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1.
BMC Public Health ; 23(1): 141, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670366

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity, and imposes a substantial financial burden on society. However, few studies have examined the role of individual socioeconomic status (SES) in temporal trends of COPD prevalence and economic cost. This study aimed to uncover the changing prevalence and economic burden of COPD across socioeconomic gradients in rural southwest China. METHODS: Data were collected from two cross-sectional health interviews and examination surveys administered 10 years apart among individuals aged ≥ 35 years in rural China. A prevalence-based cost-of-illness method was used to estimate the cost of COPD. The individual socioeconomic position (SEP) index was constructed using principal component analysis. Post-bronchodilator spirometry tests were performed for each participant. RESULTS: From 2011 to 2021, the prevalence of COPD increased from 8.7% to 12.8% (P < 0.01), while the economic cost of COPD increased 1.9-fold. Unit hospital costs and outpatient costs increased 1.57-fold and 1.47-fold, while unit medication costs fell by 10.6%. Increasing prevalence was also observed when the data were stratified by sex, age, ethnicity, level of education, level of income, and SEP (P < 0.05). Men, ethnic minorities, and those with a lower educational level, lower income, or lower SEP had a higher prevalence of COPD than their counterparts both in 2011 and 2021 (P < 0.05). Unit outpatient costs and medication costs increased with patients' SEP in both survey years (P < 0.05). CONCLUSIONS: The prevalence and economic costs of COPD increased substantially across all socioeconomic gradients in rural southwest China in the decade from 2011 and 2021. Future COPD prevention and management interventions as well as efforts to improve access to affordable COPD medication and treatment should focus in particular on ethnic minority and low SEP populations.


Assuntos
Estresse Financeiro , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Fatores Socioeconômicos , Etnicidade , Prevalência , Estudos Transversais , Grupos Minoritários , Doença Pulmonar Obstrutiva Crônica/epidemiologia , China/epidemiologia
2.
Int J Infect Dis ; 128: 157-165, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608788

RESUMO

OBJECTIVES: The effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV). METHODS: We analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated. RESULTS: Children who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV. CONCLUSION: Oseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children.

3.
Anticancer Res ; 43(2): 613-620, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697107

RESUMO

BACKGROUND/AIM: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases. MATERIALS AND METHODS: Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3+ T-cell infiltration. RESULTS: T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group. CONCLUSION: The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Linfócitos T , Anticorpos Monoclonais/farmacologia , Receptores de Antígenos de Linfócitos T alfa-beta , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Antígenos de Linfócitos T
4.
BMC Med Genomics ; 16(1): 9, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36650547

RESUMO

BACKGROUND: Retinitis pigmentosa (RP) is the most common type of inherited retinopathy. At least 69 genes for RP have been identified. A significant proportion of RP, however, remains genetically unsolved. In this study, the genetic basis of a Chinese consanguineous family with presumed autosomal recessive retinitis pigmentosa (arRP) was investigated. METHODS: Overall ophthalmic examinations, including funduscopy, decimal best-corrected visual acuity, axial length and electroretinography (ERG) were performed for the family. Genomic DNA from peripheral blood of the proband was subjected to whole exome sequencing. In silico predictions, structural modelling, and minigene assays were conducted to evaluate the pathogenicity of the variant. RESULTS: A novel homozygous variant (NM_003320.4: c.1379A > G) in the TUB gene was identified as a candidate pathogenic variant in this parental consanguineous pedigree. This variant co-segregated with the disease in this pedigree and was absent in 118 ethnically matched healthy controls. It's an extremely rare variant that is neither deposited in population databases (1000 Genomes, ExAC, GnomAD, or Exome Variant Server) nor reported in the literature. Phylogenetic analysis indicated that the Asn residue at codon 460 of TUB is highly conserved across diverse species from tropicalis to humans. It was also completely conserved among the TUB, TULP1, TULP2, and TULP3 family proteins. Multiple bioinformatic algorithms predicted that this variant was deleterious. CONCLUSIONS: A novel missense variant in TUB was identified, which was probably the pathogenic basis for arRP in this consanguineous family. This is the first report of a homozygous missense variant in TUB for RP.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Retinite Pigmentosa , Humanos , Análise Mutacional de DNA , Genes Recessivos , Mutação , Mutação de Sentido Incorreto , Linhagem , Filogenia , Retinite Pigmentosa/genética , Proteínas Adaptadoras de Transdução de Sinal/genética
5.
Acta Biomater ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36638944

RESUMO

Postoperative pain management would benefit significantly from an anesthetic that could take effect in an on-demand manner. An ultrasound would be an appropriate tool for such nanoplatform because it is widely used in clinical settings for ultrasound-guided anesthesia. Herein, we report a nanoplatform for postoperative on-demand pain management that can effectively enhance their analgesic time while providing ultrasonic imaging. Levobupivacaine and perfluoropentane were put into dendritic mesoporous silica and covered with red blood cell membranes to make the pain relief last longer in living organisms. The generated nanoplatform with gas-producing capability is ultrasonic responsive and can finely escape from the lysosomal in cells under ultrasound irradiation, maximizing the anesthetic effect with minimal toxicity. Using an incision pain model in vivo, levobupivacaine's sustained and controlled release gives pain reduction for approximately 3 days straight. The duration of pain relief is over 20 times greater than with a single injection of free levobupivacaine. Effective pain management was reached in vivo, and the pain reduction was enhanced by repeated ultrasonic irradiation. There was no detectable systemic or tissue injury under either of the treatments. Thus, our results suggest that nanoplatform with lysosomal escape capability can provide a practical ultrasound imaging-guided on-demand pain management strategy. STATEMENT OF SIGNIFICANCE: On-demand pain management is essential to postoperative patients. However, the traditional on-demand pain management strategy is hampered by the limited tissue penetration depth of near-infrared stimuli and the lack of proper imaging guidance. The proposed research is significant because it provides a nanoplatform for deep penetrated ultrasound controlled pain management under clinical applicable ultrasound imaging guidance. Moreover, the nanoplatform with prolonged retention time and lysosomal escape capability can provide long-term pain alleviation. Therefore, our results suggest that nanoplatform with lysosomal escape capability can provide an effective strategy for ultrasound imaging-guided on-demand pain management.

6.
Pest Manag Sci ; 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683402

RESUMO

BACKGROUND: The green lacewing Chrysoperla nipponensis is an important natural enemy of many insect pests and exhibits reproductive diapause to overwinter. Our previous studies showed that adult C. nipponensis entered reproductive diapause under short-day photoperiod. However, the molecular mechanism underlying the diapause maintenance of C. nipponensis is still unknown. RESULTS: The total lipid and triglyceride content showed a reservation and degradation of energy during the diapause of C. nipponensis. Thus, we performed combined transcriptomic and proteomic analyses of female reproductive diapause in C. nipponensis at three ecophysiological phages (initiation, maintenance and termination). A total of 64,388 unigenes and 5,532 proteins were identified from transcriptome and proteome. An in-depth dissection of gene-expression dynamics revealed that the differentially expressed genes and proteins were predominately involved in the lipids and carbohydrates metabolic pathways, especially fatty acid metabolism, metabolic pathways and citrate cycle. Among of these genes, TIM, CLK, JHAMT2, PMK, HMGS, HMGR, FKBP39, Kr-h1, Phm, ECR, IR1, ILP3, ILP4, mTOR, ACC, LSD1 and LSD2 were differentially expressed in the diapause and non-diapause female adults of C. nipponensis. Their expression patterns were consistent with the occurrence of the process of vitellogenesis and the expression of either Vg or VgR. CONCLUSION: Our findings indicated that diapause adult C. nipponensis accumulated more energy to overwinter. Transcriptomic and proteomic analyses suggested candidate key genes involved in the maintenance of C. nipponensis during adult reproductive diapause. Taken together, these results provide an in-depth knowledge to understand the maintenance mechanism of C. nipponensis during adult reproductive diapause. This article is protected by copyright. All rights reserved.

7.
J Ethnopharmacol ; : 116198, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36690307

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

9.
Angew Chem Int Ed Engl ; : e202216799, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602264

RESUMO

A simple, broad-scope rhodium(I)/chiral diene catalytic system for challenging asymmetric intramolecular cyclopropanation of various tri-substituted allylic diazoacetates was successfully developed. The low coordination state RhI -complex exhibits an extraordinarily high degree of tolerance to the variation in the extent of substitution of the allyl double bond, thus allowing the efficient construction of a wide range of penta-substituted, fused-ring cyclopropanes bearing three contiguous stereogenic centers, including two quaternary carbon stereocenters, in a highly enantioselective manner with ease at catalyst loading as low as 0.1 mol %. The stereoinduction mode of this RhI -carbene-directed asymmetric intramolecular cyclopropanation was investigated by DFT calculations, indicating that π-π stacking interactions between the aromatic rings of chiral diene ligand and diazo substrate play a key role in the control of the reaction enantioselectivity.

10.
J Am Chem Soc ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629383

RESUMO

Copper-based catalysts are widely explored in electrochemical CO2 reduction (CO2RR) because of their ability to convert CO2 into high-value-added multicarbon products. However, the poor stability and low selectivity limit the practical applications of these catalysts. Here, we proposed a simple and efficient asymmetric low-frequency pulsed strategy (ALPS) to significantly enhance the stability and the selectivity of the Cu-dimethylpyrazole complex Cu3(DMPz)3 catalyst in CO2RR. Under traditional potentiostatic conditions, Cu3(DMPz)3 exhibited poor CO2RR performance with the Faradaic efficiency (FE) of 34.5% for C2H4 and FE of 5.9% for CH4 as well as the low stability for less than 1 h. We optimized two distinguished ALPS methods toward CH4 and C2H4, correspondingly. The high selectivities of catalytic product CH4 (FECH4 = 80.3% and above 76.6% within 24 h) and C2H4 (FEC2H4 = 70.7% and above 66.8% within 24 h) can be obtained, respectively. The ultralong stability for 300 h (FECH4 > 60%) and 145 h (FEC2H4 > 50%) was also recorded with the ALPS method. Microscopy (HRTEM, SAED, and HAADF) measurements revealed that the ALPS method in situ generated and stabilized extremely dispersive and active Cu-based clusters (∼2.7 nm) from Cu3(DMPz)3. Meanwhile, ex situ spectroscopies (XPS, AES, and XANES) and in situ XANES indicated that this ALPS method modulated the Cu oxidation states, such as Cu(0 and I) with C2H4 selectivity and Cu(I and II) with CH4 selectivity. The mechanism under the ALPS methods was explored by in situ ATR-FTIR, in situ Raman, and DFT computation. The ALPS methods provide a new opportunity to boost the selectivity and stability of CO2RR.

11.
J Environ Manage ; 329: 116984, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563441

RESUMO

The virtual water trade (VWT) has been proposed as a means of balancing national water budgets while also saving water globally. Since humans require both sufficient quantity and quality of water, the drivers of VWT flows should be thoroughly examined, including its three components. Multiregional input-output (MRIO) and gravity methods are used to investigate the influence of multiple factors on the green, blue, and grey water trading flows among 177 countries in 2014. Several factors were found to be strongly correlated with the grey water trade, offering valuable insight into water resource management, especially about water pollution. The findings verify the driving effects of socio-economic status and agricultural activities on virtual water trade. The study shows that the influence of water resources endowment on the virtual water trade flow is relatively small compared to economic structure in determining virtual water trade flows. The paper contributes to the research on the interaction between virtual water trade and various factors, which can assist decision-makers in optimizing economic structure by integrating water quantity and quality factors and realize sustainable management of water resources.


Assuntos
Condução de Veículo , Abastecimento de Água , Humanos , Recursos Hídricos , Agricultura , Água , China
12.
ACS Nano ; 17(1): 636-647, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36524746

RESUMO

Developing highly efficient and stable noble-metal-free electrocatalysts for water splitting is critical for producing clean and sustainable energy. Here, we design a hierarchical transition metal hydroxide/sulfide (NiFe(OH)x-Ni3S2/NF) electrode with dual heterointerface coexistence using a cation exchange-induced surface reconfiguration strategy. The electrode exhibits superior electrocatalytic activities, achieving low overpotentials of 55 mV for hydrogen evolution and 182 mV for oxygen evolution at 10 mA cm-2. Furthermore, the assembled two-electrode system requires voltages as low as 1.55 and 1.62 V to deliver industrially relevant current densities of 500 and 1000 mA cm-2, respectively, with excellent durability for over 200 h, which is comparable to commercial electrolysis. Theoretical calculations reveal that the hierarchical heterostructure increases the electronic delocalization of the Fe and Ni catalytic centers, lowering the energy barrier of the rate-limiting step and promoting O2 desorption. Finally, by implementing the catalysts in a solar-driven water electrolysis system, we demonstrate a record and durable solar-to-hydrogen (STH) conversion efficiency of up to 20.05%. This work provides a promising strategy for developing low-cost and high-efficiency bifunctional catalysts for a large-scale solar-to-hydrogen generation.

13.
Sci Total Environ ; 863: 160898, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36521595

RESUMO

The integrated system of microbial electrosynthesis (MES) coupled with chain elongation has been considered a promising platform for carboxylic acids production. However, this biotechnology is still in its infancy, and many limitations are needed to be transcended, such as low electron transfer efficiency between cathode and microbes. In this study, nano zero-valent iron (NZVI) was employed to improve carboxylic acid production in the integrated system, and the promotion mechanisms were revealed. Results suggested that the highest production concentrations of acetate, butyrate, and caproate were observed at 7.5 g/L optimized NZVI dosage, increasing the total yield and coulomb efficiency by 23.7 % and 40.3 % compared to the control. Mechanism studies indicated that the hydrogen and electron released by the anaerobic corrosion of NZVI could be used as additional reducing equivalents, thereby enhancing the electron transfer performance. Besides, NZVI was also proven to facilitate the formation of electroactive biofilms according to the results of biofilm characterization and total DNA. In functional microbes' respect, the moderate NZVI enriched the chain elongator in biofilm, like Clostridium_sensu-stricto_12, and upregulated the activities of key enzymes of homoacetogenesis and chain elongation metabolic pathways, like carbon-monoxide dehydrogenase and hydroxyacyl-CoA dehydratase. This study provided the evidence and revealed how NZVI assisted carboxylic acid production from CO2 via chain elongation in MES.


Assuntos
Dióxido de Carbono , Ferro , Dióxido de Carbono/metabolismo , Acetatos , Biotecnologia , Anaerobiose
14.
Anticancer Res ; 43(1): 105-114, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36585204

RESUMO

BACKGROUND/AIM: Colorectal cancer is the third most common cancer globally, and the poor prognosis of patients with metastatic colorectal cancer (mCRC) warrants urgent attention. We previously obtained 10 candidate serum biomarkers for mCRC. Our aim with this study was to determine the prognostic performance of the pre-treatment serum C-C motif chemokine ligand 7 (CCL7) concentration in patients with mCRC. PATIENTS AND METHODS: Protein concentrations of CCL7 were examined using ELISA and immunohistochemistry for serum (n=110) and surgical specimens (n=85), respectively, of patients with mCRC. The relationship between protein concentration and prognosis was examined using Cox regression analysis, receiver operator characteristic curve analysis and the Kaplan-Meier method. RESULTS: The overall survival (OS) of patients with high concentrations of serum CCL7 was significantly poorer than that of patients with low concentrations. Patients with a high CCL7 concentration in the stroma had significantly poorer outcomes than those with a low concentration. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 were significantly higher in the high-CCL7 group, compared to those in the low-CCL7 group. Univariate and multivariate analysis revealed that serum CCL7 concentration was a significant prognostic factor for mCRC. The combination of serum CCL and CEA concentrations was also useful in this regard (area under the curve=0.71). CONCLUSION: The combined pre-treatment serum levels of CCL7 and CEA are useful prognostic biomarkers for mCRC.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Antígeno Carcinoembrionário , Prognóstico , Neoplasias Colorretais/patologia , Ligantes , Biomarcadores Tumorais , Estudos Retrospectivos , Quimiocina CCL7
15.
Environ Sci Technol ; 57(2): 1186-1197, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36580422

RESUMO

Cities have been envisioned as biological organisms as the integral part of nature's energy and material flows. Recent advances in urban scaling research have uncovered systematic changes in socioeconomic rates and infrastructural networks as urban population increases, providing predictive contents for the comparison between cities and organisms. However, it is still unclear how and why larger and smaller cities may differ in their per capita environmental impacts. Here, we study scaling patterns of urban energy, water, and waste flows as well as other relevant measures in Chinese cities. We divide cities into different groups using an algorithm that automatically assigns cities to clusters with distinct scaling patterns. Despite superlinear scaling of urban GDP, as predicted by urban scaling theories, resource consumption, such as the supply of electricity and water, and waste generation, such as wastewater and domestic waste, do not show significant deviations from linear scaling. The lengths of resource pipelines scale linearly in most cases, as opposed to sub-linearity predicted by theory. Furthermore, we show two competing forces underlying the overall observed effects of scale: a higher population density tends to decrease per capita resource consumption and infrastructure provisions, while intensified socioeconomic activities have the opposite effect.


Assuntos
Meio Ambiente , Água , Humanos , Cidades , População Urbana , China
16.
J Agric Food Chem ; 71(1): 311-319, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36571252

RESUMO

Mycotoxins have substantial impacts on agricultural production and food preservation. Some have high similarities in bioactivity but subtle differences on structures from various fungal producers. Understanding of their complex cross-biosynthesis will provide new insights into enzyme functions and food safety. Here, based on structurally related mycotoxins, such as aurovertins, asteltoxin, and citreoviridin, we showed that methyltransferase (MT)-catalyzed methylation is required for efficient oxidation and polyketide stability. MTs have broad interactions with polyketide synthases and flavin-containing monooxygenases (FMOs), while MT AstB is required for FMO AstC functionality in vivo. FMOs have common catalysis on pyrone-polyene intermediates but different catalytic specificity and efficiency on oxidative intermediates for the selective production of more toxic and complex mycotoxins. Thus, the subtle protein interaction and elaborate versatile catalysis of biosynthetic enzymes contribute to the efficient and selective biosynthesis of these structure-related mycotoxins and provide the basis to re-evaluate and control mycotoxins for agricultural and food safety.


Assuntos
Micotoxinas , Policetídeos , Micotoxinas/química , Policetídeos/metabolismo , Metiltransferases , Policetídeo Sintases/metabolismo , Catálise
17.
Environ Int ; 171: 107649, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36470121

RESUMO

BACKGROUND: Meningitis can cause devastating epidemics and is susceptible to climate change. It is unclear how temperature variability, an indicator of climate change, is associated with meningitis incidence. METHODS: We used global meningitis incidence data along with meteorological and demographic data over 1990-2019 to identify the association between temperature variability and meningitis. We also employed future (2020-2100) climate data to predict meningitis incidence under different emission levels (SSPs: Shared Socioeconomic Pathways). RESULTS: We found that the mean temperature variability increased by almost 3 folds in the past 30 years. The largest changes occurred in Australasia, Tropical Latin America, and Central Sub-Saharan Africa. With a logarithmic unit increase in temperature variability, the overall global meningitis risk increases by 4.8 %. Australasia, Central Sub-Saharan Africa, and High-income North America are the most at-risk regions. Higher statistical differences were identified in males, children, and the elderly population. Compared to high-emission (SSP585) scenario, we predicted a median reduction of 85.8 % in meningitis incidence globally under the low-emission (SSP126) climate change scenario by 2100. CONCLUSION: Our study provides evidence for temperature variability being in association with meningitis incidence, which suggests that global actions are urgently needed to address climate change and to prevent meningitis occurrence.

18.
Metabolism ; : 155372, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36470472

RESUMO

Reduced mitochondrial ATP synthase (ATPS) capacity plays crucial roles in the pathogenesis of metabolic disorders. However, there is currently no effective strategy for synchronously stimulating the expressions of ATPS key subunits to restore its assembly. This study determined the roles of mitochondrial protein FAM3A in regulating the activity and assembly of ATPS's in hepatocytes. FAM3A is localized in mitochondrial matrix, where it interacts with F1-ATPS to initially activate ATP synthesis and release, and released ATP further activates P2 receptor-Akt-CREB pathway to induce FOXD3 expression. FOXD3 synchronously stimulates the transcriptions of ATPS key subunits and assembly genes to increase its assembly and capacity, augmenting ATP synthesis and inhibiting ROS production. FAM3A, FOXD3 and ATPS expressions were reduced in livers of diabetic mice and NAFLD patients. FOXD3 expression, ATPS capacity and ATP content were reduced in various tissues of FAM3A-deficient mice with dysregulated glucose and lipid metabolism. Hepatic FOXD3 activation increased ATPS assembly to ameliorate dysregulated glucose and lipid metabolism in obese mice. Hepatic FOXD3 inhibition or knockout reduced ATPS capacity to aggravate HFD-induced hyperglycemia and steatosis. In conclusion, FAM3A is an active ATPS component, and regulates its activity and assembly by activating FOXD3. Activating FAM3A-FOXD3 axis represents a viable strategy for restoring ATPS assembly to treat metabolic disorders.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36461785

RESUMO

Efficient biosynthesis of microbial bioactive natural products (NPs) is beneficial for the survival of producers, while self-protection is necessary to avoid self-harm resulting from over-accumulation of NPs. The underlying mechanisms for the effective but tolerable production of bioactive NPs is not well understood. Here in the biosynthesis of two fungal polyketide mycotoxins aurovertin E (1) and asteltoxin (4), we show that the cyclases in the gene clusters promote the release of the polyketide backbone, and reveal that a signal peptide is crucial for their subcellular localization and full activity. Meanwhile, the fungus adopts enzymatic acetylation as the major detoxification pathway of 1. If intermediates are over-produced, the non-enzymatic shunt pathways work as salvage pathways to avoid excessive accumulation of the toxic metabolites for self-protection. These findings provided new insights into the interplay of efficient backbone release and multiple detoxification strategies for the production of fungal bioactive NPs.

20.
Transl Res ; 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36586533

RESUMO

Liquid biopsy has the advantage of diagnosing diseases in a noninvasive manner. Seminal plasma contains secretions from the bilateral testes, epididymides, seminal vesicles, bulbourethral glands, and the prostate. These organs are relatively small and contain delicate tubes that are prone to damage by invasive diagnosis. Cell-free seminal nucleic acids are a newly emerged item in liquid biopsy. Here, we present a comprehensive overview of all known cell-free DNA and cell-free RNAs (mRNA, miRNA, lncRNA, circRNA, piRNA, YRNA, tsRNA, etc.) and discuss their roles as biomarker candidates in liquid biopsy. With great advantages, including high stability, sensitivity, representability, and noninvasiveness, cell-free DNA/RNAs may be developed as promising biomarkers for the screening, diagnosis, prognosis, and follow-up of diseases in semen-secreting organs. Moreover, RNAs in semen may participate in important processes, including sperm maturation, early embryo development, and transgenerational disease inheritance, which may be developed as potential treatment targets for future clinical use.

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