RESUMEN

Zinc is a significant source of heavy metal pollution that poses risks to both human health and biodiversity. Excessive concentrations of zinc can hinder the growth and development of insects and trigger cell death through oxidative damage. The midgut is the main organ affected by exposure to heavy metals. The silkworm, a prominent insect species belonging to the Lepidoptera class and widely used in China, serves as a model for studying the genetic response to heavy metal stress. In this study, high-throughput sequencing technology was employed to investigate detoxification-related genes in the midgut that are induced by zinc exposure. A total of 11,320 unigenes and 14,723 transcripts were identified, with 553 differentially expressed genes (DEGs) detected, among which 394 were up-regulated and 159 were down-regulated. The Gene Ontology (GO) analysis revealed that 452 DEGs were involved in 18 biological process subclasses, 14 cellular component subclasses and 8 molecular functional subclasses. Furthermore, the KEGG analysis demonstrated enrichment in pathways such as Protein digestion, absorption and Lysosome. Validation of the expression levels of 9 detoxification-related DEGs through qRT-PCR confirmed the accuracy of the RNA-seq results. This study not only contributes new insights into the detoxification mechanisms mechanism of silkworms against zinc contamination, but also serves as a foundation basis for understanding the molecular detoxification processes in lepidopteran insects.

RESUMEN

Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

Asunto(s)

Anticuerpos Monoclonales Humanizados , ADN Polimerasa II , Mutación , Neoplasias , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias/genética , Neoplasias/tratamiento farmacológico , ADN Polimerasa II/genética , ADN Polimerasa III/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Adulto , Anciano de 80 o más Años

RESUMEN

Hybrid speciation plays an important role in species diversification. The establishment of reproductive isolation is crucial for hybrid speciation, and the identification of diverse types of hybrids, particularly homoploid hybrid species, contributes to a comprehensive understanding of this process. Reaumuria songarica is a constructive shrub widespread in arid Central Asia. Previous studies have inferred that the R. songarica populations in the Gurbantunggut Desert (GuD) originated from homoploid hybridizations between its eastern and western lineages and may have evolved into an incipient species. To further elucidate the genetic composition of different hybrid populations and to determine the species boundary of this hybrid lineage, we investigated the overall phylogeographic structure of R. songarica based on variation patterns of five cpDNA and one nrITS sequences across 32 populations. Phylogenetic analyses demonstrated that within the GuD lineage, the Wuerhe population evolved directly from ancestral lineages, whereas the others originated from hybridizations between the eastern and western lineages. PCoA and genetic barrier analysis supported the subdivision of the GuD lineage into the southern (GuD-S) and northern (GuD-N) groups. Populations in the GuD-S group had a consistent genetic composition and the same ancestral female parent, indicating that they belonged to a homoploid hybrid lineage. However, the GuD-N group experienced genetic admixture of the eastern and western lineages on nrITS and cpDNA, with some populations inferred to be allopolyploid based on ploidy data. Based on cpDNA haplotypes, BEAST analyses showed that the GuD-S and GuD-N groups originated after 0.5 Ma. Our results suggest that multiple expansions and contractions of GuD, driven by Quaternary climatic oscillations and the Kunlun-Yellow River tectonic movement, are important causes of the complex origins of R. songarica populations in northern Xinjiang. This study highlights the complex origins of the Junggar Basin flora and the underappreciated role of hybridization in increasing its species diversity.

RESUMEN

Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of ß-glucan, ergothioneine, ergosterol, and carotenoids. ß-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli.

Asunto(s)

Histidina Quinasa , Neurospora crassa , Especies Reactivas de Oxígeno , Neurospora crassa/genética , Neurospora crassa/metabolismo , Histidina Quinasa/genética , Histidina Quinasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Esporas Fúngicas/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Animales , Regulación Fúngica de la Expresión Génica , Artrópodos/genética , Artrópodos/microbiología , Mutación , Adaptación Fisiológica/genética , Ergosterol/metabolismo , beta-Glucanos/metabolismo , Antioxidantes/metabolismo , Carotenoides/metabolismo , Ergotioneína

RESUMEN

SIGNIFICANCE: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H2S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential ther-apeutic significance for these diseases. RECENT ADVANCES: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, mus-cle contraction under high fever, arthritis, and disc herniation, can be alleviated by sup-plementing H2S. H2S may be conducive to the development of multiple myeloma. The mechanism of H2S effect on the musculoskeletal system has been elucidated. A variety of H2S donors and nano-delivery systems provide prospects for H2S-based therapies. CRITICAL ISSUES: Related research remains at the level of cell or animal experiments, and clinical research is lacking. The role of H2S in more musculoskeletal disorders remains largely unknown. The importance of musculoskeletal diseases has not been widely con-cerned. Targeted delivery of H2S remains a challenging task. FUTURE DIRECTION: Develop therapeutic drugs for musculoskeletal diseases based on H2S and test their safety, efficacy, and tolerance. Explore the combination of current musculo-skeletal disease drugs with H2S releasing components to improve efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use.

RESUMEN

Hydrogen sulfide (H2S), an endogenous gasotransmitter, plays a key role in several critical physiological and pathological processes in vivo, including vasodilation, anti-infection, anti-tumor, anti-inflammation, and angiogenesis. In colorectal cancer (CRC), aberrant overexpression of H2S-producing enzymes has been observed. Due to the important role of H2S in the proliferation, growth, and death of cancer cells, H2S can serve as a potential target for cancer therapy. In this review, we thoroughly analyzed the underlying mechanism of action of H2S in CRC from the following aspects: the synthesis and catabolism of H2S in CRC cells and its effect on cell signal transduction pathways; the inhibition effects of exogenous H2S donors with different concentrations on the growth of CRC cells and the underlying mechanism of H2S in garlic and other natural products. Furthermore, we elucidate the expression characteristics of H2S in CRC and construct a comprehensive H2S-related signaling pathway network, which has important basic and practical significance for promoting the clinical research of H2S-related drugs.

RESUMEN

Microbial seed coatings serve as effective, labor-saving, and ecofriendly means of controlling soil-borne plant diseases. However, the survival of microbial agents on seed surfaces and in the rhizosphere remains a crucial challenge. In this work, we embedded a biocontrol bacteria (Bacillus subtilis ZF71) in sodium alginate (SA)/pectin (PC) hydrogel as a seed coating agent to control Fusarium root rot in cucumber. The formula of SA/PC hydrogel was optimized with the highest coating uniformity of 90 % in cucumber seeds. SA/PC hydrogel was characterized using rheological, gel content, and water content tests, thermal gravimetric analysis, and Fourier transform infrared spectroscopy. Bacillus subtilis ZF71 within the SA/PC hydrogel network formed a biofilm-like structure with a high viable cell content (8.30 log CFU/seed). After 37 days of storage, there was still a high number of Bacillus subtilis ZF71 cells (7.23 log CFU/seed) surviving on the surface of cucumber seeds. Pot experiments revealed a higher control efficiency against Fusarium root rot in ZF71-SA/PC cucumber seeds (53.26 %) compared with roots irrigated with a ZF71 suspension. Overall, this study introduced a promising microbial seed coating strategy based on biofilm formation that improved performance against soil-borne plant diseases.

RESUMEN

The mutual regulation between hydrogen sulfide (H2S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H2S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H2S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H2S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H2S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H2S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H2S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.

RESUMEN

Background: As hypertensive heart disease (HHD) presents a significant public health challenge globally, we analysed its global, regional, and national burdens and trends from 1990 to 2019. Methods: We used data from the Global Burden of Disease (GBD) 2019 study, focussing on the age-standardised prevalence rates (ASPRs) of HHD prevalence, age-standardised disability-adjusted life year (DALY) rates, average annual percentage change (AAPC), and risk factor attributions. We compared the HHD burden across sociodemographic index (SDI) strata, gender, age groups, and 204 countries and territories. Results: In 2019, the global prevalence of HHD was estimated at 18 598 thousand cases, with DALYs reaching 21 508 thousand. From 1990 to 2019, the ASPRs increased (AAPC = 0.21; 95% confidence interval (CI) = 0.17, 0.24), while the age-standardised DALY rates decreased (AAPC = -0.45; 95% CI = -1.23, -0.93). We observed the highest increase in ASPRs in high-middle SDI quantile countries, and an overall negative correlation between age-standardised DALY rates and SDI. Individuals above 70 years of age were the most affected, particularly elderly women. There has been a significant increase in HHD burden attributed to high body mass index (BMI) since 1990. The burden of HHD is concentrated in the middle SDI quintile, with population ageing and growth being major drivers for the increase in DALYs. We identified opportunities for reducing age-standardised DALY rates in the middle SDI quintile or lower. Conclusion: Despite a declining trend in the age-standardised DALY rates, the ASPRs of HHD continue to rise, especially in high-middle SDI regions. Meanwhile, countries in middle and lower SDI quintiles face a higher burden of age-standardised DALY rates. Targeted attention towards elderly women and controlling high BMI, alongside enhancing hypertension and HHD management awareness, is crucial for reducing the global burden of HHD.

Asunto(s)

Años de Vida Ajustados por Discapacidad , Carga Global de Enfermedades , Salud Global , Hipertensión , Humanos , Carga Global de Enfermedades/tendencias , Femenino , Masculino , Prevalencia , Hipertensión/epidemiología , Salud Global/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Adulto , Cardiopatías/epidemiología , Factores de Riesgo , Anciano de 80 o más Años , Años de Vida Ajustados por Calidad de Vida , Adulto Joven

RESUMEN

Air pollution, particularly fine particulate matter and gaseous pollutants including NO2 and NOx, presents significant public health challenges. While the harmful effects of these pollutants are well-documented, the molecular mechanisms underlying their impact on health remain incompletely understood. In this study, we utilized genome-wide association study (GWAS) data from the UK Biobank, expression quantitative trait loci (eQTL) data from the Genotype-Tissue Expression (GTEx) project, and protein quantitative trait loci (pQTL) data from the Atherosclerosis Risk in Communities (ARIC) study to conduct comprehensive analyses using the Unified Test for Molecular Signatures (UTMOST), Transcriptome-wide Association Studies (TWAS), and Proteome-wide Association Studies (PWAS). To integrate and synthesize these analyses, we developed the AirSigOmniTWP Hub, a specialized platform designed to consolidate and interpret the results from UTMOST, TWAS, and PWAS. TWAS analysis identified a significant association between PM10 exposure and the gene INO80E in females (P = 4.37×10⁻5, FDR = 0.0383), suggesting a potential role in chromatin remodeling. PWAS analysis revealed a significant association between NOx exposure and the gene PIP in females (P = 2.28×10⁻5, FDR = 0.0299), implicating its involvement in inflammatory pathways. Additionally, UTMOST analyses uncovered significant associations between various pollutants and genes including NCOA4P3 and SPATS2L with PM2.5 exposure, indicating potential mechanisms related to transcriptional regulation and gene-environment interactions.

RESUMEN

OBJECTIVES: To investigate whether high concentration iodinated contrast media (CM), compared with low concentration CM, could reduce pain and discomfort levels in patients who had level II and III venous conditions. METHODS: This prospective, single-center study enrolled patients who had level II and III venous conditions and underwent abdominal contrast-enhanced CT scan between July 2021 and February 2022. The venous condition to establish peripheral venous access for CM injection was graded using the Intravenous Access Scoring system, of which level II and III indicated poor venous condition and difficult venous access. Patients received iomeprol 400 in high concentration group and ioversol 320 in low group at an identical iodine delivery rate of 1.12 gI/s. The primary outcomes were pain and comfort levels. The secondary outcomes included adverse events and image quality. Patients rated pain intensity via Numerical Rating Scale and comfort level via Visual Analogue Scale with higher scores indicating higher levels of pain and discomfort. Quantitative and qualitative image assessment were compared between two groups. Continuous variables were compared using Student's t test or Mann-Whitney U test. Categorical variables were compared using χ2 test, χ2 test for trend or Fisher's exact test. RESULTS: A total of 206 patients (mean age, 60.13 ± 12.14 years; 81 males) were included with 99 in the high concentration group and 107 in the low concentration group. The high group had significantly lower pain scores (median 1 [IQR: 0-2] vs 2 (IQR 2-4), p < 0.001) and comfort scores (1 [IQR: 0-3] vs 3 [IQR: 2-5], p < 0.001) than the low group. Incidence of CM extravasation did not significantly differ (1.0 % vs 4.5 %, p = 0.214). No hypersensitivity reaction was observed. Qualitative assessment showed higher clarity scores of intrahepatic hepatic artery and portal vein in the high group. Quantitative assessment results were comparable between two groups. CONCLUSION: High concentration iodinated CM could lower pain intensity and improve comfort levels without comprising image quality of CT scan. High concentration CM is a preferable choice in patients with poor venous conditions during contrast-enhanced CT scan.

Asunto(s)

Medios de Contraste , Yopamidol , Dimensión del Dolor , Tomografía Computarizada por Rayos X , Humanos , Medios de Contraste/efectos adversos , Medios de Contraste/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Yopamidol/análogos & derivados , Yopamidol/administración & dosificación , Yopamidol/efectos adversos , Ácidos Triyodobenzoicos/efectos adversos , Ácidos Triyodobenzoicos/administración & dosificación , Anciano , Radiografía Abdominal/métodos , Dolor Abdominal/diagnóstico por imagen , Dolor Abdominal/prevención & control , Dolor Abdominal/inducido químicamente

RESUMEN

Chitosan, as a kind of naturally occurring green and degradable material for the preservation of perishable foods, was investigated in this study with the objective of enhancing its preservation performances. Herein, lignin was modified using the solvent fractionation method (modified lignin, ML, including ML1-ML3), while natural clinoptilolite zeolite was modified using the alkali modification method (modified clinoptilolite zeolite, MCZ, including MCZ1-MCZ5). After optimizing the conditions, it was discovered that incorporating both ML3 and MCZ3 into pure chitosan-based membranes might be conducive to fabricate chitosan-based composite membranes for the preservation of perishable foods. As-prepared composite membranes possessed better visible light transmittance, antioxidant activity, and carbon dioxide/oxygen selectivity, resulting in improved preservation effects on the model perishable foods such as bananas, cherry tomatoes, and cheeses. These findings might indicate promising applications for chitosan-based composite membranes with modified lignin and zeolite in the field of eco-friendly degradable materials for the preservation of perishable foods.

Asunto(s)

Quitosano , Conservación de Alimentos , Lignina , Zeolitas , Quitosano/química , Zeolitas/química , Lignina/química , Conservación de Alimentos/métodos , Conservación de Alimentos/instrumentación , Tecnología Química Verde , Queso/análisis , Antioxidantes/química , Solanum lycopersicum/química , Embalaje de Alimentos/instrumentación

RESUMEN

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Disulfuros , Glicoproteínas Hemaglutininas del Virus de la Influenza , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Anticuerpos Antivirales/inmunología , Ratones , Disulfuros/química , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Anticuerpos Neutralizantes/inmunología , Femenino , Protección Cruzada/inmunología , Reacciones Cruzadas , Humanos , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/virología , Epítopos/inmunología , Epítopos/genética , Epítopos/química , Multimerización de Proteína , Virus de la Influenza B/inmunología , Virus de la Influenza B/genética , Virus de la Influenza B/química

RESUMEN

Dry reforming of methane (DRM) to syngas is an important route to co-convert CH4 and CO2. However, the highly endothermic nature of DRM induces the thermocatalysis to commonly operate at high temperatures that inevitably causes coke deposition through pyrolysis of methane. Herein, benefiting from the mass spectrometric experiments complemented with quantum chemical calculations, we have discovered that the bimetallic oxide cluster Rh2CoO- can mediate the co-conversion of CH4 and CO2 at room temperature giving rise to two free H2 molecules and two adsorbed CO molecules (COads). The only elementary step requiring the input of external energy (e.g., high temperature) is desorption of COads from the reaction intermediate Rh2CoOC2O2-. The doping effect of Co has also been clarified that the Co could tune the charge distribution and orbital energy of the active metal Rh, enabling the enhancement of cluster reactivity toward C-H activation, which is essential to facilitating the DRM to syngas. This work not only underlines the importance of temperature control over elementary steps in practical thermocatalysis but also identifies a promising active species containing the late 3d transition metal to drive DRM to syngas. The findings could provide novel insights into design of bimetallic catalysts for co-conversion of CH4 and CO2 at low temperatures.

RESUMEN

Atomic oxygen radical anion (O•-) represents an important type of reactive centre that exists in both chemical and biological systems. Gas-phase atomic clusters can be studied under isolated and well controlled conditions. Studies of O•--containing clusters in the gas-phase provide a unique strategy to interpret the chemistry of O•- radicals at a strictly molecular level. This review summarizes the research progresses made since 2013 for the reactivity of O•- radicals in the atomically precise metal oxide clusters including negatively charged, nanosized, and neutral heteronuclear clusters benefitting from the development of advanced experimental techniques. New electronic and geometric factors to control the reactivity and product selectivity of O•- radicals under dark and photo-irradiation conditions have been revealed. The detailed mechanisms of O•- generation have been discussed for the reaction systems of nanosized and heteroatom-doped metal oxide clusters. The catalytic reactions mediated by the O•- radicals in metal clusters have also been successfully established and the microscopic mechanisms about the dynamic generation and depletion of O•- radicals have been clearly understood. The studies of O•- containing metal oxide clusters in the gas-phase provided new insights into the chemistry of reactive oxygen species in related condensed-phase systems.

RESUMEN

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.

Asunto(s)

Sulfuro de Hidrógeno , Enfermedades de la Piel , Sulfuro de Hidrógeno/metabolismo , Humanos , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/metabolismo , Animales , Piel/metabolismo

RESUMEN

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

RESUMEN

Studies investigating the relationship between dietary vitamin B1 intake and risk of Hyperuricemia (HU) are scarce, the present study aimed to examine the association of dietary vitamin B1 intake and HU among adults. This cross-sectional study included 5750 adults whose data derived from National Health and Nutrition Examination Survey (NHANES) from March 2017 to March 2020. The dietary intake of vitamin B1 was assessed using 24-h dietary recall interviews. The characteristics of study participants were grouped into five levels according to the levels of vitamin B1 quintile. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of HU, according to the vitamin B1 intake quintile for male and female separately. The dose-response relationship was determined by the restricted cubic spline (RCS). Smoothed curve fitting was used to assess serum uric acid concentration versus dietary vitamin B1 intake in the study population. The prevalence of hyperuricemia was 18.90% (20.15% and 17.79% for males and females, respectively) in the United States from March 2017 to March 2020. Multiple logistic regression analyses showed that in the male population, the HU ratio (OR) of vitamin B1 intake in Q2 to Q5 compared with the lowest quintile (Q1) was 0.75 (95% CI 0.52, 1.09), 0.70 (95% CI 0.48, 1.02), 0.66 (95% CI 0.44, 0.99) and 0.55 (95% CI 0.34, 0.90). The P for trend was 0.028. In women, the ORs for vitamin B1 intake Q2 to Q5 were 0.87 (95% CI 0.64, 1.19), 0.97 (0.68-1.38), 1.05 (0.69-1.60) and 0.75 (0.42-1.34), respectively. The P for trend was 0.876. The RCS curve revealed a linear relationship between vitamin B1 intake and the risk of hyperuricemia in men (P nonlinear = 0.401). Smoothed curve fitting demonstrated a negative association between vitamin B1 intake and serum uric acid concentration in men, whereas there was no significant association between dietary vitamin B1 intake and the risk of hyperuricemia in women. In the US adult population, dietary vitamin B1 intake was negatively associated with hyperuricemia in males.

Asunto(s)

Hiperuricemia , Encuestas Nutricionales , Tiamina , Ácido Úrico , Humanos , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Hiperuricemia/etiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , Ácido Úrico/sangre , Tiamina/administración & dosificación , Tiamina/sangre , Prevalencia , Dieta , Oportunidad Relativa , Factores de Riesgo , Anciano , Estados Unidos/epidemiología

RESUMEN

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Asunto(s)

Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Xantenos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Xantenos/síntesis química , Xantenos/farmacología , Xantenos/química , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Descubrimiento de Drogas , Estructura Molecular