Landscape of human organoids: Ideal model in clinics and research.

In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

Radiomics analysis of pancreas based on dual-energy computed tomography for the detection of type 2 diabetes mellitus.

Objective: To utilize radiomics analysis on dual-energy CT images of the pancreas to establish a quantitative imaging biomarker for type 2 diabetes mellitus. Materials and methods: In this retrospective study, 78 participants (45 with type 2 diabetes mellitus, 33 without) underwent a dual energy CT exam. Pancreas regions were segmented automatically using a deep learning algorithm. From these regions, radiomics features were extracted. Additionally, 24 clinical features were collected for each patient. Both radiomics and clinical features were then selected using the least absolute shrinkage and selection operator (LASSO) technique and then build classifies with random forest (RF), support vector machines (SVM) and Logistic. Three models were built: one using radiomics features, one using clinical features, and a combined model. Results: Seven radiomic features were selected from the segmented pancreas regions, while eight clinical features were chosen from a pool of 24 using the LASSO method. These features were used to build a combined model, and its performance was evaluated using five-fold cross-validation. The best classifier type is Logistic and the reported area under the curve (AUC) values on the test dataset were 0.887 (0.73-1), 0.881 (0.715-1), and 0.922 (0.804-1) for the respective models. Conclusion: Radiomics analysis of the pancreas on dual-energy CT images offers potential as a quantitative imaging biomarker in the detection of type 2 diabetes mellitus.

LncRNA MEG3 Restrains Hepatic Lipogenesis via the FOXO1 Signaling Pathway in HepG2 Cells.

Nonalcoholic fatty liver disease (NAFLD) become a main public health concern, and is characterized by lipid accumulation in the hepatocytes. We found that overexpression of lncRNA MEG3 significantly reduced the expression of FOXO1, ACC1, and FAS, and subsequently decreased the lipid accumulation in HepG2 cells. Moreover, inhibition of lncRNA MEG3 could increase the lipid accumulation and the mRNA and protein levels of FOXO1, ACC1, and FAS. Further study showed that lncRNA MEG3 regulates the lipogenesis process by inhibiting the entry of FOXO1 into the nucleus translocation. Our study demonstrated that lncRNA MEG3 regulates de novo lipogenesis by decreasing the expression and nucleus translocation of FOXO1 in HepG2 cells, suggesting that lncRNA MEG3 could be a promising therapeutic target in lipid metabolic disorders.

Spin-State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification.

Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4)∙4H2O (H2quinha = quinaldichydroxamic acid, HClsal = 5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4)·3H2O (HClsaldt = 4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S = 0 to high-spin S = 1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm-1 to 423 cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

Beneficial effects of maintaining liver function during hepatic arterial infusion chemotherapy combined with tyrosine kinase and programmed cell death protein-1 inhibitors on the outcomes of patients with unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: Combination therapy is the primary treatment for unresectable hepatocellular carcinoma (u-HCC). The hepatic functional reserve is also critical in the treatment of HCC. In this study, u-HCC was treated with combined hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and programmed cell death protein-1 (PD-1) inhibitors to analyze the therapeutic response, progression-free survival (PFS), and safety. METHODS: One hundred sixty-two (162) patients with u-HCC were treated by combination therapy of HAIC, TKIs, and PD-1 inhibitors. PFS was assessed by Child-Pugh (CP) classification subgroups and the change in the CP score during treatment. RESULTS: The median PFS was 11.7 and 5.1 months for patients with CP class A (CPA) and CP class B (CPB), respectively (p = 0.013), with respective objective response rates of 61.1 and 27.8% (p = 0.002) and conversion rates of 16 and 0% (p = 0.078). During treatment, the CP scores in patients with CPA worsened less in those with complete and partial response than in those with stable and progressive disease. In the CP score 5, patients with an unchanged CP score had longer PFS than those with a worsened score (Not reached vs. 7.9 months, p = 0.018). CPB was an independent factor negatively affecting treatment response and PFS. Patients with CPA responded better to the combination therapy and had fewer adverse events (AEs) than those with CPB. CONCLUSIONS: Thus, triple therapy is more beneficial in patients with good liver function, and it is crucial to maintain liver function during treatment.

Mild therapeutic hypothermia upregulates the O-GlcNAcylation level of COX10 to alleviate mitochondrial damage induced by myocardial ischemia-reperfusion injury.

OBJECTIVE: Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia-reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia-reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia-reperfusion injury and the O-GlcNAcylation level of COX10. METHODS: We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia-reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. RESULTS: Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia-reperfusion injury. In vivo, MTH effectively alleviates ischemia-reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. CONCLUSIONS: In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia-reperfusion injury, which provides important theoretical basis for the clinical application of MTH.

Mining local and global spatiotemporal features for tactile object recognition.

The tactile object recognition (TOR) is highly important for environmental perception of robots. The previous works usually utilize single scale convolution which cannot simultaneously extract local and global spatiotemporal features of tactile data, which leads to low accuracy in TOR task. To address above problem, this article proposes a local and global residual (LGR-18) network which is mainly consisted of multiple local and global convolution (LGC) blocks. An LGC block contains two pairs of local convolution (LC) and global convolution (GC) modules. The LC module mainly utilizes a temporal shift operation and a 2D convolution layer to extract local spatiotemporal features. The GC module extracts global spatiotemporal features by fusing multiple 1D and 2D convolutions which can expand the receptive field in temporal and spatial dimensions. Consequently, our LGR-18 network can extract local-global spatiotemporal features without using 3D convolutions which usually require a large number of parameters. The effectiveness of LC module, GC module and LGC block is verified by ablation studies. Quantitative comparisons with state-of-the-art methods reveal the excellent capability of our method.

Efficient degradation and detoxification of structurally different dyes and mixed dyes by LAC-4 laccase purified from white-rot fungi Ganoderma lucidum.

The purpose of this study is to evaluate the decolorization ability and detoxification effect of LAC-4 laccase on various types of single and mixed dyes, and lay a good foundation for better application of laccase in the efficient treatment of dye pollutants. The reaction system of the LAC-4 decolorizing single dyes (azo, anthraquinone, triphenylmethane, and indigo dyes, 17 dyes in total) were established. To explore the decolorization effect of the dye mixture by LAC-4, two dyes of the same type or different types were mixed at the same concentration (100 mg/L) in the reaction system containing 0.5 U laccase, and time-course decolorization were performed on the dye mixture. The combined dye mixtures consisted of azo + azo, azo + anthraquinone, azo + indigo, azo + triphenylmethane, indigo + triphenylmethane, and triphenylmethane + triphenylmethane. The results obtained in this study were as follows. Under optimal conditions of 30 °C and pH 5.0, LAC-4 (0.5 U) can efficiently decolorize four different types of dyes. The 24-hour decolorization efficiencies of LAC-4 for 800 mg/L Orange G and Acid Orange 7 (azo), Remazol Brilliant Blue R (anthraquinone), Bromophenol Blue and Methyl Green (triphenylmethane), and Indigo Carmine (indigo) were 75.94%, 93.30%, 96.56%, 99.94%, 96.37%, and 37.23%, respectively. LAC-4 could also efficiently decolorize mixed dyes with different structures. LAC-4 can achieve a decolorization efficiency of over 80% for various dye mixtures such as Orange G + Indigo Carmine (100 mg/L+100 mg/L), Reactive Orange 16 + Methyl Green (100 mg/L+100 mg/L), and Remazol Brilliant Blue R + Methyl Green (100 mg/L+100 mg/L). During the decolorization process of the mixed dyes by laccase, four different interaction relationships were observed between the dyes. Decolorization efficiencies and rates of the dyes that were difficult to be degraded by laccase could be greatly improved when mixed with other dyes. Degradable dyes could greatly enhance the ability of LAC-4 to decolorize extremely difficult-to-degrade dyes. It was also found that the decolorization efficiencies of the two dyes significantly increased after mixing. The possible mechanisms underlying the different interaction relationships were further discussed. Free, but not immobilized, LAC-4 showed a strong continuous batch decolorization ability for single dyes, two-dye mixtures, and four-dye mixtures with different structures. LAC-4 exhibited high stability, sustainable degradability, and good reusability in the continuous batch decolorization. The LAC-4-catalyzed decolorization markedly reduced or fully abolished the toxic effects of single dyes (azo, anthraquinone, and indigo dye) and mix dyes (nine dye mixtures containing four structural types of dyes) on plants. Our findings indicated that LAC-4 laccase had significant potential for use in bioremediation due to its efficient degradation and detoxification of single and mixed dyes with different structural types.

Propranolol can correct prolonged QT intervals in patients with cirrhosis.

Background: Prolonged QT intervals are extremely common in patients with cirrhosis and affect their treatment outcomes. Propranolol is often used to prevent gastroesophageal variceal hemorrhage in patients with cirrhosis; however, it is uncertain whether propranolol exerts a corrective effect on QT interval prolongation in patients with cirrhosis. Aim: The study aimed to investigate the therapeutic effects of propranolol on patients with cirrhosis and prolonged QT intervals. Methods: A retrospective cohort study approach was adopted. Patients with cirrhosis complicated by moderate-to-severe gastroesophageal varices, who were hospitalized at the Affiliated Hospital of Guangdong Medical University between 1 December 2020 and 31 November 2022, were included in the study. The patients were divided into the propranolol and control groups based on whether they had received propranolol. Upon admission, the patients underwent tests on liver and kidney functions, electrolytes, and coagulation function, as well as abdominal ultrasonography and electrocardiography. In addition to conventional treatment, the patients were followed up after the use or non-use of propranolol for treatment and subsequently underwent reexamination of the aforementioned tests. Results: The propranolol group (26 patients) had an average baseline corrected QT (QTc) interval of 450.23 ± 37.18 ms, of which 14 patients (53.8%) exhibited QTc interval prolongation. Follow-up was continued for a median duration of 7.00 days after the administration of propranolol and conventional treatment. Electrocardiographic reexamination revealed a decrease in the QTc interval to 431.04 ± 34.64 ms (p = 0.014), and the number of patients with QTc interval prolongation decreased to five (19.2%; p < 0.001). After treatment with propranolol and multimodal therapy, QTc interval normalization occurred in nine patients with QTc interval prolongation, leading to a normalization rate of 64.3% (9/14). The control group (n = 58) had an average baseline QTc interval of 453.74 ± 30.03 ms, of which 33 patients (56.9%) exhibited QTc interval prolongation. After follow-up for a median duration of 7.50 days, the QTc interval was 451.79 ± 34.56 ms (p = 0.482), and the number of patients with QTc interval prolongation decreased to 30 (51.7%; p = 0.457). The QTc interval normalization rate of patients in the control group with QTc interval prolongation was merely 10.0% (3/33), which was significantly lower than that in the propranolol group (p < 0.001). Conclusion: In patients with cirrhosis complicated by QT interval prolongation, the short-term use of propranolol aids in correction of a long QT interval and provides positive therapeutic value for cirrhotic cardiomyopathy.

Cellular mechanism underlying leptin-induced anion secretion of rat epididymal epithelial cells.

BACKGROUND: A large number of studies have shown that leptin plays an important role in the regulation of fertility via the hypothalamus-pituitary-gonad axis. However, its peripheral function in epididymis was still elusive. OBJECTIVE: The purpose of this study was to determine the pro-secretion effect of leptin on the rat epididymal epithelium. MATERIALS AND METHODS: In the present study, real-time quantitative polymerase chain reaction, western blot, and immunohistochemical analysis were employed to detect the expression pattern of leptin receptors in rat epididymis. The pro-secretion effect of leptin on epididymal epithelial cells was measured by short-circuit current, and the prostaglandin E2 and cyclic adenosine monophosphate level was evaluated by enzyme-linked immunosorbent assay. RESULTS: We verified that the leptin receptor was located on the epididymal epithelium, with a relatively high expression level in corpus and cauda epididymis. Ussing chamber experiments showed that leptin stimulated a significant rise of the short-circuit current in rat epididymal epithelial cells, which could be abolished by the specific leptin receptor antagonist peptide Allo-aca, or by removing the ambient Cl- and HCO3 -. Furthermore, the leptin-stimulated short-circuit current response could be abrogated by blocking the apical cystic fibrosis transmembrane regulator or the basolateral Na+-K+-2Cl- cotransporter. Our pharmacological experiments manifested that interfering with the prostaglandin H synthase-2-prostaglandin E2-EP2/EP4-adenylate cyclase pathways could significantly blunt the cystic fibrosis transmembrane regulator-mediated anion secretion induced by leptin. The enzyme-linked immunosorbent assay demonstrated that leptin could induce a substantial increase in prostaglandin E2 release and cyclic adenosine monophosphate synthesis of primary cultured rat cauda epididymal epithelial cells. Our data also suggested that JAK2, ERK, and PI3K-dependent phosphorylation may be involved in the activation of prostaglandin H synthase-2 and the subsequent prostaglandin E2 production. CONCLUSIONS: The present study demonstrated the pro-secretion function of leptin in rat epididymal epithelium via the activation of cystic fibrosis transmembrane regulator and Na+-K+-2Cl- cotransporter, which was dependent on the paracrine/autocrine prostaglandin E2 stimulated EP2/EP4-adenylate cyclase pathways, and thus contributed to the formation of an appropriate microenvironment essential for sperm maturation.

Sophoraflavanone G Inhibits RANKL-Induced Osteoclastogenesis via MAPK/NF-κB Signaling Pathway.

Osteoporosis is a common chronic bone metabolism disorder characterized by decreased bone mass and reduced bone density in the bone tissue. Osteoporosis can lead to increased fragility of the skeleton, making it prone to brittle fractures. Osteoclasts are macrophage-like cells derived from hematopoietic stem cells, and their excessive activity in bone resorption leads to lower bone formation than absorption during bone remodeling, which is one of the important factors inducing osteoporosis. Therefore, how to inhibit osteoclast formation and reducing bone loss is an important direction for treating osteoporosis. Sophoraflavanone G, derived from Sophora flavescens Alt and Rhizoma Drynariae, is a flavonoid compound with various biological activities. However, there have been few studies on osteoporosis and osteoclasts so far. Therefore, we hypothesize that genistein G can inhibit osteoclast differentiation, alleviate bone loss phenomenon, and conduct in vitro and in vivo experiments for research and verification purposes.

Bionic Scotopic Adaptation Transistors for Nighttime Low Illumination Imaging.

Human vision excels in perceiving nighttime low illumination due to biological feedforward adaptation. Replicating this ability in biomimetic vision using solid-state devices has been highly sought after. However, emulating scotopic adaptation, entailing a confluence of efficient photoexcitation and dynamic carrier modulation, presents formidable challenges. Here, we demonstrate a low-power and bionic scotopic adaptation transistor by coupling a light-absorption layer and an electron-trapping layer at the bottom of the semiconducting channel, enabling simultaneous achievement of efficient generation of free photocarriers and adaptive carrier accumulation within a single device. This innovation empowers our transistor to exhibit sensitivity-potentiated characteristics after adaptation, detecting scotopic-level illumination (0.001 lx) with exceptional photosensitivity up to 103 at low voltages below 2 V. Moreover, we have successfully replicated diverse scotopic vision functions, encompassing time-dependent visual threshold enhancement, light intensity-dependent adaptation index, imaging contrast enhancement for nighttime low illumination imaging, opening an opportunity for artificial night vision.

Discovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers.

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

Shared and distinct electroencephalogram microstate abnormalities across schizophrenia, bipolar disorder, and depression.

BACKGROUND: Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear. METHODS: This study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design. RESULTS: Our research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups. CONCLUSIONS: Our findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.

Identify Potential Causal Relationships Between Cortical Thickness, Mismatch Negativity, Neurocognition, and Psychosocial Functioning in Drug-Naïve First-Episode Psychosis Patients.

BACKGROUND: Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP. METHODS: We enrolled 28 drug-naïve FEP and 34 age and sex-matched healthy controls. Clinical symptoms, neurocognition, psychosocial functioning, auditory duration MMN, and T1 structural magnetic resonance imaging data were collected. We measured CT in the superior temporal gyrus (STG), a primary MMN-generating region. RESULTS: We found a significant negative correlation between MMN amplitude and bilateral CT of STG (CT_STG) in FEP (left: r = -.709, P < .001; right: r = -.612, P = .008). Multiple mediation models revealed that a thinner left STG cortex affected functioning through both direct (24.66%) and indirect effects (75.34%). In contrast, the effects of the right CT_STG on functioning were mainly mediated through MMN and neurocognitive pathways. CONCLUSIONS: Bilateral CT_STG showed significant association with MMN, and MMN plays a mediating role between CT and cognition. Both MMN alone and its interaction with cognition mediated the effects of structural alterations on psychosocial function. The decline in overall function in FEP may stem from decreased CT_STG, leading to subsequent MMN deficits and neurocognitive dysfunction. These findings underline the crucial role of MMN in elucidating how subtle structural alterations can impact neurocognition and psychosocial function in FEP.

Exploring Control Authority Preferences in Robotic Arm Assistance for Power Wheelchair Users.

This paper uses mixed methods to explore the preliminary design of control authority preferences for an Assistive Robotic Manipulator (ARM). To familiarize users with an intelligent robotic arm, we perform two kitchen task iterations: one with user-initiated software autonomy (predefined autonomous actions) and one with manual control. Then, we introduce a third scenario, enabling users to choose between manual control and system delegation throughout the task. Results showed that, while manually switching modes and controlling the arm via joystick had a higher mental workload, participants still preferred full joystick control. Thematic analysis indicates manual control offered greater freedom and sense of accomplishment. Participants reacted positively to the idea of an interactive assistive system. Users did not want to ask the system to only assist, by taking over for certain actions, but also asked for situational feedback (e.g., 'How close am I (the gripper)?', 'Is the lid centered over the jug?'). This speaks to a future assistive system that ensures the user feels like they drive the system for the entirety of the task and provides action collaboration in addition to more granular situational awareness feedback.

Intercalated PtCo Electrocatalyst of Vanadium Metal Oxide Increases Charge Density to Facilitate Hydrogen Evolution.

Efforts to develop high-performance electrocatalysts for the hydrogen evolution reaction (HER) are of utmost importance in ensuring sustainable hydrogen production. The controllable fabrication of inexpensive, durable, and high-efficient HER catalysts still remains a great challenge. Herein, we introduce a universal strategy aiming to achieve rapid synthesis of highly active hydrogen evolution catalysts using a controllable hydrogen insertion method and solvothermal process. Hydrogen vanadium bronze HxV2O5 was obtained through controlling the ethanol reaction rate in the oxidization process of hydrogen peroxide. Subsequently, the intermetallic PtCoVO supported on two-dimensional graphitic carbon nitride (g-C3N4) nanosheets was prepared by a solvothermal method at the oil/water interface. In terms of HER performance, PtCoVO/g-C3N4 demonstrates superior characteristics compared to PtCo/g-C3N4 and PtCoV/g-C3N4. This superiority can be attributed to the notable influence of oxygen vacancies in HxV2O5 on the electrical properties of the catalyst. By adjusting the relative proportions of metal atoms in the PtCoVO/g-C3N4 nanomaterials, the PtCoVO/g-C3N4 nanocomposites show significant HER overpotential of η10 = 92 mV, a Tafel slope of 65.21 mV dec-1, and outstanding stability (a continuous test lasting 48 h). The nanoarchitecture of a g-C3N4-supported PtCoVO nanoalloy catalyst exhibits exceptional resistance to nanoparticle migration and corrosion, owing to the strong interaction between the metal nanoparticles and the g-C3N4 support. Pt, Co, and V simultaneous doping has been shown by Density Functional Theory (DFT) calculations to enhance the density of states (DOS) at the Fermi level. This augmentation leads to a higher charge density and a reduction in the adsorption energy of intermediates.

New role of platelets in schizophrenia: predicting drug response.

Background: Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear. Aims: We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables. Methods: A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes. Results: PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p<0.001) and haloperidol (F=3.59, p=0.029). It exhibited a positive association with white blood cell count and metabolic indicators. Higher baseline PLTc was observed in non-responders, particularly in those defined by the PANSS-negative subscale. In the structural equation model, PLTc, white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores. Moreover, higher baseline PLTc was observed in individuals with less metabolic change, although this association was no longer significant after accounting for baseline metabolic values. Conclusions: Platelet parameters, specifically PLTc, are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia. Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation. Given PLTc's easy measurement and clinical relevance, it warrants increased attention from psychiatrists. Trial registration number: ChiCTR-TRC-10000934.

Conditional survival and annual hazard of death in older patients with esophageal cancer receiving definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy is one of the primary treatment modalities for older patients with esophageal cancer (EC). However, the evolution of prognosis over time and the factors affected non-EC deaths remain inadequately studied. We examined the conditional survival and annual hazard of death in older patients with EC after chemoradiotherapy. METHODS: We collected data from patients aged 65 or older with EC registered in the Surveillance, Epidemiology, and End Results database during 2000-2019. Conditional survival was defined as the probability of survival given a specific time survived. Annual hazard of death was defined the yearly event rate. Restricted cubic spline (RCS) analysis identified the association of age at diagnosis with mortality. RESULTS: Among 3739 patients, the 3-year conditional overall survival increased annually by 7-10%. Non-EC causes accounted for 18.8% of deaths, predominantly due to cardio-cerebrovascular diseases. The hazard of death decreased from 40 to 10% in the first 6 years and then gradually increased to 20% in the tenth year. Non-EC causes surpassed EC causes in hazard starting 5 years post-treatment. RCS indicated a consistent increase in death hazard with advancing age, following a linear relationship. The overall cohort was divided into two groups: 65-74 and ≥ 75 years old, with the ≥ 75-year-old group showing poorer survival and earlier onset of non-EC deaths (HR = 1.36, 95% CI: 1.15-1.62, P < 0.001). Patients with early-stage disease (I-II) had higher risks of death from non-EC causes (HR = 0.82, 95% CI: 0.68-0.98, P = 0.035). Tumor histology had no significant impact on non-EC death risk (HR = 1.17, 95% CI: 0.98-1.39, P = 0.081). CONCLUSIONS: Survival probability increases with time for older patients with EC treated with chemoradiotherapy. Clinicians and patients should prioritize managing and preventing age-related comorbidities, especially in older cohorts and those with early-stage disease.

Infection with SARS-CoV-2 can cause pancreatic impairment.

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (ß) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor ß. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.