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Sleep and wake have global effects on brain physiology, from molecular changes 1 – 4 and neuronal activities to synaptic plasticity 3 – 7 . Sleep–wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep 8 – 11 . Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene 12 , have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses 4 – 6 . Thus, the phosphorylation–dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep–wake homeostasis. A subset of synaptic proteins are cumulatively phosphorylated during wakefulness and dephosphorylated during sleep, in accordance with sleep need; this may represent a common mechanism underlying regulation of both synaptic homeostasis and sleep–wake homeostasis.

Background Locally advanced non-small cell lung cancer (NSCLC) has the potential for surgical cure after neoadjuvant immunotherapy in the era of immunotherapy. In this study, we conducted a meta-analysis of published data to systematically assess the efficacy and safety of neoadjuvant chemoimmunotherapy for stage III NSCLC. Methods A comprehensive search was conducted on the Cochrane Library, PubMed, Web of Science, and Embase databases from January, 2000 to September, 2024 to identify studies concentrated on neoadjuvant chemoimmunotherapy followed by surgery for treating stage III NSCLC. The effectiveness and safety data were collected for meta-analysis. Study endpoints included resection rate, major pathological response (MPR), pathological complete response (pCR), objective response rate (ORR), treatment-related adverse events (TRAEs), severe adverse events (SAEs). Data analysis was conducted using R 4.1.3 software, and P  < 0.05 was considered statistically significant. Results A total of 1043 patients from 22 studies were included in this meta-analysis, of whom 892 cases underwent surgery. The pooled MPR rate, pCR rate, and ORR rate were 65%, 38%, and 73%, respectively. The pooled incidence of TRAEs was 84% and the pooled incidence of SAEs was 13%. The results of the subgroup analysis showed that nivolumab- and pembrolizumab-based neoadjuvant chemoimmunotherapy showed a higher MPR rate (nivolumab 69%, pembrolizumab 68%) and pCR rate (nivolumab 51%, pembrolizumab 38%) than other immune checkpoint inhibitors (ICIs). Conclusion Neoadjuvant chemoimmunotherapy demonstrates clinical benefits for patients with stage III NSCLC.

Environmental pollution, especially water pollution, is becoming increasingly serious. Organic dyes are one type of the harmful pollutants that pollute groundwater and destroy ecosystems. In this work, a series of graphitic carbon nitride (g-C3N4)/ZnO photocatalysts were facilely synthesized through a grinding method using ZnO nanoparticles and g-C3N4 as the starting materials. According to the results, the photocatalytic performance of 10 wt.% CN-200/Z-500 (CN-200, which g-C3N4 was 200 kGy, referred to the irradiation metering. Z-500, which ZnO was 500 °C, referred to the calcination temperature) with the CN-200 exposed to electron beam radiation was better than those of either Z-500 or CN-200 alone. This material displayed a 98.9% degradation rate of MB (20 mg/L) in 120 min. The improvement of the photocatalytic performance of the 10 wt.% CN-200/Z-500 composite material was caused by the improvement of the separation efficiency of photoinduced electron–hole pairs, which was, in turn, due to the formation of heterojunctions between CN-200 and Z-500 interfaces. Thus, this study proposes the application of electron-beam irradiation technology for the modification of photocatalytic materials and the improvement of photocatalytic performance.

Organic pollutants were one of the main sources of environmental pollutants. The degradation of organic pollutants through photocatalytic technology was one of the effective solutions. By preparing zinc oxide(ZnO) nanowires modified with sodium-doped conjugated 2,4,6-triaminopyrimidin-g-C3N4 (NaTCN) heterojunction (ZnO/NaTCN), the photocatalytic performance of NaTCN modified with different ratios of ZnO was systematically studied. The photocatalytic performance was studied through the degradation performance of methyl blue (MB) dye. The results showed that 22.5 wt% ZnO/NaTCN had the best degradation effect on MB dye. The degradation rate of MB reached 98.54% in 70 min. After three cycles, it shows good cycling stability (degradation rate is 96.99%) for dye degradation. It was found that there are two types of active species: ·OH and h+, of which h+ is the main active species produced by photocatalytic degradation of dyes. The excellent degradation performance was attributed to the fact that ZnO facilitated the extraction and transport of photogenerated carriers. The doping of sodium facilitated charge transfer. The NaTCN conjugated system promoted the extraction and transfer of photogenerated carriers. It provided guidance for designing efficient composite catalysts for use in other renewable energy fields.

Photocatalysis is one of the most effective ways to solve environmental problems by solving pollutants. This article designed and prepared a conjugated system of 2,4,6-triaminopyrimidine-g-C3N4 (TAP-CN) to modify ZnO NWs. We systematically studied the photocatalytic performance of ZnO NWs modified with different ratios of TAP-CN. The results showed that 9 wt% TAP-CN-30/ZnO NWs had the best degradation effect on Rhodamine B dye. The degradation rate was 99.36% in 80 min. The excellent degradation performance was attributed to the TAP-CN conjugated system promoting photo-generated charge transfer. This work provided guidance for designing efficient composite catalysts for application in other renewable energy fields.

Graphitic carbon nitride (g‐C3N4) is a highly recognized two‐dimensional semiconductor material known for its exceptional chemical and physical stability, environmental friendliness, and pollution‐free advantages. These remarkable properties have sparked extensive research in the field of energy storage. This review paper presents the latest advances in the utilization of g‐C3N4 in various energy storage technologies, including lithium‐ion batteries, lithium‐sulfur batteries, sodium‐ion batteries, potassium‐ion batteries, and supercapacitors. One of the key strengths of g‐C3N4 lies in its simple preparation process along with the ease of optimizing its material structure. It possesses abundant amino and Lewis basic groups, as well as a high density of nitrogen, enabling efficient charge transfer and electrolyte solution penetration. Moreover, the graphite‐like layered structure and the presence of large π bonds in g‐C3N4 contribute to its versatility in preparing multifunctional materials with different dimensions, element and group doping, and conjugated systems. These characteristics open up possibilities for expanding its application in energy storage devices. This article comprehensively reviews the research progress on g‐C3N4 in energy storage and highlights its potential for future applications in this field. By exploring the advantages and unique features of g‐C3N4, this paper provides valuable insights into harnessing the full potential of this material for energy storage applications. This review serves as a comprehensive guide, shedding light on the promising advances and future prospects of utilizing graphitic carbon nitride (g‐C3N4) in energy storage devices. By examining the distinctive features and capabilities of g‐C3N4, this paper not only provides valuable insights but also paves the way for further exploration and innovation in the realm of multifunctional materials for energy storage.

It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people’s quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain , pain management , chronic pain , opiods , NSAIDs , and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.

The development of a stable and highly active photocatalyst has garnered significant attention in the field of wastewater treatment. In this study, a novel technique involving a facile stirring method was devised to fabricate an array of g-C3N4/ZnO nanowire (ZnO NW) composites. Through the introduction of g-C3N4 to augment the generation of electron-hole pairs upon exposure to light, the catalytic efficacy of these composites was found to surpass that of the pristine ZnO NWs when subjected to simulated sunlight. The photocatalytic performance of a 20 mg·L−1 methylene blue solution was found to be highest when the doping rate was 25 wt%, resulting in a degradation rate of 99.1% after 60 min. The remarkable enhancement in catalytic efficiency can be ascribed to the emergence of a captivating hetero-junction at the interface of g-C3N4 and ZnO NWs, characterized by a harmoniously aligned band structure. This alluring arrangement effectively curtailed charge carrier recombination, amplified light absorption, and augmented the distinct surface area, culminating in a notable boost to the photocatalytic prowess. These findings suggest that the strategic engineering of g-C3N4/ZnO NW heterostructures holds tremendous promise as a pioneering avenue for enhancing the efficacy of wastewater treatment methodologies.

Background Tumor mutational burden (TMB) is a recognized biomarker for predicting immunotherapy efficacy in non-small cell lung cancer (NSCLC). Its assessment requires whole-exome sequencing (WES), but the high cost and stringent sample requirements of WES limit its clinical application. This study aims to assess the predictive value of accessible systemic inflammation markers for identifying high TMB lung cancer populations. Methods WES was performed on tumor samples and paired peripheral blood from 72 lung adenocarcinoma patients. Genomic analysis identified mutation patterns across different TMB groups. Systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR), were collected. Generalized linear models and restricted cubic spline (RCS) plots were used to explore the predictive value of these markers for TMB. The Xgboost model assessed the importance of each variable for TMB prediction. Results Among the 72 lung adenocarcinoma patients, missense mutations were the most common, with single nucleotide variants being the predominant mutation type. The most frequently mutated genes were EGFR (35%), TP53 (33%), and TTN (24%). Compared to the low TMB group, the high TMB group showed a higher proportion of C > A single nucleotide variants, along with significantly increased frequencies of TP53 (56% vs. 11%, p  < 0.001) and TTN (42% vs. 6%, p  < 0.001) mutations. Five de novo mutational signatures were extracted, each contributing differently across TMB strata. Multivariate generalized linear modeling indicated that higher TMB was significantly associated with elevated NLR (β = 0.272, 95% CI: 0.146–0.398), elevated PLR (β = 0.021, 95% CI: 0.012–0.030), and reduced LMR (β = –0.117, 95% CI: –0.212 to –0.028). Restricted cubic spline analyses further demonstrated non-linear associations between TMB and both NLR and PLR. The XGBoost model identified T stage, LMR and BMI as the most influential variables associated with TMB. Conclusion This study reveals distinct mutational characteristics among different TMB groups in Chinese lung adenocarcinoma patients and demonstrates that systemic inflammatory markers can serve as preliminary indicators for identifying high TMB lung cancer populations.

Background Propylea japonica is a widely distributed natural enemy insect that preys on aphids, whiteflies, and other pests. Owing to its exceptional environmental adaptability, this species serves as an effective biological control agent. However, the molecular mechanisms underlying its environmental adaptation remain poorly understood. Results Phylogenetic analysis revealed that Coccinellidae diverged from other Coleoptera approximately 194.88 million years ago, and P. japonica and Harmonia axyridis diverged approximately 91.94 million years ago. Collinearity analysis revealed significant fission and fusion events during the chromosomal evolution of P. japonica . Notably, comparative genomic analysis revealed the following five potential key mechanisms underlying the environmental adaptability of P. japonica : (1) sensory specialization: odorant-binding proteins and water sensation genes may enhance prey and water detection; (2) genome stability: histone-mediated chromatin resilience may maintain genome integrity and developmental plasticity under stress; (3) energy trade-offs: prioritizing detoxification or immunity under toxin exposure may reduce the amount of resources allocated to growth or reproduction, enhancing niche adaptation; (4) developmental robustness: juvenile hormone signaling and embryonic development pathways potentially ensure developmental stability; (5) dispersal adaptation: enhanced development of wings and flight muscles and chitinase activity may facilitate colonization to escape extreme climates or resource scarcity. Conclusions Through comparative genomic analysis, this study provides insights into the divergence history of Coleoptera and reveals a dynamic pattern of chromosomal evolution in P. japonica , clarifying the genetic basis of its environmental adaptation. Future studies should prioritize the functional validation of candidate genes linked to these five key mechanisms to better elucidate their specific contributions to environmental adaptation. This work advances the molecular understanding of ecological adaptation in predatory insects, providing actionable perspectives for optimizing biocontrol strategies.