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A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques.
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Hepatoid adenocarcinoma (HAC) is a poorly differentiated extrahepatic tumor that can produce alpha-fetoprotein (AFP). The literature does not provide a comprehensive understanding of the prognostic factors for HAC. Therefore, we present a novel nomogram to predict the cancer-specific survival (CSS) of patients with HAC. We analyzed 265 cases of HAC from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. Using a Cox proportional hazard regression model, we identified several risk factors and incorporated them into our predictive nomogram. The nomogram's predictive ability was assessed by utilizing the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC). Results from a multivariate Cox regression showed that CSS was independently correlated with liver metastasis, surgery, and chemotherapy. Our nomogram had a C-index of 0.71 (95% CI 0.71-0.96). Furthermore, calibration curves demonstrated concordance between the predicted survival probability from the nomogram and the observed survival probability. The areas under the curve (AUC) for 6-month, 1-, and 3-year survival were 0.80, 0.82, and 0.88, respectively. Our study successfully formulated a prognostic nomogram that offers promising predictions for the 6-month, 1-, and 3-year CSS of patients with HAC. This nomogram holds potential for practical use in guiding treatment decisions and designing clinical trials.
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OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.
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Espectrometria de Massas em Tandem , Água , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Formiatos , Extração em Fase Sólida/métodosRESUMO
Developing efficient adsorbents for acetylene purification from multicomponent mixtures is of critical significance in the chemical industry, but the trade-off between regenerability and selectivity significantly restricts practical industrial applications. Here, we report ultramicroporous metal-organic frameworks with acetylene-affinity channels to enhance electrostatic interaction between C2H2 and frameworks for the efficient one-step purification of C2H2 from C2H2/CO2/C2H4 mixtures, in which the electrostatic interaction led to high regenerability. The obtained SNNU-277 exhibits significantly higher adsorption capacity for C2H2 than that for both C2H4 and CO2 at 298 K and 0.1 bar, while an ultrahigh selectivity of C2H2/C2H4 (100.6 at 298 K) and C2H2/CO2 (32.8 at 298 K) were achieved at 1 bar. Breakthrough experiments validated that SNNU-277 can efficiently separate C2H2 from C2H2/C2H4/CO2 mixtures. CO2 and C2H4 broke through the adsorption column at 4 and 14.8 min g-1, whereas C2H2 was detected until 177.6 min g-1 at 298 K. Theoretical calculations suggest that the framework is electrostatically compatible with C2H2 and electrostatically repels C2H4 and CO2 in the mixed components. This work highlights the importance of rational pore engineering for maximizing the electrostatic effect with the preferentially absorbed guest molecule for efficient multicomponent separation.
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Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.
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Oryza , Oryza/genética , Melhoramento Vegetal , Reprodução , Evolução Biológica , Hibridização GenéticaRESUMO
Seeking an effective and safe scheme is the common goal of clinical treatment of tumor patients. In recent years, traditional Chinese medicine has attracted more and more attention in order to discover new drugs with good anti-tumor effects. Oroxylin A (OA) is a compound found in natural Oroxylum indicum and Scutellaria baicalensis Georgi plants and has been used in the treatment of various cancers. Studies have shown that OA has a wide range of powerful biological activities and plays an important role in neuroprotection, anti-inflammation, anti-virus, anti-allergy, anti-tumor and so on. OA shows high efficacy in tumor treatment. Therefore, it has attracted great attention of researchers all over the world. This review aims to discuss the anti-tumor effects of OA from the aspects of cell cycle arrest, induction of cell proliferation and apoptosis, induction of autophagy, anti-inflammation, inhibition of glycolysis, angiogenesis, invasion, metastasis and reversal of drug resistance. In addition, the safety and toxicity of the compound were also discussed. As a next step, to clarify the benefits and adverse effects of Oroxylin A in cancer patients further experiments, especially clinical trials, are needed.
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Flavonoides , Neoplasias , Humanos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Apoptose , Proliferação de Células , Autofagia , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: The inflammatory response is acknowledged as a crucial pathological aspect of spinal cord injury (SCI). Tetramethylpyrazine (TMP) has been demonstrated to possess neuroprotective properties within the central nervous system via its anti-inflammatory mechanisms. This study aims to investigate the molecular mechanism by which TMP alleviates SCI from an anti-inflammatory standpoint. METHODS: The SCI model was established using the MASCIS impactor device. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was utilised to assess rat locomotion. Nissl and Golgi staining were used to observe neuron and dendritic spine morphology, respectively. A transmission electron microscope was used to observe the microcosmic morphology of the axon. ELISA kits were used to measure the concentrations of IL-1ß and IL-18 in the spinal cord. Immunofluorescence staining was used to detect P2X7R+/IBA-1+ cells, and Western blot and RT-qPCR were used to analyze the protein and mRNA expression of P2X7R in the spinal cord. Additionally, Western blot was used to detect NLRP3 and Cleaved-Caspase-1 (p20), the critical proteins in the NLRP3 inflammasome pathway. RESULTS: TMP ameliorated the microcosmic morphology of the axon and had an inhibitory effect on the concentrations of IL-1ß and IL-18 after SCI. Furthermore, TMP inhibited the expression of both P2X7R and critical proteins of the NLRP3 inflammasome pathway on microglia after SCI. The aforementioned effects of TMP exhibit similarities to those of BBG (P2X7R antagonist); however, they can be effectively reversed by BzATP (P2X7R activator). CONCLUSION: TMP alleviated SCI via reducing tissue damage, neuroinflammation, and the expression of P2X7R, NLRP3, IL-1ß, and IL-18.
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Anti-Inflamatórios , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Pirazinas , Traumatismos da Medula Espinal , Animais , Ratos , Anti-Inflamatórios/uso terapêutico , Inflamassomos , Interleucina-18 , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/etiologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Ratos Sprague-Dawley , Medula Espinal , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismoRESUMO
Staphylococcus aureus inhabits diverse habitats including food waste and wastewater treatment plants. Cases of S. aureus-induced infection are commonly reported worldwide. The emergence of antimicrobial resistance (AMR) of S. aureus is a growing public health threat worldwide. Here, we longitudinally monitored global trends in antibiotic resistance genes (ARGs) of 586 S. aureus strains, isolated between 1884 and 2022. The ARGs in S. aureus exhibited a significant increase over time (P < 0.0001). Mobile genetic elements play a crucial role in the transfer of ARGs in S. aureus strains. The structural equation model results revealed a significant correlation between the human development index and rising antibiotic consumption, which subsequently leads to an indirect escalation of AMR in S. aureus strains. Lastly, a machine learning algorithm successfully predicted the AMR risk of global terrestrial S. aureus with over 70% accuracy. Overall, these findings provided valuable insights for managing AMR in S. aureus.
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Eliminação de Resíduos , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Alimentos , Farmacorresistência BacterianaRESUMO
Activated sludge (AS) plays a vital role in removing organic pollutants and nutrients from wastewater. However, the risks posed by horizontal gene transfer (HGT) between bacteria in AS are still unclear. Here, a total of 478 high-quality non-redundant metagenome-assembled genomes (MAGs) were obtained. >50 % and 5 % of MAGs were involved in at least one HGT and recent HGT, respectively. Most of the transfers (82.4 %) of antimicrobial resistance genes (ARGs) occurred among the classes of Alphaproteobacteria and Gammaproteobacteria. The bacteria involved in the transfers of virulence factor genes (VFGs) mainly include Alphaproteobacteria (42.3 %), Bacteroidia (19.2 %), and Gammaproteobacteria (11.5 %). Moreover, the number of ARGs and VFGs in the classes of Alphaproteobacteria and Gammaproteobacteria was higher than that in other bacteria (P < 0.001). Mobile genetic elements were important contributors to ARGs and VFGs in AS bacteria. These results have implications for the management of antimicrobial resistance and virulence in activated sludge microorganisms.
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Antibacterianos , Esgotos , Esgotos/microbiologia , Virulência/genética , Antibacterianos/farmacologia , Genes Bacterianos , Transferência Genética Horizontal , Farmacorresistência Bacteriana/genética , Bactérias/genética , Fatores de Virulência/genéticaRESUMO
BACKGROUND: Danon disease (DD), in which mutations in the X-linked lysosome-associated membrane protein-2 (LAMP-2) gene result in hypertrophic cardiomyopathy, is a rare disease, reported primarily in small samples or cases. However, with the development of cardiac magnetic resonance imaging and genetic technology in recent years, the number of reports has increased. CASE SUMMARY: We report a case of DD in an adolescent male patient, confirmed by genetic testing. The patient was admitted to our hospital with complaints of a three-year history of chest tightness and shortness of breath. His preliminary clinical diagnosis is hypertrophic cardiomyopathy. Our report includes the patient's clinical course from hospital admission to death, step-by-step diagnosis, treatment course, and noninvasive imaging features. We highlight how a noninvasive diagnostic approach, based solely on clinical and imaging "red flags" for DD, can be used to achieve a diagnosis of DD with a high degree of confidence. CONCLUSION: DD is a very dangerous cardiomyopathy, and it is necessary to achieve early diagnosis and treatment.
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BACKGROUND: Disitamab Vedotin is a novel antibody-drug conjugate (ADC) drug targeting HER2, which has shown a potential synergistic effect between Disitamab Vedotin and immune checkpoint inhibitors (ICIs). Therefore, we plan to conduct a retrospective real-world study to evaluate the efficacy and safety of Disitamab Vedotin monotherapy or combined with ICIs in the treatment of advanced or metastatic solid tumors. METHODS: This retrospective study involved patients with locally advanced or metastatic solid tumors who were treated with Disitamab Vedotin monotherapy or combined with ICIs at West China Hospital of Sichuan University from July 2019 to June 2023. The observation items included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: This study included 49 patients, out of which 34 patients were treated with Disitamab Vedotin plus ICIs and 15 patients received Disitamab Vedotin alone. In all patients, the median PFS was 10 months. The 6-month and 1-year OS rates were 91.1% and 82.3%, respectively. Eighteen (36.7%) patients achieved a partial response, and sixteen (32.7%) patients had stable disease. The combination therapy of Disitamab Vedotin plus ICIs showed a higher ORR (44.1% vs. 20.0%) and a longer median PFS (14 vs. 8 months) compared to Disitamab Vedotin alone. The median PFS for patients expressed with HER2 2+/3+ was 10 months and was not reached for patients expressed with HER2 0/1+. Grade 3-4 TRAEs occurred in 14.7% of patients who received the combination treatment and in 26.7% of patients who received Disitamab Vedotin alone. CONCLUSIONS: Our study showed that Disitamab-Vedotin-based treatment, alone or in combination with ICIs, exerted considerable prognosis and good tolerance in patients with locally advanced or metastatic solid tumors, regardless of the HER2 expression levels. Whether combination therapy with ICIs provides greater therapeutic benefits compared to monotherapy needs to be further explored through randomized controlled trials.
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Imunoconjugados , Segunda Neoplasia Primária , Neoplasias , Humanos , Imunoconjugados/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Neoplasias/tratamento farmacológicoRESUMO
Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.
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Antígenos de Neoplasias , Neoplasias Colorretais , Humanos , Antígenos de Neoplasias/genética , Imunoterapia , Peptídeos , Resultado do Tratamento , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genéticaRESUMO
BACKGROUND: Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to two years and to identify the critical exposure periods. METHODS: A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24 months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. RESULTS: The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). CONCLUSION: Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first two years, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033 kb).
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Introduction: Dryland ecosystems face serious threats from climate change. Establishing the spatial pattern of ecosystem multifunctionality, maximum height and the correlation of biodiversity patterns with climate change is important for understanding changes in complex ecosystem processes. However, the understanding of their relationships across large spatial areas remains limited in drylands. Methods: Accordingly, this study examined the spatial patterns of ecosystem multifunctionality, maximum height and considered a set of potential environmental drivers by investigating natural shrub communities in Northwest China. Results: We found that the ecosystem multifunctionality (EMF) and maximum height of shrub communities were both affected by longitude, which was positively correlated with the precipitation gradient. Specifically, the EMF was driven by high precipitation seasonality, and the maximum height was driven by high precipitation stability during the growing season. Among the multiple biodiversity predictors, species beta diversity (SD-beta) is the most common in determining EMF, although this relationship is weak. Discussion: Unlike tree life form, we did not observe biodiversity-maximum height relationships in shrub communities. Based on these results, we suggest that more attention should be paid to the climatical fluctuations mediated biodiversity mechanisms, which are tightly correlated with ecosystem's service capacity and resistance capacity under a rapid climate change scenario in the future.
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BACKGROUND: Trimodality therapy (TMT) is a mature alternative to radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC) who seek to preserve their primary bladder or are inoperable due to comorbidities. To date, there has been increasing evidence of the effectiveness of TMT as an alternative to RC. In contrast, no literature has stated the effectiveness of neoadjuvant chemotherapy combined with RC (NAC + RC) compared with TMT. OBJECTIVE: We aimed to compare the prognosis between patients receiving TMT and NAC + RC. METHODS: The clinicopathological characteristics of patients with T2-4aN0M0 MIBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models and KaplanâMeier survival curves were used for the survival analysis. Propensity-score matching (PSM) was applied to determine the differences between the two groups. The primary outcome was cancer-specific survival (CSS), and the secondary outcome was overall survival (OS). RESULTS: In total, 1,175 patients with MIBC who underwent TMT (n = 822) or NAC + RC (n = 353) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. After 1:1 PSM, the final patient sample included 303 pairs. The prognosis of patients receiving NAC + RC was significantly better than that of patients receiving TMT in both unmatched and matched cohorts (5-year CSS: before PSM, 75.4% vs. 50.6%, P < 0.0001; after PSM, 76.3% vs. 49.5%, P < 0.0001; 5-year OS: before PSM, 71.7% vs. 37.4%, P < 0.0001; after PSM, 71.7% vs. 31.4%, P < 0.0001). The survival advantages of NAC + RC remained remarkable in the stratified analysis of most factors after PSM. Multivariate Cox regression analysis showed that being older than 68 years old, unmarried, grade III/IV, T3-4a stage, and undergoing TMT independently correlated with poor OS. CONCLUSION: Thus, in this study, patients with MIBC receiving NAC + RC presented with a better prognosis than those receiving TMT.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Idoso , Bexiga Urinária/patologia , Terapia Neoadjuvante , Cistectomia/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Músculos/patologia , Estudos Retrospectivos , Invasividade Neoplásica/patologiaRESUMO
Gut played a potent role in onset and progression of metabolic disorders, presenting an exciting direction for diabetes prevention. Here, the anti-diabetic effects of White hyacinth bean polysaccharides (WHBP) were observed, including the reduction of blood glucose levels and improvement of intestinal impairment in type 2 diabetes mellitus (T2DM) rats. Further data concerning intestinal protection suggested that WHBP restored intestinal barrier, as evidenced by inhibition of intestinal pathological damage, up-regulation of Zonula occluden-1 expression and manipulation of the redox system in T2DM rats. Moreover, WHBP-mediated anti-diabetic effects were in parallel with the adjustment of changes in gut microbiota composition of T2DM rats. Meanwhile, hypersecretion of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone levels, which were critical coordinators of the hypothalamic-pituitary-adrenal (HPA) axis, were suppressed in T2DM rats exposed to WHBP, indicating that WHBP-mediated health benefits were referring to regulate brain feedback in reduction of HPA axis. Concomitantly, further suggested and expanded on gut-brain communication by data of microbial metabolites short-chain fatty acids, mediators of gut-brain interactions, were remarkably raised in cecum contents of T2DM rats subjected to WHBP. Collectively, WHBP performed anti-diabetic effects were associated with control of microbiota-gut-brain axis implicated in intestinal barrier, HPA axis, gut microbiota and their metabolites.
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Diabetes Mellitus Tipo 2 , Hyacinthus , Ratos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Eixo Encéfalo-Intestino , Sistema Hipófise-Suprarrenal/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismoRESUMO
Global warming impacts crop production and threatens food security. Elevated temperatures are sensed by different cell components. Temperature increases are classified as either mild warm temperatures or excessively hot temperatures, which are perceived by distinct signaling pathways in plants. Warm temperatures induce thermomorphogenesis, while high-temperature stress triggers heat acclimation and has destructive effects on plant growth and development. In this review, we systematically summarize the heat-responsive genetic networks in Arabidopsis and crop plants based on recent studies. In addition, we highlight the strategies used to improve grain yield under heat stress from a source-sink perspective. We also discuss the remaining issues regarding the characteristics of thermosensors and the urgency required to explore the basis of acclimation under multifactorial stress combination.
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Arabidopsis , Resposta ao Choque Térmico , Resposta ao Choque Térmico/genética , Plantas , Temperatura Alta , Temperatura , Arabidopsis/metabolismoRESUMO
Vibrio parahaemolyticus is a common pathogen, and has emerged with multiple antimicrobial resistance (AMR). However, few studies have conducted large-scale investigations of AMR and virulence trends of V. parahaemolyticus worldwide. This study longitudinally monitored antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) trends of 1540 V. parahaemolyticus isolates isolated from 1951 to 2021. The number of ARGs in V. parahaemolyticus isolates distinctly increased over the years (P = 5.9e-10), while the number of VFGs decreased significantly (P < 2.2e-16). However, the number of VFGs of isolates isolated from humans has not changed significantly over the years (R = 0.013, P = 0.74), suggesting that the pathogenic risk to humans has not been reduced. Besides, mobile genetic elements are important contributors to ARGs in V. parahaemolyticus (R = 0.34, P < 2.2e-16), but have no promoting effect on VFGs (P = 0.50). The structural equation model illustrated that the human development index promoted the consumption of antibiotics, thereby indirectly promoting an increase in the AMR of the V. parahaemolyticus isolates. Finally, the random forest was performed to predict the ARG and VFG risks of global terrestrial V. parahaemolyticus isolates, and successfully map these threats with over 80% accuracy. This study aimed to evaluate the global risks posed by AMR and virulence, which helps to develop methods specifically targeting V. parahaemolyticus to mitigate these threats.
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Anti-Infecciosos , Vibrio parahaemolyticus , Humanos , Antibacterianos/farmacologia , Vibrio parahaemolyticus/genética , Farmacorresistência Bacteriana/genética , Algoritmo Florestas AleatóriasRESUMO
Background: Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury. Objective: To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI. Methods: We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria. Results: Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy. Conclusion: Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.
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This study aims to present a sustainably releasing system of exosomes-fibrin combinate loaded on tantalum-coating titanium implants. We hope to investigate potential effects of the system on osseointegration between tantalum coating titanium implants and its surrounding bone tissue. Exosomes derived from rabbit bone marrow stromal cells (rBMSCs) and fibrin were deposited onto the micro-nanostructure tantalum coating surface (Ta + exo + FI) and compared to control groups, including tantalum coating (Ta), tantalum coating loaded exosomes (Ta + exo) and tantalum coating loaded fibrin (Ta + FI). The optimal concentration of loading exosomes, exosomes uptake capacity by BMSCs, and the effect of controlled-release by fibrin were assessed by laser scanning confocal microscope (LCSM) and microplate reader. The optimal concentration of exosomes was 1 µg/µL. Adhesion, proliferation, and osteogenic differentiation ability of BMSCs on different materials were assessed in vitro. Finally, osseointegrative capacity of Ta, Ta + exo, Ta + FI, Ta + exo + FI implants in rabbit tibia were respectively evaluated with histology and bone-implant contact ratio (BIC%). It was demonstrated that exosome sustained-release system with fibrin loading on the tantalum coating was successfully established. Fibrin contribute to exosomes release extension from 2d to 6d. Furthermore, Ta + exo + FI significantly promoted adhesion, proliferation, and osteogenic differentiation of BMSCs. In vivo, the implants in Ta + exo + FI group displayed the highest osseointegrative capability than those in other groups. It is concluded that this exosome delivery system on the implants may be an effective way for tantalum coating titanium implants to promote osseointegration between implant and its surrounding bone tissue.