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BACKGROUND: Cocaine-one of the most frequently abused illicit drugs among persons living with HIV [people living with HIV (PLWH)]-slows the decline of viral production after antiretroviral therapy and is associated with higher HIV viral load, more rapid HIV progression, and increased mortality. SETTING: We examined the impact of cocaine use on the CD4+ T-cell HIV latent reservoir (HLR) in virally suppressed PLWH participating in a national, longitudinal cohort study of the natural and treated history of HIV in the United States. METHODS: CD4+ T-cell genomic DNA from 434 women of diverse ancestry (ie, 75% Black, 14% Hispanic, 12% White) who self-reported cocaine use (ie, 160 cocaine users, 59 prior users, 215 non-users) was analyzed using the Intact Proviral HIV DNA Assay, measuring intact provirus per 106 CD4+ T cells. FINDINGS: HIV latent reservoir size differed by cocaine use (ie, median [interquartile range]: 72 [14-193] for never users, 165 [63-387] for prior users, 184 [28-502] for current users), which was statistically significantly larger in both prior (P = 0.023) and current (P = 0.001) cocaine users compared with never users. CONCLUSIONS: Cocaine use may contribute to a larger replication competent HLR in CD4+ T cells among virologically suppressed women living with HIV. Our findings are important because women are underrepresented in HIV reservoir studies and in studies of the impact of cocaine use on outcomes among PLWH.

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Linfocitos T CD4-Positivos , Trastornos Relacionados con Cocaína , Infecciones por VIH , Carga Viral , Latencia del Virus , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Trastornos Relacionados con Cocaína/epidemiología , Estudios Longitudinales , VIH-1/genética , Estados Unidos/epidemiología , ADN Viral , Cocaína

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BACKGROUND: The study aimed to evaluate how maternal pre-pregnant body mass index (BMI) impacts participant recruitment and retention. METHODS: Participants were enrolled in a longitudinal study between 30 and 36 weeks of pregnancy as having normal weight (pre-pregnant BMI ≥ 18.5 and <25 kg/m2) or obesity (pre-pregnant BMI ≥ 30.0 kg/m2). Recruitment channels included Facebook, email, newspaper, phone calls, radio advertisements, flyers, and word-of-mouth. The stages of recruitment included eligibility, consent, and completion. Pearson's chi-square tests were used to evaluate the relationship between BMI and enrollment outcomes. RESULTS: Recruitment yielded 2770 total prospective participants. After screening, 141 individuals were eligible, 83 consented, and 60 completed the study. Facebook was the most successful method for identifying eligible pregnant patients with obesity, while a higher percentage of participants recruited through word-of-mouth and flyers consented to the study. Pre-pregnant BMI was significantly associated with the stage of recruitment completed by the participant (p = 0.04), whereby individuals eligible for the study with obesity were less likely to consent and complete study visits. CONCLUSION: We demonstrated that maternal obesity was significantly associated with enrollment outcomes in a longitudinal birth cohort study. This study showed that pre-pregnancy BMI influenced study participation. Therefore, tailored recruitment strategies to enhance the recruitment and enrollment of individuals with obesity in maternal-infant health research may be necessary.

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The living cell creates a unique internal molecular environment that is challenging to characterize. By combining single-molecule displacement/diffusivity mapping (SM d M) with physiologically active extracts prepared from Xenopus laevis eggs, we sought to elucidate molecular properties of the cytoplasm. Quantification of the diffusion coefficients of 15 diverse proteins in extract showed that, compared to in water, negatively charged proteins diffused ∼50% slower, while diffusion of positively charged proteins was reduced by ∼80-90%. Adding increasing concentrations of salt progressively alleviated the suppressed diffusion observed for positively charged proteins, signifying electrostatic interactions within a predominately negatively charged macromolecular environment. To investigate the contribution of RNA, an abundant, negatively charged component of cytoplasm, extracts were treated with ribonuclease, which resulted in low diffusivity domains indicative of aggregation, likely due to the liberation of positively charged RNA-binding proteins such as ribosomal proteins, since this effect could be mimicked by adding positively charged polypeptides. Interestingly, negatively charged proteins of different sizes showed similar diffusivity suppression in extract, which are typically prepared under conditions that inhibit actin polymerization. Restoring or enhancing actin polymerization progressively suppressed the diffusion of larger proteins, recapitulating behaviors observed in cells. Together, these results indicate that molecular interactions in the crowded cell are defined by an overwhelmingly negatively charged macromolecular environment containing cytoskeletal networks. Significance Statement: The complex intracellular molecular environment is notably challenging to elucidate and recapitulate. Xenopus egg extracts provide a native yet manipulatable cytoplasm model. Through single-molecule microscopy, here we decipher the cytoplasmic environment and molecular interactions by examining the diffusion patterns of diverse proteins in Xenopus egg extracts with strategic manipulations. These experiments reveal an overwhelmingly negatively charged macromolecular environment with crosslinked meshworks, offering new insight into the inner workings of the cell.

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Background: Drug users are a high-risk group for HIV infection and are prominent HIV carriers. Given the emergence of new drugs, we explored current drug-using behaviors, HIV infections, and the correlation between drug-using behaviors and HIV infection risk among drug users from 2014 to 2021. Objective: We aimed to identify the prevalence of HIV infection risk among drug users and explore drug use behaviors based on the updated data, which could provide evidence for the precision of HIV prevention strategies among drug users. Methods: Data were collected from sentinel surveillance of drug users in rehabilitation centers and communities in Hangzhou (2014-2021), including sociodemographic characteristics, HIV awareness, drug use, risky sexual behaviors, and HIV infection status. Multivariate logistic regression was used to identify the factors influencing HIV infection and risky sexual behaviors among drug users. Results: In total, 5623 drug users (male: n=4734, 84.19%; age: mean 38.38, SD 9.94 years) were included. New drugs dominated among the participants (n=3674, 65.34%). The main mode of drug use was noninjection (n=4756, 84.58%). Overall, for 27.45% (n=1544) of injected drugs in the last month before the investigation, the average daily injection frequency was 3.10 (SD 8.24). Meanwhile, 3.43% of participants shared needles. The incidence of sexual behaviors after drug use was 33.13% (n=1863), with 35.75% (n=666) of them using a condom in the last time. Overall, 116 participants tested positive for HIV antibodies (infection rate=2.06%). New drug users exhibited more postuse sexual behaviors than traditional drug users (odds ratio [OR] 7.771, 95% CI 6.126-9.856; P<.001). HIV-aware drug users were more likely to engage in risky sexual behaviors (OR 1.624, 95% CI 1.152-2.291; P=.006). New-type drug users were more likely to engage in unprotected sexual behavior (OR 1.457, 95% CI 1.055-2.011; P=.02). Paradoxically, drug users with greater HIV awareness were more prone to engaging in unprotected sexual behavior (OR 5.820, 95% CI 4.650-7.284; P<.001). Women engaged less in unprotected sex than men (OR 0.356, 95% CI 0.190-0.665; P=.001). HIV rates were higher among injecting drug users (OR 2.692, 95% CI 0.995-7.287; P=.04) and lower among drug users who used condoms during recent sex than those who did not (OR 0.202, 95% CI 0.076-0.537; P=.001). Higher education levels were associated with higher HIV infection rates. However, there was no significant correlation between HIV cognition level and HIV infection. Conclusions: New drug types and noninjection were the main patterns in last 7 years. Using new types of drugs, rather than traditional drugs, was associated with an increased risk of HIV infection. Injection drug use was a risk factor for HIV infection. HIV awareness among drug users was high, but the incidence of risky sexual behaviors remained high. Therefore, it is important to promote the behavioral transformation of high-risk populations from cognition to attitude, and then to taking protective measures.

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Consumidores de Drogas , Infecciones por VIH , Asunción de Riesgos , Trastornos Relacionados con Sustancias , Humanos , Masculino , China/epidemiología , Infecciones por VIH/epidemiología , Estudios Transversales , Femenino , Adulto , Consumidores de Drogas/estadística & datos numéricos , Consumidores de Drogas/psicología , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/epidemiología , Prevalencia , Factores de Riesgo , Conducta Sexual/estadística & datos numéricos , Adulto Joven , Vigilancia de Guardia , Adolescente

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Carcinoma Hepatocelular , Medios de Contraste , Neoplasias Hepáticas , Ultrasonografía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Ultrasonografía/métodos , Óxidos , Compuestos Férricos , Hierro , Fluorocarburos , Sensibilidad y Especificidad , Reproducibilidad de los Resultados

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Solid bases are valuable catalysts for industrial syntheses. However, controlling the basicity of these catalysts remains a challenge. Ga4B2O9, due to µ3-O within its structure, could behave as a special solid base catalyst exhibiting intrinsic Lewis basicity. In this work, a sol-gel method was proposed to obtain continuously adjustable acidity and basicity of the metal borate catalyst (AlxGa1-x)4B2O9. According to the results of NH3-TPD, CO2-TPD, and the systematic experimental design, Lewis basic sites originating from GaO5 groups in (AlxGa1-x)4B2O9 boost the Strecker reaction rather than the Lewis acid sites related to unsaturated Al. This work illustrates the possible application of bulk-type solid solutions with simultaneous Lewis acid and base sites for the first time. A reaction mechanism has also been proposed based on the catalytic reaction results.

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Neoplasias Gastrointestinales , Humanos , Neoplasias Gastrointestinales/inmunología , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/terapia , Metástasis de la Neoplasia , Animales , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Terapia Molecular Dirigida

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Background: The current clinical treatment of chronic obstructive pulmonary disease (COPD) mainly uses drugs to improve symptoms, but these drugs cannot reverse the progression of the disease and the pathological changes in lung tissue. This study aimed to investigate the effects and mechanisms of Liver X receptors (LXRs) in ozone (O3)-induced airway inflammation and remodeling in mice. Methods: Wild mice and LXR deficient mice were exposed to O3 twice a week for 6 weeks. Some wild mice were intraperitoneally injected with T0901317 (a LXR agonist) before O3 exposure. Wild mice were exposed to ambient air and intraperitoneally injected with normal saline (NS) as control group. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected to evaluate airway inflammation, airway remodeling and lipid disorder. Results: After O3 exposure, LXR deficient mice showed severe airway inflammation and airway remodeling compared with the wild mice. There were a lot of foamy macrophages appeared in BALF of LXR deficient mice. The inflammatory proteins such as myeloid differentiation primary response protein 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) in the lung tissues of LXR deficient mice were significantly increased compared with the wild mice. In wild mice exposed to O3, T0901317 treatment can alleviate airway inflammation, airway remodeling and foamy macrophages in BALF. And MyD88 and IRAK expression in lung tissue were also attenuated by T0901317 treatment. Conclusions: LXRs play protective roles in O3-induced lipid accumulation, airway inflammation and airway remodeling.

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Neoplasias Intestinales , Tumores Neuroendocrinos , Nomogramas , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/terapia , Neoplasias Intestinales/mortalidad , Neoplasias Intestinales/terapia , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/terapia , Estudios de Cohortes , Femenino , Masculino

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INTRODUCTION AND OBJECTIVES: We initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups. RESULTS: Our findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055). CONCLUSIONS: Camrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.

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DNA N6-methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors. Herein, we report the discovery of a highly potent ALKBH1 inhibitor, 1H-pyrazole-4-carboxylic acid derivative 29. The structure-activity relationship of this series of compounds was also discussed. Because of the poor cell membrane permeability of 29, we prepared a prodrug of 29 (29E), which showed excellent cellular activities. In gastric cancer cell lines HGC27 and AGS, 29E treatment significantly increased the abundance of 6mA, inhibited cell viability, and upregulated the AMP-activated protein kinase (AMPK) signaling pathway. In addition, the hydrolysis product 29 showed high exposure in mice after administration of 29E. Collectively, this research provides a new potent ALKBH1 inhibitor, which could serve as a lead compound for subsequent drug development.

Asunto(s)

Histona H2a Dioxigenasa, Homólogo 1 de AlkB , Antineoplásicos , Inhibidores Enzimáticos , Pirazoles , Neoplasias Gástricas , Humanos , Relación Estructura-Actividad , Histona H2a Dioxigenasa, Homólogo 1 de AlkB/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Línea Celular Tumoral , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacología , Ácidos Carboxílicos/síntesis química , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Simulación del Acoplamiento Molecular , Ratones Desnudos , Ratones Endogámicos BALB C

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Sensorineural hearing loss (SNHL) represents a significant clinical challenge, predominantly attributed to oxidative stress-related mechanisms. In this work, we report an innovative antioxidant strategy for mitigating SNHL, utilizing synthetically engineered allomelanin nanoparticles (AMNPs). Empirical evidence elucidates AMNPs' profound capability in free radical neutralization, substantiated by a significant decrement in reactive oxygen species (ROS) levels within HEI-OC1 auditory cells exposure to cisplatin or hydrogen peroxide (H2O2). Comparative analyses reveal that AMNPs afford protection against cisplatin-induced and noise-induced auditory impairments, mirroring the effect of dexamethasone (DEX), a standard pharmacological treatment for acute SNHL. AMNPs exhibit notable cytoprotective properties for auditory hair cells (HCs), effectively preventing ototoxicity from cisplatin or H2O2 exposure, as confirmed by both in vitro assays and cultured organ of Corti studies. Further in vivo research corroborates AMNPs' ability to reverse auditory brainstem response (ABR) threshold shifts resulting from acoustic injury, concurrently reducing HCs loss, ribbon synapse depletion, and spiral ganglion neuron degeneration. The therapeutic benefits of AMNPs are attributed to mitigating oxidative stress and inflammation within the cochlea, with transcriptome analysis indicating downregulated gene expression related to these processes post-AMNPs treatment. The pronounced antioxidative and anti-inflammatory effects of AMNPs position them as a promising alternative to DEX for SNHL treatment.

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Herein, we report polyphosphonate covalent organic frameworks (COFs) constructed via P-O-P linkages. The materials are synthesized via a single-step condensation reaction of the charge-assisted hydrogen-bonded organic framework, which is constructed from phenylphosphonic acid and 5,10,15,20-tetrakis[p-phenylphosphonic acid]porphyrin and is formed by simply heating its hydrogen-bonded precursor without using chemical reagents. Above 210 °C, it becomes an amorphous microporous polymeric structure due to the oligomerization of P-O-P bonds, which could be shown by constant-time solid-state double-quantum 31P nuclear magnetic resonance experiments. The polyphosphonate COF exhibits good water and water vapor stability during the gas sorption measurements, and electrochemical stability in 0.5 M Na2SO4 electrolyte in water. The reported family of COFs fills a significant gap in the literature by providing stable microporous COFs suitable for use in water and electrolytes. Additionally, we provide a sustainable synthesis route for the COF synthesis. The narrow pores of the COF effectively capture CO2.

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Globally, approximately 6-20% of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.

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PURPOSE: Anterior temporal lobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE), and Stereoelectroencephalography (SEEG) plays a critical role in precisely localizing the epileptogenic zone (EZ). This study aimed to explore the effect of SEEG on the long-term outcomes of different side ATL. METHODS: From March 2012 to February 2020, a retrospective analysis was conducted on 231 TLE patients who underwent standard ATL surgery. According to the surgical sides and the utilization of SEEG during preoperative evaluation, the patients were categorized into four groups, with a follow-up period exceeding two years. RESULTS: Among the 231 TLE patients, the probability of being seizure-free two years after the surgery was 80.52%, which decreased to 65.65% after five years. There was no significant difference in outcomes between SEEG and non-SEEG patients. For overall and non-SEEG patients, there was no significant difference in short-term outcomes between different surgical sides. However, the long-term outcomes of right ATL patients were significantly better than left. Interestingly, for patients who underwent SEEG, there was no significant difference in both short-term and long-term outcomes between different surgical sides. CONCLUSION: Some TLE patients encounter challenges in localizing the EZ through non-invasive evaluation, necessitating the use of SEEG for precise localization. Furthermore, their seizure outcomes after surgery can be the same with the patients who have a clear epileptogenic zone in non-invasive evaluation. And SEEG patients can achieve a more stable long-term prognosis than non-SSEEG patients.

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OBJECTIVE: Association between mitochondrial dysfunction and osteoarthritis (OA) has been consistently investigated, yet their genetic association remains obscure. In this study, mitochondrial-related genes were used as instrumental variables to proxy for mitochondrial dysfunction, and summary data of knee OA (KOA) were used as outcome to examine their genetic association. METHODS: We obtained 1136 mitochondrial-related genes from the human MitoCarta3.0 database. Genetic proxy instruments for mitochondrial-related genes from studies of corresponding gene expression (n = 31,684) and protein (n = 35,559) quantitative trait locus (eQTLs and pQTLs), respectively. Aggregated data for KOA (62,497 KOA cases and 333,557 controls) were extracted from the largest OA genome-wide association study (GWAS). We integrated QTL data with KOA GWAS data to estimate their genetic association using summary data-based Mendelian randomization analysis (SMR). Additionally, we implemented Bayesian colocalization analysis to reveal whether suggestive mitochondrial-related genes and KOA were driven by a same genetic variant. Finally, to validate the primary findings, replication study (24,955 cases and 378,169 controls) and multi-SNP-based SMR (SMR-multi) test was performed. RESULTS: Through SMR analysis, we found that the expression levels of 2 mitochondrial-related genes were associated with KOA risk. Specifically, elevated gene expression levels of the IMMP2L (odds ratio [OR] = 1.056; 95% confidence interval [CI] = 1.030-1.082; P-FDR = 0.004) increased the risk of KOA. Conversely, increased gene expression levels of AKAP10 decreased the risk of KOA (OR = 0.955; 95% CI, 0.934-0.977; P-FDR = 0.019). Colocalization analysis demonstrated that AKAP10 (PP.H4 = 0.84) and IMMP2L (PP.H4 = 0.91) shared the same genetic variant with KOA. In addition, consistent results were found in replication study and SMR-multi test, further demonstrating the reliability of our findings. CONCLUSIONS: In summary, our analyses revealed the genetic association between mitochondrial dysfunction proxied by mitochondrial-related genes and KOA, providing new insight into potential pathogenesis of KOA. Furthermore, these identified candidate genes offer the possibility of clinical drug target development for KOA. Key points • This is the first SMR study to explore the genetic association between mitochondrial dysfunction proxied by mitochondrial-related genes and KOA. • Sufficient evidence to support genetic association between the expression levels of AKAP10 and IMMP2L, and KOA • Our MR analysis may provide novel new insight into potential pathogenesis of KOA. • These identified candidate genes offer the possibility of clinical drug target development for KOA.

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Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats' reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor ß1 (TGF-ß1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-ß1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

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MAIN CONCLUSION: The PcHsp70-5 enhances drought stress tolerance in transgenic Arabidopsis thaliana by upregulating stress tolerance genes and antioxidant enzyme activities. Heat shock proteins (HSPs) constitute a class of evolutionarily conserved proteins synthesized by organisms in response to various adverse environmental stimuli such as elevated temperatures, drought, hormonal fluctuations, high salt concentrations, and mechanical stress. However, research on HSPs has predominantly focused on model plants and crops, whereas their functions in desert plants have not been well investigated. This study analyzed the transcriptome of Pugionium cornutum and identified the complete ORFs of 25 genes of the PcHsp70 family genes. Their expression levels under drought stress were investigated using existing RNA-seq data. PcHsp70-5 genes exhibited high expression levels in both roots and leaves under drought stress. Consequently, the PcHsp70-5 genes were cloned and transformed into Arabidopsis thaliana for further analysis of their roles in drought stress response. Real-time fluorescence quantitative PCR (qRT-PCR) analysis demonstrated that both, drought stress and ABA, induced PcHsp70-5 expression. Under drought conditions, transgenic Arabidopsis plants exhibited markedly enhanced growth compared to wild-type plants, as evidenced by improved survival rates, root length, fresh weight, chlorophyll content, and reduced levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in leaves, indicating that PcHsp70-5 overexpression mitigated growth inhibition and oxidative damage induced by drought stress. Subsequent research revealed that PcHsp70-5 overexpression significantly augmented the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and increased the proline content in transgenic Arabidopsis under drought conditions, alongside a significant increase in the expression levels of genes related to stress tolerance. This suggests that PcHsp70-5 enhances drought stress tolerance in transgenic Arabidopsis by upregulating stress tolerance genes and antioxidant enzyme activities.

Asunto(s)

Brassicaceae , Regulación de la Expresión Génica de las Plantas , Proteínas HSP70 de Choque Térmico , Estrés Fisiológico , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/fisiología , Sequías , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Transcriptoma , Brassicaceae/genética , Brassicaceae/fisiología

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Glaesserella parasuis (GPS) can cause severe systemic inflammation in pigs, resulting in huge economic losses to the pig industry. At present, no effective method is available for the prevention and control of GPS infection. Molecular breeding for disease resistance is imminent, but disease-resistance genes have not been identified. To study the mechanism of systemic acute inflammation caused by GPS, we established three in vitro infection models (3D4/21 cells, PK15 cells, and PAVEC cells) according to its infection path. There was no significant difference in apoptosis among the three kinds of cells after 12 h of continuous GPS stimulation, while inflammatory factors were significantly upregulated. Subsequent transcriptome analysis revealed 1969, 1207, and 3564 differentially expressed genes (DEGs) in 3D4/21 cells, PK15 cells, and PAVEC cells, respectively, after GPS infection. Many of the DEGs were predicted to be associated with inflammatory responses (C3, CD44, etc.); cell proliferation, growth and apoptosis; gene expression; and protein phosphorylation. Key signaling pathways, including S100 family signaling, bacteria and virus recognition, and pathogen-induced cytokine storm signaling, were enriched based on Ingenuity Pathway Analysis (IPA). Furthermore, a total of three putative transmembrane receptors and two putative G-protein-coupled receptors, namely F3, ICAM1, PLAUR, ACKR3, and GPRC5A, were identified by IPA among the three types of cells. ACKR3 and GPRC5A play pivotal roles in bacterial adhesion, invasion, host immune response and inflammatory response through the S100 family signaling pathway. Our findings provide new insights into the pathological mechanisms underlying systemic inflammation caused by GPS infection in pigs, and they lay a foundation for further research on disease-resistance breeding to GPS.

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Haemophilus parasuis , Inflamación , Transducción de Señal , Enfermedades de los Porcinos , Animales , Porcinos , Haemophilus parasuis/genética , Haemophilus parasuis/patogenicidad , Transducción de Señal/genética , Inflamación/genética , Inflamación/microbiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/genética , Enfermedades de los Porcinos/inmunología , Infecciones por Haemophilus/veterinaria , Infecciones por Haemophilus/genética , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/inmunología , Transcriptoma/genética , Perfilación de la Expresión Génica , Línea Celular , Apoptosis/genética

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Taking the nonlocal effect into account, the vibration governing differential equation and boundary conditions of a magnetostrictive composite cantilever resonator were established based on the Euler magnetoelastic beam theory. The frequency equation and vibration mode function of the composite cantilever were obtained by means of the separation of variables method and the analytic solution of ordinary differential equations. The lateral deflection, vibration governing equations, and boundary conditions were nondimensionalized. Furthermore, the natural frequency and modal function of the composite beam were quantitatively analyzed with different nonlocal parameters and transverse geometry dimensions using numerical examples. Compared with the results without considering the nonlocal effect, the influence of the nonlocal effect on the vibration characteristics was analyzed. The numerical results show that the frequency shift and frequency band narrowing of the magnetostrictive cantilever resonator are induced by nonlocal effects. In particular, the high-frequency vibration characteristics, such as vibration amplitude and modal node of the composite beam, are significantly affected. These analysis results can provide a reference for the functional design and optimization of magnetostrictive resonators.