The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma.

Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of datasets in the Cancer Dependency Map Project revealed many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA-seq, ATAC-seq, and CUT&RUN results identified pathways directly regulated by ADA2B include MTORC1 signaling, MYC, E2F, and MM-specific MAF oncogenic programs. We discovered that ADA2B is recruited to MAF and MYC gene targets, and that MAF shares a majority of its targets with MYC in MM cells. Furthermore, we found the SANT domain of ADA2B is required for interaction with both GCN5 and PCAF acetyltransferases, incorporation into SAGA, and ADA2B protein stability. Our findings uncover previously unknown SAGA KAT module-dependent mechanisms controlling MM cell growth, revealing a vulnerability that might be exploited for future development of MM therapy.

Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

Eosinophil Recovery Time Is Associated with Clinical Outcomes in Patients with Type A Acute Aortic Dissection: a Retrospective Cohort Study.

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD.Clinical trial registration number: NCT05409677.

Highly Efficient Photodynamic Hydrogel with AIE-Active Photosensitizers toward Methicillin-Resistant Staphylococcus aureus Ultrafast Imaging and Killing.

Methicillin-resistant Staphylococcus aureus (MRSA) causes great health hazards to society because most antibiotics are ineffective. Photodynamic treatment (PDT) has been proposed to combat MRSA due to the advantage of imaging-guided no-drug resistance therapy. However, the traditional photosensitizers for PDT are limited by aggregation-caused quenching for imaging and low photodynamic antibacterial efficiency. In this work, we synthesize a new aggregation-induced emission (AIE) photosensitizer (APNO), which can ultrafast distinguish between Gram-positive and Gram-negative bacteria within 3 s by AIE-active photosensitizer imaging. Meanwhile, APNO can generate antibacterial reactive oxygen species under light irradiation, which holds potential for antibacterial PDT. Then, APNO is loaded by PHEAA hydrogel to obtain a highly efficient photodynamic hydrogel (APNO@gel). In vitro results show complete inhibition of MRSA by APNO@gel under lower-power light irradiation. Transcriptome analysis is performed to investigate antibacterial mechanism of APNO@gel. Most importantly, APNO@gel also exhibits significant inhibition and killing ability of MRSA in the MRSA wound infection model, which will further promote rapid wound healing. Therefore, the photodynamic hydrogel provides a promising strategy toward MRSA ultrafast imaging and killing.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

Optical controlled and nuclear targeted CECR2 competitor to downregulate CSF-1 for metastatic breast cancer immunotherapy.

The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs. To amplify the immunotherapeutic effect, a chimeric peptide-based and optical controlled CECR2 competitor (designated as N-PB) is constructed to enhance the nuclear targeted delivery of Bro and initiate an immunogenic cell death (ICD). In vivo results indicate a favorable breast cancer targeting ability and primary tumor suppression effect of N-PB under optical irradiation. Importantly, N-PB downregulates CSF-1 by competitive inhibition of CECR2 and NF-κB(RelA) interactions, thus inhibiting immunosuppressive M2-like TAMs while improving the antitumorigenic M1-like phenotype. Ultimately, the systemic anti-tumor immunity is activated to suppress the metastatic breast cancer in an optical controlled manner. This study provides a promising therapeutic target and reliable strategy for metastatic breast cancer treatment by interrupting immunosuppressive crosstalk between tumor cells and macrophages.

Bibliometric analysis and global trends in uterus transplantation.

AIM: The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. METHODS: The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to December 15, 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. RESULTS: A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, which is followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility, respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. CONCLUSIONS: UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.

The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. METHODS: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways' activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein-protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. RESULTS: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. CONCLUSION: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

Wound healing rates in COPD patients undergoing traditional pulmonary rehabilitation versus tailored Wound-Centric interventions.

This comparative cross-sectional study, conducted at Shanghai Pulmonary Hospital, aimed to evaluate the efficacy of tailored wound-centric interventions (TWCI) versus traditional pulmonary rehabilitation (TPR) in enhancing wound healing in patients with chronic obstructive pulmonary disease (COPD). Enrolling 340 patients with confirmed COPD, the study randomly assigned participants to either the TWCI or TPR group for a 12-week programme. The primary outcome measured was the rate of wound healing, with secondary outcomes including changes in pulmonary function tests (PFTs) and quality of life (QoL) scores. The TWCI group received a customized programme integrating standard pulmonary rehabilitation with specific wound care strategies, such as enhanced oxygen therapy, nutritional supplementation, and infection control measures. In contrast, the TPR group underwent a conventional pulmonary rehabilitation programme without targeted wound care interventions. Wound healing rates, PFTs, and QoL scores were assessed at the end of the intervention and 3 months post-intervention. The TWCI group demonstrated a statistically significant improvement in wound healing rates compared with the TPR group. The TWCI group had a 15% higher rate of reduction in wound size, a 10% rise in complete healing rates, and a 20% drop in infection rates (p < 0.05). Specifically, TWCI group exhibited higher rates of wound size reduction, complete healing, and decreased infection rates. Additionally, long-term pulmonary function and overall quality of life improvements were more pronounced in the tailored group, underscoring the benefits of a personalized approach to managing COPD and wound care. The study concluded that integrating wound-specific care strategies with pulmonary rehabilitation significantly enhances health outcomes in COPD patients with wounds. These findings supported the adoption of customized, multidisciplinary care plans, suggesting that tailored interventions can offer a comprehensive solution to the complex needs of COPD patients, potentially redefining best practices in chronic disease management.

Superconductivity in Ca-intercalated bilayer graphene: C2CaC2.

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

Kai-xin-san improves cognitive impairment in D-gal and Aß25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood. AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota. MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aß25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments. RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant. CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits.

Background: Acute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression. Methods: Employing a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis. Results: Our investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis. Conclusion: This study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response.

Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1ß secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.

A mechanochemical process to capture and separate carbon dioxide from natural gas using boron nitride nanosheets.

Addressing climate change is a critical and pressing matter that requires immediate attention to mitigate its severe repercussions. In order to enhance the capture and separation of carbon dioxide from natural gas and nitrogen gas, it is imperative to develop new capture materials and more efficient storage processes. In this study, we introduce an innovative environmentally friendly storage and separation technique. Through a controlled mechanochemical process, a substantial amount of carbon dioxide (103.6 wt%) was successfully captured within boron nitride. This process also excels at effectively isolating carbon dioxide from a gas mixture containing natural gas (CH4) or nitrogen due to its superior adsorption selectivity for CO2 over the other two gases. The stored carbon dioxide can be released upon heating, and this procedure can be repeated several times (minimum four times), indicating a game changing process in CO2 gas capture and separation technology with the advantages of green, low cost and efficiency.

Flexible Supercapacitor with Wide Electrochemical Stable Window Based on Hydrogel Electrolyte.

Hydrogel electrolyte can endow supercapacitors with excellent flexibility, which has developed rapidly in recent years. However, the water-rich structures of hydrogel electrolyte are easy to freeze at subfreezing and dry at high temperatures, which will affect its energy storage characteristics. The low energy density of micro supercapacitors also hinders their development. Herein, a strategy is proposed to reduce the free water activity in the hydrogel to improve the operating voltage and the energy density of the device, which is achieved through the synergistic effect of the hydrogel skeleton, N, N'-dimethylformamide (DMF), NaClO4 and water. High concentrations of DMF and NaClO4 are introduced into sodium alginate/polyacrylamide (SA/PAAM) hydrogel through solvent exchange to obtain SA/PAAM/DMF/NaClO4 hydrogel electrolyte, which exhibited a high ionic conductivity of 82.1 mS cm-1, a high breaking strength of 563.2 kPa, and a wide voltage stability window of 3.5 V. The supercapacitor devices are assembled by the process of direct adhesion of the hydrogel electrolyte and  laser induced graphene (LIG). The micro-supercapacitor exhibited an operating voltage of 2.0 V, with a specific capacitance of 2.41 mF cm-2 and a high energy density of 1.34 µWh cm-2, and it also exhibit a high cycle stability, good flexibility, and integration performance.

Deciphering dynamic interactions between spermatozoa and the ovarian microenvironment through integrated multi-omics approaches in viviparous black rockfish (Sebastes schlegelii).

The ovarian microenvironment plays a critical role in ensuring the reproductive success of viviparous teleosts. However, the molecular mechanism underlying the interaction between spermatozoa and the ovarian microenvironment has remained elusive. This study aimed to contribute to a better understanding to this process in black rockfish (Sebastes schlegelii) utilizing integrated multi-omics approaches. The results demonstrated significant upregulation of ovarian complement-related proteins and pattern recognition receptors, along with remodeling of glycans on the surface of spermatozoa at early spermatozoa-storage stage (one month after mating). As spermatozoa were stored over time, ovarian complement proteins were progressively repressed by tryptophan and hippurate, indicating a remarkable adaptation of spermatozoa to the ovarian microenvironment. Near fertilization, a notable upregulation of cellular junction proteins was observed. The study revealed that spermatozoa bind to ZPB2a protein through GSTM3 and that ZPB2a promoted spermatozoa survival and movement in a GSTM3-dependent manner. These findings shed light on a key mechanism influencing the dynamics of spermatozoa in the female reproductive tract, providing valuable insights into the molecular networks regulating spermatozoa adaptation and survival in species with internal fertilization.

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity.

BACKGROUND: Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. METHODS: Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. RESULTS: Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. CONCLUSIONS: Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

A UPLC-MS/MS method for simultaneous determination of arachidonic acid, stearic acid, and related endocannabinoids in human plasma.

Endocannabinoids (eCBs) exert considerable influence over energy metabolism, lipid metabolism, and glucose metabolism within the human body. Among the most biologically active cannabinoids identified thus far are 2-arachidonoylglycerol (2-AG), arachidonoyl ethanolamide (AEA), 1-stearoylglycerol (1-SRG), and stearoyl ethanolamide (SEA), which are derived from arachidonic acid (AA) and stearic acid (SA). However, despite the unique in bioactivities exhibited by eCBs, their determination in plasma has been hindered by the lack of sensitive analytical methods. The aim of this study was to develop and validate a highly sensitive and rapid method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for accurate measurement of AEA, SEA, 2-AG, 1-SRG, AA, and SA levels in human plasma samples. Sample preparation involved a protein precipitation method and a methyl tert-butyl ether liquid-liquid extraction method. Chromatographic separation was accomplished by utilizing an ACQUITY UPLC BEH C8 column with a mobile phase of acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, flowing at a rate of 0.35 mL/min. AA-d8, 2-AG-d5, and AEA-d8 were selected as deuterated internal standards. The analytes were determined with MRM in both positive and negative ion mode. The lower limit of quantification ranged from 0.1 to 400 ng/mL, and the correlation coefficient (R2) was >0.99. Inter-day and intra-day precision exhibited values of 0.55-13.29% and 0.62%-13.90%, respectively. Recovery and matrix effect were within the range of 77.7%-109.7%, and 90.0%-113.5%, respectively. Stability tests confirmed the acceptability of all analytes. To demonstrate the effectiveness of the approach, it was implemented to assess and compare plasma samples from healthy volunteers (n = 49) and individuals with non-alcoholic fatty liver disease (NAFLD) (n = 62). The study revealed significant differences in AEA, SEA, AA, and SA levels between the two groups.