CircaKB: a comprehensive knowledgebase of circadian genes across multiple species.

Circadian rhythms, which are the natural cycles that dictate various physiological processes over a 24-h period, have been increasingly recognized as important in the management and treatment of various human diseases. However, the lack of sufficient data and reliable analysis methods have been a major obstacle to understanding the bidirectional interaction between circadian variation and human health. We have developed CircaKB, a comprehensive knowledgebase of circadian genes across multiple species. CircaKB is the first knowledgebase that provides systematic annotations of the oscillatory patterns of gene expression at a genome-wide level for 15 representative species. Currently, CircaKB contains 226 time-course transcriptome datasets, covering a wide variety of tissues, organs, and cell lines. In addition, CircaKB integrates 12 computational models to facilitate reliable data analysis and identify oscillatory patterns and their variations in gene expression. CircaKB also offers powerful functionalities to its users, including easy search, fast browsing, strong visualization, and custom upload. We believe that CircaKB will be a valuable tool and resource for the circadian research community, contributing to the identification of new targets for disease prevention and treatment. We have made CircaKB freely accessible at https://cdsic.njau.edu.cn/CircaKB.

Theoretical Study of the NO Reduction Mechanism on Biochar Surfaces Modified by Li and Na Single Adsorption and OH Co-Adsorption.

Theoretical and experimental investigations have shown that biochar, following KOH activation, enhances the efficiency of NO removal. Similarly, NaOH activation also improves NO removal efficiency, although the underlying mechanism remains unclear. In this study, zigzag configurations were employed as biochar models. Density functional theory (DFT) was utilized to examine how Li and Na single adsorption and OH co-adsorption affect the reaction pathways of NO reduction on the biochar surface. The rate constants for all reaction-determining steps (RDSs) within a temperature range of 200 to 1000 K were calculated using conventional transition state theory (TST). The results indicate a decrease in the activation energy for NO reduction reactions on biochar when activated by Li and Na adsorption, thus highlighting their beneficial role in NO reduction. Compared to the case with Na activation, Li-activated biochar exhibited superior performance in terms of the NO elimination rate. Furthermore, upon the adsorption of the OH functional group onto the Li-decorated and Na-decorated biochar models (LiOH-decorated and NaOH-decorated chars), the RDS energy barriers were higher than those of Li and Na single adsorption but easily overcome, suggesting effective NO reduction. In conclusion, Li-decorated biochar showed the highest reactivity due to its low RDS barrier and exothermic reaction on the surface.

MOF-Derived Pt/ZrO2 Carbon Electrocatalyst for Efficient Hydrogen Evolution.

One type of porous carbon nanomaterial decorated by abundant Pt/ZrO2 nanoparticles can be conveniently prepared, which is pyrolyzed from flower-shaped Zr-based UiO-67 precursor with a small amount of H2PtCl6 molecules in its large pores. In addition, the obtained Pt/ZrO2 carbon electrocatalyst can bring efficient electrocatalytic hydrogen evolution performance and long-term stability.

Centrosome Protein 78 Is Overexpressed in Muscle-Invasive Bladder Cancer and Is Associated with Tumor Molecular Subtypes and Mutation Signatures.

BACKGROUND Centrosome aberrations have long been linked to tumorigenesis. Centrosome protein 78 (CEP78) is a centrosome component that is required to regulate the cell cycle, but its role in bladder cancer has not been elucidated. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and immunohistochemistry were used to examine the expression of CEP78 in bladder cancer tissues and adjacent non-cancer tissues. RESULTS Analysis of the RNA-Seq data from the TCGA (The Cancer Genome Atlas) MIBC cohort (n=408) revealed that CEP78 was overexpressed in tumor tissues, which was confirmed with fresh-frozen and formalin-fixed paraffin-embedded specimens collected from 28 and 33 MIBC patients, respectively, in the present study. The clinicopathological relevance of CEP78 was further investigated. High CEP78 expression was found to be correlated with non-papillary histological type, luminal, basal-squamous and neuronal molecular subtypes, TP53 mutation, RB1 mutation, wild-type FGFR3, PPARG fusion and amplification, high total number of single-nucleotide variants, and high neoantigen load, but it was not associated with tumor stages or overall survival. CONCLUSIONS The results of this study suggest that CEP78 plays in a role in promoting the development of MIBC and could be a novel diagnostic and therapeutic target.

Large-Scale Identification of AbaR-Type Genomic Islands in Acinetobacter baumannii Reveals Diverse Insertion Sites and Clonal Lineage-Specific Antimicrobial Resistance Gene Profiles.

AbaR-type genomic islands (AbaRs) are important elements responsible for antimicrobial resistance in Acinetobacter baumannii This study performed a large-scale identification of AbaRs to understand their distribution and compositions of antimicrobial resistance genes. We identified 2.89-kb left-end and 1.87-kb right-end conserved sequences (CSs) and developed a bioinformatics approach to identify AbaRs, using the CSs as signatures, in 3,148 publicly available genomes. AbaRs were prevalent in A. baumannii, being found in 2,091 genomes. They were sparse in other Acinetobacter species and confined only to this genus. Results from 111 complete genomes showed that over 85% of AbaRs resided on chromosomes. The external flanks adjacent to the inverted repeats available in all identified CSs were mapped to an AbaR-free chromosome or searched in the NCBI database for empty loci to define insertion sites. Surprisingly, 84 insertion sites with diverse origins were revealed, including 51 scattered on the chromosome, 20 plasmid borne, 12 located on prophages, transposons, ISAba1, complex AbaRs, and genomic islands of other types, and one uncharacterized, and some were strongly associated with clonal lineages. Finally, we found 994 antimicrobial resistance genes covering 28 unique genes from 70.9% (299/422) of intact AbaRs currently available. The resistance gene profiles displayed an apparent clonal lineage-specific pattern, highlighting the distinct features of AbaRs in global clone 1 (GC1) and GC2. The tet(B) gene was highly specific to the AbaRs in GC2. In conclusion, AbaRs have diverse insertion sites on the chromosome and mobile genetic elements (MGEs) and display distinct antimicrobial resistance gene profiles in different clonal lineages.

In Silico Typing and Comparative Genomic Analysis of IncFIIK Plasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles.

IncFIIK plasmids are associated with the acquisition and dissemination of multiple-antimicrobial resistance in Klebsiella pneumoniae and often encountered in clinical isolates of this species. Since the phylogeny and evolution of IncFIIK plasmids remain unclear, here we performed large-scale in silico typing and comparative analysis of these plasmids in publicly available bacterial/plasmid genomes. IncFIIK plasmids are prevalent in K. pneumoniae, being found in 69% of sequenced genomes, covering 66% of sequenced STs (sequence types), but sparse in other Enterobacteriaceae IncFIIK replicons have three lineages. One IncFIIK allele could be found in distinct K. pneumoniae STs, highlighting the lateral genetic flow of IncFIIK plasmids. A set of 77 IncFIIK plasmids with full sequences were further analyzed. A pool of 327 antibiotic resistance genes or remnants were annotated in 75.3% of these plasmids. Plasmid genome comparison reiterated that they often contain other replicons belonging to IncFIA, IncFIB, IncFIIYp, IncFIIpCRY, IncR, IncL, and IncN groups and that they share a conserved backbone featuring an F-like conjugation module that has divergent components responsible for regulation and mating pair stabilization. Further epidemiological studies of IncFIIK plasmids are required due to the sample bias of K. pneumoniae genomes in public databases. This study provides insights into the evolution and structures of IncFIIK plasmids.

Rod-Shaped Au@Ce Nano-Platforms for Enhancing Photodynamic Tumor Collaborative Therapy.

Tumor photodynamic therapy (PDT) relies on intratumoral free radicals, while the limited oxygen source and the depletion of tissue oxygen may exacerbate the hypoxia. As the treatment progresses, there will eventually be a problem of insufficient free radicals. Here, it is found that Au@CeO2 nano-rods (Au@Ce NRs), assembled by gold nano-rods (Au NRs) and ceria nanoparticles (CeO2 NPs), can efficaciously absorb near-infrared light (NIR) to promote the release of oxygen and free radicals. Au@Ce NRs exhibit a higher proportion of Ce3+ (Ce2O3) after oxygen release, while Ce3+ is subsequently oxidized to Ce4+ (CeO2) by trace H2O2. Interestingly, Au@Ce NRs re-oxidized by trace H2O2 can re-releasing oxygen and free radicals again upon NIR treatment, achieving oxygenation/oxygen evolution, similar to charging/discharging. This loop maximizes the conversion of limited oxygen source into highly cytotoxic free radicals. As a result, when B16-F10 cells are treated by NIR/Au@Ce NRs, more tumor cells undergo apoptosis, consistent with the higher level of free radicals. Importantly, NIR/Au@Ce NRs successfully suppresses tumor growth and promotes the generation of epidermal collagen fibers in the transplanted tumor model. Therefore, the rod-shaped Au@Ce NRs provide an ideal platform for maximizing the utilization of intratumoral oxygen sources and improving the treatment of melanoma.

CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice.

Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses.

A rapid expansion of hospitals: the adaptation of multi-campus hospitals under the Chinese healthcare system.

In recent years, China's healthcare system has undergone significant changes to meet the increasing demands of its growing population. One notable development is the rapid expansion of hospitals, particularly the adaptation of multi-campus hospitals. These multi-campus hospitals have become increasingly popular due to the many advantages that single-campus hospitals lack, including the ability to; improve medical service quality, reduce operating costs, and facilitate the development of healthcare services in rural areas. In this study, we discuss the advantages that this type of medical facility offers and identify existing and potential problems that could hinder the development of multi-campus hospitals. Additionally, we propose appropriate solutions to mitigate these problems. Overall, we propose that there should be more communication between multi-campus hospitals and other healthcare providers.

How Does Problematic Internet Use Influence Chinese Rural Adolescent Externalizing Problem Behaviors? The Mediating Role of Mental Health and the Moderating Role of Parental Knowledge.

This study aims to provide a new perspective on the relationship between problematic Internet use and externalizing problem behavior among adolescents. Many studies have focused on the relationship between problematic Internet use and adolescent externalizing problem behavior; however, research on the underlying mechanism remain understudied. Altogether, 1161 Chinese rural adolescents aged 13-17 years completed a self-report questionnaire. The results indicate that: (1) Problematic Internet use has a negative effect on rural adolescent externalizing problem behaviors; (2) mental health has an effect on the relationship between problematic Internet use and externalizing problem behaviors; and (3) parental knowledge may moderate the indirect effect by attenuating the relationship between problematic Internet use and externalizing problem behaviors. Regarding these findings, this study has discussed the potential reasons and provided some practical suggestions to improve problematic Internet use among rural adolescents.

Parenting style and children emotion management skills among Chinese children aged 3-6: the chain mediation effect of self-control and peer interactions.

Drawing on ecosystem theory, which is based on the interaction of family environment, individual characteristics, and social adaptation, this study aimed to examine the effects of parenting style on emotion management skills and the mediating roles of self-control and peer interactions among Chinese children aged 3-6 years. Some studies have investigated the relationship between parenting style and emotion management skills. However, research on the underlying mechanisms is still deficient. A sample of 2,303 Chinese children completed the PSDQ-Short Version, the Self-Control Teacher Rating Questionnaire, the Peer Interaction Skills Scale, and the Emotion Management Skills Questionnaire. The results show that: (1) Authoritarian parenting style negatively predicted children's emotion management skills, self-control, and peer interactions; (2) Authoritative parenting style positively predicted children's emotion management skills, self-control, and peer interactions; (3) Structural equation models indicated that self-control and peer interactions partially mediated the effects of authoritarian and authoritative parenting styles. The parenting style of Chinese children aged 3-6 years is related to emotion management skills, and self-control and peer interactions have chain mediating effects between parenting style and children's emotion management skills. These results provide further guidance for the prevention and intervention of emotional and mental health problems in children.

The association between authoritarian parenting style and peer interactions among Chinese children aged 3-6: an analysis of heterogeneity effects.

This study explores the effects of authoritarian parenting styles on children's peer interactions, an aspect often overlooked in the existing literature that primarily focuses on family environmental factors. Data was collected through anonymous child-report questionnaires completed by 2,303 parents and teachers of children aged 3-6 years. The findings reveal that (1) authoritarian parenting significantly hinders children's peer interactions; (2) the negative effects of authoritarian parenting differ based on gender, age, and family composition: (a) girls generally exhibit higher peer interactions than boys, with authoritarian parenting having a stronger impact on boys' peer interactions; (b) peer interactions increase significantly with age, and younger children are more susceptible to the negative effects of authoritarian parenting; (c) children with siblings have higher peer interactions, and authoritarian parenting style has a greater influence on their interactions compared to only children. The study discusses potential reasons and provides practical suggestions for families to make informed parenting style choices based on these findings.

Associations between teacher-student relationship and externalizing problem behaviors among Chinese rural adolescent.

The primary objective of this study is to present a fresh perspective on the correlation between teacher-student relationships and externalizing problem behaviors among adolescents. While previous research has examined this connection, there is still an insufficient understanding of the underlying mechanisms. Moreover, the crucial role of peer relationships, mental health, and parental knowledge has been overlooked. In this study, a total of 6,919 Chinese rural adolescents aged 13-19 years participated by completing an anonymous self-report questionnaire. The results show that: (1) teacher-student relationship has a protective effect against the development of externalizing problem behaviors; (2) peer relationship and mental health both have a mediating role in the relationship between teacher-student relationship and externalizing problem behaviors; (3) teacher-student relationship can indirectly affect externalizing problem behaviors through the chain mediation of peer relationship and mental health; (4) parental knowledge plays a moderating role between the teacher-student relationship and externalizing problem behaviors. As the level of parental knowledge increases among rural adolescents, the impact of the teacher-student relationship on externalizing problem behaviors becomes more pronounced; and (5) the impact of teacher-student relationship on externalizing problem behaviors has no significant gender differences. Given the study's empirical outcomes, we discuss potential explanations and advocate for a comprehensive pedagogical approach to mitigate rural adolescent externalizing behaviors. This entails nurturing teacher-student relations, fostering inclusive peer environments, emphasizing mental health literacy, and synergizing with caregivers for a holistic home-school intervention.

The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer.

Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.

A minimal genome design to maximally guarantee fertile inter-subspecific hybrid rice.

Hybrid rice has made considerable contributions to achieve the ambitious goal of food security for the world's population. Hybrid rice from indica/xian and japonica/geng subspecies shows much higher heterosis and is thereby an important innovation in promoting rice production in the next decade. However, such inter-subspecific hybrid rice has long suffered from serious hybrid sterility, which is a major challenge that needs to be addressed. In this study, we performed a genome design strategy to produce fertile inter-subspecific hybrid by creation of wide compatibility varieties that are able to overcome hybrid sterility. Based on combined genetic analyses in two indica-japonica crosses, we determined that four hybrid sterility loci, S5, f5, pf12 and Sc, are the major QTLs controlling inter-subspecific hybrid sterility and thus the minimal targets that can be manipulated for breeding sub-specific hybrid rice. We then cloned the pf12 locus, one of the most effective loci for hybrid male sterility, by map-based cloning, and showed that artificial disruption of pf12A gene at this locus could successfully rescue hybrid fertility. We further dissected the genetic basis of wide compatibility using three pairwise crosses from a wide-compatibility variety Dular and representative indica and japonica varieties. On this basis, we constructed and assembled different combinations of naturally compatible alleles of four loci, S5, Sc, pf12, and f5, and found that the improved lines could fully recover pollen and embryo sac fertility in test-crossed F1s, thereby completely fulfilling the demands of inter-subspecific hybrid spikelet fertility in agricultural production. This breeding scheme would facilitate redesign of future inter-subspecific hybrid rice with a higher yield potential.

Profiling Fusobacterium infection at high taxonomic resolution reveals lineage-specific correlations in colorectal cancer.

The bacterial genus Fusobacterium promotes colorectal cancer (CRC) development, but an understanding of its precise composition at the species level in the human gut and the relevant association with CRC is lacking. Herein, we devise a Fusobacterium rpoB amplicon sequencing (FrpoB-seq) method that enables the differentiation of Fusobacterium species and certain subspecies in the microbiota. By applying this method to clinical tissue and faecal samples from CRC patients, we detect 62 Fusobacterium species, including 45 that were previously undescribed. We additionally reveal that Fusobacterium species may display different lineage-dependent functions in CRC. Specifically, a lineage (designated L1) including F. nucleatum, F. hwasookii, F. periodonticum and their relatives (rather than any particular species alone) is overabundant in tumour samples and faeces from CRC patients, whereas a non-enriched lineage (designated L5) represented by F. varium and F. ulcerans in tumours has a positive association with lymphovascular invasion.

Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis.

OBJECTIVE: Thyroid hormones (THs) regulate multiple physiological activities in the liver, including cellular metabolism, differentiation, and cell growth, and play important roles in the pathogenesis of hepatocellular carcinoma (HCC). Thyroid peroxidase (TPO) is a key molecule involved in the THs synthesis and signaling pathway. As an epigenetic modification, DNA methylation has a critical role in tumorigenesis with diagnostic potential. However, the connection between THs and DNA methylation has been rarely investigated. METHODS: The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning, and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays, and evaluated their clinical implications. RESULTS: We identified that the methylation of the TPO promoter was downregulated in the HCC tissues (P<0.0001) with a mean difference ranging from 18.5% to 22.3%. This methylation pattern correlated with several clinical factors, including a multi-satellite tumor, fibrous capsule, and the presence of tumor thrombus. The receiver operator characteristic (ROC) curve analysis further confirmed that the percent methylated reference (PMR) values for TPO were predictive of the tumor [the area under the curve (AUC) ranged from 0.755 to 0.818] and the thrombosis in the HCC patients (the AUC ranged from 0.706 to 0.777). CONCLUSION: These findings demonstrated that epigenetic alterations of TPO, as indicated by the PMR values, were a potential biomarker for HCC patients with tumor thrombosis.

A newly developed PCR-based method revealed distinct Fusobacterium nucleatum subspecies infection patterns in colorectal cancer.

Fusobacterium nucleatum, which has four subspecies (nucleatum, animalis, vincentii and polymorphum), plays an important role in promoting colorectal cancer (CRC). However, as there is no efficient method of differentiating these subspecies in the context of a rich gut microbiota, the compositions in CRC remain largely unknown. In this study, a PCR-based differentiation method enabling profiling of F. nucleatum infection in CRC at the subspecies level was developed. Based on the analysis of 53 F. nucleatum genomes, we identified genetic markers specific to each subspecies and designed primers for the conserved sequences of those markers. The PCR performance of the primers was tested with F. nucleatum and non-nucleatum Fusobacterium strains, and complete consistence with taxonomy was achieved. Additionally, no non-specific amplification occurred when using human DNA. The method was then applied to faecal (n = 58) and fresh-frozen tumour tissue (n = 100) samples from CRC patients, and wide heterogeneity in F. nucleatum subspecies compositions in the gut microbiota among CRC patients was observed. Single-subspecies colonization was common, whereas coexistence of four subspecies was rare. Subspecies animalis was most prevalent, while nucleatum was not frequently detected. The results of this study contribute to our understanding of the pathogenicity of F. nucleatum at the subspecies level and the method developed has potential for clinical and epidemiological use.

Association between circulating insulin-like growth factor 1 and risk of all-cause and cause-specific mortality.

BACKGROUND: Insulin-like growth factor 1 (IGF1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF1 concentrations influence early death risk in the general population remains largely unknown. METHODS: We included 380 997 participants who had serum IGF1 measurement and no history of cancer, cardiovascular disease (CVD), or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. RESULTS: Over a median follow-up of 8.8 years, 10 753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF1 levels and mortality. Compared to the fifth decile of IGF1, the lowest decile was associated with 39% (95% CI: 29-50%), 20% (95% CI: 8-34%), and 39% (95% CI: 14-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7-28%) and 38% (95% CI: 11-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. CONCLUSIONS: Our findings indicate that both low and high concentrations of serum IGF1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF1 in early death occurrence and possible implications for mitigating the risk.