Search

Distracted driving poses a serious threat to traffic safety and remains a widespread problem, highlighting the crucial need for effective recognition of distracted drivers. However, developing models that can generalize across diverse and changing real-world driving conditions is profoundly challenging. Variations in factors like lighting, weather, vehicle type, and drivers complicate generalization. Addressing this critical limitation is key to building recognition models with robust performance for practical deployment. This study presents a novel two-stage unsupervised domain adaptation framework to tackle the important challenge of recognizing distracted drivers across differing environments. The framework first constructs softly assigned class prototypes capturing underlying data structure by aggregating features locally and reweighting sample-prototype relationships globally, which increases the accuracy of class representations. The framework then aligns the probabilities between test samples and prototypes across source and target domains using soft distributional alignment, reducing domain gaps without explicit labeling of the target data. A growth control function balances prototype alignment with classification and adversarial losses. Experiments on distracted driver and object recognition datasets demonstrate this two-stage approach outperforms previous methods, especially under changing driving environments, which is an important problem distracted driving detection research must overcome to effectively enhance road safety.

Gouty arthritis is a chronic and progressive disease characterized by high urate levels in the joints and by an inflammatory immune microenvironment. Clinical data indicate that urate reduction therapy or anti-inflammatory therapy alone often fails to deliver satisfactory outcomes. Here we have developed a smart biomimetic nanosystem featuring a ‘shell’ composed of a fusion membrane derived from M2 macrophages and exosomes, which encapsulates liposomes loaded with a combination of uricase, platinum-in-hyaluronan/polydopamine nanozyme and resveratrol. The nanosystem targets inflamed joints and promotes the accumulation of anti-inflammatory macrophages locally, while the uricase and the nanozyme reduce the levels of urate within the joints. Additionally, site-directed near-infrared irradiation provides localized mild thermotherapy through the action of platinum and polydopamine, initiating heat-induced tissue repair. Combined use of these components synergistically enhances overall outcomes, resulting in faster recovery of the damaged joint tissue.

Purpose: The purpose of this paper is to examine the impact of two typical relationship management approaches (trust relationship with suppliers and reciprocity) on manufacturer resilience in the context of the COVID-19 crisis. Moreover, this paper aims to deepen the understanding of environmental uncertainty's moderating effect on the association between the trust relationship with suppliers (TRS) and reciprocity. Design/methodology/approach: Structural equation modeling has been used to test the hypotheses on 361 Chinese manufacturing firms' managers and independent directors during the COVID-19 crisis. Findings: The results reveal that reciprocity positively enhances three dimensions of manufacturer resilience, namely, preparedness, responsiveness and recovery capability. Reciprocity positively mediates the relationships between TRS and preparedness, responsiveness and recovery capability. Moreover, environmental uncertainty moderates the association between TRS and reciprocity. Practical implications: This study highlights the critical role of reciprocity, the relational governance approach, in enhancing manufacturer resilience in practice. This paper suggests that during emergencies such as the COVID-19 pandemic, managers should adopt trust and reciprocity in supplier relationship governance to strengthen the resilience of manufacturing companies and adapt effective strategies according to the environment. Originality/value: This study is unique in developing new scales of manufacturer resilience through interviews and surveys with Chinese manufacturers and theoretical research. Based on the social capital theory and social exchange theory, this study shed light on the role of trust and reciprocity. It also bridges relational governance theory with the literature on manufacturing firm resilience literature to help manufacturers better understand the transdisciplinary links between relationship management and resilient operations in emergencies. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral small vessel disease (CSVD) commonly exists in patients with symptomatic intracranial atherosclerotic disease (sICAD). We aimed to investigate the associations of hemodynamic features of sICAD lesions with imaging markers and overall burden of CSVD.Patients and methods: Patients with anterior-circulation sICAD (50%–99% stenosis) were analyzed in this cross-sectional study. Hemodynamic features of a sICAD lesion were quantified by translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) via CT angiography-based computational fluid dynamics modeling. PR ⩽median was defined as low (“abnormal”) PR, and WSSR ⩾ fourth quartile as high (“abnormal”) WSSR. For primary analyses, white matter hyperintensities (WMHs), lacunes, and cortical microinfarcts (CMIs) were assessed in MRI and summed up as overall CSVD burden, respectively in ipsilateral and contralateral hemispheres to sICAD. Enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) were assessed for secondary analyses.Results: Among 112 sICAD patients, there were more severe WMHs, more lacunes and CMIs, and more severe overall CSVD burden ipsilaterally than contralaterally (all p< 0.05). Abnormal PR and WSSR (vs normal PR and WSSR) was significantly associated with moderate-to-severe WMHs (adjusted odds ratio = 10.12, p= 0.018), CMI presence (5.25, p= 0.003), and moderate-to-severe CSVD burden (12.55; p= 0.033), ipsilaterally, respectively independent of contralateral WMHs, CMI(s), and CSVD burden. EPVSs and CMBs were comparable between the two hemispheres, with no association found with the hemodynamic metrics.Discussion and conclusion: There are more severe WMHs and CMI(s) in the hemisphere ipsilateral than contralateral to sICAD. The hemodynamic significance of sICAD lesions was independently associated with severities of WMHs and CMI(s) ipsilaterally.

Bcr-Abl is successfully applied to drug discovery as a CML therapeutic target, but point mutation resistance has become a major challenge in the clinical treatment of CML. Our previous studies have shown that the introduction of amino acids as flexible linkers and heterocyclic structures as HBMs can achieve potent inhibition of Bcr-AblT315I. In continuation of these studies, we further enriched the linker types by developing a library of compounds with tert-leucine or serine as a linker. Biological results showed that these compounds exhibited enhanced inhibition against Bcr-AblWTand Bcr-AblT315Ikinases as well as improved antiproliferative activity in leukemia cell assays compared to previously disclosed compounds. In particular, compounds TL8, TL10, BS4, BS10, SR5and SR11exhibited potent inhibitory activities against Ba/F3 cells bearing a T315I mutant. Additionally, compounds TL8, BS4and SR5effectively induced K562 cell apoptosis, arrested the cell cycle at the S or G2/M phase, and inhibited the phosphorylation of Bcr-Abl and STAT5 in a dose-dependent manner. Docking studies verified the rationality of tert-leucine or serine as a flexible linker and indicated that phenylpyridine with an amide side chain favored the potency of these inhibitors. Moreover, ADME prediction suggested that the tested compounds had a favorable safety profile. Thus, tert-leucine or serine can be used as a promising class of flexible linkers for Bcr-Abl inhibitors with heterocyclic structures as HBMs, and compounds BS4, SR5, and especially TL8, can be used as starting points for further optimization.

Stimulus-responsive polymers have found widespread use in biomedicine due to their ability to alter their own structure in response to various stimuli, including internal factors such as pH, reactive oxygen species (ROS), and enzymes, as well as external factors like light. In the context of atherosclerotic cardiovascular diseases (CVDs), stimulus-response polymers have been extensively employed for the preparation of smart nanocarriers that can deliver therapeutic and diagnostic drugs specifically to inflammatory lesions. Compared with traditional drug delivery systems, stimulus-responsive nanosystems offer higher sensitivity, greater versatility, wider applicability, and enhanced biosafety. Recent research has made significant contributions towards designing stimulus-responsive polymer nanosystems for CVDs diagnosis and treatment. This review summarizes recent advances in this field by classifying stimulus-responsive polymer nanocarriers according to different responsiveness types and describing numerous stimuli relevant to these materials. Additionally, we discuss various applications of stimulus-responsive polymer nanomaterials in CVDs theranostics. We hope that this review will provide valuable insights into optimizing the design of stimulus-response polymers for accelerating their clinical application in diagnosing and treating CVDs.

AbstractHuman papillomavirus (HPV) is the infectious etiological agent for diseases such as cervical cancer. Developing HPV vaccines is of great significance for cancer prevention. During the development of polyvalent HPV vaccines, such as 9-valent and 15-valent HPV vaccines, specifical identification of different HPV antigen is very important. The homemade HPV31 L1 VLPs was used as an immunogen to generate HPV 31 monoclonal antibodies (mAbs) through hybridoma cell culture. We generated several mAbs through hybridoma cell culture and selected two specific neutralizing antibodies, 19B2 and 19C4, which were further analyzed and characterized for binding activity, neutralizing activity, and specificity by enzyme-linked immunosorbent assays (ELISA). It is shown that both 19B2 and 19C4 could specifically recognize HPV31 L1 virus-like particles (VLPs). These two specific mAbs were further used to assemble a HPV31 antigen ELISA test kit. The assembled kit with high detection performance could be widely applied for the quantitative detection of HPV31 antigen during vaccine production as well as in the preliminary analysis of HPV31 infection.

Non-noble metal oxides have emerged as potential candidate electrocatalysts for acidic oxygen evolution reactions (OERs) due to their earth abundance; however, improving their catalytic activity and stability simultaneously in strong acidic electrolytes is still a major challenge. In this work, we report Co3O4@carbon core–shell nanoparticles on 2D graphite sheets (Co3O4@C-GS) as mixed-dimensional hybrid electrocatalysts for acidic OER. The obtained Co3O4@C-GS catalyst exhibits a low overpotential of 350 mV and maintains stability for 20 h at a current density of 10 mA cm–2in H2SO4(pH = 1) electrolyte. X-ray photoelectron and X-ray absorption spectroscopies illustrate that the higher content of Co3+sites boosts acidic OER. OperandoRaman spectroscopy reveals that the catalytic stability of Co3O4@C nanoparticles during the acidic OER is enhanced by the introduction of graphite sheets. This interface engineering of non-noble metal sites with high valence states provides an efficient approach to boost the catalytic activity and enhance the stability of noble-metal-free electrocatalysts for acidic OER.

The inhalation exposure of pesticide applicators and residents who live close to pesticide-treated fields is a worldwide concern in public health. Quantitative assessment of exposure to pesticide inhalation health risk highlights the need to accurately assess the bioaccessibility rather than the total content in ambient air. Herein, we developed an in vitromethod to estimate the inhalation bioaccessibility of emamectin benzoate and validated its applicability using a rat plasma pharmacokinetic bioassay. Emamectin benzoate was extracted using the Gamble solution, with an optimized solid-to-liquid ratio (1/250), extraction time (24 h), and agitation (200 rpm), which obtained in vitroinhalation bioaccessibility consistent with its inhalation bioavailability in vivo(32.33%). The margin of exposure (MOE) was used to assess inhalation exposure risk. The inhalation unit exposures to emamectin benzoate of applicators and residents were 11.05–28.04 and 0.02–0.04 ng/m3, respectively, varying markedly according to the methods of application, e.g., formulations and nozzles. The inhalation risk assessment using present application methods appeared to be acceptable; however, the MOE of emamectin benzoate might be overestimated by 32% without considering inhalation bioaccessibility. Collectively, our findings contribute insights into the assessment of pesticide inhalation exposure based on bioaccessibility and provide guidance for the safe application of pesticides.

Methane dry reforming (MDR) is of great interest for its efficient consumption of greenhouse gases and the production of valuable syngas. The interfaces of metal and boron nitride (BN) are expected to enhance the catalytic activity and inhibit coke formation. Herein, the composite of layered metal oxides (NiMgAlOx) and BN was constructed to form the interface-confined NiMgAlOx/BN (Ni-MAO/BN) catalysts, and the unique promotion effects of a triple interface in Ni catalysts were unraveled. The triple interface among the Ni, BN, and MgAlOxoxides enhances the sintering resistance of the developed catalysts, which endows the developed catalysts with excellent adsorption/activation capacity of CH4and CO2as well as superb stability during a long-term MDR activity test. The abundant bicarbonate (HCO3*) species in the Ni-MAO/BN catalysts demonstrates that the triple interface significantly enhances gas activation. Meanwhile, the dynamic variation of HCO3* and CO3* species further proves the inhibition of deep CH4cracking and the fast reaction rate over the Ni-MAO/BN catalysts. The negligible graphitic carbon observed in the operando Raman spectra and the produced large amount of H2/CO demonstrate not only the excellent coke resistance but also the strengthened activation capability of CO2and CH4. This work elucidates the role of interfacial effects on gas activation and provides innovative insights into the design of highly efficient Ni catalysts for MDR.

Cancer has become the primary reason for industrial countries death. Although first-line treatments have achieved remarkable results in inhibiting tumors, they could have serious side effects because of insufficient selectivity. Therefore, specific localization of tumor cells is currently the main desire for cancer treatment. In recent years, cell-penetrating peptides (CPPs), as a kind of promising delivery vehicle, have attracted much attention because they mediate the high-efficiency import of large quantities of cargos in vivoand vitro. Unfortunately, the poor targeting of CPPs is still a barrier to their clinical application. In order to solve this problem, researchers use the various characteristics of tumor microenvironment and multiple receptors to improve the specificity toward tumors. This review focuses on the characteristics of the tumor microenvironment, and introduces the development of strategies and peptides based on these characteristics as drug delivery system in the tumor-targeted therapy.

Human calcitonin (hCT) is a polypeptide hormone that participates in calcium-phosphorus metabolism. Irreversible aggregation of 32-amino acid hCT into β-sheet-rich amyloid fibrils impairs physiological activity and increases the risk of medullary carcinoma of the thyroid. Amyloid-resistant hCT derivatives substituting critical amyloidogenic residues are of particular interest for clinical applications as therapeutic drugs against bone-related diseases. Uncovering the aggregation mechanism of hCT at the molecular level, therefore, is important for the design of amyloid-resistant hCT analogues. Here, we investigated the aggregation dynamics of hCT, non-amyloidogenic salmon calcitonin (sCT), and two hCT analogues with reduced aggregation tendency─TL-hCT and phCT─using long timescale discrete molecular dynamics simulations. Our results showed that hCT monomers mainly adopted unstructured conformations with dynamically formed helices around the central region. hCT self-assembled into helix-rich oligomers first, followed by a conformational conversion into β-sheet-rich oligomers with β-sheets formed by residues 10–30 and stabilized by aromatic and hydrophobic interactions. Our simulations confirmed that TL-hCT and phCT oligomers featured more helices and fewer β-sheets than hCT. Substitution of central aromatic residues with leucine in TL-hCT and replacing C-terminal hydrophobic residue with hydrophilic amino acid in phCT only locally suppressed β-sheet propensities in the central region and C-terminus, respectively. Having mutations in both central and C-terminal regions, sCT monomers and dynamically formed oligomers predominantly adopted helices, confirming that both central aromatic and C-terminal hydrophobic residues played important roles in the fibrillization of hCT. We also observed the formation of β-barrel intermediates, postulated as the toxic oligomers in amyloidosis, for hCT but not for sCT. Our computational study depicts a complete picture of the aggregation dynamics of hCT and the effects of mutations. The design of next-generation amyloid-resistant hCT analogues should consider the impact on both amyloidogenic regions and also take into account the amplification of transient β-sheet population in monomers upon aggregation.

In order to solve the problems of low recognition accuracy, low-recall rate and low absolute value of F1-score in traditional online English learning data anomaly identification methods, a new anomaly identification of English online learning data based on local outlier factor is proposed. English online learning data resources are utilised to be mined using K-nearest neighbours and local reachability density, and a unified data set is created by integrating data from different sources and formats. The information source model of the data set is abstracted as a tuple, and English online learning data anomaly identification is achieved by implementing the local outlier factor threshold in the tuple. The experimental results show that the proposed method has an identification accuracy of over 90%, a maximum recall rate of 98% and a high absolute F1-score, indicating good identification performance.

AbstractThe aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02–9.75, P= 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02–0.25, P< 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

We report Ca2–xIrO4nanocrystals exhibit record stability of 300 h continuous operation and high iridium mass activity (248 A gIr–1at 1.5 VRHE) that is about 62 times that of benchmark IrO2. Lattice-resolution images and surface-sensitive spectroscopies demonstrate the Ir-rich surface layer (evolved from one-dimensional connected edge-sharing [IrO6] octahedrons) with high relative content of Ir5+sites, which is responsible for the high activity and long-term stability. Combining operandoinfrared spectroscopy with X-ray absorption spectroscopy, we report the first direct observation of key intermediates absorbing at 946 cm–1(Ir6+═O site) and absorbing at 870 cm–1(Ir6+OO– site) on iridium-based oxides electrocatalysts, and further discover the Ir6+═O and Ir6+OO– intermediates are stable even just from 1.3 VRHE. Density functional theory calculations indicate the catalytic activity of Ca2IrO4is enhanced remarkably after surface Ca leaching, and suggest IrOO– and Ir═O intermediates can be stabilized on positive charged active sites of Ir-rich surface layer.

This was a retrospective study that compared outcomes in pediatric intestinal failure (IF) patients that were switched from ethanol lock therapy (ELT) to sodium bicarbonate lock therapy (SBLT). The primary outcome was rate of catheter-related blood stream infections (CRBSI). The secondary outcomes were number of hospitalizations, emergency room (ER) visits, central venous catheter (CVC)-related complications. In 4 patients, median rates of CRBSI were 2.77 (interquartile range [IQR] 0.6–5.6) on ELT versus 0 on SBLT per 1000 catheter days (P= 0.17). The median rates of hospitalizations and ER visits for CVC-related complications were 6.1 (IQR 3.2–10.2) on ELT versus 0 on SBLT (IQR 0–0; P= 0.11) and 2.8 (IQR 2–3.6) on ELT versus 1.8 (IQR 0–3.7) on SBLT per 1000 catheter days (P= 0.50), respectively. Rates of CVC-related complications were similar. No adverse events were reported. SBLT may be safe and effective for pediatric IF.

The flavor quality of brown yogurt is affected by the different fermentation methods. In this study, we investigated the effects of probiotics (Lactiplantibacillus plantarumS58), prebiotics (oat β-glucan), and synbiotics (Lactiplantibacillus plantarumS58 combined with oat β-glucan) on physicochemical properties, consumer acceptance, flavor substances, and metabolites of brown yogurt. The results showed that the addition of probiotics and synbiotics significantly shortened the curdling time of brown yogurt (30 min and 40 min, respectively), and synbiotics improved the physicochemical properties and flavor components of the yogurt. Compared with the control group, the volatile flavor substances in the synbiotic yogurt, such as acetophenone, 2-decanone, and octanoic acid, were significantly increased. Sensory analysis of 111 consumers showed that the sample of synbiotic brown yogurt was highly accepted and close to the ideal point. Synbiotic fermentation alters the metabolic profile of yogurt, increasing the levels of beneficial metabolites and reducing harmful metabolites. In conclusion, synbiotic brown yogurt achieved the highest quality. This study provides a theoretical basis and data support for the development of brown yogurt with high probiotic activity and a unique flavor.

Harnessing the full potential of Ni-rich single-crystal cathodes (LiNixMnyCo1-x-yO2, NMC) for next-generation high-energy lithium batteries is hindered by their slow reaction kinetics and susceptibility to interfacial decay. Our research introduces a novel strategy utilizing triethyl phosphate (TEP) and fluoroethylene carbonate (FEC) to optimize the Li+solvation environment, lowering the coordination number and diminishing the energy threshold for Li+transport. Mechanistic studies indicate that this intervention not only accelerates the Li+transfer at the electrode/electrolyte interface but also catalyzes the development of a robust LiF-rich CEI layer. As a result, the single-crystal NMC83 cathode exhibits remarkable high-rate discharge capacities of approximately 209 mAh g−1at 0.1 C and 192 mAh g−1at 0.5 C. The robust CEI layer also mitigates parasitic reactions, substantially improving the cycle life, with capacity retention increasing from 46.1 % to 88.2 % after 300 cycles at 1 C. This work underscores the transformative impact of solvation sheath engineering on the interfacial dynamics of single-crystal cathodes, paving the way for more durable and efficient energy storage solutions.

Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post‐interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal‐to‐noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform‐based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques. Engineering nanoplatforms for atherosclerotic plaques theranostics have attracted extensive attention due to their exceptional sensitivity, deep tissue penetration, superior bioavailability, and high signal‐to‐noise ratio. In this review, various nanoplatform‐based molecular imaging modalities and therapeutic approaches for the diagnosis and treatment of atherosclerotic plaques are summarized.

ABSTRACTCardiac fibrosis (CF) and heart failure (HF) are common heart diseases, and severe CF can lead to HF. In this study, we tried to find their common potential molecular markers, which may help the diagnosis and treatment of CF and HF. RNA library construction and high-throughput sequencing were performed. The DESeq2 package in R was used to screen differentially expressed mRNAs (DEmRNAs), differentially expressed lncRNA (DElncRNAs) and differentially expressed miRNA (DEmiRNAs) between different samples. The common DEmRNAs, DElncRNAs and DEmiRNAs for the two diseases were obtained. The ConsensusPathDB (CPDB) was used to perform biological function enrichment for common DEmRNAs. Gene interaction network was constructed to screen out key genes. Subsequently, real-time polymerase chain reaction (RT-PCR) verification was performed. Lastly, GSE104150 and GSE21125 data sets were utilized for expression validation and diagnostic analysis. There were 1477 DEmRNAs, 502 DElncRNAs and 36 DEmiRNAs between CF and healthy control group. There were 607 DEmRNAs, 379DElncRNAs,s and 42 DEmiRNAs between HF and healthy control group. CH and FH shared 146 DEmRNAs, 80 DElncRNAs, and 6 DEmiRNAs. Hsa-miR-144-3p, CCNE2, C9orf72, MAP3K20-AS1, LEF1-AS1, AC243772.2, FLJ46284, and AC239798.2 were key molecules in lncRNA-miRNA-mRNA network. In addition, hsa-miR-144-3p and CCNE2 may be considered as potential diagnostic gene biomarkers in HF. In this study, the identification of common biomarkers of CF and HF may help prevent CF to HF transition as early as possible.

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candidaspecies being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 [ELISA]) were evaluated. We observed no changes in the abundance of total fungal species (alpha diversity) between groups. Samples with identifiable Candidaspp. were present in 4 of 19 (21%) ASD + GI, in 5 of 9 (56%) ASD - GI, and in 4 of 16 (25%) TD children (overall P= 0.18). The presence of Candidaspp. did not correlate with behavioral or GI symptoms (P= 0.38, P= 0.5, respectively). Fecal calprotectin was normal in all but one child. Finally, there was no significance in serum dectin-1 levels, suggesting no increased fungal immunity in children with ASD. Our data suggest that fungi are present at normal levels in the stool of children with ASD and are not associated with gut inflammation.

Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape autodigestion by digestive enzymes. Here we show that human PDAC tumour cells use gasdermin E (GSDME), a pore-forming protein, to mediate digestive resistance. GSDME facilitates the tumour cells to express mucin 1 and mucin 13, which form a barrier to prevent chymotrypsin-mediated destruction. Inoculation of GSDME−/−PDAC cells results in subcutaneous but not orthotopic tumour formation in mice. Inhibition or knockout of mucin 1 or mucin 13 abrogates orthotopic PDAC growth in NOD-SCID mice. Mechanistically, GSDME interacts with and transports YBX1 into the nucleus where YBX1 directly promotes mucin expression. This GSDME–YBX1–mucin axis is also confirmed in patients with PDAC. These findings uncover a unique survival mechanism of PDAC cells in pancreatic microenvironments.

In this paper, we study a diffusive SIR epidemic model with saturated incidence rate and discontinuous treatments under Neumann boundary conditions. Firstly, the existence and boundedness of the solution of the system are addressed. Then, on the basis of the differential inclusions theory, we analysis the existence of endemic equilibrium. Furthermore, by constructing different appropriate Lyapunov functions, we investigate the global asymptotic stability of the disease free equilibrium(DFE) and the endemic equilibrium(EE), respectively. Additionally, numerical simulations are given to confirm the correctness of theorem. Finally, we give a brief conclusion and discussion in the end of the paper.

Pathological aggregation of intrinsically disordered tau protein, driven by the interactions between microtubule-binding (MTB) domains, is associated with Alzheimer’s disease. The MTB domain contains either three or four repeats with sequence similarities. Compared to amyloid β, many aspects of the misfolding and aggregation mechanisms of tau are largely unknown. In this study, we systematically investigated the dynamics of monomer misfolding and dimerization of each MTB repeat using atomistic discrete molecular dynamic simulations. Our results revealed that all the four repeat monomers (R1–R4) were very dynamic, featuring frequent conformational conversion and lacking stable conformations. While R1, R2, and R4 monomers occasionally adopted partially helical conformations, R3 monomers frequently formed β-sheets. In dimerization simulations, R3 displayed the strongest aggregation propensity with high β-sheet contents, while R1 was the least prone to aggregation. The R2 and R4 dimers contained both helix and β-sheet structures. The β-sheets in R4 assemblies were dominant with β-hairpin conformation. In R2 and R3 dimers, intermolecular β-sheets were mainly driven by residues around the paired helical filament (PHF) regions. Residues around the PHF6* in R2 and PHF6 in R3 had significantly higher intermolecular contacts than other regions, suggesting that these residues play a key role in the amyloid aggregation of tau. Our results on the structural ensembles and early aggregation dynamics of each tau MTB repeat will help understand the nucleation and fibrillization of tau.

•The RNA-binding protein IGF2BP2 is down-regulated in ccRCC tissues and cell lines, and IGF2BP2 inhibits ccRCC metastasis in vivoand in vitro.•IGF2BP2 enhances CKB expression by binding to CKB mRNA and stabilizing its mRNA, thereby inhibiting ccRCC metastasis.•Our findings demonstrate a novel insight for IGF2BP2 on ccRCC tumorigenesis via affecting mRNA stability.

Lithium-rich manganese-based cathode (LRM) materials are considered the most promising cathode for the next-generation high-energy-density Li-ion batteries due to their high specific discharge capacity. However, the current mainstream LRM materials exhibit a polycrystalline morphology, and the degradation of this morphology during extended cycling exacerbates structural distortions, leading to poor cycle stability. Herein, a spinel phase encapsulated single-crystal LRM material with a particle size of about 500 nm is prepared through a simple molten-salt assistant solid-state synthesis method utilizing traditional polycrystalline LRM precursor, followed by boric acid treatment. Combined with various characterizations, the surface coating layer of obtained single-crystal LRM materials is identified as spinel Li4Mn5O12with a thickness of about 5 nm, which effectively enhances Li+diffusion kinetics. Benefited from the collaborative strategy of single crystallization and spinel coating which strength Li+conduction and suppresses particle cracking, the single-crystal LRM materials achieve a specific discharge capacity of 296.3 mAh g−1at 0.1 C (1 C = 250 mA g−1), yielding a capacity retention of 97.4% after 300 cycles at 1 C. This study offers a universal and easy industrial scale-up approach for developing single-crystal LRM cathode materials with long cycling stability, which promotes the commercial utilization of single-crystal LRM cathode.

The intestinal microbiota influences the development and function of the mucosal immune system. However, the exact mechanisms by which commensal microbes modulate immunity is not clear. We previously demonstrated that commensal Bacteroides ovatusATCC 8384 reduces mucosal inflammation. Herein, we aimed to identify immunomodulatory pathways employed by B. ovatus. In germ-free mice, mono-association with B. ovatusshifted the CD11b+/CD11c+and CD103+/CD11c+dendritic cell populations. Because indole compounds are known to modulate dendritic cells, B. ovatuscell-free supernatant was screened for tryptophan metabolites by liquid chromatography–tandem mass spectrometry and larger quantities of indole-3-acetic acid were detected. Analysis of cecal and fecal samples from germ-free and B. ovatusmono-associated mice confirmed that B. ovatuscould elevate indole-3-acetic acid concentrations in vivo. Indole metabolites have previously been shown to stimulate immune cells to secrete the reparative cytokine IL-22. Addition of B. ovatuscell-free supernatant to immature bone marrow–derived dendritic cells stimulated IL-22 secretion. The ability of IL-22 to drive repair in the intestinal epithelium was confirmed using a physiologically relevant human intestinal enteroid model. Finally, B. ovatusshifted the immune cell populations in trinitrobenzene sulfonic acid–treated mice and up-regulated colonic IL-22 expression, effects that correlated with decreased inflammation. Our data suggest that B. ovatus–produced indole-3-acetic acid promotes IL-22 production by immune cells, yielding beneficial effects on colitis.

CD8+T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.

To determine the demographics, potential risk factors, endoscopic interventions and outcomes relating to gastric bezoars in pediatric patients; and comparing results with previously published literature. Retrospective series by chart review of patients identified by International Classification of Diseases-9 codes 938 and 935, using the following Medical Subject Headings: 1, term bezoar; 2, Keywords gastric bezoar*or gastric foreign body*. Thirty pediatric patients between ages of 2 to 18 years were found with gastric bezoars, with a female predominance. Majority had a phytobezoar. Six patients were diagnosed with dysautonomia, implying possible role of autonomic dysfunction contributing to abnormal gastric retention. Frequent symptoms included abdominal pain, nausea and vomiting, a decrease in appetite, and unintentional weight loss. A higher prevalence of underlying gastrointestinal disorders was found in those with bezoars. Nuclear medicine gastric emptying scan performed in 13 children was significantly abnormal in only 4 of these children. Most patients were treated with endoscopic removal of the bezoar. Endoscopic removal was accomplished by Roth net, generally requiring multiple passes. At follow-up, most of the children had improvement of symptoms, with bezoar recurrence in 1 patient. This is to our knowledge the largest series of gastric bezoars in pediatrics. On the basis of our review, phytobezoars may be under-reported in pediatrics. Bezoars should be considered in children presenting with chronic abdominal pain, nausea, and vomiting; even in developmentally normal children and those with normal gastric emptying. We suggest that dysautonomia and underlying gastrointestinal disorders may be potential risk factors.

Background: Hypopharyngeal carcinoma is characterized by a high degree of malignancy. The most common pathological type is squamous cell carcinoma (HSCC). Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most widely used chemotherapeutic drugs nowadays and cisplatin resistance is a major problem in current treatment strategies. Clinical researchers have reported that high autophagy levels often caused insensitivity to chemotherapy, a common phenomenon that greatly reduces the therapeutic effect in cisplatin- resistant tumor cell lines. 3-methyladenine (3-MA), an inhibitor of PI3K, plays a vital role in forming and developing autophagosomes. Therefore, we speculate that the use of 3-MA may reduce cisplatin resistance in hypopharyngeal squamous cell carcinoma (HSCC). Methods: Part I: Cisplatin-resistant FaDu cell line (Human hypopharyngeal squamous cell carcinoma cells) was established and cultured. Cell counting kit-8 was used to detect drug resistance. An inverted microscope was used to observe the morphological changes at different concentrations, then the survival rate was calculated. After MDC staining, the autophagic vacuoles were observed by fluorescence microscopy. The expression of Beclin1 from each group was confirmed by RT-PCR and Western blot method. Part II: 3-MA was applied for cisplatin-resistant cells intervention, Beclin1 was knocked down by plasmid transfection. Cell cycle was detected using flow cytometry assay, apoptosis with necrosis was detected by staining with propidium iodide (PI). CCK-8 was used to observe the cell survival rate in each group. The expression of autophagy-related protein Beclin1, LC3I, LC3II, Atg-5 and P62 in each group was verified by Western blot analysis. Results: Cisplatin-resistant FaDu cell line can be stably constructed by cisplatin intervention. Compared with normal group, autophagy and its related protein Beclin1 expression were enhanced in cisplatin resistant FaDu cells. Autophagy inhibition group showed significant cell cycle changes, mainly manifested by G1 arrest, increased apoptosis rate and significantly decreased survival rate at 24h level. The number of autophagy vacuoles were significantly reduced in the 3-MA group. Furthermore, Western blot showed that expression of Beclin1, lc3-I, lc3-II, atg-5 protein decreased significantly after 3-MA intervention, while the expression of p62 upregulated, which also confirmed autophagy flow was blocked. Conclusion: Our work confirmed that enhanced autophagy is an important cause of cisplatin resistance in FaDu cells. The use of 3-MA can significantly reduce autophagy level and arresting its cell cycle, promote apoptosis and reverse the cisplatin resistance condition, this effect is partly mediated by inhibition of Beclin-1 expression. Our data provide a theoretical basis for the application of 3-MA in overcoming cisplatin resistance in hypopharyngeal cancer.

Silent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-ß or IFN-? upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.

1,1‐Difluoroethylated aromatic compounds are of increasing importance in agrochemicals and pharmaceuticals. The direct introduction of difluoroethyl (CF2CH3) group(s) onto aromatic rings using CH3CF2Cl, an inexpensive and available raw material, still remains a great challenge because of the relatively inert C−Cl bond of CH3CF2Cl. Herein, we disclose a nickel‐catalyzed 1,1‐difluoroethylation of (hetero)aryl halides with CH3CF2Cl. The reaction exhibits good functional‐group tolerance and is regarded as a practical method for synthesis of (1,1‐difluoroethyl)arenes. 1,1‐Difluoroethylation: A nickel‐catalyzed 1,1‐difluoroethylation of (hetero)aryl halides with 1,1‐difluoroethyl chloride (CH3CF2Cl) has been successfully developed. This method exhibits good tolerance to functional groups, providing a general access to (1,1‐difluoroethyl)arenes.

Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+memory T (Tmem) cells by regulating redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+Tmemcells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8+Tmemcells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1and Ppargc1a(which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes. As a result, FoxO1 and PGC-1α cooperatively upregulate Pck1expression, therefore directing the carbon flow along the gluconeogenic pathway to glycogen and the pentose phosphate pathway. These results reveal that ketogenesis acts as an unusual metabolic pathway in CD8+Tmemcells, linking epigenetic modification required for memory development.

Ni-rich single-crystalline layered cathodes have garnered significant attention due to their high energy density and thermal stability. However, they experience severe capacity degradation caused by lattice strain and interfacial side reactions during practical applications. In this study, an effective yttrium modification method is employed to stabilize the structure of Ni-rich single-crystalline LiNi0.83Mn0.05Co0.12O2(SC-NMC83) to solve these issues. This innovative approach successfully immobilizes oxygen within the material, preventing crack formation while simultaneously broadening the diffusion path of Li+. The yttrium-modified sample (SC-NMC83-Y) exhibits a superior capacity retention compared to the SC-NMC83 sample, with values of 90% and 76.1% after 100 cycles, respectively. This work demonstrates the promising potential of a doping strategy for Ni-rich single-crystalline cathodes and paves a pathway for its practical implementation, such as all-solid-state batteries.

Polysaccharides, which are well-known natural macromolecules, have been recognized for their protective effects on neurons and their influence on extracellular dopamine levels in the brain. It is crucial to investigate the impact of plant polysaccharides on neurotransmission, particularly regarding the vesicular storage and exocytosis of neurotransmitters. In this study, we demonstrated the possibility of studying how the polysaccharide from Glochidion eriocarpumChamp.(GPS) affects vesicle dopamine content and the dynamics of exocytosis in pheochromocytoma (PC12) cells using single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC). Our results unambiguously demonstrate that GPS effectively enhances vesicular neurotransmitter content and alters the dynamics of exocytosis, favoring a smaller fraction of content released in exocytotic release, thereby inducing the partial release mode. These significant effects are attributed to GPS’s efficient elevation of calcium influx, significant alteration in the composition of exocytosis-related membrane lipids, and enhancement of free radical scavenging ability. These findings not only establish GPS as a promising candidate for preventive or therapeutic interventions against neurodegenerative disorders but also reiterate the importance of screening native neurologic drugs with single-vesicle electrochemical approaches, the combination of SCA and IVIEC, from a neurotransmitter-centric perspective.

Human calcitonin (hCT) regulates calcium–phosphorus metabolism, but its amyloid aggregation disrupts physiological activity, increases thyroid carcinoma risk, and hampers its clinical use for bone-related diseases like osteoporosis and Paget’s disease. Improving hCT with targeted modifications to mitigate amyloid formation while maintaining its function holds promise as a strategy. Understanding how each residue in hCT’s amyloidogenic core affects its structure and aggregation dynamics is crucial for designing effective analogues. Mutants F16L-hCT and F19L-hCT, where Phe residues in the core are replaced with Leu as in nonamyloidogenic salmon calcitonin, showed different aggregation kinetics. However, the molecular effects of these substitutions in hCT are still unclear. Here, we systematically investigated the folding and self-assembly conformational dynamics of hCT, F16L-hCT, and F19L-hCT through multiple long-time scale independent atomistic discrete molecular dynamics (DMD) simulations. Our results indicated that the hCT monomer primarily assumed unstructured conformations with dynamic helices around residues 4–12 and 14–21. During self-assembly, the amyloidogenic core of hCT14–21converted from dynamic helices to β-sheets. However, substituting F16L did not induce significant conformational changes, as F16L-hCT exhibited characteristics similar to those of wild-type hCT in both monomeric and oligomeric states. In contrast, F19L-hCT exhibited substantially more helices and fewer β-sheets than did hCT, irrespective of their monomers or oligomers. The substitution of F19L significantly enhanced the stability of the helical conformation for hCT14–21, thereby suppressing the helix-to-β-sheet conformational conversion. Overall, our findings elucidate the molecular mechanisms underlying hCT aggregation and the effects of F16L and F19L substitutions on the conformational dynamics of hCT, highlighting the critical role of F19 as an important target in the design of amyloid-resistant hCT analogs for future clinical applications.

In recent years, domestic and international policies to support energy-efficient buildings have been intensively introduced, and a consensus has been reached in the direction of green buildings. Building photovoltaic integration is a key technology to solve the demand for electricity in energy-efficient buildings. Meanwhile, prefabricated assembly house construction, as a common construction technology in the current building field, has the advantages of a short construction period, low project cost, a wide range of applications, and high structural stability. Green building and building industrialization are the direction of future construction industry development, combining building photovoltaic (PV) integration with assembly building, breaking down the whole structure into simple components in the factory standardization, batch production, and then on-site assembly, can reduce the mold cost, speed up the construction speed, and improve economic efficiency. The PV solar integrated assembled facade is in line with the concept of energy saving, low carbon, and environmental protection, with significant social benefits, which helps to promote rapidly in the market. In this article, by analyzing the performance and characteristics of PV modules, we propose the design method of PV-integrated prefabricated components for assembled buildings based on sensing technology, extract relevant design parameters from the database of building PV-integrated components, and test the feasibility of the modeling scheme in four stages of engineering design. The use of the results shows that the method of this article can target to improve the accuracy of PV-integrated prefabricated components, ensure the efficiency of component production and processing, and play an important role in supporting the widespread application of modern construction technology for building PV-integrated prefabricated assemblies.

ABSTRACTExtraintestinal pathogenic Escherichia coli(ExPEC) is an important zoonotic pathogen. Recently, ExPEC has been reported to be an emerging problem in pig farming. However, the mechanism of pathogenicity of porcine ExPEC remains to be revealed. In this study, we constructed a transposon (Tn) mutagenesis library covering Tn insertion in over 72% of the chromosome-encoded genes of a virulent and multi-drug resistant porcine ExPEC strain PCN033. By using a mouse infection model, a transposon-directed insertion site sequencing (TraDIS) assay was performed to identify in vivofitness factors. By comparing the Tn insertion frequencies between the input Tn library and the recovered library from different organs, 64 genes were identified to be involved in fitness during systemic infection. 15 genes were selected and individual gene deletion mutants were constructed. The in vivofitness was evaluated by using a competitive infection assay. Among them, ΔfimGwas significantly outcompeted by the WT strain in vivoand showed defective adhesion to host cells. rfawhich was involved in lipopolysaccharide biosynthesis was shown to be critical for in vivofitness which may have resulted from its role in the resistance to serum killing. In addition, several metabolic genes including fepB, sdhC, fepG, gltS, dcuA, ccmH, ddpD, narU, glpD, malM, and yabLand two regulatory genes metJand baeSwere shown as important determinants of in vivofitness of porcine ExPEC. Collectively, this study performed a genome-wide screening for in vivofitness factors which will be important for understanding the pathogenicity of porcine ExPEC.

Although graphite phase carbon nitride quantum dots (GCN QDs) showed some advantages in the electrochemiluminescence (ECL) analytical research, the low ECL efficiency limited the potential sensing application. Herein, we synthesized sulfur-doped graphite phase carbon nitride quantum dots (S-GCN QDs) to fabricate a sandwich sensor based on amplified surface plasmon coupling ECL (SPC-ECL) mode. Sulfur doping can change the surface states of QDs effectively and produced new element vacancy. As a result, the ECL efficiency of S-GCN QDs was 2.5× over GCN QDs. Furthermore, compared with the big gap between the ECL peak of GCN QDs (620 nm) and the absorption peak of Au NPs, the doped sulfur elements in S-GCN QDs generated new ECL emission peaks at 555 nm, which was closed to the absorption peak of Au NPs at 530 nm. Due to the wavelength-dependent surface plasmon coupling effect, the ECL peak of S-GCN QDs at 555 nm had greater amplitude of enhancement in the sensing system. The proposed biosensor can quantify the K-RAS gene from 50 fM to 1 nM with a limit of detection (LOD) of 16 fM. We were the first to provide insight into the role of wavelength-dependent surface plasmon coupling in enhancing the sensitivity of ECL biosensor.

Clinical applications of antiangiogenic agents profoundly affect tumor cell behaviors via the resultant hypoxia. To date, how the hypoxia regulates tumor cells remains unclear. Here, we show that hypoxia promotes the growth of human breast tumorigenic cells that repopulate tumors [tumor-repopulating cells (TRCs)] in vitro and in vivo. This stimulating effect is ascribed to hypoxia-induced reactive oxygen species (ROS) that activates Akt and NF-κB, dependent on the attenuated tricarboxylic acid (TCA) cycle. We find that fumarate is accumulated in the TCA cycle of hypoxic TRCs, leading to glutathione succination, NADPH/NADP+decrease, and an increase in ROS levels. Mechanistically, hypoxia-increased HIF-1α transcriptionally downregulates the expression of mitochondrial phosphoenolpyruvate carboxykinase (PCK2), leading to TCA cycle attenuation and fumarate accumulation. These findings reveal that hypoxia-reprogrammed TCA cycle promotes human breast TRCs growth via a HIF-1α-downregulated PCK2 pathway, implying a need for a combination of an antiangiogenic therapy with an antioxidant modulator.

We consider a general piecewise deterministic Markov process (PDMP) X= {Xt}t⩾0with a measure-valued generator A, for which the conditional distribution function of the inter-occurrence time is not necessarily absolutely continuous. A general form of the exponential martingales that are associated with Xis given by $$M_t^f = \frac{{f({X_t})}}{{f({X_0})}}{\left[ {S\exp (\int_{(0,t]} {\frac{{dL{{(Af)}_g}}}{{f({X_{g - }})}}} )} \right]^{ - 1}}.$$Mtf=f(Xt)f(X0)[Sexp(∫(0,t]dL(Af)gf(Xg−))]−1.By considering this exponential martingale to be a likelihood-ratio process, we define a new probability measure and show that the process Xis still a general PDMP under the new probability measure. We additionally find the new measure-valued generator and its domain. To illustrate our results, we investigate the continuous-time compound binomial model.

Infant colic is a characteristic group of behaviors seen in young infants. The most prominent feature is prolonged crying. Additional characteristics, including clenching of the fists and flexion of the hips, have led to the suggestion that these behaviors are related to abdominal discomfort. In this article, we show emerging evidence to support the concept that infant colic could represent gut inflammation and microbial dysbiosis that impacts brain function and even brain development.

CD8+memory T (Tm) cells are fundamental for protective immunity against infections and cancers1–5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells. Abrogation of Pck1–glycogen–PPP decreases GSH/GSSG ratios and increases levels of reactive oxygen species (ROS), leading to impairment of CD8+Tm formation and maintenance. Importantly, this metabolic regulatory mechanism could be readily translated into more efficient T-cell immunotherapy in mouse tumour models. Glycogen metabolism controls memory T cells. Ma et al. show that the metabolic gene PCK1promotes glycogen formation, which is used in the pentose phosphate pathway, generating glutathione that is important for counteraction of ROS and thus promotion of memory T-cell maintenance, and resulting in improved antitumour immunity.

The MoS2nanostructure has been widely studied as a co-catalyst for photocatalytic H2production, but itself is seldom studied as a photocatalyst. Herein, we synthesized bicrystalline (1T embedded in 2H phase) MoS2thin nanolayers with sulfur vacancies by a simple hydrothermal method. The ratio of 1T to 2H and the relative concentration of sulfur vacancies could be adjusted by changing the Mo-precursor (Na2MoO4and (NH4)2MoS4) and hydrothermal temperature. It was found that MoS2nanolayers synthesized from (NH4)2MoS4(i.e., MoS2(NMoS)) tended to form flower-shaped aggregates, while those from Na2MoO4(i.e., MoS2(NaMo)) overlapped and went across each other to form a mesoporous structure. More interestingly, MoS2(NMoS) had a high relative content of 1T phase and sulfur vacancies than MoS2(NaMo). Thus, MoS2(NMoS) demonstrated a H2production rate that was two times higher than that of MoS2(NaMo), which most likely resulted from the exposure of more active edge sites, the presence of more sulfur vacancies, the higher number of photo-excited electrons, and enhanced electron separation and transfer in MoS2(NMoS). MoS2(NMoS) also showed promising cycle performance for H2production (20 cycles with 94% retention efficiency) and superior performance to reported MoS2nanostructures. The important findings in this work could provide an alternative way to design a unique and efficient MoS2-based photocatalyst.