Human-unique brain cell clusters are associated with learning disorders and human episodic memory activity.

The advanced evolution of the human cerebral cortex forms the basis for our high-level cognitive functions. Through a comparative analysis of single-nucleus transcriptome data from the human neocortex and that of chimpanzees, macaques, and marmosets, we discovered 20 subgroups of cell types unique to the human brain, which include 11 types of excitatory neurons. Many of these human-unique cell clusters exhibit significant overexpression of genes regulated by human-specific enhancers. Notably, these specific cell clusters also express genes associated with disease risk, particularly those related to brain dysfunctions like learning disorders. Furthermore, genes linked to cortical thickness and human episodic memory encoding activities show heightened expression within these cell subgroups. These findings underscore the critical role of human brain-unique cell clusters in the evolution of human brain functions.

Filicinic acid based meroterpenoids from Hypericum elodeoides and their anti-Alzheimer's disease effects.

(±)-Elodeoidileons A-L (1-12), 12 pairs of previously undescribed filicinic acid based meroterpenoids were isolated from Hypericum elodeoides with unique linear or angular 6/6/6 ring core. Modern spectroscopic techniques, modified Mosher's method and quantum chemical calculations were used to identify the planner structures and configurations of 1-12. Additionally, the potential biosynthetic pathways for 1-12 were anticipated. Moreover, biological activity assessments suggested that 1a, 5a, and 11b could activate Retinoid X receptor-α (RXRα) transcription and enhance the ATP-binding cassette transporter A1 (ABCA1) protein's expression. Fluorescence titration assay suggested that 1a might have a direct interaction with the RXRα-LBD protein, with an estimated Kd value of 5.85 µM. Moreover, molecular docking study confirmed the binding of 1a to RXRα and further validated by cellular thermal shift assay (CETSA). Thus, compound 1a may promote ß-amyloid (Aß) clearance by targeting RXRα and upregulating the expression of the ABCA1 protein, showing promise as anti-Alzheimer's agent.

Exploring the relationship between pyroptosis and inflammatory bone loss: Evidence from a cigarette smoke-induced osteoporosis mouse model.

Smoking is by far one of the greatest public health threats and is recognized as an important predisposing factor for osteoporosis. Exposure to cigarette smoke (CS) has been reported to be associated with inflammation-associated diseases through the induction of pyroptosis. Nevertheless, the correlation between pyroptosis and bone loss induced by CS remains uninvestigated. Here, a mouse model of mainstream smoke exposure-induced osteoporosis was established. µCT, biomechanical testing, and immunohistochemical staining of bone tissue were used to assess the deleterious effects of CS on bone metabolism. In vitro, the effects of cigarette smoke extracts (CSE) on mouse primary bone marrow-derived mesenchymal stem cells (BMSCs) were tested by cell viability assays, gene and protein expression assays, and alizarin red staining. The utilization of the pyroptosis inhibitor MCC950 served to confirm the critical role of BMSCs pyroptosis in CS-induced osteoporosis. Our results indicated that exposure to mainstream smoke led to a notable decrease in the quantity of osteoblasts and hindered the process of osteogenic differentiation in mice. Additionally, there was a significant increase in the expression of pyroptosis-related proteins in the bone marrow. The inhibitory effects of CSE on cell viability and osteogenic differentiation of BMSCs were found to be dose-dependent in vitro. However, the presence of the pyroptosis inhibitor MCC950 significantly improved the impaired osteogenic differentiation and bone mineralization caused by CSE. These results highlight the crucial involvement of BMSCs pyroptosis in the development of bone loss induced by CS. In summary, the findings of this study provide novel evidence that CS exerts a detrimental effect on the process of osteogenesis in BMSCs through the induction of pyroptosis, ultimately leading to bone loss. Inhibition of pyroptosis effectively attenuated the toxicological effects of CS on BMSCs, providing a new target for preventing inflammatory osteoporosis.

Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

Suicide among patients with oral cancer: A population-based study.

BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity.

Background: Impaired sensitivity to thyroid hormones (TH) was associated with metabolic syndrome. The study aimed to explore the association between central TH sensitivity indices and insulin resistance (IR) in euthyroid adults with obesity. Methods: This cross-sectional study enrolled 293 euthyroid outpatients with obesity in Beijing Chao-Yang Hospital. We used the thyroid feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotrophic T4 resistance index (TT4RI) to indicate central TH sensitivity. IR was assessed by homeostasis model assessment of insulin resistance (HOMA-IR), hepatic insulin resistance index (hepatic-IR), the Matsuda index, and the adipose tissue insulin resistance index (Adipo-IR). Participants were categorized according to tertiles of TH sensitivity indices. We used multiple linear regressions to explore the associations. Results: There was a significant stepwise increase in HOMA-IR and Adipo-IR from the lowest to the highest tertiles of TH sensitivity indices (all P<0.05). After adjustment for age, sex, body mass index, hypertension, hyperlipidemia, and diabetes, only Adipo-IR was significantly associated with TH sensitivity indices. On average, each unit increased in TFQI, TSHI, and TT4RI was associated with 1.19 (P=0.053), 1.16 (P=0.04), and 1.01 (P=0.03) units increased in Adipo-IR, respectively. There was no significant association between TH sensitivity indices and HOMA-IR, hepatic-IR, and the Matsuda index after adjustment for other risk factors. Conclusions: Reduced central TH sensitivity was associated with increased adipose tissue insulin resistance in euthyroid adults with obesity. The results further confirmed the importance of TH sensitivity on metabolic diseases.

Rolling up 2D WSe2 Nanosheets to 1D Anisotropic Nanoscrolls for Polarization-Sensitive Photodetectors.

The intrinsic low-symmetry crystal structures or external geometries of low-dimensional materials are crucial for polarization-sensitive photodetection. However, these inherently anisotropic materials are limited in variety, and their anisotropy is confined to specific crystal directions. Transforming 2D semiconductors, such as WSe2, from isotropic 2D nanosheets into anisotropic 1D nanoscrolls expands their application in polarization photodetection. Despite this considerable potential, research on polarization photodetection based on nanoscrolls remains scarce. Here, the uniform crystalline orientation of WSe2 nanoscrolls is achieved conveniently and efficiently by applying ethanol droplets to vapor deposition-grown bilayer WSe2 nanosheets. Angle-resolved polarized Raman spectroscopy of WSe2 nanoscrolls demonstrates vibrational anisotropy. Photodetectors based on these nanoscrolls show competitive overall performance with a broadband detection range from 405 to 808 nm, a competitive on/off ratio of ≈900, a high detectivity of 3.4 × 108 Jones, and a fast response speed of ≈30 ms. Additionally, WSe2 nanoscroll-based photodetectors exhibit strong polarization-sensitive detection with a maximum dichroic ratio of 1.5. More interestingly, due to high photosensitivity, the WSe2 nanoscroll detectors can easily record sequential puppy images. This work reveals the potential of WSe2 nanoscrolls as excellent polarization-sensitive photodetectors and provides new insights into the development of high-performance optoelectronic devices.

Planetary gearbox fault classification based on tooth root strain and GAF pseudo images.

Traditional signal processing methods based on acceleration signals can determine whether a fault has occurred in a planetary gearbox. However, acceleration signals are severely affected by interference, causing difficulties in fault identification. This study proposes a gear fault classification method based on root strain and pseudo images. Firstly, fiber optic sensors are employed to directly acquire strain data from the ring gear root. Next, the strain signals are preprocessed using resampling and a time-domain synchronous averaging algorithm. The processed signals are encoded into two-dimensional images using Gramian Angular Fields (GAF). Then, CN-EfficientNet with contrast learning is proposed to analyze and extract deeper fault features from the image texture features. In the classification experiments for different types of faults, the accuracy reached 96.84%. The results indicate that the method can effectively accomplish the task of fault classification in planetary gearboxes. Comparative experiments with other common classification models further indicate the superior performance of the proposed learning model. Visualization based on Grad-CAM provides interpretability for the fault recognition network's results and reveals the underlying mechanism for its excellent classification performance.

Vps34 sustains Treg cell survival and function via regulating intracellular redox homeostasis.

The survival and suppressive function of regulatory T (Treg) cells rely on various intracellular metabolic and physiological processes. Our study demonstrates that Vps34 plays a critical role in maintaining Treg cell homeostasis and function by regulating cellular metabolic activities. Disruption of Vps34 in Treg cells leads to spontaneous fatal systemic autoimmune disorder and multi-tissue inflammatory damage, accompanied by a reduction in the number of Treg cells, particularly eTreg cells with highly immunosuppressive activity. Mechanistically, the poor survival of Vps34-deficient Treg cells is attributed to impaired endocytosis, intracellular vesicular trafficking and autophagosome formation, which further results in enhanced mitochondrial respiration and excessive ROS production. Removal of excessive ROS can effectively rescue the death of Vps34-deficient Treg cells. Functionally, acute deletion of Vps34 within established Treg cells enhances anti-tumor immunity in a malignant melanoma model by boosting T-cell-mediated anti-tumor activity. Overall, our results underscore the pivotal role played by Vps34 in orchestrating Treg cell homeostasis and function towards establishing immune homeostasis and tolerance.

Prediction of non-muscle invasive bladder cancer recurrence using deep learning of pathology image.

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Research on Acid Aging and Damage Pattern Recognition of Glass Fiber-Reinforced Plastic Oil and Gas Gathering Pipelines Based on Acoustic Emission.

Pipelines extend thousands of kilometers to transport and distribute oil and gas. Given the challenges often faced with corrosion, fatigue, and other issues in steel pipes, the demand for glass fiber-reinforced plastic (GFRP) pipes is increasing in oil and gas gathering and transmission systems. However, the medium that is transported through these pipelines contains multiple acid gases such as CO2 and H2S, as well as ions including Cl-, Ca2+, Mg2+, SO42-, CO32-, and HCO3-. These substances can cause a series of problems, such as aging, debonding, delamination, and fracture. In this study, a series of aging damage experiments were conducted on V-shaped defect GFRP pipes with depths of 2 mm and 5 mm. The aging and failure of GFRP were studied under the combined effects of external force and acidic solution using acoustic emission (AE) techniques. It was found that the acidic aging solution promoted matrix damage, fiber/matrix desorption, and delamination damage in GFRP pipes over a short period. However, the overall aging effect was relatively weak. Based on the experimental data, the SSA-LSSVM algorithm was proposed and applied to the damage pattern recognition of GFRP. An average recognition rate of up to 90% was achieved, indicating that this method is highly suitable for analyzing AE signals related to GFRP damage.

Oleic Acid and Linoleic Acid Enhances the Biocontrol Potential of Metarhizium rileyi.

Metarhizium rileyi is a wide spread insect fungi with a good biocontrol potentiality to various pests, particularly noctuid insects. However, it is characterized by its slow growth, its sensitivity to abiotic stress, and the slow speed of kill to pests, which hinder its use compared with other entomopathogenic fungi. In this study, the responses of M. rileyi to eight types of lipids were observed; among the lipids, oleic acid and linoleic acid significantly promoted the growth and development of M. rileyi and enhanced its stress tolerances and virulence. An additional mechanistic study demonstrated that exogenous oleic acid and linoleic acid significantly improved the conidial germination, appressorium formation, cuticle degradation, and cuticle infection, which appear to be largely dependent on the up-regulation of gene expression in growth, development, protective, and cuticle-degrading enzymes. In conclusion, exogenous oleic acid and linoleic acid enhanced the stress tolerances and virulence of M. rileyi via protecting conidial germination and promoting cuticle infection. These results provide new insights for the biopesticide development of M. rileyi.

An amplification-free CRISPR-Cas12a assay for titer determination and composition analysis of the rAAV genome.

The viral genome titer is a crucial indicator for the clinical dosing, manufacturing, and analytical testing of recombinant adeno-associated virus (rAAV) gene therapy products. Although quantitative PCR and digital PCR are the common methods used for quantifying the rAAV genome titer, they are limited by inadequate accuracy and robustness. The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a biosensor is being increasingly used in virus detection; however, there is currently no report on its application in the titer determination of gene therapy products. In the present study, an amplification-free CRISPR-Cas12a assay was developed, optimized, and applied for rAAV genome titer determination. The assay demonstrated high precision and accuracy within the detection range of 4 × 109 and 1011 vg/mL. No significant difference was observed between the Cas12a and qPCR assay results (p < 0.05, t test). Moreover, Cas12a exhibited similar activity on both single-stranded and double-stranded DNA substrates. Based on this characteristic, the titers of positive-sense and negative-sense strands were determined separately, which revealed a significant difference between their titers for an in-house reference AAV5-IN. This study presents the inaugural report of a Cas12a assay developed for the titer determination and composition analysis of the rAAV genome.

TSH is independently associated with remnant cholesterol in euthyroid adults: a cross-sectional study based on 29,708 individuals.

PURPOSE: The study aims to investigate the relationship between thyroid-stimulating hormone (TSH) and remnant cholesterol (RC) in euthyroid adults. METHODS: The adults who were recruited for the study had undergone physical examination at Beijing Chao-Yang Hospital. High RC levels were defined as the upper quartile of RC levels in males and females, respectively. The relationship between TSH and RC was assessed using the logistic and linear regression models. RESULTS: A total of 29,708 adults (14,347 males and 15,361 females) were enrolled in this study. RC ≥ 0.77 mmol/L in males and RC ≥ 0.60 mmol/L in females were defined as high RC levels. With increasing serum TSH levels, the percentage of adults with high RC levels increased. The odds ratios (ORs (95% confidence intervals (CIs)) for high RC levels increased as TSH quartiles (Q) rose after full adjustments [males: Q2 1.11 (1.00-1.24), P < 0.05; Q3 1.03 (0.92-1.15), P > 0.05; Q4 1.25 (1.12-1.40), P < 0.001; and females: Q2 1.07 (0.96-1.20), P > 0.05; Q3 1.17 (1.05-1.31), P < 0.01, Q4 1.33 (1.20-1.48), P < 0.001, all P for trend < 0.001], using Q1 as the reference. CONCLUSION: Higher TSH levels were independently associated with higher RC levels in euthyroid adults, this underscoring the significance of regulating TSH levels appropriately.

Hierarchically porous and flexible chitin-fiber/melamine-sponge composite filter with high-loading of PdAu nanoparticles for effective hydrodechlorination of chlorophenols.

Hydrodechlorination has emerged as a promising technique for detoxifying chlorophenols (CPs) in wastewater, but it suffers from sluggish reaction kinetics and limited durability due to the lack of effective and stable catalysts. Herein, a composite filter consisting of melamine-sponge (MS), chitin fiber (CF) and ultrafine PdAu nanoparticles (PdAu/CF-MS) has been designed for continuous hydrodechlorination of CPs by using formic acid as a H-donor and sodium formate as a promoter. Benefitting from the dense active sites, rich porosity, and synergetic interaction of Pd/Au, the PdAu/CF-MS filter exhibits excellent hydrodechlorination performance (∼ 100 % conversion) towards 4-chlorophenol (1 mM, fluxes below 6100 mL·h-1·g-1) and outstanding durability (over 500 h at 61 mL·h-1·g-1), surpassing most reported counterparts (usually deactivated within 200 h or several cycles). Moreover, other CPs can also be effectively dechlorinated by the PdAu/CF-MS filter. The catalytic system proposed herein will provide a promising candidate for the detoxification of wastewater containing toxic CPs.

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

Controlled growth of asymmetric chiral TeOx for broad-spectrum, high-responsivity and polarization-sensitive photodetection.

Low-dimensional nanostructures, especially one-dimensional materials, exhibit remarkable anisotropic characteristics due to their low symmetry, making them promising candidates for polarization-sensitive photodetection. Here, we present a chemical vapor deposition synthesis method for tellurium suboxide (TeOx), confirming the practicality of photodetectors constructed from TeOx nanowires (NWs) in high-responsivity, broadband, and polarization-sensitive detection. By precisely controlling the thermodynamics and kinetics of TeOx NWs growth, we achieve large-scale growth of TeOx NWs with highly controllable dimensions and propose a method to induce intrinsic built-in strain in TeOx NWs. Photodetectors based on quasi-one-dimensional TeOx NWs with ohmic contact demonstrate broadband spectral response (638-1550 nm), high responsivity (13 700 mA·W-1), and superior air stability. Particularly, owing to the inherent structural anisotropy of the photodetectors, they exhibit polarization-sensitive photodetection, with anisotropy ratios of 1.70 and 1.71 at 638 and 808 nm, respectively.

MiR-322-5p is involved in regulating chondrocyte proliferation and differentiation in offspring's growth plate of maternal gestational diabetes.

Pregestational diabetes mellitus (PGDM) has an impact on fetal bone formation, but the underlying mechanism is still obscure. Although miRNAs have been extensively investigated throughout bone formation, their effects on fetal bone development caused by PGDM still need clarification. This study intends to examine the mechanism by which hyperglycemia impairs the bone formation of offspring via miR-322-5p (miR-322). In this study, miR-322 was selected by systemically screening utilizing bioinformatics and subsequent validation experiments. Using streptozotocin (STZ)-induced diabetic mice and ATDC5 cell lines, we found that miR-322 was abundantly expressed in the proliferative and hypertrophic zones of the growth plate, and its expression pattern was disturbed in the presence of hyperglycemia, suggesting that miR-322 is involved in the chondrocyte proliferation and differentiation in absence/presence of hyperglycemia. This observation was proved by manipulating miR-322 expression in ATDC5 cells by transfecting mimic and inhibitor of miR-322. Furthermore, Adamts5, Col12a1, and Cbx6 were identified as the potential target genes of miR-322, verified by the co-transfection of miR-322 inhibitor and the siRNAs, respectively. The evaluation criteria are the chondrocyte proliferation and differentiation and their relevant key gene expressions (proliferation: Sox9 and PthIh; differentiation: Runx2 and Col10a1) after manipulating the gene expressions in ATDC5 cells. This study revealed the regulative role miR-322 on chondrocyte proliferation and differentiation of growth plate by targeting Adamts5, Col12a1, and Cbx6 in hyperglycemia during pregnancy. This translational potential represents a promising avenue for advancing our understanding of bone-related complications in diabetic pregnancy and mitigating bone deficiencies in diabetic pregnant individuals, improving maternal and fetal outcomes.

New insight into the exotic states strongly coupled with the DD‾∗ from the Tcc.

We have investigated the internal structure of the open- and hidden-charmed (DD∗/D¯D∗) molecules in the unified framework. We first fit the experimental lineshape of the Tcc+ state and extract the DD∗ interaction, from which the Tcc+ is assumed to arise solely. Then we obtain the DD‾∗ interaction by charge conjugation. Our results show that the DD‾∗ interaction is attractive but insufficient to form X(3872) as a bound state. Instead, its formation requires the crucial involvement of the coupled channel effect between the DD¯∗ and cc¯ components, although the cc¯ accounts for approximately 1% only. Besides X(3872), we have obtained a higher-energy state around 3957.9 MeV with a width of 16.7 MeV, which may be a potential candidate for the X(3940). In JPC=1+- sector, we have found two states related to the iso-scalar X̃(3872) and hc(2P), respectively. Our combined study provides valuable insights into the nature of these DD∗/DD¯∗ exotic states.

Therapeutic effect of the metaverse on mental health.

López del Hoyo et al collections reported the meta verse based on the virtual reality, augmented reality and artificial intelligence could be used in the therapy of mental health, although there were still some challenges. This manuscript reported that the meta verse is a prospective method to improve the prognosis of mental health problems.