Clinical significance of the modified Naples prognostic score in patients with stage II-III colon cancer undergoing curative resection: a retrospective study from the real world.

Background: The Naples prognostic score (NPS) determined by the nutritional and inflammatory condition of an individual is attracting growing attention for predicting postoperative outcomes in a variety of malignancies. The study aimed to assess the clinical significance of a modified NPS (M-NPS) and establish and validate nomograms incorporating M-NPS in curative stage II-III colon cancer patients. Methods: We retrospectively analyzed 328 stage II-III colon cancer patients receiving radical surgical resection at our hospital from January 2011 to December 2016. Kaplan-Meier (KM) survival analysis and Cox regression analysis were executed for overall survival (OS) and cancer-specific survival (CSS). Independent predictive indicators were applied to develop nomograms. The model's performance was evaluated using many different methods. Results: Of a total of 328 cases, 153 cases were in group 0, 145 in group 1, and 30 in group 2. In terms of OS or CSS, there were obvious differences between groups 0 and 1, and between groups 0 and 2. Age, obstruction, N stage, gross tumor type, and M-NPS group were independent prognostic indicators for OS, while obstruction, gross tumor type, M-NPS group, and N stage were independent predictive parameters for CSS. Furthermore, the training and validation sets were randomly allocated among a cohort of 328 patients. OS and CSS prediction nomograms were developed. In the training and validation cohort, the C-index and ROC analysis showed good discrimination, calibration curves exhibited an excellent level of consistency between model-predicted survival and actual survival outcomes, and DCA curves demonstrated good clinical performance. Conclusion: M-NPS is a reliable survival predictor in patients with curative stage II-III colon cancer. Nomograms incorporating M-NPS for OS and CSS have good predictive performance and clinical utility.

Essentiality of SLC7A11-mediated nonessential amino acids in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains a rapidly growing global health burden. Here, we report that the nonessential amino acid (NEAA) transporter SLC7A11 plays a key role in MASLD. In patients with MASLD, we found high expression levels of SLC7A11 that were correlated directly with clinical grade. Using both loss-of-function and gain-of-function genetic models, we found that Slc7a11 deficiency accelerated MASLD progression via classic cystine/cysteine deficiency-induced ferroptosis, while serine deficiency and a resulting impairment in de novo cysteine production were attributed to ferroptosis-induced MASLD progression in mice overexpressing hepatic Slc7a11. Consistent with these findings, we found that both serine supplementation and blocking ferroptosis significantly alleviated MASLD, and the serum serine/glutamate ratio was significantly lower in these preclinical disease models, suggesting that it might serve as a prognostic biomarker for MASLD in patients. These findings indicate that defects in NEAA metabolism are involved in the progression of MASLD and that serine deficiency-triggered ferroptosis may provide a therapeutic target for its treatment.

MOF Nanosheet-Functionalized Poly(lactic acid) Meta-membranes for Long-Term Air Purification and Intelligent Monitoring.

The wide use of conventional polymeric air filters is causing a dramatically increasing accumulation of plastic and microplastic pollution. The development of poly(lactic acid) (PLA) fibrous membranes for efficient air purification is of important significance but frequently challenged by the rapid decay of filtration performance due to the intrinsically poor electret properties of PLA. Here, we propose an electroactivity promotion methodology, involving the one-step synthesis and homogeneous incorporation of high-dielectric ZIF-8 nanosheets (ZIFNSs), to facilitate interfacial polarization and fiber refinement during electrospinning of PLA nanofibers. The preparative electrospun PLA/ZIFNS meta-membranes exhibited an unusual combination of significantly reduced nanofiber diameter (∼462 nm), enhanced surface potential (approaching 10 kV), and increased surface activity and facilitated the formation of electroactive phases. With well-controlled morphological features, the highly electroactive PLA/ZIFNS meta-membranes exhibited exceptional filtration efficiencies for PM2.5 and PM0.3 (99.2 and 96.0%, respectively) even at the highest airflow rate of 85 L/min, in clear contrast to that of its pure PLA counterpart (only 79.3 and 74.6%). Arising from the increased electroactivity and active contact sites, remarkable triboelectric performance and self-charging mechanisms were demonstrated for the PLA/ZIFNS meta-membranes, contributing to long-term efficient PM0.3 filtration (97.5% for over 360 min). Moreover, as triggered by physiological activities like respiration and speaking, the electroactive PLA/ZIFNS meta-membranes enabled real-time monitoring with high sensitivity and specificity. The proposed strategy affords significant promotion of electroactivity and triboelectric performance for PLA nanofibers, which may motivate the development of ecofriendly protective membranes for respiratory healthcare and real-time monitoring.

Improved antitumor effectiveness of oncolytic HSV-1 viruses engineered with IL-15/IL-15Rα complex combined with oncolytic HSV-1-aPD1 targets colon cancer.

Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

The Aqueous Extract of Hemerocallis citrina Baroni Improves the Lactation-Promoting Effect in Bovine Mammary Epithelial Cells through the PI3K-AKT Signaling Pathway.

Insufficient milk supply is a widespread issue faced by women globally and associated with a higher risk of health problems in infants and mothers. Hemerocallis citrina Baron, commonly known as daylily, is a perennial edible plant often used in traditional Asian cuisine to promote lactation. However, the active compound(s) and mechanism of its lactation-promoting effect remain unclear. This study aimed to confirm the traditional use of daylily in promoting lactation and investigate its potential active components and underlying molecular mechanisms. Our results showed that the aqueous extracts of H. citrina Baroni (HAE) significantly enhanced milk production, and the serum levels of lactation-related hormones, and promoted mammary gland development in lactating rats, as well as increased the levels of milk components in bovine mammary epithelial cells (BMECs) (p < 0.05). UHPLC-Q-Exactive Orbitrap-MS analysis revealed that hexamethylquercetin (HQ) is the representative flavonoid component in HAE, accounting for 42.66% of the total flavonoids. An integrated network pharmacology and molecular docking analysis suggested that HQ may be the potential active flavonoid in HAE that promotes lactation, possibly supporting lactation by binding to key target proteins such as STAT5A, PIK3CA, IGF1R, TP53, CCND1, BCL2, INS, AR, and DLD. Cell experiments further demonstrated that HQ could promote cell proliferation and the synthesis of milk proteins, lactose, and milk fat in BMECs. Transcriptomic analysis combined with a quantitative reverse transcription polymerase chain reaction (RT-qPCR) revealed that both HAE and HQ exert a lactation-promoting function mainly through regulating the expression of key genes in the PI3K-Akt signaling pathway.

The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs.

In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR mediated HCO-3 secretion and the vacuolar-type H+ ATPase (V-ATPase) proton secretion. We hypothesized that in Cystic Fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solutions by measuring changes in a pH dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1. The pH-dependent translocation of V-ATPase in ex vivo and in vivo preparations was measured using immunolocalization of V-ATPase. We found that bafilomycin sensitive proton secretion stopped when the ASL pH was less than 7.10. In non-CF pigs and mice, we found that V-ATPase was localized in the apical membrane, and internalized when the lungs were instilled with a pH 6.8 solution.Studies where we immediately fixed lungs from pigs revealed apical V-ATPase detection in non-CF piglets and less apical detection in CF piglets. Our data suggest that V-ATPase in small airways is internalized when the ASL pH is acidic. The decrease in apical localization of V-ATPase in CF pigs is consistent with an acidic ASL pH.

Genetic structure and selective sweeps in Kirghiz sheep using SNP50K bead chip.

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity's impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction.Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources.

Population structure and selective signature of Kirghiz sheep by Illumina Ovine SNP50 BeadChip.

Objective: By assessing the genetic diversity and associated selective traits of Kirghiz sheep (KIR), we aim to uncover the mechanisms that contribute to sheep's adaptability to the Pamir Plateau environment. Methods: This study utilized Illumina Ovine SNP50 BeadChip data from KIR residing in the Pamir Plateau, Qira Black sheep (QBS) inhabiting the Taklamakan Desert, and commonly introduced breeds including Dorper sheep (DOR), Suffolk sheep (SUF), and Hu sheep (HU). The data was analyzed using principal component analysis, phylogenetic analysis, population admixture analysis, kinship matrix analysis, linkage disequilibrium analysis, and selective signature analysis. We employed four methods for selective signature analysis: fixation index (Fst), cross-population extended homozygosity (XP-EHH), integrated haplotype score (iHS), and nucleotide diversity (Pi). These methods aim to uncover the genetic mechanisms underlying the germplasm resources of Kirghiz sheep, enhance their production traits, and explore their adaptation to challenging environmental conditions. Results: The test results unveiled potential selective signals associated with adaptive traits and growth characteristics in sheep under harsh environmental conditions, and annotated the corresponding genes accordingly. These genes encompass various functionalities such as adaptations associated with plateau, cold, and arid environment (ETAA1, UBE3D, TLE4, NXPH1, MAT2B, PPARGC1A, VEGFA, TBX15 and PLXNA4), wool traits (LMO3, TRPS1, EPHA5), body size traits (PLXNA2, EFNA5), reproductive traits (PPP3CA, PDHA2, NTRK2), and immunity (GATA3). Conclusion: Our study identified candidate genes associated with the production traits and adaptation to the harsh environment of the Pamir Plateau in Kirghiz sheep. These findings provide valuable resources for local sheep breeding programs. The objective of this study is to offer valuable insights for the sustainable development of the Kirghiz sheep industry.

An Observation of the Microstructure of Cervical Mucus in Cows during the Proestrus, Estrus, and Metestrus Stages and the Impact on Sperm Penetration Ability.

Cervical mucus not only provides energy for sperm but also forms a barrier to block sperm. This paper aims to study the microstructure of cervical mucus in dairy cows during the proestrus, estrus, and metestrus and its effect on sperm permeability. The experiment collected cervical mucus from 60 Holstein cows during these phases, then observed the different shapes of the mucus after crystallization, classified the mucus, and analyzed its proportions. Scanning electron microscopy was used to observe the ultrastructure of the cervical mucus and measure the micro-pore sizes, followed by sperm permeability tests using mucus from different estrous stages and counting the number of permeated sperm. The results indicate that cervical mucus from cows in different estrous phases includes four types (L, S, P, G), with each type constituting a different proportion. During the proestrus, the L type was significantly more prevalent than the other types (p < 0.05); during estrus, the S type was significantly more prevalent than the other types (p < 0.05); and during the metestrus, the p type was significantly more prevalent than the other types (p < 0.05). The micro-pore sizes of the same type of cervical mucus did not show significant differences across different estrous phases (p > 0.05). However, within the same estrous phase, there were significant differences in the micro-pore sizes among the four types (p < 0.05). The number of sperm that permeated the cervical mucus during estrus and metestrus was significantly higher than during the proestrus (p < 0.05). This study provides data support for the research on cervical mucus in dairy cows.

Mesenchymal stem cells arouse myocardial NAD+ metabolism to alleviate microgravity-induced cardiac dysfunction.

After prolonged space operations, astronauts showed maladaptive atrophy within mostly left-ventricular myocardium, resulting in cardiac dysfunction. However, the mechanism of cardiac dysfunction under microgravity conditions is unclear, and the relevant prevention and treatment measures also need to be explored. Through simulating the microgravity environment with a tail suspension (TS) model, we found that long-term exposure to microgravity promotes aging of mouse hearts, which is closely related to cardiac dysfunction. The intravenous administration of adipose-derived mesenchymal stem cells (ADSCs) emerged preventive and therapeutic effect against myocardial senescence and the decline in cardiac function. Plasma metabolomics analysis suggests the loss of NAD+ in TS mice and motivated myocardial NAD + metabolism and utilization in ADSCs-treated mice, likely accounting for ADSCs' function. Oral administration of nicotinamide mononucleotide (NMN, a NAD + precursor) showed similar therapeutic effect to ADSCs treatment. Collectively, these data implicate the effect of ADSCs in microgravity-induced cardiac dysfunction and provide new therapeutic ideas for aging-related maladaptive cardiac remodeling.

Genetic analysis of key agronomic traits of local sheep breeds in Xinjiang, China.

The formation of sheep (Ovis aries) breeds is influenced by different ecological environments and populations with different living habits, resulting in the development of germplasm resources with stable genetic key agronomic traits. Thus, investigating the genetic mechanisms behind various agronomic traits can enhance the conservation and utilization of diverse sheep breeds. Here, we explored the sheep variome and selection signatures using the Ovine Infinium HD SNP BeadChip (600 K SNPs) from 23 sheep breeds, comprising a total of 1215 sheep. The genetic mechanisms of wool quality and tail morphology were analyzed by selective sweep and genome-wide association study. Based on the results of within-population selective sweep analysis, we performed gene network analysis and divided them into 6 gene communities. We identified genetic regions containing genes linked to sheep wool and tail, which have been and may continue to be important targets for breeding and selection. Furthermore, our results revealed the expression profiles of genes in these regions across different biological systems. Our study provides insights into categorizing sheep breeds into distinct gene communities, as well as references for constructing genetic network pathways related to key agronomic traits in sheep and other domestic animals.

Palmitoylation regulates myelination by modulating the ZDHHC3-Cadm4 axis in the central nervous system.

The downregulation of Cadm4 (Cell adhesion molecular 4) is a prominent feature in demyelination diseases, yet, the underlying molecular mechanism remains elusive. Here, we reveal that Cadm4 undergoes specific palmitoylation at cysteine-347 (C347), which is crucial for its stable localization on the plasma membrane (PM). Mutation of C347 to alanine (C347A), blocking palmitoylation, causes Cadm4 internalization from the PM and subsequent degradation. In vivo experiments introducing the C347A mutation (Cadm4-KI) lead to severe myelin abnormalities in the central nervous system (CNS), characterized by loss, demyelination, and hypermyelination. We further identify ZDHHC3 (Zinc finger DHHC-type palmitoyltransferase 3) as the enzyme responsible for catalyzing Cadm4 palmitoylation. Depletion of ZDHHC3 reduces Cadm4 palmitoylation and diminishes its PM localization. Remarkably, genetic deletion of ZDHHC3 results in decreased Cadm4 palmitoylation and defects in CNS myelination, phenocopying the Cadm4-KI mouse model. Consequently, altered Cadm4 palmitoylation impairs neuronal transmission and cognitive behaviors in both Cadm4-KI and ZDHHC3 knockout mice. Importantly, attenuated ZDHHC3-Cadm4 signaling significantly influences neuroinflammation in diverse demyelination diseases. Mechanistically, we demonstrate the predominant expression of Cadm4 in the oligodendrocyte lineage and its potential role in modulating cell differentiation via the WNT-ß-Catenin pathway. Together, our findings propose that dysregulated ZDHHC3-Cadm4 signaling contributes to myelin abnormalities, suggesting a common pathological mechanism underlying demyelination diseases associated with neuroinflammation.

Catalytic Edges in One-Dimensional Covalent Organic Frameworks for the Oxygen Reduction Reaction.

Metal-free covalent organic frameworks (COFs) are employed in oxygen reduction reactions (ORR) because of their diverse structural units and controllable catalytic sites, and the edge sites have high catalytic activity than the basal sites. However, it is still challenge to modulate the edge sites in COFs, because the extended frameworks in two- or three-dimensional topologies resulted in limited edge parts. In this study, we have demonstrated the edge site modulation engineering based on one dimensional (1D) COFs to catalyze the ORR, which featured distinct edge groups-carbonyl, diaminopyrazine, phenylimidazole, and benzaldehyde imidazole units. The synthesized COFs had same ordered frameworks, similar pore structure, but had different electronic states of the carbons along the edge sites, which results in tailored catalytic properties. Notably, the COF functionalized with a phenylimidazole edge group exhibited superior catalytic performance compared to the other synthesized COFs. And the theoretical calculation further revealed the different edge sites have tunable binding ability of the intermediates OOH*, which contributed modulated activity. Our findings introduce a novel way for designing COFs optimized for ORR applications through molecular level control of edge sites.

Nobiletin, an activator of the pyruvate kinase isozyme M1/M2 protein, upregulated the glycolytic signalling pathway and alleviated depressive-like behaviour caused by artificial light exposure at night in zebrafish.

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway.

Synchronously Formed Hetero- and Hollow Core-Branch Nanostructure Toward Wideband Electromagnetic Wave Absorption.

The intrinsic limitation of low electrical conductivity of MoSe2 resulted in inferior dielectric properties, which restricts its electromagnetic wave absorption (EMWA) performances. Herein, a bimetallic selenide of MoSe2/CoSe2@N-doped carbon (NC) composites with hollow core-branch nanostructures are synthesized via the selenization treatment of MoO3 nanorods coated with ZIF-67. By adjusting the mass ratio of ZIF-67 to MoO3, the electromagnetic parameters and morphologies of composites are finely tuned, further ameliorating the impedance matching and EMWA performances. The involvement of NC improves the electronic conductivity of the composites. The synchronously formed heterostructure not only facilitates charge transfer but also leads to the accumulation and uneven distribution of charges, thus enhancing the conductive loss and polarization loss. The hollow core-branch nanostructure provides abundant conductive networks, heterointerfaces, and voids, significantly enhancing the EMWA property. Density functional theory implies that the heterostructures effectively boost charge transport and change charge distribution, which heightens the conductive loss and polarization loss. As a result, the composites demonstrate a minimum reflection loss value of -53.53 dB at 9.04 GHz, alongside a maximum effective absorption bandwidth of 6.32 GHz. This work offers invaluable insights into novel structural designs for future research and applications.

Advancing Single-Particle Analysis in Synthetic Chemical Systems: A Forward-Looking Discussion.

Single-particle analysis (SPA) is a fundamental method of cryo-electron microscopy developed to resolve the structures of biological macromolecules. This method has seen significant success in structural biology, yet its potential applications in synthetic chemical systems remain underexplored. In this perspective article, SPA and associated electron microscopy techniques are first briefly introduced. It is then proposed that SPA is well-suited for structural analysis of chemical systems where discrete, identical macromolecules can be readily obtained. Applicable systems include various clusters such as coinage metal clusters, metal-oxo/sulfur clusters, metal-organic clusters, and supramolecular compounds like coordination cages and metallo-supramolecular cages. When high-quality large single crystals are unattainable, SPA provides an alternative method for determining their structures. Beyond these end products, it is suggested that SPA can be instrumental in studying synthetic intermediates of materials with specific building units, such as metal-organic frameworks and zeolites. Given that various intermediates coexist in the reaction system, a purification step is necessary before conducting SPA, which can be facilitated by soft-landing electrospray ionization mass spectrometry.

Beyond Single-Cycle Autonomous Molecular Machines: Light-Powered Shuttling in a Multi-Cycle Reaction Network.

Biomolecular machines autonomously convert energy into functions, driving systems away from thermodynamic equilibrium. This energy conversion is achieved by leveraging complex, kinetically asymmetric chemical reaction networks that are challenging to characterize precisely. In contrast, all known synthetic molecular systems in which kinetic asymmetry has been quantified are well described by simple single-cycle networks. Here, we report on a unique light-driven [2]rotaxane that enables the autonomous operation of a synthetic molecular machine with a multi-cycle chemical reaction network. Unlike all prior systems, the present one exploits a photoactive macrocycle, which features a different photoreactivity depending on the binding sites at which it resides. Furthermore, E to Z isomerization reverses the relative affinity of the macrocycle for two binding sites on the axle, resulting in a multi-cycle network. Building on the most recent theoretical advancements, this work quantifies kinetic asymmetry in a multi-cycle network for the first time. Our findings represent the simplest rotaxane capable of autonomous shuttling developed so far and offer a general strategy to generate and quantify kinetic asymmetry beyond single-cycle systems.

Smart hydrogel composite for microenvironmental humidity regulation in cigar storage.

Environmental humidity profoundly influences various life activities, especially for plants that depend heavily on optimal humidity for growth. The humidity index is particularly crucial for preserving the functionality of plant leaves, notably in economically valuable plants such as cigar tobacco. This paper introduces a novel dual-layer moisturizing material, a PAS-PDMS composite, based on polyacrylamide/solketal (PAS) hydrogel and polydimethylsiloxane (PDMS). This material features a unique hierarchical water release mechanism. Comprehensive analyses, including thermogravimetric analysis, Fourier-transform infrared spectroscopy, low-field nuclear magnetic resonance, and dynamic water adsorption studies, confirm the water migration and humidity control mechanisms of the PAS-PDMS composite. This smart hydrogel composite regulates microenvironmental humidity bidirectionally. When applied to cigar boxes for storage, it stabilizes internal humidity at approximately 65%, maintaining this level for over 20 days. Furthermore, the PAS-PDMS composite exhibits superior mechanical properties and light transmittance, achieving an exceptional transmittance of 84%. In conclusion, the PAS-PDMS composite offers intelligent humidity control, providing a novel approach to the storage and preservation of cigars.

A Novel Role for the Longevity-Associated Protein SLC39A11 as a Manganese Transporter.

The identification of aging- and longevity-associated genes is important for promoting healthy aging. By analyzing a large cohort of Chinese centenarians, we previously found that single-nucleotide polymorphisms (SNPs) in the SLC39A11 gene (also known as ZIP11) are associated with longevity in males. However, the function of the SLC39A11 protein remains unclear. Here, we found that SLC39A11 expression is significantly reduced in patients with Hutchinson-Gilford progeria syndrome (HGPS). In addition, we found that zebrafish with a mutation in slc39a11 that significantly reduces its expression have an accelerated aging phenotype, including a shortened average lifespan, muscle atrophy and reduced swimming, impaired muscle regeneration, gut damage, and abnormal morphology in the reproductive system. Interestingly, these signs of premature aging were more pronounced in male zebrafish than in females. RNA-sequencing analysis revealed that cellular senescence may serve as a potential mechanism for driving this slc39a11 deficiency-induced phenotype in mutant zebrafish. Moreover, immunofluorescence showed significantly increased DNA damage and reactive oxygen species signaling in slc39a11 mutant zebrafish. Using inductively coupled plasma mass spectrometry (ICP-MS), we found that manganese significantly accumulates in slc39a11 mutant zebrafish, as well as in the serum of both global Slc39a11 knockout and hepatocyte-specific Slc39a11 knockout mice, suggesting that this metal transporter regulates systemic manganese levels. Finally, using cultured human fibroblasts, we found that both knocking down SLC39A11 and exposure to high extracellular manganese increased cellular senescence. These findings provide compelling evidence that SLC39A11 serves to protect against the aging process, at least in part by regulating cellular manganese homeostasis.

Early decompressive surgery improves long-term prognosis in patients with intracerebral hemorrhage.

BACKGROUND: Multiple studies have shown that early decompressive surgery in patients with intracerebral hemorrhage can effectively limit hematoma expansion, reduce perihematomal edema, and improve prognosis. However, these studies are limited by small sample sizes and short follow-up times. OBJECTIVE: To analyze the effect of early decompressive surgery on the long-term prognosis of patients with cerebral hemorrhage and identify the influencing factors for poor prognosis. METHODS: A retrospective analysis of 78 patients with cerebral hemorrhage admitted between January 2020 and December 2022 was conducted. Patients were divided into early and delayed surgery groups for comparison of outcomes such as mortality rate, modified Rankin Scale score, and Short Form-36 scores. Additionally, factors influencing long-term prognosis were analyzed through logistic regression based on significant differences observed between groups. RESULTS: The early decompressive surgery group showed superior outcomes with lower mortality rates, modified Rankin Scale (mRS) scores, hematoma expansion rates, and perihematomal edema volumes compared to the delayed surgery group (P< 0.05). Additionally, age, preoperative Glasgow Coma Scale (GCS) score, preoperative hematoma volume, and a history of hypertension or diabetes were identified as independent prognostic factors for patients with cerebral hemorrhage, with odds ratios (ORs) greater than 1. CONCLUSIONS: Early decompressive surgery can improve the long-term prognosis and quality of life of patients with cerebral hemorrhage, reduce mortality rates, and decrease hematoma expansion and perihematomal edema. Older patients, those with higher preoperative hematoma volume and GCS score, and those with coexisting hypertension and diabetes should be given special attention to decrease the occurrence of adverse prognosis.