RESUMO
Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44-like, an R2R3-MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44-like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling-mediated salt and drought tolerance. Furthermore, we found that MdMYB44-like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44-like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44-like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44-like-MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44-like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44-like precisely modulates ABA-mediated salt and drought tolerance in apples through the MdPYL8-MdPP2CA module.
Assuntos
Arabidopsis , Malus , Malus/genética , Malus/metabolismo , Resistência à Seca , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Cloreto de Sódio/farmacologia , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Estresse FisiológicoRESUMO
BACKGROUND: Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. RESULTS: Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. CONCLUSIONS: Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.
Assuntos
Cyprinidae , Ecossistema , Animais , Filogenia , Cyprinidae/genética , Genômica , Água do Mar , Adaptação Fisiológica/genéticaRESUMO
Recent genomic analyses of evolutionary radiations suggest that ancient introgression may facilitate rapid diversification and adaptive radiation. The loach genus Triplophysa, a genus with most species endemic to Tibetan Plateau, shows ecological diversity and rapid evolution and represents a potential example of adaptive radiation linked to the uplift of the Tibetan Plateau. Here, we interrogate the complex evolutionary history of Triplophysa fishes through the analysis of whole-genome sequences. By reconstructing the phylogeny of Triplophysa, quantifying introgression across this clade, and simulating speciation and migration processes, we confirm that extensive gene flow events occurred across disparate Triplophysa species. Our results suggest that introgression plays a more substantial role than incomplete lineage sorting in underpinning phylogenetic discordance in Triplophysa. The results also indicate that genomic regions affected by ancient gene flow exhibit characteristics of lower recombination rates and nucleotide diversity and may associate with selection. Simulation analysis of Triplophysa tibetana suggests that the species may have been affected by the Gonghe Movement in the third uplift of the Tibetan Plateau, resulting in founder effects and a subsequent reduction in Ne.
Assuntos
Altitude , Cipriniformes , Animais , Filogenia , Tibet , Cipriniformes/genética , Adaptação Fisiológica/genéticaRESUMO
BACKGROUND: Immune-checkpoint blockade (ICB) therapy shows promise for treating aggressive triple-negative breast cancer (TNBC). However, only some patients benefit from ICB, revealing an urgent need for identifying novel strategies for sensitizing patients to ICB. Previously, the authors demonstrated that type-I protein arginine methyltransferases (PRMTs) regulated antiviral innate-immune responses in TNBC by altering RNA splicing. This study aimed to explore the effects of targeting type-I PRMTs on the tumor microenvironment (TME) and the efficacy of ICB therapy against TNBC. METHODS: Single-cell transcriptomic analysis was performed to investigate the effects of type-I PRMT inhibition on the TME, especially T-cell subsets. Single-cell T-cell receptor sequencing was performed to analyze the diversity and dynamics of the T-cell repertoire. A syngeneic murine model of TNBC was used to evaluate the therapeutic efficacy and immune memory effect of combining a type-I PRMT inhibitor (MS023) with an anti-programmed cell death protein 1 (PD-1) antibody. RESULTS: Type-I PRMT inhibition combined with anti-PD-1 therapy reduced tumor growth. Mechanistically, type-I PRMT inhibition reshaped the TME. Increased CD8 T-cell infiltration was verified using flow cytometry. Increased clonotypes and clonal diversity were also observed after MS023 treatment, which contributed to immune memory following combination treatment. CONCLUSIONS: Targeting type-I PRMT can potentially improve immunotherapeutic efficacies in patients with TNBC. By enhancing the tumor immunogenicity and promoting a more favorable immune microenvironment, this combined approach may enable more patients with TNBC to benefit from immunotherapies.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Receptor de Morte Celular Programada 1 , Proteína-Arginina N-Metiltransferases/genética , Imunoterapia , Morte Celular , Microambiente TumoralRESUMO
Transfer RNAs (tRNAs) are essential for translation, and tRNA expression and modifications are regulated by many factors. However, the interplay between the microbiome and host tRNA profiles through host-microbiome interactions has not been explored. In this study, we investigated host-microbiome interactions via the tRNA profiling of four tissue types from germ-free and specific pathogen-free mice. Our analyses reveal that cytosolic and mitochondrial tRNA expression and tRNA modifications in the host are reprogrammed in a tissue-specific and microbiome-dependent manner. In terms of tRNA expression, the intestines and brains are more sensitive to the influence of the microbiome than the livers and kidneys. In terms of tRNA modifications, cytosolic tRNAs show more obvious changes in the livers and kidneys in the presence of the microbiome. Our findings reveal a previously unexplored relationship among the microbiome, tRNA abundance, and epitranscriptome in a mammalian host.
Assuntos
Microbiota , Transcriptoma , Animais , Camundongos , Microbiota/genética , Mitocôndrias/genética , Processamento Pós-Transcricional do RNA , RNA de Transferência/genética , RNA de Transferência/metabolismoRESUMO
Enzyme-driven micro/nanomotors (MNMs) have demonstrated potentials in the biomedical field because of their excellent biocompatibility, versatility, and fuel bioavailability. However, the fragility of enzymes limits their practical application, because of their susceptibility to denaturation and degradation in realistic scenarios. Herein, a simple yet versatile and effective approach is reported to preserve the enzymatic activity and propulsion capability of enzymatic MNMs under various harsh conditions using metal organic frameworks (MOFs) as a protective shell. Urease can be encapsulated within the exoskeleton of zeolitic imidazolate framework-8 (ZIF-8) via biomimetic mineralization to form ZIF-8@urease (ZU-I) nanomotors that exhibit self-propulsion in the presence of urea. When exposed to harsh conditions, including high temperature, presence of proteases, and organic solvents, the ZU-I nanomotors still maintained their activity and mobility, whereas ZIF-8 with externally modified urease (ZU-O) nanomotors with externally modified urease as a control rapidly lost their motion capabilities owing to the inactivation of urease. Furthermore, ZU-I nanomotors exhibit effectively enhanced diffusion within the small intestine fluid, achieving a fourfold higher mucus penetration than the ZU-O nanomotors. The results highlight the effectiveness of using MOFs as protective shells for enzyme nano-engines, which can greatly advance the practical applications of enzymatic MNMs under realistic conditions, especially for biomedical purpose.
Assuntos
Estruturas Metalorgânicas , UreaseRESUMO
Energy conversion and transfer of enzyme-catalyzed reactions at molecular level are an interesting and challenging scientific topic that helps understanding biological processes in nature. In this study, it is demonstrated that enzyme-catalyzed reactions can enhance diffusion of surrounding molecules and thus accelerate cargo transport within 1D micro/nanochannels. Specifically, urease is immobilized on the inner walls of silica micro/nano-tubes to construct bio-catalytically active micro/nanochannels. The catalytic reaction inside the channels drives a variety of cargoes, including small dye molecules, polymers, and rigid nanoparticles (e.g., quantum dots, QDs), to pass through these micro/nanochannels much faster than they will by free diffusion. The enhanced diffusion of molecular species inside the channels is validated by direct observation of the Brownian motion of tracer particles, and further confirmed by significantly enhanced Raman intensity of reporter molecules. Finite element and Brownian dynamics simulations provide a theoretical understanding of these experimental observations. Furthermore, the effect of the channels' size on the diffusion enhancement is examined. The acceleration effect of the cargo transport through these enzymatically active micro/nanochannels can be turned on or off via chemical activators or inhibitors. This study provides valuable insights on the design of biomimetic channels capable of controlled and efficient transmembrane transport.
RESUMO
A hydrophobic Ni-PTFE modified electrode has been prepared by constant current and cathodic electroplating with a nickel sheet as substrate in a PTFE suspension. Then the Ni-PTFE modified electrode was used for electroreduction from aromatic amide to diarylimide. The electrochemical characterizations such as cyclic voltammogram, EIS, polarization curves, and electrode stability have been carried out by electrochemical workstation. The structure of the electroreduction product diarylimide was characterized by 1H NMR, FT-IR, MS(Mass Spectrum), and EA(Elemental Analyzer). Based on the hydrophobicity of the electrode, an approach suggested that the phenyl ketone radical may be formed by electroreductive deamination at the cathode. With the construction of C-N bond by the radical coupling, the electrocatalytic reduction may be comprised of a one-electron process including an ECC (Electrochemical-Chemical-Chemical) process. The electroreduction of aromatic amide to diarylimide may be controlled by both charge migration and concentration polarization. Electrocatalytic reduction of aromatic amides on Ni-PTFE modified electrodes is all well conversion ratio.
RESUMO
PURPOSE: To construct a venous thromboembolism (VTE) risk assessment model specifically for inpatients with cancer. METHOD: Patients were included according to the inclusion criteria. Univariate and multivariate analyses of all variables were included to develop a VTE risk assessment model applicable to the derivation cohort. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to test the fit degree and identification validity of the model. The patient data from separate validation cohorts verified the external population. RESULT: A total of 944 cancer patients were included in this study. Alfalfa-inpatient-CAT model, a risk assessment model for VTE in hospitalized cancer patients, was established, which mainly includes hypertension, surgical history (nearly one month), history of VTE, peripherally inserted central venous catheters (PICC), chemotherapy, PT < 12.85 s, D-dimer ≥ 1.805 µg/mL, hemoglobin ≤ 114.5 g/L, CRP ≥ 7.575 mg/L. Hosmer-Lemeshow test results showed P = 0.353 > 0.05, (χ2 = 8.872, Df = 8). The area under ROC curve was 0.906 [95%CI (0.881-0.930), P < 0.001]. The authenticity evaluation in the model database showed that the risk of thrombosis in the high-risk group (score ≥ 3) was 72.63%, significantly higher than that in the low-risk group (score 0-2) (27.37%) [χ2 = 144.00, Df = 1, P < 0.001]. CONCLUSION: This study developed a new VTE risk assessment model - Alfalfa-inpatient-CAT model - for hospitalized cancer patients at high risk of thrombosis. This model has a good fitting degree and discriminant validity. It is expected to provide some reference for the clinical treatment of inpatients with cancer through continuous optimization.
Assuntos
Pacientes Internados , Medicago sativa , Neoplasias , Tromboembolia Venosa , Humanos , Neoplasias/complicações , Masculino , Medição de Risco/métodos , Feminino , Pessoa de Meia-Idade , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Idoso , Fatores de Risco , Curva ROC , Adulto , Trombose/etiologiaRESUMO
BACKGROUND: The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients. PATIENTS AND METHODS: This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications. RESULTS: A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. CONCLUSION: This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Fibrilação Atrial , Citocromo P-450 CYP3A , Rivaroxabana , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Citocromo P-450 CYP3A/genética , Proteínas de Neoplasias/genética , Polimorfismo Genético , Estudos Prospectivos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinéticaRESUMO
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA, which is derived, at least in part, from inverted repeat Alu elements. Together, our results represent a shift in understanding the antitumor mechanism of type I PRMT inhibitors and provide a rationale and biomarker approach for the clinical development of type I PRMT inhibitors.
Assuntos
Proteína-Arginina N-Metiltransferases , Neoplasias de Mama Triplo Negativas , Biomarcadores , Linhagem Celular Tumoral , Humanos , Interferons/uso terapêutico , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Emulsion droplets on the colloidal length scale are a model system of frictionless compliant spheres. Direct imaging studies of the microscopic structure and dynamics of emulsions offer valuable insights into fundamental processes, such as gelation, jamming, and self-assembly. A microscope, however, can only resolve the individual droplets in a densely packed emulsion if the droplets are closely index-matched to their fluid medium. Mitigating perturbations due to gravity additionally requires the droplets to be density-matched to the medium. Creating droplets that are simultaneously index-matched and density-matched has been a long-standing challenge for the soft-matter community. The present study introduces a method for synthesizing monodisperse micrometer-sized siloxane droplets whose density and refractive index can be precisely and independently tuned by adjusting the volume fraction of three silane precursors. A systematic optimization protocol yields fluorescently labeled ternary droplets whose densities and refractive indexes match, to the fourth decimal place, those of aqueous solutions of glycerol or dimethylsiloxane. Because all of the materials in this system are biocompatible, we functionalize the droplets with DNA strands to endow them with programmed inter-droplet interactions. Confocal microscopy then reveals both the three-dimensional structure and the network of droplet-droplet contacts in a class of self-assembled droplet gels, free from gravitational effects. This experimental toolbox creates opportunities for studying the microscopic mechanisms that govern viscoelastic properties and self-assembly in soft materials.
Assuntos
DNA , Emulsões , Emulsões/química , DNA/química , Refratometria , Siloxanas/químicaRESUMO
INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.
Assuntos
Fraturas Ósseas , Osteoporose , Humanos , Densidade Óssea , Osteoporose/epidemiologia , Fraturas Ósseas/epidemiologia , Antebraço , CháRESUMO
BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication during or after angiography, usually transient and reversible. CIE diagnosis is challenging due to the absence of no formal diagnostic criteria. CIE can mimic stroke symptoms, including visual disturbances, seizures, confusion, coma, and focal neurological deficits. This case reports neurological deficit reversal in a CIE patient due to the embolization of an intracranial aneurysm, the second angiographic procedure in six days. CASE PRESENTATION: A 77-year-old woman was admitted to the hospital for headaches. The cerebral computed tomography (CT) scan indicated a subarachnoid hemorrhage. The first digital subtraction angiography (DSA) identified an aneurysm of 4 mm ∗ 3 mm in size in the M1 segment of the right middle cerebral artery (MCA). Then, embolization surgery was performed for the cerebral aneurysm, which was successful. However, the patient had post-operative headaches, slurred speech, epilepsy, limb weakness, and delirium post-procedure. The non-contrast cerebral CT indicated widespread edema in the right cerebral hemisphere. The patient was diagnosed with CIE and treated with symptomatic supportive therapy. Eventually, the patient's neurological deficits and cerebral edema improved significantly. CONCLUSIONS: The current case emphasized the importance of early diagnosis and symptomatic treatment of CIE. Thus, CIE should be the first consideration during the differential diagnosis of a patient having acute neurological impairment after repeated DSA.
Assuntos
Aneurisma Intracraniano , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Feminino , Humanos , Idoso , Angiografia Digital , CefaleiaRESUMO
BACKGROUND AND OBJECTIVE: Transcranial magnetic stimulation (TMS) is considered as a promising treatment option for post-stroke cognitive impairment (PSCI).Some meta-analyses have indicated that TMS can be effective in treating cognitive decline in stroke patients, but the quality of the studies included and the methodologies employed were less than satisfactory. Thus, this meta-analysis aimed to evaluate the efficacy and safety of TMS for treating post-stroke cognitive impairment. METHODS: We searched online databases like PubMed, Embase, Cochrane Library, and Web of Science to retrieve randomized controlled trials (RCTs) of TMS for the treatment of patients with PSCI. Two independent reviewers identified relevant literature, extracted purpose-specific data, and the Cochrane Risk of Bias Assessment Scale was utilized to assess the potential for bias in the literature included in this study. Stata 17.0 software was used for data analysis. RESULTS: A total of 10 studies involving 414 patients were included. The results of the meta-analysis showed that TMS was significantly superior to the control group for improving the overall cognitive function of stroke patients (SMD = 1.17, 95% CI [0.59, 1.75], I2 = 86.1%, P < 0.001). Subgroup analyses revealed that high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), and intermittent theta burst stimulation (iTBS) all have a beneficial effect on the overall cognitive function of stroke patients. However, another subgroup analysis failed to demonstrate any significant advantage of TMS over the control group in terms of enhancing scores on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and Rivermead Behavioral Memory Test (RBMT) scales. Nonetheless, TMS demonstrated the potential to enhance the recovery of activities of daily living in stroke patients, as indicated by the Modified Barthel Index (MBI) (SMD = 0.76; 95% CI [0.22, 1.30], I2 = 52.6%, P = 0.121). CONCLUSION: This meta-analysis presents evidence supporting the safety and efficacy of TMS as a non-invasive neural modulation tool for improving global cognitive abilities and activities of daily living in stroke patients. However, given the limited number of included studies, further validation of these findings is warranted through large-scale, multi-center, double-blind, high-quality randomized controlled trials. PROSPERO REGISTRATION NUMBER: CRD42022381034.
Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/psicologia , Cognição/fisiologia , Resultado do TratamentoRESUMO
The process of harmless treatment of livestock manure produces a large amount of odor, which poses a potential threat to human and livestock health. A vertical fermentation tank system is commonly used for the environmentally sound treatment of chicken manure in China, but the composition and concentration of the odor produced and the factors affecting odor emissions remain unclear. In this study, we investigated the types and concentrations of odors produced in the mixing room (MR), vertical fermenter (VF), and aging room (AR) of the system, and analyzed the effects of bacterial communities and metabolic genes on odor production. The results revealed that 34, 26 and 26 odors were detected in the VF, MR and AR, respectively. The total odor concentration in the VF was 66613 ± 10097, which was significantly greater than that in the MR (1157 ± 675) and AR (1143 ± 1005) (P < 0.001), suggesting that the VF was the main source of odor in the vertical fermentation tank system. Methyl mercaptan had the greatest contribution to the odor produced by VF, reaching 47.82%, and the concentration was 0.6145 ± 0.2164 mg/m3. The abundance of metabolic genes did not correlate significantly with odor production, but PICRUSt analysis showed that cysteine and methionine metabolism involved in methyl mercaptan production was significantly more enriched in MR and VF than in AR. Bacillus was the most abundant genus in the VF, with a relative abundance significantly greater than that in the MR (P < 0.05). The RDA results revealed that Bacillus was significantly and positively correlated with methyl mercaptan. The use of large-scale aerobic fermentation systems to treat chicken manure needs to focused on the production of methyl mercaptan.
RESUMO
The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways.
Assuntos
Apoptose , Cisplatino , Mitocôndrias , Espécies Reativas de Oxigênio , Resposta a Proteínas não Dobradas , Humanos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/genética , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacosRESUMO
KEY MESSAGE: MdERF023 is a transcription factor that can reduce salt tolerance by inhibiting ABA signaling and Na+/H+ homeostasis. Salt stress is one of the principal environmental stresses limiting the growth and productivity of apple (Malus × domestica). The APETALA2/ethylene response factor (AP2/ERF) family plays key roles in plant growth and various stress responses; however, the regulatory mechanism involved has not been fully elucidated. In the present study, we identified an AP2/ERF transcription factor (TF), MdERF023, which plays a negative role in apple salt tolerance. Stable overexpression of MdERF023 in apple plants and calli significantly decreased salt tolerance. Biochemical and molecular analyses revealed that MdERF023 directly binds to the promoter of MdMYB44-like, a positive modulator of ABA signaling-mediated salt tolerance, and suppresses its transcription. In addition, MdERF023 downregulated the transcription of MdSOS2 and MdAKT1, thereby reducing the Na+ expulsion, K+ absorption, and salt tolerance of apple plants. Taken together, these results suggest that MdERF023 reduces apple salt tolerance by inhibiting ABA signaling and ion transport, and that it could be used as a potential target for breeding new varieties of salt-tolerant apple plants via genetic engineering.
Assuntos
Regulação da Expressão Gênica de Plantas , Malus , Proteínas de Plantas , Tolerância ao Sal , Transdução de Sinais , Fatores de Transcrição , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Malus/genética , Malus/metabolismo , Malus/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Tolerância ao Sal/genética , Sódio/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Since May 2022, mpox outbreaks have been occurring in non-mpox endemic areas, with the main population affected being men who have sex with men (MSM). Outbreak prevention and control depend not only on the effectiveness of vaccines but also on people's willingness to receive these vaccines. Currently, there is lack of synthesis on the overall rates and influence factors of MSMs' willingness to vaccinate against mpox. Therefore, we systematically reviewed studies that assessed the willingness of MSM to receive mpox vaccine. METHODS: Studies reporting mpox vaccination intentions among MSM were included by searching five databases (PubMed, Web of Science, EMBASE, CINAHL, and SCOPUS) from inception to May 12, 2024. The quality of the included literature was assessed using Joanna Briggs Institute's critical appraisal tool. The data analysis software is Stata17. The systematic review has been registered with Prospero (registration ID: CRD42023452357). RESULTS: Twenty cross-sectional studies were included in the review. Meta-analysis results showed that the pooled willingness rate of vaccinate against mpox was 77.0% (95% CI: 73-81%, I2 = 99.4%). According to subgroup analysis, study countries (P = 0.002), research sample size (P = 0.001), and whether participants were infected with HIV (P = 0.002) may be sources of heterogeneity. The results of the meta-analysis of influencing factors showed that more number of sexual partners (OR: 2.24, 95%CI: 1.86-2.69), pre-exposure prophylaxis use (OR: 6.04, 95%CI: 4.80-7.61), history of sexually transmitted infections (OR: 2.96, 95%CI: 2.33-3.76), confidence in the vaccine's effectiveness (OR: 2.79, 95%CI: 2.04-3.80) and safety (OR: 10.89, 95%CI: 5.22-22.72), fear of mpox infection (OR: 2.47, 95%CI: 2.11-2.89) and epidemics (OR: 2.87, 95%CI: 2.22-3.70), high mpox knowledge (OR: 2.35, 95%CI: 1.51-3.66), and the belief that people at high risk should be prioritized for vaccination (OR: 3.09, 95%CI: 1.40-6.84) were the facilitators of vaccine willingness. In addition, as a secondary outcome, meta-analysis results showed a pooled unwillingness rate of 16% (95% CI: 13-20%, I2 = 98.1%, 9 studies). CONCLUSION: Willingness to vaccinate mpox was high among MSM, but some participants still had negative attitudes towards vaccination. Therefore, the Ministry of Public Health should develop targeted and effective strategies against those influencing factors to prevent and manage mpox outbreaks.
Assuntos
Homossexualidade Masculina , Humanos , Masculino , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologiaRESUMO
Experiments were conducted in this study on the co-hydropyrolysis of three components of biomass (cellulose, hemicellulose, and lignin) and HDPE by using SR-Pd/Trap-HZ-5 as catalyst. To control the variable, we use the same experiment conditions in co-hydropyrolysis: Si/Al ratio of 50, Pd load 1 %, catalyst to reactant ratio of 1 : 10, 1â MPa, 400 °C, reaction time 1â h. Use XRD, TEM, BET, and NH3-TPD to confirm catalyst successful synthesis; use pine sawdust (PW) co-hydropyrolysis with HDPE to analyse catalytic activity; and use GC/MS to characterize the chemical composition of the bio-oil from the co-hydropyrolysis of biomass components and HDPE. The results show that cellulose has a significant synergistic effect with aromatic hydrocarbon production, whose selectivity was 93.3 %; hemicellulose has a synergistic effect; aromatic selectivity can reach 75.1 %; and a negative synergistic effect between lignin and HDPE was shown as the selectivity of aromatic hydrocarbons decreased from 62.1 % to 15.6 %.