Marine thermal fluctuation induced gluconeogenesis by the transcriptional regulation of CgCREBL2 in Pacific oysters.

Marine thermal fluctuation profoundly influences energy metabolism, physiology, and survival of marine life. In the present study, short-term and long-term high-temperature stresses were found to affect gluconeogenesis by inhibiting PEPCK activity in the Pacific oyster (Crassostrea gigas), which is a globally distributed species that encounters significant marine thermal fluctuations in intertidal zones worldwide. CgCREBL2, a key molecule in the regulation of gluconeogenesis, plays a critical role in the transcriptional regulation of PEPCK in gluconeogenesis against high-temperature stress. CgCREBL2 was able to increase the transcription of CgPEPCK by either binding the promoter of CgPEPCK gene or activating CgPGC-1α and CgHNF-4α after short-term (6 h) high-temperature stress, while only by binding CgPEPCK after long-term (60 h) high-temperature stress. These findings will further our understanding of the effect of marine thermal fluctuation on energy metabolism on marine organisms.

A New Perspective on Stroke Research: Unraveling the Role of Brain Oxygen Dynamics in Stroke Pathophysiology.

Stroke, a leading cause of death and disability, often results from ischemic events that cut off the brain blood flow, leading to neuron death. Despite treatment advancements, survivors frequently endure lasting impairments. A key focus is the ischemic penumbra, the area around the stroke that could potentially recover with prompt oxygenation; yet its monitoring is complex. Recent progress in bioluminescence-based oxygen sensing, particularly through the Green enhanced Nano-lantern (GeNL), offers unprecedented views of oxygen fluctuations in vivo. Utilized in awake mice, GeNL has uncovered hypoxic pockets within the cerebral cortex, revealing the brain's oxygen environment as a dynamic landscape influenced by physiological states and behaviors like locomotion and wakefulness. These findings illuminate the complexity of oxygen dynamics and suggest the potential impact of hypoxic pockets on ischemic injury and recovery, challenging existing paradigms and highlighting the importance of microenvironmental oxygen control in stroke resilience. This review examines the implications of these novel findings for stroke research, emphasizing the criticality of understanding pre-existing oxygen dynamics for addressing brain ischemia. The presence of hypoxic pockets in non-stroke conditions indicates a more intricate hypoxic scenario in ischemic brains, suggesting strategies to alleviate hypoxia could lead to more effective treatments and rehabilitation. By bridging gaps in our knowledge, especially concerning microenvironmental changes post-stroke, and leveraging new technologies like GeNL, we can pave the way for therapeutic innovations that significantly enhance outcomes for stroke survivors, promising a future where an understanding of cerebral oxygenation dynamics profoundly informs stroke therapy.

Subject-Independent Wearable P300 Brain-Computer Interface Based on Convolutional Neural Network and Metric Learning.

OBJECTIVE: The calibration procedure for a wearable P300 brain-computer interface (BCI) greatly impact the user experience of the system. Each user needs to spend additional time establishing a decoder adapted to their own brainwaves. Therefore, achieving subject independent is an urgent issue for wearable P300 BCI needs to be addressed. METHODS: A dataset of electroencephalogram (EEG) signals was constructed from 100 individuals by conducting a P300 speller task with a wearable EEG amplifier. A framework is proposed that initially improves cross-subject consistency of EEG features through a common feature extractor. Subsequently, a simple and compact convolutional neural network (CNN) architecture is employed to learn an embedding sub-space, where the mapped EEG features are maximally separated, while pursuing the minimum distance within the same class and the maximum distance between different classes. Finally, the model's generalization capability was further optimized through fine-tuning. RESULTS: The proposed method significantly boosts the average accuracy of wearable P300 BCI to 73.23 ±7.62% without calibration and 78.75±6.37% with fine-tuning. CONCLUSION: The results demonstrate the feasibility and excellent performance of our dataset and framework. SIGNIFICANCE: A calibration-free wearable P300 BCI system is feasible, suggesting significant potential for practical applications of the wearable P300 BCI system.

Ceftazidime-avibactam: Combination therapy versus monotherapy in the challenge of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae.

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.

Comparison of postoperative analgesia by thoracoscopic-guided thoracic paravertebral block and thoracoscopic-guided intercostal nerve block in uniportal video-asssited thoracic surgery: a prospective randomized controlled trial.

BACKGROUND: Thoracoscopic-guided thoracic paravertebral nerve block (TG-TPVB) and thoracoscopic-guided intercostal nerve block (TG-INB) are two postoperative analgesia technology for thoracic surgery. This study aims to compared the analgesic effect of TG-TPVB and TG-INB after uniportal video-asssited thoracic surgery (UniVATS). METHODS: Fifty-eight patients were randomly allocated to the TG-TPVB group and the TG-INB group. The surgical time of nerve block, the visual analog scale (VAS) scores, the consumption of sufentanil and the number of patient-controlled intravenous analgesic (PCIA) presses within 24 h after surgery, the incidence of adverse reactions were compared between the two groups. RESULTS: The VAS scores were significantly lower during rest and coughing at 2, 6, 12, and 24 h in the TG-TPVB group than in the TG-INB group (P < 0.05). The consumption of sufentanil and the number of PCIA presses within 24 h after surgery were significantly lower in the TG-TPVB group than in the TG-INB group (P < 0.001).The surgical time of nerve block was significantly shorter in the TG-TPVB group than in the TG-INB group (P < 0.001). The incidence of bleeding at the puncture point was lower in the TG-TPVB group than that in the TG-INB group (P < 0.05). CONCLUSION: TG-TPVB demonstrated superior acute pain relieve after uniVATS, shorter surgical time and non-inferior adverse effects than TG-INB.

Reproductive Concerns Among Young Adult Women With Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Systemic cancer treatments pose threats to fertility, leading to concerns regarding fertility and parenthood in young adult women with breast cancer (YAWBC). This systematic review aimed to synthesize existing evidence on reproductive concerns (RCs) among YAWBC and identify areas where further research in needed. METHODS: A systematic review was conducted. Nine English and Chinese databases were searched for studies from inception to June 2023. A meta-analysis was employed to pool RC levels measured using the Reproductive Concerns After Cancer scale (RCAC scale; possible total scores: 18-90). Narrative synthesis was conducted in cases where a meta-analysis could not be performed. RESULTS: Twenty-four cross-sectional studies across seven countries were included in this review. The prevalence of RCs among YAWBC ranged from 21.75% to 80%. The pooled mean total score on the overall RCAC scale was 55.84 (95% confidence interval: 53.26-58.43). "Personal health," "child's health," and "fertility potential" were the top three types of RCs among YAWBC. Sociodemographic, clinical, and psychosocial factors were found to be associated with RCs among YAWBC. Additionally, significant correlations among RCs, nonadherence to treatment, depression, and quality of life were also identified among YAWBC. CONCLUSION: RCs are a common issue among YAWBC, and age, parenthood status, fertility desire, and chemotherapy treatment are important factors associated with RCs among these women. Further research is needed to clarify RC-related factors to provide evidence aimed at tailoring interventions to mitigate RCs among YWBC.

Survival Analysis and Prognostic Factors After Endonasal Resection of Advanced Olfactory Neuroblastomas: A Single Institution Experience.

OBJECTIVES: To explore the prognostic factors in patients with advanced olfactory neuroblastoma (ONB) underwent endoscopic surgery. MATERIALS AND METHODS: Retrospective medical records were reviewed of patients with pathologically proven ONB who underwent endoscopic surgical resection. Clinicopathological characteristics including patient demographics, treatment, complications, follow-up, and outcomes were analyzed. Kaplan-Meier overall survival (OS) and disease-free survival (DFS) curves were plotted. Univariate and multivariate Cox regression models were used to determine prognostic factors. RESULTS: Eighty-five patients with Kadish stage C ONB were examined. According to the various staging systems used, most patients harbored modified Kadish stage C (78.8%). Twenty-six patients (30.6%) underwent bony skull base resection, 11 (12.9%) underwent dura resection, and 24 (28.2%) underwent additional intracranial resection that included the olfactory bulb and duct. Median follow-up was 39 months. Five-year OS and DFS rates were 83.7% and 74.9%, respectively. Five-year OS was 100% in patients treated with bony skull base resection and 77.5% in those who were not (P = .052). Dura resection did not improve OS. Multivariate Cox regression analysis identified perioperative complications (P = .009), gross total resection (P = .004), orbital invasion (P = .014), postoperative radiotherapy (P = .030), and bony skull base resection (P = .019) as independent prognostic predictors. CONCLUSION: For patients with advanced ONB, endoscopic surgery in conjunction with radiotherapy and chemotherapy is effective and safe. Dura resection should be performed with caution in selected patients to balance survival and complications. Postoperative radiotherapy is important to improve OS and DFS.

The P2X7 receptor mediates NADPH transport across the plasma membrane.

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation.

UBE2S facilitates glioblastoma progression through activation of the NF-κB pathway via attenuating K11-linked ubiquitination of AKIP1.

BACKGROUND: Rapid proliferation is a hallmark of glioblastoma multiforme (GBM) and a major contributor to its recurrence. Aberrant ubiquitination has been implicated in various diseases, including cancer. In our preliminary studies, we identified Ubiquitin-conjugating enzyme E2S (UBE2S) as a potential glioma biomarker, exhibiting close associations with glioma grade and protein phosphatase 1, regulatory subunit 105 (Ki67) expression levels. However, the underlying molecular mechanisms remained elusive. NF-κB is an important signaling pathway that promotes GBM proliferation. Direct intervention targeting NF-κB has not yielded the expected results, prompting the exploration of new molecules for regulating NF-κB as a new direction. METHODS: This study employed methods including yeast two-hybrid and immunoprecipitation to uncover the interaction between UBE2S and A kinase interacting protein 1 (AKIP1). Laser confocal microscopy was used to observe the localization of UBE2S and AKIP1. Dual luciferase reporter genes were utilized to observe the activation of NF-κB. RESULTS: Our findings demonstrate that UBE2S deficiency significantly impedes GBM progression, both in vitro and in vivo. Mechanistically, UBE2S plays a crucial role in recruiting Ubiquitin Specific Peptidase 15 (USP15), facilitating the removal of K11-linked ubiquitination on AKIP1. This action enhances AKIP1 stability within the GBM context. The resulting increase in AKIP1 levels further augments nuclear factor kappa-B (NF-κB) transcriptional activity, leading to the upregulation of downstream genes regulated by the NF-κB pathway, thereby promoting GBM progression. CONCLUSIONS: In summary, our findings reveal the role of the UBE2S/AKIP1-NF-κB axis in regulating GBM progression and provide novel evidence supporting UBE2S as a potential drug target for GBM.

Machine learning based on clinical information and integrated CT radiomics to predict local recurrence of stage Ia lung adenocarcinoma after microwave ablation.

PURPOSE: To develop and compare three different machine learning-based models of clinical information and integrated radiomics features predicting the local recurrence of stage Ia lung adenocarcinoma after microwave ablation (MWA) for assisting clinical decision-making. MATERIALS AND METHODS: The data of 360 patients with stage Ia lung adenocarcinoma receiving MWA were included in the training (n = 208), internal test (n = 90), and external test (n = 64) sets based on the inclusion and exclusion criteria. The predictors associated with local recurrence were identified using univariate and multivariate analyses of clinical information. The integrated radiomics features were extracted from pre-MWA and post-MWA (scanned immediately after the ablation) CT images, and ten radiomics features were selected by the t-test and least absolute shrinkage and selection operator (LASSO). The L2-logistic regression of machine learning was applied for the clinical model, CT radiomics model and combined model including clinical predictors and radiomics features. Model performance was evaluated by the receiver operating characteristic (ROC) and decision curve analysis (DCA). RESULTS: The ablative margin was an independent clinical predictor (p = 0.001, odds ratio [OR] = 0.46, 95%CI: 0.29, 0.73). The combined model showed the highest area under the curve (AUC) value among the three models (training: 0.86, 95%CI: 0.81, 0.91; internal test: 0.93, 95%CI: 0.87, 0.98; external test: 0.89, 95%CI: 0.79, 0.96). CONCLUSION: The combined model could accurately predict the local recurrence of stage Ia lung adenocarcinoma after MWA to better support a clinical decision.

Unveiling the overlooked small-sized microbiome in river ecosystems.

Enriching microorganisms using a 0.22-µm pore size is a general pretreatment procedure in river microbiome research. However, it remains unclear the extent to which this method loses microbiome information. Here, we conducted a comparative metagenomics-based study on microbiomes with sizes over 0.22 µm (large-sized) and between 0.22 µm and 0.1 µm (small-sized) in a subtropical river. Although the absolute concentration of small-sized microbiome was about two orders of magnitude lower than that of large-sized microbiome, sequencing only large-sized microbiome resulted in a significant loss of microbiome diversity. Specifically, the microbial community was different between two sizes, and 347 genera were only detected in small-sized microbiome. Small-sized microbiome had much more diverse viral community than large-sized fraction. The viruses had abundant ecological functions and were hosted by 825 species of 169 families, including pathogen-related families. Small-sized microbiome had distinct antimicrobial resistance risks from large-sized microbiome, showing an enrichment of eight antibiotic resistance gene (ARG) types as well as the detection of 140 unique ARG subtypes and five enriched risk rank I ARGs. Draft genomes of five major resistant pathogens having diverse ecological and pollutant-degrading functions were only assembled in small-sized microbiome. These findings provide novel insights into river ecosystems, and highlight the overlooked small-sized microbiome in the environment.

Discovery and demonstration of the temperature stress response functions of Dermatophagoides farinae proteins 1 and 2.

BACKGROUND: Dermatophagoides farinae proteins (DFPs) are abundantly expressed in D. farinae; however, their functions remain unknown. Our previous transcriptome sequencing analyses revealed that the basal expression of DFP1 and DFP2 in D. farinae was high and, more importantly, upregulated under temperature stress. Therefore, DFPs were speculated to exert a temperature stress response function. RESULTS: Real-time quantitative polymerase chain reaction detection revealed that both DFP1 and DFP2 were significantly upregulated under temperature stress. Particularly, DFP1 was upregulated under cold stress. Electrophoresis of D. farinae total proteins revealed an increased abundance of DFP1 and DFP2 (40-55 kDa bands) under temperature stress, which was corroborated by the mass spectrometry results. After silencing DFP1 and DFP2 further, temperature stress led to decreases in gene expression and survival rates. Moreover, DFP1 was identified as the upstream regulator of DFP2. CONCLUSION: This study highlights the temperature stress response functions of DFP1 and DFP2 at the mRNA and protein levels. These results provide important insights for applying DFP1 and DFP2 as potential target genes for the molecular prevention and control of D. farinae to prevent allergic diseases. The newly established methods provide methodological guidance for the study of genes with unknown functions in mites.

Integrated metabolomic and transcriptomic analysis reveals variation in the metabolites of Dendrobium officinale, Dendrobium huoshanense, Dendrobium nobile.

INTRODUCTION: Dendrobium is a perennial herb of the genus Dendrobium in the orchid family. Generally, Dendrobium officinale (TP) and Dendrobium huoshanense (HS) are both considered to have the function of yin-nourishing, while Dendrobium nobile (JC) has better efficacy of heat-clearing. However, because of the wide variety of Dendrobium species, the classification and clinical application of Dendrobium are often confused clearly distinguished in different medicinal uses. OBJECTIVE: In order to compare the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) of the three Dendrobium. METHODS: We selected TP, HS, and JC cultivated on stone for metabolomic and transcriptomic analyses between 2 and 3 years. RESULTS: The results showed that a total of 489 metabolites were obtained, including 72 were DAMs. The 72 DAMs were mainly enriched in metabolic pathways and biosynthesis of secondary metabolites. Transcriptome analysis results showed that 1,038 annotated DEGs were identified among the three Dendrobium species. The comprehensive analysis showed that the three Dendrobium differed in the distribution of the content of four major active components: flavonoids, amino acids, alkaloids, and sugars and alcohols, among which the DAMs and DEGs were mainly enriched in metabolic pathways and secondary metabolite biosynthesis. CONCLUSION: In this study, metabolomics and transcriptomics were utilized to compare the differences among the three species of Dendrobium, to provide theoretical references for future research and selection of different species of Dendrobium based on different medicinal uses, and to lay the foundation for further research on the biosynthesis of flavonoids in Dendrobium.

A CLIC1 network coordinates matrix stiffness and the Warburg effect to promote tumor growth in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/ß-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.

Exploring the potential mechanisms of Rehmannia glutinosa in treating sepsis based on network pharmacology.

The present study utilized network pharmacology to identify therapeutic targets and mechanisms of Rehmannia glutinosa in sepsis treatment. RNA-sequencing was conducted on peripheral blood samples collected from 23 sepsis patients and 10 healthy individuals. Subsequently, the RNA sequence data were analyzed for differential expression. Identification of active components and their putative targets was achieved through the HERB and SwissTarget Prediction databases, respectively. Functional enrichment analysis was performed using GO and KEGG pathways. Additionally, protein-protein interaction networks were constructed and survival analysis of key targets was conducted. Single-cell RNA sequencing provided cellular localization data, while molecular docking explored interactions with central targets. Results indicated significant involvement of identified targets in inflammation and Th17 cell differentiation. Survival analysis linked several targets with mortality rates, while molecular docking highlighted potential interactions between active components and specific targets, such as rehmaionoside a with ADAM17 and rehmapicrogenin with CD81. Molecular dynamics simulations confirmed the stability of these interactions, suggesting Rehmannia glutinosa's role in modulating immune functions in sepsis.

Electrochemically Enabled Hydroxyphosphorylation of 1,3-Enynes to Access Phosphinyl-Substituted Propargyl Alcohols.

Catalytic difunctionalization with the direct activation of (O)P-H bonds has been recently established as a potentially robust platform to generate valuable organophosphorus compounds. In terms of 1,3-enynes, despite of the various catalytic methods developed for hydrophosphorylation, the radical-mediated hetero-functionalization of two different atoms has been less explored. In this study, we disclosed an electrochemically induced hydroxyphosphorylation of 1,3-enynes for the construction of phosphinyl-substituted propargyl alcohols. The system involves the direct activation of both arylphosphine oxides and oxygen in ambient air with no external metal or additive needed. The use of electrochemistry ensures the regioselective, atom-economic and eco-friendly for the difunctionalization process. This strategy highlights the advantages of mild reaction conditions, readily available starting materials and broad substrate scope, showing its practical synthetic value in organic synthesis.

Non-target discovery and risk prediction of per- and polyfluoroalkyl substances (PFAS) and transformation products in wastewater treatment systems.

Wastewater treatment plants (WWTPs) serve as the main destination of many wastes containing per- and polyfluoroalkyl substances (PFAS). Here, we investigated the occurrence and transformation of PFAS and their transformation products (TPs) in wastewater treatment systems using high-resolution mass spectrometry-based target, suspect, and non-target screening approaches. The results revealed the presence of 896 PFAS and TPs in aqueous and sludge phases, of which 687 were assigned confidence levels 1-3 (46 PFAS and 641 TPs). Cyp450 metabolism and environmental microbial degradation were found to be the primary metabolic transformation pathways for PFAS within WWTPs. An estimated 52.3 %, 89.5 %, and 13.6 % of TPs were believed to exhibit persistence, bioaccumulation, and toxicity effects, respectively, with a substantial number of TPs posing potential health risks. Notably, the length of the fluorinated carbon chain in PFAS and TPs was likely associated with increased hazard, primarily due to the influence of biodegradability. Ultimately, two high riskcompounds were identified in the effluent, including one PFAS (Perfluorobutane sulfonic acid) and one enzymatically metabolized TP (23-(Perfluorobutyl)tricosanoic acid@BTM0024_cyp450). It is noteworthy that the toxicity of some TPs exceeded that of their parent compounds. The results from this study underscores the importance of PFAS TPs and associated environmental risks.