Carboxyl-functionalized dual pH/temperature-responsive poly(N-vinylcaprolactam) microgels based on isogenous comonomers for smart window applications.

Stimuli-responsive poly(N-vinylcaprolactam) (PVCL)-based microgels, which could response to small external environmental changes, have attracted great interests in the fields of biomedicine and nanotechnology. However, the preparation of such microgels meets severe challenge due to their low incorporation efficiency and thermoresponsivity passivation. To address these issues, we select 3-(tert-butoxycarbonyl)-N-vinylcaprolactam (TBVCL), a carboxyl-functionalized VCL derivative, as a comonomer to develop pH/temperature dual-responsive microgels. TBVCL, with a structure similar to VCL, enhances incorporation efficiency and colloidal stability, while reducing thermoresponsivity passivation. The volume phase transition temperature (VPTT) of the microgels can be adjusted over a broad range (19.0-49.5 °C). Notably, the radial swelling ratios of the microgels can be modulated by pH, achieving a maximum swelling ratio of 3. The distinct changes in dissolution-precipitation behavior under different temperatures or pH conditions make these microgels suitable for applications such as smart windows and sensors. Furthermore, this novel approach for fabricating microgels with pH-tunable phase-transition temperatures demonstrates significant potential for the controlled release of nanoparticles (e.g., drugs, catalysts, and quantum dots) and the development of smart nanocrystal-polymer composite sensors.

Coronary artery bypass grafting in dialysis patients: a propensity score-matched analysis.

BACKGROUND: Patients undergoing dialysis treatment have long been recognized as having an elevated risk of developing coronary artery disease necessitating coronary artery bypass grafting (CABG). However, the prognostic implications of CABG in dialysis-dependent patients remain underexplored. This study aimed to comprehensively assess both short- and long-term outcomes in dialysis-dependent patients undergoing CABG. METHODS: In this retrospective analysis, we meticulously matched 55 dialysis-dependent patients with 55 non-dialysis patients, controlling for baseline characteristics including age, sex, etiology, and date of surgery. All patients underwent CABG treatment at our institution between January 2014 and June 2022. We conducted a comparative analysis of postoperative complications and survival rates between the two groups. RESULTS: Our findings revealed that the dialysis-dependent group exhibited a significantly higher incidence of postoperative complications compared to the non-dialysis group (92.7% vs. 61.8%; p < 0.001). Furthermore, the 5-year survival rates were notably diminished among dialysis patients relative to their non-dialysis counterparts (46.2 ± 7.9% vs. 58.2 ± 12.1%, p = 0.045). Consistently, dialysis patients exhibited decreased 5-year cardiac-event-free rates in contrast to non-dialysis patients (31.6 ± 7.6% vs. 58.8 ± 11.3%, p = 0.041). Predictably, several baseline parameters were identified as significant risk factors contributing to adverse outcomes among dialysis patients, including a history of smoking, diabetes mellitus, congestive heart failure upon admission, and the requirement for intraoperative concomitant surgery (p = 0.006, p = 0.043, p = 0.017, p = 0.003, respectively). CONCLUSIONS: This study underscores the poorer prognosis associated with CABG treatment in dialysis-dependent patients. Notably, baseline factors such as a smoking history, diabetes mellitus, congestive heart failure upon admission, and the need for intraoperative concomitant surgery were all independently linked to increased mortality in this patient population.

Research on Engineering the Saccharomyces uvarum for Constructing a High Efficiency to Degrade Malic Acid and Low Yield of Diacetyl Biosynthesis Pathway.

Diacetyl is a flavor compound in wine with a low threshold (1-2 mg/L). It is produced during alcoholic fermentation (AF) Saccharomyces and malolactic fermentation (MLF) initiated by lactic acid bacteria (LAB). Whereas, the environment after AF suppresses the normal metabolism of LAB after AF. Researchs have shown the influence on diacetyl mechanisms of the genes ILV2, ILV6, ILV3, ILV5, BDH1, BDH2, and gene aldB from Lactobacillus plantarum in Saccharomyce uvarum WY1. While we found that the diacetyl contents produced by mutants after MLF (Co-fermentation and Seq-fermentation) were significantly improved compared to AF alone. Moreover, the genes mae1 and mae2 from S. pombe, and gene mleS from L. lactis exhibited significant effect on deacidification in our previous study, but the diacetyl of the mutants showed obvious improvement in this study. Thus the effects of association mutation of genes (ILV2, ILV6, ILV3, ILV5, BDH1, BDH2, aldB, mae1, and mleS) on deacidification, diacetyl and other flavors (organic acids, higher alcohols and esters) metabolism in S. uvarum after AF were detected in the study. Among all the mutants, strains V6AmS, V635mS, and V6B12mS showed the most favorable results. Specifically, the L-malic acid contents decreased to 1.26 g/L, 1.18 g/L, and 1.19 g/L, respectively. Concurrently, diacetyl levels were reduced by 52.56%, 61.84%, and 65.31%. The production of n-propanol increased by 18.84%, 20.89%, and 28.12%, whereas isobutanol levels decreased by 37.01%, 42.36%, and 44.04%, and isoamyl alcohol levels decreased by 19.28%, 19.79%, and 16.74%, compared to the parental strain WY1. Additionally, the concentration of lactate ester in the wine increased to 13.162 mg/L, 14.729 mg/L, and 14.236 mg/L, respectively.

Energy Reserve Allocation in the Trade-Off between Migration and Reproduction in Fall Armyworm.

Striking a trade-off between migration and reproduction becomes imperative during long-range migration to ensure proper energy allocation. However, the mechanisms involved in this trade-off remain poorly understood. Here, we used a takeoff assay to distinguish migratory from non-migratory individuals in the fall armyworm, which is a major migratory insect worldwide. Migratory females displayed delayed ovarian development and flew further and faster than non-migratory females during tethered flight. Transcriptome analyses demonstrated an enrichment of fatty acid genes across successive levels of ovarian development and different migratory behaviors. Additionally, genes with roles in phototransduction and carbohydrate digestion along with absorption function were enriched in migratory females. Consistent with this, we identified increased abdominal lipids in migratory females that were mobilized to supply energy to the flight muscles in the thorax. Our study reveals that the fall armyworm faces a trade-off in allocating abdominal triglycerides between migration and reproduction during flight. The findings provide valuable insights for future research on this trade-off and highlight the key energy components involved in this strategic balance.

Clinical and genetic insights into ABCA12 variants in three Chinese families with ichthyosis: Genotype-phenotype correlation.

Autosomal recessive congenital ichthyosis (ARCI) comprises a series of non-syndromic ichthyoses. Pathogenic variants in several genes associated with ARCI have so far been identified. Notably, the variants in ABCA12 play a pivotal role in the pathology of ARCI. In this study, we report three Chinese families with compound heterozygous variants in the ABCA12 gene, including two novel variants and four reported variants. Clinical and genetic analyses were conducted to explore the genotype-phenotype correlation among the patients. Immunohistochemistry and transcriptome sequencing were utilized to assess the impact of pathogenic ABCA12 variants on skin homeostasis, revealing decreased levels of ABCA12 and claudin-1, alongside increased levels of involucrin and S100A8. In conclusion, our findings contribute to updating the genotype-phenotypic correlation and provide additional evidence for the long-term use of retinoic acid drugs in patients with causative ABCA12 variants.

Tomentediline A: A isoquinoline alkaloids with undescribed carbon skeleton from Corydalis tomentella.

Two undescribed isoquinolines (1-2), including one undescribed carbon skeleton isoquinoline together with six known ones (4-9) as well as an undescribed amide (3) and three known ones (10-12) were isolated from C. tomentella. Their planar structures and absolute configurations were elucidated by extensive analyses of UV, NMR, HRESIMS, DP4+ statistical analysis and ECD calculations, respectively. Tomentediline A (1) is an isoquinoline alkaloid dimer that forms an undescribed carbon carbon bond at the C-13 position of (2H)-protoberberine in a natural product discovered for the first time. Meantime, 1 exerted moderate cytotoxicity against the U251 cell lines, indicating that the undescribed dimer skeleton of isoquinoline compound has the potential for anti-glioma.

Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance.

The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that Abelmoschus manihot polysaccharide (AMP) fortifies the intestinal mucus barrier by increasing mucus production, which plays a crucial role in the AMP-mediated amelioration of colitis. IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10. Moreover, bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila. These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota. This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

The long-term transformation of FeIII-AsV coprecipitates at room temperature under oxic conditions: New insights for the fate and the speciation of As.

The long-term stability of FeIII-AsV coprecipitates, a typically hydrometallurgical or naturally produced As-bearing wastes in tailings or in other environments, is critical to evaluating the As risk caused by them. A wide pH range, different Fe/As molar ratios, reaction media, and neutralization reagents were considered in order to find the mechanisms controlling the fate of As during the 1640 days of transformation at 25 °C. The results indicated that at pH 4 and 12, As continuously released from the solid phase. The components and their proportions determined the fate of As at pH 4. However, at pH 12, crystalline calcium carbonates (CCA) formed due to the CO2 in the air and this combined with the adsorption capacity of As on the 2-line ferrihydrite controlling the fate of As. If pH changed to 8 and 10, yukonite formed after the release of As. The CCA also appeared in the presence of Ca. Therefore, these two processes controlled the fate of As at this pH range. These findings are important for understanding and predicting the transport of As under various environmental conditions. The technology chosen for As remediation in soils and As removal from waste waters will also be benefit from these results.

Early-Life Exposure to 4-Hydroxy-4'-Isopropoxydiphenylsulfone Induces Behavioral Deficits Associated with Autism Spectrum Disorders in Mice.

Exposure to bisphenol A (BPA) during gestation and lactation is considered to be a potential risk factor for autism spectrum disorder (ASD) in both humans and animals. As a novel alternative to BPA, 4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP) is frequently detected in breast milk and placental barrier systems, suggesting potential transmission from the mother to offspring and increased risk of exposure. Gestation and lactation are critical periods for central nervous system development, which are vulnerable to certain environmental pollutants. Herein, we investigated the behavioral impacts and neurobiological effects of early-life exposure to BPSIP (0.02, 0.1, and 0.5 mg/kg body weight/day) in mice offspring. Behavioral studies indicated that BPSIP exposure induced ASD-like behaviors, including elevated anxiety-related behavior and decreased spatial memory, in both male and female pups. A distinct pattern of reduced social novelty was observed only in female offspring, accompanied by significant alterations in antioxidant levels. Transcriptome analysis demonstrated that differentially expressed genes (DEGs) were mainly enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, a decrease in the protein levels of complex IV (COX IV) across all tested populations suggests a profound impact on mitochondrial function, potentially leading to abnormal energy metabolism in individuals with autism. Additionally, changes in synaptic proteins, evidenced by alterations in synapsin 1 (SYN1) and postsynaptic density protein-95 (PSD95) levels in the cerebellum and hippocampus, support the notion of synaptic involvement. These findings suggest that BPSIP may induce sex-specific neurotoxic effects that involve oxidative stress, energy generation, and synaptic plasticity.

Real-Time Monitoring of mtDNA Aggregation and Mitophagy Induced by a Fluorescent Platinum Complex in Living Cells.

Mitochondrial DNA (mtDNA) is pivotal for mitochondrial morphology and function. Upon mtDNA damage, mitochondria undergo quality control mechanisms, including fusion, fission, and mitophagy. Real-time monitoring of mtDNA enables a deeper understanding of its effect on mitochondrial function and morphology. Controllable induction and real-time tracking of mtDNA dynamics and behavior are of paramount significance for studying mitochondrial function and morphology, facilitating a deeper understanding of mitochondria-related diseases. In this work, a fluorescent platinum complex was designed and developed that not only induces mitochondrial DNA (mtDNA) aggregation but also triggers mitochondrial autophagy (mitophagy) through the MDV pathway for damaged mtDNA clearance in living cells. Additionally, this complex allows for the real-time monitoring of these processes. This complex may serve as a valuable tool for studying mitochondrial microautophagy and holds promise for broader applications in cellular imaging and disease research.

Design and synthesis of 7-azaindole derivatives as potent CDK8 inhibitors for the treatment of acute myeloid leukemia.

It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)phenyl)-3-(m-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI50 MV4-11 = 1.97 ± 1.24 µM). This compound also exhibited excellent inhibitory activity against CDK8 (IC50 = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addition, acute toxicity at a dose of 1000 mg kg-1 indicated the low toxicity of this compound.

Spatial spillover effect and driving factors of urban carbon emissions in the Yellow River Basin using nighttime light data.

Yellow River Basin (YRB) is a pivotal region for energy consumption and carbon emissions (CEs) in China, with cities emerging as the main sources of regional CEs. This highlights their critical role in achieving regional sustainable development and China's carbon neutrality. Consequently, there is a pressing need for a detailed exploration of the urban spillover effects and an in-depth analysis of the complex determinants influencing CEs within the YRB. Remote sensing data provide optimal conditions for conducting extensive studies across large geographical areas and extended time periods. This study integrates DMSP/OLS and NPP/VIIRS nighttime light datasets for a longitudinal analysis of urban CEs in the YRB. Using a harmonized dataset from DMSP/OLS and NPP/VIIRS nighttime light from 2007 to 2021, this study quantifies CEs of 58 prefecture-level cities in the YRB. By combining ESDA, STIRPAT model and spatial econometric model, this investigation further clarifies empirically the spatial spillover effects and driving factors of urban CEs. The analysis delineates a phase-wise augmentation in urban CEs, converging towards a distinct spatial distribution characterized by "lower reach > middle reach > upper reach". The spatial autocorrelation tests unravel a complex interplay between agglomeration and differentiation patterns within urban CEs, underscored by pronounced spatial lock-in phenomena. Significantly, this study demonstrates that urbanization, economic development, energy consumption structure, green coverage rate, industrial structure, population, technological progress, and FDI each exhibit varied direct and indirect effect on urban CEs. Furthermore, it elaborates on potential policy implications and future research directions, offering crucial insights for formulating CEs mitigation strategies to advance sustainable development.

CRY1 is involved in the take-off behaviour of migratory Cnaphalocrocis medinalis individuals.

BACKGROUND: Numerous insect species undertake long-distance migrations on an enormous scale, with great implications for ecosystems. Given that take-off is the point where it all starts, whether and how the external light and internal circadian rhythm are involved in regulating the take-off behaviour remains largely unknown. Herein, we explore this issue in a migratory pest, Cnaphalocrocis medinalis, via behavioural observations and RNAi experiments. RESULTS: The results showed that C. medinalis moths took off under conditions where the light intensity gradually weakened to 0.1 lx during the afternoon or evening, and the take-off proportions under full spectrum or blue light were significantly higher than that under red and green light. The ultraviolet-A/blue light-sensitive type 1 cryptochrome gene (Cmedcry1) was significantly higher in take-off moths than that of non-take-off moths. In contrast, the expression of the light-insensitive CRY2 (Cmedcry2) and circadian genes (Cmedtim and Cmedper) showed no significant differences. After silencing Cmedcry1, the take-off proportion significantly decreased. Thus, Cmedcry1 is involved in the decrease in light intensity induced take-off behaviour in C. medinalis. CONCLUSIONS: This study can help further explain the molecular mechanisms behind insect migration, especially light perception and signal transmission during take-off phases.

Identification of Siglec-10 as a new dendritic cell checkpoint for cervical cancer immunotherapy.

BACKGROUND: The occurrence of chronic inflammation resulting from infection with human papillomaviruses is an important factor in the development of cervical cancer (CC); thus, deciphering the crosstalk between the tumor microenvironment and innate immune cells during the establishment of immune tolerance is vital for identifying potential treatment strategies. METHODS: Single-cell RNA sequencing data and primary tumor samples from patients with CC were used to evaluate the functional role of Siglec-10 on dendritic cells (DCs). Patient-derived tumor fragment platforms were used to examine the ability of Siglec-10 blockade to reinvigorate DC-mediate T-cell activation and tumor clearance. RESULTS: Here, we demonstrated that Siglec-10 is a prominent inhibitory checkpoint for DCs infiltrated in CC. CC epithelial cells use their aberrant surface sialylated structures to induce the transformation of conventional DCs into phenotypes characterized by low immunogenicity and high immunotolerance. Additionally, Siglec-10+ DCs suppress the function of adaptive T cells via galectin-9 signaling to strengthen the immunosuppressive CC microenvironment. Disturbance of Siglec-10 signaling restored the DC-mediated tumoricidal response and increased adaptive T cells sensitivity to programmed cell death protein 1 inhibition. CONCLUSION: Our study confirms the checkpoint role of Siglec-10 on DCs and proposes that targeting Siglec-10 may be a promising avenue for immunotherapy against CC.

Immuno-inflammatory pathogenesis in ischemic heart disease: perception and knowledge for neutrophil recruitment.

Ischemic heart disease (IHD) can trigger responses from the innate immune system, provoke aseptic inflammatory processes, and result in the recruitment and accumulation of neutrophils. Excessive recruitment of neutrophils is a potential driver of persistent cardiac inflammation. Once recruited, neutrophils are capable of secreting a plethora of inflammatory and chemotactic agents that intensify the inflammatory cascade. Additionally, neutrophils may obstruct microvasculature within the inflamed region, further augmenting myocardial injury in the context of IHD. Immune-related molecules mediate the recruitment process of neutrophils, such as immune receptors and ligands, immune active molecules, and immunocytes. Non-immune-related molecular pathways represented by pro-resolving lipid mediators are also involved in the regulation of NR. Finally, we discuss novel regulating strategies, including targeted intervention, agents, and phytochemical strategies. This review describes in as much detail as possible the upstream molecular mechanism and external intervention strategies for regulating NR, which represents a promising therapeutic avenue for IHD.

Effects of Heterologous Expression of Genes Related L-Malic acid Metabolism in Saccharomyces uvarum on Flavor Substances Production in Wine.

During malolactic fermentation (MLF) of vinification, the harsh L-malic acid undergoes transformation into the milder L-lactic acid, and via decarboxylation reactions it is catalyzed by malolactic enzymes in LAB. The use of bacterial malolactic starter cultures, which usually present challenges in the industry as the suboptimal conditions after alcoholic fermentation (AF), including nutrient limitations, low temperatures, acidic pH levels, elevated alcohol, and sulfur dioxide concentrations after AF, lead to "stuck" or "sluggish" MLF and spoilage of wines. Saccharomyces uvarum has interesting oenological properties and provides a stronger aromatic intensity than Saccharomyces cerevisiae in AF. In the study, the biological pathways of deacidification were constructed in S. uvarum, which made the S. uvarum carry out the AF and MLF simultaneously, as different genes encoding malolactic enzyme (mleS or mleA), malic enzyme (MAE2), and malate permease (melP or MAE1) from Schizosaccharomyces pombe, Lactococcus lactis, Oenococcus oeni, and Lactobacillus plantarum were heterologously expressed. For further inquiry, the effect of L-malic acid metabolism on the flavor balance in wine, the related flavor substances, higher alcohols, and esters production, were detected. Of all the recombinants, the strains WYm1SN with coexpression of malate permease gene MAE1 from S. pombe and malolactic enzyme gene mleS from L. lactis and WYm1m2 with coexpression of gene MAE1 and malate permease gene MAE2 from S. pombe could reduce the L-malic acid contents to about 1 g/L, and in which the mutant WYm1SN exhibited the best effect on the flavor quality improvement.

The effect and potential mechanism of inulin combined with fecal microbiota transplantation on early intestinal immune function in chicks.

Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-ß secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.

Influence of stress on self-injury among Chinese left-behind adolescents is not cast in stone: Synergistic roles of family protective factors.

BACKGROUND: Left-behind adolescents are vulnerable to stressful life events and often engage in nonsuicidal self-injury (NSSI), which is a growing public concern in China. However, little is known about the synergistic protective effect of family resources on the relationship between stressful life events and NSSI in these adolescents. OBJECTIVE: Based on theories of family socialization and resilience, the aim of this study was to examine the synergistic protective role of maternal knowledge and mother-child cohesion in buffering the effect of stressful life events on NSSI in father-absent left-behind adolescents. METHODS: This study used two-wave longitudinal data. The analytical sample included 673 adolescents (Mage = 13.47 ± 1.11 years, 48 % male) who were enlisted from 4 junior high schools in rural China. Respondents completed questionnaires on stressful life events, parental knowledge, parent-child cohesion, and NSSI at two-time points. RESULTS: The effects of stressful life events on NSSI were significant in father-absent left-behind adolescents. Additionally, maternal knowledge moderated the associations between stressful life events and NSSI in father-absent left-behind adolescents. Moreover, maternal knowledge and mother-child cohesion were found to play synergistic protective roles in the relationship between stressful life events and NSSI. In father-absent left-behind adolescents, only high maternal knowledge and high-quality mother-child cohesion could eliminate the negative effect of stressful life events on NSSI. CONCLUSION: The findings underscore the synergistic protective roles of maternal knowledge and mother-child cohesion in buffering the negative effect of stressful life events on NSSI in father-absent left-behind adolescents. Both maternal knowledge and mother-child cohesion should be considered in interventions aimed at reducing NSSI in these adolescents.