Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. METHODS: The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. RESULTS: We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4-94.1%) and specificity of 90.0% (95% CI: 81.9-95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. CONCLUSION: TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021.

Phenylethylammonium bromide-assisted solution-phase ligand exchange in CsPbBr3quantum dot solar cells.

CsPbBr3quantum dots (QDs) have excellent optical properties and good phase stability, but the long-chain ligands on their surfaces affect the charge transfer between QDs. Here, we propose a simple ligand exchange strategy: solution-phase ligand exchange. By adding an acetone solution of phenylethylammonium bromide to the purification process of CsPbBr3QDs, the long-chain ligands were effectively replaced and the electric coupling between QDs was improved. As a result, the power conversion efficiency of the solar cell was increased from 1.95% to 2.83%. Meanwhile, the stability of the devices was significantly improved in the unencapsulated case.

Salt-tolerant plant growth-promoting bacteria as a versatile tool for combating salt stress in crop plants.

Soil salinization poses a great threat to global agricultural ecosystems, and finding ways to improve the soils affected by salt and maintain soil health and sustainable productivity has become a major challenge. Various physical, chemical and biological approaches are being evaluated to address this escalating environmental issue. Among them, fully utilizing salt-tolerant plant growth-promoting bacteria (PGPB) has been labeled as a potential strategy to alleviate salt stress, since they can not only adapt well to saline soil environments but also enhance soil fertility and plant development under saline conditions. In the last few years, an increasing number of salt-tolerant PGPB have been excavated from specific ecological niches, and various mechanisms mediated by such bacterial strains, including but not limited to siderophore production, nitrogen fixation, enhanced nutrient availability, and phytohormone modulation, have been intensively studied to develop microbial inoculants in agriculture. This review outlines the positive impacts and growth-promoting mechanisms of a variety of salt-tolerant PGPB and opens up new avenues to commercialize cultivable microbes and reduce the detrimental impacts of salt stress on plant growth. Furthermore, considering the practical limitations of salt-tolerant PGPB in the implementation and potential integration of advanced biological techniques in salt-tolerant PGPB to enhance their effectiveness in promoting sustainable agriculture under salt stress are also accentuated.

Different frequencies of water deficit irrigation treatments improve fruit quality of Zitian seedless grapes under on-tree storage.

In this study, we assessed the impact of varied water deficit irrigation frequencies (T1: 2.5 L/4 days; T2: 5 L/8 days; CK: 5 L/4 days) on Zitian Seedless grapes from veraison to post-ripening. Notably, total soluble solids increased during on-tree storage compared to at maturity, while total anthocyanin content decreased, particularly in CK (60.16%), T1 (62.35%), and less in T2 (50.54%). Glucose and fructose levels increased significantly in T1 and T2, more so in T2, but slightly declined in CK. Tartaric acid content increased by 41.42% in T2. Moreover, compared to regular irrigation, water deficit treatments enhanced phenolic metabolites and volatile compounds, including chlorogenic acid, various flavonoids, viniferin, hexanal, 2-nonenal, 2-hexen-1-ol, (E)-, 3-hydroxy-dodecanoic acid, and 1-hexanol, etc. Overall, the T2 treatment outperformed T1 and CK in maintaining grape quality. This study reveals that combining on-tree storage with water deficit irrigation not only improves grape quality but also water efficiency.

Electrochemically Dealloying Engineering toward Integrated Monolithic Electrodes with Superior Electrochemical Li-Storage Properties.

Integrated monolithic electrodes (IMEs) free of inactive components demonstrate great potential in boosting energy-power densities and cycling life of lithium-ion batteries. However, their practical applications are significantly limited by low active substance loading (< 4.0 mg cm-2 and 1.0 g cm-3), complicated manufacturing process, and high fabrication cost. Herein, employing industrial Cu-Mn alloy foil as a precursor, a simple neutral salt solution-mediated electrochemical dealloying strategy is proposed to address such problems. The resultant Cu-Mn IMEs achieve not only a significantly larger active material loading due to the in situ generated Cu2O and MnOx (ca. 16.0 mg cm-2 and 1.78 g cm-3), simultaneously fast transport of ions and electrons due to the well-formed nanoporous structure and built-in Cu current collector, but also high structural stability due to the interconnected ligaments and suitable free space to relieve the volume expansion upon lithiation. As a result, they demonstrate remarkable performances including large specific capacities (> 5.7 mAh cm-2), remarkable pseudocapacitive effect despite the battery-type constitutes, long cycling life, and good working condition in a lithium-ion full cell. This study sheds new light on the further development of IMEs, enriches the existing dealloying techniques, and builds a bridge between the two.

Diagnosis of malignant body fluids via cancer-universal methylation in cell-free DNA.

BACKGROUNDDifferentiating malignant from nonmalignant body fluids remains a clinical challenge because of the unsatisfying performance of conventional cytology. We aimed to improve the sensitivity and ubiquity of cancer cell detection by assaying universal cancer-only methylation (UCOM) markers in supernatant cell-free DNA (cfDNA).METHODSAn observational prospective cohort including 1,321 nonmalignant and malignant body fluids of multiple cancers was used to develop and validate a cfDNA UCOM methylation diagnostic assay. All samples were divided into 2 portions for cytology and supernatant cfDNA methylation analysis.RESULTSThe significant hypermethylation of a potentially novel UCOM marker, TAGMe, together with the formerly reported PCDHGB7, was identified in the cfDNA of malignant body fluid samples. The combined model, cell-free cancer-universal methylation (CUE), was developed and validated in a prospective multicancer cohort with markedly elevated sensitivity and specificity, and was further verified in a set containing additional types of malignant body fluids and metastases. In addition, it remained hypersensitive in detecting cancer cells in cytologically negative malignant samples.CONCLUSIONcfDNA methylation markers are robust in detecting tumor cells and are applicable to diverse body fluids and tumor types, providing a feasible complement to current cytology-based diagnostic analyses.TRIAL REGISTRATIONThis study was registered at Chictr.org.cn (ChiCTR2200060532).FUNDINGNational Natural Science Foundation of China (32270645, 31872814, 32000505, 82170088), the National Key R&D Program of Ningxia Hui Autonomous region (2022BEG01003), Shanghai Municipal Key Clinical Specialty (shslczdzk02201), Science and Technology Commission of Shanghai Municipality (20DZ2261200, 20DZ2254400), and Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101).

Ferroptosis resists intracellular Vibrio splendidus AJ01 mediated by ferroportin in sea cucumber Apostichopus japonicus.

Ferroptosis, a kind of programmed cell death, is characterized with iron-dependent lipid ROS buildup, which is considered as an important cellular immunity in resisting intracellular bacterial infection in mammalian macrophages. In this process, lipid ROS oxidizes the bacterial biofilm to inhibit intracellular bacteria. However, the function of ferroptosis in invertebrate remains unknown. In this study, the existence of ferroptosis in Apostichopus japonicus coelomocytes was confirmed, and its antibacterial mechanism was investigated. First, our results indicated that the expression of glutathione peroxidase (AjGPX4) was significantly inhibited by 0.21-fold (p < 0.01) after injecting A. japonicus with the ferroptosis inducer RSL3, and the contents of MDA (3.93-fold, p < 0.01), ferrous iron (1.40-fold, p < 0.01), and lipid ROS (3.10-fold, p < 0.01) were all significantly increased under this condition and simultaneously accompanied with mitochondrial contraction and disappearance of cristae, indicating the existence of ferroptosis in the coelomocytes of A. japonicus. Subsequently, the contents of ferrous iron (1.40-fold, p < 0.05), MDA (2.10-fold, p < 0.01), ROS (1.70-fold, p < 0.01), and lipid ROS (2.50-fold, p < 0.01) were all significantly increased, whereas the mitochondrial membrane potential and GSH/GSSG were markedly decreased by 0.68-fold (p < 0.05) and 0.69-fold (p < 0.01) under Vibrio splendidus (AJ01) infection. This process could be reversed by the iron-chelating agent deferoxamine mesylate, which indicated that AJ01 could induce coelomocytic ferroptosis. Moreover, the results demonstrated that the intracellular AJ01 load was clearly decreased to 0.49-fold (p < 0.05) and 0.06-fold (p < 0.01) after treating coelomocytes with RSL3 and ferrous iron, which indicated that enhanced ferroptosis could inhibit bacterial growth. Finally, subcellular localization demonstrated that ferrous iron efflux protein ferroportin (AjFPN) and intracellular AJ01 were co-localized in coelomocytes. After AjFPN interference (0.58-fold, p < 0.01), the signals of ferrous iron and lipid ROS levels in intracellular AJ01 were significantly reduced by 0.38-fold (p < 0.01) and 0.48-fold (p < 0.01), indicating that AjFPN was an important factor in the introduction of ferroptosis into intracellular bacteria. Overall, our findings indicated that ferroptosis could resist intracellular AJ01 infection via AjFPN. These findings provide a novel defense mechanism for aquatic animals against intracellular bacterial infection.

The NLRP3 inhibitor, OLT1177 attenuates brain injury in experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It has been reported activation of NLRP3 inflammasome after intracerebral hemorrhage (ICH) ictus exacerbates neuroinflammation and brain injury. We hypothesized that inhibition of NLRP3 by OLT1177 (dapansutrile), a novel NLRP3 inflammasome inhibitor, could reduce brain edema and attenuate brain injury in experimental ICH. METHODS: ICH was induced by injection of autologous blood into basal ganglia in mice models. Sixty-three C57Bl/6 male mice were randomly grouped into the sham, vehicle, OLT1177 (Dapansutrile, 200 mg/kg intraperitoneally) and treated for consecutive three days, starting from 1 h after ICH surgery. Behavioral test, brain edema, brain water content, blood-brain barrier integrity and vascular permeability, cell apoptosis, and NLRP3 and its downstream protein levels were measured. RESULTS: OLT1177 significantly reduced cerebral edema after ICH and contributed to the attenuation of neurological deficits. OLT1177 could preserve blood-brain barrier integrity and lessen vascular leakage. In addition, OLT1177 preserved microglia morphological shift and significantly inhibited the activation of caspase-1 and release of IL-1ß. We also found that OLT1177 can protect against neuronal loss in the affected hemisphere. CONCLUSIONS: OLT1177 (dapansutrile) could significantly attenuate the brain edema after ICH and effectively alleviate the neurological deficit. This result suggests that the novel NLRP3 inhibitor, OLT1177, might serve as a promising candidate for the treatment of ICH.

Genomic evidence for climate-linked diversity loss and increased vulnerability of wild barley spanning 28 years of climate warming.

The information on how plant populations respond genetically to climate warming is scarce. Here, landscape genomic and machine learning approaches were integrated to assess genetic response of 10 wild barley (Hordeum vulgare ssp. spontaneum; WB) populations in the past and future, using whole genomic sequencing (WGS) data. The WB populations were sampled in 1980 and again in 2008. Phylogeny of accessions was roughly in conformity with sampling sites, which accompanied by admixture/introgressions. The 28-y climate warming resulted in decreased genetic diversity, increased selection pressure, and an increase in deleterious single nucleotide polymorphism (dSNP) numbers, heterozygous deleterious and total deleterious burdens for WB. Genome-environment associations identified some candidate genes belonging to peroxidase family (HORVU2Hr1G057450, HORVU4Hr1G052060 and HORVU4Hr1G057210) and heat shock protein 70 family (HORVU2Hr1G112630). The gene HORVU2Hr1G120170 identified by selective sweep analysis was under strong selection during the climate warming of the 28-y, and its derived haplotypes were fixed by WB when faced with the 28-y increasingly severe environment. Temperature variables were found to be more important than precipitation variables in influencing genomic variation, with an eco-physiological index gdd5 (growing degree-days at the baseline threshold temperature of 5 °C) being the most important determinant. Gradient forest modelling revealed higher predicted genomic vulnerability in Sede Boqer under future climate scenarios at 2041-2070 and 2071-2100. Additionally, estimates of effective population size (Ne) tracing back to 250 years indicated a forward decline in all populations over time. Our assessment about past genetic response and future vulnerability of WB under climate warming is crucial for informing conservation efforts for wild cereals and rational use strategies.

Dietary Bacillus cereus LS2 protects juvenile sea cucumber Apostichopus japonicus against Vibrio splendidus infection.

This study aimed to investigate the effects of Bacillus cereus LS2 on the growth performance, innate immunity, intestinal microbiota, and disease resistance of sea cucumber Apostichopus japonicus. After feeding with LS2 for 30 days, results showed that dietary with LS2 had a significant improvement in the growth rate and immune parameters (including total coelomocytes counts, phagocytosis, respiratory burst, and immune-related enzymes) of juvenile sea cucumbers. Subsequently, transcriptome sequencing and qRT-PCR verification were performed to analyze the potential mechanism of LS2 diet and thus improve the immune response of A. japonicus. GO and KEGG pathway analysis indicated that LS2 can primarily activate the "Lectins" and "complement and coagulation cascades" pathways to modulate the innate immunity of the sea cucumbers. Furthermore, 16S rRNA sequencing was used to analyze the intestinal microbial composition of sea cucumbers after dietary with LS2. Results showed that Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the most prevalent phyla in A. japonicus intestinal microbiota. The abundance of Actinobacteria (46.20%) and Bacteroidetes (12.80%) were significantly higher in the LS2 group, whereas the relative abundance of Proteobacteria (49.98%) and Firmicutes (14.97%) were higher in the control group. The LDA scores of Nocardiaceae and Rhodococcus were also the highest taxa after the dietary administration of LS2, indicating that Actinobacteria phylum played a pivotal role in the intestinal microbial function of A. japonicus. Overall, these results suggested that feeding with Bacillus LS2 may be beneficial for A. japonicus farming.

Recent advances in pH-sensitive indicator films based on natural colorants for smart monitoring of food freshness: a review.

As a new type of packaging method, natural pigment-based pH-sensitive indicator film packaging can be used to intelligently monitor food freshness, provide consumers with intuitive food freshness information, and own the advantages of small size, low cost and intuitive accuracy. Based on the introduction of the principle of natural pigment in pH-sensitive indicator film intelligent packaging, this paper reviews the types of natural pigment indicators (such as anthocyanins, curcumin) and film-forming matrix materials, and systematically discusses the research progress of their application in freshness monitoring in various foods, and points out the limitations of this intelligent packaging in practical applications. In order to provide natural pigment in the application and promotion of pH-sensitive indicator film packaging for monitoring food freshness, further research and development works are required to overcome the current limitations. The needs for further research and developments are outlined.

Association of serum cytokines with coronary chronic total occlusion and their role in predicting procedural outcomes.

BACKGROUND: Cytokines are strongly associated with coronary artery disease (CAD); however, few studies have explored the relevance of cytokines in coronary chronic total occlusion (CTO). This study aimed to clarify the association of cytokines with CTO and its procedural outcomes. METHODS: A total of 526 patients with suspected CAD but not acute myocardial infarction were enrolled and divided into CTO (n = 122) and non-CTO (n = 404) groups based on coronary angiography. Furthermore, serum levels of 12 cytokines [Interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α (TNF-α), interferon-α (IFN-α), and IFN-γ] were measured for each patient. RESULTS: Patients with CTO had higher rates of male (P = 0.001), smoking (P = 0.014), and diabetes (P = 0.008); higher levels of IL-6 (P < 0.001), total triglycerides (P = 0.020), serum creatine (P = 0.001), and high-sensitivity troponin I (P = 0.001); and lower IL-4 (P < 0.001), total cholesterol (P = 0.027), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) levels compared to those without CTO. IL-4 (OR = 0.216, 95%CI:0.135-0.345, P < 0.001), IL-6 (OR = 1.248, 95%CI:1.165-1.337, P < 0.001), and HDL-C (OR = 0.047, 95%CI:0.010-0.221, P < 0.001) were identified as independent predictors of CTO. And good predictive performance (AUC = 0.876) for CTO, with a sensitivity of 81.96% and specificity of 81.19%, could be achieved by combining these three predictors. Furthermore, patients with procedural success had younger age (P = 0.004) and lower serum IL-6 levels (P = 0.039) compared to those with procedural failure, and IL-6 levels (OR = 0.962, 95%CI: 0.931-0.995, P = 0.023) were associated with procedural success. CONCLUSION: IL-4, IL-6, and HDL-C levels were strongly associated with CTO, and IL-6 also linked to procedural outcomes of CTO.

One Molecular Probe with Opposite Enantioselective Fluorescence Enhancement at Two Distinct Emissions.

It is discovered that one enantiomer of a chiral substrate can greatly enhance the fluorescence of one molecular probe at one emitting signal (λ1 = 517 nm), while the opposite enantiomer of the substrate greatly enhances the fluorescence of the same probe at a distinctively different emission (λ2 = 575 nm). This probe is made of a 1,1'-binaphthyl-based chiral dialdehyde that in combination with Zn2+ under slightly acidic conditions shows a chemoselective and enantioselective fluorescent response to histidine. The opposite enantioselective fluorescent responses of the probe at two emissions allow it to be used to determine both the concentration and the enantiomeric composition of the substrate using a single probe. The mechanistic study has revealed two very different reaction pathways when the two enantiomers of the substrate are treated with the probe. These reaction pathways generate two different products, one dimeric and another polymeric, with very different emissions.

Quasi-Solid Polymer Electrolyte with Multiple Lithium-Ion Transport Pathways by In Situ Thermal-Initiating Polymerization.

Solid polymer electrolytes (SPEs) are considered to be attractive candidates for rechargeable batteries on account of their high safety and flexible processability. However, the restricted polymer segmental dynamics limit the Li+ conduction of SPEs. Herein, a composite electrolyte membrane was prepared via in situ thermal-initiating polymerization of diethylene glycol diacrylate (DEGDA) in a poly(vinylidene fluoride) frameworks (PVDF FMs) electrospun in advance. As a quasi-solid polymer electrolyte (QSPE), it provides multiple transport highways for Li+ built by the C═O or C-O or C═O/C-O groups in poly(diethylene glycol) diacrylate (PDEGDA), respectively, proved by density functional theory calculations together with the high-resolution 7Li solid-state nuclear magnetic resonance spectra. Since the interaction between Li+ and C═O is weaker than that between Li+ and C-O, Li+ tends to move along C═O dominating paths in PDEGDA/PVDF FMs QSPEs, even skipping back to C═O nodes from the original C-O dominating way. Multiple transport patterns facilitate Li+ migration within PDEGDA/PVDF FMs QSPEs, contributing to the ionic conductivity of 1.41 × 10-4 S cm-1 at 25 °C and the Li+ transference number of 0.454. Ascribing to the wetting capability of the monomer to the electrodes in use, compatible electrolyte/electrode interfaces with low interface resistance and compact cells were acquired by the in situ polymerization. Protective lithiated oligomers (RCOOLi) and LiF are enriched at the Li anode surface, promoting a lasting stable Li plating/stripping over 2000 h. By applying the QSPEs in LiFePO4 cell, a capacity of 157.7 mAh g-1 with almost 100% coulombic efficiency during 200 cycles is achieved at 25 °C.

Time-dependent and selective microglia-mediated removal of spinal synapses in neuropathic pain.

Neuropathic pain is a debilitating condition resulting from damage to the nervous system. Imbalance of spinal excitation and inhibition has been proposed to contribute to neuropathic pain. However, the structural basis of this imbalance remains unknown. Using a preclinical model of neuropathic pain, we show that microglia selectively engulf spinal synapses that are formed by central neurons and spare those of peripheral sensory neurons. Furthermore, we reveal that removal of inhibitory and excitatory synapses exhibits distinct temporal patterns, in which microglia-mediated inhibitory synapse removal precedes excitatory synapse removal. We also find selective and gradual increase in complement depositions on dorsal horn synapses that corresponds to the temporal pattern of microglial synapse pruning activity and type-specific synapse loss. Together, these results define a specific role for microglia in the progression of neuropathic pain pathogenesis and implicate these immune cells in structural remodeling of dorsal horn circuitry.

Engineering CoP Alloy Foil to a Well-Designed Integrated Electrode Toward High-Performance Electrochemical Energy Storage.

Nanostructured integrated electrodes with binder-free design show great potential to solve the ever-growing problems faced by currently commercial lithium-ion batteries such as insufficient power and energy densities. However, there are still many challenging problems limiting practical application of this emerging technology, in particular complex manufacturing process, high fabrication cost, and low loading mass of active material. Different from existing fabrication strategies, here using a CoP alloy foil as a precursor  a simple neutral salt solution-mediated electrochemical dealloying method to well address the above issues is demonstrated. The resultant freestanding mesoporous np-Co(OH)x /Co2 P product possesses not only active compositions of high specific capacity and large electrode packing density (>3.0 g cm-3 ) to meet practical capacity requirements, high-conductivity and well-developed nanoporous framework to achieve simultaneously fast ion and electron transfer, but also interconnected ligaments and suitable free space to ensure strong structural stability. Its comprehensively excellent electrochemical energy storage (EES) performances in both lithium/sodium-ion batteries and lithium-ion capacitors can further illustrate the effectiveness of the integrated electrode preparation strategy, such as remarkable reversible specific capacities/capacitances, dominated pseudo-capacitive EES mechanism, and ultra-long cycling life. This study provides new insights into preparation and design of high-performance integrated electrodes for practical applications.

A portable and miniaturized lab-on-fiber sensor based on a responsive Fabry-Perot resonance cavity for the detection of thiocyanate.

Thiocyanate (SCN-) detection is highly significant because of the toxicity of SCN-. Herein, a portable and miniaturized lab-on-fiber (LOF) sensor is reported for the detection of SCN- through integrating a Fabry-Perot (F-P) optical resonance cavity based on anionic-responsive metal-insulator-metal (MIM) onto an optical fiber tip. The responsive MIM optical resonance cavity is constructed with an intermediate cationic polymer brush layer (poly[2-(methacryloyloxy)ethyl] trimethylammonium chloride, PMETAC) and two silver layers via a facile in situ "layer-by-layer" construction method. When the fabricated LOF sensor was immersed in SCN- solutions, an obvious reflection dip shift can be observed, which is feasible for the quantitative detection of SCN-. What's more, the fabricated LOF sensor exhibits outstanding selectivity and anti-interference against other interfering anions. Furthermore, the fabricated LOF sensor also displays other excellent advantages endowed by the polymer brush film, such as a fast response rate and outstanding reproducibility. Therefore, it is believed that the fabricated miniaturized LOF sensor would show great potential as a portable sensor in future applications, such as environmental monitoring and clinical diagnosis.

Post-veraison different frequencies of water deficit strategies enhance Reliance grapes quality under root restriction.

In this study, two water deficit treatments in the same amount of water but with different frequencies (T1: 2.5 L per 4 d and T2: 5 L per 8 d) were performed on Reliance grapevines from veraison until harvest to explore their effects on grape berries quality under root restriction. Results showed that glucose, fructose and sucrose contents were increased, while malic acid, tartaric acid and citric acid contents were decreased under two treatments. Meanwhile, water deficits also promoted the accumulation of phenylalanine and proline. For phenols, anthocyanins, resveratrol and flavonols contents in the water deficit groups were significantly higher than those in the control group. In addition, two water deficit treatments increased the characteristic aromas contents, especially the esters contents. Overall, T2 treatment had a better effect than T1 treatment. This study provided an idea for improving water use efficiency and grape quality.

N-Phenyl-substituted poly(benzimidazole imide)s with high glass transition temperature and low coefficient of thermal expansion.

To obtain high thermostable materials for flexible display substrates, a series of copoly(benzimidazole imide)s was prepared using 5-amine-2-(4-aminobenzene)-1-phenyl-benzimidazole (N-PhPABZ) and 6(5)-amino-2-(4-aminobenzene)-benzimidazole (PABZ). Incorporating N-phenyl groups effectively healed the brittleness of the poly(benzimidazole imide)s (PBIIs) derived from pyromellitic dianhydride (PMDA), and the resultant homo- and copoly(benzimidazole imide)s displayed an outstandingly high glass transition temperature (T g > 450 °C) and a low coefficient of thermal expansion (CTE < 10 ppm K-1). Furthermore, the influence of removing intermolecular hydrogen bonds on the properties of these poly(benzimidazole imide)s was systematically analyzed. These data provide a feasible method to prepare superheat-resistant poly(benzimidazole imide)s without H-bonding.

Long-term male-specific chronic pain via telomere- and p53­mediated spinal cord cellular senescence.

Mice with experimental nerve damage can display long­lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53­mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53­positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male­specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male­specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53­specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male­specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.