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1.
Nature ; 615(7950): 87-93, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36859582

RESUMO

Water resources sustainability in High Mountain Asia (HMA) surrounding the Tibetan Plateau (TP)-known as Asia's water tower-has triggered widespread concerns because HMA protects millions of people against water stress1,2. However, the mechanisms behind the heterogeneous trends observed in terrestrial water storage (TWS) over the TP remain poorly understood. Here we use a Lagrangian particle dispersion model and satellite observations to attribute about 1 Gt of monthly TWS decline in the southern TP during 2003-2016 to westerlies-carried deficit in precipitation minus evaporation (PME) from the southeast North Atlantic. We further show that HMA blocks the propagation of PME deficit into the central TP, causing a monthly TWS increase by about 0.5 Gt. Furthermore, warming-induced snow and glacial melt as well as drying-induced TWS depletion in HMA weaken the blocking of HMA's mountains, causing persistent northward expansion of the TP's TWS deficit since 2009. Future projections under two emissions scenarios verified by satellite observations during 2020-2021 indicate that, by the end of the twenty-first century, up to 84% (for scenario SSP245) and 97% (for scenario SSP585) of the TP could be afflicted by TWS deficits. Our findings indicate a trajectory towards unsustainable water systems in HMA that could exacerbate downstream water stress.


Assuntos
Altitude , Mudança Climática , Dessecação , Previsões , Abastecimento de Água , Humanos , Ásia , Mudança Climática/estatística & dados numéricos , Abastecimento de Água/estatística & dados numéricos , Tibet , Congelamento , Neve , Imagens de Satélites , Chuva , Oceano Atlântico , Camada de Gelo , Conservação dos Recursos Hídricos
2.
Planta ; 259(3): 62, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319463

RESUMO

MAIN CONCLUSION: The operation of 8HGO-ISY fusion enzymes can increase nepetalactol flux to iridoid biosynthesis, and the Gj8HGO-CrISY expression in Gardenia jasminoides indicates that seco-iridoids and closed-ring iridoids share a nepetalactol pool. Nepetalactol is a common precursor of (seco)iridoids and their derivatives, which are a group of noncanonical monoterpenes. Functional characterization of an 8HGO (8-hydroxygeraniol oxidoreductase) from Catharanthus roseus, a seco-iridoids producing plant, has been reported; however, the 8HGO from G. jasminoides with plenty of closed-ring iridoids remains uninvestigated. In this work, a Gj8HGO was cloned and biochemically characterized. In addition, the relatively low production of nepetalactol in plants and engineered microbial host is likely to be attributed to the fact that Cr8HGO and CrISY (iridoid synthase) are substrate-promiscuous enzymes catalyzing unexpected substrates to the undesired products. Herein, a bifunctional enzyme consisting of an 8HGO fused to an ISY was designed for the proximity to the substrate and recycling of NADP+ and NADPH cofactor to reduce the undesired intermediate in the synthesis of nepetalactol. Of four fusion enzymes (i.e., Gj8HGO-GjISY, Gj8HGO-GjISY2, Gj8HGO-GjISY4, and Gj8HGO-CrISY), interestingly, only the last one can enable cascade reaction to form cis-trans-nepetalactol. Furthermore, we establish a reliable Agrobacterium-mediated transformation system. The expression of Gj8HGO-CrISY in G. jasminoides led to a significant enhancement of nepetalactol production, about 19-fold higher than that in wild-type plants, which further resulted in the twofold to fivefold increase of total iridoids and representative iridoid such as geniposide, indicating that seco-iridoids in C. roseus and closed-ring iridoids in G. jasminoides share a nepetalactol pool. All results suggest that 8HGO and ISY can be manipulated to maximize metabolic flux for nepetalactol and iridoid production.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Catharanthus , Gardenia , Terpenos , Oxirredutases , Catharanthus/genética , Iridoides
3.
J Transl Med ; 22(1): 326, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566102

RESUMO

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Imunoterapia , Receptores ErbB/genética , Antibacterianos/uso terapêutico
4.
J Org Chem ; 89(5): 2885-2894, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38355424

RESUMO

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve. Herein, nickel-catalyzed reductive cross-coupling reactions between propargyl acetates and substituted vinyl chlorosilanes for the synthesis of tetrasubstituted silylallenes are described. Therein, metallic zinc is a crucial reductant that effectively enables two electrophilic reagents to selectively construct C(sp2)-Si bonds. Additionally, a Ni-catalyzed reductive mechanism involving a radical process is proposed on the basis of deuteration-labeled experiments.

5.
J Org Chem ; 89(1): 281-290, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38109762

RESUMO

A visible-light-driven photoredox dialkylation of styrenes with α-carbonyl alkyl bromides and pyridin-1-ium salts for the synthesis of polysubstituted 1,4-dihydropyridines is reported. This reaction enables the formation of two new C(sp3)-C(sp3) bonds in a single reaction step and provides a strategy that employs pyridin-1-ium salts as the functionalized alkylating reagents via dearomatization to directly trap the resulting alkyl radicals from radical addition of alkenes and then terminate the alkene dialkylation.

6.
Arterioscler Thromb Vasc Biol ; 43(8): e303-e322, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37199156

RESUMO

BACKGROUND: Numerous genome-wide association studies revealed that SNPs (single nucleotide polymorphisms) at the PHACTR1 (phosphatase and actin regulator 1) locus strongly correlate with coronary artery disease. However, the biological function of PHACTR1 remains poorly understood. Here, we identified the proatherosclerotic effect of endothelial PHACTR1, contrary to macrophage PHACTR1. METHODS: We generated global (Phactr1-/-) and endothelial cell (EC)-specific (Phactr1ECKO) Phactr1 KO (knockout) mice and crossed these mice with apolipoprotein E-deficient (Apoe-/-) mice. Atherosclerosis was induced by feeding the high-fat/high-cholesterol diet for 12 weeks or partially ligating carotid arteries combined with a 2-week high-fat/high-cholesterol diet. PHACTR1 localization was identified by immunostaining of overexpressed PHACTR1 in human umbilical vein ECs exposed to different types of flow. The molecular function of endothelial PHACTR1 was explored by RNA sequencing using EC-enriched mRNA from global or EC-specific Phactr1 KO mice. Endothelial activation was evaluated in human umbilical vein ECs transfected with siRNA targeting PHACTR1 and in Phactr1ECKO mice after partial carotid ligation. RESULTS: Global or EC-specific Phactr1 deficiency significantly inhibited atherosclerosis in regions of disturbed flow. PHACTR1 was enriched in ECs and located in the nucleus of disturbed flow areas but shuttled to cytoplasm under laminar flow in vitro. RNA sequencing showed that endothelial Phactr1 depletion affected vascular function, and PPARγ (peroxisome proliferator-activated receptor gamma) was the top transcription factor regulating differentially expressed genes. PHACTR1 functioned as a PPARγ transcriptional corepressor by binding to PPARγ through the corepressor motifs. PPARγ activation protects against atherosclerosis by inhibiting endothelial activation. Consistently, PHACTR1 deficiency remarkably reduced endothelial activation induced by disturbed flow in vivo and in vitro. PPARγ antagonist GW9662 abolished the protective effects of Phactr1 KO on EC activation and atherosclerosis in vivo. CONCLUSIONS: Our results identified endothelial PHACTR1 as a novel PPARγ corepressor to promote atherosclerosis in disturbed flow regions. Endothelial PHACTR1 is a potential therapeutic target for atherosclerosis treatment.


Assuntos
Aterosclerose , PPAR gama , Animais , Humanos , Camundongos , Aterosclerose/metabolismo , Colesterol , Estudo de Associação Genômica Ampla , Camundongos Knockout , PPAR gama/genética
7.
Br J Nutr ; 131(4): 622-629, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-37772623

RESUMO

Systolic blood pressure (SBP) is significantly associated with body composition in children and adolescents. However, which one of the components of body composition is the dominant contributor to SBP in children and adolescents remains unclear. We, therefore, aimed to determine the dominant contributor to SBP among components of body composition in a large cohort of American children and adolescents derived from the National Health and Nutrition Examination Survey with cross-sectional analysis. In total, 13 618 children and adolescents (median age 13 years; 6107 girls) with available data on whole-body dual-emission X-ray absorptiometry measurements were included. Multiple linear regression showed that SBP was associated with higher total fat-free mass in boys (ß = 0·49, P < 0·001) and girls (ß = 0·47, P < 0·001) and with higher total fat mass only in boys (ß = 0·12, P < 0·001) after adjustment for covariates. When taking fat distribution into consideration, SBP was associated with higher trunk fat mass (boys: ß = 0·28, P < 0·001; girls: ß = 0·15, P < 0·001) but negatively associated with leg fat mass (Boys: ß = -0·14, P < 0·001; Girls: ß = -0·11, P < 0·001), in both boys and girls. Dominance analysis showed that total fat-free mass was the dominant contributor to SBP (boys: 49 %; girls: 55·3 %), followed by trunk fat mass (boys: 32·1 %; girls: 26·9 %); leg fat mass contributed the least to SBP in boys (18·9 %) and girls (17·8 %). Our findings indicated that total fat-free mass was not only associated with SBP but also the most dominant contributor to SBP variation in American children and adolescents.


Assuntos
Composição Corporal , Masculino , Criança , Feminino , Humanos , Adolescente , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Estudos Transversais , Inquéritos Nutricionais
8.
Fish Shellfish Immunol ; 144: 109241, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992914

RESUMO

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a pervasive intracellular signal transduction pathway, involving in biological processes such as cell proliferation, differentiation, apoptosis and immune regulation. In this study, seven STAT genes, STAT1, STAT1-like, STAT2, STAT3, STAT4, STAT5a and STAT5b, were identified and characterized in spotted seabass (Lateolabrax maculatus). Analyses of multiple sequence alignment, genomic organization, phylogeny and conserved synteny were conducted to infer the evolutionary conservation of these genes in the STAT family. The results of the bioinformatics analysis assumed that STAT1 and STAT1-like might be homologous to STAT1a and STAT1b, respectively. Furthermore, the expression of the seven genes were detected in eight tissues of healthy spotted seabass, which revealed that they were expressed in a variety of tissues, mainly in gill, spleen and muscle, and extremely under-expression in liver. The expression of the seven genes in gill, head-kidney, spleen and intestine were significantly induced by lipopolysaccharide (LPS) or Edwardsiella tarda challenge. The expression of most of the LmSTATs were up-regulated, and the highest expression levels at 12 h after LPS stimulation, however, the LmSTATs were down-regulated by E. tarda infection. The results of subcellular localization show that the native LmSTAT1, LmSTAT1-like, LmSTAT2, LmSTAT3 and LmSTAT5a were localized in the cytoplasm, but they were translocated into the nucleus after LPS stimulation. Whereas, LmSTAT4 and LmSTAT5b were translocation into the nucleus whether with LPS stimulation or not. Overall, this is the first study to systematically revealed the localization of STAT members in fish, and indicated that LmSTATs participate in the process of protecting the host from pathogens invasion in the form of entry into nucleus.


Assuntos
Bass , Lipopolissacarídeos , Animais , Lipopolissacarídeos/farmacologia , Proteínas de Peixes , Fator de Transcrição STAT1/genética , Janus Quinases/genética , Genoma
9.
J Phys Chem A ; 128(1): 225-234, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38146005

RESUMO

This work reports six new full-dimensional adiabatic potential energy surfaces (PESs) of the N3 system (four 4A″ states and two 2A″ states) at the MRCI + Q/AVQZ level of theory that correlated to N2(X1Σg+) + N(4S), N2(X1Σg+) + N(2D), N2(A3Σu+) + N(4S), N2(B3Πg) + N(4S), N2(W3Δu) + N(4S), and N(4S) + N(4S) + N(4S) channels. The neural networks with a proper account of the nuclear permutation invariant symmetry of N3 were employed to fit the PESs based on about 4000 ab initio points. The accuracy of the PESs was validated by excellent agreement on the equilibrium bond length, vertical excitation energy, and dissociation energy with experimental values. Two possible mechanisms of the formation of N2(A) were found. One is that the collision occurs between N2(X) and N(4S) in the 14A″ state, followed by a nonadiabatic transition through the conical intersection with the 24A″ PES, resulting in the formation of the N2(A) + N(4S) product. The other takes place in the collision among three N(4S) atoms in the adiabatic 24A″ state, and then, N2(A) + N(4S) is formed. This is the first systematical research of the N3 system focusing on the formation of the excited states of N2 via both adiabatic and nonadiabatic pathways.

10.
Biomed Eng Online ; 23(1): 16, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326806

RESUMO

BACKGROUND: Previous studies have reported that abnormal interlimb coordination is a typical characteristic of motor developmental delay (MDD) during human movement, which can be visually manifested as abnormal motor postures. Clinically, the scale assessments are usually used to evaluate interlimb coordination, but they rely heavily on the subjective judgements of therapists and lack quantitative analysis. In addition, although abnormal interlimb coordination of MDD have been studied, it is still unclear how this abnormality is manifested in physiology-related kinematic features. OBJECTIVES: This study aimed to evaluate how abnormal interlimb coordination of MDD during infant crawling was manifested in the stability of joints and limbs, activation levels of synergies and intrasubject consistency from the kinematic synergies of tangential velocities of joints perspective. METHODS: Tangential velocities of bilateral shoulder, elbow, wrist, hip, knee and ankle over time were computed from recorded three-dimensional joint trajectories in 40 infants with MDD [16 infants at risk of developmental delay, 11 infants at high risk of developmental delay, 13 infants with confirmed developmental delay (CDD group)] and 20 typically developing infants during hands-and-knees crawling. Kinematic synergies and corresponding activation coefficients were derived from those joint velocities using the non-negative matrix factorization algorithm. The variability accounted for yielded by those synergies and activation coefficients, and the synergy weightings in those synergies were used to measure the stability of joints and limbs. To quantify the activation levels of those synergies, the full width at half maximum and center of activity of activation coefficients were calculated. In addition, the intrasubject consistency was measured by the cosine similarity of those synergies and activation coefficients. RESULTS: Interlimb coordination patterns during infant crawling were the combinations of four types of single-limb movements, which represent the dominance of each of the four limbs. MDD mainly reduced the stability of joints and limbs, and induced the abnormal activation levels of those synergies. Meanwhile, MDD generally reduced the intrasubject consistency, especially in CDD group. CONCLUSIONS: These features have the potential for quantitatively evaluating abnormal interlimb coordination in assisting the clinical diagnosis and motor rehabilitation of MDD.


Assuntos
Articulação do Cotovelo , Movimento , Humanos , Lactente , Fenômenos Biomecânicos , Movimento/fisiologia , Joelho , Mãos
11.
Nutr Metab Cardiovasc Dis ; 34(3): 590-597, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37996372

RESUMO

BACKGROUND AND AIM: Heart failure (HF) is an important complication of ST-elevation myocardial infarction (STEMI), including early- and late-onset HF. This study aimed to investigate the association between insulin resistance (IR)-related parameters triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) index and early-onset HF in STEMI between sexes. METHODS AND RESULTS: This cross-sectional study included patients with STEMI who underwent primary percutaneous coronary intervention (PCI) between January 2016 and September 2022. Patients were divided into tertiles according to TyG/TyG-BMI index levels in males and females. The presence of early-onset HF was compared between tertiles in both sexes. Moreover, patients were stratified according to the tertiles of TyG/Tyg-BMI index. Differences in early-onset HF of STEMI were compared between males and females in each tertile group. 1118 patients were included in this study, 20.3% of whom were females. The incidence rate of early-onset HF was significantly higher in females than in males (29% vs. 14.8%). TyG-BMI index was negatively correlated with early-onset HF. In both females and males, there was no difference in the occurrence of early-onset HF between the highest and lowest TyG/TyG-BMI index groups. Sex disparity was observed in females who had a significantly higher prevalence of early-onset HF than males in each TyG/TyG-BMI index tertile group; however, after adjustment, the differences disappeared. CONCLUSIONS: For patients with STEMI who undergo primary PCI, the incidence of early-onset HF is higher in females than in males. The TyG/TyG-BMI index do not contribute to the difference in early-onset HF between sexes.


Assuntos
Insuficiência Cardíaca , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Masculino , Humanos , Índice de Massa Corporal , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Estudos Transversais , Intervenção Coronária Percutânea/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Glucose , Triglicerídeos
12.
BMC Pulm Med ; 24(1): 60, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281045

RESUMO

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder. Numerous investigations have found a strong inherent relationship between OSA and hypothyroidism. Studies suggest that lymphocytes may be involved in the development of hypothyroidism in patients with OSA. This study aimed to assess the association between lymphocytes and hypothyroidism in OSA patients. PATIENTS AND METHODS: This study involved 920 patients with OSA who underwent nocturnal sleep monitoring, thyroid function testing, and routine blood tests. In patients with OSA, logistic regression analysis indicated independent predictors of hypothyroidism. The cutoff level of lymphocyte count was determined using a receiver operating characteristic (ROC) analysis to predict the occurrence of hypothyroidism in individuals with OSA. RESULTS: This study comprised 920 OSA patients (617 males and 303 women), 879 with normal thyroid function, and 41 with hypothyroidism, with a hypothyroidism incidence of 4.46%. In the entire OSA population and male OSA patients, the number of lymphocytes was significantly higher in the hypothyroid group than in the control group (p = 0.002 and 0.020, respectively). In addition, among the OSA population younger than 60 years old and patients with mild to moderate OSA, lymphocytes were found to be considerably more in the hypothyroid group than in the euthyroid group. Lymphocyte count, ESS, and sex were all independent predictors of hypothyroidism development in OSA patients. According to ROC curve analysis, the risk of hypothyroidism increases with increasing lymphocyte count in the total patient population, with an optimal diagnostic cutoff point of 2.5 (× 10*9/L). CONCLUSIONS: The prevalence of hypothyroidism in patients with OSA increases as the number of lymphocytes increases. Lymphocyte count can be used as an independent predictor of the occurrence of hypothyroidism, and it has a diagnostic value for OSA combined with hypothyroidism.


Assuntos
Hipotireoidismo , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Sono , Curva ROC , Linfócitos
13.
Aging Clin Exp Res ; 36(1): 35, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345775

RESUMO

BACKGROUND: Body fat mass (FM) is associated with multiple organ damage. However, data regarding the relationship between various organ damage and FM are rare in the elderly. Therefore, we aim to perform an analysis on the relationship between organ damage and FM in a geriatric cohort. METHODS: 3331 participants were included in this analysis. Based on age, body height, body weight, waist circumference, and race, we calculated FM with the established formula. Organ damage, including arterial stiffening, lower extremity atherosclerosis, left ventricular hypertrophy (LVH), micro-albuminuria, and chronic kidney disease (CKD), were measured and calculated with standard methods. RESULTS: All organ damage parameters were significantly related to FM (all p < 0.001). In univariate logistics regression, the highest quartile of FM was tied to the increased risk of arterial stiffening, lower extremity atherosclerosis, LVH, micro-albuminuria, and CKD (all p < 0.05). After adjustment, participants with higher quantiles of FM had a significantly increased odd ratio (OR) for arterial stiffening [OR = 1.51, 95% confidence interval (CI): 1.15-1.99, p = 0.002] and LVH (OR = 1.99, 95% CI: 1.48-2.67, p < 0.001). Moreover, FM was linearly associated with arterial stiffening and LVH in total population and gender subgroups. Independent of confounders, FM was significantly correlated with arterial stiffening, lower extremity atherosclerosis, LVH and CKD in female, while was only related to LVH in male. CONCLUSIONS: Among various organ damage, elevated FM is significantly and independently associated with arterial stiffening and LVH in the elderly. Compared with men, women with increased FM are more likely to have multiple organ damage.


Assuntos
Aterosclerose , Hipertensão , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Idoso , Fatores de Risco , Vida Independente , Albuminúria/epidemiologia , China/epidemiologia
14.
Biochem Genet ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267617

RESUMO

The aim of this study was to investigate the underlying mechanism of miR-9-5p in airway smooth muscle cells (ASMCs) of asthmatic mice. An asthmatic mouse model was established through the intraperitoneal injection of ovalbumin. Histopathological changes in lung tissues of asthmatic mice were observed using HE staining. ASMCs was identified using immunofluorescence staining and cell morphology. The mRNA expressions of miR-9-5p, KLF5, and IL-1ß were measured using RT-qPCR. Additionally, CCK8 assay and flow cytometry were applied for ASMC proliferation and apoptosis, respectively. The protein levels of OPN, KLF5, and IL-1ß were assessed using western blotting. The results showed that miR-9-5p was abnormally downregulated in lung tissues and ASMCs of asthmatic mice. Dual-Luciferase Reporter Assay and Chromatin immunoprecipitation confirmed that miR-9-5p targeted KLF5 that bounds to IL-1ß promoter. Besides, miR-9-5p negatively regulated IL-1ß mRNA and protein level via KLF5. Moreover, miR-9-5p was found to positively regulate ASMC apoptosis, negatively regulate ASMC proliferation and OPN protein expression, albeit with partial reversal by KLF5. Mechanistically, the regulation of ASMC proliferation and apoptosis by miR-9-5p is achieved by targeting KLF5/IL-1ß axis.

15.
Nano Lett ; 23(9): 3954-3962, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37096810

RESUMO

Stripy states, consisting of a collection of stripy spin textures, are the precursors of skyrmion crystals (SkXs). The common belief is that stripy states and SkXs are topologically unconnected and that transitions between SkXs and stripy states are phase transitions. Here, we show that both stripy states and SkXs are skyrmion condensates and they are topologically equivalent. By gradually tuning the stripe whose width goes from smaller than to larger than skyrmion-skyrmion separation, the structure of a skyrmion condensate transforms smoothly and continuously from various stripy phases, including helical states and mazes, to crystals, showing that stripy states are topologically connected to SkXs.

16.
J Environ Manage ; 355: 120503, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38457894

RESUMO

The global concern regarding the adverse effects of heavy metal pollution in soil has grown significantly. Accurate prediction of heavy metal content in soil is crucial for environmental protection. This study proposes an inversion analysis method for heavy metals (As, Cd, Cr, Cu, Ni, Pb) in soil based on hyperspectral and machine learning algorithms for 21 soil reference materials from multiple provinces in China. On this basis, an integrated learning model called Stacked RF (the base model is XGBoost, LightGBM, CatBoost, and the meta-model is RF) was established to perform soil heavy metal inversion. Specifically, three popular algorithms were initially employed to preprocess the spectral data, then Random Forest (RF) was used to select the best feature bands to reduce the impact of noise, finally Stacking and four basic machine learning algorithms were used to establish comparisons and analysis of inversion model. Compared with traditional machine learning methods, the stacking model showcases enhanced stability and superior accuracy. Research results indicate that machine learning algorithms, especially ensemble learning models, have better inversion effects on heavy metals in soil. Overall, the MF-RF-Stacking model performed best in the inversion of the six heavy metals. The research results will provide a new perspective on the ensemble learning model method for soil heavy metal content inversion using data of hyperspectral characteristic bands collected from soil reference materials.


Assuntos
Metais Pesados , Poluentes do Solo , Solo , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Metais Pesados/análise , China , Aprendizado de Máquina
17.
Glob Chang Biol ; 29(4): 1054-1061, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36408718

RESUMO

Atmospheric nitrogen (N) deposition is composed of both inorganic nitrogen (IN) and organic nitrogen (ON), and these sources of N may exhibit different impacts on ecosystems. However, our understanding of the impacts of N deposition is largely based on experimental gradients of INs or more rarely ONs. Thus, the effects of N deposition on ecosystem productivity and biodiversity may be biased. We explored the differential impacts of N addition with different IN:ON ratios (0:10, 3:7, 5:5, 7:3, and 10:0) on aboveground net primary productivity (ANPP) of plant community and plant diversity in a typical temperate grassland with a long-term N addition experiment. Soil pH, litter biomass, soil IN concentration, and light penetration were measured to examine the potential mechanisms underlying species loss with N addition. Our results showed that N addition significantly increased plant community ANPP by 68.33%-105.50% and reduced species richness by 16.20%-37.99%. The IN:ON ratios showed no significant effects on plant community ANPP. However, IN-induced species richness loss was about 2.34 times of ON-induced richness loss. Soil pH was positively related to species richness, and they exhibited very similar response patterns to IN:ON ratios. It implies that soil acidification accounts for the different magnitudes of species loss with IN and ON additions. Overall, our study suggests that it might be reasonable to evaluate the effects of N deposition on plant community ANPP with either IN or ON addition. However, the evaluation of N deposition on biodiversity might be overestimated if only IN is added or underestimated if only ON is added.


Assuntos
Ecossistema , Pradaria , Nitrogênio , Biodiversidade , Biomassa , Plantas , Solo
18.
Eur J Nucl Med Mol Imaging ; 50(7): 1940-1953, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36786817

RESUMO

BACKGROUND: Despite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients. METHODS: The study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina. RESULTS: During a median follow-up of 15 months (interquartile range (IQR) 11-20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) ([Formula: see text]) and coronary flow reserve (CFR) ([Formula: see text]) were significantly lower in the MACE group. Optimal thresholds of sMBF<3.16 and CFR<2.52 were extracted from the ROC curves, and both impaired sMBF (HR: 15.08; 95% CI 2.95-77.07; [Formula: see text]) and CFR (HR: 6.51; 95% CI 1.43-29.65; [Formula: see text]) were identified as prognostic factors for MACEs. Only sMBF<3.16 (HR: 11.20; 95% CI 2.04-61.41; [Formula: see text]) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06, [Formula: see text]; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10). CONCLUSION: The preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Imagem de Perfusão do Miocárdio , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Angiografia Coronária/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Imagem de Perfusão do Miocárdio/métodos
19.
Environ Res ; 236(Pt 2): 116787, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37517494

RESUMO

Zinc ion (Zn2+) is a frequently occurring heavy metal in livestock wastewater. The effects of Zn2+ on the physicochemical properties and the microbial distribution of activated sludge are essential to controlling nitrogen removal performance. Nevertheless, there are raw studies on the effects of Zn2+ on nitrogen removal. This study investigated the effect of Zn2+ on the treatment performance of livestock wastewater in a sequencing batch reactor (SBR). The results indicated the low Zn2+ concentrations could improve nitrogen removal performance. However, as the Zn2+ concentration increased, the total nitrogen (TN) removal performance of the reactor gradually deteriorated. When the Zn2+ concentration was 90.00 mg/L, the TN removal efficiency was the lowest, only 2.40%. The contents of the Extracellular polymeric substance (EPS) presented a trend of first increasing and then decreasing with the increase of Zn2+ concentration, and the main reason was the decrease of protein-like and tryptophan-like. The 16SrRNA analysis indicated that Zn2+ within a specific concentration could increase the operational taxonomic units (OTUs) number, microbial richness, and diversity of microorganisms in the SBR. However, with Zn2+ concentration exceeding 10.00 mg/L, the relative abundance of denitrification functional bacteria (Dechloromonas, Nitrospira, and Thauera) decreased.


Assuntos
Microbiota , Águas Residuárias , Animais , Gado , Eliminação de Resíduos Líquidos/métodos , Zinco/análise , Matriz Extracelular de Substâncias Poliméricas , Reatores Biológicos/microbiologia , Desnitrificação , Esgotos/microbiologia , Nitrogênio/análise , Bactérias/genética
20.
Nutr Metab Cardiovasc Dis ; 33(3): 577-583, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36646605

RESUMO

BACKGROUND AND AIMS: Inflammation closely correlates with atherosclerosis and cardiovascular disease (CVD). Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammation index that can be obtained by routine blood tests. We aimed to investigate the associations between MHR and atherosclerosis and arteriosclerosis. METHODS AND RESULTS: We enrolled 2451 participants from the Northern Shanghai Study. Atherosclerosis (carotid plaque (CP), lower extremity atherosclerotic (LEA) assessed by ankle-brachial index) and arteriosclerosis (arterial stiffness (AS) assessed by carotid-femoral pulse wave velocity) were measured using standard methods. In the univariable logistic regression model, higher MHR was significantly associated with increased AS, CP, and LEA risk. In the multivariable logistic regression model, after adjustment for age, sex, hypertension, diabetes mellitus, body mass index, smoking habit, low-density lipoprotein cholesterol, and family history of premature CVD, quartile 4 (Q4) of MHR was associated with an increased risk of AS (odds ratio (OR) = 1.41; 95% confidence interval (CI):1.05-1.88; P fortrend = 0.036), CP (OR = 1.35; 95%CI:1.04-1.77; P for trend = 0.044), and LEA (OR = 2.23; 95%CI:1.49-3.35; P for trend< 0.001). Similar results were observed when MHR was analyzed as a continuous variable. The restricted cubic spline (RCS) curve showed that the association between MHR and AS was nonlinear (P nonlinear = 0.021), but not LEA (P nonlinear = 0.177) or CP (P nonlinear = 0.72). CONCLUSION: MHR presents a linear association with atherosclerosis and a nonlinear association with arteriosclerosis in the elderly Chinese population. These findings may indicate the need for early assessment and intervention for inflammation. The registration number for clinical trials: NCT02368938.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Placa Aterosclerótica , Humanos , Idoso , Lipoproteínas HDL , Monócitos , Análise de Onda de Pulso , População do Leste Asiático , Fatores de Risco , China/epidemiologia , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol , Inflamação
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