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1.
Nature ; 600(7887): 81-85, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34853456

RESUMO

Understanding the structure and dynamic process of water at the solid-liquid interface is an extremely important topic in surface science, energy science and catalysis1-3. As model catalysts, atomically flat single-crystal electrodes exhibit well-defined surface and electric field properties, and therefore may be used to elucidate the relationship between structure and electrocatalytic activity at the atomic level4,5. Hence, studying interfacial water behaviour on single-crystal surfaces provides a framework for understanding electrocatalysis6,7. However, interfacial water is notoriously difficult to probe owing to interference from bulk water and the complexity of interfacial environments8. Here, we use electrochemical, in situ Raman spectroscopic and computational techniques to investigate the interfacial water on atomically flat Pd single-crystal surfaces. Direct spectral evidence reveals that interfacial water consists of hydrogen-bonded and hydrated Na+ ion water. At hydrogen evolution reaction (HER) potentials, dynamic changes in the structure of interfacial water were observed from a random distribution to an ordered structure due to bias potential and Na+ ion cooperation. Structurally ordered interfacial water facilitated high-efficiency electron transfer across the interface, resulting in higher HER rates. The electrolytes and electrode surface effects on interfacial water were also probed and found to affect water structure. Therefore, through local cation tuning strategies, we anticipate that these results may be generalized to enable ordered interfacial water to improve electrocatalytic reaction rates.

2.
Stroke ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38920043

RESUMO

BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.

3.
J Org Chem ; 89(6): 4098-4112, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38421813

RESUMO

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

4.
Int J Colorectal Dis ; 39(1): 99, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926205

RESUMO

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Microambiente Tumoral , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Quimiorradioterapia , Resultado do Tratamento , Estudos Retrospectivos
5.
Environ Res ; 258: 119460, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906451

RESUMO

To investigate the inhibitory effects of various transition metal ions on nitrogen removal and their underlying mechanisms, the single and combined effects of Cu2+ Ni2+ and Zn2+ on Heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria Acinetobacter sp. TAC-1 were studied in a batch experiment system. The results revealed that increasing concentrations of Cu2+ and Ni2+ had a detrimental effect on the removal of ammonium nitrogen (NH4+-N) and total nitrogen (TN). Specifically, Cu2+ concentration of 10 mg/L, the TN degradation rate was 55.09%, compared to 77.60% in the control group. Cu2+ exhibited a pronounced inhibitory effect. In contrast, Zn2+ showed no apparent inhibitory effect on NH4+-N removal and even enhanced TN removal at lower concentrations. However, when the mixed ion concentration of Zn2++Ni2+ exceeded 5 mg/L, the removal rates of NH4+-N and TN were significantly reduced. Moreover, transition metal ions did not significantly impact the removal rates of chemical oxygen demand (COD). The inhibition model fitting results indicated that the inhibition sequence was Cu2+ > Zn2+ > Ni2+. Transcriptome analysis demonstrated that metal ions influence TAC-1 activity by modulating the expression of pivotal genes, including zinc ABC transporter substrate binding protein (znuA), ribosomal protein (rpsM), and chromosome replication initiation protein (dnaA) and DNA replication of TAC-1 under metal ion stress, leading to disruptions in transcription, translation, and cell membrane structure. Finally, a conceptual model was proposed by us to summarize the inhibition mechanism and possible response strategies of TAC-1 bacteria under metal ion stress, and to address the lack of understanding regarding the influence mechanism of TAC-1 on nitrogen removal in wastewater co-polluted by metal and ammonia nitrogen. The results provided practical guidance for the management of transition metal and ammonia nitrogen co-polluted water bodies, as well as the removal of high nitrogen.

6.
Lipids Health Dis ; 23(1): 194, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909243

RESUMO

BACKGROUND: Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. METHODS: C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. RESULTS: Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1ß. CONCLUSION: These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.


Assuntos
Autofagia , Catepsina B , Doenças Desmielinizantes , Gotículas Lipídicas , Lisofosfatidilcolinas , Camundongos Endogâmicos C57BL , MicroRNAs , Microglia , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Microglia/patologia , Camundongos , Gotículas Lipídicas/metabolismo , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/patologia , Catepsina B/metabolismo , Catepsina B/genética , Lisofosfatidilcolinas/metabolismo , Modelos Animais de Doenças , Masculino , Regulação da Expressão Gênica , Linhagem Celular
7.
Gynecol Endocrinol ; 40(1): 2360085, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38813955

RESUMO

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.


Assuntos
Insuficiência Ovariana Primária , Estresse Psicológico , Humanos , Insuficiência Ovariana Primária/psicologia , Insuficiência Ovariana Primária/etiologia , Insuficiência Ovariana Primária/terapia , Feminino , Estresse Psicológico/complicações , Estresse Oxidativo/fisiologia , Fatores de Risco , Depressão/etiologia
8.
Metab Brain Dis ; 39(1): 147-171, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37542622

RESUMO

Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/diagnóstico , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Genômica , Proteínas de Ligação a RNA/genética
9.
Spinal Cord ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849489

RESUMO

STUDY DESIGN: Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI. SETTING: Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University. METHODS: Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR. RESULTS: OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice. CONCLUSIONS: OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.

10.
J Insect Sci ; 24(3)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38809687

RESUMO

Huanglongbing (HLB), a devastating citrus disease caused by Candidatus Liberibacter asiaticus, is efficiently vectored by the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae). Tamarixia radiata (Waterston) plays a crucial role as an ectoparasitoid, preying on D. citri nymphs. By collecting and identifying headspace volatiles from fifth instar nymphs of D. citri using a gas chromatograph-mass spectrometer (GC-MS), we obtained a collection of 9 volatile compounds. These compounds were subsequently chosen to investigate the electrophysiological and behavioral responses of female T. radiata. At a concentration of 10 µg/µl, 9 compounds were compared with cis-3-hexen-1-ol (control), resulting in trans-2-nonenal inducing the highest relative electroantennogram (EAG) value, followed by hexanal, heptanal, n-heptadecane, tetradecanal, n-tetradecane, n-pentadecane, 1-tetradecanol, and 1-dodecanol. The top 5 EAG responses of female T. radiata to these compounds were further investigated through EAG dose-response experiments. The results showed positive dose-responses as concentrations increased from 0.01 to 10 µg/µl. In Y-tube olfactometer bioassays, female T. radiata exhibited a preference for specific compounds. They were significantly attracted to tetradecanal at a concentration of 10 µg/µl and trans-2-nonenal at 0.01 µg/µl, while no significant attraction was observed toward hexanal, heptanal, or n-heptadecane. Our report is the first to demonstrate that volatiles produced by D. citri nymphs attract T. radiata, which suggests that this parasitoid may utilize nymph volatiles to locate its host.


Assuntos
Hemípteros , Ninfa , Compostos Orgânicos Voláteis , Animais , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Hemípteros/fisiologia , Feminino , Vespas/fisiologia , Fenômenos Eletrofisiológicos , Comportamento Animal/efeitos dos fármacos , Antenas de Artrópodes/fisiologia , Antenas de Artrópodes/efeitos dos fármacos
11.
Opt Express ; 31(16): 26301-26313, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710493

RESUMO

We have developed a simple time-bin phase encoding quantum key distribution system, using the optical injection locking technique. This setup incorporates both the merits of simplicity and stability in encoding, and immunity to channel disturbance. We have demonstrated the field implementation of quantum key distribution over long-distance deployed aerial fiber automatically. During the 70-day field test, we achieved approximately a 1.0 kbps secure key rate with stable performance. Our work takes an important step toward widespread implementation of QKD systems in diverse and complex real-life scenarios.

12.
Opt Express ; 31(16): 26335-26343, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710496

RESUMO

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

13.
Opt Lett ; 48(20): 5281-5284, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37831847

RESUMO

Accurately lateral displacement measurement is essential for a vast of non-contact sensing technologies. Here, we introduce a high-precision lateral displacement measurement method based on differential wavefront sensing (DWS). Compared to the conventional differential power sensing (DPS) method, the DWS method based on phase readout has the potential to achieve a higher resolution. The beam lateral displacement can be obtained by the curvature distribution of the wavefront on the surface of the detector. According to the theoretical model of the DWS method, the sensitivity of the lateral displacement can be greatly improved by increasing the wavefront curvature of the measured laser beam by means of lenses. An optical system for measuring the lateral displacement of the laser beam is built and calibrated by a high-precision hexapod. The experimental results show that the DWS-based lateral displacement measurement achieves a resolution of 40 pm/Hz1/2 (at 1-10 Hz) with a linear range of about 40 µm, which is consistent with the theoretical model. This technique can be applied to high-precision multi-degree-of-freedom interferometers.

14.
Anesthesiology ; 139(3): 262-273, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37440205

RESUMO

BACKGROUND: Individualized positive end-expiratory pressure (PEEP) guided by dynamic compliance improves oxygenation and reduces postoperative atelectasis in nonobese patients. The authors hypothesized that dynamic compliance-guided PEEP could also reduce postoperative atelectasis in patients undergoing bariatric surgery. METHODS: Patients scheduled to undergo laparoscopic bariatric surgery were eligible. Dynamic compliance-guided PEEP titration was conducted in all patients using a downward approach. A recruitment maneuver (PEEP from 10 to 25 cm H2O at 5-cm H2O step every 30 s, with 15-cm H2O driving pressure) was conducted both before and after the titration. Patients were then randomized (1:1) to undergo surgery under dynamic compliance-guided PEEP (PEEP with highest dynamic compliance plus 2 cm H2O) or PEEP of 8 cm H2O. The primary outcome was postoperative atelectasis, as assessed with computed tomography at 60 to 90 min after extubation, and expressed as percentage to total lung tissue volume. Secondary outcomes included Pao2/inspiratory oxygen fraction (Fio2) and postoperative pulmonary complications. RESULTS: Forty patients (mean ± SD; 28 ± 7 yr of age; 25 females; average body mass index, 41.0 ± 4.7 kg/m2) were enrolled. Median PEEP with highest dynamic compliance during titration was 15 cm H2O (interquartile range, 13 to 17; range, 8 to 19) in the entire sample of 40 patients. The primary outcome of postoperative atelectasis (available in 19 patients in each group) was 13.1 ± 5.3% and 9.5 ± 4.3% in the PEEP of 8 cm H2O and dynamic compliance-guided PEEP groups, respectively (intergroup difference, 3.7%; 95% CI, 0.5 to 6.8%; P = 0.025). Pao2/Fio2 at 1 h after pneumoperitoneum was higher in the dynamic compliance-guided PEEP group (397 vs. 337 mmHg; group difference, 60; 95% CI, 9 to 111; P = 0.017) but did not differ between the two groups 30 min after extubation (359 vs. 375 mmHg; group difference, -17; 95% CI, -53 to 21; P = 0.183). The incidence of postoperative pulmonary complications was 4 of 20 in both groups. CONCLUSIONS: Postoperative atelectasis was lower in patients undergoing laparoscopic bariatric surgery under dynamic compliance-guided PEEP versus PEEP of 8 cm H2O. Postoperative Pao2/Fio2 did not differ between the two groups.


Assuntos
Atelectasia Pulmonar , Síndrome do Desconforto Respiratório , Feminino , Humanos , Respiração com Pressão Positiva/métodos , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/prevenção & controle , Obesidade/complicações , Pulmão , Síndrome do Desconforto Respiratório/complicações
15.
Inorg Chem ; 62(49): 20314-20324, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37991983

RESUMO

Functionalized crystalline solids based on metal-organic frameworks (MOFs) enable efficient luminescence detection and high proton conductivity, making them crucial in the realms of environmental monitoring and clean energy. Here, two structurally and functionally distinct zinc-based MOFs, [Zn(TTDPa)(bodca)]·H2O (1) and [Zn(TTDPb)(bodca)]·H2O (2), were successfully designed and synthesized using 3,6-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPa) and 2,5-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPb) as ligands, in the presence of bicyclo[2.2.2]octane-1,4-dicarboxylic acid (H2bodca). Both 1 and 2 display a three-dimensional (3D) structure with 5-fold interpenetration, and notably, 2 forms a larger one-dimensional pore measuring 17.16 × 10.81 Å2 in size. Fluorescence experiments demonstrate that 1 and 2 can function as luminescent sensors for nitrofurantoin (NFT) and nitrofurazone (NFZ) with low detection limits, remarkable selectivity, and good recyclability. A comprehensive analysis was conducted to investigate the differing sensing effects of compounds 1 and 2 and to explore potential sensing mechanisms. Additionally, at 328 K and 98% relative humidity, 1 and 2 exhibit proton conductivity values of 2.13 × 10-3 and 4.91 × 10-3 S cm-1, respectively, making them suitable proton-conducting materials. Hence, the integration of luminescent sensing and proton conductivity in monophasic 3D Zn-MOFs holds significant potential for application in intelligent multitasking devices.

16.
Acta Pharmacol Sin ; 44(10): 2075-2090, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37344564

RESUMO

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI). In this study, we investigated the role of PXR in CKD. Adenine diet-induced CKD (AD) model was established in wild-type and PXR humanized (hPXR) mice, respectively, which were treated with pregnenolone-16α-carbonitrile (PCN, 50 mg/kg, twice a week for 4 weeks) or rifampicin (RIF, 10 mg·kg-1·d-1, for 4 weeks). We showed that both PCN and RIF, which activated mouse and human PXR, respectively, improved renal function and attenuated renal fibrosis in the two types of AD mice. In addition, PCN treatment also alleviated renal fibrosis in unilateral ureter obstruction (UUO) mice. On the contrary, PXR gene deficiency exacerbated renal dysfunction and fibrosis in both adenine- and UUO-induced CKD mice. We found that PCN treatment suppressed the expression of the profibrotic Wnt7a and ß-catenin in AD mice and in cultured mouse renal tubular epithelial cells treated with TGFß1 in vitro. We demonstrated that PXR was colocalized and interacted with p53 in the nuclei of tubular epithelial cells. Overexpression of p53 increased the expression of Wnt7a, ß-catenin and its downstream gene fibronectin. We further revealed that p53 bound to the promoter of Wnt7a gene to increase its transcription and ß-catenin activation, leading to increased expression of the downstream profibrotic genes, which was inhibited by PXR. Taken together, PXR activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling pathway.


Assuntos
Receptor de Pregnano X , Insuficiência Renal Crônica , Via de Sinalização Wnt , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Fibrose , Mamíferos/metabolismo , Receptor de Pregnano X/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/tratamento farmacológico , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Rifampina/farmacologia
17.
J Headache Pain ; 24(1): 126, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37718436

RESUMO

BACKGROUND: In recent years, headache disorders have garnered significant attention as a pressing global health issue. This concern is especially pronounced in low- to middle-income countries and exhibits a notable increase in prevalence among adolescents and young adults. Such a surge in these disorders has invariably diminished the quality of life for affected individuals. Despite its global impact, comprehensive studies exploring the ramifications of headache disorders in the younger population remain scant. Our study endeavored to quantify the global prevalence of headache disorders in individuals between the ages of 15 and 39, over a three-decade span from 1990 to 2019. METHODS: Our study, conducted from 1990 to 2019, evaluated the impact of headache disorders, specifically migraines and tension-type headaches (TTH), in 204 different countries and territories. This comprehensive assessment included a detailed analysis of incidence rates, prevalence, and disability-adjusted life-years (DALYs) across various demographics such as age, gender, year, geographical location, and Socio-demographic Index (SDI). RESULTS: In 2019, there were an estimated 581,761,847.2 migraine cases globally (95% UI: 488,309,998.1 to 696,291,713.7), marking a 16% increase from 1990. Concurrently, TTH cases numbered at 964,808,567.1 (95% UI: 809,582,531.8 to 1,155,235,337.2), reflecting a 37% rise since 1990. South Asia reported the highest migraine prevalence with 154,490,169.8 cases (95% UI: 130,296,054.6 to 182,464,065.6). High SDI regions exhibited the most substantial migraine prevalence rates both in 1990 (22,429 per 100,000 population) and 2019 (22,606 per 100,000 population). Among the five SDI classifications, the middle SDI region recorded the highest tally of TTH cases in both 1990 (210,136,691.6 cases) and 2019 (287,577,250 cases). Over the past 30 years, East Asia experienced the most pronounced surge in the number of migraine cases. On the whole, there was a discernible positive correlation between the disease burden of migraine and TTH and the SDI. CONCLUSION: Migraine and TTH represent formidable challenges in global health. The intensity of their impact exhibits marked disparities across nations and is distinctly elevated among women, individuals within the 30-39 age bracket, and populations characterized by a high SDI. The results of our research emphasize the imperative of assimilating migraine and TTH management into contemporary healthcare paradigms. Such strategic integration holds the potential to amplify public cognizance regarding pertinent risk factors and the spectrum of therapeutic interventions at hand.


Assuntos
Transtornos da Cefaleia , Transtornos de Enxaqueca , Cefaleia do Tipo Tensional , Adolescente , Feminino , Humanos , Adulto Jovem , Adulto , Cefaleia do Tipo Tensional/epidemiologia , Carga Global da Doença , Qualidade de Vida , Transtornos de Enxaqueca/epidemiologia
18.
Environ Monit Assess ; 195(8): 970, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37466699

RESUMO

River sediment is vital in containing water pollution and strengthening water remediation. This paper has conducted a study on the microecological health assessment of the sediment and water body of Guixi River in Dianjiang, Chongqing, China, using metagenomics sequencing and microbial biological integrity index (M-IBI) technology. The analysis of physical and chemical characteristics shows that the concentration of TN varies from 2.62 to 9.76 mg/L in each sampling section, and the eutrophication of the water body is relatively severe. The proportion of Cyanobacteria in the sampling section at the sink entrance is higher than that of other sites, where there are outbreaks of water blooms and potential hazards to human health. The dominant functions of each site include carbon metabolism, TCA cycle, and pyruvate metabolism. In addition, the main virulence factors and antibiotic resistance genes in sediment are Type IV pili (VF0082), LOS (CVF494), MymA operon (CVF649), and macrolide resistance genes macB, tetracyclic tetA (58), and novA. Correlation analysis of environmental factors and microorganisms was also performed, and it was discovered that Thiothrix and Acidovorax had obvious gene expression in the nitrogen metabolism pathway, and the Guixi River Basin had a self-purification capacity. Finally, based on the microecological composition of sediment and physical and chemical characteristics of the water body, the health assessment was carried out, indicating that the main pollution area was Dianjiang Middle School and the watershed near the sewage treatment plant. The findings should theoretically support an in-depth assessment of the water environment's microecological health.


Assuntos
Monitoramento Ambiental , Metagenômica , Rios , Poluentes Químicos da Água , China , Poluentes Químicos da Água/análise , Farmacorresistência Bacteriana , Genes Bacterianos , Humanos
19.
Can J Infect Dis Med Microbiol ; 2023: 8508975, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124122

RESUMO

Objective: This study aims to assess the effectiveness of surveillance inspections conducted by the provincial health committee in Quanzhou city during a COVID-19 outbreak in reducing false-positive results in SARS-CoV-2 RT-PCR assays. Method: The team conducted on-site inspections of laboratories that participated in mass screening, recording any violations of rules. Results: The positive cases in five rounds of mass screening were 23, 173, and 4 in Licheng District, Fengze District, and Luojang District, respectively. The false-positive rates in the five rounds of mass screening were 0.0099%, 0.0063%, 0.0018%, 0.0006%, and 0%, respectively. The study also recorded that the number of violations in the seven selected laboratories was 36, 68, 69, 42, 60, 54 and 47. The corresponding false-positive rates were 0.0012%, 0.0060%, 0.0082%, 0.0032%, 0.0060%, 0.0027%, and 0.0021%, respectively. The study found a positive correlation between false-positive rates and the number of violations (r = 0.905, P=0.005), and an inverse correlation between false-positive rates and the frequency of surveillance inspections (r = -0.950, P < 0.001). Conclusion: Daily surveillance inspection in laboratories can remind laboratories to strictly comply with standard procedures, focus on laboratory quality control, and reduce the occurrence of false-positive cases in SARS-CoV-2 nucleic acid tests to some extent. This study recommends that government decision-making departments establish policies and arrange experts to conduct daily surveillance inspections to improve laboratory quality control.

20.
Angew Chem Int Ed Engl ; 62(30): e202306381, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37254230

RESUMO

Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi-substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report a low-valent CoH-catalyzed facial-selective cyclopropene hydroalkylation to access multi-substituted cyclopropanes. This reaction exhibits a broad substrate scope of alkyl halides and cyclopropenes and tolerates many functional groups. Moderate-to-good facial-selectivity is obtained without any directing groups. Mechanism studies provide evidence that alkyl radicals are generated from alkyl halides and irreversible CoH insertion is responsible for the facial-selectivity. Our preliminary exploration demonstrates that asymmetric cyclopropene hydroalkylation can be realized without conspicuous auxiliary groups.

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