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Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3' UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors. Further, we introduce untranslated tumor mutational burden (uTMB), a metric reflecting the amount of somatic functional MapUTR variants of a tumor and show its potential in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), demonstrating their cancer-driving potential. Our study elucidates the function of tens of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.

MotivationDouble-stranded RNAs (dsRNAs) are potent triggers of innate immune responses upon recognition by cytosolic dsRNA sensor proteins. Identification of endogenous dsRNAs helps to better understand the dsRNAome and its relevance to innate immunity related to human diseases.ResultsHere, we report dsRID (double-stranded RNA identifier), a machine-learning-based method to predict dsRNA regions in silico, leveraging the power of long-read RNA-sequencing (RNA-seq) and molecular traits of dsRNAs. Using models trained with PacBio long-read RNA-seq data derived from Alzheimer's disease (AD) brain, we show that our approach is highly accurate in predicting dsRNA regions in multiple datasets. Applied to an AD cohort sequenced by the ENCODE consortium, we characterize the global dsRNA profile with potentially distinct expression patterns between AD and controls. Together, we show that dsRID provides an effective approach to capture global dsRNA profiles using long-read RNA-seq data.Availability and implementationSoftware implementation of dsRID, and genomic coordinates of regions predicted by dsRID in all samples are available at the GitHub repository: https://github.com/gxiaolab/dsRID.

The hydrodynamic performance of a barge-type floating offshore wind turbine (FOWT) with a moonpool is studied in frequency domain with reference to the Ideol-Floatgen design. The correction of the viscous damping of the moonpool is considered. First, the resonance modes of the moonpool are analyzed. Then, the hydrodynamic coefficients of the FOWT under regular waves and the motion responses under irregular waves are investigated. Finally, the safety of the FOWT is verified with respect to the DNV standards. The results show that the dynamic pitch and nacelle acceleration of the barge-type FOWT meet the safety requirements under both operating and survival conditions. The investigation of the coupling effects of the platform motion and the moonpool resonance shows that the motion of the platform will cause the shift of the piston mode frequency of the moonpool and the reduction of the piston mode response amplitude, the frequency of the sloshing mode is basically unaffected, but the response amplitude of the first-order sloshing mode is increased. The motion responses of the barge-type FOWT with and without the moonpool are compared. It is found that the moonpool can reduce the motion response of the FOWT, and improve the overall hydrodynamic performance of the FOWT. The platform length, moonpool length and platform draught are parametrically analyzed. Surge, heave, pitch response RMS values and the nacelle acceleration response RMS value are used as the indicators of comparison. It is found that the increase of the platform length could effectively reduce the four response RMS values of the FOWT under both operating and survival conditions, the increase of the moonpool length will reduce the four response RMS values of the FOWT under the operating condition, and the increase of the platform draught could significantly reduce the four response RMS values of the FOWT under the survival condition, the heave and pitch response RMS values increase with the augmentation of the draught under the operating condition.

Abstract Background To explore the associations between anxiety and depression symptoms and academic burnout among children and adolescents in China, and to examine the role of resilience and self-efficacy in addressing academic burnout. Methods A total of 2,070 students in grades 4–8 were recruited from two primary and three middle schools in Shanghai, completed the Elementary School Student Burnout Scale (ESSBS), the Multidimensional Anxiety Scale for Children-Chinese (MASC-C), the Center for Epidemiological Studies Depression Scale (CES-D), the Connor-Davidson Resilience Scale (CD-RISC), and the General Self-Efficacy Scale (GSES), with 95.04% effective response rate. Multivariable regression analyses examining the associations between anxiety / depression symptoms and academic burnout (as well as the associations between resilience / self-efficacy and academic burnout) were performed using STATA 16.0 and SmartPLS 3.0. Results Anxiety symptoms (β = 0.124, p

To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study. A transcriptome-wide association study highlights the Trpv2 ion channel as a key locus for cocaine self-administration as well as identifying 17 additional genes, including Arhgef26, Slc18b1, and Slco5a1. We find numerous instances where alternate splice site selection or RNA editing altered transcript abundance. Our work emphasizes the importance of Trpv2, an ionotropic cannabinoid receptor, for the response to cocaine.

Abstract Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R tdTomato mice to lethally irradiated Ackr1 −/− mice (Ackr1 −/− chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Abstract Background The popularity of e-cigarettes is on the rise among current cigarette users. Therefore, there are concerns about their health implications. This study examined the impact of health-related social media use on e-cigarette use among current cigarette users. It assesses the mediating influence of online anti-tobacco messages and the moderating role of the harm perception of e-cigarettes. Methods This study was focused on 563 current cigarette users from the 2022 Health Information National Trends Survey (HINTS). Three tasks were performed: (1) assessing the direct and indirect impacts of health-related social media use on e-cigarette use among current cigarette users, (2) exploring the mediating role of exposure to online anti-tobacco messages, and (3) examining the moderating influence of e-cigarette harm perception on the path from anti-tobacco messages to e-cigarette use. Results Health-related social media use was positively associated with current cigarette users’ e-cigarette use directly (bp = 0.183, p

Polyether amines are versatile compounds characterized by a flexible structure, consisting of polyoxypropylene and polyoxyethylene as the backbone, with amine groups at each end. They have widespread applications in various industrial processes and daily life. Despite their versatility, the utilization of polyether amines as base catalysts is rare. In this study, one kind of three-arm polyether amine 1 was employed as an environmentally friendly, cost-effective catalyst for the aerobic oxidation of thiophenols, leading to the synthesis of disulfides. The oxidative coupling of thiols serves as a fundamental pathway for the production of disulfides, which are vital in both chemical and biological processes. In contrast to known methods for thiol oxidation, this polyether amine-based catalytic process eliminates the need for expensive stoichiometric oxidants and minimizes the formation of over-oxidized by-products. Using a mere 0.5 mol % of the polyether amine 1 as the catalyst, a remarkable > 96% yield was achieved for all 16 tested substrates, encompassing a diverse range of functional groups, under the catalytic aerobic oxidation conditions. Furthermore, it is noteworthy that over 90% of the polyether amine catalyst can be efficiently recovered for reuse without loss of activity, making this a sustainable and cost-effective catalytic approach.

Highlights The anti-adhesion effect of polylactic acid (PLA) membrane with diamond-like carbon (DLC) depositing is 44.72%, enhanced by 23.11% compared to PLA. DLC deposited on PLA membranes has been shown to effectively reduce the levels of reactive oxygen species, leading to a decrease in the expression of pro-inflammatory cytokines within peritendinous adhesion tissue. DLC decelerates PLA biodegradation and lactic production, which reduces the number of CD68+CD206+ macrophages within peritendinous adhesion tissue.

Abstract Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3′ UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors. Further, we introduce untranslated tumor mutational burden (uTMB), a metric reflecting the amount of somatic functional MapUTR variants of a tumor and show its potential in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), demonstrating their cancer-driving potential. Our study elucidates the function of tens of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.

RNA editing, the endogenous modification of nucleic acids, is known to be altered in genes with important neurological function in schizophrenia (SCZ). However, the global profile and molecular functions of disease-associated RNA editing remain unclear. Here, we analyzed RNA editing in postmortem brains of four SCZ cohorts and uncovered a significant and reproducible trend of hypoediting in patients of European descent. We report a set of SCZ-associated editing sites via WGCNA analysis, shared across cohorts. Using massively parallel reporter assays and bioinformatic analyses, we observed that differential 3' untranslated region (3'UTR) editing sites affecting host gene expression were enriched for mitochondrial processes. Furthermore, we characterized the impact of two recoding sites in the mitofusin 1 (MFN1) gene and showed their functional relevance to mitochondrial fusion and cellular apoptosis. Our study reveals a global reduction of editing in SCZ and a compelling link between editing and mitochondrial function in the disease.

Abstract DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non‐homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer. It is shown that USP25 deubiquitinates SHLD2 at the K64 site, which enhances its binding with REV7 and promotes NHEJ. Furthermore, USP25 deficiency impairs NHEJ‐mediated DNA repair and reduces class switch recombination (CSR) in USP25‐deficient mice. USP25 is overexpressed in a subset of colon cancers. Depletion of USP25 sensitizes colon cancer cells to IR, 5‐Fu, and cisplatin. TRIM25 is also identified, an E3 ligase, as the enzyme responsible for degrading USP25. Downregulation of TRIM25 leads to an increase in USP25 levels, which in turn induces chemoresistance in colon cancer cells. Finally, a peptide that disrupts the USP25‐SHLD2 interaction is successfully identified, impairing NHEJ and increasing sensitivity to chemotherapy in PDX model. Overall, these findings reveal USP25 as a critical effector of SHLD2 in regulating the NHEJ repair pathway and suggest its potential as a therapeutic target for cancer therapy.

Prolonged high temperature is a critical environmental factor contributing to the mass mortality of clams in summer. We investigated the growth and development of Cyclina sinensis cultured at different temperatures (25, 28, 31, and 34 °C) and their physiological and biochemical responses following a long period of exposure. The mortality rates at 31 °C and 34 °C were significantly higher than at 25 °C and 28 °C after 48 d (P < 0.05). The overall survival rates at 25 °C and 28 °C did not differ significantly from the control group (at natural seawater temperature), but were significantly lower at 31 °C and 34 °C (P < 0.05). The growth parameters of C. sinensis in all of the experimental groups were significantly higher than in the control group (P < 0.05), with the highest specific growth rate at 28 °C. The shell to soft tissue ratio was greatly increased in the 31 °C and 34 °C groups and was significantly higher than in the other groups after 32 d (P < 0.05). The condition factor at 28 °C was significantly higher than in the other groups (P < 0.05), and started to decline after 32 days at 31 °C and 34 °C. The hepatopancreatic and gonadotropic indexes were significantly lower at 31 °C and 34 °C than in the control group (P < 0.05). Appropriate temperature rises increased the filtration rate and ingestion rate but these were clearly inhibited at 31 °C and 34 °C. The activities of superoxide dismutase, catalase, acid phosphatase (ACP), and lysozyme (LZM) were significantly reduced at 31 °C and 34 °C (P < 0.05). The activities of ACP, LZM, amylase, and the proteases were significantly increased at 28 °C (P < 0.05). Our study showed that high temperatures accelerate the growth of shells but inhibit the growth of soft tissues, negatively affecting the development, physiology, and biochemistry of C. sinensis. Cyclina sinensis demonstrates better overall performance at 28 °C, but aquaculture production would be severely affected if the temperature reaches, or exceeds 31 °C.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

RNA editing modifies single nucleotides of RNAs, regulating primary protein structure and protein abundance. In recent years, the diversity of proteins and complexity of gene regulation associated with RNA editing dysregulation has been increasingly appreciated in oncology. Large-scale shifts in editing have been observed in bulk tumors across various cancer types. However, RNA editing in single cells and individual cell types within tumors has not been explored. By profiling editing in single cells from lung adenocarcinoma biopsies, we found that the increased editing trend of bulk lung tumors was unique to cancer cells. Elevated editing levels were observed in cancer cells resistant to targeted therapy, and editing sites associated with drug response were enriched. Consistent with the regulation of antiviral pathways by RNA editing, higher editing levels in cancer cells were associated with reduced antitumor innate immune response, especially levels of natural killer cell infiltration. In addition, the level of RNA editing in cancer cells was positively associated with somatic point mutation burden. This observation motivated the definition of a new metric, RNA editing load, reflecting the amount of RNA mutations created by RNA editing. Importantly, in lung cancer, RNA editing load was a stronger predictor of patient survival than DNA mutations. This study provides the first single cell dissection of editing in cancer and highlights the significance of RNA editing load in cancer prognosis.SignificanceRNA editing analysis in single lung adenocarcinoma cells uncovers RNA mutations that correlate with tumor mutation burden and cancer innate immunity and reveals the amount of RNA mutations that strongly predicts patient survival. See related commentary by Luo and Liang, p. 351.

Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which is significantly under-explored. Here, we present an in-depth study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and read biases. Applied to PacBio RNA-seq data, L-GIREMI affords a high accuracy in RNA editing identification. Additionally, our analysis uncovered novel insights about RNA editing occurrences in single molecules and double-stranded RNA structures. L-GIREMI provides a valuable means to study nucleotide variants in long-read RNA-seq.

The zebra finch (Taeniopygia guttata), a representative oscine songbird species, has been widely studied to investigate behavioral neuroscience, most notably the neurobiological basis of vocal learning, a rare trait shared in only a few animal groups including humans. In 2019, an updated zebra finch genome annotation (bTaeGut1_v1.p) was released from the Ensembl database and is substantially more comprehensive than the first version published in 2010. In this study, we utilized the publicly available RNA-seq data generated from Illumina-based short-reads and PacBio single-molecule real-time (SMRT) long-reads to assess the bird transcriptome. To analyze the high-throughput RNA-seq data, we adopted a hybrid bioinformatic approach combining short and long-read pipelines. From our analysis, we added 220 novel genes and 8,134 transcript variants to the Ensembl annotation, and predicted a new proteome based on the refined annotation. We further validated 18 different novel proteins by using mass-spectrometry data generated from zebra finch caudal telencephalon tissue. Our results provide additional resources for future studies of zebra finches utilizing this improved bird genome annotation and proteome.

ObjectiveThis study aimed to compare enhanced depth imaging optical coherence tomography (EDI-OCT) features of exudative retinal detachment (ERD) type and optic disc (OD) swelling type Vogt–Koyanagi–Harada (VKH) disease.MethodsHospitalized VKH patients were retrospectively reviewed and classified into the ERD type and the OD swelling type. The EDI-OCT features were then analyzed.ResultsThe study included 32 ERD type and 15 OD swelling type VKH patients at the acute uveitis stage. The interval between the onset of ocular symptoms and the start of treatment in OD swelling type VKH disease was significantly longer compared to the ERD type (p < 0.001). A fuzzy or lost pattern of the choroidal vasculature was observed in 100% of VKH patients of both types. Moreover, high frequencies (greater than or equal to 50%) of fluctuations in the internal limiting membrane, interdigitation zone disruption, ERD, retinal pigment epithelium (RPE) folds, and ellipsoid zone disruption were observed in both types. Patients with OD swelling type VKH disease exhibited higher frequencies of OD swelling and hyperreflective substances above the RPE (p < 0.001 and p = 0.003, respectively), with lower frequencies of ERD and bacillary layer detachment (p = 0.012 and p < 0.001, respectively). At the convalescence stage, changes in the EDI-OCT images of 10 ERD type and 5 OD swelling type VKH patients were analyzed. The frequencies of the OCT features decreased with similar trends in both types of VKH disease.ConclusionAlthough ERD type and OD swelling type VKH disease have their own unique characteristics, they share common EDI-OCT features. The Fuzzy or lost pattern of the choroidal vasculature that indicates choroidal inflammation may serve as a diagnostic aid for VKH disease, especially for the OD swelling type and the early-stage ERD type.

BackgroundNeglect is a common form of abuse, and long-term care facilities record higher incidences of this abuse. Given that older adult care workers are the main workforce in these facilities, their neglectful behavior requires public health attention. Internal individual characteristics can lead to older adult abuse, and managing workers who abuse older adults may require various methods. This study aimed to identify the profiles of neglect among older adult care workers in long-term care facilities and explore the influencing factors of neglect.MethodsIn this cross-sectional study, a convenience sample of older adult care workers from 15 long-term care facilities in Shandong Province (N = 421) completed a questionnaire on the characteristics associated with neglect. Latent profile analysis was used to identify distinct neglect profiles and promote the understanding of individual characteristics associated with varying levels of neglect. One-way analysis of variance and multivariate logistic regression analyses were used to examine the population characteristic differences.ResultsOlder adult care workers exhibited three neglect profiles, namely, the “low-risk group,” “medium-risk group,” and “high-risk group.” Males, participants with no employment qualification certificate, and those who did not attend regular training represented the majority of those in the “high-risk group.” Participants with a monthly income of more than ¥ 4,000 and nursing 1–2 older adults simultaneously represented the majority of those in the “low-risk group.”ConclusionLong-term care facility administrators should tailor interventions to individual care worker profiles to reduce neglect behaviors and improve care levels.

PODXL, a protein that is dysregulated in multiple cancers, plays an important role in promoting cancer metastasis. In this study, we report that RNA editing promotes the inclusion of a PODXL alternative exon. The resulting edited PODXL long isoform is more prone to protease digestion and has the strongest effects on reducing cell migration and cisplatin chemoresistance among the three PODXL isoforms (short, unedited long, and edited long isoforms). Importantly, the editing level of the PODXL recoding site and the inclusion level of the PODXL alternative exon are strongly associated with overall patient survival in Kidney Renal Clear Cell Carcinoma (KIRC). Supported by significant enrichment of exonic RNA editing sites in alternatively spliced exons, we hypothesize that exonic RNA editing sites may enhance proteomic diversity through alternative splicing, in addition to amino acid changes, a previously under-appreciated aspect of RNA editing function.

Objective The Prydz Bay belt in East Antarctica recorded two significant tectono-thermal events, the Grenvillian event and the Pan-African event, which are considered to be closely related to the evolution of the Rodinia and Gondwana supercontinents. However, the geological history and the tectonic nature of the two events remain controversial. Methods Mineralogical and petrological analyses, phase equilibria modelling and zircon geochronology are combined to investigate the spinel−cordierite granulite from the Mirror Peninsula in order to better understand the tectono-thermal history of the Prydz Bay belt. Results The spinel−cordierite granulite contains different stages of mineral assemblages. The major stage of mineral assemblage involves cordierite, spinel, biotite, sillimanite, K-feldspar and minor garnet and ilmenite. The later stage of mineral assemblage is indicated by the emergence of magnetite as the increasing volumes of biotite and cordierite. Minor garnet and corundum are locally preserved, implying the mineral reaction ‘g+cor→sp+sill’ and more garnet and corundum in the peak stage. The garnet grains consist of 70%−72% almandine, 20%−22% pyrope, ~4% grossularite and ~4% spessartine. The XFe (Fe2+/(Fe2++Mg2+)) of representative garnet grains ranges from 0.77 to 0.80. The spinel exhibits an XFe range from 0.80 to 0.86. Different cordierite grains have similar compositions with Al of 3.89−3.93 a.p.f.u (atoms per formula unit) and XFe of 0.32−0.36. Biotite has high TiO2 (4.13%−5.23%) and Ti (0.23−0.30 a.p.f.u). K-feldspar grains consist of 78%−85% orthoclase, 15%−23% albite and ~1% anorthite. Based on the mineral compositions and phase equilibrium modelling, the pressure−temperature (P−T) conditions of the major stage of mineral assemblage are constrained to 870−910 °C and 0.64−0.69 GPa, followed by later retrogression to 810−820°C and 0.49−0.53 GPa. A peak stage with higher P−T conditions (T>910 ℃, P>0.69 GPa) can be inferred based on the relict peak minerals and characteristic mineral compositions (e.g. Ti in biotite). Zircon grains commonly show core-mantle-rim structures in cathodoluminescence (CL) images. The LA−ICP−MS zircon U−Pb dating analyses reveal a wide age range from 613±7 Ma to 877±9 Ma (except a maximum of 916±11 Ma) for the cores. The zircon bright rims yield a weighted mean age of 526±8 Ma with a wide range of Th/U (0.06−1.23), mostly higher than 0.1. Conclusion Based on the results, a few conclusions can be drawn: (1) The spinel−cordierite granulite recorded medium−low pressure/high-ultrahigh temperature metamorphism with a clockwise P−T evolution path and high dT/dP. (2) The results of zircon geochronological analysis show that zircon cores mainly record U−Pb ages in the range of 800~600 Ma, younger than typical ages of Grenvillian events, which may reflect younger inherited zircon cores or significant isotopic resetting. (3) The age of ~530 Ma of zircon rims is interpreted to represent the post-peak cooling stage of the Pan-African tectono-thermal event. [Significance] This study examined the P−T conditions and the zircon ages of the spinel−cordierite granulite in the Mirror Peninsula. In combination with previous results, the P−T−t path constructed for the spinel−cordierite granulite provides new constraints on the evolution of the Prydz Bay belt during the Pan-African period.

Abstract Background The prevalence of caregiving in the United States has increased from 16.6% to 19.2% during the period between 2015 and 2020. Caregivers play a critical public health role post-pandemic and as the population ages. However, caregiving can be detrimental to the health of caregivers. Many studies have shown that communication and connectedness are effective forms of health intervention for caregivers, but how this can be achieved requires further investigation. Objective This study aimed to investigate the indirect effect of caregiving on problems of alcohol drinking through psychological distress. Moreover, this study aimed to provide initial evidence of the distinct effects of online and offline communication and connectedness on caregivers' well-being. Methods The predictions were evaluated by examining responses to the Health Information National Trends Survey 2020 (n = 3,865). A mediation analysis was conducted to test the mediating effect of psychological distress on the association between caregiving and alcohol drinking. A second-level moderation analysis was performed. The online communication and connectedness, social media use for health, and the offline type, marital or romantic partnership, were tested as moderators to lessen the psychological distress of caregiving. Results A competitive mediation was identified. We found a positive indirect effect from caregiving to alcohol drinking mediated by psychological distress (b p = .0017, p

Abstract To further explore the mechanism of “the longer storage time, the better bioactivity” of aged Guang Chenpi, the dry pericarp of Citrus reticulata ‘Chachi’ (CRC), a series of activity assessments were performed on spleen deficiency mice. The constituents in CRC with different storage years were analyzed by LC‐Q‐Orbitrap/MS. A total of 53 compounds were identified, and CRC stored for more than 5 years showed higher flavonoid content, especially that of polymethoxyflavones. Anti‐spleen deficiency bioactivity analysis among various CRC with different storage years showed aged CRC (stored for more than 3 years) could significantly alleviate fatigue and depression behaviors much better, increase D‐xylose and gastrin secretion, and upregulate the expression of the linking protein occludin in the colon walls. Results from 16S rDNA sequencing showed that aged CRC could downregulate the abundance of Enterococcus, Gemmata, Citrobacter, Escherichia_Shigella, and Klebsiella, which were significantly overrepresented in the model group. Bacteroides, Muribaculum, Alloprevotella, Paraprevotella, Alistipes, Eisenbergiella, and Colidextribacter were downregulated in the model group but enriched in the CRC groups. At last, the spectrum‐effect relationship analysis indicated that flavonoids such as citrusin III, homoeriodictyol, hesperidin, nobiletin, and isosinensetin in aged CRC showed the highest correlation with better activity in ameliorating spleen deficiency by regulating gut microbiota. Flavonoids contribute most to discriminating aged CRC and could disclose the basis of “the longer storage time, the better bioactivity” of aged Guang Chenpi.

Abstract Background Prior research has investigated the influence of social media on e-cigarette use among adolescents, predominantly through the display of e-cigarette content and advertisements. However, the psychological mechanism underlying this relationship remains underexplored. This study aims to address the mediating effect of youths internalizing problems and elucidate the moderating effect of academic performance from a longitudinal perspective. Methods Panel data from the Public Assessment of Tobacco and Health (PATH) Study Waves 3–5 (2015–2019) were utilized in this study. The sample consisted of 3,975 youths between the ages of 12 and 17 years old. A moderated mediation model was utilized for analyses. Results Adolescents using social media more frequently in Wave 3 reported higher odds of internalizing problems in Wave 4 (bp = 0.061, p

Mud crab reovirus (MCRV) is one of the most fatal pathogens of the mud crab Scylla paramamonsain. The outbreak and epidemic of MCRV has seriously affected the healthy development of the mud crab aquaculture industry. To limit MCRV transmission from breeding crabs to larva, we attempt to establish a more sensitive and practical diagnostic method for screening MCRV-free crabs. The primers of the present diagnostic methods for MCRV are based on the VP1 gene (MCRV RNA polymerase gene), and the low expression level of this gene limits the sensitivity of the diagnostic method. Therefore, it is necessary to select the target gene with the highest expression level for the detection primer to improve the sensitivity of the diagnostic method. In addition, the current diagnostic methods require gill samples for virus detection, which requires killing the mud crabs before sampling. This sampling method is obviously not suitable for screening MCRV-free breeding crabs. Therefore, it is necessary to develop a less invasive sampling method for breeding crabs. In this study, a SYBR Green fluorescent quantitative diagnostic method was developed to screen MCRV-free breeding crabs. To improve the sensitivity of the detection, we initially analyzed the relative load of MCRV in the main tissues of infected mud crabs. The viral load in the hemolymph was the highest of all the tissues. The expression levels of 13 putative genes of MCRV were detected in the hemolymph. The relative expression level of the VP11 gene was the highest. Finally, specific primers were designed based on the conserved region of the VP11 gene sequence to establish a SYBR Green qRT-PCR (quantitative reverse-transcription PCR) detection method to accurately detect 50 copies/µL of viral nucleic acid in a sample. Considering the advantages of tissue and target gene selection, the sensitivity of this method should be significantly higher than that of preexisting detection methods. This diagnostic method is very specific for MCRV and no specific amplification was observed using nucleic acid samples containing 5 different kinds of common crustacean pathogens (MCDV, WSSV, DIV1, EHP, and Vibrio parahemolyticus). Compared to other methods of extracting RNA by killing and grinding the gill tissues of crabs, we can select MCRV-free crabs by sampling very small amounts of hemolymph (as low as 20 µL). All of the healthy crabs screened by this method were able to hold eggs that hatched normally. To test the effectiveness of this method, 22 breeding crabs and 20 commercial crabs were screened for MCRV. The positive rates were 54.55% and 85.00%, respectively. In addition, we analyzed the proliferation of MCRV in the mud crabs, and found that MCRV proliferates exponentially in the early stage, then enters a plateau phase, and no crabs died during the infection period of seven days. In conclusion, this study established a highly-sensitive and practical detection method for MCRV in breeding crabs, which can meet the requirements for MCRV-free breeding crab screening with low damage to the breeders. We also investigated the pathogenic infection mechanisms.

Abstract Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS’s anti-CC effects, and SS’s inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.

The incorporation of antioxidants in food products is essential to prevent or delay deterioration, thereby addressing food spoilage. Thiol compounds, recognized for their natural antioxidant properties, are widely used in various foods; however, their antioxidant capacity is often limited. This study investigates the potential enhancement of thiol antioxidant capacity through the addition of a soluble, low-toxic inorganic Sm-cluster. Our findings demonstrate that the Sm-cluster significantly bolsters the antioxidant efficacy of thiol compounds. We explored, for the first time, the in vitro antioxidant activities of an Sm-oxo/hydroxy cluster combined with a cysteine derivative for potential food applications. The composition exhibited a robust inhibition of aromatic aldehyde flavor compound oxidation and displayed strong, dose-dependent DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging activity. Notably, the antioxidant activity of the Sm-cluster/cysteine derivative was further enhanced under strong visible light conditions, which typically increased the likelihood of oxidation. These results suggest that the combination of inorganic cluster and thiol compounds presents a promising natural alternative to traditional antioxidants in the food industry.

Optimizing lanthanide catalyst performance with organic ligands often encounters significant challenges, including susceptibility to water or oxygen and complex synthesis pathways. To address these issues, our research focuses on developing inorganic lanthanide clusters with enhanced stability and functionality. In this study, we introduce the [Sm6O(OH)8(H2O)24]I8(H2O)8 cluster (Sm-OC) as a sustainable and efficient catalyst for the aerobic oxidation of thiols under heating conditions. The Sm-OC catalyst demonstrated remarkable stability, outstanding recyclability, and excellent chemoselectivity across a diverse range of functional groups in 38 different tests. Notably, it enables efficient unsymmetrical disulfide synthesis and prevents the formation of over-oxidized by-products, highlighting its superior performance. This Sm-OC catalyst provides a practical and robust tool for the precise construction of versatile disulfides, thus establishing a template for the broader use of lanthanide clusters in organic synthesis.

A sustainable bioeconomy in agricultural and agro-industrial production must inevitably involve the sustainable use of agricultural residues through zero-waste processes. Corn cob is considered crucial agricultural waste as 278 and 293 million tons were produced worldwide in 2022 and 2023, respectively. Corn cob hydrolysates, which are abundant in xylose and glucose, could be efficiently utilized for xylitol and ethanol production through the cultivation of recycling the yeast strain Candida magnoliae TISTR 5664 in the single-stage and sequential-stage co-production of these products. The statistically significant maxima (p ≤ 0.05) ethanol concentrations were improved by 7.8% (49.9–51.7 g/L or 91.3–95.6% of the theoretical) from the single stage of ethanol production employing recycled cells and 9.9% (50.9–54.1 g/L or 77.3–83.9% of the theoretical) from the second step of sequential-stage co-production using recycled cells without xylitol accumulation. Conversely, the single-stage xylitol production utilizing recycled cells under microaerobic conditions resulted in a statistically significant lower (p ≤ 0.05) xylitol concentration by two folds relative to the control, while ethanol concentration was elevated by almost double. The statistically significant maximum (p ≤ 0.05) xylitol was achieved at 25.9 g/L (58.6% of the theoretical) when sequential-stage co-production was initiated in the first step with fresh inoculum only and not recycled cells. The sequential-stage co-production of xylitol and ethanol presented the potential for statistically significant improvement (p ≤ 0.05) of both xylitol and ethanol production processes.