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1.
J Exp Bot ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623889

RESUMO

Cassava is one of the most important tuber crops that is used for food, starch and bio-energy. However, cassava is susceptible to a number of diseases, especially cassava bacterial blight (CBB). Nitric oxide (NO) and hydrogen peroxide (H2O2) regulate plant growth and development, as well as stress responses. However, no direct relationships between the enzymes involved in the metabolic enzymes that produce and process these key signaling molecules has been demonstrated. Here, we provide evidence for the interaction between the nitrate reductase 2 (MeNR2) and catalase 1 (MeCAT1) proteins in vitro and in vivo, using yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays, respectively. MeNR2 is a positive regulator and MeCAT1 is a negative regulator of CBB resistance. MeNR2 was localized in the nucleus, cell membrane and peroxisome, while MeCAT1 was localized in the peroxisomes. The interactions between MeNR2 and MeCAT1 also had effects of their respective enzyme activities. Taken together, the data presented here suggested that there is coordination between H2O2 and NO signaling in cassava disease resistance, through the interactions between MeCAT1 and MeNR2.

2.
Langmuir ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136076

RESUMO

Heavy metal ion wastewater is a pressing and inescapable issue that is closely related to human health and ecological security due to its toxicity, carcinogenicity, and the unmanageable property of this type of wastewater. Metal-Organic Frameworks (MOFs) are a class of crystalline nanoporous materials with flexible designability and controllability, showing great potential in the field of adsorption and purification of heavy metals in wastewater. In this Perspective, we first discuss the harm of different heavy metal ions and briefly expound virtues of MOFs for pollutant adsorption. Then, we mainly summarize the recent advances in the construction of different metal-based MOFs (Zr-based, Zn-based, Co-based, Al-based, etc.) and their research progress in heavy metal ions adsorption. Furthermore, various types of MOF additives can often be effectively applied for heavy metal ion adsorption by functional modification or with other materials composition. Additionally, several commonly used adsorption kinetics and isotherm models are also detailed to help an in-depth understanding of the adsorption mechanism. Finally, the challenges and opportunities of MOFs for heavy metal ion adsorption are additionally discussed, and this review may provide new insight for other potential water purification applications.

3.
BMC Endocr Disord ; 24(1): 92, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38890672

RESUMO

BACKGROUND: The interrelation between metabolic syndrome (MetS) and Parkinson's disease (PD) likely arises from shared pathological mechanisms. This study thus aims to examine the impact of MetS and its components on PD. METHODS: This study utilized data extracted from the National Health and Nutrition Examination Survey database spanning 1999 to 2020. The random forest algorithm was applied to fill in the missing data. Propensity score optimal full matching was conducted. The data were adjusted by total weights derived from both sampling and matching weights. The weighted data were utilized to create multifactor logistic regression models. Odds ratios (ORs) and average marginal effects, along with their corresponding 95% confidence intervals (CIs), were calculated. RESULTS: MetS did not significantly affect the risk of PD (OR: 1.01; 95% CI: 0.77, 1.34; P = 0.92). Hypertension elevated the risk of PD (OR: 1.33; 95% CI: 1.01, 1.76; P = 0.045), accompanied by a 0.26% increased probability of PD occurrence (95% CI: 0.01%, 0.52%; P = 0.04). Diabetes mellitus (DM) had a 1.38 times greater likelihood of developing PD (OR:1.38; 95% CI: 1.004, 1.89; P = 0.046), corresponding to a 0.32% increased probability of PD occurrence (95% CI: -0.03%, 0.67%; P = 0.07). Nevertheless, no correlation was observed between hyperlipidemia, waist circumference and PD. CONCLUSION: MetS does not affect PD; however, hypertension and DM significantly increase the risk of PD.


Assuntos
Síndrome Metabólica , Doença de Parkinson , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Inquéritos Nutricionais , Hipertensão/epidemiologia , Hipertensão/complicações , Adulto
4.
BMC Cardiovasc Disord ; 24(1): 161, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491418

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori), according to a number of recent observational studies, is connected to atherosclerosis (AS). However, the link between H. pylori and AS is debatable. METHODS: In order to calculate the causal relationship between H. pylori and AS, we employed a two-sample Mendelian randomization (MR) analysis. The data for H. pylori were obtained from the IEU GWAS database ( https://gwas.mrcieu.ac.uk/datasets/ ) and the data for AS were obtained from the Finngen GWAS database ( https://r5.finngen.fi/ ). We selected single nucleotide polymorphisms with a threshold of 5 × 10-6 from earlier genome-wide association studies. MR was performed mainly using the inverse variance weighted (IVW) method. To ensure the reliability of the findings, We performed a leave-one-out sensitivity analysis to test for sensitivity. F-value was used to test weak instrument. RESULTS: A positive causal relationship between H. pylori OMP antibody levels and peripheral atherosclerosis was shown by our two-sample MR analysis (odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.14-1.54, P = 0.26E-03) using IVW. Additionally, there was a causative link between coronary atherosclerosis and H. pylori VacA antibody levels (IVW OR = 1.06, 95% CI = 1.01-1.10, P = 0.016). All the F-values were above 10. CONCLUSIONS: This MR study discovered a causal link between H. pylori and AS. Different antibodies have different effects, so future researches are needed to figure out the exact mechanisms behind this link.


Assuntos
Aterosclerose , Helicobacter pylori , Humanos , Helicobacter pylori/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Aterosclerose/diagnóstico , Aterosclerose/genética , Anticorpos Antibacterianos
5.
Nutr Neurosci ; 27(5): 460-469, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37254575

RESUMO

OBJECTIVES: The growing global burden of pain is gradually expanding from the medical field to public health. Dietary inflammatory potential correlates with inflammatory markers, and inflammation is one of the main mechanisms of pain. METHODS: This study explored the association between dietary inflammatory index (DII) and pain from the NHANES database on DII and pain (neck pain, low back pain, joint pain, and headache or migraine) using logistic regression and stratified analysis. RESULTS: The results show a stronger association between DII and joint pain (Q4 of DII adjusted-OR = 1.23, 95% CI = 1.08-1.40, P = 0.003) and headache or migraine (Q4 of DII adjusted-OR = 1.31, 95% CI = 1.15-1.48, P < 0.001), but no association is found in neck pain (Q4 of DII adjusted-OR = 1.03, 95% CI = 0.89-1.20, P = 0.65) and low back pain (Q4 of DII adjusted-OR = 1.04, 95% CI = 0.92-1.17, P = 0.54). After stratifying the data according to demographics, differences in the relationship between DII and pain are found at different levels of the population. DISCUSSION: This study identifies high DII as a risk factor for joint pain and headache or migraine.


Assuntos
Dor Lombar , Transtornos de Enxaqueca , Adulto , Humanos , Inquéritos Nutricionais , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Cervicalgia/epidemiologia , Cervicalgia/etiologia , Dieta , Inflamação/epidemiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , Artralgia , Transtornos de Enxaqueca/epidemiologia
6.
Pediatr Res ; 93(4): 1085-1095, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35835848

RESUMO

BACKGROUND: Late-Onset Neonatal Sepsis (LOS) is a rare condition, involving widespread infection, immune disruption, organ dysfunction, and often death. Because exposure to pathogens is not completely preventable, identifying susceptibility factors is critical to characterizing the pathophysiology and developing interventions. Prior studies demonstrated both genetics and infant sex influence susceptibility. Our study was designed to identify LOS associated genetic variants. METHODS: We performed an exploratory genome wide association study (GWAS) with 224 LOS cases and 273 controls from six European countries. LOS was defined as sepsis presenting from 3 to 90 days of age; diagnosis was established by clinical criteria consensus guidelines. We tested for association with both autosomal and X-chromosome variants in the total sample and in sex-stratified analyses. RESULTS: In total, 71 SNPs associated with neonatal sepsis at p < 1 × 10-4 in at least one analysis. Most importantly, sex-stratified analyses revealed associations with multiple SNPs (28 in males and 16 in females), but no variants from single-sex analyses associated with sepsis in the other sex. Pathway analyses showed NOTCH signaling is over-represented among genes linked to these SNPS. CONCLUSION: Our results indicate genetic susceptibility to LOS is sexually dimorphic and corroborate that NOTCH signaling plays a role in determining risk. IMPACT: Genes associate with late onset neonatal sepsis. Notch pathway genes are overrepresented in associations with sepsis. Genes associating with sepsis do not overlap between males and females. Sexual dimorphism can lead to sex specific treatment of sepsis.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Masculino , Lactente , Feminino , Humanos , Sepse Neonatal/genética , Estudo de Associação Genômica Ampla , Sepse/genética , Caracteres Sexuais , Europa (Continente)
7.
Clin Exp Rheumatol ; 41(9): 1768-1776, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36826804

RESUMO

OBJECTIVES: We aimed to discriminate subpopulations of peripheral natural killer (NK) cells of patients with systemic lupus erythematosus (SLE) and evaluate their usability in monitoring disease activity. METHODS: The total number of NK cells and their subpopulations were determined by flow cytometry in 68 patients with SLE and 35 healthy controls. Clinical data were extracted from medical records, including serum anti-double-stranded-DNA (anti-dsDNA), complement C3 and C4, and urine protein. Disease activity in patients with SLE was assessed using the SLE Disease Activity Index-2000 (SLEDAI-2K). RESULTS: The percentages and absolute numbers of NK cells decreased, and the proportions of three major NK cell subsets defined by cell maturation status altered in SLE patients. The frequency of CD56brightCD16- NK (immature, Im NK) cells increased, while that of the CD57+CD56dimCD16- subset (mature, more differentiated, MD NK) decreased in patients with high-activity SLE, resulting in a significant increase in the Im NK-to-MD NK ratio as compared with that in patients with low-activity SLE. The area under the receiver operating characteristic curve indicated that the ratio was 0.722 in severe SLE and 0.773 in lupus nephritis, with optimal cut-off levels of 0.075 and 0.108, respectively. The ratio correlated positively with the SLEDAI-2K score, proteinuria, and serum anti-dsDNA antibody levels but negatively with C3 and C4 levels. CONCLUSIONS: Our data indicate that the imbalance in Im NK and MD NK cells may play a role in lupus development and serve as a predictive biomarker to assess disease activity and renal involvement in patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/diagnóstico , Biomarcadores , Citometria de Fluxo/métodos , Células Matadoras Naturais
8.
Rheumatol Int ; 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37750894

RESUMO

We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio.

9.
J Virol ; 95(12)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-33789997

RESUMO

Enteroviruses belong to the genus Enterovirus of the family Picornaviridae and include four human enterovirus groups (EV-A to -D): the epidemic of enteroviruses such as human enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) is a threat to global public health. Enteroviral protein 2C is the most conserved nonstructural protein among all enteroviruses and possesses RNA helicase activity that plays pivotal roles during enteroviral life cycles, which makes 2C an attractive target for developing antienterovirus drugs. In this study, we designed a peptide, named 2CL, based on the structure of EV-A71 2C. This peptide effectively impaired the oligomerization of EV-A71 2C protein and inhibited the RNA helicase activities of 2C proteins encoded by EV-A71 and CVA16, both of which belong to EV-A, and showed potent antiviral efficacy against EV-A71 and CVA16 in cells. Moreover, the 2CL treatment elicited a strong in vivo protective efficacy against lethal EV-A71 challenge. In addition, the antiviral strategy of targeting the 2C helicase activity can be applied to inhibit the replication of EV-B. Either 2CL or B-2CL, the peptide redesigned based on the 2CL-corresponding sequence of EV-Bs, could exert effective antiviral activity against two important EV-Bs, coxsackievirus B3 and echovirus 11. Together, our findings demonstrated that targeting the helicase activity of 2C with a rationally designed peptide is an efficient antiviral strategy against enteroviruses, and 2CL and B-2CL show promising clinical potential to be further developed as broad-spectrum antienterovirus drugs.IMPORTANCE Enteroviruses are a large group of positive-sense single-stranded RNA viruses and include numerous human pathogens, such as enterovirus A71 (EV-A71), coxsackieviruses, and echoviruses. However, no approved EV antiviral drugs are available. Enteroviral 2C is the most conserved nonstructural protein among all enteroviruses and contains the RNA helicase activity critical for the viral life cycle. Herein, according to the structure of EV-A71 2C, we designed a peptide that effectively inhibited the RNA helicase activities of EV-A71- and coxsackievirus A16 (CVA16)-encoded 2C proteins. Moreover, this peptide exerted potent antiviral effects against EV-A71 and CVA16 in cells and elicited therapeutic efficacy against lethal EV-A71 challenge in vivo Furthermore, we demonstrate that the strategy of targeting the 2C helicase activity can be used for other relevant enteroviruses, including coxsackievirus B3 and echovirus 11. In summary, our findings provide compelling evidence that the designed peptides targeting the helicase activity of 2C could be broad-spectrum antivirals for enteroviruses.


Assuntos
Antivirais/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Enterovirus Humano A/efeitos dos fármacos , Infecções por Enterovirus/tratamento farmacológico , Peptídeos/farmacologia , RNA Helicases/antagonistas & inibidores , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Antivirais/química , Antivirais/uso terapêutico , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Linhagem Celular , Desenho de Fármacos , Enterovirus Humano A/química , Enterovirus Humano A/fisiologia , Enterovirus Humano B/efeitos dos fármacos , Enterovirus Humano B/fisiologia , Infecções por Enterovirus/virologia , Humanos , Camundongos , Camundongos Endogâmicos ICR , Peptídeos/química , Peptídeos/uso terapêutico , RNA Helicases/metabolismo , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
10.
Clin Rehabil ; 36(9): 1186-1198, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35469457

RESUMO

OBJECTIVE: To assess the effects of dual-task training on gait and balance in stroke patients.Data sources: A systematic review of PubMed, Web of Science, Embase and Cochrane Library from their inception through 20 August 2021. REVIEW METHODS: The bibliography was screened to identify randomized controlled trials that applied dual-task training to rehabilitation function training in stroke patients. Two reviewers independently screened references, selected relevant studies, extracted data and assessed risk of bias using the Cochrane tool of bias. The primary outcome was the gait and balance parameters. RESULTS: A total of 1992 studies were identified and 15 randomized controlled trials were finally included (512 individuals) were analyzed. A meta-analysis was performed and a beneficial effect on rehabilitation training was found. Compared to patients who received conventional rehabilitation therapy, those who received dual-task training showed greater improvement in step length (MD = 3.46, 95% CI [1.01, 5.92], P = 0.006), cadence (MD = 4.92, 95% CI [3.10, 6.74], P < 0.001) and berg balance scale score (MD = 3.10, 95% CI [0.11, 6.09], P = 0.040). There were no differences in the improvements in gait speed (MD = 2.89, 95% CI [ - 2.02, 7.80], P = 0.250) and timed up and go test (MD = -2.62, 95% CI [ - 7.94, 2.71], P = 0.340) between dual-task and control groups. CONCLUSION: Dual-task training is an effective training for rehabilitation of stroke patients in step length and cadence, however, the superiority of dual-task training for improving balance function needs further discussion.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Terapia por Exercício , Marcha , Humanos , Equilíbrio Postural , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Estudos de Tempo e Movimento
11.
J Gen Virol ; 102(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33891535

RESUMO

RNA-remodelling proteins, including RNA helicases and chaperones, function to remodel structured RNAs and/or RNA-protein interactions and play indispensable roles in viral life cycles. Guaico Culex virus (GCXV) is the first uncovered animal-infected multicomponent virus with segmented positive-sense genomic RNAs. GCXV belongs to the Jingmenvirus group, a diverse clade of segmented viruses that are related to the prototypically unsegmented Flavivirus. However, little is known about the exact functions of the GCXV-encoded proteins. Here, we show that the putative non-structural protein (NSP) 2 on segment 2 of GCXV functions as an RNA helicase that unwinds RNA helix bidirectionally in an adenosine triphosphate (ATP)-dependent manner, and an RNA chaperone that remodels structured RNAs and facilitates RNA strand annealing independently of ATP. Together, our findings are the first demonstration of RNA-remodelling activity encoded by Jingmenvirus and highlight the functional significance of NSP2 in the GCXV life cycle.


Assuntos
Culex/virologia , RNA Helicases/genética , Proteínas não Estruturais Virais/genética , Vírus não Classificados/genética , Animais , Chaperonas Moleculares/genética , Dobramento de Proteína , RNA Viral/metabolismo , Replicação Viral
12.
Langmuir ; 35(40): 12908-12913, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31525936

RESUMO

Metal-organic frameworks (MOFs) are a class of customizable porous material, which have shown good performance in separation processes, because of their large surface area and molecular recognition property. Although the effects of chemical structure of MOFs on their separation performance were extensively studied, the exploration of their surface properties was still limited. This work demonstrated a MOF nanosheet with large amount of coordinatively unsaturated metal sites, Cu(BDC) (copper(II) benzenedicarboxylate), where the unsaturated Cu sites were utilized to selectively adsorb organic molecules with Lewis basicity. This work also investigated the direct growth of Cu(BDC) on the cellulose substrate, where the MOF nanosheets were immobilized on the cellulose substrate, enabling the composite material for practical applications. The heterogeneous nucleation and growth of MOF nanosheets on the cellulose were achieved by tuning the basicity of solution and reaction temperature. We believe this direct growth approach can be applied to other MOF composite materials for separation and purification purposes, as well as other applications involving molecular recognition properties of MOFs, such as sensing, catalysis, and enzyme immobilization.

13.
Chemosphere ; 350: 141034, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38147926

RESUMO

The removal of Cr(VI) from aqueous solutions using microscale zerovalent iron (mZVI) shows promising potential. However, the surface passivation of mZVI particles hinders its widespread application. In this study, we prepared tannic acid (TA) modified mZVI composite (TA-mZVI) by a simple sonication method. The introduction of TA allowing TA-mZVI composite to adsorb Cr(VI) rapidly under electrostatic forces attraction, guarantying TA-mZVI exhibited remarkable Cr(VI) removal capacity with a maximum adsorption capacity of 106.1 mg⋅g-1. At an initial pH of 3, it achieved a rapid removal efficiency of 96.2% within just 5 min, which was 7.7 times higher than that of mZVI. Various characterizations, including XPS and CV analysis, indicated that the formation of TA-Fe complexes accelerates electron transfer. In addition, TA endows functional groups to TA-mZVI, raising the dispersion and stability and serves as a protective layer hindering passivation. Further mechanistic analysis revealed that Cr(VI) removal by TA-mZVI followed an adsorption-reduction-precipitation mechanism, with TA mitigating the surface passivation of mZVI and facilitating the reduction of most Cr(VI) to Cr(III). Batch cyclic experiments revealed that TA-mZVI exhibited satisfactory performance, maintaining over 85% Cr(VI) removal even after five cycles and minimally affected by various coexisting ions. With notable advantages in cost-effectiveness, ease-synthesis and recovery, this work provides a great promise for developing efficient reactive adsorbent for addressing Cr(VI) contamination in aqueous solutions.


Assuntos
Ferro , Polifenóis , Poluentes Químicos da Água , Ferro/química , Poluentes Químicos da Água/análise , Cromo/química , Adsorção , Água
14.
J Colloid Interface Sci ; 659: 1015-1028, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38241973

RESUMO

In this study, we prepared a micron zero-valent iron/N-doped graphene-like biochar (mZVI/NGB) composite using a mechanochemical method for tetracycline (TC) degradation through O2 activation. The mZVI and NGB components formed a strong coupling catalytic system, with mZVI acting as an electron pool and NGB as a catalyst for H2O2 generation. Under circumneutral pH (5.0-6.8), the mZVI/NGB composite exhibited exceptional TC removal efficiency, reaching nearly 100 % under optimal conditions. It also showed good tolerance to co-existing anions, such as Cl-, SO42-, and humic acid. Further studies found that the TC degradation mechanism was mainly ascribed to the non-radical pathway (1O2 and electron transfer), and the Fe2+/Fe3+ redox cycle on the composite's surface also played a crucial role in maintaining catalytic activity. This research contributes to the development of advanced materials for sustainable and effective water treatment, addressing pharmaceutical pollutant contamination in water sources.


Assuntos
Carvão Vegetal , Grafite , Poluentes Químicos da Água , Ferro/química , Peróxido de Hidrogênio , Antibacterianos , Tetraciclina/química , Poluentes Químicos da Água/química
15.
Heliyon ; 10(12): e32636, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39022106

RESUMO

Sustainable development is crucial for alleviating poverty among farmers. In this study, we examined the impact, and the mechanism underlying this impact, of the adoption of agricultural machinery services by farmers on their relative poverty from a multidimensional poverty perspective by employing the logit and ordered logit models and the Karlson-Holm-Breen (KHB) method. These results indicate that adopting agricultural machinery services can significantly reduce the probability of relative poverty among farmers, thereby expediting the sustainability of rural development. However, this poverty-reduction effect varies based on age and sex. The adoption of agricultural machinery services mainly reduces poverty by increasing farmers' human capital. Training in employment skills and non-agricultural work experience are the main transmission mechanisms. Therefore, the socialization of agricultural machinery services can be used as an effective policy tool to reduce relative poverty in developing countries, promote sustained improvements in farmers' incomes, and achieve sustainability in rural development.

16.
J Alzheimers Dis ; 98(3): 1053-1067, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38489177

RESUMO

Background: The X chromosome is often omitted in disease association studies despite containing thousands of genes that may provide insight into well-known sex differences in the risk of Alzheimer's disease (AD). Objective: To model the expression of X chromosome genes and evaluate their impact on AD risk in a sex-stratified manner. Methods: Using elastic net, we evaluated multiple modeling strategies in a set of 175 whole blood samples and 126 brain cortex samples, with whole genome sequencing and RNA-seq data. SNPs (MAF > 0.05) within the cis-regulatory window were used to train tissue-specific models of each gene. We apply the best models in both tissues to sex-stratified summary statistics from a meta-analysis of Alzheimer's Disease Genetics Consortium (ADGC) studies to identify AD-related genes on the X chromosome. Results: Across different model parameters, sample sex, and tissue types, we modeled the expression of 217 genes (95 genes in blood and 135 genes in brain cortex). The average model R2 was 0.12 (range from 0.03 to 0.34). We also compared sex-stratified and sex-combined models on the X chromosome. We further investigated genes that escaped X chromosome inactivation (XCI) to determine if their genetic regulation patterns were distinct. We found ten genes associated with AD at p < 0.05, with only ARMCX6 in female brain cortex (p = 0.008) nearing the significance threshold after adjusting for multiple testing (α = 0.002). Conclusions: We optimized the expression prediction of X chromosome genes, applied these models to sex-stratified AD GWAS summary statistics, and identified one putative AD risk gene, ARMCX6.


Assuntos
Doença de Alzheimer , Humanos , Masculino , Feminino , Doença de Alzheimer/genética , Transcriptoma , Predisposição Genética para Doença/genética , Cromossomo X , Encéfalo , Polimorfismo de Nucleotídeo Único/genética , Estudo de Associação Genômica Ampla
17.
Int J Rheum Dis ; 27(4): e15131, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563679

RESUMO

OBJECTIVE: To evaluate the incidence and associated factors of initial and recurrent severe infections in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: SLE patients that first hospitalized between 2010 and 2021 were studied retrospectively and divided into SLE with and without baseline severe infection groups. The primary outcome was the occurrence of severe infection during follow-up. Cox regression models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for initial and recurrent severe infections. RESULTS: Among 1051 first hospitalized SLE patients, 164 (15.6%) had severe infection on admission. During a median follow-up of 4.1 years, 113 (10.8%) patients reached severe infection outcomes, including 27 with reinfection and 86 with initial severe infection (16.5% vs. 9.7%, p = .010). Patients with baseline severe infection had a higher cumulative incidence of reinfection (p = .007). After adjusting for confounding factors, renal involvement, elevated serum creatinine, hypoalbuminemia, cyclophosphamide, and mycophenolate mofetil treatment were associated with an increased risk of severe infection, especially initial severe infection. Low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use significantly increased the risk of recurrent severe infection, with adjusted HR (95% CI) of 3.15 (1.22, 8.14), 3.60 (1.56, 8.28), and 2.14 (1.01, 5.76), respectively. Moreover, baseline severe infection and low immunoglobulin had a multiplicative interaction on reinfection, with adjusted RHR (95% CI) of 3.91 (1.27, 12.09). CONCLUSION: In this cohort of SLE, patients with severe infection had a higher risk of reinfection, and low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use were independent risk factors for recurrent severe infection.


Assuntos
Lúpus Eritematoso Sistêmico , Reinfecção , Humanos , Estudos Retrospectivos , Ciclofosfamida/efeitos adversos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Fatores de Risco , Imunoglobulinas , China/epidemiologia
18.
Org Lett ; 26(14): 2751-2757, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37486800

RESUMO

We report a new class of highly effective, benzooxaphosphole-based, water-soluble ligands in the application of Suzuki-Miyaura cross-coupling reactions for sterically hindered substrates in aqueous media. The catalytic activities of the coupling reactions were greatly enhanced by the addition of catalytic amounts of organic phase transfer reagents, such as tetraglyme and tetrabutylammonium bromide. The optimized general protocol can be conducted with a low catalyst load, thereby providing a practical solution for these reactions. The viability of this new Suzuki-Miyaura protocol was demonstrated with various substrates to generate important building blocks, including heterocycles, for the synthesis of biologically active compounds.

19.
Biotechnol Genet Eng Rev ; : 1-19, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36960749

RESUMO

To explore how to control the estrogen level in vivo by regulating the activity of the estrogen receptor in the development of breast cancer drugs, multiple-featured evaluation methods were first applied to screen the molecular descriptors of compounds according to the information of antagonist ERα provided in this study. Combining the methods of Extreme Gradient Boost (XGBoost), Light Gradient Boosting Machine (LightGBM) and Random Forest (RF), a stacking-integrated regression model for quantitatively predicting the ERα (estrogen receptors alpha) activity of breast cancer candidate drug was constructed, which considered the compounds acting on the target and their biological activity data, a series of molecular structure descriptors as the independent variables, and the biological activity values as the dependent variables. Then, three classification methods of XGBoost, LightGBM, and Gradient Boosting Decision Tree (GBDT) were selected and the voting strategy was applied to build five ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) classification prediction models. Finally, two schemes based on genetic algorithm (GA) were used to optimize the model and provide predictions for optimizing the biological activity and ADMET properties of ERα antagonists simultaneously. Results showed that the model prediction has strong practical significance, which can guide the structural optimization of existing active compounds and improve the activity of anti-breast cancer candidate drugs.

20.
Methods Mol Biol ; 2629: 305-330, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36929083

RESUMO

Genetic variants can alter response to drugs and other therapeutic interventions. The study of this phenomenon, called pharmacogenomics, is similar in many ways to other types of genetic studies but has distinct methodological and statistical considerations. Genetic variants involved in the processing of exogenous compounds exhibit great diversity and complexity, and the phenotypes studied in pharmacogenomics are also more complex than typical genetic studies. In this chapter, we review basic concepts in pharmacogenomic study designs, data generation techniques, statistical analysis approaches, and commonly used methods and briefly discuss the ultimate translation of findings to clinical care.


Assuntos
Farmacogenética , Projetos de Pesquisa , Farmacogenética/métodos , Testes Farmacogenômicos , Fenótipo
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