Estresse Proteotóxico
6.
Nat Commun ; 15(1): 4653, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821942

RESUMO

Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Heterogeneidade Genética , Neoplasias Pulmonares , Camundongos Endogâmicos NOD , Camundongos SCID , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Feminino , Sequenciamento do Exoma , Genômica/métodos , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Xenoenxertos , Modelos Animais de Doenças , Idoso , Pessoa de Meia-Idade
7.
Nat Nanotechnol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740933

RESUMO

Constructing effective antidotes to reduce global health impacts induced by alcohol prevalence is a challenging topic. Despite the positive effects observed with intravenous applications of natural enzyme complexes, their insufficient activities and complicated usage often result in the accumulation of toxic acetaldehyde, which raises important clinical concerns, highlighting the pressing need for stable oral strategies. Here we present an effective solution for alcohol detoxification by employing a biomimetic-nanozyme amyloid hydrogel as an orally administered catalytic platform. We exploit amyloid fibrils derived from ß-lactoglobulin, a readily accessible milk protein that is rich in coordinable nitrogen atoms, as a nanocarrier to stabilize atomically dispersed iron (ferrous-dominated). By emulating the coordination structure of the horseradish peroxidase enzyme, the single-site iron nanozyme demonstrates the capability to selectively catalyse alcohol oxidation into acetic acid, as opposed to the more toxic acetaldehyde. Administering the gelatinous nanozyme to mice suffering from alcohol intoxication significantly reduced their blood-alcohol levels (decreased by 55.8% 300 min post-alcohol intake) without causing additional acetaldehyde build-up. Our hydrogel further demonstrates a protective effect on the liver, while simultaneously mitigating intestinal damage and dysbiosis associated with chronic alcohol consumption, introducing a promising strategy in effective alcohol detoxification.

8.
Viruses ; 16(4)2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38675915

RESUMO

The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles (FPs) generated during production have different antigenic and immunogenic properties. However, the antigen detection methods currently used were established without considering the differences in antigenicity between EPs and FPs. There is also a lack of other effective analytical methods for detecting the different particle forms, which hinders the consistency between batches of products. In this study, we analyzed the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) in characterizing the EPs and FPs of EV71. Our results showed that the proportions of the two forms could be quantified simultaneously by SV-AUC. We also determined the repeatability and accuracy of this method and found that both parameters were satisfactory. We assessed SV-AUC for bulk vaccine quality control, and our findings indicated that SV-AUC can be used effectively to analyze the percentage of EPs and FPs and monitor the consistency of the process to ensure the quality of the vaccine.


Assuntos
Enterovirus Humano A , Ultracentrifugação , Enterovirus Humano A/imunologia , Enterovirus Humano A/isolamento & purificação , Ultracentrifugação/métodos , Humanos , Vacinas Virais/imunologia , Vacinas de Produtos Inativados/imunologia , Vírion/imunologia , Vírion/isolamento & purificação , Doença de Mão, Pé e Boca/virologia , Doença de Mão, Pé e Boca/prevenção & controle , China , Controle de Qualidade
10.
J Hazard Mater ; 469: 133997, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38508115

RESUMO

Maternal exposure to glucocorticoids has been associated with adverse outcomes in offspring. However, the consequences and mechanisms of gestational exposure to prednisone on susceptibility to osteoporosis in the offspring remain unclear. Here, we found that gestational prednisone exposure enhanced susceptibility to osteoporosis in adult mouse offspring. In a further exploration of myogenic mechanisms, results showed that gestational prednisone exposure down-regulated FNDC5/irisin protein expression and activation of OPTN-dependent mitophagy in skeletal muscle of adult offspring. Additional experiments elucidated that activated mitophagy significantly inhibited the expression of FNDC5/irisin in skeletal muscle cells. Likewise, we observed delayed fetal bone development, downregulated FNDC5/irisin expression, and activated mitophagy in fetal skeletal muscle upon gestational prednisone exposure. In addition, an elevated total m6A level was observed in fetal skeletal muscle after gestational prednisone exposure. Finally, gestational supplementation with S-adenosylhomocysteine (SAH), an inhibitor of m6A activity, attenuated mitophagy and restored FNDC5/irisin expression in fetal skeletal muscle, which in turn reversed fetal bone development. Overall, these data indicate that gestational prednisone exposure increases m6A modification, activates mitophagy, and decreases FNDC5/irisin expression in skeletal muscle, thus elevating osteoporosis susceptibility in adult offspring. Our results provide a new perspective on the earlier prevention and treatment of fetal-derived osteoporosis.


Assuntos
Fibronectinas , Osteoporose , Humanos , Camundongos , Feminino , Animais , Gravidez , Prednisona/metabolismo , Fibronectinas/metabolismo , Exposição Materna , Mitofagia , Músculo Esquelético/metabolismo , Fatores de Transcrição/metabolismo , Osteoporose/induzido quimicamente
11.
J Hazard Mater ; 470: 134142, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38555669

RESUMO

Low testosterone (T) levels are associated with many common diseases, such as obesity, male infertility, depression, and cardiovascular disease. It is well known that environmental cadmium (Cd) exposure can induce T decline, but the exact mechanism remains unclear. We established a murine model in which Cd exposure induced testicular T decline. Based on the model, we found Cd caused mitochondrial fusion disorder and Parkin mitochondrial translocation in mouse testes. MFN1 overexpression confirmed that MFN1-dependent mitochondrial fusion disorder mediated the Cd-induced T synthesis suppression in Leydig cells. Further data confirmed Cd induced the decrease of MFN1 protein by increasing ubiquitin degradation. Testicular specific Parkin knockdown confirmed Cd induced the ubiquitin-dependent degradation of MFN1 protein through promoting Parkin mitochondrial translocation in mouse testes. Expectedly, testicular specific Parkin knockdown also mitigated testicular T decline. Mito-TEMPO, a targeted inhibitor for mitochondrial reactive oxygen species (mtROS), alleviated Cd-caused Parkin mitochondrial translocation and mitochondrial fusion disorder. As above, Parkin mitochondrial translocation induced mitochondrial fusion disorder and the following T synthesis repression in Cd-exposed Leydig cells. Collectively, our study elucidates a novel mechanism through which Cd induces T decline and provides a new treatment strategy for patients with androgen disorders.


Assuntos
Cádmio , Poluentes Ambientais , Células Intersticiais do Testículo , Testículo , Testosterona , Ubiquitina-Proteína Ligases , Masculino , Animais , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Cádmio/toxicidade , Testosterona/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Poluentes Ambientais/toxicidade , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Camundongos Endogâmicos C57BL , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética
12.
Oral Oncol ; 151: 106759, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38507991

RESUMO

OBJECTIVES: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). METHODS: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. CONCLUSION: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Humanos , Prognóstico , Carcinoma Adenoide Cístico/patologia , Carga Tumoral , Fatores de Tempo , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/patologia , Estudos Retrospectivos
13.
Cancers (Basel) ; 16(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473297

RESUMO

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

15.
Medicine (Baltimore) ; 103(6): e37229, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335396

RESUMO

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.


Assuntos
Terapia por Acupuntura , Acupuntura , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Terapia por Acupuntura/efeitos adversos , Terapia Combinada
16.
Nat Commun ; 15(1): 1353, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355624

RESUMO

There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.


Assuntos
Infertilidade Masculina , Análise do Sêmen , Animais , Humanos , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Pai , Infertilidade Masculina/genética , Metiltransferases , Obesidade/metabolismo , Sêmen/metabolismo , Tretinoína
17.
RMD Open ; 10(1)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233074

RESUMO

BACKGROUND: Indeterminate readout of the quantitative interferon-γ release test (QFT) for Mycobacterium tuberculosis screening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) signalling. METHODS: We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-γ was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy. RESULTS: 104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p<0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-γ response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8+ T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-γ response. CONCLUSION: The PD-1/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8+ T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-γ response in patients with SLE.


Assuntos
Linfócitos T CD8-Positivos , Lúpus Eritematoso Sistêmico , Humanos , Linfócitos T CD8-Positivos/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Células B de Memória , Antígeno B7-H1/fisiologia , Ligantes , Rituximab , Lúpus Eritematoso Sistêmico/complicações
18.
Environ Res ; 246: 118191, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38218522

RESUMO

Water scarcity has threatened the sustainability of human life, ecosystem evolution, and socio-economic development. However, previous studies have often lacked a comprehensive consideration of the impact of water quality and existing solutions, such as inter-basin water transfer and unconventional water resources, on water scarcity. In this paper, an improved approach was proposed to quantify water scarcity levels by comprehensively considering surface water quality and multiple solutions. China's water scarcity was first assessed at a high spatial resolution on a monthly basis over the 5-year period from 2014 to 2018. Then, the driving factors including water quality and solutions were identified by a geographic detector model. Finally, an in-depth investigation was conducted to unravel the effects of water quantity solutions (i.e., inter-basin water transfer and unconventional water use), and water quality solutions (i.e., improving surface water quality) on alleviating water scarcity. Based on monthly assessments considering water quality and multiple existing solutions, the results showed that over half of the national population (∼777 million) faced water scarcity for at least one month of the year. Agricultural water use and inadequate water quality were the main driving factors responsible for China's water scarcity. Over four-fifths of the national population (∼1.10 billion) could benefit from alleviated water scarcity through a combination of water quantity and quality solutions. However, the existing solutions considered were insufficient to completely resolve water scarcity in China, especially in Northern China, persisting as a challenging issue. The results obtained from this study provided a better understanding of China's water scarcity, which could contribute to guiding future efforts aimed at alleviating water scarcity and ensuring water security in China.


Assuntos
Ecossistema , Qualidade da Água , Humanos , Insegurança Hídrica , China , Dinâmica Populacional
19.
Adv Healthc Mater ; 13(7): e2301146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176000

RESUMO

Ribonucleic acids (RNA) play active roles within cells or viruses by catalyzing biological reactions, controlling gene expression, and communicating responses to cellular signals. Rapid monitoring RNA variation has become extremely important for appropriate clinical decisions and frontier biological research. However, the most widely used method for RNA detection, nucleic acid amplification, is restricted by a mandatory temperature cycling period of ≈1 h required to reach target detection criteria. Herein, a direct detection approach via single-atom site integrated surface-enhanced Raman scattering (SERS) monitoring nucleic acid pairing reaction, can be completed within 3 min and reaches high sensitivity and extreme reproducibility for COVID-19 and two other influenza viruses' detection. The mechanism is that a single-atom site on SERS chip, enabled by positioning a single-atom oxide coordinated with a specific complementary RNA probe on chip nanostructure hotspots, can effectively bind target RNA analytes to enrich them at designed sites so that the binding reaction can be detected through Raman signal variation. This ultrafast, sensitive, and reproducible single-atom site SERS chip approach paves the route for an alternative technique of immediate RNA detection. Moreover, single-atom site SERS is a novel surface enrichment strategy for SERS active sites for other analytes at ultralow concentrations.


Assuntos
Nanopartículas Metálicas , Ácidos Nucleicos , Reprodutibilidade dos Testes , Limite de Detecção , Nanopartículas Metálicas/química , RNA , Análise Espectral Raman/métodos , Ouro/química
20.
Adv Mater ; 36(16): e2311151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38182407

RESUMO

Solar-driven interfacial evaporation (SDIE) has played a pivotal role in optimizing water-energy utilization, reducing conventional power costs, and mitigating environmental impacts. The increasing emphasis on the synergistic cogeneration of water and green electricity through SDIE is particularly noteworthy. However, there is a gap of existing reviews that have focused on the mechanistic understanding of green power from water-electricity cogeneration (WEC) systems, the structure-activity relationship between efficiency of green energy utilization in WEC and material design in SDIE. Particularly, it lacks a comprehensive discussion to address the challenges faced in these areas along with potential solutions. Therefore, this review aims to comprehensively assess the progress and future perspective of green electricity from WEC systems by investigating the potential expansion of SDIE. First, it provides a comprehensive overview about material rational design, thermal management, and water transportation tunnels in SDIE. Then, it summarizes diverse energy sources utilized in the SDIE process, including steaming generation, photovoltaics, salinity gradient effect, temperature gradient effect, and piezoelectric effect. Subsequently, it explores factors that affect generated green electricity efficiency in WEC. Finally, this review proposes challenges and possible solution in the development of WEC.

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