Metabolomics efficiently discriminates monozygotic twins in peripheral blood.

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine.

Identification of attractants for adult Spodoptera litura based on the interaction between odorant-binding protein 34 and host volatiles.

Odorant-binding proteins (OBPs) play key roles in host plant location by insects, and can accordingly serve as important targets for the development of attractants. In this study, we detected the high expression of SlitOBP34 in male antennae of Spodoptera litura. Subsequently, the fluorescence competitive binding experiments displayed that the SlitOBP34 protein has binding affinity for different ligands. Then, protein-ligand interaction analyses found the presence of six amino acid residues may serve as key recognition sites. Further electroantennographic and biobehavioral assessments revealed that the electrophysiological responses of male antennae were evoked in response to stimulation with the six identified host volatiles, and that these volatiles attracted male moths to varying extents. Notably, low concentrations of benzaldehyde, 1-hexanol, and cis-3-hexenyl acetate were found to have significant attractant effects on male moths, thereby identifying these three host volatiles as potential candidates for the development of male attractants. These findings advance our current understanding of the olfactory-encoded mechanisms of host plants selection in S. litura and have enabled us to develop novel adult attractants for controlling the pest in the future.

Binding properties of chemosensory protein 4 in Riptortus pedestris to aggregation pheromones.

In insects, chemosensory proteins (CSPs) play an important role in the perception of the external environment and have been widely used for protein-binding characterization. Riptortus pedestris has received increased attention as a potential cause of soybean staygreen syndrome in recent years. In this study, we found that RpedCSP4 expression in the antennae of adult R. pedestris increased with age, with no significant difference in expression level observed between males and females, as determined through quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, we investigated the ability of RpedCSP4 to bind various ligands (five aggregated pheromone components and 13 soybean volatiles) using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP4 binds to three aggregated pheromone components of R. pedestris, namely, ((E)-2-hexenyl (Z)-3-hexenoate (E2Z3), (E)-2-hexenyl (E)-2-hexenoate (E2E2), and (E)-2-hexenyl hexenoate (E2HH)), and that its binding capacities are most stable under acidic condition. Finally, the structure and protein-ligand interactions of RpedCSP4 were further analyzed via homology modeling, molecular docking, and targeted mutagenesis experiments. The L29A mutant exhibited a loss of binding ability to these three aggregated pheromone components. Our results show that the olfactory function of RpedCSP4 provides new insights into the binding mechanism of RpedCSPs to aggregation pheromones and contributes to discover new target candidates that will provide a theoretical basis for future population control of R. pedestris.

Barriers and facilitators in implementing early essential newborn care of well-born babies in low- and middle-income countries: A mixed-method systematic review.

BACKGROUND: Evidences have demonstrated the effectiveness of early essential newborn care. However, the implementation of early essential newborn care is suboptimal. The aim is to identify and synthesise the barriers and facilitators impacting the implementation of early essential newborn care in low- and middle-income countries. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, CNKI, Wan Fang Data, SinoMed and Google Scholar. METHODS: Two authors independently screened, performed quality assessment using the Mixed Methods Appraisal Tool and extracted data. This review includes papers that reported the barriers and facilitators of implementing early essential newborn care in low- and middle-income countries from the view of healthcare providers. Barriers and facilitators were coded according to the consolidated framework for implementation research in a deductive way and then been inducted into five common themes. This review followed synthesis without meta-analysis reporting guideline. RESULTS: A total of 28 studies were included. Five inductive common themes influencing implementing early essential newborn care in low- and middle-income countries were system-level healthcare factors, healthcare providers' knowledge and beliefs, the requirements of mothers or families, adapting to routine practice and the working climate of organisation. CONCLUSION: The factors were from system level, facility level and individual level and were inducted into five themes. Based on this review, decision-makers could tailor implementing strategies to narrow the gap between the evidence and implementation. RELEVANCE TO CLINICAL PRACTICE: The study offers guidance for health professionals to identify barriers and facilitators in implementing early essential newborn care and make tailored strategies when implementing early essential newborn care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contributions.

Effects of Perineal Warm Compresses during the Second Stage of Labor on Reducing Perineal Trauma and Relieving Postpartum Perineal Pain in Primiparous Women: A Systematic Review and Meta-Analyses.

Non-pharmaceutical midwifery techniques, including perineal warm compresses, to improve maternal outcomes remain controversial. The aims of this study are to assess the effects of perineal warm compresses on reducing perineal trauma and postpartum perineal pain relief. This systematic review included randomized controlled trials (RCTs). We searched seven bibliographic databases, three RCT register websites, and two dissertation databases for publications from inception to 15 March 2023. Chinese and English publications were included. Two independent reviewers conducted the risk of bias assessment, data extraction, and the evaluation of the certainty of the evidence utilizing the Cochrane risk of bias 2.0 assessment criteria, the Review Manager 5.4, and the online GRADEpro tool, respectively. Seven RCTs involving 1362 primiparous women were included. The combined results demonstrated a statistically significant reduction in the second-, third- and/or fourth- degree perineal lacerations, the incidence of episiotomy, and the relief of the short-term perineal pain postpartum (within two days). There was a potential favorable effect on improving the integrity of the perineum. However, the results did not show a statistically significant supportive effect on reducing first-degree perineal lacerations and the rate of perineal lacerations requiring sutures. In summary, perineal warm compresses effectively reduced the second-, third-/or fourth-degree perineal trauma and decreased the short-term perineal pain after birth.

Topless-related 2 conferred cadmium accumulation in wheat.

Wheat is a vital food crop that faces threats from various abiotic and biotic stresses. Understanding the molecular mechanism of cadmium (Cd) resistance can provide valuable insights into the tolerance of wheat. Plant proteins known as Topless/Topless-Related (TPL/TPR) play a role in growth, development, defense regulation, and stress response. In this study, we identified TaTPR2 as being induced by Cd stress treatment. Upon Cd treatment, wheat plants overexpressing TaTPR2 exhibited better growth compared to wild-type (WT) plants. Moreover, the transgenic lines showed reduced accumulation of reactive oxygen species (ROS), along with significantly higher activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) compared to WT plants. Additionally, the transgenic lines exhibited lower levels of malondialdehyde (MDA) and electrolyte leakage compared to WT plants. Further analysis revealed that TabHLH41 directly binds to the E-box motif of the TaTPR2 promoter and positively regulates its expression. Overall, the overexpression of TaTPR2 in transgenic wheat resulted in reduced accumulation of Cd and ROS. These findings highlight the significance of the TabHLH41-TaTPR2 pathway as a crucial response to Cd stress in wheat.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors.

BACKGROUND: The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. AIM: To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. METHODS: Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. RESULTS: Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. CONCLUSION: Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

A chromosome-level genome assembly of the forestry pest Coronaproctus castanopsis.

As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.

Association of histone modification with the development of schizophrenia.

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

Copper-Catalyzed Directed Hydroindolation/Annulation Sequence of Alkynes with Indoles via Copper Carbenes.

Described herein is an efficient copper-catalyzed tandem alkyne indolylcupration-initiated 1,2-indole migration/6π-electrocyclic reaction of allene-ynamides with indoles by the in situ-generated metal carbenes. This method allows the efficient synthesis of valuable indole-fused spirobenzo[f]indole-cyclohexanes with high regio- and stereoselectivity. In addition, this reaction affords rapid access to the functionalized spirobenzo[f]indole-cyclohexanes in the absence of indoles by a presumable 5-exo-dig cyclization/Friedel-Crafts alkylation via copper-containing all-carbon 1,4-dipoles.

Copper(I)-Catalyzed Indolyl Ynamide Oxidation/Dearomatization: Divergent and Regioselective Synthesis of Valuable Indoline Scaffolds.

A highly convenient copper(I)-catalyzed oxidation-initiated cyclopropanation of indolyl ynamide for the rapid construction of indole-fused cyclopropane-lactams is described, which represents, to the best of our knowledge, the first non-noble-metal-catalyzed indolyl ynamide oxidation/dearomatization by the in situ generated α-oxo copper carbenes. Compared to hydrazone and diazo, the use of alkynes as carbene precursors allows cyclopropanation to occur under a safe and convenient pathway. Moreover, this transformation can lead to the divergent synthesis of pentacyclic spiroindolines involving the reversal of ynamide regioselectivity by engineering substrate structures.

Chronic restraint stress induces depression-like behaviors and alterations in the afferent projections of medial prefrontal cortex from multiple brain regions in mice.

INTRODUCTION: The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated. METHODS: In the present study, C57BL/6 J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively. RESULTS: The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala. CONCLUSION: Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.

Gustatory Receptor 206 Participates in the Foraging Behavior of Larvae of Polyphagous Pest Spodoptera litura.

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection.

Background: Tousled-like kinase 2 (TLK2) is integral to DNA repair, replication, and cell cycle regulation, crucial for maintaining genome stability and integrity. However, the expression and prognostic value of TLK2 in hepatitis B viral (HBV) -related hepatocellular carcinoma (HCC) remains unclear. Methods: We examined TLK2 expression and prognostic implications in pan-cancer by using diverse databases. Subsequently, TLK2 expression in HBV-related HCC tissues and adjacent tissues was assessed using quantitative real-time PCR and immunohistochemistry. The prognostic value of TLK2 was assessed through ROC curves, time-dependent ROC curves, Cox regression, Kaplan-Meier curve, and decision curve analysis. Additionally, analyses of immune infiltration, protein-protein interactions, key molecules of tumor-related signaling pathways, molecular subtypes, and TLK2-associated differentially expressed genes (DEGs) were conducted, along with GO/KEGG and GSEA enrichment analyses. Results: TLK2 expression was significantly higher in HCC tissues compared to adjacent tissues and correlated with gender, AFP levels, albumin-bilirubin (ALBI) grade, microvascular invasion (MVI), maximum tumor diameter, tumor number, and TNM stage. TLK2 overexpression emerged as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. An integrated OS nomogram model, incorporating TLK2, age, ALBI grade, MVI, and tumor number, displayed enhanced prognostic capability (C-index: 0.765, 95% CI: 0.732-0.798) in predicting OS and has a higher net benefit than the TNM stage. Moreover, TLK2 expression correlated closely with immune cell infiltration and key molecules of signaling pathways. Functional enrichment analyses highlighted significant associations with DNA duplex unwinding, double-strand break repair, DNA replication, cell cycle, E2F targets, G2M checkpoint, and MYC targets V1. Conclusion: TLK2 is notably overexpressed in HBV-related HCC and emerges as a promising prognostic biomarker, necessitating further validation.

Pretreatment Non-Invasive Biomarkers as Predictors to Estimate Portal Vein Tumor Thrombosis (PVTT) Risk and Long-Term Survival in HBV-Related Hepatocellular Carcinoma Patients Without PVTT.

Background: PVTT is a hallmark of advanced hepatocellular carcinoma (HCC). We aim to explore the influence of non-invasive biomarkers on the occurrence of PVTT and develop and validate models for predicting prognosis in HBV-related HCC patients without PVTT. Methods: A total of 1026 HBV-related HCC patients without PVTT were enrolled, with 515 in the training cohort, 216 in the internal validation cohort, and 295 in the external validation cohort. We conducted Cox regression analyses to discern the independent risk factors associated with PVTT events, PFS, and OS, then constructed and validated predictive models. The predictive and discriminatory capabilities of models were assessed using the calibration, time-dependent ROC, and DCA curves. Results: In our study, 136 patients (13.3%) experienced PVTT events during the follow-up period. The Cox regression analysis unveiled that male gender, AAPR ≤0.49, APRI >0.48, extrahepatic metastasis, and multiple tumors were independent risk factors for PVTT. In the training cohort, non-invasive biomarkers (AAR and APRI), AFP, ascites, and tumor-related characteristics (extrahepatic metastasis, tumor diameter, tumor number, and PVTT event) were independent risk factors for both OS and PFS, whereas age and ALBI grade independently correlated with OS. The C-indexes of OS and PFS nomogram models were 0.795 and 0.733 in the training cohort, 0.765 and 0.716 in the internal validation cohort, and 0.780 and 0.722 in the external validation cohort, respectively. Our models demonstrated strong predictive and discriminative abilities in all cohorts and yielded a greater net benefit compared to three traditional staging systems. Conclusion: Non-invasive biomarkers are expected to be reliable predictors for assessing PVTT risk and predicting prognosis among HBV-related HCC patients without PVTT.

Application and outlooks of new minimally-invasive techniques in fetal surgery / 医疗卫生装备

Development and current problems of fetal surgery were introduced. Application and research frontiers of new minimally-invasive techniques were elaborated from the aspects of intraoperative imaging diagnosis and navigation, new-type minimally-invasive instrument,energy therapy and robot technique for diagnosis and treatment.Current bottlenecks and future outlooks of new minimally-invasive techniques in fetal surgery were analyzed. Great clinical potential of new minimally-invasive techniques in fetal surgery was stated.It's pointed out that how to integrate diagnosis and therapy and apply them to real clinical treatment would be the focus of future research.

Recent application and outlooks of fluorescent diagnostic techniques in clinic / 医疗卫生装备

Current problems and demands of intraoperative diagnosis were presented. Basic theories and classification of fluorescent diagnostic techniques were introduced, and the advantages compared with traditional pathology were also analyzed.Current research and application status of fluorescent diagnostic techniques were summarized and analyzed in two aspects:spectroscopy analysis and image analysis,and it was indicated that fluorescent diagnosis was important for research and clinical application.Furthermore,future development directions of fluorescent diagnostic techniques were analyzed,and improving accuracy and combining diagnosis with clinical treatment were growing trends in fluorescent diagnostic techniques.