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1.
Nat Commun ; 15(1): 1268, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341443

RESUMO

The Li-S battery is a promising next-generation battery chemistry that offers high energy density and low cost. The Li-S battery has a unique chemistry with intermediate sulphur species readily solvated in electrolytes, and understanding their implications is important from both practical and fundamental perspectives. In this study, we utilise the solvation free energy of electrolytes as a metric to formulate solvation-property relationships in various electrolytes and investigate their impact on the solvated lithium polysulphides. We find that solvation free energy influences Li-S battery voltage profile, lithium polysulphide solubility, Li-S battery cyclability and the Li metal anode; weaker solvation leads to lower 1st plateau voltage, higher 2nd plateau voltage, lower lithium polysulphide solubility, and superior cyclability of Li-S full cells and Li metal anodes. We believe that relationships delineated in this study can guide the design of high-performance electrolytes for Li-S batteries.

2.
J Inflamm Res ; 17: 823-836, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344308

RESUMO

Purpose: Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators. Patients and Methods: Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. Results: A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834-0.9). The LASSO model AUC was 0.864, 95% CI (0.828-0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO. Conclusion: Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis.

3.
Dev Biol ; 509: 1-10, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38311164

RESUMO

Saliva is vital to oral health, fulfilling multiple functions in the oral cavity. Three pairs of major salivary glands and hundreds of minor salivary glands contribute to saliva production. The secretory acinar cells within these glands include two distinct populations. Serous acinar cells secrete a watery saliva containing enzymes, while mucous acinar cells secrete a more viscous fluid containing highly glycosylated mucins. Despite their shared developmental origins, the parotid gland (PG) is comprised of only serous acinar cells, while the sublingual gland (SLG) contains predominantly mucous acinar cells. The instructive signals that govern the identity of serous versus mucous acinar cell phenotypes are not yet known. The homeobox transcription factor Nkx2.3 is uniquely expressed in the SLG. Disruption of the Nkx2.3 gene was reported to delay the maturation of SLG mucous acinar cells. To examine whether Nkx2.3 plays a role in directing the mucous cell phenotype, we analyzed SLG from Nkx2.3-/- mice using RNAseq, immunostaining and proteomic analysis of saliva. Our results indicate that Nkx2.3, most likely in concert with other transcription factors uniquely expressed in the SLG, is a key regulator of the molecular program that specifies the identity of mucous acinar cells.

4.
Environ Res ; 249: 118383, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38331152

RESUMO

Zonation is a typical pattern of soil distribution and species assembly across riparian habitats. Microorganisms are essential members of riparian ecosystems and whether soil microbial communities demonstrate similar zonation patterns and how bulk and rhizosphere soil microorganisms interact along the elevation (submergence stress) gradient remain largely unknown. In this study, bulk and rhizosphere (dominant plant) soil samples were collected and investigated across riparian zones where the submergence stress intensity increased as the elevation decreased. Results showed that the richness of bacterial communities in bulk and rhizosphere soil samples was significantly different and presented a zonation pattern along with the submergence stress gradient. Bulk soil at medium elevation that underwent moderate submergence stress had the most abundant bacterial communities, while the species richness of rhizobacteria at low elevation that experienced serious submergence stress was the highest. Additionally, principal coordinate analysis (PCoA) and significance tests showed that bulk and rhizosphere soil samples were distinguished according to the structure of bacterial communities, and so were bulk or rhizosphere soil samples from different elevations. Redundancy analysis (RDA) and Mantel test suggested that bacterial communities of bulk soil mainly relied on the contents of soil organic matter, total carbon (TC), total nitrogen (TN), sodium (Na), calcium (Ca) and magnesium (Mg). Contrastingly, the contents of Na and Mg were the main factors explaining the variation in rhizobacterial community composition. Correlation and microbial source tracking analyses showed thatthe relationship of bulk and rhizosphere soil bacteria became much stronger, and the rhizosphere soil may get more bacterial communities from bulk soil with the increase in submergence severity. Our results suggest that the abiotic and biotic components of the riparian ecosystem are closely covariant along the submergence stress gradient and imply that the bacterial community may be a key node linking soil physiochemical properties and vegetation communities.

6.
J Vet Sci ; 25(1): e18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38311330

RESUMO

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated . Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.


Assuntos
Doenças dos Bovinos , Mastite Bovina , Bovinos , Feminino , Animais , Mastite Bovina/diagnóstico , Indústria de Laticínios , Fazendas , Leite
7.
NEJM Evid ; 3(1): EVIDe2300298, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38320519

RESUMO

Multiple therapeutic advances in recent years have significantly improved outcomes for patients with metastatic prostate cancer, including utilization of combination androgen receptor (AR) pathway inhibitors and/or taxane chemotherapy in earlier, hormone-sensitive disease.1 Unfortunately, patients typically still develop metastatic castration-resistant prostate cancer (mCRPC), the lethal form of disease with limited prognosis. Despite castration resistance, the majority of patients with mCRPC continue to have AR-dependent disease through a variety of mechanisms, including emergence of AR mutations, amplifications, splice variants, and persistent AR activation via alternative pathways of androgen production.2.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Androgênios/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Mutação
8.
Adv Sci (Weinh) ; : e2306478, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308132

RESUMO

Fast screening strategies that enable high-throughput evaluation and identification of desired variants from diversified enzyme libraries are crucial to tailoring biocatalysts for the synthesis of D-allulose, which is currently limited by the poor catalytic performance of ketose 3-epimerases (KEases). Here, the study designs a minimally equipment-dependent, high-throughput, and growth-coupled in vivo screening platform founded on a redesigned D-allulose-dependent biosensor system. The genetic elements modulating regulator PsiR expression levels undergo systematic optimization to improve the growth-responsive dynamic range of the biosensor, which presents ≈30-fold facilitated growth optical density with a high signal-to-noise ratio (1.52 to 0.05) toward D-allulose concentrations from 0 to 100 mm. Structural analysis and evolutionary conservation analysis of Agrobacterium sp. SUL3 D-allulose 3-epimerase (ADAE) reveal a highly conserved catalytic active site and variable hydrophobic pocket, which together regulate substrate recognition. Structure-guided rational design and directed evolution are implemented using the growth-coupled in vivo screening platform to reprogram ADAE, in which a mutant M42 (P38N/V102A/Y201L/S207N/I251R) is identified with a 6.28-fold enhancement of catalytic activity and significantly improved thermostability with a 2.5-fold increase of the half-life at 60 °C. The research demonstrates that biosensor-assisted growth-coupled evolutionary pressure combined with structure-guided rational design provides a universal route for engineering KEases.

10.
Endocrine ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306009

RESUMO

PURPOSE: Adrenal and extra-adrenal paragangliomas (PGLs) are a group of neuroendocrine tumors (NETs) with strong heterogeneity, which often express somatostatin receptor subtype 2 A (SSTR2A). However, the association between SSTR2A expression and genetic status of PGLs remains unclear. The purpose of the study was to identify whether various pathogenic variants (PVs) had an impact on SSTR2A expression in PGLs. METHODS: This retrospective study included 184 patients with pathologically confirmed PGLs. The immunohistochemical expression of SSTR2A were studied in 184 tumors and PVs were tested in 159 tumor samples. Clinical and genetic data were compared in SSTR2A positive and negative PGLs. RESULTS: SSTR2A was positive in 63.6% (117/184) of all tumors. PGLs with negative SSTR2A were more likely to be extra-adrenal (37.0% vs 18.0%; P = 0.005) and exhibited a considerably greater proportion of PVs (75.4% vs. 49.0%; P = 0.001) than those with positive SSTR2A. Compared to those without PVs, a higher proportion of PGLs with PVs in cluster 1B (P = 0.004) and cluster 2 (P = 0.004) genes, especially VHL (P = 0.009), FGFR1 (P = 0.010) and HRAS (P = 0.007), were SSTR2A negative. SSTR2A was positive in all tumors (4/4) with SDHx PVs and in 87.5% (7/8) of metastatic PGLs. CONCLUSIONS: SSTR2A negativity was correlated with extra-adrenal tumor location and PVs in cluster 1B and cluster 2 genes such as VHL, FGFR1 and HRAS. Immunohistochemistry of SSTR2A should be taken into consideration in the personalized management of PGLs.

11.
Adv Clin Exp Med ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38318775

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by immune hyperactivation. The overall survival (OS) of adults with secondary HLH remains suboptimal and new treatment strategies are needed. OBJECTIVES: This study aimed to compare the efficacy of different regimens in the treatment of secondary HLH in adults and analyze the prognostic factors affecting patient survival. MATERIAL AND METHODS: The clinical data of 245 adults with secondary HLH admitted to our hospital from January 2016 to October 2021 were analyzed retrospectively. The patients were divided into 3 groups according to different treatment regimens: corticosteroids therapy + chemotherapy + supportive treatment group (JHZ group), chemotherapy + supportive treatment group (HZ group) and corticosteroids therapy + supportive treatment group (JZ group). The clinical efficacy was compared among the 3 groups after treatment, and progression-free survival (PFS) and overall survival (OS) were calculated. Additionally, risk factors associated with prognosis were also analyzed with Cox regression analysis. RESULTS: The objective response rate (ORR) in the JHZ group was higher than that in the HZ group and JZ group, but there was no significant difference between the 3 groups. Also, the patients in the JHZ group had the longest OS and median PFS. Further Cox regression analysis suggested that hyperbilirubinemia was an independent risk factor for OS in secondary HLH patients. CONCLUSIONS: A combination of corticosteroids therapy, chemotherapy and supportive therapy is superior to the other 2 regimens in the clinical benefit in the treatment of secondary HLH in adults, and thus may be a preferred and feasible treatment regimen. Moreover, hyperbilirubinemia was a risk factor for prognosis that has crucial guiding significance for clinical treatment of patients with secondary HLH.

12.
Sci Rep ; 14(1): 2751, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302600

RESUMO

To evaluate the association of uric acid (UA) with adverse outcomes and its potential mediator in patients with left ventricular diastolic dysfunction (LVDD) and pulmonary hypertension (PH). We retrospectively analyzed 234 patients with LVDD and PH. The baseline characteristics of patients with low UA (≤ 330 µmol/L) group were compared with high UA (> 330 µmol/L) group. Adverse outcomes included all-cause mortality, cardiac death and heart failure (HF) hospitalization. Their association with UA and the mediator were evaluated using Cox regression and mediation analysis. The mediation proportion was further quantified by the R mediation package. During a mean follow-up of 50 ± 18 months, there were 27 all-cause deaths, 18 cardiovascular deaths and 41 incidents of HF hospitalization. Multivariable Cox regression analysis showed UA was an independent risk factor of adverse outcomes in LVDD and PH patients, even after adjusting for age, sex, body mass index, medical histories, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, eGFR, BNP and medications. The hazard ratios (HRs) for UA (per 10 µmol/L increase) were as below: for all-cause mortality, HR 1.143, 95% CI 1.069-1.221, P < 0.001; for cardiac death, HR 1.168, 95% CI 1.064-1.282, P = 0.001; for HF hospitalization, HR 1.093, 95% CI 1.035-1.155, P = 0.001. Neutrophil-to-lymphocyte ratio (NLR) played a partial mediation role in the association, and the mediation proportion for NLR on the UA-adverse outcomes were 21%, 19% and 17%, respectively. In patients of LVDD with PH, higher UA level was independently correlated with adverse outcomes. Furthermore, NLR partially mediated the effect of UA on the risk of all-cause mortality, cardiac death and HF hospitalization.


Assuntos
Insuficiência Cardíaca , Hipertensão Pulmonar , Disfunção Ventricular Esquerda , Humanos , Ácido Úrico , Hipertensão Pulmonar/complicações , Estudos Retrospectivos , Neutrófilos , Morte
13.
Plant Physiol Biochem ; 207: 108410, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38310725

RESUMO

Improving wheat drought resistance is of great significance for grain production and food security. Hexokinases (HXKs) play a role in sugar signal transduction and are involved in abiotic stress responses in wheat. To clarify the relationship between HXKs and drought stress in wheat, we used the rice active oxygen induction gene OsHXK1 as a reference sequence and the homologously cloned wheat TaHXK7-1A gene. TaHXK7-1A was localized in the nucleus and cell membrane. Under drought stress, over-expression of TaHXK7-1A increased the contents of O2·ï¼ and malondialdehyde (MDA) and significantly up-regulated the respiratory burst oxidative homologue (RBOHs) genes in transgenic Arabidopsis. In addition, the over-expression of TaHXK7-1A inhibited the growth of Arabidopsis seedlings and increased ROS accumulation under 6 % exogenous glucose treatment. Gene silencing of TaHXK7-1 decreased the contents of O2·ï¼ and MDA in wheat leaves under drought stress, and the RBOHs was significantly down-regulated, which improved the drought resistance of wheat. The results of yeast one-hybrid, EMSA, and dual-luciferase assays showed that TabHLH148-5A bound to the E-box motif of the TaHXK7-1A promoter and inhibited the expression of TaHXK7-1A. In addition, yeast two-hybrid and luciferase complementation imaging assays showed that TaHXK7-1A interacted with TaGRF3-4A. These results indicate that the glucose sensor TaHXK7-1A was negatively regulated by TabHLH148-5A, interacted with TaGRF3-4A, and negatively regulated wheat drought resistance by regulating RBOHs expression and inducing ROS production, thus providing a theoretical basis for revealing the molecular mechanism of wheat drought resistance.

15.
Sci Immunol ; : eadj4748, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38330097

RESUMO

CD11c+ atypical B cells (ABCs) are an alternative memory B cell lineage associated with immunization, infection, and autoimmunity. However, the factors that drive the transcriptional program of ABCs have not been identified, and the function of this population remains incompletely understood. Here we identified candidate transcription factors associated with the ABC population based on a human tonsillar B cell single cell dataset. We identified CD11c+ B cells in mice with a similar transcriptomic signature to human ABCs, and using an optimized CRISPR-Cas9 knockdown screen, we observed that loss of zinc finger E-box binding homeobox 2 (Zeb2) impaired ABC formation. Furthermore, ZEB2 haplo-insufficient Mowat Wilson syndrome (MWS) patients have decreased circulating ABCs in the blood. In Cd23Cre/+Zeb2fl/fl mice with impaired ABC formation, ABCs were dispensable for efficient humoral responses after Plasmodium sporozoite immunization but were required to control recrudescent blood-stage malaria. Immune phenotyping revealed that ABCs drive optimal T follicular helper (Tfh) cell formation and germinal center (GC) responses and they reside at the red/white pulp border likely permitting better access to pathogen antigens for presentation. Collectively, our study shows that ABC formation is dependent upon Zeb2, and these cells can limit recrudescent infection by sustaining GC reactions.

16.
Exp Ther Med ; 27(3): 118, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361519

RESUMO

Pancreatic cancer (PC) is a deadly and aggressive disease, which is characterized by poor prognosis. It has been reported that glutathione peroxidase 3 (GPX3) is involved in the development of several types of cancer. The present study aimed to explore the regulatory role of GPX3 in PC and uncover its underlying mechanism. Bioinformatics analysis was initially carried out to predict the expression profile of GPX3 in PC and its association with prognosis. The expression levels of GPX3 were also detected in PC cells by reverse transcription-quantitative PCR and western blot analysis. Following transfection to induce GPX3 overexpression, the proliferation ability of PC cells was assessed by Cell Counting Kit-8, colony formation and 5-ethynyl-2'-deoxyuridine incorporation assays. In addition, wound healing and Transwell assays were performed to evaluate the migration and invasion abilities of PC cells. Cell apoptosis was assessed by flow cytometric analysis. The expression levels of epithelial-mesenchymal transition (EMT)-, apoptosis-, and JNK signaling-related proteins were detected by western blot analysis. Additionally, for rescue experiments, JNK signaling was activated following cell treatment with anisomycin. The results showed that GPX3 was downregulated in PC and its expression was associated with favorable prognosis. In addition, cell transfection-induced GPX3 overexpression markedly inhibited cell proliferation, migration and invasion, and inhibited EMT. In addition, GPX3 improved the chemo-sensitivity of PC and gemcitabine (GEM)-resistant PC cells to GEM. Furthermore, GPX3 significantly suppressed JNK/c-Jun signaling in PC, while anisomycin treatment reversed the inhibitory effects of GPX3 on the malignant behavior and chemo-resistance of PC cells. The results of the present study indicated that GPX3 could serve as a tumor suppressor in PC via inhibiting JNK/c-Jun signaling, thus providing novel insights into the treatment of PC.

17.
Sensors (Basel) ; 24(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38400483

RESUMO

Optimizing jamming strategies is crucial for enhancing the performance of cognitive jamming systems in dynamic electromagnetic environments. The emergence of frequency-agile radars, capable of changing the carrier frequency within or between pulses, poses significant challenges for the jammer to make intelligent decisions and adapt to the dynamic environment. This paper focuses on researching intelligent jamming decision-making algorithms for Intra-Pulse Frequency Agile Radar using deep reinforcement learning. Intra-Pulse Frequency Agile Radar achieves frequency agility at the sub-pulse level, creating a significant frequency agility space. This presents challenges for traditional jamming decision-making methods to rapidly learn its changing patterns through interactions. By employing Gated Recurrent Units (GRU) to capture long-term dependencies in sequence data, together with the attention mechanism, this paper proposes a GA-Dueling DQN (GRU-Attention-based Dueling Deep Q Network) method for jamming frequency selection. Simulation results indicate that the proposed method outperforms traditional Q-learning, DQN, and Dueling DQN methods in terms of jamming effectiveness. It exhibits the fastest convergence speed and reduced reliance on prior knowledge, highlighting its significant advantages in jamming the subpulse-level frequency-agile radar.

18.
Nat Commun ; 15(1): 1593, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383438

RESUMO

Advances in cryo-electron microscopy (cryo-EM) imaging technologies have led to a rapidly increasing number of cryo-EM density maps. Alignment and comparison of density maps play a crucial role in interpreting structural information, such as conformational heterogeneity analysis using global alignment and atomic model assembly through local alignment. Here, we present a fast and accurate global and local cryo-EM density map alignment method called CryoAlign, that leverages local density feature descriptors to capture spatial structure similarities. CryoAlign is a feature-based cryo-EM map alignment tool, in which the employment of feature-based architecture enables the rapid establishment of point pair correspondences and robust estimation of alignment parameters. Extensive experimental evaluations demonstrate the superiority of CryoAlign over the existing methods in terms of both alignment accuracy and speed.

19.
Front Chem ; 12: 1369937, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389723

RESUMO

Ti-bearing blast furnace slag is a kind of solid waste produced by Pangang Group Company through the blast furnace smelting method. A variety of valuable components can be extracted from the Ti-bearing blast furnace slag after acidolysis with concentrated sulphuric acid. In order to study the kinetics of acidolysis, this paper investigated the effects of the acidolysis temperature, acid-slag ratio and raw material particle size on the overall extraction rate of Ti4+, Mg2+ and Al3+ components at different reaction times, and simulated the acidolysis process by using the unreacted shrinking core model. The results showed that the acidolysis process was controlled by internal diffusion with an apparent activation energy of 19.05 kJ mol-1 and the semi-empirical kinetic equation of the acidolysis process was obtained.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38349834

RESUMO

Brain-computer interfaces (BCIs) can enable direct communication with assistive devices by recording and decoding signals from the brain. To achieve high performance, many electrodes will be used, such as the recently developed invasive BCIs with channel numbers up to hundreds or even thousands. For those high-throughput BCIs, channel selection is important to reduce signal redundancy and invasiveness while maintaining decoding performance. However, such endeavour is rarely reported for invasive BCIs, especially those using deep learning methods. Two deep learning-based methods, referred to as Gumbel and STG, were proposed in this paper. They were evaluated using the Stereo-electroencephalography (SEEG) signals, and compared with three other methods, including manual selection, mutual information-based method (MI), and all channels (all channels without selection). The task is to classify the SEEG signals into five movements using channels selected by each method. When 10 channels were selected, the mean classification accuracies using Gumbel, STG (referred to as STG-10), manual selection, and MI selection were 65%, 60%, 60%, and 47%, respectively, whilst the accuracy was 59% using all channels (no selection). In addition, an investigation of the selected channels showed that Gumbel and STG have successfully identified the pre-central and post-central areas, which are closely related to motor control. Both Gumbel and STG successfully selected the informative channels in SEEG recordings while maintaining decoding accuracy. This study enables future high-throughput BCIs using deep learning methods, to identify useful channels and reduce computing and wireless transmission pressure.


Assuntos
Interfaces Cérebro-Computador , Aprendizado Profundo , Humanos , Eletroencefalografia/métodos , Encéfalo , Movimento , Algoritmos , Imaginação
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