Scalable Cathodic H2O2 Electrosynthesis using Cobalt-Coordinated Nanocellulose Electrocatalyst.

Converting hierarchical biomass structure into cutting-edge architecture of electrocatalysts can effectively relieve the extreme dependency of nonrenewable fossil-fuel-resources typically suffering from low cost-effectiveness, scarce supplies, and adverse environmental impacts. A cost-effective cobalt-coordinated nanocellulose (CNF) strategy is reported for realizing a high-performance 2e-ORR electrocatalysts through molecular engineering of hybrid ZIFs-CNF architecture. By a coordination and pyrolysis process, it generates substantial oxygen-capturing active sites within the typically oxygen-insulating cellulose, promoting O2 mass and electron transfer efficiency along the nanostructured Co3O4 anchored with CNF-based biochar. The Co-CNF electrocatalyst exhibits an exceptional H2O2 electrosynthesis efficiency of ≈510.58 mg L-1 cm-2 h-1 with an exceptional superiority over the existing biochar-, or fossil-fuel-derived electrocatalysts. The combination of the electrocatalysts with stainless steel mesh serving as a dual cathode can strongly decompose regular organic pollutants (up to 99.43% removal efficiency by 30 min), showing to be a desirable approach for clean environmental remediation with sustainability, ecological safety, and high-performance.

Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.

Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.

Antifungal Activity and Mechanism of Physcion against Sclerotium rolfsii, the Causal Agent of Peanut Southern Blight.

Peanut southern blight, caused by the soil-borne pathogen Sclerotium rolfsii, is a widespread and devastating epidemic. Frequently, it is laborious to effectively control by labor-intensive foliar sprays of agrochemicals due to untimely find. In the present study, seed treatment with physcion (PHY) at doses of 0.08, 0.16, and 0.32 g AI kg-1 seed significantly improved the growth and photosynthetic activity of peanuts. Furthermore, PHY seed treatment resulted in an elevated enzymatic activity of key enzymes in peanut roots, including peroxidase, superoxide dismutase, polyphenol oxidase, catalase, lipoxygenase, and phenylalanine ammonia-lyase, as well as an increase in callus accumulation and lignin synthesis at the infection site, ultimately enhancing the root activity. This study revealed that PHY seed treatment could promote the accumulation of reactive oxygen species, salicylic acid (SA), and jasmonic acid (JA)/ethylene (ET) in peanut roots, while also decreasing the content of malondialdehyde levels in response to S. rolfsii infection. The results were further confirmed by transcriptome data and metabolomics. These findings suggest that PHY seed treatment activates the plant defense pathways mediated by SA and JA/ET in peanut roots, enhancing the resistance of peanut plants to S. rolfsii. In short, PHY is expected to be developed into a new plant-derived immunostimulant or fungicide to increase the options and means for peanut disease control.

Epigenomic features associated with body temperature stabilize tissues during cold exposure in cold-resistant pigs.

Cold stress in low-temperature environments can trigger changes in gene expression, but epigenomics regulation of temperature stability in vital tissues, including the fat and diencephalon, is still unclear. Here, we explore the cold-induced changes in epigenomic features in the diencephalon and fat tissues of two cold-resistant Chinese pig breeds, Min and Enshi black (ES) pigs, utilizing H3K27ac CUT&Tag, RNA-seq, and selective signature analysis. Our results show significant alterations in H3K27ac modifications in the diencephalon of Min pigs and the fat of ES pigs after cold exposure. Dramatic changes in H3K27ac modifications in Min pigs are primarily associated with genes involved in energy metabolism and hormone regulation, whereas those in ES pigs are primarily associated with immunity-related genes. Moreover, transcription factors PRDM1 and HSF1, which show evidence of selection, are enriched in genomic regions presenting cold-responsive alterations in H3K27ac modification in the Min pig diencephalon and ES pig fat, respectively. Our results indicate the diversity of epigenomic response mechanisms to cold exposure between Min and ES pigs, providing unique epigenetic resources for studies of low-temperature adaptation in large mammals.

Differential expression of ADRB1 causes different responses to norepinephrine in adipocytes of Duroc-Landrace-Yorkshire pigs and min pigs.

Research has shown that pigs from different regions exhibit varying responses to cold stimuli. Typically, cold stimuli induce browning of white adipose tissue mediated by adrenaline, promoting non-shivering thermogenesis. However, the molecular mechanisms underlying differential response of pig breeds to norepinephrine are unclear. The aim of this study was to investigate the differences and molecular mechanisms of the effects of norepinephrine (NE) treatment on adipocytes of Min pigs (a cold-resistant pig breed) and Duroc-Landrace-Yorkshire (DLY) pigs. Real time-qPCR, western blot, and immunofluorescence were performed following NE treatment on cell cultures of adipocytes originating from Min pigs (n = 3) and DLY pigs (n = 3) to assess the expressions of adipogenesis markers, beige fat markers, and mitochondrial biogenesis markers. The results showed that NE did not affect browning of adipocytes in DLY pigs, whereas promoted browning of adipocytes in Min pigs. Further, the expression of ADRB1 (Adrenoceptor Beta 1, ADRB1) was higher in subcutaneous adipose tissue and adipocytes of Min pigs than those of DLY pigs. Overexpression of ADRB1 in DLY pig adipocytes enhanced sensitivity to NE, exhibiting decreased adipogenesis markers, upregulated beige fat markers, and increased mitochondrial biogenesis. Conversely, adipocytes treated with ADRB1 antagonist in Min pigs resulted in decreased cellular sensitivity to NE. Further studies revealed differential CpG island methylation in ADRB1 promoter region, with lower methylation levels in Min pigs compared to DLY pigs. In conclusion, differential methylation of the ADRB1 promoter region leads to different ADRB1 expression, resulting in varying responsiveness to NE in adipocytes of two pig breeds. Our results provide new insights for further analysis of the differential cold responsiveness in pig breeds from different regions.

Bidirectional Two-Sample Mendelian Randomization Study of Immunoglobulin G N-Glycosylation and Senescence-Associated Secretory Phenotype.

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189-0.969) and GP17 (OR = 0.709, 95%CI = 0.504-0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95% CI = 1.384-3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95% CI =1.008-1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95% CI = 1.003-1.261) and GP24 (OR = 1.222, 95% CI = 1.046-1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95% CI = 1.048-1.537) and GP15 (OR = 1.297, 95% CI = 1.072-1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms.

Multi-omics reveals the role of MCM2 and hnRNP K phosphorylation in mouse renal aging through genomic instability.

The process of aging is characterized by structural degeneration and functional decline, as well as diminished adaptability and resistance. The aging kidney exhibits a variety of structural and functional impairments. In aging mice, thinning and graying of fur were observed, along with a significant increase in kidney indices compared to young mice. Biochemical indicators revealed elevated levels of creatinine, urea nitrogen and serum uric acid, suggesting impaired kidney function. Histological analysis unveiled glomerular enlargement and sclerosis, severe hyaline degeneration, capillary occlusion, lymphocyte infiltration, tubular and glomerular fibrosis, and increased collagen deposition. Observations under electron microscopy showed thickened basement membranes, altered foot processes, and increased mesangium and mesangial matrix. Molecular marker analysis indicated upregulation of aging-related ß-galactosidase, p16-INK4A, and the DNA damage marker γH2AX in the kidneys of aged mice. In metabolomics, a total of 62 significantly different metabolites were identified, and 10 pathways were enriched. We propose that citrulline, dopamine, and indoxyl sulfate have the potential to serve as markers of kidney damage related to aging in the future. Phosphoproteomics analysis identified 6656 phosphosites across 1555 proteins, annotated to 62 pathways, and indicated increased phosphorylation at the Ser27 site of Minichromosome maintenance complex component 2 (Mcm2) and decreased at the Ser284 site of heterogeneous nuclear ribonucleoprotein K (hnRNP K), with these modifications being confirmed by western blotting. The phosphorylation changes in these molecules may contribute to aging by affecting genome stability. Eleven common pathways were detected in both omics, including arginine biosynthesis, purine metabolism and biosynthesis of unsaturated fatty acids, etc., which are closely associated with aging and renal insufficiency.

Iridium-Based Alkaline Hydrogen Oxidation Reaction Electrocatalysts.

The hydroxide exchange membrane fuel cells (HEMFCs) are promising but lack of high-performance anode hydrogen oxidation reaction (HOR) electrocatalysts. The platinum group metals (PGMs) have the HOR activity in alkaline medium two to three orders of magnitude lower than those in acid, leading to the high required PGMs amount on anode to achieve high HEMFC performance. The mechanism study demonstrates the hydrogen binding energy of the catalyst determines the alkaline HOR kinetics, and the adsorbed OH and water on the catalyst surface promotes HOR. Iridium (Ir) has a unique advantage for alkaline HOR due to its similar hydrogen binding energy to Pt and enhanced adsorption of OH. However, the HOR activity of Ir/C is still unsatisfied in practical HEMFC applications. Further fine tuning the adsorption of the intermediate on Ir-based catalysts is of great significance to improve their alkaline HOR activity, which can be reasonably realized by structure design and composition regulation. In this concept, we address the current understanding about the alkaline HOR mechanism and summarize recent advances of Ir-based electrocatalysts with enhanced alkaline HOR activity. We also discuss the perspectives and challenges on Ir-based electrocatalysts in the future.

Pioneer Transcription Factors: The First Domino in Zygotic Genome Activation.

Zygotic genome activation (ZGA) is a pivotal event in mammalian embryogenesis, marking the transition from maternal to zygotic control of development. During the ZGA process that is characterized by the intricate cascade of gene expression, who tipped the first domino in a meticulously arranged sequence is a subject of paramount interest. Recently, Dux, Obox and Nr5a2 were identified as pioneer transcription factors that reside at the top of transcriptional hierarchy. Through co-option of retrotransposon elements as hubs for transcriptional activation, these pioneer transcription factors rewire the gene regulatory network, thus initiating ZGA. In this review, we provide a snapshot of the mechanisms underlying the functions of these pioneer transcription factors. We propose that ZGA is the starting point where the embryo's own genome begins to influence development trajectory, therefore in-depth dissecting the functions of pioneer transcription factors during ZGA will form a cornerstone of our understanding for early embryonic development, which will pave the way for advancing our grasp of mammalian developmental biology and optimizing in vitro production (IVP) techniques.

Knowledge mapping of paediatric fever-a visual analysis based on CiteSpace.

Objective: This study aimed to analyse the research hotspots and frontiers in the field of paediatric fever between 2013 and 2023. Methods: The included articles were visually analysed using CiteSpace 6.1.R6 software. Results: A total of 2,662 Chinese-language articles and 1,456 English-language articles were included in the study. Based on the Chinese literature, research groups were identified represented by Xinmin Li, Jinling Hong and Hongshuang Luo. Based on the English literature, research groups were formed represented by Henriette Moll, Santiago Mintegi and Elizabeth Alpern. Tianjin University of Traditional Chinese Medicine was the institution with the largest number of publications in the Chinese literature, and the Centers For Disease Control And Prevention was the institution with the largest number of publications in the English literature. The research on paediatric fever mainly focused on mechanism exploration, green treatment and clinical management. Conclusion: Several relatively stable research groups have been formed. Future studies on the differential diagnosis, rational drug use, standardised management and clinical practice guidelines for paediatric fever are needed.

Kv3.1 Interaction with UBR5 Is Required for Chronic Inflammatory Pain.

Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K+ channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain.

Methylation synthetic lethality: Exploiting selective drug targets for cancer therapy.

In cancer, synthetic lethality refers to the drug-induced inactivation of one gene and the inhibition of another in cancer cells by a drug, resulting in the death of only cancer cells; however, this effect is not present in normal cells, leading to targeted killing of cancer cells. Recent intensive epigenetic research has revealed that aberrant epigenetic changes are more frequently observed than gene mutations in certain cancers. Recently, numerous studies have reported various methylation synthetic lethal combinations involving DNA damage repair genes, metabolic pathway genes, and paralogs with significant results in cellular models, some of which have already entered clinical trials with promising results. This review systematically introduces the advantages of methylation synthetic lethality and describes the lethal mechanisms of methylation synthetic lethal combinations that have recently demonstrated success in cellular models. Furthermore, we discuss the future opportunities and challenges of methylation synthetic lethality in targeted anticancer therapies.

A High-Mobility n-Type Noncovalently-Fused-Ring Polymer for High-Performance Organic Thermoelectrics.

Conjugated polymers are emerging as competitive candidates for organic thermoelectrics (OTEs). However, to make the device truly pervasive, both p- and n-type conjugated polymers are essential. Despite great efforts, no n-type equivalents to the p-type benchmark PEDOT:PSS exist to date mainly due to the low electrical conductivity (σ). Herein, a near-amorphous n-type conjugated polymer, namely pDFSe, is reported with high σ by achieving the synergy between charge transport and doping efficiency. The polymer pDFSe is synthesized based on an acceptor-triad moiety of diketopyrrolopyrrole-difluorobenzoselenadiazole-diketopyrrolopyrrole (DFSe), which has the noncovalently-fused-ring structure to reinforce the backbone rigidity. Furthermore, an axisymmetric thiophene-selenophene-thiophene donor is introduced, which enables the formation of near-amorphous microstructures. The above merits ensure good doping efficiency without scarifying efficient intrachain charge-carrier transport. Thus, pDFSe-based n-type transistors exhibit high electron mobility up to 6.15 cm2 V-1 s-1, much higher than its reference polymer pDSe without the noncovalently-fused-ring structure (0.77 cm2 V-1 s-1). Further upon n-doping, pDFSe demonstrates excellent σ of 62.6 S cm-1 and maximum power factor of 133.1 µW m-1 K-2, which are among the highest values reported for solution-processed n-type polymers. The results demonstrate the great potential of near-amorphous n-type conjugated polymers with noncovalently-fused-ring structure for the next-generation OTEs.

Balance between carbon gain and loss in warmer environments: impacts on photosynthesis and leaf respiration in four temperate tree species.

The temperature sensitivities of photosynthesis and respiration remain a key uncertainty in predicting how forests will respond to climate warming. We grew seedlings of four temperate tree species, including Betula platyphylla, Fraxinus mandshurica, Juglans mandshurica and Tilia amurensis, at three temperature regimes (ambient, +2°C and +4°C in daytime air temperature). We investigated net photosynthesis (Anet25), maximum rate of RuBP-carboxylation (Vcmax25) and RuBP- regeneration (Jmax25), stomatal conductance (gs25), mesophyll conductance (gm25), leaf respiration (Rleaf) in dark (Rdark25) and in light (Rlight25) at 25°C in all species. Additionally, we examined the temperature sensitivities of Anet, Vcmax, Jmax, Rdark and Rlight in F. mandshurica. Our findings showed that the warming-induced decreases in Anet25, Vcmax25 and Jmax25 were more prevalent in the late-successional species T. amurensis. Warming had negative impacts on gs25 in all species. Overall, Anet25 was positively correlated with Vcmax25 and Jmax25 across all growth temperatures. However, a positive correlation between Anet25 and gs25 was observed only under warming conditions, and gs25 was negatively associated with vapor pressure deficit (VPD). This implies that the VPD-induced decrease in gs25 was responsible for the decline in Anet25 at higher temperatures. The optimum temperature of Anet in F. mandshurica increased by 0.59°C per 1.0°C rise in growth temperature. While +2°C elevated the thermal optima of Jmax, it did not affect the other temperature sensitivity parameters of Vcmax and Jmax. Rdark25 was not affected by warming in any species, and Rlight25 was stimulated in T. amurensis. The temperature response curves of Rdark and Rlight in F. mandshurica were not altered by warming, implying a lack of thermal acclimation The ratios of Rdark25 and Rlight25 to Anet25 and Vcmax25 in T. amurensis increased with warming. These results suggest that Anet and Rleaf did not acclimate to warming synchronously in these temperate tree species.

Green apple production delivers environmental and economic benefits in China.

Concerning negative impacts of conventional agriculture on global climate change and environmental degradation due to relying on intensive use of synthetic inputs, sustainable alternative farming systems are gaining popularity worldwide. The green farming system is an integrated production strategy focusing particularly on chemical fertilizer reduction coupling with organic manure inputs in China. Despite its rapid growth as a more sustainable system over past decades, green farming systems have not been systematically evaluated to date. We used apple production as a representative case to assess the sustainability of green farming systems. Across major apple-producing regions in China, green farming reduced chemical fertilizer nitrogen (N) by 46.8% (from 412 to 219 kg ha-1) and increased manure N by 33.1% (from 171 to 227 kg ha-1) on average than the conventional, leading to enhanced N use efficiency by 7.27 to 20.27% and reduced N losses by 8.92% to11.56%, while also resulted in slightly lower yields of 4.34% to13.8% in four provinces. Soil fertility in green orchards improved through increased soil organic matter, total N, and available major nutrients. Our cradle-to-farm gate life cycle assessment revealed that green farming reduced helped mitigated greenhouse gas (GHG) emissions by an average of 12.6%, potentially contributing to an annual reduction of 165,239 t CO2 eq annually in major apple-producing areas. Additionally, green farming achieved 39.3% higher profitability (7180 $ ha-1yr-1) at the farmer level. Our study demonstrated the potential of green apple production in approaching agriculture green development in China. These findings provide insights to advance understanding of sustainable alternative farming systems and perspectives towards sustainable development in global agriculture.

SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets.

Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of the elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various aging-related signaling pathways and exert protective effect on many human diseases. SIRT1 functioned as an important role in the occurrence and progression of sarcopenia through regulating key pathways related to protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance and autophagy in skeletal muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and SIRT1/live kinase B1 (LKB1)/AMPK pathways. However, the specific mechanisms of these processes have not been fully illuminated. Currently, several SIRT1-mediated interventions on sarcopenia have been preliminarily developed, such as SIRT1 activator polyphenolic compounds, exercising and calorie restriction. In this review, we summarized the predominant mechanisms of SIRT1 involved in sarcopenia and therapeutic modalities targeting the SIRT1 signaling pathways for the prevention and prognosis of sarcopenia.

Global associations between long-term exposure to PM2.5 constituents and health: A systematic review and meta-analysis of cohort studies.

Existing studies on the most impactful component remain controversial, hindering the optimization of future air quality standards that concerns particle composition. We aimed to summarize the health risk associated with PM2.5 components and identify those components with the greatest health risk. We performed a meta-analysis to quantify the combined health effects of PM2.5 components, and used the meta-smoothing to produce the pooled concentration-response (C-R) curves. Out of 8954 initial articles, 80 cohort studies met the inclusion criteria, including a total of 198.08 million population. The pooled C-R curves demonstrated approximately J-shaped association between total mortality and exposure to BC, and NO3-, but U-shaped and inverted U-shaped relationship withSO42- and OC, respectively. In addition, this study found that exposure to various elements, including BC,SO42-NO3-, NH4+, Zn, Ni, and Si, were significantly associated with an increased risk of total mortality, with Ni presenting the largest estimate. And exposure to NO3-, Zn, and Si was positively associated with an increased risk of respiratory mortality, while exposure to BC, SO42-, and NO3- showed a positive association with risk of cardiovascular mortality. For health outcome of morbidity, BC was notably associated with a higher incidence of asthma, type 2 diabetes and stroke. Subgroup analysis revealed a higher susceptibility to PM2.5 components in Asia compared to Europe and North America, and females showed a higher vulnerability. Given the significant health effects of PM2.5 components, governments are advised to introduce them in regional monitoring and air quality control guidelines. ENVIRONMENTAL IMPLICATION: PM2.5 is a complex mixture of chemical components from various sources, and each component has unique physicochemical properties and uncertain toxicity, posing significant threat to public health. This study systematically reviewed cohort studies on the association between long-term exposure to 13 PM2.5 components and the risk of morbidity and mortality. And we applied the meta-smoothing approach to establish the pooled concentration-response associations between PM2.5 components and mortality globally. Our findings will provide strong support for PM2.5 components monitoring and the improvement of air quality-related regulations. This will aid in helping to enhance health intervention strategies and mitigating public exposure to detrimental particulate matter.

Research advances in predicting the expansion of hypertensive intracerebral hemorrhage based on CT images: an overview.

Hematoma expansion (HE) is an important risk factor for death or poor prognosis in patients with hypertensive intracerebral hemorrhage (HICH). Accurately predicting the risk of HE in patients with HICH is of great clinical significance for timely intervention and improving patient prognosis. Many imaging signs reported in literatures showed the important clinical value for predicting HE. In recent years, the development of radiomics and artificial intelligence has provided new methods for HE prediction with high accuracy. Therefore, this article reviews the latest research progress in CT imaging, radiomics, and artificial intelligence of HE, in order to help identify high-risk patients for HE in clinical practice.

Dynamic interfacial electrostatic energy harvesting via a single wire.

Spontaneously occurred electrostatic breakdown releases enormous energy, but harnessing the energy remains a notable challenge due to its irregularity and instantaneity. Here, we propose a revolutionary method that effectively harvests the energy of dynamic interfacial electrostatic breakdown by simply imbedding a conductive wire (diameter, 25 micrometers) beneath dielectric materials to regulate the originally chaotic and distributed electrostatic energy resulted from contact electrification into aggregation, effectively transforming mechanical energy into electricity. A point-charge physical model is proposed to explain the power generation process and output characteristics, guide structural design, and enhance output performance. Furthermore, a quantified triboelectric series including 72 dielectric material pairs is established for materials choice and optimization. In addition, a high voltage of over 10 kilovolts is achieved using polytetrafluoroethylene and polyethylene terephthalate. This work opens a door for effectively using electrostatic energy, offering promising applications ranging from novel high-voltage power sources, smart clothing, and internet of things.

Targeting the TRIM14/USP14 Axis Enhances Immunotherapy Efficacy by Inducing Autophagic Degradation of PD-L1.

Immunotherapy has greatly improved cancer treatment in recent years by harnessing the immune system to target cancer cells. The first immunotherapeutic agent approved by the US Food and Drug Administration (FDA) was interferon a (IFNa). Treatment with IFNa can lead to effective immune activation and attenuate tumor immune evasion, but persistent treatment has been shown to elicit immune suppressive effects. Here, we identified an autophagy-dependent mechanism by which IFNa triggers tumor immune evasion by upregulating PD-L1 to suppress the anti-tumor activity of CD8+ T cells. Mechanistically, IFNa increased transcription of TRIM14, which recruited the deubiquitinase USP14 to inhibit the autophagic degradation of PD-L1. USP14 removed K63-linked ubiquitin chains from PD-L1, impairing its recognition by the cargo receptor p62 (also known as SQSTM1) for subsequent autophagic degradation. Combining the USP14 inhibitor IU1 with IFNa and anti-CTLA4 treatment effectively suppressed tumor growth without significant toxicity. This work suggests a strategy for targeting selective autophagy to abolish PD-L1-mediated cancer immune evasion.