Hippocampal SorCS2 overexpression represses chronic stress-induced depressive-like behaviors by promoting the BDNF-TrkB system.

BACKGROUND: Emerging data has demonstrated that in mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Thus, it is possible that SorCS2 plays a role in the pathophysiology of depression by regulating the BDNF-TrkB system. METHODS: In the present study, SorCS2 expression in different brain regions [hippocampus, medial prefrontal cortex (mPFC), hypothalamus, amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc)] was thoroughly investigated in the chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression. The changes in depressive-like behaviors, the hippocampal BDNF signaling cascade, and amounts of hippocampal immature neurons were further investigated after SorCS2 overexpression by microinjection of the adenovirus associated virus vector containing the coding sequence of mouse SorCS2 (AAV-SorCS2) into the hippocampus of mice exposed to CSDS or CUMS. RESULTS: It was found that both CSDS and CUMS significantly decreased the protein and mRNA expression of SorCS2 in the hippocampus but not in other brain regions. Chronic stress also notably downregulated the level of hippocampal SorCS2-TrkB binding in mice. In contrast, AAV-based genetic overexpression of hippocampal SorCS2 fully reversed the chronic stress-induced not only depressive-like behaviors but also decreased SorCS2-TrkB binding, BDNF signaling pathway, and amounts of immature neurons in the hippocampus of mice. CONCLUSION: All these results suggest that enhancing the hippocampal SorCS2 expression protects against chronic stress, producing antidepressant-like actions. Hippocampal SorCS2 may participate in depression neurobiology and be a potential antidepressant target. SIGNIFICANCE STATEMENT: Targeting of proteins to distinct subcellular compartments is essential for neuronal activity and modulated by VPS10P domain receptors which include SorCS2. In mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Our study is the first direct evidence preliminarily showing that SorCS2 plays a role in depression neurobiology. It was found that chronic stress induced not only depressive-like behaviors but also decreased SorCS2 expression in the hippocampus. Chronic stress did not affect SorCS2 expression in the mPFC, hypothalamus, amygdala, VTA, or NAc. In contrast, genetic overexpression of hippocampal SorCS2 prevented against chronic stress, producing antidepressant-like actions in mice. Thus, hippocampal SorCS2 is a potential participant underlying depression neurobiology and may be a novel antidepressant target. Our study may also extend the knowledge of the neurotrophic hypothesis of depression.

CD276 Promotes an Inhibitory Tumor Microenvironment in Hepatocellular Carcinoma and is Associated with Poor Prognosis.

Background: CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME). Methods: The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system. Results: CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8+ T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1-derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration. Conclusion: CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.

Conversion of Carbon Dioxide into a Series of CBxOy- Compounds Mediated by LaB3,4O2- Anions: Synergy of the Electron Transfer and Lewis Pair Mechanisms to Construct B-C Bonds.

Converting CO2 into value-added products containing B-C bonds is a great challenge, especially for multiple B-C bonds, which are versatile building blocks for organoborane chemistry. In the condensed phase, the B-C bond is typically formed through transition metal-catalyzed direct borylation of hydrocarbons via C-H bond activation or transition metal-catalyzed insertion of carbenes into B-H bonds. However, excessive amounts of powerful boryl reagents are required, and products containing B-C bonds are complex. Herein, a novel method to construct multiple B-C bonds at room temperature is proposed by the gas-phase reactions of CO2 with LaBmOn- (m = 1-4, n = 1 or 2). Mass spectrometry and density functional theory calculations are applied to investigate these reactions, and a series of new compounds, CB2O2-, CB3O3-, and CB3O2-, which possess B-C bonds, are generated in the reactions of LaB3,4O2- with CO2. When the number of B atoms in the clusters is reduced to 2 or 1, there is only CO-releasing channel, and no CBxOy- compounds are released. Two major factors are responsible for this quite intriguing reactivity: (1) Synergy of electron transfer and boron-boron Lewis acid-base pair mechanisms facilitates the rupture of C═O double bond in CO2. (2) The boron sites in the clusters can efficiently capture the newly formed CO units in the course of reactions, favoring the formation of B-C bonds. This finding may provide fundamental insights into the CO2 transformation driven by clusters containing lanthanide atoms and how to efficiently build B-C bonds under room temperature.

Prenatal endocrine-disrupting chemicals exposure and impact on offspring neurodevelopment: A systematic review and meta-analysis.

PURPOSE: Considering that endocrine disruptors have certain effects on fetal growth, we conducted a systematic review of epidemiological literature to elucidate the correlation between exposure to endocrine-disrupting chemicals during pregnancy and the neurodevelopment of offspring. METHOD: We systematically explored PubMed, Web of Science, and CINAHL databases from inception to April 4, 2023. References from pertinent studies were reviewed, and data regarding the link between maternal prenatal EDC exposure and offspring neurological development were compiled. A domain-based approach was used to evaluate studies of neurodevelopmental effects in children ≤3 years old by two reviewers, including cognition, motor, behavior, language, and non-verbal ability. RESULTS: A comprehensive search yielded 45,373 articles, from which 48 articles, involving 26,005 mother-child pairs, met the criteria and were subsequently included in our analysis. The results revealed that EDC exposure during pregnancy had a significant impact on offspring neurobehavior development, especially in cognition, motor, and language. Our findings indicated adverse associations between prenatal exposure to metals and offspring cognition (before 12 months: ß coefficient: -0.28; 95% CI, -0.50 to -0.06; 1 to 3 years old: ß coefficient: -0.55; 95% CI: -1.08 to -0.02). Furthermore, metals (ß coefficient: -0.71; 95% CI: -1.23 to -0.19) and phthalates (ß coefficient: -0.69; 95% CI: -1.05 to -0.33) exposure exhibited detrimental effects on motor development from1 to 3 years old, while poly-fluoroalkyl substances were linked to the disruption of offspring language development (ß coefficient: -1.01; 95% CI: -1.90 to -0.11) within this timeframe. Additionally, exposure to EDCs during pregnancy had a negative impact on cognition development among girls from 12 to 36 months of age (ß coefficient: -0.53; 95% CI: -1.01 to -0.06). CONCLUSION: Prenatal exposure to EDCs, especially metals, phthalates and, poly-fluoroalkyl substances, was associated with disrupting the development of offspring neurobehavior in the short and long term. Additionally, cognitive development showed gender differences due to prenatal endocrine-disrupting chemicals exposure.

Unveiling the Mechanism of Phenamacril Resistance in F. graminearum: Computational and Experimental Insights into the C423A Mutation in FgMyoI.

Phenamacril (PHA) is a highly selective fungicide for controlling fusarium head blight (FHB) mainly caused by F. graminearum and F. asiaticum. However, the C423A mutation in myosin I of F. graminearum (FgMyoI) leads to natural resistance to PHA. Here, based on the computational approaches and biochemical validation, we elucidate the atomic-level mechanism behind the natural resistance of F. graminearum to the fungicide PHA due to the C423A mutation in FgMyoI. The mutation leads to a rearrangement of pocket residues, resulting in increased size and flexibility of the binding pocket, which impairs the stable binding of PHA. MST experiments confirm that the mutant protein FgMyoIC423A exhibits significantly reduced affinity for PHA compared to wild-type FgMyoI and the nonresistant C423K mutant. This decreased binding affinity likely underlies the development of PHA resistance in F. graminearum. Conversely, the nonresistant C423K mutant retains sensitivity to PHA due to the introduction of a strong hydrogen bond donor, which facilitates stable binding of PHA in the pocket. These findings shed light on the molecular basis of PHA resistance and provide new directions for the creation of new myosin inhibitors.

In Vitro Ciclopirox Glucuronidation in Liver Microsomes from Humans and Various Experimental Animals.

BACKGROUND AND OBJECTIVE: Ciclopirox is a widely used antifungal drug, redisposition of which has drawn increasing attentions due to multiple promising activities. The drug undergoes extensive glucuronidation, which acts as a major obstacle in the ongoing novel application and still remains poorly understood. The current study aims to phenotype ciclopirox glucuronidation pathway and as well to decipher the related species differences. METHODS: Ciclopirox glucuronidation was investigated in liver microsomes from humans (HLM) and various experimental animals. Assays with recombinant uridine diphosphate glucuronosyltransferases (UGTs), enzyme kinetic analyses and selective inhibitors were used to determine the role of individual UGTs in ciclopirox glucuronidation. RESULTS: HLM is highly active in ciclopirox glucuronidation with Michaelis-Menten constant (Km), maximum velocity (Vmax), and intrinsic clearance (CLint) values of 139 µM, 7.89 nmol/min/mg, and 56 µL/min/mg, respectively. UGT1A9 displays by far the highest activity, whereas several other isoforms (UGT1A6, UGT1A7, and UGT1A8) catalyze formation of traced glucuronides. Further kinetic analysis demonstrates that UGT1A9 has a closed Km value (167 µM) to HLM. UGT1A9 selective inhibitor (magnolol) can potently inhibit ciclopirox glucuronidation in HLM with the IC50 value of 0.12 µM. The reaction displays remarkable differences across liver microsomes from mice, rats, cynomolgus monkey, minipig, and beagle dog, with the CLint values in the range of 26-369 µL/min/mg. In addition, ciclopirox glucuronidation activities of experimental animals' liver microsomes were less sensitive to magnolol than that of HLM. CONCLUSIONS: Ciclopirox glucuronidation displays remarkable species differences with UGT1A9 as a dominant contributor in humans. It is suggested that the pharmacological or toxicological effects of ciclopirox may be UGT1A9 and species dependent.

Luspatercept enhances hemoglobin levels in a Chinese boy with congenital sideroblastic anemia: A case report.

BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia. CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 1012/L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period. CONCLUSION: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

An atlas of causal association between micronutrients and osteoarthritis.

OBJECTIVE: This study examines the causal relationships between serum micronutrients and site-specific osteoarthritis (OA) using Mendelian Randomization (MR). METHODS: This study performed a two-sample MR analysis to explore causal links between 21 micronutrients and 11 OA outcomes. These outcomes encompass overall OA, seven site-specific manifestations, and three joint replacement subtypes. Sensitivity analyses using MR methods, such as the weighted median, MR-Egger, and MR-PRESSO, assessed potential horizontal pleiotropy and heterogeneity. Genome-wide association summary statistical data were utilized for both exposure and outcome data, including up to 826,690 participants with 177,517 OA cases. All data was sourced from Genome-wide association studies datasets from 2009 to 2023. RESULTS: In the analysis of associations between 21 micronutrients and 11 OA outcomes, 15 showed Bonferroni-corrected significance (P < 0.000216), without significant heterogeneity or horizontal pleiotropy. Key findings include strong links between gamma-tocopherol and spine OA (OR = 1.70), and folate with hand OA in finger joints (OR = 1.15). For joint replacements, calcium showed a notable association with a reduced likelihood of total knee replacement (TKR) (OR = 0.52) and total joint replacement (TJR) (OR = 0.56). Serum iron was significantly associated with an increased risk of total hip replacement (THR) (OR = 1.23), while folate indicated a protective effect (OR = 0.95). Various sex-specific associations were also uncovered. CONCLUSION: These findings underscore the critical role of micronutrients in osteoarthritis, providing valuable insights for preventive care and potential enhancement of treatment outcomes.

The effect of large channel-based foraminoplasty on lumbar biomechanics in percutaneous endoscopic discectomy: a finite element analysis.

BACKGROUND: This study aimed to evaluate the effect of foraminoplasty using large-channel endoscopy during TESSYS on the biomechanics of the lumbar spine. METHODS: A complete lumbar spine model, M1, was built using 3D finite elements, and models M2 and M3 were constructed to simulate the intraoperative removal of the superior articular process of L5 using a trephine saw with diameters of 5 mm and 8.5 mm, respectively, and applying normal physiological loads on the different models to simulate six working conditions-anterior flexion, posterior extension, left-right lateral bending, and left-right rotation-to investigate the displacement and facet joint stress change of the surgical segment, and the disc stress change of the surgical and adjacent segments. RESULTS: Compared with the M1 model, the M2 and M3 models showed decreased stress at the L4-5 left FJ and a significant increase in stress at the right FJ in forward flexion. In the M2 and M3 models, the L4-5 FJ stresses were significantly greater in left lateral bending or left rotation than in right lateral bending or right rotation. The right FJ stress in M3 was greater during left rotation than that in M2, and that in M2 was greater than that in M1. The L4-5disc stress in the M3 model was greater during posterior extension than that in the M1 and M2 models. The L4-5disc stress in the M3 model was greater in the right rotation than in the M2 model, and that in the M2 model was greater than that in the M1 model. CONCLUSION: Foraminoplasty using large-channel endoscopy could increase the stress on the FJ and disc of the surgical segment, which suggested unnecessary and excessive resection should be avoided in PTED to minimize biomechanical disruption.

Micronutrient-Associated Single Nucleotide Polymorphism and Mental Health: A Mendelian Randomization Study.

PURPOSE: Previous studies have demonstrated the link between micronutrients and mental health. However, it remains uncertain whether this connection is causal. We aim to investigate the potential causal effects of micronutrients on mental health based on linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) analysis. METHODS: Utilizing publicly available genome-wide association study (GWAS) summary datasets, we performed LDSC and MR analysis to identify candidate micronutrients with potential causal effects on mental health. Single nucleotide polymorphisms (SNPs) significantly linked with candidate micronutrients with a genome-wide significance level (p < 5 × 10-8) were selected as instrumental variables (IVs). To estimate the causal effect of candidate micronutrients on mental health, we employed inverse variance weighted (IVW) regression. Additionally, two sensitivity analyses, MR-Egger and weighted median, were performed to validate our results. RESULTS: We found evidence supporting significant causal associations between micronutrients and mental health. LDSC detected several candidate micronutrients, including serum iron (genetic correlation = -0.134, p = 0.032) and vitamin C (genetic correlation = -0.335, p < 0.001) for attention-deficit/hyperactivity disorder (ADHD), iron-binding capacity (genetic correlation = 0.210, p = 0.037) for Alzheimer's disease (AD), and vitamin B12 (genetic correlation = -0.178, p = 0.044) for major depressive disorder (MDD). Further MR analysis suggested a potential causal relationship between vitamin B12 and MDD (b = -0.139, p = 0.009). There was no significant heterogeneity or pleiotropy, indicating the validity of the findings. CONCLUSION: In this study, we identified underlying causal relationships between micronutrients and mental health. Notably, more research is necessary to clarify the underlying biological mechanisms by which micronutrients affect mental health.

Investigating the involvement of potato (Solanum tuberosum L.) StPHR1 gene in the combined stress response to phosphorus deficiency and aluminum toxicity.

Phosphorus deficiency and aluminum toxicity in acidic soils are important factors that limit crop yield. To further explore this issue, we identified 18 members of the StPHR gene family in the potato genome in this study. Through bioinformatics analysis, we found that the StPHR1 gene, an important member of this family, exhibited high expression levels in potato roots, particularly under conditions of phosphorus deficiency and aluminum toxicity stress. This suggested that the StPHR1 gene may play a crucial regulatory role in potato's resistance to phosphorus deficiency and aluminum toxicity. To validate this hypothesis, we conducted a series of experiments on the StPHR1 gene, including subcellular localization, GUS staining for tissue expression, heterologous overexpression, yeast two-hybrid hybridization, and bimolecular fluorescence complementation (BiFC). The results demonstrated that the StPHR1 gene is highly conserved in plants and is localized in the nucleus of potato cells. The heterologous overexpression of the gene in Arabidopsis plants resulted in a growth phenotype that exhibited resistance to both aluminum toxicity and phosphorus deficiency. Moreover, the heterologous overexpressing plants showed reduced aluminum content in the root system compared to the control group. Furthermore, we also identified an interaction between StPHR1 and StALMT6. These results highlight the potential application of regulating the expression of the StPHR1 gene in potato production to enhance its adaptation to the dual stress of phosphorus deficiency and high aluminum toxicity in acidic soils.

CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.

Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many healthcare settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the diagnosis of fusion-driven leukemias. We validated these assays using diagnostic APL and CML patient samples from academic centers and dried blood spots from low-resource environments, demonstrating 100% sensitivity and specificity. We identified assay optimizations to enable the use of these tests outside of tertiary cancer centers and clinical laboratories, enhancing the potential impact of this technology. Rapid point-of-care diagnostics can improve outcomes in cancer patients by expanding access to therapies for highly treatable diseases that would otherwise lead to serious adverse outcomes due to delayed or missed diagnoses.

Oxidative stress induces ferroptosis in tendon stem cells by regulating mitophagy through cGAS-STING pathway.

Tendinopathy is one of the most prevalent sports injury diseases in orthopedics. However, there is no effective treatment or medicine. Recently, the discovery of tendon stem cells (TSCs) provides a new perspective to find new therapeutic methods for Tendinopathy. Studies have shown that oxidative stress will inevitably cause TSCs injury during tendinopathy, but the mechanism has not been fully elucidated. Here, we report the oxidative damage of TSCs induced by H2O2 via ferroptosis, as well, treatment with H2O2 raised the proportion of mitochondria engulfed by autophagosomes in TSCs. The suppression of mitophagy by Mdivi-1 significantly attenuates the H2O2-induced ferroptosis in TSCs. Mechanically, H2O2 actives the cGAS-STING pathway, which can regulate the level of mitophagy. Interfering with cGAS could impair mitophagy and the classical ferroptotic events. In the rat model of tendinopathy, interference of cGAS could relieve tendon injury by inhibiting ferroptosis. Overall, these results provided novel implications to reveal the molecular mechanism of tendinopathy, by which pointed to cGAS as a potential therapeutic target for the treatment of tendinopathy.

Photoelectrochemical analysis of Pb2+ based on Au@PTCA Schottky junction with Pb2+-G quadruplex structure.

Herein, a novel photoelectrochemical (PEC) aptasensor using gold nanoparticles@3,4,9,10-perylene tetracarboxylic (Au@PTCA) Schottky junction as the effective optoelectronic material and lead ion (Pb2+)-G quadruplex structure as the efficient quencher was constructed for the detection of Pb2+ with high sensitivity and excellent selectivity. Au@PTCA Schottky junction, which was proposed by the in situ reduction of Au NPs on the PTCA surface, exhibited a strong unidirectional conductivity, which could generate a significantly enhanced PEC signal compared with the pure PTCA. The Pb2+-G quadruplex structure with a large spatial hindrance effect was formed when the target Pb2+ was present owing to the occurrence of the specific recognition between Pb2+ and its aptamer S1. The formation of a Pb2+-G quadruplex structure effectively quenched the initial signal generated by the Au@PTCA Schottky junction, which was derived from restricted electron transport and light transmission. The obtained prominently decreased PEC signal could achieve the quantitative detection of Pb2+ from 0.5 pM to 500 nM, with a low detection limit of 0.17 pM. The preparation time of this PEC aptasensor was 13 h, and the time for PEC measurement depended on the illumination time, which switched off-on-off for 10 s-20 s-10 s. The study proposed here with high sensitivity and excellent selectivity for Pb2+ analysis offered a novel and reliable tool for environmental monitoring related to heavy metal ions.

Body shape from birth to adulthood is associated with skeletal development: A Mendelian randomization study.

BACKGROUND: Observational studies have shown that childhood obesity is associated with adult bone health but yield inconsistent results. We aimed to explore the potential causal association between body shape and skeletal development. METHODS: We used two-sample Mendelian randomization (MR) to estimate causal relationships between body shape from birth to adulthood and skeletal phenotypes, with exposures including placental weight, birth weight, childhood obesity, BMI, lean mass, fat mass, waist circumference, and hip circumference. Independent genetic instruments associated with the exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding large-scale genome-wide association studies. The inverse-variance weighted analysis was chosen as the primary method, and complementary MR analyses included the weighted median, MR-Egger, weighted mode, and simple mode. RESULTS: The MR analysis shows strong evidence that childhood (ß = -1.29 × 10-3, P = 8.61 × 10-5) and adulthood BMI (ß = -1.28 × 10-3, P = 1.45 × 10-10) were associated with humerus length. Tibiofemoral angle was negatively associated with childhood BMI (ß = -3.60 × 10-1, P = 3.00 × 10-5) and adolescent BMI (ß = -3.62 × 10-1, P = 2.68 × 10-3). In addition, genetically predicted levels of appendicular lean mass (ß = 1.16 × 10-3, P = 1.49 × 10-13), whole body fat mass (ß = 1.66 × 10-3, P = 1.35 × 10-9), waist circumference (ß = 1.72 × 10-3, P = 6.93 × 10-8) and hip circumference (ß =1.28 × 10-3, P = 4.34 × 10-6) were all associated with tibia length. However, we found no causal association between placental weight, birth weight and bone length/width. CONCLUSIONS: This large-scale MR analysis explores changes in growth patterns in the length/width of major bone sites, highlighting the important role of childhood body shape in bone development and providing insights into factors that may drive bone maturation.

Preparation of MPN@Zein-PpIX Membrane and Its Antibacterial Properties.

For antibacterial purposes, a photothermal and photodynamic antibacterial membrane was prepared through electrospinning. We used zein as the substrate and introduced Protoporphyrin IX (PpIX) into the protein structure. Then, we used electrospinning technology to weave the modified zein into a fiber structure. We finally introduced a metallic polyphenol network (MPN) coating on the fiber surface to form the final membrane: MPN@Zein-PpIX. Then, we investigated the photothermal and photodynamic properties of the membrane and assessed its antibacterial activity with in vitro agar plate counting methods. The MPN@Zein-PpIX membrane exhibited good singlet oxygen generation and excellent photothermal conversion. Additionally, it showed good antibacterial capacity in vitro, owing to the combination of photothermal and photodynamic properties. Our research provides a simple approach to prepare a multifunctional membrane with excellent antibacterial ability. We used the electrospinning technique to anchor PpIX onto zein to produce a fiber membrane (Zein-PpIX) that can be adhered in situ to improve the biocompatibility of PpIX, and the MPN makes the membrane surface more hydrophilic and more accessible to adhere to biological tissues. The MPN@Zein-PpIX membrane provided new ideas for combining PDT and PTT, and it had great potential for use in the antibacterial application field.

The Role of Gut Microbiota in the Neuroprotective Effects of Selenium in Alzheimer's Disease.

The objective of the present review was to provide a timely update on the molecular mechanisms underlying the beneficial role of Se in Alzheimer's disease pathogenesis, and discuss the potential role of gut microbiota modulation in this neuroprotective effect. The existing data demonstrate that selenoproteins P, M, S, R, as well as glutathione peroxidases and thioredoxin reductases are involved in regulation of Aß formation and aggregation, tau phosphorylation and neurofibrillary tangles formation, as well as mitigate the neurotoxic effects of Aß and phospho-tau. Correspondingly, supplementation with various forms of Se in cellular and animal models of AD was shown to reduce Aß formation, tau phosphorylation, reverse the decline in brain antioxidant levels, inhibit neuronal oxidative stress and proinflammatory cytokine production, improve synaptic plasticity and neurogenesis, altogether resulting in improved cognitive functions. In addition, most recent findings demonstrate that these neuroprotective effects are associated with Se-induced modulation of gut microbiota. In animal models of AD, Se supplementation was shown to improve gut microbiota biodiversity with a trend to increased relative abundance of Lactobacillus, Bifidobacterium, and Desulfivibrio, while reducing that of Lachnospiracea_NK4A136, Rikenella, and Helicobacter. Moreover, the relative abundance of Se-affected taxa was significantly associated with Aß accumulation, tau phosphorylation, neuronal oxidative stress, and neuroinflammation, indicative of the potential role of gut microbiota to mediate the neuroprotective effects of Se in AD. Hypothetically, modulation of gut microbiota along with Se supplementation may improve the efficiency of the latter in AD, although further detailed laboratory and clinical studies are required.

Genome-wide identification of the sorghum OVATE gene family and revelation of its expression characteristics in sorghum seeds and leaves.

The OVATE gene family plays an important role in regulating the development of plant organs and resisting stress, but its expression characteristics and functions in sorghum have not been revealed. In this study, we identified 26 OVATE genes in the sorghum BTx623 genome, which were divided into four groups and distributed unevenly across 9 chromosomes. Evolutionary analysis showed that after differentiation between sorghum and Arabidopsis, the OVATE gene family may have experienced unique expansion events, and all OVATE family members were negatively selected. Transcriptome sequencing and RT-qPCR results showed that OVATE genes in sorghum showed diverse expression characteristics, such as gene SORBl_3001G468900 and SORBl_3009G173400 were significantly expressed in seeds, while SORBI_3005G042700 and SORBI_3002G417700 were only highly expressed in L1. Meantime, in the promoter region, a large number of hormone-associated cis-acting elements were identified, and these results suggest that members of the OVATE gene family may be involved in regulating specific development of sorghum leaves and seeds. This study improves the understanding of the OVATE gene family of sorghum and provides important clues for further exploration of the function of the OVATE gene family.