Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design.

The interleukin 1 (IL-1) pathway signals through IL-1 receptor type 1 (IL-1R1) and emerges as a central mediator for systemic inflammation. Aberrant IL-1 signaling leads to a range of autoinflammatory diseases. Here, we identified a de novo missense variant in IL-1R1 (p.Lys131Glu) in a patient with chronic recurrent multifocal osteomyelitis (CRMO). Patient PBMCs showed strong inflammatory signatures, particularly in monocytes and neutrophils. The p.Lys131Glu substitution affected a critical positively charged amino acid, which disrupted the binding of the antagonist ligand, IL-1Ra, but not IL-1α or IL-1ß. This resulted in unopposed IL-1 signaling. Mice with a homologous mutation exhibited similar hyperinflammation and greater susceptibility to collagen antibody-induced arthritis, accompanied with pathological osteoclastogenesis. Leveraging the biology of the mutation, we designed an IL-1 therapeutic, which traps IL-1ß and IL-1α, but not IL-1Ra. Collectively, this work provides molecular insights and a potential drug for improved potency and specificity in treating IL-1-driven diseases.

Spatially Confined Microcells: A Path toward TMD Catalyst Design.

With the ability to maximize the exposure of nearly all active sites to reactions, two-dimensional transition metal dichalcogenide (TMD) has become a fascinating new class of materials for electrocatalysis. Recently, electrochemical microcells have been developed, and their unique spatial-confined capability enables understanding of catalytic behaviors at a single material level, significantly promoting this field. This Review provides an overview of the recent progress in microcell-based TMD electrocatalyst studies. We first introduced the structural characteristics of TMD materials and discussed their site engineering strategies for electrocatalysis. Later, we comprehensively described two distinct types of microcells: the window-confined on-chip electrochemical microcell (OCEM) and the droplet-confined scanning electrochemical cell microscopy (SECCM). Their setups, working principles, and instrumentation were elucidated in detail, respectively. Furthermore, we summarized recent advances of OCEM and SECCM obtained in TMD catalysts, such as active site identification and imaging, site monitoring, modulation of charge injection and transport, and electrostatic field gating. Finally, we discussed the current challenges and provided personal perspectives on electrochemical microcell research.

A Scalable Ultramicroporous Coordination Network for Ethylene Separation from the Quaternary Mixture.

Adsorptive ethylene separation from the C2H2/C2H4/C2H6/CO2 four-component gas mixture provides a low-energy input solution for industrial ethylene purification, yet it is still a great challenge. Herein, we report a facile scaled-up synthesis of a stable ultramicroporous coordination network of Zn-CO3-datz (Hdatz = 3,5-diamine-1,2,4-triazole), which enables selective adsorption of C2H2, C2H4 and CO2 over C2H4, thanks to its specific pore environment supported by GCMC simulation of gas adsorption sites. Dynamic breakthrough experiments exhibited efficient one-step production of polymer-grade (≥99.95%) C2H4 from the quaternary C2H4/C2H2/C2H6/CO2 (1/1/1/1) mixture, with excellent C2H4 productivity of 0.12 mol kg-1 at 298 K. Moreover, it can be easily synthesized in kilogram scale with an affordable and low-cost ligand, rendering its further potential industrial applications.

Risk factors of venous thromboembolism for liver tumors: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a significant complication in liver tumors patients, and understanding the associated risk factors is essential for effective risk assessment, prevention, and management strategies. This systematic review and meta-analysis aimed to identify key risk factors and their clinical implications for VTE in liver tumors patients. METHODS: A comprehensive search of multiple databases was conducted to identify relevant studies. Eligible studies were selected, and odds ratios (ORs) and 95% confidence intervals (CIs) were extracted and synthesized for meta-analysis. RESULTS: A total of 11 studies involving 73,652 liver tumors patients and 2049 VTE cases were included. The analysis identified several significant risk factors for VTE in liver tumors patients. Age (≥65 years), male gender, high BMI, diabetes, hepatitis B and C infections, elevated D-dimer and AST levels, reduced albumin levels, and MELD score were all associated with increased VTE risk. CONCLUSION: This systematic review and meta-analysis revealed several key risk factors for VTE in liver tumors patients, these findings highlight the importance of risk assessment, prevention, and management strategies in this high-risk population. Further research with larger sample sizes and standardized methods is needed to strengthen the existing evidence and validate these findings.

Unveiling the regulatory mechanisms of salicylate degradation gene cluster cehGHIR4 in Rhizobium sp. strain X9.

In a previous study, the novel gene cluster cehGHI was found to be involved in salicylate degradation through the CoA-mediated pathway in Rhizobium sp. strain X9 (Mol Microbiol 116:783-793, 2021). In this study, an IclR family transcriptional regulator CehR4 was identified. In contrast to other regulators involved in salicylate degradation, cehR4 forms one operon with the gentisyl-CoA thioesterase gene cehI, while cehG and cehH (encoding salicylyl-CoA ligase and salicylyl-CoA hydroxylase, respectively) form another operon. cehGH and cehIR4 are divergently transcribed, and their promoters overlap. The results of the electrophoretic mobility shift assay and DNase I footprinting showed that CehR4 binds to the 42-bp motif between genes cehH and cehI, thus regulating transcription of cehGH and cehIR4. The repeat sequences IR1 (5'-TTTATATAAA-3') and IR2 (5'-AATATAGAAA-3') in the motif are key sites for CehR4 binding. The arrangement of cehGH and cehIR4 and the conserved binding motif of CehR4 were also found in other bacterial genera. The results disclose the regulatory mechanism of salicylate degradation through the CoA pathway and expand knowledge about the systems controlled by IclR family transcriptional regulators.IMPORTANCEThe long-term residue of aromatic compounds in the environment has brought great threat to the environment and human health. Microbial degradation plays an important role in the elimination of aromatic compounds in the environment. Salicylate is a common intermediate metabolite in the degradation of various aromatic compounds. Recently, Rhizobium sp. strain X9, capable of degrading the pesticide carbaryl, was isolated from carbaryl-contaminated soil. Salicylate is the intermediate metabolite that appeared during the degradation of carbaryl, and a novel salicylate degradation pathway and the involved gene cluster cehGHIR4 have been identified. This study identified and characterized the IclR transcription regulator CehR4 that represses transcription of cehGHIR4 gene cluster. Additionally, the genetic arrangements of cehGH and cehIR4 and the binding sites of CehR4 were also found in other bacterial genera. This study provides insights into the biodegradation of salicylate and provides an application in the bioremediation of aromatic compound-contaminated environments.

Vaginal homeostasis features of Vulvovaginal Candidiasis through vaginal metabolic profiling.

Vulvovaginal candidiasis (VVC) is an inflammatory disease primarily infected by Candida albicans. The condition has good short-term treatment effects, high recurrence, and seriously affects the quality of life of women. Metabolomics has been applied to research a variety of inflammatory diseases. In the present study, the vaginal metabolic profiles of VVC patients and healthy populations (Cnotrol (CTL)) were explored by a non-targeted metabolomics approach. In total, 211 differential metabolites were identified, with the VVC group having 128 over-expressed and 83 under-expressed metabolites compared with healthy individuals. Functional analysis showed that these metabolites were mainly involved in amino acid metabolism and lipid metabolism. In addition, network software analysis indicated that the differential metabolites were associated with mitogen-activated protein kinase (MAPK) signaling and NF-κB signaling. Further molecular docking suggested that linoleic acid can bind to the acyl-CoA synthetase 1 (ACSL1) protein, which has been shown to be associated with multiple inflammatory diseases and is an upstream regulator of the MAPK and NF-κB signaling pathways that mediate inflammation. Therefore, our preliminary analysis results suggest that VVC has a unique metabolic profile. Linoleic acid, a significantly elevated unsaturated fatty acid in the VVC group, may promote VVC development through the ACSL1/MAPK and ACSL1/NF-κB signaling pathways. This study's findings contribute to further exploring the mechanism of VVC infection and providing new perspectives for the treatment of Candida albicans vaginal infection.

Candida albicans is the main pathogen that causes VVC. Through non-targeted metabolomics, this study shows that VVC caused by C. albicans has unique vaginal metabolic characteristics, the changed metabolites might provide useful diagnostic and therapeutic methods for VVC.

Long non-coding RNA SNHG17 contributes to the progression of pancreatic adenocarcinoma by modulating miR-32-5p/EZH2/STAT3 signaling.

BACKGROUND: Adenocarcinoma of the pancreas (PAAD) is one of the most malignant tumors in the gastrointestinal tract. Long-chain noncoding RNAs (lncRNAs) are non-coding RNAs that are expressed in a variety of cancers. The purpose of this study is to study the expression, biology functions, and molecular mechanism of lncRNA SNHG17 in PAAD. METHODS: In this study, qRT-PCR was used to measure the relative expression of SNHG17 and miR-32-5p in PAAD. In order to investigate the effect of SNHG17 and miR-32-5p on the proliferation, migration and invasion of PAAD cells, we performed a variety of tests including CCK-8, colony formation, scratch and transwell assays. Furthermore, SNHG17 and miR-32-5p interactions were confirmed by a luciferase reporter gene test. RESULTS: Our results indicate that the expression of SNHG17 in PAAD is elevated, and in vitro studies have shown that SNHG17 enhances the proliferation of PAAD cells, Mechanistically, it has been shown that SNHG17 can direct target miR-32-5p in PAAD cells, thus promoting the proliferation of PAAD cells, migration, and invasion. Furthermore, SNHG17 has been found to activate EZH2/STAT3 signaling pathway through miR-32-5p in PAAD cells. CONCLUSION: Our results show that SNHG17 plays a key role in the progression of PAAD by activating STAT3 signaling via regulation of miR-32-5p and EZH2.Identifying these new regulatory pathways may shed light on the underlying mechanism of PAAD and offer a potential therapeutic target for this fatal disease.

Association of variants and expression levels of MYOD1 gene with carcass and muscle characteristic traits in domestic pigeons.

This study was to investigate the correlations of myogenic differentiation 1 (MYOD1) gene polymorphisms with carcass traits and its expression with breast muscle development in pigeons. Four SNPs were found in the pigeon MYOD1 gene. Correlation analysis showed that individuals with AA genotype at both SNPs g.2967A > G (p < .01) and g.3044G > A (p < .05) have significantly higher live weight (LW), carcass weight (CW), semi-eviscerated weight (SEW), eviscerated weight (EW) and breast muscle weight (BMW). Moreover, the two SNPs also had the same significant effects on MYOD1 mRNA expression levels in breast muscle of pigeons, ie, the AA genotype showed higher MYOD1 mRNA expression levels. The diameter and cross-section area of muscle fibers continuously increased from 0w to 4w (p < .05), accompanied with the increasing expression of MYOD1 gene, while the density decreased (p < .05) dramatically from 0w to 1w and continuously fell over in the next few weeks (p > .05). What's more, the expression level of MYOD1 gene was positively correlated with a diameter (r = 0.937, p < .05) and cross-sectional area (r = 0.956, p < .01) of myofiber, and negatively correlated with density (r = -0.769, p < .01). The results showed that individuals with AA genotype at both SNPs g.2967A > G and g.3044G > A have showed higher carcass traits (LW, CW, SEW, EW, and BMW) and higher MYOD1 mRNA expression level in breast muscle than AB and BB genotypes. Moreover, the expression level of MYOD1 gene was closely correlated with muscle characteristic traits, indicating variants of MYOD1 gene was closely related to muscle development and could be a potential candidate gene in marker-assisted selection of pigeons.

Second-victim experience and support among nurses in mainland China.

AIMS: To investigate the experience and support of nurses as second victims in adverse events and explore factors. BACKGROUND: Adverse events have significant negative influences on healthcare professionals. However, there is still a lack of research on the impacts of individual and event factors. METHODS: A cross-sectional survey via a self-report electronic questionnaire was sent to approximately 6400 nurses from six tertiary comprehensive hospitals in mainland China. The socio-demographic, adverse event-related information and second-victim experience and support questionnaires were used. RESULTS: Approximately 2897 (45.26%) of nurses were involved in at least one adverse event that mainly caused psychological distress. Male nurses, Grade I adverse events, public reports and discussions of adverse events were related to the second-victim reaction. Discussing with a respected colleague was the most strongly desired form of support. CONCLUSIONS: Chinese nurses have reported a high prevalence of psychological reactions. Follow-up studies must consider other potential factors. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should consider the factors that affect second victims and provide support based on the expectations of nurses. Psychological first-aid and immediate and mid- to long-term support strategies should be provided to help the second victim alleviate distress.

HbSnRK2.6 Functions in ABA-Regulated Cold Stress Response by Promoting HbICE2 Transcriptional Activity in Hevea brasiliensis.

Low temperature remarkably limits rubber tree (Hevea brasiliensis Muell. Arg.) growth, latex production, and geographical distribution, but the underlying mechanisms of Hevea brasiliensis cold stress response remain elusive. Here, we identified HbSnRK2.6 as a key component in ABA signaling functions in phytohormone abscisic acid (ABA)-regulated cold stress response in Hevea brasiliensis. Exogenous application of ABA enhances Hevea brasiliensis cold tolerance. Cold-regulated (COR) genes in the CBF pathway are upregulated by ABA. Transcript levels of all five HbSnRK2.6 members are significantly induced by cold, while HbSnRK2.6A, HbSnRK2.6B, and HbSnRK2.6C can be further activated by ABA under cold conditions. Additionally, HbSnRK2.6s are localized in the cytoplasm and nucleus, and can physically interact with HbICE2, a crucial positive regulator in the cold signaling pathway. Overexpression of HbSnRK2.6A or HbSnRK2.6B in Arabidopsis extensively enhances plant responses to ABA and expression of COR genes, leading to increased cold stress tolerance. Furthermore, HbSnRK2.6A and HbSnRK2.6B can promote transcriptional activity of HbICE2, thus, increasing the expression of HbCBF1. Taken together, we demonstrate that HbSnRK2.6s are involved in ABA-regulated cold stress response in Hevea brasiliensis by regulating transcriptional activity of HbICE2.

Activity and Stability Boosting of an Oxygen-Vacancy-Rich BiVO4 Photoanode by NiFe-MOFs Thin Layer for Water Oxidation.

The introduction of oxygen vacancies (Ov) has been regarded as an effective method to enhance the catalytic performance of photoanodes in oxygen evolution reaction (OER). However, their stability under highly oxidizing environment is questionable but was rarely studied. Herein, NiFe-metal-organic framework (NiFe-MOFs) was conformally coated on oxygen-vacancy-rich BiVO4 (Ov-BiVO4 ) as the protective layer and cocatalyst, forming a core-shell structure with caffeic acid as bridging agent. The as-synthesized Ov-BiVO4 @NiFe-MOFs exhibits enhanced stability and a remarkable photocurrent density of 5.3±0.15 mA cm-2 at 1.23 V (vs. RHE). The reduced coordination number of Ni(Fe)-O and elevated valence state of Ni(Fe) in NiFe-MOFs layer greatly bolster OER, and the shifting of oxygen evolution sites from Ov-BiVO4 to NiFe-MOFs promotes Ov stabilization. Ovs can be effectively preserved by the coating of a thin NiFe-MOFs layer, leading to a photoanode of enhanced photocurrent and stability.

[Current situation analysis and supervision suggestions of traditional Chinese medicine health food claiming to enhance immune function].

Number of products claiming to enhance immunity function ranks first among all the approved health food products,and number of products whose formula contains Chinese medicine accounts for two thirds of all the products claiming to enhance immunity function. Chinese medicine allowed to be used in health food has a specified range,and the safety of raw materials is generally higher.The usage amount of raw materials shall not exceed the upper limit stipulated in the literature or regulations. The claim of enhancement of immunity function is put forward by western medicine based on modern pharmacology and nutriology. However,immunity is wide in scope and complex in mechanism. The health food that contains Chinese medicine plays an active effect in enhancement of immunity under the guidance of Chinese medicine theory in many ways such as immune organs,immune cells and immune molecules. In this article,the author first analyzed the current use of raw materials for health food,then summarized the approved health food claiming to enhance immunity function,and conducted statistical analysis on the enhancement of immunity for traditional Chinese medicine(TCM)health food,use of raw materials,compatibility of raw materials,conducted in-depth analysis on health food formula,safety,health function,quality control and production process from the perspectives of technical review,supervision and management. Finally,some suggestions on registration and supervision of TCM health food claiming to enhance immunity function were put forward from the perspectives of problems found in the supervision and from the demand of TCM health food in the future.

[Some thoughts on health food formulated with traditional Chinese medicine].

The health food industry is an important support for the big health industry and the strategy of healthy China. The Chinese medicine prescription health food has exceeded 60% of the total declared health food. However,the main basis for its function evaluation,the Technical Specification for Inspection and Evaluation of Health Food,was abolished in 2018,and 27 of them were based on modern medical and nutritional theories. Quantitative efficacy evaluation methods in western pharmacology are short of function claims and function evaluation methods reflecting the characteristics of traditional Chinese medicine,which could affect the health food industry to a certain extent. Therefore,the establishment of the evaluation mechanism of Chinese medicine prescription health food which conforms to the positioning of health food and the theory of traditional Chinese medicine is helpful for the healthy development of health food industry. In this paper,this problem was explained from five aspects. First,how to differentiate the positioning of Chinese medicine prescription health food from ordinary food and medicine,and how to embody the characteristics of Chinese medicine. Secondly,the relationship between traditional Chinese medicine prescription health food and Chinese patent medicine. Thirdly,how to scientifically and reasonably determine the raw materials of traditional Chinese medicine prescription health food. Fourthly,how to explain the function claim of traditional Chinese medicine prescription health food,and how to evaluate its function scientifically and reasonably. Fifthly,the functional evaluation of Chinese herbal medicine prescription health food is connected with other national scientific and technological strategies. In this paper,a preliminary analysis of the Chinese medicine prescription health food was conducted from the above five aspects,and some personal views and suggestions were put forward,hoping to provide reference for the competent authorities and researchers.

[Current situation and research strategy of quality control of health food containing Chinese materia medica].

Health food containing Chinese materia medica has many advantages in health preservation and reducing the risk of disease occurrence,which meets people's demands for " great health" and " preventive treatment of disease". However,due to its complex ingredients,diverse quality of raw materials,as well as the vagueness and lack of integrity for existing quality standards,chaos is caused in the health food market,which restricts its healthy development and also poses new challenges to the quality control of healthy food. At present,the total component content or single component content is determined in most functional/marker component examinations. Safety and microbial detection methods fail to cover the contamination range of the raw materials of Chinese materia medica.Therefore,it is impossible to meet the purpose of ensuring authenticity,safety and efficacy. In recent years,a lot of Chinese materia medica extracts have been used as raw materials for food products,but many extracts lack standards. The author believes that the quality control of health food containing Chinese materia medicas should start with the quality control of Chinese materia medica extracts. In this way,product quality is controlled from source to ensure product consistency; secondly,the overall quality control should be strengthened to ensure the authenticity of the products; the scope of safety inspection shall be expanded to fundamentally ensure the safety of products. At the same time,we should strengthen the quality control of whole process and strengthen the overall quality control of raw materials to produce health food of high quality.

[Research,evaluation,industry status and development strategy of traditional Chinese medicine functional food].

With the development of social economy,people's demand for health services is growing rapidly. As health resource with Chinese characteristics,health food containing Chinese materia medica have broad prospect and great market space for development.However,at present,there are still many problems of health food containing Chinese materia media in the research,development,evaluation and market application. In addition,due to lack of theoretical support of traditional Chinese medicine(TCM) in the research and development of health food containing Chinese materia media,blurred boundaries between health food containing Chinese materia media and other health products as well as TCM are present,lacking of TCM characteristics. In the evaluation process of health food containing Chinese materia media,the construction of functional food laws,regulations and evaluation norms is relatively lagging behind,which can't meet the needs of health food containing Chinese materia media research and development,severely restricting the development of health food containing Chinese materia media. Based on the research and evaluation of health food containing Chinese materia media,the existing problems were reviewed and the reasons for the deficiencies were analyzed in this paper. Guided by the theory of TCM,based on the constitution identification in TCM,and combined with modern scientific and technological means,a new research and development mode of functional food was put forward in this paper to distinguish health food containing Chinese materia media from TCM as well as general health products. Nevertheless,we should ensure the vitality of Chinese medicine health products with original thinking and scientific and technological connotations,and accelerate the harmonious,rapid and sustainable development of Chinese medicine health industry.

[Study on function evaluation of health food containing Chinese materia medica based on data mining].

Homology of medicine and food is an important content in Chinese medicine and also works as the basis for guiding the development of compound health food containing Chinese materia medica. The top products,supplements,health care prescriptions,and medicinal meals in traditional herbal texts are the theoretical treasures of Chinese medicine compound health foods. With the implementation of the National Healthy China 2030,China's major health industry faces with tremendous opportunities. It is necessary to develop a batch of compound health food containing Chinese materia medica with Chinese medicine characteristics,in line with the needs of the country and society. Domestic research on compound health food containing Chinese materia medica mainly focuses on the extraction of functional components,preparation molding processes,quality standards,and efficacy evaluation. However,there are still some deficiencies in the related characteristics of traditional Chinese medicine(TCM) theory and function,evaluation criteria of efficacy and safety,new product R&D evaluation system and R&D platform. Based on a large number of previous studies by this laboratory,the views in nature,flavor and efficacy relationship were put forward in this paper. Based on the establishment of the Chinese medicine function-pharmacology-clinical application database system,the Chinese medicine compatibility database system,the Chinese medicine nature and flavor modern research database system,and the evaluation platform for animal models of Chinese medicine; the efficacy study,safety evaluation system,new product research and development evaluation system as well as research and development platform were established,providing a basis for the development and evaluation of compound health food containing Chinese materia medica. The modern scientific connotation of the core efficacy of compound health food containing Chinese materia medica was explained as well,helpful to promote the research and development of compound health food containing Chinese materia medica and play an important role in general health.

The C. elegans COE transcription factor UNC-3 activates lineage-specific apoptosis and affects neurite growth in the RID lineage.

Mechanisms that regulate apoptosis in a temporal and lineage-specific manner remain poorly understood. The COE (Collier/Olf/EBF) transcription factors have been implicated in the development of many cell types, including neurons. Here, we show that the sole Caenorhabditis elegans COE protein, UNC-3, together with a histone acetyltransferase, CBP-1/P300, specifies lineage-specific apoptosis and certain aspects of neurite trajectory. During embryogenesis, the RID progenitor cell gives rise to the RID neuron and RID sister cell; the latter undergoes apoptosis shortly after cell division upon expression of the pro-apoptotic gene egl-1. We observe UNC-3 expression in the RID progenitor, and the absence of UNC-3 results in the failure of the RID lineage to express a Pegl-1::GFP reporter and in the survival of the RID sister cell. Lastly, UNC-3 interacts with CBP-1, and cbp-1 mutants exhibit a similar RID phenotype to unc-3. Thus, in addition to playing a role in neuronal terminal differentiation, UNC-3 is a cell lineage-specific regulator of apoptosis.

Curcumin inhibits the proliferation and induces apoptosis in HT-29 cell lines through a reactive oxygen species (ROS)-dependent mechanism.

Curcumin, a natural pigment extracted from Curcuma longa, has anti-carcinogenic activities in many cancer cell lines. The molecular mechanism of apoptosis induced by curcumin are still unknown. In the current study, we investigated the roles of reactive oxygen species in curcumin stimulated apoptosis in HT-29 cells. Curcumin significantly reduced cell viability, induced apoptosis, activated caspase-3 activity and stimulated concentration-dependent release of ROS. Inhibition of ROS generation by scavengers suppressed apoptosis and Bcl-2 expression induced by curcumin, indicating the critical roles of ROS in the apoptotic process. However, caspase-3 inhibitor (z-VAD-FMK) couldn't completely inhibit the curcumin induced apoptosis, indicating ROS mediated apoptosis may be caspase-independent. Together, our findings showed that ROS played significant roles in the apoptosis induced by curcumin in HT-29 cells.

Nup62, associated with spindle microtubule rather than spindle matrix, is involved in chromosome alignment and spindle assembly during mitosis.

An increasing number of the active mitotic functions of nucleoporins in the distinct steps of mitosis have been assigned over the past few years. As one of FG-repeats containing nucleoporins, Nup62 has been found to be involved in nuclear transport, cell migration, virus infection, and cell cycle regulation. However, the role and mechanism of Nup62 in mitotic regulation have not been fully revealed. In this paper, it was revealed that a fraction of Nup62 was associated with mitotic spindle microtubule instead of spindle matrix, and the localization of Nup62 in the mitotic spindle depended on its three coiled-coil domains rather than Crm1, although Nup62 strongly interacted with Crm1 during mitosis. Moreover, depletion of Nup62 by small interference of RNA seriously induced the defects of chromosome alignment and spindle assembly although the bipolar spindle was observed in most of the Nup62 knock-down cells. Notably, congression of polar chromosome defect was observed in more than 30% of Nup62 knock-down cells. These findings revealed that Nup62 was a novel mitotic spindle associated nucleoporin and involved in chromosome alignment and spindle assembly.

Midlife gene expressions identify modulators of aging through dietary interventions.

Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespan-modifying genes. Intriguingly, mitochondrial gene expression correlated with lifespan and anticorrelated with aging-related pathological changes, whereas peroxisomal gene expression showed an opposite trend. Both organelles produce reactive oxygen species, a proposed causative factor of aging. This finding implicates a contribution of peroxisome to aging. Consistent with this hypothesis, lowering the expression levels of peroxisome proliferation genes decreased the cellular peroxide levels and extended the lifespan of Drosophila melanogaster and Caenorhabditis elegans. These findings show that transcriptional changes resulting from dietary interventions can effectively reflect causal factors in aging and identify previously unknown or under-appreciated longevity pathways, such as the peroxisome pathway.