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1.
Artigo em Inglês | MEDLINE | ID: mdl-38955332

RESUMO

Stabilized and metallic light elements hydrides have provided a potential route to achieve the goal of room-temperature superconductors at moderate or ambient pressures. Here, we have performed systematic DFT theoretical calculations to examine the effects of different light elements C and N atoms doped in cubic K4B8H32hydrides on the superconductivity at low pressures. As a result of various atoms substituting, we have found that metallic K4B8-xMxH32(M = C, N) hydrides are dynamically stable at 50 GPa, band structures and density of states indicate that sizeableTccorrelates with a high B-H density of states at the Fermi level. With the increasing of B atoms in K4B8-xMxH32hydrides, the density of states values at Fermi level have been improved due to the delocalized electrons in B-H bonds, which result in strong electron-phonon coupling (EPC) interaction and increase theTcfrom 19.04 to 77.07 K for KC2H8and KB2H8at 50 GPa. The NH4unit in stable K4B7NH32hydrides has weakened the EPC and led to low Tc value of 21.47 K. Our results suggest the light elements hydrides KB2H8and K4B7CH32could estimate highTcvalues at 50 GPa, and the boron hydrides would be potential candidates to design or modulate hydrides superconductors with highTcat moderate or ambient pressures.

2.
Front Public Health ; 12: 1413604, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957204

RESUMO

Background: We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic. Methods: TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic. Results: A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%). Conclusion: The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic.


Assuntos
COVID-19 , Tuberculose , Humanos , COVID-19/mortalidade , Feminino , Pessoa de Meia-Idade , Masculino , Estados Unidos/epidemiologia , Adulto , Idoso , Tuberculose/mortalidade , Fatores Sexuais , Idoso de 80 Anos ou mais , Pandemias
3.
Physiol Plant ; 176(4): e14434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38981863

RESUMO

Anthocyanin is a type of plant secondary metabolite beneficial to human health. The anthocyanin content of vegetable and fruit crops signifies their nutritional quality. However, the molecular mechanism of anthocyanin accumulation, especially tissue-specific accumulation, in Caitai, as well as in other Brassica rapa varieties, remains elusive. In the present study, taking advantage of three kinds of Caitai cultivars with diverse colour traits between leaves and stems, we conducted a comparative transcriptome analysis and identified the molecular pathway of anthocyanin biosynthesis in Caitai leaves and stems, respectively. Our further investigations demonstrate that bHLH42, which is robustly induced by MeJA, closely correlates with tissue-specific accumulation of anthocyanins in Caitai; bHLH42 upregulates the expression of flavonoid/anthocyanin biosynthetic pathway genes to activate anthocyanin biosynthesis pathway, importantly, overexpression of bHLH42 significantly improves the anthocyanin content of Caitai. Our analysis convincingly suggests that bHLH42 induced by jasmonic acid signalling plays a crucial role in tissue-specific accumulation of anthocyanins in Caitai.


Assuntos
Acetatos , Antocianinas , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Ciclopentanos , Flavonoides , Regulação da Expressão Gênica de Plantas , Oxilipinas , Proteínas de Plantas , Antocianinas/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Flavonoides/metabolismo , Acetatos/metabolismo , Acetatos/farmacologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Reguladores de Crescimento de Plantas/metabolismo
4.
Acta Pharmacol Sin ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992121

RESUMO

Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

5.
ACS Nano ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976792

RESUMO

Hybrid-dimensional heterojunction transistor (HDHT) photodetectors (PDs) have achieved high responsivities but unfortunately are still with unacceptably slow response speeds. Here, we propose a MASnI3/MoS2 HDHT PD, which exhibits the possibility to obtain high responsivity and fast response simultaneously. By exploring the detailed photoelectric responses utilizing a precise optoelectronic coupling simulation, the electrical performance of the device is optimally manipulated and the underlying physical mechanisms are carefully clarified. Particularly, the influence and modulation characteristics of the trap effects on the carrier dynamics of the PDs are investigated. We find that the localized trap effect in perovskite, especially at its top surface, is primarily responsible for the high responsivity and long response time; moreover, it is normally hard to break such a responsivity-speed trade-off due to the inherent limitation of the trap effect. By synergistically coupling the photogating effect, trap effect, and gate regulation, we indicate that it is possible to achieve an enhancement of the responsivity-bandwidth product by about 3 orders of magnitude. This study facilitates a fine modulation of the responsivity-speed relationship of hybrid-dimensional PDs, enabling breaking the traditional responsivity-speed trade-off of many PDs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38973378

RESUMO

Per- and polyfluoroalkyl substances (PFASs), especially as emerging compounds, have been widely detected in coastal seawater. However, the awareness of the interaction between PFASs at environmental concentrations and marine diatoms is still limited. In this study, Skeletonema costatum was exposed to three co-existing PFASs, namely hexafluoropropylene oxide dimer acid (HFPO-DA), 6 : 2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES), and perfluoroethylcyclohexane sulfonate (PFECHS) (15-300 ng L-1 in total), for 14 days. In the 300 ng L-1 test group, the significant down-regulation of chlorophyllide a in porphyrin metabolism, light-harvesting capacity and carbon fixation were the main inhibitory mechanisms of photosynthesis by emerging PFASs at the 14th day compared to the 8th day, which indicated that they may have a shading effect on S. costatum. Additionally, mixed PFASs could also activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by up-regulating gene gp91 and down-regulating genes CaM4 and NDPK2 to generate excessive ROS. This resulted in a decrease in the algal biomass, which would further weaken the primary productivity of S. costatum. Our findings illustrated that mixed emerging PFASs at environmental concentrations may interfere with the carbon balance of marine diatoms.

8.
Foods ; 13(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38998500

RESUMO

Porphyromonas gingivalis is crucial for the pathogenesis of periodontitis. This research investigated the effects of the fruit-derived flavonoid phloretin and its analogs on the growth of pure P. gingivalis and the flora of P. gingivalis mixed with the symbiotic oral pathogens Fusobacterium nucleatum and Streptococcus mitis. The results showed that the tested flavonoids had little effect on the biofilm amount of pure P. gingivalis, but significantly reduced the biofilm amount of mixed flora to 83.6~89.1%. Biofilm viability decreased to 86.7~92.8% in both the pure- and mixed-bacterial groups after naringenin and phloretin treatments. SEM showed that phloretin and phlorizin displayed a similar and remarkable destructive effect on P. gingivalis and the mixed biofilms. Transcriptome analysis confirmed that biofilm formation was inhibited by these flavonoids, and phloretin significantly regulated the transcription of quorum sensing. Phlorizin and phloretin reduced AI-2 activity to 45.9% and 55.4%, respectively, independent of the regulation of related gene transcription. This research marks the first finding that these flavonoids possess anti-biofilm properties against P. gingivalis and its intricate bacterial community, and the observed performance variations, driven by structural differences, underscore the existence of intriguing structure-activity relationships.

9.
Biol Trace Elem Res ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012411

RESUMO

Cadmium (Cd) is a highly toxic heavy metal that can cause severe liver damage in both humans and animals. However, the specific genes responsible for Cd-induced hepatotoxicity are still not fully understood. Therefore, the aim of this study was to identify the key genes associated with Cd-induced liver damage. To achieve this, we utilized the GSE19662 dataset from the Gene Expression Omnibus (GEO), which consisted of rat hepatocyte samples treated with cadmium chloride (CdCl2) as well as control groups. By focusing on rat hepatocytes treated with 0.10 ppm of CdCl2, the study identified 851 differentially expressed genes (DEGs), with 438 genes being upregulated and 413 genes being downregulated. Gene Ontology (GO) analysis revealed that these DEGs were primarily involved in inflammatory responses, xenobiotic metabolic processes, and the response to drugs and xenobiotic stimuli. Finally, the study identified several hub genes, including CYP2E1, CYP3A62, CYP2C11, CYP2C13, CYP2B3, HSP90B1, HSP90AA1, GSTA2, and MAPK8, which were associated with CdCl2-induced liver damage. Furthermore, pathway analysis demonstrated that these hub genes were mainly linked to pathways involved in chemical carcinogenesis, metabolic processes, steroid hormone biosynthesis, retinol metabolism, linoleic acid metabolism, arachidonic acid metabolism, inflammatory mediator regulation, Ras, and protein processing in the endoplasmic reticulum. In conclusion, this study provides important insights into the molecular mechanisms underlying Cd-induced liver damage.

10.
Front Microbiol ; 15: 1428958, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993495

RESUMO

Starting in 2015, the widespread prevalence of hydropericardium-hepatitis syndrome (HHS) has led to considerable financial losses within China's poultry farming industry. In this study, pathogenicity assessments, whole-genome sequencing, and analyses were conducted on 10 new isolates of the novel genotype FAdV-4 during a HHS outbreak in Guangxi Province, China, from 2019 to 2020. The results indicated that strains GX2019-010 to GX2019-013 and GX2019-015 to GX2019-018 were highly virulent, while strain GX2020-019 exhibited moderate virulence. Strain GX2019-014 was characterized as a wild-type strain with low virulence, displaying no pathogenic effects when 0.5 mL containing 106 TCID50 virus was inoculated into the muscle of specific pathogen-free (SPF) chickens at 4 weeks of age, while 107 TCID50 and 108 TCID50 resulted in mortality rates of 80 and 100%, respectively. The whole genomes of strains GX2019-010 to GX2019-013, GX2019-015 to GX2019-018, and GX2020-019 showed high homology with other Chinese newly emerging highly pathogenic FAdV-4 strains, whereas GX2019-014 was closer to nonmutant strains and shared the same residues with known nonpathogenic strains (B1-7, KR5, and ON1) at positions 219AA and 380AA of the Fiber-2 protein. Our work enriches the research on prevalent strains of FAdV-4 in China, expands the knowledge on the virulence diversity of the novel genotype FAdV-4, and provides valuable reference material for further investigations into the key virulence-associated genetic loci of FAdV-4.

11.
Environ Sci Pollut Res Int ; 31(32): 44691-44716, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965108

RESUMO

Constructed wetland (CW), a promising, environmentally responsible, and effective green ecological treatment technology, is actively involved in the treatment of various forms of wastewater. Low temperatures will, however, lead to issues including plant dormancy, decreased microbial activity, and ice formation in CWs, which will influence how well CWs process wastewater. Applying CWs successfully and continuously in cold areas is extremely difficult. Therefore, it is crucial to find solutions for the pressing issue of increasing the CWs' ability to process wastewater at low temperatures. This review focuses on the effect of cold climate on CWs (plants, substrates, microorganisms, removal effect of pollutants). It meticulously outlines current strategies to enhance CWs' performance under low-temperature conditions, including modifications for the improvement and optimization of the internal components (i.e., plant and substrate selection, bio-augmentation) and enhancement of the external operation conditions of CWs (such as process combination, effluent recirculation, aeration, heat preservation, and operation parameter optimization). Finally, future perspectives on potential research directions and technological innovations that could strengthen CWs' performance in cold climates are prospected. This review aims to contribute valuable insights into the operation strategies, widespread implementation, and subsequent study of CWs in colder climate regions.


Assuntos
Clima Frio , Áreas Alagadas , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Temperatura Baixa
12.
Front Vet Sci ; 11: 1419312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015104

RESUMO

H5, H7, and H9 are pivotal avian influenza virus (AIV) subtypes that cause substantial economic losses and pose potential threats to public health worldwide. In this study, a novel triplex fluorescence reverse transcription-loop-mediated isothermal amplification (TLAMP) assay was developed in which traditional LAMP techniques were combined with probes for detection. Through this innovative approach, H5, H7, and H9 subtypes of AIV can be simultaneously identified and differentiated, thereby offering crucial technical support for prevention and control efforts. Three primer sets and composite probes were designed based on conserved regions of the haemagglutinin gene for each subtype. The probes were labelled with distinct fluorophores at their 3' ends, which were detached to release the fluorescence signal during the amplification process. The detection results were interpreted based on the colour of the TLAMP products. Then, the reaction conditions were optimized, and three primer sets and probes were combined in the same reaction system, resulting in a TLAMP detection assay for the differential diagnosis of AIV subtypes. Sensitivity testing with in vitro-transcribed RNA revealed that the detection limit of the TLAMP assay was 205 copies per reaction for H5, 360 copies for H7, and 545 copies for H9. The TLAMP assay demonstrated excellent specificity, no cross-reactivity with related avian viruses, and 100% consistency with a previously published quantitative polymerase chain reaction (qPCR) assay. Therefore, due to its simplicity, rapidity, sensitivity, and specificity, this TLAMP assay is suitable for epidemiological investigations and is a valuable tool for detecting and distinguishing H5, H7, and H9 subtypes of AIV in clinical samples.

13.
Bot Stud ; 65(1): 15, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967711

RESUMO

Quinoa (Chenopodium quinoa, 2n = 4x = 36), a super pseudocereal crop, has been introduced into China nearly 60 years. Many excellent varieties have been developed through massive selection; however, few are developed through mutagenesis breeding. In this study, the 'Longli-4' variety, locally cultivated in Gansu province, Northwest China, was selected for experimentation. The grains of 'Longli-4' were treated with ethyl methanesulfonate (EMS) at a concentration of 0.8% for 8 h. Nine plants from independent M2 families were randomly selected to investigate the mutagenesis effect of EMS on the quinoa genome. The results indicated that the single nucleotide polymorphisms (SNPs) induced by EMS were unevenly distributed across all 18 chromosomes, with an average mutation frequency of 91.2 SNPs/Mb, ranging from 4.5 to 203.5 SNPs/Mb. A significant positive correlation between the number of SNPs and chromosome length was identified through linear model analysis. Transitions from G/C to A/T were the most predominated in all variant categories, accounting for 34.4-67.2% of the mutations, and SNPs were significantly enriched in intergenic regions, representing 69.2-75.1% of the total mutations. This study provides empirical support for the application of low concentration EMS treatment in quinoa breeding.

14.
Endocrine ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824220

RESUMO

Male cases diagnosed COVID-19 with more complications and higher mortality compared with females, and the overall consequences of male sex hormones and semen parameters deterioration were observed in COVID-19 patients, whereas the involvement and mechanism for spermatogenic cell remains unclear. The study was aimed to investigate the infection mode of S protein (D614G) pseudovirus (pseu-S-D614G) to spermatogenic cells, as well as the influence on cell growth. Both mouse spermatogonia (GC-1 cell, immortalized spermatogonia) and spermatocyte (GC-2 cell, immortalized spermatocytes) were used to detect the infection of pseu-S-D614G of SARS-CoV-2, and further explored the effect of SARS-CoV-2-spike protein (S-protein) and SARS-CoV-2-spike protein (omicron) (O-protein) on GC-1 cell apoptosis and proliferation. The data showed that the pseu-S-D614G invaded into GC-1 cells through either human ACE2 (hACE2) or human CD147 (hCD147), whereas GC-2 cells were insensitive to viral infection. In addition, the apoptosis and proliferation suppression inflicted by S-protein and O-protein on GC-1 cells was through Bax-Caspase3 signaling rather than arresting cell cycle progression. These findings suggest that CD147, apart from ACE2, may be a potential receptor for SARS-CoV-2 infection in testicular tissues, and that the apoptotic effect was induced in spermatogonia cells by S-protein or O-protein, eventually resulted in the damage to male fertility.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38824476

RESUMO

This study aimed to investigate the cross-sectional associations between regional Alzheimer's disease (AD) biomarkers, including tau, ß-amyloid (Aß), and brain volume, within the Papez circuit, and neuropsychological functioning across the preclinical and clinical spectrum of AD. We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 251 Aß-positive participants. Participants were categorized into three groups based on the Clinical Dementia Rating (CDR): 73 individuals with preclinical AD (CDR = 0), 114 with prodromal AD (CDR = 0.5), and 64 with clinical AD dementia (CDR ≥ 1). Linear regression analyses, adjusted for age, gender, and education years, were employed to evaluate the associations between five regions of interest (the hippocampus, para-hippocampus, entorhinal cortex, posterior cingulate cortex, and thalamus) and five neuropsychological tests across the three imaging modalities. In the preclinical stage of AD, flortaucipir PET was associated with impaired global cognition and episodic memory (range standardized ß = 0.255-0.498, p < 0.05 corrected for multiple comparisons), while florbetapir PET and brain volume were marginally related to global cognition (range standardized ß = 0.221-0.231, p < 0.05). In the clinical stages of AD (prodromal and dementia), both increased flortaucipir uptake and decreased brain volume were significantly associated with poorer global neuropsychological and episodic memory performance (range standardized ß = 0.222-0.621, p < 0.05, most regions of interest survived correction for multiple comparisions). However, a slight relationship was observed between florbetapir uptake and poorer global cognitive function. The regions most affected by flortaucipir PET were the hippocampus, para-hippocampus, and posterior cingulate cortex. During the clinical stages, the hippocampus and entorhinal cortex exhibited the most significant volumetric changes. Tau PET and brain volume measurements within the Papez circuit are more sensitive indicators of early cognitive deficits in AD than Aß PET. Furthermore, during the clinical stages of AD, both flortaucipir PET and brain volume of the Papez circuit are closely correlated with cognitive decline. These findings underscore the importance of integrating multiple biomarkers for the comprehensive evaluation of AD pathology and its impact on cognition.

16.
Sci Rep ; 14(1): 12679, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830880

RESUMO

With the rapid development of imaging technology and comprehensive treatment in modern medicine, the early diagnosis rate of breast cancer is constantly improving, and the prognosis is also improving; As breast cancer patients survive longer, the risk of developing second primary cancers increases. Since both breast and thyroid are Hormone receptor sensitive organs, which are regulated by hypothalamus pituitary target gland endocrine axis, changes in body endocrine status may lead to the occurrence of these two diseases in succession or simultaneously. This study extracted clinical data and survival outcomes of breast cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2019. After matching the case and controls with propensity scores, the selected patients were randomly split into training and test datasets at a ratio of 7:3. Univariate and multivariate COX proportional regression analysis is used to determine independent risk factors for secondary thyroid cancer and construct a column chart prediction model. Age, ethnicity, whether radiotherapy, tumor primary location, N stage, M stage were identified by Cox regression as independent factors affecting secondary thyroid cancer in patients with breast cancer patients, and a risk factor nomogram was established to predict patients' 3 and 5 year survival probabilities. The AUC values for 3 and 5 years in the training set were 0.713, 0.707, and the c-index was 0.693 (95% CI 0.67144, 0.71456), and the AUC values for 3 and 5 years in the validation set were 0.681, 0.681, and the c-index was 0.673 (95% CI 0.64164, 0.70436), respectively.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Pontuação de Propensão , Programa de SEER , Neoplasias da Glândula Tireoide , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Segunda Neoplasia Primária/epidemiologia , Idoso , Adulto , Nomogramas , Prognóstico , Modelos de Riscos Proporcionais
17.
Water Res ; 260: 121944, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38909422

RESUMO

The surface microlayer (SML) is an important air water interface layer, known as the skin of the ocean, which has chemical enrichment properties. Chemical enrichment in the SML can affect the occurrence of pollutants in the underlying water and air samples. Although the enrichment of per- and polyfluorinated substances (PFAS), a class of persistent organic pollutants of high concern, has been reported in the SML, information on the behavior of unknown PFAA-precursors in SML is lacked, and it is not clear whether there is a similar PFAS enrichment in suspended particulate matter (SPM) in the SML. Therefore, to investigate these questions, we conducted a systematic survey of 24 PFAS in 11 paired water and SPM samples from the SML and underlying water (U50cm and U2m) from the Duliujian River, which flows to the Bohai sea in Tianjin, China. The ∑PFAS mean concentrations in the water and SPM samples were 38.2 ng/L and 64.6 ng/g dw, respectively. The PFAS concentrations of PFAS in the SML were higher than those in the underlying water, and the enrichment factors (EFs) were greater in the SPM than that in the water. The long-chain PFAS EFs were greater than those for short-chain PFAS, indicating that the EFs were positively correlated with the hydrophobicity. Moreover, by applying the total oxidizable precursor (TOP) assay, the unknown PFAA-precursors (C5-C12) in the water and SPM contributed 11.4∼86.4 mol% and 7.1∼88.0 mol% to total PFAS, respectively. The ecological risk of the targeted PFAS in the SML was relatively higher than that in the underlying water, indicating that PFAS in the SML require more attention. Preliminary estimates indicate that the PFAS-enriched SML is an important exposure route that poses a potential risk to wildlife in rivers and oceans.

18.
Acta Diabetol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831202

RESUMO

AIM: Liver fibrosis (LF) is a common complication of diabetes mellitus (DM). Studies have found that vitamin D (VD), as a modifiable factor has been reported to be associated with LF. The relationship between serum VD concentration and LF in DM patients has rarely been reported. The aim of this study was to assess the association between serum VD concentration and LF in DM patients. METHODS: In this cross-sectional study, data of DM patients aged ≥ 45 years were extracted from the National Health and Nutrition Examination Survey (NHANES 2017-2018). Serum VD concentration was measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Vibration controlled transient elastography (VCTE) was used to measure liver stiffness. Covariates included sociodemographic information, lifestyles, laboratory data, diseases history were extracted from the database. The weighted univariable and multivariable logistic regression models were utilized to explore the association between serum VD concentration and LF in DM patients, and were described as odds ratio (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on BMI, liver steatosis, hypertension and dyslipidemia were further assessed the association. RESULTS: A total of 799 patients were included, of which 188 (23.53%) had LF. Higher serum VD concentration was associated with the lower odds of LF (OR = 0.33, 95% CI 0.19-0.59) and advanced LF (OR = 0.31, 95% CI 0.17-0.55) in DM patients after adjustment for race, liver steatosis, BMI, smoking, drinking, AST, ALT and physical activity, especially in patients with liver steatosis (OR = 0.28, 95% CI 0.13-0.59) and dyslipidemia (OR = 0.31, 95% CI 0.14-0.66), respectively. CONCLUSIONS: High serum VD concentration may have a potential benefit for maintain the liver health in DM patients.

19.
Chem Sci ; 15(22): 8311-8322, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38846391

RESUMO

Drug resistance in tumor cells remains a persistent clinical challenge in the pursuit of effective anticancer therapy. XIAP, a member of the inhibitor of apoptosis protein (IAP) family, suppresses apoptosis via its Baculovirus IAP Repeat (BIR) domains and is responsible for drug resistance in various human cancers. Therefore, XIAP has attracted significant attention as a potential therapeutic target. However, no XIAP inhibitor is available for clinical use to date. In this study, we surprisingly observed that arsenic trioxide (ATO) induced a rapid depletion of XIAP in different cancer cells. Mechanistic studies revealed that arsenic attacked the cysteine residues of BIR domains and directly bound to XIAP, resulting in the release of zinc ions from this protein. Arsenic-XIAP binding suppressed the normal anti-apoptosis functions of BIR domains, and led to the ubiquitination-dependent degradation of XIAP. Importantly, we further demonstrate that arsenic sensitized a variety of apoptosis-resistant cancer cells, including patient-derived colon cancer organoids, to the chemotherapy drug using cisplatin as a showcase. These findings suggest that targeting XIAP with ATO offers an attractive strategy for combating apoptosis-resistant cancers in clinical practice.

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