Ambient electrosynthesis of urea with nitrate and carbon dioxide over a CuRu alloy catalyst.

Urea synthesis under mild conditions starting from the electrocatalytic coupling of carbon dioxide (CO2) and nitrate represents a promising alternative experimentally to conquer the huge energy consumption in the industrial Haber-Bosch process. Herein, an electrocatalyst consisting of CuRu alloy nanoparticles on carbonized cellulose (CuRu-CBC) is designed and realizes the urea yield rate of 394.85 ± 16.19 µg h-1 mgcat-1 and an ultrahigh faradaic efficiency (FE) of 68.94 ± 3.05% at -0.55 V (vs. RHE) under ambient conditions. Further XAS analyses indicated that the favored internal electron transfer between Cu and Ru dual active sites significantly improved the C-N coupling activity. Various characterizations, including in situ ATR-SEIRAS and DEMS analysis highlighted the favorable generation of key intermediates *CO and *NH, making CuRu-CBC a promising catalyst for urea synthesis.

A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events.

A remaining challenge for genetically encoded voltage indicators (GEVIs) is the reliable detection of excitatory postsynaptic potentials (EPSPs). Here, we developed ASAP5 as a GEVI with enhanced activation kinetics and responsivity near resting membrane potentials for improved detection of both spiking and subthreshold activity. ASAP5 reported action potentials (APs) in vivo with higher signal-to-noise ratios than previous GEVIs and successfully detected graded and subthreshold responses to sensory stimuli in single two-photon trials. In cultured rat or human neurons, somatic ASAP5 reported synaptic events propagating centripetally and could detect ∼1-mV EPSPs. By imaging spontaneous EPSPs throughout dendrites, we found that EPSP amplitudes decay exponentially during propagation and that amplitude at the initiation site generally increases with distance from the soma. These results extend the applications of voltage imaging to the quantal response domain, including in human neurons, opening up the possibility of high-throughput, high-content characterization of neuronal dysfunction in disease.

Mitochondrial DNA copy number associated dementia risk by somatic mutations and frailty.

Mitochondrial dysfunction is linked to physical impairment and dementia. Mitochondrial DNA copy number (mtDNAcn) from blood may predict cognitive decline and dementia risk, but the effect of somatic mutations or frailty is unknown. We estimated mtDNAcn using fastMitoCalc and microheteroplasmies using mitoCaller, from Whole Genome Sequencing (WGS) data. In 189,566 participants free of dementia at study entry (mean age = 56 ± 8), we examined the association between mtDNAcn and subsequent dementia diagnosis using Cox regression. Cognition was assessed in a subset on average 8.9 years later. We examined the associations between mtDNAcn and cognitive measures using multivariable linear regression, adjusted for demographic factors, mtDNAcn-related parameters, and apolipoprotein E ε4 status. We further stratified by frailty and microheteroplasmies. Over an average follow-up of 13.2 years, 3533 participants developed dementia. Each SD higher mtDNAcn (16) was associated with 4.2% lower all-cause dementia hazard (HR = 0.958, p = 0.030), 6% lower non-AD dementia hazard (HR = 0.933, p = 0.022), and not-AD dementia hazard. The associations between mtDNAcn and all-cause dementia and non-AD dementia were stronger among those who were pre-frail or frail or with higher microheteroplasmies. Higher mtDNAcn was associated with higher DSST scores (p = 0.036) and significant only among those with higher microheteroplasmies or frailty (p = 0.029 and 0.048, respectively). mtDNAcn was also associated with delta TMT and paired associate learning only in pre-frail/frail participants (p = 0.007 and 0.045, respectively). Higher WGS-based mtDNAcn in human blood is associated with lower dementia risk, specifically non-AD dementia, and specific cognitive function. The relationships appear stronger in high somatic mutations or frailty. Future studies are warranted to investigate biological underpinnings.

A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.

The efficacy and safety of self-amplifying mRNA (saRNA) have been demonstrated in COVID-19 vaccine applications. Unlike conventional non-replicating mRNA (nrmRNA), saRNA offers a key advantage: its self-replication mechanism fosters efficient expression of the encoded protein, leading to substantial dose savings during administration. Consequently, there is a growing interest in further optimizing the expression efficiency of saRNA. In this study, in vitro adaptive passaging of saRNA is conducted under exogenous interferon pressure, which revealed several mutations in the nonstructural protein (NSP). Notably, two stable mutations, Q48P and I113F, situated in the NSP3 macrodomain (MD), attenuated its mono adenosine diphosphate ribose (MAR) hydrolysis activity and exhibited decreased replication but increased payload expression compared to wild-type saRNA (wt saRNA). Transcriptome sequencing analysis unveils diminished activation of the double-stranded RNA (dsRNA) sensor and, consequently, a significantly reduced innate immune response compared to wt saRNA. Furthermore, the mutant saRNA demonstrated less translation inhibition and cell apoptosis than wt saRNA, culminating in higher protein expression both in vitro and in vivo. These findings underscore the potential of reducing saRNA replication-dependent dsRNA-induced innate immune responses through genetic modification as a valuable strategy for optimizing saRNA, enhancing payload translation efficiency, and mitigating saRNA cytotoxicity.

Single-cell multi-omics identify novel regulators required for osteoclastogenesis during aging.

Age-related osteoporosis manifests as a complex pathology that disrupts bone homeostasis and elevates fracture risk, yet the mechanisms facilitating age-related shifts in bone marrow macrophages/osteoclasts (BMMs/OCs) lineage are not fully understood. To decipher these mechanisms, we conducted an investigation into the determinants controlling BMMs/OCs differentiation. We performed single-cell multi-omics profiling on bone marrow samples from mice of different ages (1, 6, and 20 months) to gain a holistic understanding of cellular changes across time. Our analysis revealed that aging significantly instigates OC differentiation. Importantly, we identified Cebpd as a vital gene for osteoclastogenesis and bone resorption during the aging process. Counterbalancing the effects of Cebpd, we found Irf8, Sox4, and Klf4 to play crucial roles. By thoroughly examining the cellular dynamics underpinning bone aging, our study unveils novel insights into the mechanisms of age-related osteoporosis and presents potential therapeutic targets for future exploration.

Identification and expression of prognostic-related genes in kidney renal clear cell carcinoma and their possible regulatory mechanisms.

Background: Many factors affect the prognosis of kidney renal clear cell carcinoma (KIRC). Early diagnosis can significantly improve the prognosis of KIRC patients. Therefore, a method needs to be developed to diagnose KIRC early, predict patient prognosis, and improve personalized treatments. The objective of this study is to utilize bioinformatics tools and public database resources to identify differentially expressed genes (DEGs) between renal cancer tissues and adjacent normal tissues, and to further screen for prognostic-related genes (PRGs) of KIRC. Methods: KIRC was studied using R language and FunRich software and several databases, including the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham cancer data analysis Portal (UALCAN), and Tumor Immune Estimation Resource (TIMER) databases. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expression of multiple genes in KIRC and adjacent normal tissues. Results: There were substantial differences in immune cell infiltration between the KIRC and adjacent normal tissues in the GSE40435 and GSE46699 datasets. In addition, we screened multiple PRGs of KIRC by combining the GEO and TCGA data. The UALCAN database verified that some representative PRGs were differently expressed depending on the lymph node metastasis status, grade, and stage of KIRC. The qRT-PCR results confirmed the expression of the PRGs in KIRC and adjacent normal tissues. Through the GO and KEGG analyses, interaction analysis, and TIMER database, we found that the prognosis of KIRC was closely related to immune microenvironment and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling. Conclusions: Our findings could contribute to the prognosis prediction of KIRC, the selection of personalized treatments, and the early diagnosis of KIRC.

Association analysis of mitochondrial DNA heteroplasmic variants: Methods and application.

We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.001. Notably, when 5 % or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31 % of African Ancestry, mean age of 62, with 58 % women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the RNR1 and RNR2 genes (p < 0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (p < 0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations.

A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Achieving optical transparency in live animals with absorbing molecules.

Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.

Large language multimodal models for new-onset type 2 diabetes prediction using five-year cohort electronic health records.

Type 2 diabetes mellitus (T2DM) is a prevalent health challenge faced by countries worldwide. In this study, we propose a novel large language multimodal models (LLMMs) framework incorporating multimodal data from clinical notes and laboratory results for diabetes risk prediction. We collected five years of electronic health records (EHRs) dating from 2017 to 2021 from a Taiwan hospital database. This dataset included 1,420,596 clinical notes, 387,392 laboratory results, and more than 1505 laboratory test items. Our method combined a text embedding encoder and multi-head attention layer to learn laboratory values, and utilized a deep neural network (DNN) module to merge blood features with chronic disease semantics into a latent space. In our experiments, we observed that integrating clinical notes with predictions based on textual laboratory values significantly enhanced the predictive capability of the unimodal model in the early detection of T2DM. Moreover, we achieved an area greater than 0.70 under the receiver operating characteristic curve (AUC) for new-onset T2DM prediction, demonstrating the effectiveness of leveraging textual laboratory data for training and inference in LLMs and improving the accuracy of new-onset diabetes prediction.

Effects of Vitamin C on the Gonad Growth, Texture Traits, Collagen Content and Synthesis Related Gene Expression of Sea Urchin (Mesocentrotus nudus).

The market value of sea urchin gonads is determined by the specific characteristics associated with gonad size and texture. Formulated feeds can effectively promote the gonad growth of sea urchins but cannot assure essential gonad texture traits. The objective of this study was to investigate the impact of vitamin C (VC) on the gonad growth, texture, collagen content, and the expression of genes involved in the collagen synthesis of sea urchins (Mesocentrotus nudus). Graded amounts of VC (0, 3000 and 6000 mg/kg) were supplemented to make three formulated feeds. Fresh kelp (Saccharina japonica) was used as the control diet. Each diet was randomly distributed to three tanks of M. nudus. The results indicated that the gonadosomatic index (GSI) and texture traits of M. nudus fed C3000 were significantly greater than those fed C0 and C6000. Collagen type I (Col I) in the gonads of M. nudus fed C3000 showed significantly greater areas than those fed C0 and C6000. Consistently, the expression levels of collagen alpha-1 (colp1α) of M. nudus fed C3000 were significantly higher than those fed C0 and C6000. As for the transforming growth factor beta (tgf-ß)/Smads pathway, the expression levels of collagen synthesis genes (tgf-ß receptor 1 and 2, smad nuclear-interacting protein 1 (snip1) and prolyl 4-hydroxylase subunit beta (p4hß)) in the C3000 group were significantly greater than those in the C0, C6000 and kelp groups. On the contrary, the expression levels of collagen degradation genes (lysyl oxidase-like 2 (loxl2) and matrix metalloproteinase 14 (mmp14)) in the C3000 group were significantly lower than those in the C0, C6000 and kelp groups. In conclusion, VC at an addition level of 3000 mg/kg significantly increased the gonad texture and collagen contents of M. nudus, which could be accomplished by increasing collagen synthesis and inhibiting collagen degradation through the tgf-ß/Smads pathway. These results could contribute to better understanding the beneficial effects of VC addition on the gonad texture quality of M. nudus.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic ß cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

Oligodendrocytes and myelin limit neuronal plasticity in visual cortex.

Developmental myelination is a protracted process in the mammalian brain1. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age2-4. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity5. During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and myelination in adolescent mice. In adult mice lacking adolescent oligodendrogenesis, a brief period of monocular deprivation led to a significant decrease in visual cortex responses to the deprived eye, reminiscent of the plasticity normally restricted to adolescence. This enhanced functional plasticity was accompanied by a greater turnover of dendritic spines and coordinated reductions in spine size following deprivation. Furthermore, inhibitory synaptic transmission, which gates experience-dependent plasticity at the circuit level, was diminished in the absence of adolescent oligodendrogenesis. These results establish a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of developmental myelination acting as a functional brake on neuronal plasticity.

Nanoplastics exposure simplifies the network structure of sea cucumber (Apostichopus japonicus) gut microbiota and improves cluster randomness.

Nanoplastics (NPs) are abundant in ocean environments, leading to environmental pollution and notable disruptions to the physiological functions of marine animals. To investigate the toxic effects of NPs on echinoderms, specifically sea cucumbers (Apostichopus japonicus), they were exposed to varying concentrations of NPs (0, 102, 104 particles/L) for 14 d. Subsequently, the 102 particles/L exposure group was purified for 35 d to elucidate the impact of both NPs exposure and purification on the intestinal bacteria structure and function. The results showed that the richness and variety of intestinal bacteria in sea cucumbers significantly reduced under NPs exposure, and then they could be restored to the pre-exposure treatment state after 35 d of purification. With the increase of NPs exposure concentration in the environment, the intestinal core bacteria gradually changed from Firmicutes and Proteobacteria to Pseudoalteromonas and Vibrio. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database annotated that the gut microbiota of sea cucumbers was significantly downregulated in the glycosylation, carbohydratic and amino acid metabolic pathways (P < 0. 05), exogenous substance biodegradation and metabolism, DNA replication and repair pathways were significantly up-regulated (P < 0.05) under the exposure of NPs. In addition, nanoplastics exposure simplified the symbiotic network relationships of the gut bacteria, reduced the selective effect of host on the intestinal bacteria, and increased stochasticity. In conclusion, waterborne NPs can adversely affect the structure and function of sea cucumber intestinal bacteria, with these effects persisting for a duration. However, as the purification time lengthens, these adverse effects gradually diminish. This study aims to provide some theoretical basis for the biotoxic effects of NPs.

Study on Low-Velocity Impact and Residual Compressive Mechanical Properties of Carbon Fiber-Epoxy Resin Composites.

Room temperature drop hammer impact and compression after impact (CAI) experiments were conducted on carbon fiber-epoxy resin (CF/EP) composites to investigate the variation in impact load and absorbed energy, as well as to determine the residual compressive strength of CF/EP composites following impact damage. Industrial CT scanning was employed to observe the damage morphology after both impact and compression, aiding in the study of impact-damage and compression-failure mechanisms. The results indicate that, under the impact load, the surface of a CF/EP composite exhibits evident cratering as the impact energy increases, while cracks form along the length direction on the back surface. The residual compressive strength exhibits an inverse relationship with the impact energy. Impact damage occurring at an energy lower than 45 J results in end crushing during the compression of CF/EP composites, whereas energy exceeding 45 J leads to the formation of long cracks spanning the entire width of the specimen, primarily distributed symmetrically along the center of the specimen.

An 8-(Diazomethyl) Quinoline Derivatized Acyl-CoA in Silico Mass Spectral Library Reveals the Landscape of Acyl-CoA in Aging Mouse Organs.

Acyl-Coenzyme As (acyl-CoAs) are essential intermediates to incorporate carboxylic acids into the bioactive metabolic network across all species, which play important roles in lipid remodeling, fatty acids, and xenobiotic carboxylic metabolism. However, due to the poor liquid chromatographic behavior, the relatively low mass spectrometry (MS) sensitivity, and lack of authentic standards for annotation, the in-depth untargeted profiling of acyl-CoAs is challenging. We developed a chemical derivatization strategy of acyl-CoAs by employing 8-(diazomethyl) quinoline (8-DMQ) as the labeling reagent, which increased the detection sensitivity by 625-fold with good peak shapes. By applying the MS/MS fragmentation rules learned from the MS/MS spectra of 8-DMQ-acyl-CoA authentic standards, an 8-DMQ-acyl-CoA in silico mass spectral library containing 33,344 high-resolution tandem mass spectra of 8,336 acyl-CoA species was created. The in silico library facilitated the high-throughput and automatic annotation of acyl-CoA using multiple metabolomic data processing tools, such as NIST MS Search and MSDIAL. The feasibility of the in silico library in a complex sample was demonstrated by profiling endogenous acyl-CoAs in multiple organs of an aging mouse. 53 acyl-CoA species were annotated, including 12 oxidized fatty acyl-CoAs and 3 novel nonfatty acyl-CoAs. False positive annotations were further screened by developing an eXtreme Gradient Boosting (XGBoost) based retention time prediction model. The organ distribution and the aging dynamics of acyl-CoAs in a mouse model were discussed for the first time, which helped to elucidate the organ-specific function of acyl-CoAs and the role of different acyl-CoA species during aging.

[Curative effect analysis of anterior cervical discectomy and fusion in patients with cervical spondylosis of vertebral artery type].

OBJECTIVE: To investigate the clinical effect of anterior cervical discectomy and fusion (ACDF) in the treatment of cervical spondylosis of vertebral artery type(CSA). METHODS: The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed. There were 25 males and 17 females, aged from 30 to 74 years old with an average of (53.9±11.0) years old. There were 18 cases with single-segment lesions, 17 cases with two-segment lesions, and 7 cases with three-segment lesions. The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score (CHE), the Neck Disability Index (NDI) and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months. RESULTS: All 42 ACDF patients were followed up for 6 to 30 months with an average of (14.0±5.2) months. The operative time ranged from 95 to 220 min with an average of (160.38±36.77) min, the intraoperative blood loss ranged from 30 to 85 ml with an average of (53.60±18.98) ml. Tow patients had mild postoperative dysphagia, which improved with symptomatic treatment such as nebulized inhalation. CHE score decreased from (4.05±0.96) preoperatively to (2.40±0.70) at 6 months postoperatively (t=12.97, P<0.05). The number of improved vertigo at 6 months postoperatively was 38, with an improvement rate of 90.5%. NDI score was reduced from (34.43±8.04) preoperatively to (20.76±3.91) at 6 months postoperatively (t=11.83, P<0.05). The cervical curvature Cobb angle improved from (8.04±6.70)° preoperatively to (12.42±5.23)° at 6 months postoperatively (t=-15.96, P<0.05). CONCLUSION: The ACDF procedure has outstanding clinical efficacy in treating CSA. The operation can rapidly relieve patients' episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature. However, it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in patients, and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.

Impact-resistant supercapacitor by hydrogel-infused lattice.

The safety of energy storage devices is increasingly crucial due to the growing requirements for application under harsh conditions. Effective methods for enhancing robustness without compromising functionality are necessary. Here we present an impact-resistant, ready-to-use supercapacitor constructed from self-healable hydrogel electrolyte-infused lattice electrodes. Three-dimensional-printed carbon-coated silicon oxycarbide current collectors provide mechanical protection, with compressive stress, Young's modulus, and energy absorption up to 70.61 MPa, 2.75 GPa, and 92.15 kJ/m3, respectively. Commercially viable polyaniline and self-healable polyvinyl alcohol hydrogel are used as active coatings and electrolytes. I-wrapped package structured supercapacitor electrode exhibits a static specific capacitance of 585.51 mF/cm3 at 3 mA/cm3, with an energy density of 97.63 µWh/cm3 at a power density of 0.5 mW/cm3. It maintains operational integrity under extreme conditions, including post-impact with energy of 0.3 J/cm3, dynamic loading ranging from 0 to 18.83 MPa, and self-healing after electrolyte damage, demonstrating its promise for applications in extreme environments.

Discovery of novel ULK1 inhibitors through machine learning-guided virtual screening and biological evaluation.

Aim: Build a virtual screening model for ULK1 inhibitors based on artificial intelligence. Materials & methods: Build machine learning and deep learning classification models and combine molecular docking and biological evaluation to screen ULK1 inhibitors from 13 million compounds. And molecular dynamics was used to explore the binding mechanism of active compounds. Results & conclusion: Possibly due to less available training data, machine learning models significantly outperform deep learning models. Among them, the Naive Bayes model has the best performance. Through virtual screening, we obtained three inhibitors with IC50 of µM level and they all bind well to ULK1. This study provides an efficient virtual screening model and three promising compounds for the study of ULK1 inhibitors.

[Box: see text].

Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through MALAT1/miR-138-5p/SLC7A11 Coexpression Regulation.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.