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Perfluorooctane sulfonate (PFOS), an emerging persistent organic pollutant, has been controversial in its impact on cognitive functions. Our previous research has confirmed that the sub-chronic PFOS exposure leads to neuronal apoptosis in the cerebral cortex, impairing cognitive functions in normal mice. However, our current study presents a surprising finding: sub-chronic exposure to PFOS effectively reduces cognitive impairments in Alzheimer's disease (AD) mice and significantly retards the disease's progression. Our results indicate that PFOS exposure upregulates the expression level of insulin-degrading enzyme (IDE) in the prefrontal cortex (PFC) of AD mice, thereby selectively enhancing the amyloid-beta (Aβ) clearance pathway without affecting the Aβ production. Moreover, PFOS exposure inhibits microglial proliferation and reduces inflammatory cytokines levels in the PFC of AD mice, providing further supporting for the pivotal role of IDE in attenuating AD progression under PFOS exposure. Collectively, our study is the first to demonstrate that sub-chronic PFOS exposure can alleviates cognitive impairments in AD pathology, with the IDE-mediated Aβ clearance pathway potentially playing a critical role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The impacts of L-glutamate (L-Glu) treatment on chilling injury (CI), Ca 2+ signaling, mitochondrial ultrastructure, and metabolisms of reactive oxygen species (ROS), γ-aminobutyric acid (GABA), energy of prune fruit under chilling stress were studied. The results found that the optimal concentration of L-Glu to suppress CI occurrence and maintain quality in prune fruit was 0.1 g L -1 , which also enhanced the PdGLRs expression, cytoplasmic Ca 2+ concentration, the contents of CaM, and CML under cold stress. Moreover, L-Glu treatment could reduce ROS accumulation and increase GABA content, and energy level, contributing to maintaining the integrity of the mitochondrial structure in cold-stored prune fruit. More importantly, PdGLRs expression and CaM/CML content positively correlated with antioxidant enzyme activities, GABA shunt, and energy status in prune fruit. These results indicated that the enhanced cold resistance of L-Glu-treated prunes might be attributed to the activated Ca 2+ signaling, thus improving the antioxidant capacity, GABA, and energy levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Air pollution is detrimental to pregnancy adversely affecting maternal and child health. Our objective was to unravel epigenetic mechanisms mediating the effect of preconception, periconception, and gestational exposure to inhaled air pollutants (AP) upon the maternal and placental-fetal phenotype and explore the benefit of an omega-3 rich dietary intervention. To this end, we investigated intranasal instilled AP during 8 weeks of preconception, periconception, and gestation (G; D0 to 18) upon GD16-19 maternal mouse metabolic status, placental nutrient transporters, placental-fetal size, and placental morphology. Prepregnant mice were glucose intolerant and insulin resistant, while pregnant mice were glucose intolerant but displayed no major placental macro-nutrient transporter changes, except for an increase in CD36. Placentas revealed inflammatory cellular infiltration with cellular edema, necrosis, hemorrhage, and an increase in fetal body weight. Upon examination of placental genome-wide epigenetic processes of DNA sequence specific 5'-hydroxymethylation (5'-hmC) and 5'-methylation (5'-mC) upon RNA sequenced gene expression profiles, revealed changes in key metabolic, inflammatory, transcriptional, and cellular processing genes and pathways. An omega-3 rich anti-inflammatory diet from preconception (8 weeks) through periconception and gestation (GD0-18), ameliorated all these maternal and placental-fetal adverse effects. We conclude that preconceptional, periconceptional and gestational exposures to AP incite a maternal inflammatory response resulting in features of pre-existing maternal diabetes mellitus with injury to the placental-fetal unit. DNA 5'-mC more than 5'-hmC mediated AP induced maternal inflammatory and metabolic dysregulation which together alter placental gene expression and phenotype. A dietary intervention partially reversing these adversities provides possibilities for a novel nutrigenomic therapeutic strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S . Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S . Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log 10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S . Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

Competing Interests: The authors declare that they have no conflict of interest.

The effects of γ-aminobutyric (GABA) on enzymatic browning, storage quality, membrane and reactive oxygen species (ROS) metabolism in fresh-cut stem lettuce were investigated. The results illustrated that GABA treatment delayed browning degree, polyphenol oxidase (PPO) activity and the expression of LsPPO. Meanwhile, higher chlorophyll and ascorbic acid contents were exhibited in GABA-treated stem lettuce, as well as the slower microbial propagation. Further investigation revealed that exogenous GABA application declined malondialdehyde content, electrolyte leakage and the enzyme activities of membrane metabolism, and the expression levels of related genes were also downregulated. In addition, GABA treatment scavenged ROS and strengthened the enzyme activities of ROS metabolism, as well as the expression levels of corresponding genes. Taken together, these findings implied that the repressed enzymatic browning and microbial propagation in GABA-treated stem lettuce were due to the inhibition of ROS accumulation, enhancement of membrane stability and increased resistance to oxidation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Marine microalgae demonstrate a notable capacity to adapt to high CO 2 and warming in the context of global change. However, the dynamics of their evolutionary processes under simultaneous high CO₂ and warming conditions remain poorly understood. Here, we analyze the dynamics of evolution in experimental populations of a model marine diatom Phaeodactylum tricornutum. We conducted whole-genome resequencing of populations under ambient, high-CO 2 , warming and high CO 2  + warming at 2-yr intervals over a 4-yr adaptation period. The common genes selected between 2- and 4-yr adaptation were found to be involved in protein ubiquitination and degradation and the tricarboxylic acid (TCA) cycle, and were consistently selected regardless of the experimental conditions or adaptation duration. The unique genes selected only by 4-yr adaptation function in respiration, fatty acid, and amino acid metabolism, facilitating adaptation to prolonged high CO 2 with warming conditions. Corresponding changes at the metabolomic level, with significant alterations in metabolites abundances involved in these pathways, support the genomic findings. Our study, integrating genomic and metabolomic data, demonstrates that long-term adaptation of microalgae to high CO 2 and/or warming can be characterized by a complex and dynamic genetic process and may advance our understanding of microalgae adaptation to global change., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Low-dimensional halide perovskites Cs 3 Cu 2 I 5 have garnered increasing attention for their exceptional luminescent properties, attributed to their stability, high photoluminescence quantum yield (PLQY), and scintillation efficiency. Here, we report the growth of transparent Cs 3 Cu 2 I 5 crystals via the Bridgman method, emphasizing precise control of melt stoichiometry for optimal performance. Through melt composition optimization, significant improvements in crystal clarity and structural integrity were achieved, enhancing transmittance from 30% to over 80% and achieving nearly 100% PLQY. Notably, it exhibited self-absorption-free behavior due to a large Stokes shift of 1.15 eV, indicative of a substantial exciton binding energy (383 meV) associated with exciton self-trapping. Lastly, under 241 Am γ-ray irradiation at 59.5 keV, the energy resolution improved to 14.9% with the transparent Cs 3 Cu 2 I 5 crystals, demonstrating its potential for high-performance scintillation applications.

Urea's transmembrane transport through urea transporters (UT) is a fundamental physiological behavior for life activities. Here, we present 11 cryo-EM structures of four UT members in resting states, urea transport states, or inactive states bound with synthetic competitive, uncompetitive or noncompetitive inhibitor. Our results indicate that the binding of urea via a conserved urea recognition motif (URM) and the urea transport via H-bond transfer along the Q Pb -T 5b -T 5a -Q Pa motif among different UT members. Moreover, distinct binding modes of the competitive inhibitors 25a and ATB3, the uncompetitive inhibitor CF11 and the noncompetitive inhibitor HQA2 provide different mechanisms for blocking urea transport and achieved selectivity through L-P pocket, UCBP region and SCG pocket, respectively. In summary, our study not only allows structural understanding of urea transport via UTs but also afforded a structural landscape of hUT-A2 inhibition by competitive, uncompetitive and noncompetitive inhibitors, which may facilitate developing selective human UT-A inhibitors as a new class of salt-sparing diuretics., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Porous triazine-based macrocycles with 22-carbon and 6-nitrogen ring atoms were efficiently synthesized and used for adsorbing bisphenol A, sulfamethoxazole, sodium dodecyl sulfate, and polyoxyethylene laural ether from aqueous media; after adsorption, simple extraction to desorb the guests from these porous macrocycles demonstrates a facile and efficient approach for porous materials to adsorb and desorb non-volatile organic compounds, thus being potentially applied to other surfactants or antibiotics.

An efficient [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with trifluoromethyl-substituted alkenes was investigated to produce a variety of 3,5-bis(fluoroalkyl)pyrazoles/pyrazolines in moderate to good yields. This protocol features obvious advantages such as easily available and stable substrates, step economy, gram-scalability and simple operation, providing a novel and practical method for the preparation of 3,5-bis(fluoroalkyl)pyrazoles/pyrazolines.

With growing concerns about environmental protection and sustainable development, the development of new biodegradable food packaging materials has become a significant focus for the future of food packaging. Polysaccharides, such as cellulose, chitosan, and starch, are considered ideal biodegradable packaging materials due to their wide availability, good biocompatibility, and biodegradability. These materials have garnered extensive attention from researchers in food packaging, leading to considerable advancements in the application of polysaccharide-based food packaging films, coatings, aerogels, and other forms. Therefore, this review focuses on the application of polysaccharide-based packaging films in food storage and preservation and discusses their preparation methods, application progress, challenges, and future development directions. Through an in-depth analysis of the existing literature, this review aims to provide sustainable and environmentally friendly solutions for the food packaging industry.

The presence of microplastics (MPs) in paddy soil has become a growing concern, yet the influence of MPs on arsenic (As) dynamics in paddy soil remains largely unexplored. A 98-day microcosm experiment was conducted to investigate the impact of MPs on As behavior in As-contaminated paddy soil. The results revealed that conventional microplastics (CMPs) reduced As concentration in porewater by 25-38 %, but substantially increased the percentage of methylated As (% MeAs) in soil by 8-23 times under 5 % dosages after 98-day incubation. In contrast, at the end of incubation, biodegradable microplastics (BMPs) at 5 % dosages notably increased As concentration in porewater and % MeAs in soil by 2-9 times and 11-395 times, respectively. The combination of network analysis and Random-Forest analysis implied that CMPs might inhibit As mobility through enhancing microbial As(III) oxidation and promote As methylation by enriching arsM-carrying microbes. However, BMPs promoted As release mainly accompanying with microbial iron reduction, and enhanced As methylation through enriching fermenting bacteria (i.e., Clostridiaceae) and arsM-carrying organic matter degrading bacteria (i.e., Gemmatimonas and Nocardia). These findings might provide broaden insights into As cycling induced by MPs and contribute to the prevention of combined pollution from As and MPs in paddy soil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Tumor-infiltrating regulatory T cells (TI-Tregs) are well-adapted to thrive in the challenging tumor microenvironment (TME) by undergoing metabolic reprogramming, notably shifting from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) for energy production. The extracellular matrix is an important component of the TME, contributing to the regulation of both tumor and immune cell metabolism patterns by activating mechanosensors such as YAP. Whether YAP plays a part in regulating TI-Treg mitochondrial function and the underlying mechanisms are yet to be elucidated., Methods: To gain insights into the effect of matrix stiffness on YAP activation in Tregs, alterations in stiffness were performed both in vitro and in vivo . YAP conditional knockout mice were used to determine the role of YAP in TI-Tregs. RNA-seq, quantitative PCR, flow cytometry, lentivirus infection and mitochondrial function assay were employed to uncover the mechanism of YAP modulating mitochondrial function in TI-Tregs. A YAP inhibitor and a low leucine diet were applied to tumor-bearing mice to seek the potential antitumor strategy., Results: In this study, we found that YAP, as a mechanotransducer, was activated by matrix stiffness in TI-Tregs. A deficiency in YAP significantly hindered the immunosuppressive capability of TI-Tregs by disrupting mitochondrial function. Mechanically, YAP enhanced mitochondrial OXPHOS by upregulating the transcription of Lars2 (Leucyl-tRNA synthetase 2, mitochondrial), which was essential for mitochondrial protein translation in TI-Tregs. Since Lars2 relied much on its substrate amino acid, leucine, the combination of a low leucine diet and YAP inhibitor synergistically induced mitochondrial dysfunction in TI-Tregs, ultimately restraining tumor growth., Conclusions: This finding uncovered a new understanding of how YAP shapes mitochondrial function in TI-Tregs in response to mechanical signals within the TME, making the combined strategy of traditional medicine and diet adjustment a promising approach for tumor therapy., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

GABA is able to increase resistance to biotic and abiotic stresses in fresh-cut fruits and vegetables. Therefore, the objective of this research was to explore the potential regulatory mechanisms of γ-aminobutyric acid (GABA) accumulation in fresh-cut stem lettuce following GABA treatment. The evidence showed that exogenous GABA stimulated the GABA shunt by elevating glutamate levels, the activities of GABA transaminase (GABA-T) and glutamate decarboxylase (GAD). Similarly, GABA stimulated polyamine metabolism by increasing the activities of 4-amino aldehyde dehydrogenase (AMADH), polyamine oxidase (PAO) and diamine oxidase (DAO), as well as elevating free polyamines, arginine and ornithine levels. Subsequently, GABA application up-regulated the expression of GABA shunt genes and polyamine metabolism genes. Additionally, GABA treatment resulted in the down-regulation of LsMYB44 and LsWRKY12 expressions. Notably, LsMYB44 bound to MYB binding sites in the LsGAD, LsGABAT1, LsADC1, LsPAO2, LsALDH7B4 promoters and repressed transcription of these genes. The interaction between LsMYB44 and LsWRKY12 was associated with the transcriptional repression of polyamine metabolism and GABA shunt genes by LsMYB44. In conclusion, LsMYB44 and LsWRKY12 downregulated the transcription of key genes of GABA shunt and polyamine metabolism in fresh-cut lettuce. This downregulation, however, was alleviated by the application of GABA, thereby promoting endogenous GABA accumulation., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Trade-offs play vital roles in evolutionary theory, linking organism performance to changing environments in the context of global change. Marine microalgae, as one of the most important groups of primary producers in the biosphere, exhibit significant trade-offs across multiple traits in response to environmental changes, such as elevated CO 2 (and consequent ocean acidification) and warming. In this review, we synthesize recent findings on the trade-offs associated with both short-term phenotypic acclimation and long-term genotypic adaptation of marine microalgae. Specifically, we discuss distinct classes of trade-offs (i.e., allocation trade-offs, acquisition trade-offs and specialist-generalist trade-offs) between multiple traits, such as growth rate, photosynthesis, nutrient acquisition, and stress tolerance. We also explored the underlying mechanisms driving these trade-offs. Finally, we discuss the broader ecological consequences of these trade-offs, such as potential shifts in species composition and ecosystem functions, and outline key research directions to better predict marine ecosystem responses to future global change scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soil salinization poses a significant global challenge, exerting adverse effects on both agriculture and ecosystems. Planting halophytes has the potential ability to improve saline-alkali land and enhance ecosystem multifunctionality (EMF). However, it remains unclear which halophytes are effective in improving saline-alkali land and what impact they have on the rhizosphere microbial communities and EMF. In this study, we evaluated the Na + absorption capability of five halophytes (Grubovia dasyphylla, Halogeton glomeratus, Suaeda salsa, Bassia scoparia, and Reaumuria songarica) and assessed their rhizosphere microbial communities and EMF. The results showed that S. salsa possessed the highest shoot (3.13 mmol g -1 ) and root (0.92 mmol g -1 ) Na + content, and its soil Na + absorption, along with B. scoparia, was significantly higher than that of other plants. The soil pH, salinity, and Na + content of the halophyte rhizospheres decreased by 6.21%, 23.49%, and 64.29%, respectively, when compared to the bulk soil. Extracellular enzymes in the halophyte rhizosphere soil, including α-glucosidase, β-glucosidase, β-1,4-N-acetyl-glucosaminidase, neutral phosphatase, and alkaline phosphatase, increased by 70.1%, 78.4%, 38.5%, 79.1%, and 64.9%, respectively. Furthermore, the halophyte rhizosphere exhibited higher network complexity of bacteria and fungi and EMF than bulk soil. The relative abundance of the dominant phyla Proteobacteria, Firmicutes, and Ascomycota in the halophyte rhizosphere soil increased by 9.4%, 8.3%, and 22.25%, respectively, and showed higher microbial network complexity compared to the bulk soil. Additionally, keystone taxa, including Muricauda, Nocardioides, and Pontibacter, were identified with notable effects on EMF. This study confirmed that euhalophytes are the best choice for saline-alkali land restoration. These findings provided a theoretical basis for the sustainable use of saline-alkali cultivated land., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Detecting residual disease is a critical clinical requirement in the peri-surgical management of patients with resectable hepatocellular carcinoma (HCC). Previous studies focused on specific genomic regions exhibiting limited sensitivity and failed to meet the minimal residual disease (MRD) testing threshold. We introduce a next-generation sequencing (NGS) based assay, informed by baseline samples, facilitating MRD detection in hepatectomized HCC patients and offering prognostic predictions., Experimental Design: This study involved 88 HCC patients who underwent surgical resections January 2016 to May 2016 in Zhongshan Hospital Fudan University. Tumor and normal tissue samples were collected during surgery, while plasma samples were obtained both before surgery and up to seven days post-surgery. Using an NGS-based personalized circulating tumor DNA assay, we analyzed MRD in both pre-surgical and post-surgical blood samples and the correlation with prognosis., Results: With a median follow-up period of 80.7 months, our findings demonstrated significant correlations between pre-surgical ctDNA tumor fractions, post-surgical plasma MRD status, and both recurrence-free survival (RFS) and overall survival (OS). Post-surgical MRD status emerged as the most significant risk factor for cancer recurrence (HR=2.17, 95% CI: 1.09-4.30, p=0.027) compared to other clinical characteristics in multivariate Cox regression analysis. Notably, MRD status showed potential as a prognostic indicator among clinically low-recurrent-risk patients, such as those with BCLC stage 0-A, CNLC stage I-II., Conclusion: Evaluating personalized MRD provided crucial prognostic insights into RFS and OS. It efficiently identified patients at high risk of recurrence, even among those initially perceived as low-risk cases.

Wheat growth process has been experiencing severe challenges arising from the adverse environment. Notably, the incidence of Fusarium crown rot (FCR), a severe soil-borne disease caused by Fusarium pseudograminearum (Fp), has significantly intensified in various wheat-growing regions, resulting in a decline in grain yield. However, the identification of wheat varieties and the exploration of effective gene resources resistant to FCR have not yet been accomplished. Here, we screened and identified the tryptophan metabolism pathway to participate in wheat resistance to FCR by correlation analysis between transcriptome and metabolome, and found that indole-3-acetaldehyde (IAAld) and melatonin, two key metabolites in the tryptophan metabolic pathway, were significantly accumulated in Fp-induced wheat stem bases. Interestingly, exogenous application of these two metabolites could significantly enhance wheat resistance against Fp. Additionally, we observed that the activity of TaALDHase, a crucial enzyme responsible for catalyzing IAAld to produce indole-3-acetic acid (IAA), was inhibited. Conversely, the activity of TaMTase, a rate-limiting involved in melatonin biosynthesis, was enhanced in the Fp-induced wheat transcriptome. Further analysis showed that TaWRKY24 could regulate IAA and melatonin biosynthesis by inhibiting the expression of TaALDHase and enhancing the transcription of TaMTase, respectively. Silencing of TaALDHase could significantly increase wheat resistance to FCR. However, interference with TaWRKY24 or TaMTase could decrease wheat resistance to FCR. Collectively, our findings demonstrate the crucial role of the tryptophan metabolism pathway in conferring resistance against FCR in wheat, thereby expanding its repertoire of biological functions within the plant system., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

G protein-coupled receptors (GPCRs) mediate most cellular responses to hormones, neurotransmitters, and environmental stimulants. However, whether GPCRs participate in tissue homeostasis through ferroptosis remains unclear. Here we identify that GPR56/ADGRG1 renders cells resistant to ferroptosis and deficiency of GPR56 exacerbates ferroptosis-mediated liver injury induced by doxorubicin (DOX) or ischemia-reperfusion (IR). Mechanistically, GPR56 decreases the abundance of phospholipids containing free polyunsaturated fatty acids (PUFAs) by promoting endocytosis-lysosomal degradation of CD36. By screening a panel of steroid hormones, we identified that 17α-hydroxypregnenolone (17-OH PREG) acts as an agonist of GPR56 to antagonize ferroptosis and efficiently attenuates liver injury before or after insult. Moreover, disease-associated GPR56 mutants were unresponsive to 17-OH PREG activation and insufficient to defend against ferroptosis. Together, our findings uncover that 17-OH PREG-GPR56 axis-mediated signal transduction works as a new anti-ferroptotic pathway to maintain liver homeostasis, providing novel insights into the potential therapy for liver injury., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The efficient synthesis of the pyrrolo[4,3,2- de ]quinoline core of the lymphostin family (compound 1 ) has been accomplished in 7 steps and 18.6% overall yield, providing an efficient method for the total synthesis and structural modification of the lymphostin family. Compound 1 showed potent inhibitory activities against PI3K/mTOR in the nanomolar range and activity against human colorectal cancer cell lines comparable to that of oxaliplatin, which could be recognized as a novel lead compound for cancer therapy.

In plant-pathogen interactions, numerous pathogens secrete polygalacturonase (PG) to degrade plants cell walls, whereas plants produce PG-inhibiting protein (PGIP) that specifically binds to pathogen-derived PG to inhibit its activity and resist pathogen infection. In the present study, we dshowed that PpPGIP1 was significantly upregulated in peaches after Monilinia fructicola infection, and the prokaryotic expression of the PpPGIP1 protein inhibited M. fructicola by mitigating its PG activity. Transient overexpression of PpPGIP1 in peaches significantly enhanced their resistance to M. fructicola. PpPGIP1 promoter had several W-box the defense elements that can bind to WRKY transcription factors. Transcriptome analysis identified 20 differentially expressed WRKY genes, including the classic disease resistance gene WRKY33. PpWRKY33 is significantly upregulated in M. fructicola infected peaches. PpWRKY33 is localized in the nucleus and can bind to the W-box in the PpPGIP1 promoter to transcriptional activate the expression of PpPGIP1. Transient overexpression PpWRKY33 upregulated PpPGIP1 expression in peaches, and silencing PpWRKY33 decreased the PpPGIP1 expression. These results indicated that PpPGIP1 positively regulates fungal disease resistance in peaches and is transcriptionally activated by PpWRKY33. These findings reveal the disease resistant role of PpPGIP1 in peaches, and provide new insights into its transcriptional regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context.—: Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal toward standardization of the Tregs assay., Objective.—: To conduct standardization studies and verify the performance of 3 commercially available reagent sets for the Tregs assay based on flow cytometry and agreement analysis for Treg detection across the different reagent sets., Design.—: The analytical performance of Tregs assay using reagent sets supplied by 3 manufacturers was evaluated after establishing the gating strategy and determining the optimal antibody concentration. Postcollection sample stability was evaluated, as well as the repeatability, reproducibility, reportable range, linearity, and assay carryover. Agreement between the different assays was assessed via Bland-Altman plots and linear regression analysis. The relationship between the frequency of CD4+CD25+CD127low/- Tregs and CD4+CD25+Foxp3+ Tregs was evaluated., Results.—: The postcollection sample stability was set at 72 hours after collection at room temperature. The accuracy, repeatability, reproducibility, and accuracy all met the requirements for clinical analysis. Excellent linearity, with R2 ≥0.9 and no assay carryover, was observed. For reportable range, a minimum of 1000 events in the CD3+CD4+ gate was required for Tregs assay. Moreover, the results for Tregs labeled by antibodies from the 3 manufacturers were in good agreement. The percentage of CD4+CD25+CD127low/- Tregs was closely correlated with CD4+CD25+Foxp3+ Tregs., Conclusions.—: This is the first study to evaluate systematically the measurement performance of Tregs in peripheral blood by flow cytometry, which provides a practical solution to verifying the performance of flow cytometry-based immune monitoring projects in clinical practice., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Heteroatom doping can change the chemical environment of carbon-based nanomaterials and improve their catalytic performance. Exploring the structure-catalytic activity relationship of heteroatom-doped carbon-based materials is of great significance for studying catalytic mechanisms and designing highly efficient catalysts, but remains a significant challenge. Recently, reactive oxygen species (ROS)-triggered electrochemiluminescence (ECL) has shown great potential for unveiling the mechanism by which heteroatom-doped carbon-based materials catalyze the oxygen reduction reaction (ORR), owing to the high sensitivity of these materials to the properties of the electrode surface. Herein, two kinds of heteroatom-doped porous carbon (denoted as NP-C and N-C) are synthesized and analyzed by monitoring the cathodic ECL of luminol-H 2 O 2 in the low negative-potential region. P, N-doped NP-C exhibits better catalytic ability for activating H 2 O 2 to generate large amounts of •OH and O 2 •- , compared with N-C. A sensitive antioxidant-mediated ECL platform is successfully developed for detecting the antioxidant levels in cells, exhibiting considerable potential for evaluating the antioxidant capacity. The relationship between the structure and catalytic mechanism of heteroatom-doped carbon-based materials is successfully explored using ECL, where this method can be universally applied to carbon-based materials., (© 2024 Wiley‐VCH GmbH.)

Thermal nonreciprocity plays a vital role in chip heat dissipation, energy-saving design, and high-temperature hyperthermia, typically realized through the use of advanced metamaterials with nonlinear, advective, spatiotemporal, or gradient properties. However, challenges such as fixed structural designs with limited adjustability, high energy consumption, and a narrow operational temperature range remain prevalent. Here, a systematic framework is introduced to achieve reconfigurable, zero-energy, and wide-temperature thermal nonreciprocity by transforming wasteful heat loss into a valuable regulatory tool. Vertical slabs composed of natural bulk materials enable asymmetric heat loss through natural convection, disrupting the inversion symmetry of thermal conduction. The reconfigurability of this system stems from the ability to modify heat loss by adjusting thermal conductivity, size, placement, and quantity of the slabs. Moreover, this structure allows for precise control of zero-energy thermal nonreciprocity across a broad temperature spectrum, utilizing solely environmental temperature gradients without additional energy consumption. This research presents a different approach to achieving nonreciprocity, broadening the potential for nonreciprocal devices such as thermal diodes and topological edge states, and inspiring further exploration of nonreciprocity in other loss-based systems., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer have poor outcomes. Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer. Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not yet been reported., Aim: To evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer., Methods: Thirty-eight patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly divided into two groups: One group received inetetamab combined with the SOX regimen, and the other group received trastuzumab combined with the SOX regimen. After 4-6 cycles, patients with stable disease received maintenance therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were the objective response rate, disease control rate, and adverse events (AEs)., Results: Thirty-seven patients completed the trial, with 18 patients in the inetetamab group and 19 patients in the trastuzumab group. In the inetetamab group, the median PFS was 8.5 months, whereas it was 7.3 months in the trastuzumab group ( P = 0.046); this difference was significant. The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months ( P = 0. 33), and the objective response rate was 50% vs 42% ( P = 0.63), respectively; these differences were not significant. Common AEs included leukopenia, thrombocytopenia, nausea, and vomiting. The incidence rates of grade ≥ 3 AEs were 56% in the inetetamab group and 47% in the trastuzumab group ( P = 0.63), with no significant difference., Conclusion: In the first-line treatment of HER2-positive advanced gastric cancer, inetetamab and trastuzumab showed comparable efficacy. The inetetamab group showed superior PFS, and both groups had good safety., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Luminescent metal-organic frameworks (LMOFs) exhibit promising applications as chemical sensors, especially for organic-linker-based LMOFs due to their unlimited structures and pre- and postfunctionality. However, it is still a challenge to introduce specific functional groups into LMOFs as reaction sites for sensing. Herein, a new luminescent zirconium-based metal-organic framework (Zr-MOF), HIAM-4009L, is reported with csq underlying net. By integrating the hydroquinone moiety into the skeleton of the organic linker via the reaction between o -diamine and aldehydes, nanosized HIAM-4009L exhibits reversible emission responses toward hypochlorous acid (HClO) and l-ascorbic acid (vitamin C, Vc) due to the switchable hydroquinone/quinone reaction. This nano-MOF can be used as a reaction-based chemical sensor for HClO and Vc detection with high selectivity and sensitivity. The present work not only provides nanosized MOFs for the reversible detection of HClO and Vc but also sheds light on the rational design of LMOFs with specific functional groups using an o -diamine- and aldehyde-based reaction.

After harvest, fruits and vegetables go through the stages of storage, transportation and sales, and how to regulate the role of preservative in different stages is an urgent problem to be solved. Herein, chitosan-stearic acid is synthesized, then interacting with trans-2-hexenal (E2H) to prepare nanoclusters. Subsequently, the temperature-sensitive liposomes were designed to encase E2H by using the special temperature-responsive open-chain phospholipids, and then combined with chitosan to obtain chitosan-based coating film for peach preservation. The thermosensitive liposomes were uniformly distributed, highly dispersed and spherical, which has excellent temperature response characteristics, and the release of active substances could be regulated in the temperature range of 10 °C-40 °C to achieve the effect of on-demand release. In addition, thermosensitive liposomes also have excellent antioxidant and antibacterial activities. Therefore, the obtained chitosan-based coating could maintain the freshness of peaches, improve the quality and extend the storage period of peaches. The edible chitosan coating and active preservative prepared in this study have potential application value in responsive intelligent active packaging., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Accurately understanding the critical elements influencing college students' professional commitment is both an urgent practical requirement and a critical theoretical proposition in today's intensely competitive job market. In order to provide new light on career development in the context of higher education, this study intends to investigate the complex interactions among college students between perceived organizational justice, academic stress, and professional commitment. Using descriptive statistics, correlation analysis, regression analysis, and structural equation modeling, we carried out a thorough investigation of H University's full-time undergraduate students in Central China in order to thoroughly examine our hypothesis. The results show that students' professional commitment is much lower when they view organizational justice to be lacking, and that there is a partial mediating role for academic stress in this relationship. Interestingly, organizational justice has a positive correlation with professional commitment and a negative correlation with academic stress. These findings provide educators and policymakers with insightful information, indicating that, in an increasingly competitive labor market, professional commitment is largely dependent on students' ability to manage their academic stress and develop a sense of organizational justice. This study adds a new understanding of career development in higher education settings by merging professional commitment research with organizational justice theory. It also has significant implications for educational practices and career support measures., (© 2024. The Author(s).)

Purpose: Establishing an immunosuppressive premetastatic niche (PMN) in distant organs is crucial for breast cancer metastasis. Vascular endothelial cells (VECs) act as barriers to transendothelial cell migration. However, the immune functions of PMNs remain unclear. Tumour cell-released autophagosomes (TRAPs) are critical modulators of antitumour immune responses. Herein, we investigated the mechanism through which TRAPs modulate the immune function of pulmonary VECs in lung PMN in breast cancer., Methods: Immortalised mouse pulmonary microvascular endothelial cells were incubated with TRAPs in vitro. RNA sequencing, flow cytometry, and western blotting were employed to assess immunosuppressive function and mechanism. In vivo, TRAP-trained and autophagy-deficient tumour mice were used to detect immunosuppression, and high-mobility group box 1 (HMGB1)-deficient TRAP-trained and TLR4 knockout mice were utilised to investigate the underlying mechanisms of pulmonary VECs. Additionally, the efficacy of anti-programmed cell death ligand-1 (PD-L1) immunotherapy was evaluated in early tumour-bearing mice., Results: HMGB1 on TRAPs surfaces stimulated VECs to upregulate PD-L1 via a TLR4-MyD88-p38/STAT3 signalling cascade that depended on the cytoskeletal movement of VECs. Importantly, PD-L1 on TRAP-induced VECs can inhibit T cell function, promote lung PMN immunosuppression, and result in more pronounced lung metastasis. Treatment with anti-PD-L1 reduces lung metastasis in early stage tumour-bearing mice., Conclusions: These findings revealed a novel role and mechanism of TRAP-induced immunosuppression of pulmonary VECs in lung PMN. TRAPs and their surface HMGB1 are important therapeutic targets for reversing immunosuppression, providing a new theoretical basis for the treatment of early stage breast cancer using an anti-PD-L1 antibody., (© 2024. Springer Nature Switzerland AG.)

Background: Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation., Methods: This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects' speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex., Discussion: Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach., Trial Registration: Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023., (© 2024. The Author(s).)

Inherently chiral medium-ring derivatives have important applications in many research fields, such as materials science, molecular recognition, and asymmetric catalysis. However, the enantioselective assembly of these molecules, especially by organocatalytic strategies, remains a formidable challenge, and few methods are available. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) formal high-order (5 + 3) annulation of 1-(2-indolyl)naphthalen-2-ols with ynals. In the presence of an NHC pre-catalyst, base, Lewis acid and oxidant, this protocol enables the catalytic formation of C-C and C-O bonds, providing practical and facile access to an array of inherently chiral saddle-shaped eight-membered lactones featuring an oxocin-2-one scaffold with structural diversity in good efficiency and excellent enantiocontrol. Moreover, the scale-up preparation and representative late-stage transformations of the eight-membered lactones further demonstrate the application potential of this synthetic technology., (© 2024. The Author(s).)

Ocean acidification (OA) interacts with multiple environmental drivers, such as temperature, nutrients, and ultraviolet radiation (UVR), posing a threat to marine primary producers. In this study, we conducted a quantitative meta-analysis of 1001 experimental assessments from 68 studies to examine the combined effects of OA and multiple environmental drivers (e.g., light, nutrient) on the biochemical compositions of marine primary producers. The results revealed significant positive effects of each environmental driver and their interactions with OA according to Hedge's d analysis. The results revealed significant positive effects of multiple environmental drivers and their interactions with OA. Additive effects dominated (71%), with smaller proportions of antagonistic (20%) and synergistic interactions (9%). The antagonistic interactions, although fewer, had a substantial impact, causing OA and other environmental drivers to interact antagonistically. Significant differences were observed among taxonomic groups: haptophytes and rhodophytes were negatively affected, while bacillariophytes were positively affected by OA. Our findings also indicated that the interactions between OA and multiple environmental drivers varied depending on specific type of the environmental driver, suggesting a modulating role of OA on the biochemical compositions of marine primary producers in response to global change. In summary, our study elucidates the complex interactions between OA and multiple environmental drivers on marine primary producers, highlighting the varied impacts on biochemical compositions and elemental stoichiometry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Tandem repeat (TR) variation is associated with gene expression changes and numerous rare monogenic diseases. Although long-read sequencing provides accurate full-length sequences and methylation of TRs, there is still a need for computational methods to profile TRs across the genome. Here we introduce the Tandem Repeat Genotyping Tool (TRGT) and an accompanying TR database. TRGT determines the consensus sequences and methylation levels of specified TRs from PacBio HiFi sequencing data. It also reports reads that support each repeat allele. These reads can be subsequently visualized with a companion TR visualization tool. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of 98.38%, allowing a single repeat unit difference. In six samples with known repeat expansions, TRGT detected all expansions while also identifying methylation signals and mosaicism and providing finer repeat length resolution than existing methods. Additionally, we released a database with allele sequences and methylation levels for 937,122 TRs across 100 genomes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Although cinnamaldehyde (CA) is an excellent antimicrobial agent, its application in the food industry was limited by its volatility and lack of antimicrobial persistence. Herein, aminated hollow mesoporous silica (NH 2 -HMSN) was prepared by selective etching and amino-modified. Subsequently, long-acting antibacterials with regulated release (NH 2 -HMSN@CA) were obtained by using NH 2 -HMSN as cinnamaldehyde carrier. NH 2 -HMSN@CA can effectively regulate the release of CA, and has 100 % inhibition effect on the growth of E. coli, S. aureus and C. acutatum. In addition, nanocellulose/NH 2 -HMSN@CA (CHA) coating film was prepared for postharvest preservation of loquat. The coating film effectively improved the storage quality and shelf life of loquat, and delayed the postharvest decay of loquat. The prepared coating film active packaging for long-term preservation is expected to provide a scheme for promoting sustainable preservation of postharvest loquat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Granulocyte colony-stimulating factor (G-CSF) activates the PI3K/Akt pathway to exert neuroprotective effects. The current study aimed to determine if G-CSF reverses behavioral deficits, even after motor malfunction occurs in Paraquat (PQ)-treated mice., Methods: Male C57BL/6 mice (8 weeks old) were divided into 3 groups: PQ + G-CSF-treated group (N.=8); PQ + saline-treated group (N.=8); and saline-treated control group (N.=8). Spontaneous locomotor activity was evaluated together with the pole test. The DA, 3, 4-dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA) levels in the bilateral striatum were determined by HPLC. The number of substantia nigra pars compacta tyrosine hydroxylase (TH)-immunoreactive neurons was calculated using an unbiased cell counting stereology method, the activities of total GSH-PX and SOD, and the malondialdehyde (MDA) content were assessed., Results: After G-CSF treatment, spontaneous motor activity and the Tturn and TLA times in the CSF group were significantly lower than the control group, and the striatal dopamine level in the striatum and the number of TH-positive neurons in the substantia nigra (SN) were significantly increased compared to the control group (5478±654 vs. 3647±488 DA neurons, P<0.05). Compared to the control group, the GSH-PX and SOD activities were increased, while the MDA level was significantly decreased in the SN (P<0.05)., Conclusions: The data strongly suggest that G-CSF reverses behavioral deficits in PQ-treated mice with movement disorders. Thus, G-CSF may be utilized as a prospective drug candidate for the treatment of Parkinson's disease.

Chitosan is an ideal coating film for food preservation, but the performance of a single chitosan coating film is not good. Herein, the liposome was prepared by embedding copper nanoparticles (CuNPs) and thyme essential oil (TEO) in the hydrophilic and hydrophobic double-domain structure formed by phospholipids, and combining with chitosan to obtain a chitosan-based coating film for litchi preservation. The liposome was well-dispersed and stable with an average particle size of about 190 nm. The liposome showed excellent controllable release properties, and the cumulative release rate of TEO was 65.17 % and that of CuNPs was 15.17 % after 7 days. Furthermore, the oxygen and water vapor barrier properties of the coating film were greatly improved. Importantly, the film possessed effective antioxidant, antibacterial activity and excellent safety, which presents a better fresh-keeping effect on litchi. This study provides insights into the design and manufacture of food packaging for controllable and long-lasting preservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The effects of hydrogen sulfide (H 2 S) on chilling injury (CI), reactive oxygen species (ROS) metabolism, sugar metabolism, pentose phosphate pathway (PPP), and membrane lipid metabolism in loquat fruit throughout the refrigerated period were investigated in this study. The findings indicated that H 2 S application restrained the increase in internal browning (IB), malondialdehyde (MDA) content, and electrolyte leakage, while sustaining higher total phenolic and total flavonoid levels, and lower soluble quinone content in loquat fruit. Besides, H 2 S promoted antioxidant accumulation and increased antioxidant enzyme activities by the regulation of ROS metabolism, along with increasing fructose and glucose levels and reducing power by activating sugar metabolism and PPP. Furthermore, H 2 S treatment retarded the degradation of phospholipids and fatty acids in loquat fruit by modulating membrane lipid metabolism relevant enzyme activities. These findings indicated that H 2 S application mitigated CI in loquat fruit by alleviating oxidative stress and maintaining cell membrane structural integrity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The simultaneous detection of multiple analytes through a single fluorescence sensor is highly attractive. In this study, phosphorus-doped graphitic carbon nitride quantum dots (P-CNQDs) were developed, achieving multi-mode sensing through three distinct response mechanisms. The preparation involved using melamine as the carbon and nitrogen source and ammonium dihydrogen phosphate as the phosphorus source. Uniform and narrowly distributed P-CNQDs were successfully synthesized through chemical oxidation and hydrothermal methods, with an average size of 2.4 nm. These unique P-CNQDs exhibited fluorescence quenching through photo-induced electron transfer (PET) in response to Ag + . Additionally, the formation of hydrogen bonds and coordination interactions between P-CNQDs-Ag + and ciprofloxacin (CIP) led to a pronounced fluorescence response to CIP by the chelation enhanced fluorescence (CHEF) mechanism. Furthermore, leveraging the principle of fluorescence resonance energy transfer (FRET), P-CNQDs-CIP served as a ratio fluorescence sensor for riboflavin (RF), enabling ultra-sensitive detection of RF. The combination of PET, CHEF, and FRET response mechanisms successfully facilitated multi-mode sensing for Ag + , CIP, and RF. The detection ranges were 0.05-100 μM, 0.002-2 μM, and 0.05-60 μM, with corresponding lowest detection limits of 17.1 nM, 1.1 nM, and 29.2 nM, respectively. This versatile sensor has been effectively applied to real samples, including the detection of river water and vitamin B 2 tablets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Traumatic brain injury (TBI) is an acquired insult to the brain caused by an external mechanical force, potentially resulting in temporary or permanent impairment. Microglia, the resident immune cells of the central nervous system, are activated in response to TBI, participating in tissue repair process. However, the underlying epigenetic mechanisms in microglia during TBI remain poorly understood. ARID1A (AT-Rich Interaction Domain 1 A), a pivotal subunit of the multi-protein SWI/SNF chromatin remodeling complex, has received little attention in microglia, especially in the context of brain injury. In this study, we generated a Arid1a cKO mouse line to investigate the potential roles of ARID1A in microglia in response to TBI. We found that glial scar formation was exacerbated due to increased microglial migration and a heightened inflammatory response in Arid1a cKO mice following TBI. Mechanistically, loss of ARID1A led to an up-regulation of the chemokine CCL5 in microglia upon the injury, while the CCL5-neutralizing antibody reduced migration and inflammatory response of LPS-stimulated Arid1a cKO microglia. Importantly, administration of auraptene (AUR), an inhibitor of CCL5, repressed the microglial migration and inflammatory response, as well as the glial scar formation after TBI. These findings suggest that ARID1A is critical for microglial response to injury and that AUR has a therapeutic potential for the treatment of TBI., (© 2024. The Author(s).)

Background: Total knee replacement (TKA) is a frequent modality performed in patients with knee osteoarthritis (OA). The aim of this study was to perform a meta-analysis and systematic review to evaluate the efficacy after TKA by gait analysis in patients with OA., Methods: PubMed, EMBASE, the Cochrane library, and Web of Science were searched for relevant studies from inception to July 2024. STATA SE 14.0 software was used for statistical analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guideline., Results: A total of 2525 reports were identified with 24 studies meeting pre-designed inclusion criteria. Several gait parameters were investigated. In patients with knee OA after TKA, there existed an increase in the Max knee flexion (WMD, 3.12; 95% CI, 0.93 to 5.32; I 2  = 73.9%, P < 0.001), the Cadence (WMD, 4.05; 95% CI, 2.28 to 5.82; I 2  = 48.9%, P = 0.068), the stride length (WMD, 0.05; 95% CI, 0.01 to 0.09; I 2  = 77.1%, P < 0.001), the walking speed (WMD, 0.08; 95% CI, 0.02 to 0.14; I 2  = 93.3%, P < 0.001), and the step length (WMD, 0.04; 95% CI, 0.00 to 0.07; I 2  = 89.3%, P < 0.001) while a decrease in the double support time (WMD, -0.04; 95% CI, - 0.08 to -0.01; I 2  = 0.0%, P = 0.585). Besides, no statistically significant differences were observed in the Knee range of motion (ROM), the Max knee rotation at stance phase, the Max knee extension, the step width, the stride time and the step time. Sensitivity analysis showed that all the results were robust., Conclusions: In summary, the study found that, in patients with knee OA undergoing TKA may have great effects on improving gait parameters. If there are more high-quality studies in the future, we should make a more comprehensive evaluation of walking function by gait analysis together with other evaluation systems such as muscle strength and proprioception measurement., (© 2024. The Author(s).)

Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors., (© 2024. The Author(s).)

Mapping enhancers and target genes in disease-related cell types has provided critical insights into the functional mechanisms of genetic variants identified by genome-wide association studies (GWAS). However, most existing analyses rely on bulk data or cultured cell lines, which may fail to identify cell-type-specific enhancers and target genes. Recently, single-cell multimodal data measuring both gene expression and chromatin accessibility within the same cells have enabled the inference of enhancer-gene pairs in a cell-type-specific and context-specific manner. However, this task is challenged by the data's high sparsity, sequencing depth variation, and the computational burden of analyzing a large number of enhancer-gene pairs. To address these challenges, we propose scMultiMap, a statistical method that infers enhancer-gene association from sparse multimodal counts using a joint latent-variable model. It adjusts for technical confounding, permits fast moment-based estimation and provides analytically derived p -values. In systematic analyses of blood and brain data, scMultiMap shows appropriate type I error control, high statistical power with greater reproducibility across independent datasets and stronger consistency with orthogonal data modalities. Meanwhile, its computational cost is less than 1% of existing methods. When applied to single-cell multimodal data from postmortem brain samples from Alzheimer's disease (AD) patients and controls, scMultiMap gave the highest heritability enrichment in microglia and revealed new insights into the regulatory mechanisms of AD GWAS variants in microglia.

In this study, we have found two new species- Strophariasubrugosoannulata and Strophariamicroaeruginosa . Phylogenetic analyses, based on the internal transcribed spacer regions (ITS) and the nuclear ribosomal RNA gene (nrLSU), suggest that the two new species are distinct and monophyletic. S.subrugosoannulata is distinguished from other species of the genus Stropharia by the pileus covered with greyish-orange squamules in the centre, stipe light brown and surface covered with white triangular squamules. S.microaeruginosa differs from other species in its pileus bluish-grey when young becoming lighter towards margins, later greyish-turquoise lightens towards the edges and surface radially striate when young, lamellae adnate to subdecurrent, stipe with white squamules at the base, acanthocytes absent. The new record species from Jilin Province, Clitolyophyllumumbilicatum was also confirmed, based on morphological and molecular study. Here, we have given full descriptions of each species, colour images, illustrations and two phylogenetic trees that show the placement and relationship of the two new species and the new record are provided., Competing Interests: The authors have declared that no competing interests exist., (Di Zhang, Jun-Jie Peng, Jia-Jun Wang, A. K. Hasith Priyashnatha, Jin-Peng Liao, Hua-Xing Luo, Shi-Chen Huang, Ji-Ze Xu.)

Background: The accumulation of diverse molecular and cytogenetic variations contributes to the heterogeneity of acute myeloid leukemia (AML), a cluster of hematologic malignancies that necessitates enhanced risk evaluation for prognostic prediction and therapeutic guidance. The ubiquitin-proteasome system plays a crucial role in AML; however, the specific contributions of 49 core proteasome family members (PSMs) in this context remain largely unexplored. Methods: The expression and survival significance of 49 PSMs in AML were evaluated using the data from BeatAML2.0, TCGA, and the GEO database, mainly through the K-M plots, differential genes enrichment analysis, and candidate compounds screening via R language and statistical software. Results: we employed LASSO and Cox regression analyses and developed a model comprising three PSMs ( PSMB8 , PSMG1 , and PSMG4 ) aimed at predicting OS in adult AML patients, utilizing expression profiles from the BeatAML2.0 training datasets. Patients with higher risk scores were predominantly found in the AML-M2 subtype, exhibited poorer ELN stratification, showed no complete remission following induction therapies, and had a higher mortality status. Consistently, significantly worse OS was observed in high-risk patients across both the training and three validation datasets, underscoring the robust predictive capability of the three-PSMs model for AML outcomes. This model elucidated the distinct genetic abnormalities landscape between high- and low-risk groups and enhanced the ELN risk stratification system. Ultimately, the three-PSMs risk score captured AML-specific gene expression signatures, providing a molecular basis for selecting potential therapeutic agents. Conclusions: In summary, these findings manifested the significant potential of the PSM model for predicting AML survival and informed treatment strategies.

Circular bacteriocins are known for their structural stability and effective antimicrobial properties, positioning them as potential natural food preservatives. However, their widespread application is impeded by restricted availability. This research developed a total biosynthesis platform for circular bacteriocins, with a focus on AS-48 by involving recombinant production of the linear precursor in Escherichia coli , followed by enzymatic cyclization of the precursor into cyclic AS-48 using the ligase butelase-1 in vitro . An important discovery is that, aside from fusion tags, the C-terminal motif LE and LEKKK also could affect the expression yield of the precursor. This biosynthesis platform is both versatile and high-yielding, achieving yields of 10-20 mg/L of AS-48. Importantly, the biosynthetic AS-48 exhibited a secondary structure and antimicrobial activities comparable to those of the native molecules. As such, this work proposes an effective synthetic approach for circular bacteriocins, facilitating their advancement and application in the food industry.

Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8 + T cells and the prognosis of AML patients. To develop a CD8 + T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8 + T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8 + T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8 + T High and CD8 + T Low groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8 + T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YT declared a shared affiliation, though no other collaboration, with one of the authors RX at the time of the review., (Copyright © 2024 Li, Jin, Xiang, Li, Shen, He, Liu, Zhu, Wu, Dong, Zhao, Liu, Jin and Li.)