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1.
Nano Lett ; 24(38): 11968-11975, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39259027

RESUMO

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 625-629, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39223028

RESUMO

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.


Assuntos
Coma , Humanos , Feminino , Coma/etiologia , Transtorno Conversivo/complicações , Transtorno Conversivo/diagnóstico , Eletroencefalografia , Cataplexia/diagnóstico , Cataplexia/complicações , Orexinas/líquido cefalorraquidiano
3.
Technol Health Care ; 32(5): 2981-2993, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39093084

RESUMO

BACKGROUND: One of the main illnesses in the globe that causes impairment and death in people is stroke. In the globe today, it ranks as the second leading cause of death and the leading cause of death in China. OBJECTIVE: This paper analyses into the critical role of risk perception in developing individual awareness of stroke risk and encouraging proactive preventive health behaviors, essential for effective primary stroke prevention strategies and reduced stroke incidence. It discusses the concept of risk perception, the content and dimensions of global stroke assessment tools, and their application status, aiming to provide insights for their development and intervention research. METHODS: Risk perception encompasses subjective assessments of stroke likelihood and severity, influenced by personal experiences, knowledge of risk factors, beliefs about prevention effectiveness, and emotional responses. Global stroke assessment tools, like the Framingham Stroke Risk Score and CHA2DS2-VASc Score, evaluate stroke risk based on factors such as age, gender, blood pressure, and cholesterol levels. In order to improve risk perception and proactive health management and lower the burden of strokes, the paper assesses the advantages and disadvantages of these tools and makes recommendations for improving accessibility, customizing interventions, running educational campaigns, promoting multidisciplinary collaboration, and integrating technology. RESULTS: By combining the research tools of stroke risk perception, it is found that the evaluation tools are mostly single-dimensional evaluation tools centered on the two dimensions of onset possibility and susceptibility. CONCLUSION: Some scholars have developed multi-dimensional evaluation tools, but the evaluation population is relatively limited, and the evaluation system lacks comprehensiveness and systematization.


Assuntos
Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/prevenção & controle , Medição de Risco/métodos , Fatores de Risco , Conhecimentos, Atitudes e Prática em Saúde , Percepção
4.
Dev Cell ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39191251

RESUMO

Ergosterols are essential components of fungal plasma membranes. Inhibitors targeting ergosterol biosynthesis (ERG) genes are critical for controlling fungal pathogens, including Magnaporthe oryzae, the fungus that causes rice blast. However, the translational mechanisms governing ERG gene expression remain largely unexplored. Here, we show that the Trm6/Trm61 complex catalyzes dynamic N1-methyladenosine at position 58 (m1A58) in 51 transfer RNAs (tRNAs) of M. oryzae, significantly influencing translation at both the initiation and elongation stages. Notably, tRNA m1A58 promotes elongation speed at most cognate codons mainly by enhancing eEF1-tRNA binding rather than affecting tRNA abundance or charging. The absence of m1A58 leads to substantial decreases in the translation of ERG genes, ergosterol production, and, consequently, fungal virulence. Simultaneously targeting the Trm6/Trm61 complex and the ergosterol biosynthesis pathway markedly improves rice blast control. Our findings demonstrate an important role of m1A58-mediated translational regulation in ergosterol production and fungal infection, offering a potential strategy for fungicide development.

5.
Autophagy ; : 1-21, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39193910

RESUMO

Macroautophagy/autophagy activation in renal tubular epithelial cells protects against acute kidney injury (AKI). However, the role of immune cell autophagy, such as that involving macrophages, in AKI remains unclear. In this study, we discovered that macrophage autophagy was an adaptive response during AKI as mice with macrophage-specific autophagy deficiency (atg5-/-) exhibited higher serum creatinine, more severe renal tubule injury, increased infiltration of ADGRE1/F4/80+ macrophages, and elevated expression of inflammatory factors compared to WT mice during AKI induced by either LPS or unilateral ischemia-reperfusion. This was further supported by adoptive transfer of atg5-/- macrophages, but not WT macrophages, to cause more severe AKI in clodronate liposomes-induced macrophage depletion mice. Similar results were also obtained in vitro that bone marrow-derived macrophages (BMDMs) lacking Atg5 largely increased pro-inflammatory cytokine expression in response to LPS and IFNG. Mechanistically, we uncovered that atg5 deletion significantly upregulated the protein expression of TARM1 (T cell-interacting, activating receptor on myeloid cells 1), whereas inhibition of TARM1 suppressed LPS- and IFNG-induced inflammatory responses in atg5-/- RAW 264.7 macrophages. The E3 ubiquitin ligases MARCHF1 and MARCHF8 ubiquitinated TARM1 and promoted its degradation in an autophagy-dependent manner, whereas silencing or mutation of the functional domains of MARCHF1 and MARCHF8 abolished TARM1 degradation. Furthermore, we found that ubiquitinated TARM1 was internalized from plasma membrane into endosomes, and then recruited by the ubiquitin-binding autophagy receptors TAX1BP1 and SQSTM1 into the autophagy-lysosome pathway for degradation. In conclusion, macrophage autophagy protects against AKI by inhibiting renal inflammation through the MARCHF1- and MARCHF8-mediated degradation of TARM1.Abbreviations: AKI, acute kidney injury; ATG, autophagy related; Baf, bafilomycin A1; BMDMs, bone marrow-derived macrophages; CCL2/MCP-1, C-C motif chemokine ligand 2; CHX, cycloheximide; CQ, chloroquine; IFNG, interferon gamma; IL, interleukin; IR, ischemia-reperfusion; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; LPS, lipopolysaccharide; MARCHF, membrane associated ring-CH-type finger; NC, negative control; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3, NLR family, pyrin domain containing 3; NOS2, nitric oxide synthase 2, inducible; Rap, rapamycin; Wort, wortmannin; RT-qPCR, real-time quantitative polymerase chain reaction; Scr, serum creatinine; SEM, standard error of mean; siRNA, small interfering RNA; SYK, spleen tyrosine kinase; TARM1, T cell-interacting, activating receptor on myeloid cells 1; TAX1BP1, Tax1 (human T cell leukemia virus type I) binding protein 1; TECs, tubule epithelial cells; TNF, tumor necrosis factor; WT, wild type.

6.
Pharmaceutics ; 16(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39204399

RESUMO

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal-organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems.

7.
Inorg Chem ; 63(29): 13766-13774, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38965989

RESUMO

Solar photocatalytic H2 production from lignocellulosic biomass has attracted great interest, but it suffers from low photocatalytic efficiency owing to the absence of highly efficient photocatalysts. Herein, we designed and constructed ultrathin MoS2-modified porous TiO2 microspheres (MT) with abundant interface Ti-S bonds as photocatalysts for photocatalytic H2 generation from lignocellulosic biomass. Owing to the accelerated charge transfer related to Ti-S bonds, as well as the abundant active sites for both H2 and ●OH generation, respectively, related to the high exposed edge of MoS2 and the large specific surface area of TiO2, MT photocatalysts demonstrate good performance in the photocatalytic conversion of α-cellulose and lignocellulosic biomass to H2. The highest H2 generation rate of 849 µmol·g-1·h-1 and apparent quantum yield of 4.45% at 380 nm was achieved in α-cellulose aqueous solution for the optimized MT photocatalyst. More importantly, lignocellulosic biomass of corncob, rice hull, bamboo, polar wood chip, and wheat straw were successfully converted to H2 over MT photocatalysts with H2 generation rate of 10, 19, 36, 29, and 8 µmol·g-1·h-1, respectively. This work provides a guiding design approach to develop highly active photocatalysts via interface engineering for solar H2 production from lignocellulosic biomass.

8.
World J Gastrointest Surg ; 16(6): 1537-1547, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983355

RESUMO

BACKGROUND: The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma (ESCC) patients remained debatable. AIM: To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery. METHODS: In this retrospective, propensity score-matched study, we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019. Patients who underwent neoadjuvant therapy were excluded. We collected patients' clinicopathological features and information regarding lymph nodes, including the total number of resected lymph nodes (NRLN), and pathologically diagnosed positive lymph nodes (RPLN). SPSS and R software were used for statistical analysis. RESULTS: Among the included 1042 patients, two cohorts: ≤ 21 (n = 664) and > 21 NRLN (n = 378) were identified. The final prognostic model included four variables: T stage, N, venous thrombus, and the number of removed lymph nodes. Among them, NRLN > 21 was determined as an independent prognosticator after surgery for esophageal cancer (hazards regression = 0.66, 95% confidence interval: 0.50-0.87, P = 0.004). A nomogram was created based on the regression coefficients of the variables in the final model. In the training cohort, the predictive model displayed an uncorrected five-year overall survival C-index of 0.659, with a bootstrap-corrected C-index of 0.654. In the subgroup analysis, adjuvant chemotherapy was beneficial in the subgroup with NRLN > 21 and RPLN ≤ 0.16 and NRLN ≤ 21 and RPLN > 0.16. CONCLUSION: NRLN > 21 was an independent prognostic factor after ESCC surgery. The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

9.
Diabetes Metab Syndr Obes ; 17: 2789-2807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39072347

RESUMO

Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases. Glutaminolysis converts glutamine into the TCA cycle metabolite, alpha-ketoglutarate, via a cascade of enzymatic reactions. This metabolic pathway plays pivotal roles in inflammation, maladaptive repair, cell survival and proliferation, redox homeostasis, and immune regulation. Given the crucial role of glutaminolysis in bioenergetics and anaplerotic fluxes in kidney pathogenesis, studies on this cascade could provide a better understanding of kidney diseases, thus inspiring the development of potential methods for targeted therapy. Emerging evidence has shown that targeting glutaminolysis is a promising therapeutic strategy for ameliorating kidney disease. In this narrative review, equation including keywords related to glutamine, glutaminolysis and kidney are subjected to an exhaustive search on Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, we summarize the regulation of glutaminolysis in major kidney diseases and its underlying molecular mechanisms. Furthermore, we highlight therapeutic strategies targeting glutaminolysis and their potential clinical applications.

10.
Inorg Chem ; 63(21): 9715-9719, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38748179

RESUMO

Photocatalytic nitrogen fixation from N2 provides an alternative strategy for ammonia (NH3) production, but it was limited by the consumption of a sacrificial electron donor for the currently reported half-reaction system. Here, we use naturally abundant and renewable cellulose as the sacrificial reagent for photocatalytic nitrogen fixation over oxygen-vacancy-modified MoO3 nanosheets as the photocatalyst. In this smartly designed photocatalytic system, the photooxidation of cellulose not only generates value-added chemicals but also provides electrons for the N2 reduction reaction and results in the production of NH3 with a maximum rate of 68 µmol·h-1·g-1. Also, the oxygen vacancies provide efficient active sites for both cellulose oxygenolysis and nitrogen fixation reactions. This work represents useful inspiration for realizing nitrogen fixation coupled with the generation of value-added chemicals from N2 and cellulose through a photocatalysis strategy.

11.
Pest Manag Sci ; 80(9): 4650-4664, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38775404

RESUMO

BACKGROUND: The beet webworm, Loxostege sticticalis, a worldwide pest of many crops, performs a seasonal migration, causing periodic outbreaks in Asia, Europe and North America. Although long-distance migration is well documented in China, patterns of transboundary migration among China, Russia and Mongolia are largely unknown. We performed a phase analysis of L. sticticalis periodic outbreaks among three countries based on 30 years of historical population data, analyzed the wind systems during migration over boundary regions, and traced the migratory routes in a case study of outbreaks in 2008 by trajectory simulation. RESULTS: Highly synchronized outbreak years of L. sticticalis were observed between China and Mongolia, China and eastern Siberia, China and western Siberia, Mongolia and eastern Siberia, eastern Siberia and western Siberia from 1978 to 2008, indicating possible transboundary migration between these regions. Winds at 300-600 m altitude, where adult migration usually occurs, also showed a high probability of northwestern winds in Haila'er (China), Chita (Russia) and Choybalsan (Mongolia), favoring successful adult migration from these areas to northern and northeastern China. Back trajectory analysis further showed that the first-generation adults that caused the severe outbreak of second-generation larvae in 2008 originated from eastern Siberia, eastern Mongolia, and the boundary regions of China-Russia and China-Mongolia. CONCLUSION: Our findings demonstrated that the source of L. sticticalis outbreaks in northern China was closely related to the outbreaks in Siberia and Mongolia via long-distance transboundary windborne migration. This information will help guide international monitoring and management strategies against this notorious pest. © 2024 Society of Chemical Industry.


Assuntos
Migração Animal , Mariposas , Animais , Mariposas/fisiologia , Mongólia , Federação Russa , China , Larva/crescimento & desenvolvimento
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 254-259, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38686723

RESUMO

Dopamine,a neurotransmitter ubiquitous in the body fluids,blood,and urine of mammals and humans,is responsible for regulating their functions and metabolism.The dopamine system is involved in the neurobiological mechanisms of narcolepsy in animals and humans.However,researchers have drawn different or even opposite conclusions when measuring the dopamine level in the cerebrospinal fluid of narcolepsy patients.Studies have confirmed that the occurrence of narcolepsy is related to the irreversible loss of orexins.The autoimmune reaction caused by the interactions of environmental factors with genetic factors destroys the hypothalamic orexin neurons and reduces orexin secretion,thereby lowering the level of arousal.We introduce the research progress and current status of dopamine and clinical characterization of narcolepsy by reviewing more than 40 articles published from 1982 to 2023,aiming to provide a reference for studying the relationship between the dopamine level and clinical characterization of narcolepsy and searching for the biomarkers of type 2 narcolepsy.


Assuntos
Dopamina , Narcolepsia , Animais , Humanos , Dopamina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Narcolepsia/metabolismo , Narcolepsia/diagnóstico , Neuropeptídeos/metabolismo , Orexinas/metabolismo , Orexinas/líquido cefalorraquidiano
13.
Front Pharmacol ; 15: 1392203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633616

RESUMO

Cancer is the main cause of death in the world. There are several therapies that are in practice for cancer cure including radiotherapy, chemotherapy, and surgery. Among the chemotherapies, natural products are considered comparable safe, easily available and cost effective. Approximately 60% of cancer approved FDA drugs are natural products including vinblastine, doxorubicin, and paclitaxel. These natural products have complex structures due to which they work against cancer through different molecular pathways, STAT3, NF-kB, PI3K/AKT/mTOR, cell cycle arrest, mitochondrial dependent pathway, extrinsic apoptosis pathway, autophagy, mitophagy and ferroptosis. AA is a natural abietane diterpenoid compound from Pinus palustris and Pimenta racemose var. grissea with different pharmacological activities including anti-inflammatory, anti-convulsant, anti-obesity and anti-allergic. Recently it has been reported with its anticancer activities through different molecular mechanisms including NF-kB, PI3K/AKT, call cycle arrest at G0/G1 phase, mitochondrial dependent pathway, extrinsic apoptosis pathway, AMPK pathway and ferroptosis pathways. The literature survey reveals that there is no review on AA anticancer molecular mechanisms, therefore in current review, we summarize the anticancer molecular mechanisms of AA.

14.
Biochem Biophys Res Commun ; 706: 149767, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38484570

RESUMO

Microglial activation is a critical factor in the pathogenesis and progression of neuroinflammatory diseases. Mild hypothermia, known for its neuroprotective properties, has been shown to alleviate microglial activation. In this study, we explore the differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) in BV-2 microglial cells under different conditions: normal temperature (CN), mild hypothermia (YT), normal temperature with lipopolysaccharide (LPS), and mild hypothermia with LPS (LPS + YT). Venn analysis revealed 119 DE mRNAs that were down-regulated in the LPS + YT vs LPS comparison but up-regulated in the CN vs LPS comparison, primarily enriched in Gene Ontology terms related to immune and inflammatory responses. Furthermore, through Venn analysis of YT vs CN and LPS + YT vs LPS comparisons, we identified 178 DE mRNAs and 432 DE lncRNAs. Among these transcripts, we validated the expression of Tent5c at the protein and mRNA levels. Additionally, siRNA-knockdown of Tent5c attenuated the expression of pro-inflammatory genes (TNF-α, IL-1ß, Agrn, and Fpr2), cellular morphological changes, NLRP3 and p-P65 protein levels, immunofluorescence staining of p-P65 and number of cells with ASC-speck induced by LPS. Furthermore, Tent5c overexpression further potentiated the aforementioned indicators in the context of mild hypothermia with LPS treatment. Collectively, our findings highlight the significant role of Tent5c down-regulation in mediating the anti-inflammatory effects of mild hypothermia.


Assuntos
Hipotermia , RNA Longo não Codificante , Humanos , Lipopolissacarídeos/farmacologia , Regulação para Baixo , Microglia/metabolismo , Hipotermia/metabolismo , RNA Longo não Codificante/metabolismo
15.
World J Gastrointest Oncol ; 16(2): 364-371, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425386

RESUMO

BACKGROUND: According to clinical data, a significant percentage of patients experience pain after surgery, highlighting the importance of alleviating postoperative pain. The current approach involves intravenous self-control analgesia, often utilizing opioid analgesics such as morphine, sufentanil, and fentanyl. Surgery for colorectal cancer typically involves general anesthesia. Therefore, optimizing anesthetic management and postoperative analgesic programs can effectively reduce perioperative stress and enhance postoperative recovery. The study aims to analyze the impact of different anesthesia modalities with multimodal analgesia on patients' postoperative pain. AIM: To explore the effects of different anesthesia methods coupled with multi-mode analgesia on postoperative pain in patients with colorectal cancer. METHODS: Following the inclusion criteria and exclusion criteria, a total of 126 patients with colorectal cancer admitted to our hospital from January 2020 to December 2022 were included, of which 63 received general anesthesia coupled with multi-mode labor pain and were set as the control group, and 63 received general anesthesia associated with epidural anesthesia coupled with multi-mode labor pain and were set as the research group. After data collection, the effects of postoperative analgesia, sedation, and recovery were compared. RESULTS: Compared to the control group, the research group had shorter recovery times for orientation, extubation, eye-opening, and spontaneous respiration (P < 0.05). The research group also showed lower Visual analog scale scores at 24 h and 48 h, higher Ramany scores at 6 h and 12 h, and improved cognitive function at 24 h, 48 h, and 72 h (P < 0.05). Additionally, interleukin-6 and interleukin-10 levels were significantly reduced at various time points in the research group compared to the control group (P < 0.05). Levels of CD3+, CD4+, and CD4+/CD8+ were also lower in the research group at multiple time points (P < 0.05). CONCLUSION: For patients with colorectal cancer, general anesthesia coupled with epidural anesthesia and multi-mode analgesia can achieve better postoperative analgesia and sedation effects, promote postoperative rehabilitation of patients, improve inflammatory stress and immune status, and have higher safety.

16.
Commun Biol ; 7(1): 255, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429435

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) via the nicotinamide (NAM) salvage pathway. While the structural biochemistry of eukaryote NAMPT has been well studied, the catalysis mechanism of prokaryote NAMPT at the molecular level remains largely unclear. Here, we demonstrated the NAMPT-mediated salvage pathway is functional in the Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) for the synthesis of NAD+, and the enzyme activity of NAMPT in this bacterium is significantly higher than that of human NAMPT in vitro. Our structural analyses of Xcc NAMPT, both in isolation and in complex with either the substrate NAM or the product nicotinamide mononucleotide (NMN), uncovered significant details of substrate recognition. Specifically, we revealed the presence of a NAM binding tunnel that connects the active site, and this tunnel is essential for both catalysis and inhibitor binding. We further demonstrated that NAM binding in the tunnel has a positive cooperative effect with NAM binding in the catalytic site. Additionally, we discovered that phosphorylation of the His residue at position 229 enhances the substrate binding affinity of Xcc NAMPT and is important for its catalytic activity. This work reveals the importance of NAMPT in bacterial NAD+ synthesis and provides insights into the substrate recognition and the catalytic mechanism of bacterial type II phosphoribosyltransferases.


Assuntos
Niacinamida , Xanthomonas campestris , Humanos , Niacinamida/metabolismo , NAD/metabolismo , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Xanthomonas campestris/metabolismo , Nicotinamida Fosforribosiltransferase/química , Nicotinamida Fosforribosiltransferase/metabolismo , Fosforilação
17.
Medicine (Baltimore) ; 103(6): e37169, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335422

RESUMO

This study aimed to assess the utility of serum YKL-40 and serum dipeptidyl peptidase IV (DPP4) as biomarkers for distinguishing between type 2 (T2)-high and T2-low asthma in the Chinese population. Additionally, we sought to explore the associations of serum YKL-40 and DPP4 levels with asthma characteristics and conventional markers. A real-world observational cross-sectional study was conducted, involving a total of 75 adult asthma patients. We collected general information, including demographics and medical history. Measurements included complete blood count, fractional exhaled nitric oxide (FeNO), post-bronchodilator spirometry, serum YKL-40 and serum DPP4 levels. Asthma endotypes, T2-high and T2-low, were defined through a comprehensive review of existing literature and expert group discussions. Logistic and linear regression models were employed. Our findings indicated no significant association between serum YKL-40 or serum DPP4 levels and T2-high asthma across all models. In the fully adjusted model, their odds ratios (OR) were 0.967 (95% CI: 0.920-1.017) and 0.997 (95% CI: 0.993-1.001), respectively. Notably, serum YKL-40 exhibited a positive correlation with FeNO (ß = 0.382, 95% CI: 0.230-0.533) after adjusting for confounding factors. This association, however, diminished in patients under 40 years old (P = .24), males (P = .25), and those with FEV1%pred of 80% or higher (P = .25). Serum DPP4 demonstrated a negative correlation with FEV1/FVC in the fully adjusted model (ß: -0.005, 95% CI: -0.009, -0.000). Among Chinese adult asthma patients, a positive correlation was observed between serum YKL-40 levels and FeNO in females aged over 40 with FEV1%pred less than 80%. Additionally, a weak negative correlation was found between serum DPP4 levels and FEV1/FVC. However, neither serum YKL-40 nor serum DPP4 levels exhibited the capability to differentiate between T2-high and T2-low asthma.


Assuntos
Asma , Dipeptidil Peptidase 4 , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Proteína 1 Semelhante à Quitinase-3 , Estudos Transversais , Óxido Nítrico/análise , Biomarcadores , China/epidemiologia
18.
Sci Rep ; 13(1): 22133, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092827

RESUMO

Accumulated evidence showed that thyroid diseases induced cognitive decline. However, the relationship between thyroid hormones (THs) and cognition in older euthyroid people is still unclear. Our study aimed to estimate the association between THs within the euthyroid range and cognition in community-dwelling older adults in China. Data were extracted from a cohort study on the health status of rural older adults from the Guizhou province in China (HSRO). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured using the electrochemiluminescence immunoassay. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Linear regression and a binary logistic regression model were used to explore the relationship between THs and cognition in euthyroidism (TSH level of 0.27 ~ 4.20mIU/L). A total of 957 euthyroidism individuals were included in this study, with a mean (SD) age of 71.34 (6.35) years. In individuals with euthyroidism, serum TSH and FT3 levels were positively associated with cognition (TSH:ß = 0.06, 95% CI 0.01 ~ 0.11, P = 0.03; FT3:ß = 0.07, 95% CI 0.01 ~ 0.12, P = 0.01); and serum FT3 and TSH levels were significantly associated with cognitive domains (P < 0.05). Further, euthyroid individuals in the lowest serum FT3(OR = 1.96; 95% CI 1.27 ~ 3.03) quartile had a twofold increased risk of cognitive impairment compared to those in the highest quartile after adjusting for potential confounding factors. These findings suggested that low levels of FT3 could be an independent risk factor for cognitive impairment in older euthyroid adults. Additionally, a positive linear association exists between serum FT3 levels and cognitive domains (such as immediate memory, language, and attention). Further studies are needed to determine the underlying mechanisms and the community significance of these findings.


Assuntos
Disfunção Cognitiva , Tri-Iodotironina , Humanos , Idoso , Tiroxina , Estudos de Coortes , Hormônios Tireóideos , Tireotropina , Testes de Função Tireóidea
19.
Life Sci ; 334: 122234, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37931744

RESUMO

Intestinal ischemia-reperfusion (IIR) injury is associated with inflammation and oxidative stress, yet its precise mechanisms remain not fully understood. IIR injury is closely linked to the gut microbiota and its metabolites. The anti-inflammatory and antioxidant effects of Lactiplantibacillus plantarum are specific to IIR. In our study, we conducted a 30-day pre-treatment of SD rats with both a standard strain of Lactiplantibacillus plantarum and Lactiplantibacillus plantarum GL001. After a 7-day cessation of treatment, we induced an IIR injury model to investigate the mechanisms by which Lactiplantibacillus plantarum alleviates IIR damage. The results demonstrate that Lactiplantibacillus plantarum effectively mitigates the inflammatory and oxidative stress damage induced by IIR. Lactiplantibacillus plantarum GL001 can improve the gut microbiota by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. In IIR intestinal tissue, the levels of secondary bile acids are elevated. The content of the bacterial metabolite Calcimycin increases. Annotations of metabolic pathways suggest that Lactiplantibacillus plantarum GL001 can alleviate IIR damage by modulating calcium-phosphorus homeostasis through the regulation of parathyroid hormone synthesis, secretion, and action. Microbiota-metabolite correlation analysis reveals a significant negative correlation between calcimycin and Lactonacillus and a significant positive correlation between calcimycin and Shigella. There is also a significant positive correlation between calcimycin and secondary bile acids. Lactiplantibacillus plantarum GL001 can alleviate oxidative damage induced by IIR through improvements in gut microbiota and intestinal tissue metabolism.


Assuntos
Estresse Oxidativo , Traumatismo por Reperfusão , Ratos , Animais , Calcimicina/farmacologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Bactérias , Ácidos e Sais Biliares
20.
Front Immunol ; 14: 1213473, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37809091

RESUMO

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Rim
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