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1.
Lancet Respir Med ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39059398

RESUMEN

BACKGROUND: Currently approved targeted treatment for ROS1-rearranged non-small-cell lung cancer (NSCLC) has either inadequate intracranial activity or CNS-related toxicities. We evaluated the efficacy and safety of foritinib, a novel ALK and ROS1 inhibitor, in patients with advanced ROS1-rearranged NSCLC. METHODS: This two-part (phase 2a and 2b), multicentre, single-arm, open-label, phase 2 study was done in 29 centres in China. Eligible participants were adults (aged ≥18 years) with histologically or cytologically confirmed ROS1-rearranged, locally advanced or metastatic stage IIIB-IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 2 or less. Patients who had previously received no or one ROS1 inhibitor were enrolled into phase 2a, and patients who were naive to ROS1 inhibitor therapy were enrolled into phase 2b cohort 1. Participants in phase 2a received 80, 120, 160, or 210 mg foritinib succinate (foritinib) orally once daily over 21-day cycles; patients in phase 2b received the recommended phase 2 dose of 160 mg. The primary endpoint was objective response rate, assessed by the independent review committee in the full analysis set (ie, all participants who received at least one dose of study treatment). The safety analysis set included all participants who received at least one dose of study treatment and had available safety assessments. This study is ongoing and is registered with ClinicalTrials.gov, NCT04237805. FINDINGS: Between March 26, 2020, and Dec 29, 2022, 104 patients were enrolled and treated. Six patients who had previously received more than one ROS1 inhibitor were enrolled in phase 2a before a protocol amendment stating that patients in this phase should have received no more than one ROS1 inhibitor; these patients were included in the safety analysis but excluded from the efficacy analysis of the ROS1-inhibitor-pretreated cohort. Therefore, the efficacy analysis set (n=98) included 42 patients from phase 2a (17 who were ROS1 inhibitor naive and 25 who had previously received ROS1 inhibitor) and 56 patients from phase 2b cohort 1. In phase 2a, the objective response rate was 94% (95% CI 71-100; 16 of 17 patients) in patients who were ROS1 inhibitor naive and 40% (21-61; ten of 25) in patients who had previously received ROS1 inhibitor. In phase 2b cohort 1, the objective response rate was 88% (95% CI 76-95; 49 of 56 patients). In a prespecified exploratory analysis in 41 patients with CNS metastases at baseline, the objective response rate was 100% (95% CI 48-100; five of five patients) in patients in phase 2a who were ROS1 inhibitor naive, 40% (16-68; six of 15) in patients in phase 2a who had previously received ROS1 inhibitor, and 90% (70-99; 19 of 21) in patients in phase 2b cohort 1. Grade 3-4 treatment-related adverse events occurred in 33 (32%) of 104 patients; the most common were hyperglycaemia (12 [12%] patients) and electrocardiogram prolonged QT interval (six [6%]). Serious treatment-related adverse events occurred in 11 (11%) patients, with hyperglycaemia (six [6%]) being most common. No treatment-related adverse events led to death. INTERPRETATION: Foritinib showed systemic and intracranial antitumour activity and good tolerability in ROS1-inhibitor-naive patients with ROS1-rearranged NSCLC. Foritinib represents a promising treatment for these patients, especially in those with CNS metastases. FUNDING: Fosun Pharma, Wanbang Biopharmaceuticals, and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer.

2.
Int J Surg ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963751

RESUMEN

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

3.
Angew Chem Int Ed Engl ; : e202412179, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990010

RESUMEN

Here, we report a strategy enabling triple switchable chemo-, regio-, and stereodivergence in newly developed palladium-catalyzed cycloadditions of allenes. An asymmetric pseudo-stereodivergent cycloaddition of allenes bearing a primary leaving group at the α-position, where a dynamic kinetic asymmetric hydroalkoxylation of racemic unactivated allenes was the enantio-determining step, is realized, providing four stereoisomers [(Z,R), (Z,S), (E,S), and (E,R)] containing a di-substituted alkene scaffold and a stereogenic center. By tuning reaction conditions, a mechanistically distinctive cycloaddition is uncovered selectively with the same set of substrates. By switching the position of the leaving group of allenes, a cycloaddition involving an intermolecular O-attack is disclosed. Diverse mechanisms of the cycloaddition reactions of allenes enable rapid access to structurally and stereochemically diverse 3,4-dihydro-2H-1,4-benzoxazines in high efficiency and selectivity.

4.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1007-1016, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621908

RESUMEN

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.


Asunto(s)
Proteína HMGB1 , Ligusticum , Osteoartritis , Humanos , Ratas , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Condrocitos , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacología , Dinoprostona , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Transducción de Señal , Inflamación/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Apoptosis , ARN Mensajero/metabolismo
5.
J Sci Food Agric ; 104(10): 5816-5825, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38406876

RESUMEN

BACKGROUND: The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis. RESULTS: The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1ß, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids. CONCLUSIONS: This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.


Asunto(s)
Colitis Ulcerosa , Microbioma Gastrointestinal , Lactobacillus plantarum , Limosilactobacillus fermentum , Probióticos , Animales , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/prevención & control , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Ratones , Probióticos/administración & dosificación , Probióticos/farmacología , Masculino , Humanos , Sulfato de Dextran/efectos adversos , Colon/microbiología , Colon/inmunología , Colon/patología , Mucosa Intestinal/microbiología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Ratones Endogámicos C57BL , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/inmunología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Mucina 2/metabolismo , Mucina 2/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Interferón gamma/metabolismo , Interferón gamma/genética , Interferón gamma/inmunología , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-1/genética , Modelos Animales de Enfermedad
6.
J Agric Food Chem ; 71(51): 20801-20814, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-37991826

RESUMEN

This study aims to explore the preventive effects and underlying mechanisms of Lactobacillus fermentum CKCC1858 (CKCC1), L. fermentum CKCC1369 (CKCC2), Lactobacillus plantarum CKCC1312 (CKCC3), and Lactobacillus gasseri CKCC1913 (CKCC4) on high-fat diet combined with streptozotocin (HFD/STZ)-stimulated type 2 diabetes (T2D) in mice. Generally, the results indicated that most of the four probiotics reduced weight loss and liver and pancreas damage, significantly (p < 0.05) improved glucose metabolism by regulating glucagon-like peptide-1 (GLP-1), fasting glucose and insulin levels, and increasing expression of glucose transporters. Probiotics improved hyperlipemia, inflammation, and oxidative stress by reducing the secretion of blood lipids and proinflammatory cytokines, increasing antioxidant enzymes. Metagenomic results revealed that probiotics restored gut microbiota via enhancing (reducing) the relative abundance of beneficial bacteria (harmful bacteria) and altered specific metabolic pathways in T2D mice. CKCC1, CKCC3, and CKCC4 showed excellent effects compared to CKCC2. These results indicated that probiotics potentially prevented T2D, which is strain-specific.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Probióticos , Ratones , Animales , Lactobacillus , Microbioma Gastrointestinal/fisiología , Inflamación , Glucosa , Dieta Alta en Grasa , Estrés Oxidativo , Homeostasis
7.
Food Funct ; 14(21): 9580-9590, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37823897

RESUMEN

To investigate the effect of probiotic Lactobacillus fermentum CKCC1858, LF on the prevention of hyperlipidemia and its correlation with gut microbiota, golden hamsters were fed a high-fat diet alone or in combination with the probiotic for 6 weeks. The results showed that the LF intervention alleviated HFD-induced hyperlipidemia and liver damage, as evidenced by the reduced serum lipid profile levels and liver function markers. More importantly, the LF intervention attenuated HFD-induced microbiota dysbiosis by enhancing the abundance of SCFA-producing bacteria and reshaping the metabolic functions of the gut microbiota, likely contributing to its pronounced preventive effects on hyperlipidemia. This study elucidated the mechanism of the preventive effect of probiotics on hyperlipidemia in terms of regulating gut microbiota, and provided suggestions for regulating gut microbiota through probiotic interventions to improve lipid metabolism.


Asunto(s)
Microbioma Gastrointestinal , Hiperlipidemias , Limosilactobacillus fermentum , Enfermedades Metabólicas , Cricetinae , Animales , Dieta Alta en Grasa/efectos adversos , Mesocricetus , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/etiología
8.
Chem Sci ; 14(39): 10812-10823, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37829037

RESUMEN

A class of prochiral allenylic di-electrophiles have been introduced for the first time as three-atom synthons in cycloadditions, and a new type of [4+3] cycloaddition involving transition metal-catalyzed enantioselective sequential allenylic substitution has been successfully developed, enabling challenging seven-membered exocyclic axially chiral allenes to be accessed in good yields with good enantioselectivity. Through the addition of a catalytic amount of ortho-aminoanilines or ortho-aminophenols, the racemization of the [4+3] cycloaddition products is effectively suppressed. Mechanistic studies reveal that elusive Pd-catalyzed enantioselective intramolecular allenylic substitution rather than intermolecular allenylic substitution is the enantio-determining step in this cycloaddition. By tuning the ligands, a Pd-catalyzed enantioselective desymmetric allenylic substitution leading to linear axially chiral tri-substituted allenes or a Pd-catalyzed tandem desymmetric allenylic substitution/ß-vinylic hydrogen elimination (formal enynylation) leading to multi-functionalized 1,3-enynes is achieved chemodivergently.

9.
Mediators Inflamm ; 2023: 5133505, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37840694

RESUMEN

Sepsis is one of the most severe complications and causes of mortality in the clinic. It remains a great challenge with no effective treatment for clinicians worldwide. Inhibiting the release of proinflammatory cytokines during sepsis is considered as an important strategy for treating sepsis and improving survival. In the present study, we have observed the effect of dimethyl fumarate (DMF) on lipopolysaccharide- (LPS-) induced sepsis and investigated the possible mechanism. By screening a subset of the Johns Hopkins Drug Library, we identified DMF as a novel inhibitor of nitric oxide synthesis in LPS-stimulated RAW264.7 cells, suggesting that DMF could be a potential drug to treat sepsis. To further characterize the effect of DMF on LPS signaling, TNF-α, MCP-1, G-CMF, and IL-6 expression levels were determined by using cytokine array panels. In addition, an endotoxemia model with C57BL/6 mice was used to assess the in vivo efficacy of DMF on sepsis. The survival rate was assessed, and HE staining was performed to investigate histopathological damage to the organs. DMF was found to increase the survival of septic mice by 50% and attenuate organ damage, consistent with the reduction in IL-10, IL-6, and TNF-α (inflammatory cytokines) in serum. In vitro experiments revealed DMF's inhibitory effect on the phosphorylation of p65, IκB, and IKK, suggesting that the primary inhibitory effects of DMF can be attributed, at least in part, to the inhibition of phosphorylation of IκBα, IKK as well as nuclear factor-κB (NF-κB) upon LPS stimulation. The findings demonstrate that DMF dramatically inhibits NO and proinflammatory cytokine production in response to LPS and improves survival in septic mice, raising the possibility that DMF has the potential to be repurposed as a new treatment of sepsis.


Asunto(s)
FN-kappa B , Sepsis , Ratones , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Dimetilfumarato/farmacología , Dimetilfumarato/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Ratones Endogámicos C57BL , Sepsis/inducido químicamente , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Citocinas/metabolismo
10.
Food Funct ; 14(18): 8504-8520, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37655696

RESUMEN

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder. Compared to drug interventions, probiotic interventions may have a more enduring effect without producing any side effects. Thus, the potential of probiotics as a therapeutic approach for diabetes and other metabolic disorders has gained increasing attention in recent years. In this study, we evaluated the therapeutic efficacy of Lactobacillus gasseri CKCC1913, a potential probiotic strain, in high-fat diet-induced insulin-resistant diabetes using the C57BL/6J mouse animal model. From the results, L. gasseri CKCC1913 has been shown to increase glucose tolerance, reduce fasting blood glucose levels in diabetic mice, and reduce the expression of pro-inflammatory cytokines, such as TNF-α and IL-6. Besides, L. gasseri CKCC1913 intervention effectively alleviated oxidative stress damage by increasing SOD activity, decreasing MDA levels, reducing insulin resistance, and improving dyslipidemia caused by diabetes. The potential mechanism of L. gasseri CKCC1913 in improving metabolic health and alleviating diabetes involves an increased abundance of beneficial bacteria, such as Parabacteroides merdae, which directly produce short-chain fatty acids that help regulate immune cells and reduce inflammation. SCFAs also enter the bloodstream and promote antioxidant enzyme activity in the liver, protecting against oxidative damage. Additionally, L. gasseri CKCC1913 influences local bacterial metabolism pathways, such as the superpathway of unsaturated fatty acid biosynthesis, leading to an increase in unsaturated fatty acids, increasing high-density lipoprotein cholesterol (HDL-C) levels and improving lipid metabolism and glucose control in diabetic mice. In summary, in this study, L. gasseri CKCC1913 and its potential impact on metabolic health highlight the promising potential of probiotics as a therapeutic approach for diabetes. Future research should focus on identifying the optimal dose and duration, investigating the long-term effects and mechanisms of action, and exploring the potential use of probiotics as an adjunct to other therapies or in preventing metabolic disorders.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Lactobacillus gasseri , Animales , Ratones , Ratones Endogámicos C57BL , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/terapia , Hígado , Antioxidantes
11.
J Glob Health ; 13: 06033, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37616126

RESUMEN

Background: Though the severe prevention and control measures faced by Chinese nurses had changed during the normalisation stage of the coronavirus 2019 (COVID-19) pandemic, they still worked under great stress. Due to a lack of related evidence, we aimed to investigate the prevalence and correlates of post-traumatic stress disorder (PTSD) among Chinese nurses during the normalisation of COVID-19 pandemic prevention and control measures. Methods: Using convenience sampling, we recruited 784 nurses in Jiangsu province, China to complete a survey via their mobile devices. We used a demographic questionnaire, the Perceived Social Support Scale, the Connor-Davidson Resilience Scale, the General Self-Efficacy Scale, and The Impact of Event Scale-Revised to collect data and applied binary logistic regression analysis to identify factors associated with PTSD. Results: The prevalence of PTSD was 26.4%. Married nurses were less likely to experience PTSD than unmarried ones (odds ratio (OR) = 0.573; 95% confidence interval (CI) = 0.33-0.99, P = 0.046). Social support (OR = 0.96; 95% CI = 0.94-0.98, P = 0.000) and resilience (OR = 0.98; 95% CI = 0.97-0.99, P = 0.004) were significant predictors of PTSD. Conclusions: PTSD remained prevalent among Chinese nurses as COVID-19 pandemic prevention and control measures became normalised, with an incidence rate of 26.4%. Resilience, social support, and marital status were factors associated with PTSD. Chinese hospital management must intervene to improve resilience and social support for nurses to reduce symptoms of PTSD.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/prevención & control , Pandemias/prevención & control , Prevalencia , COVID-19/epidemiología , COVID-19/prevención & control
12.
Nutrients ; 15(15)2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37571375

RESUMEN

BACKGROUND: Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. METHODS: We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. RESULTS: During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. CONCLUSION: Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.


Asunto(s)
Calcio , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Prospectivos , Bancos de Muestras Biológicas , Reino Unido/epidemiología , Factores de Riesgo
13.
Chemosphere ; 340: 139770, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37562505

RESUMEN

Globally, reducing carbon emissions and mitigating soil heavy metal pollution pose pressing challenges. We evaluated the effects of lead (Pb) and cadmium (Cd) contamination in the field over 20 years. The five treatment groups featured Pb concentrations of 40 and 250 mg/kg, Cd concentrations of 10 and 60 mg/kg, and a combination of Pb and Cd (60 and 20 mg/kg, respectively); we also included a pollution-free control group. After 20 years, soil pH decreased notably in all treatments, particularly by 1.02 in Cd10-treated soil. In addition to the increase of SOC in Cd10 and unchanged in Pb40 treatment, the SOC was reduced by 9.62%-12.98% under the other treatments. The α diversities of bacteria and fungi were significantly changed by Cd10 pollution (both p < 0.05) and the microbial community structure changed significantly. However, there were no significant changes in bacterial and fungal communities under other treatments. Cd10 pollution reduced the numbers of Ascomycota and Basidiomycota fungi, and enhanced SOC accumulation. Compared to the control, long-term heavy Cd, Pb, and Pb-Cd composite pollution caused SOC loss by increasing Basidiomycota which promoting carbon degradation, and decreasing Proteobacteria which promoting carbon fixation via the Krebs cycle. Our findings demonstrate that heavy metal pollution mediates Carbon-cycling microorganisms and genes, impacting SOC storage.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , Carbono/metabolismo , Suelo/química , Plomo/metabolismo , Metales Pesados/análisis , Hongos , Contaminantes del Suelo/análisis
14.
Diabetes Obes Metab ; 25(12): 3599-3610, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37643990

RESUMEN

AIMS: To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. MATERIALS AND METHODS: We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. CONCLUSIONS: Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.


Asunto(s)
Bancos de Muestras Biológicas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Hemoglobina Glucada , Estudios Prospectivos , Incidencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Reino Unido/epidemiología , Factores de Riesgo
15.
Front Microbiol ; 14: 1207482, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37577418

RESUMEN

Bats have a very long evolutionary history and are highly differentiated in their physiological functions. Results of recent studies suggest effects of some host factors (e.g., phylogeny and dietary habit) on their gut microbiota. In this study, we examined the gut microbial compositions of 18 different species of bats. Results showed that Firmicutes, Gammaproteobacteria, and Actinobacteria were dominant in all fecal samples of bats. However, the difference in the diversity of gut microbiota among bats of different phylogenies was notable (p = 0.06). Various species of Firmicutes, Actinobacteria, and Gammaproteobacteria were found to contribute to the majority of variations in gut microbiota of all bats examined, and Aeromonas species were much more abundant in bats that feed on both insects and fish than in those of insectivores. The abundance of various species of Clostridium, Euryarchaeota, and ancient bacterial phyla was found to vary among bats of different phylogenies, and various species of Vibrio varied significantly among bats with different dietary habits. No significant difference in the number of genes involved in various metabolic pathways was detected among bats of different phylogenies, but the abundance of genes involved in 5 metabolic pathways, including transcription; replication, recombination, and repair; amino acid transport and metabolism; and signal transduction mechanisms, was different among bats with different dietary habits. The abundance of genes in 3 metabolic pathways, including those involved in stilbenoid, diarylheptanoid, and gingerol biosynthesis, was found to be different between insectivorous bats and bats that feed on both insects and fish. Results of this study suggest a weak association between dietary habit and gut microbiota in most bats but a notable difference in gut microbiota among bats of different phylogenies.

16.
ACS Appl Mater Interfaces ; 15(28): 33605-33611, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37392426

RESUMEN

Silver chalcogenides demonstrate great potential as flexible thermoelectric materials due to their excellent ductility and tunable electrical and thermal transport properties. In this work, we report that the amorphous/crystalline phase ratio and thermoelectric properties of the Ag2SxTe1-x (x = 0.55-0.75) samples can be modified by altering the S content. The room-temperature power factor of the Ag2S0.55Te0.45 sample is 4.9 µW cm-1 K-2, and a higher power factor can be achieved by decreasing the carrier concentration as predicted by the single parabolic band model. The addition of a small amount of excessive Te into Ag2S0.55Te0.45 (Ag2S0.55Te0.45+y) not only enhances the power factor by decreasing the carrier concentration but also reduces the total thermal conductivity due to decreased electronic thermal conductivity. Owing to the effectively optimized carrier concentration, the thermoelectric power factor and dimensionless figure of merit zT of the sample with y = 0.007 reaches, respectively, 6.2 µW cm-1 K-2 and 0.39, while the excellent plastic deformability is well maintained, demonstrating its promising potential as a flexible thermoelectric material at room temperature.

17.
BMJ Open Respir Res ; 10(1)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37353234

RESUMEN

BACKGROUND: Low vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with COPD risk and survival. METHODS: We included 403 648 participants with serum 25(OH)D measurements and free of COPD at baseline from UK Biobank. Follow-up was until 30 September 2021. Multivariable-adjusted cox regression models were applied to estimate HRs and 95% CIs for the associations of season-standardised 25(OH)D concentrations with COPD risk and survival. The restricted cubic splines were used to assess dose-response relationship. Kaplan-Meier estimation was used to create graphs of the survival curves. RESULTS: During a median follow-up of 12.3 (IQR: 11.4-13.2) years, 11 008 cases of COPD were recorded. We observed a non-linear inverse association between 25(OH)D concentrations and COPD risk. Compared with participants in the fourth quintile of 25(OH)D, those in the lowest quintile were associated with a 23% higher risk (HR, 1.23; 95% CI, 1.16 to 1.31). Stronger associations were observed for the risk in men and current smokers (Both p for interaction <0.05). In survival analyses, compared with the fourth quintile, cases in the lowest quintile had a 38% higher risk for overall death (HR, 1.38; 95% CI, 1.22 to 1.56). CONCLUSION: Our findings indicate that serum 25(OH)D concentrations are non-linearly negatively associated with incidence and mortality of COPD, suggesting a potential protective role of vitamin D in the pathogenesis of COPD.


Asunto(s)
Bancos de Muestras Biológicas , Enfermedad Pulmonar Obstructiva Crónica , Masculino , Humanos , Estudios Prospectivos , Vitamina D , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Reino Unido/epidemiología
18.
Zookeys ; 1161: 129-141, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37234737

RESUMEN

The existence of Himalayan long-eared bats, Plecotushomochrous (Chiroptera, Vespertilionidae), in China has not been previously confirmed. In this study, four bats captured with harp traps from two sites in the Maoershan National Nature Reserve in Guangxi, China were investigated. These bats have long, wide auricles, each with a prominent tragus. The length of each auricle is about the same as that of a forearm. Hairs on the ventral fur have a dark base with mixed grey and yellowish tips; those on the dorsal fur also have a dark base and are bicolored with brown tips. The thumbs are very short. A concavity is present in the front of the dorsal side of the cranium. Based on morphological characteristics and phylogeny using Cyt b gene sequences, these bats were identified as P.homochrous, thus confirming the existence of Himalayan long-eared bats in China.

19.
Sci Rep ; 13(1): 8172, 2023 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-37210438

RESUMEN

Being overweight or obese is one of the public health concerns worldwide, and its prevalence is gradually increasing. Obesity has been proven to be associated with some cancers, including upper gastrointestinal cancer (UGC). However, studies on the prevalence of obesity among residents of areas at high risk of UGC in China are minimal. The aim of this study is to assess the prevalence of obesity and its influencing factors among people aged 40-69 years (high-risk population) in high-risk areas for UGC in Jiangsu Province, southeast China. This cross-sectional study involved 45,036 subjects aged 40-69 years identified in the Rural Early Diagnosis and Treatment of UGC Project database in Jiangsu Province from 2017 to 2021. Differences in prevalence across gender and age were assessed using the Chi-square test. Using a multinomial logistic regression model, we examined independent risk factors for overweight/obesity and their gender and age differences. The prevalence of overweight, obesity, and overweight/obesity varied based on the standards used: Chinese standard (42.1%, 11.9%, and 54.0%) and WHO standard (34.7%, 4.7%, and 39.4%), respectively. Being overweight was more common in men than women, while obesity was more common in women than men. Age of 50-59 years, married, household size of 7-9, drinking, soy products, pickled food, and hot food intake were positively associated with overweight/obesity. Females, 60-69 years, higher education level, household size of 4-6, annual family income of more than 60,000 CNY, smoking, and fresh fruit intake were negatively associated with overweight/obesity. Stratified analysis showed that the effects of age, education and meat, egg and dairy products on overweight/obesity were different across gender. The impact of fresh fruit and vegetables on overweight/obesity was also heterogeneous between the younger (40-59 years) and older (60-69 years) groups. In conclusion, the prevalence of overweight and obesity is high among adults aged 40-69 years from high-risk areas for UGC of Jiangsu Province, southeast China. Independent influencing factors of being overweight/obese included gender, age, marital status, education, household size, annual family income, smoking, drinking, fresh fruit, soy products, pickled food and hot food intake, and may vary by gender and age. Screening-based interventions should be considered to control obesity levels among screened participants. Besides, heterogeneity of influencing factors across subgroups could be focused on to improve intervention effectiveness.


Asunto(s)
Neoplasias Gastrointestinales , Sobrepeso , Adulto , Masculino , Humanos , Femenino , Sobrepeso/epidemiología , Sobrepeso/complicaciones , Prevalencia , Estudios Transversales , Obesidad/etiología , Factores de Riesgo , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/complicaciones , China/epidemiología
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