Discovery of a doublecortin-like kinase 1 inhibitor to prevent inflammatory responses in acute lung injury.

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein kinase involved in neurogenesis and human cancer. Recent studies have revealed a novel functional role for DCLK1 in inflammatory signaling, thus positioning it as a novel target kinase for respiratory inflammatory disease treatment. In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKß phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory activity in an LPS-challenged acute lung injury model. These findings suggest that compound a24 may serve as a novel candidate for the development of DCLK1 inhibitors and a potential therapeutic agent for the treatment of inflammatory diseases.

The application of autofluorescence system contributes to the preservation of parathyroid function during thyroid surgery.

PURPOSE: The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS: A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS: The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION: This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.

Advancing Microfluidic Immunity Testing Systems: New Trends for Microbial Pathogen Detection.

Pathogenic microorganisms play a crucial role in the global disease burden due to their ability to cause various diseases and spread through multiple transmission routes. Immunity tests identify antigens related to these pathogens, thereby confirming past infections and monitoring the host's immune response. Traditional pathogen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs), are often labor-intensive, slow, and reliant on sophisticated equipment and skilled personnel, which can be limiting in resource-poor settings. In contrast, the development of microfluidic technologies presents a promising alternative, offering automation, miniaturization, and cost efficiency. These advanced methods are poised to replace traditional assays by streamlining processes and enabling rapid, high-throughput immunity testing for pathogens. This review highlights the latest advancements in microfluidic systems designed for rapid and high-throughput immunity testing, incorporating immunosensors, single molecule arrays (Simoas), a lateral flow assay (LFA), and smartphone integration. It focuses on key pathogenic microorganisms such as SARS-CoV-2, influenza, and the ZIKA virus (ZIKV). Additionally, the review discusses the challenges, commercialization prospects, and future directions to advance microfluidic systems for infectious disease detection.

Advances in Nucleic Acid Assays for Infectious Disease: The Role of Microfluidic Technology.

Within the fields of infectious disease diagnostics, microfluidic-based integrated technology systems have become a vital technology in enhancing the rapidity, accuracy, and portability of pathogen detection. These systems synergize microfluidic techniques with advanced molecular biology methods, including reverse transcription polymerase chain reaction (RT-PCR), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR), have been successfully used to identify a diverse array of pathogens, including COVID-19, Ebola, Zika, and dengue fever. This review outlines the advances in pathogen detection, attributing them to the integration of microfluidic technology with traditional molecular biology methods and smartphone- and paper-based diagnostic assays. The cutting-edge diagnostic technologies are of critical importance for disease prevention and epidemic surveillance. Looking ahead, research is expected to focus on increasing detection sensitivity, streamlining testing processes, reducing costs, and enhancing the capability for remote data sharing. These improvements aim to achieve broader coverage and quicker response mechanisms, thereby constructing a more robust defense for global public health security.

Topological Regulating Bismuth Nano-Semiconductor for Immunogenic Cell Death-Mediated Sonocatalytic Hyperthermia Therapy.

Immunogenic cell death (ICD) can activate the body's immune system via dead cell antigens to achieve immunotherapy. Currently, small molecule drugs have been used for ICD treatment in clinical, however, how to precisely control the induced ICD while treating tumors is of great significance for improving therapeutic efficacy. Based on this, a sono/light dual response strategy to tumor therapy and activation of ICD is proposed. A topological synthesis method is used to obtain sulfur-doped bismuth oxide Bi2 O3-x Sx (BS) using BiF3 (BF) as a template through reduction and a morphology-controllable bismuth-based nano-semiconductor with a narrow bandgap is constructed. Under the stimulation of ultrasound, BS can produce reactive oxygen species (ROS) through the sonocatalytic process, which cooperates with BS to consume glutathione and enhance cellular oxidative damage, further inducing ICD. Due to the introduction of sulfur in the reduction reaction, BS can achieve photothermal conversion under light, and combine with ROS to treat tumors. Further, with the assistance of ivermectin (IVM) to form composite (BSM), combined with sono/light dual strategy, ICD is promoted and DCs maturation is accelerated. The proposed ICD-mediated hyperthermia/sonocatalytic therapy strategy will pay the way for synergetic enhancement of tumor treatment efficacy and provide a feasible idea for controllable induction of ICD.

Construction of an La-BiVO4/O-Doped g-C3N4 Heterojunction Photocatalyst Embedded in Electrospinning Nanofibers.

BiVO4 has been widely used in the field of photocatalysis due to its nontoxic and moderate band gap. However, single BiVO4 has the disadvantages of a high recombination rate of photogenerated carriers and weak response to visible light, inhibiting its photocatalytic applications. To explore viable solutions, a hybrid material composed of lanthanum-doped bismuth vanadate (La-BiVO4) and oxygen-doped porous graphite carbon nitride (O-doped g-C3N4), i.e., La-BiVO4/O-doped g-C3N4 powder, was prepared by a facile hydrothermal reaction and low-temperature calcination. Then, the powder was loaded on polyacrylonitrile nanofibers (NFs) through the electrospinning fiber technique. Various surface science characterizations, including transmission electron microscopy and nitrogen absorption and desorption analysis, confirmed the successful synthesis of a mesoporous heterojunction material. The La3+-doping as well as the porous morphologies and larger specific surface area of the O-doped g-C3N4 ultimately improve the photocatalytic abilities via a proposed Z-scheme heterojunction mechanism. The roles of La3+-doping and morphology modification in promoting the separation of the photogenerated carriers and broadening the optical absorption range were experimentally discussed. The RhB degradation experiment indicated that the La-BiVO4/O-doped g-C3N4 powder has excellent photocatalytic activity, which is about 2.85 and 2 times higher than that of the pure BiVO4 and O-doped g-C3N4, respectively. Meanwhile, the La-BiVO4/O-doped g-C3N4 NF shows good stability and recoverability after a 10-cycle testing. Such a hybrid photocatalyst with a proposed Z-scheme heterojunction mechanism and good plasticity might pave a feasible way to fabricate a new library of photocatalysts.

In silico identification of A1 agonists and A2a inhibitors in pain based on molecular docking strategies and dynamics simulations.

Most recently, the adenosine is considered as one of the most promising targets for treating pain, with few side effects. It exists in the central nervous system, and plays a key role in nociceptive afferent pathway. It is reported that the A1 receptor (A1R) could inhibit Ca2+ channels to reduce the pain like analgesic mechanism of morphine. And, A2a receptor (A2aR) was reported to enhance the accumulation of AMP (cAMP) and released peptides from sensory neurons, resulting in constitutive activation of pain. Much evidence showed that A1R and A2aR could be served as the interesting targets for the treatment of pain. Herein, virtual screening was utilized to identify the small molecule compounds towards A1R and A2aR, and top six molecules were considered as candidates via amber scores. The molecular dynamic (MD) simulations and molecular mechanics/generalized born surface area (MM/GBSA) were employed to further analyze the affinity and binding stability of the six molecules towards A1R and A2aR. Moreover, energy decomposition analysis showed significant residues in A1R and A2aR, including His1383, Phe1276, and Glu1277. It provided basics for discovery of novel agonists and antagonists. Finally, the agonists of A1R (ZINC19943625, ZINC13555217, and ZINC04698406) and inhibitors of A2aR (ZINC19370372, ZINC20176051, and ZINC57263068) were successfully recognized. Taken together, our discovered small molecules may serve as the promising candidate agents for future pain research.

Pharmaceutical Cocrystal Discovery via 3D-SMINBR: A New Network Recommendation Tool Augmented by 3D Molecular Conformations.

Cocrystals have significant potential in various fields such as chemistry, material, and medicine. For instance, pharmaceutical cocrystals have the ability to address issues associated with physicochemical and biopharmaceutical properties. However, it can be challenging to find proper coformers to form cocrystals with drugs of interest. Herein, a new in silico tool called 3D substructure-molecular-interaction network-based recommendation (3D-SMINBR) has been developed to address this problem. This tool first integrated 3D molecular conformations with a weighted network-based recommendation model to prioritize potential coformers for target drugs. In cross-validation, the performance of 3D-SMINBR surpassed the 2D substructure-based predictive model SMINBR in our previous study. Additionally, the generalization capability of 3D-SMINBR was confirmed by testing on unseen cocrystal data. The practicality of this tool was further demonstrated by case studies on cocrystal screening of armillarisin A (Arm) and isoimperatorin (iIM). The obtained Arm-piperazine and iIM-salicylamide cocrystals present improved solubility and dissolution rate compared to their parent drugs. Overall, 3D-SMINBR augmented by 3D molecular conformations would be a useful network-based tool for cocrystal discovery. A free web server for 3D-SMINBR can be freely accessed at http://lmmd.ecust.edu.cn/netcorecsys/.

A Novel Strategy for Rapid Fluorescence Detection of FluB and SARS-CoV-2.

Undoubtedly, SARS-CoV-2 has caused an outbreak of pneumonia that evolved into a worldwide pandemic. The confusion of early symptoms of the SARS-CoV-2 infection with other respiratory virus infections made it very difficult to block its spread, leading to the expansion of the outbreak and an unreasonable demand for medical resource allocation. The traditional immunochromatographic test strip (ICTS) can detect one analyte with one sample. Herein, this study presents a novel strategy for the simultaneous rapid detection of FluB/SARS-CoV-2, including quantum dot fluorescent microspheres (QDFM) ICTS and a supporting device. The ICTS could be applied to realize simultaneous detection of FluB and SARS-CoV-2 with one test in a short time. A device supporting FluB/SARS-CoV-2 QDFM ICTS was designed and had the characteristics of being safe, portable, low-cost, relatively stable, and easy to use, ensuring the device could replace the immunofluorescence analyzer in cases where there is no need for quantification. This device does not need to be operated by professional and technical personnel and has commercial application potential.

Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT.

Renal-on-Chip Microfluidic Platform with a Force-Sensitive Resistor (ROC-FS) for Molecular Pathogenesis Analysis of Hydronephrosis.

Hydronephrosis is one of the most common diseases in urology. However, due to the difficulties in clinical trials and the lack of reliable in vitro platforms, the surgical indicators are not clear. Herein, the renal-on-chip with a force-sensitive resistor microfluidic platform was established to simulate the state of hydronephrosis. Cell counting kit-8 (CCK-8) and tight junction protein claudin-2 were detected on a renal-on-chip microfluidic platform with a force-sensitive resistor (ROC-FS). The results indicated that the ROC-FS had normal physiological functions and the cell viability on ROC-FS declined to around 40% after 48 h of hydronephrosis-simulated treatment. In addition, proteomics analysis of 15 clinical ureteropelvic junction obstruction (UPJO) samples showed that compared with normal children, a total of 50 common proteins were differentially expressed in UPJO children (P < 0.05, |log2fold change| ≥ 1). Metabolomic analysis of 39 clinical UPJO samples showed that a total of 241 metabolisms were dysregulated. Subsequent immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analysis using ROC-FS were performed to identify the clinical multi-omics results for screening. All results pointed out that the TGF-ß-related signaling pathways and arginine-related metabolism signaling pathways were dysregulated and α-SMA, AGT, and AGA might be the potential biomarkers of hydronephrosis. In addition, correlation analysis of AGT and KLK1 with differential renal function (DRF) from clinical samples indicated good correlation coefficients (R2 0.923, 0.8742, 0.6412, and 0.8347). This demonstrates the state of hydronephrosis could be significantly correlated with the biomarkers. These findings could provide a reliable reference for determining surgical biomarkers clinically, and ROC could be further used in the analysis of other kidney diseases.

Identification of a novel farnesoid X receptor agonist, kaempferol-7-O-rhamnoside, a compound ameliorating drug-induced liver injury based on virtual screening and in vitro validation.

Farnesoid X receptor (FXR), a bile acid receptor, plays an essential role in maintaining bile acid and liver homeostasis and has been recognized as an essential target for drug-induced liver injury (DILI). This study aimed to identify potential FXR agonists by virtual screening, molecular dynamics (MD) simulation, and biological assays. First, an in-house Traditional Chinese medicine compound database was screened using a virtual approach based on molecular docking to reveal potential FXR agonists. Secondly, MD was applied to analyze the process of agonist binding. Finally, the acetaminophen (APAP)-induced L02 cells model evaluated the pharmacodynamic activity of agonists treating DILI. Virtual screening results showed that kaempferol-7-O-rhamnoside was confirmed as the FXR agonist. MD results showed that kaempferol-7-O-rhamnoside could stably bind the FXR. In addition, in vitro cell-based assay showed that kaempferol-7-O-rhamnoside could promote the expression of the FXR gene and inhibit the Cyp7a1 gene expression in APAP-induced cells, significantly reducing the activities of AST, AKP and ROS, and enhancing the expression of GSH. The current study confirmed that kaempferol-7-O-rhamnoside might improve liver function by promoting proliferation, ameliorating oxidative stress, and regulating FXR target genes as observed in vitro. Therefore, in this study, discovering the FXR agonist, kaempferol-7-O-rhamnoside, provides valuable guidance for developing novel drugs against DILI.

Design, synthesis and evaluation of novel small molecules acting as Keap1-Nrf2 protein-protein interaction inhibitors.

Direct interference with Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has recently been introduced as an attractive approach to control life-threatening diseases like myocarditis. The present study aimed to investigate the potential application in myocarditis of a series of novel non-naphthalene derivatives as potential Keap1-Nrf2 PPI inhibitors. Our results indicated that the optimal compound K22 displayed the highest metabolic stability and showed notable Keap1-Nrf2 PPI inhibitory activities in vitro. K22 effectively triggered Nrf2 activation and increased the protein and mRNA expression of Nrf2-regulated genes in H9c2 cells. Moreover, pre-treatment with K22 was shown to mitigate LPS-induced damage to H9c2 cells, causing a marked decrease in the levels of inflammatory factors as well as reactive oxygen species (ROS). Furthermore, K22 was also shown to be non-mutagenic in the Ames test. Overall, our findings suggest that K22 may be a promising drug lead as a Keap1-Nrf2 PPI inhibitor for myocarditis treatment.

Left ventricular long-axis ultrasound strain (GLS) is an ideal indicator for patients with anti-hypertension treatment.

BACKGROUND: Primary hypertension is one of the most well-known risk factors for cardiovascular disease. Currently, there is still no ideal indicator for left ventricular end-diastolic pressure. METHODS: 73 hypertension patients and 37 healthy people were enrolled in this study. Each member was examined with conventional echocardiography including multiple indicators such as Peak mitral valve flow velocity (E, A), E/A, left atrial volume index (LAVl), tissue Doppler (PW-TDI) peak velocities during early and late diastolic mitral valve flow (e '), E/e ', and GLS. We have collected clinical data from all enrolled members. The above cardiac ultrasound indicators were obtained before the antihypertensive treatment, one month and three months after treatment. RESULTS: Left ventricular end-diastolic pressure (LVEDP) was positively correlated and negatively correlated with GLS (r = 0.638, P < .01) and E/e' (r = -0.578, P < .05), respectively. The hypertensives had lower e' value and higher values of GLS, E/e', and LAVI than the control group (P < .05). GLS and E/e' were significantly lower in hypertension group than those in the Control group after one month and three months of treatment (P < .05). The improvement rate of GLS was significantly higher than those in the improvement rate of e', E/e', LAVI after treatment (p < .05). CONCLUSION: The GLS improvement rate was significantly higher than those of e', E/e' after one and three-month treatment. Therefore, GLS might be a potential ideal index for patients with anti-hypertension treatment. The results obtained in this study provide useful information for further study.

Investigation of PM2.5-induced carcinogenic effects through mediation of ErbB family based on DNA methylation and transcriptomics analysis by a lung-mimicking microfluidic platform.

Fine particle (PM2.5, less than 2.5 micrometers in diameter) is regarded as a harmful carcinogen. However, the molecular mechanisms of the carcinogenic effects of ambient fine particles have not been fully elucidated, and therapeutic options to address this major public health challenge are lacking. Here, we present global gene-specific DNA methylation and transcriptomic (RNA-Seq) analyses after HBE cells were exposed to fine particles on a portable, small, and all-in-one organ-level lung-mimicking air-liquid interface exposure (MALIE) microfluidic platform. A series of cancer-related signal transduction pathways were activated. ErbB1, ErbB2, and ErbB3 gene expression altered by fine particle exposure was the result of changes in the cellular DNA methylome. The protein expression of ErbB family was inhibited by drugs and could regulate downstream Grb2/Raf pathway and Akt/MDM2 pathway. All of the above results indicated that ErbB family may be promising drug targets for air pollution-related diseases and that inhibitor drugs can be used as therapeutic options to treat these diseases.

SMINBR: An Integrated Network and Chemoinformatics Tool Specialized for Prediction of Two-Component Crystal Formation.

Two-component crystals such as pharmaceutical cocrystals and salts have been proven as an effective strategy to improve physicochemical and biopharmaceutical properties of drugs. It is not easy to select proper molecular combinations to form two-component crystals. The network-based models have been successfully utilized to guide cocrystal design. Yet, the traditional social network-derived methods based on molecular-interaction topology information cannot directly predict interaction partners for new chemical entities (NCEs) that have not been observed to form two-component crystals. Herein, we proposed an effective tool, namely substructure-molecular-interaction network-based recommendation (SMINBR), to prioritize potential interaction partners for NCEs. This in silico tool incorporates network and chemoinformatics methods to bridge the gap between NCEs and known molecular-interaction network. The high performance of 10-fold cross validation and external validation shows the high accuracy and good generalization capability of the model. As a case study, top 10 recommended coformers for apatinib were all experimentally confirmed and a new apatinib cocrystal with paradioxybenzene was obtained. The predictive capability of the model attributes to its accordance with complementary patterns driving the formation of intermolecular interactions. SMINBR could automatically recommend new interaction partners for a target molecule, and would be an effective tool to guide cocrystal design. A free web server for SMINBR is available at http://lmmd.ecust.edu.cn/sminbr/.

Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia.

A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.

CCT6A may act as a potential biomarker reflecting tumor size, lymphatic metastasis, FIGO stage, and prognosis in cervical cancer patients.

OBJECTIVE: Chaperonin-containing tailless complex polypeptide subunit 6A (CCT6A) is a critical regulator and newly identified clinical biomarker of several cancers, while its correlation with the clinical characteristics and prognosis of cervical cancer patients is unclear. Therefore, this study aimed to explore this issue. METHODS: Chaperonin-containing tailless complex polypeptide subunit 6A expression in tumor and tumor-adjacent tissues from 198 cervical cancer patients who underwent resection were detected by immunohistochemistry assay and reverse transcription-quantitative polymerase chain reaction. Besides, the clinicopathological features and survival data of cervical cancer patients were collected. RESULTS: Chaperonin-containing tailless complex polypeptide subunit 6A protein and mRNA levels were both increased in tumor tissues compared with tumor-adjacent tissues (both p < 0.001). Receiver operating characteristic curves showed that CCT6A protein (AUC: 0.774, 95% CI: 0.729-0.819) and mRNA levels (AUC: 0.904, 95% CI: 0.874-0.934) well discriminated tumor tissues from tumor-adjacent tissues. Besides, correlation analyses found that CCT6A protein and mRNA levels were positively correlated with lymph node metastasis and FIGO stage (all p < 0.05), apart from which CCT6A mRNA level was also positively associated with tumor size (p = 0.032). In addition, CCT6A protein and mRNA levels were negatively correlated with accumulating disease-free survival (both p < 0.05); meanwhile CCT6A mRNA level was negatively associated with accumulating overall survival as well (p = 0.010). CONCLUSION: Chaperonin-containing tailless complex polypeptide subunit 6A is elevated in tumor tissues, and its high expression associates with larger tumor size, lymph node metastasis, higher FIGO stage, and worse prognosis in cervical cancer patients.

A Meta-Analysis of Abnormal Glucose Metabolism in First-Episode Drug-Naive Schizophrenia.

BACKGROUND: Patients with schizophrenia exhibit a higher mortality rate compared with the general population. This mortality has been attributed predominantly by the high risk of type 2 diabetes mellitus in the patients. We aimed to assess the inherent risk of glucose metabolism abnormalities in first-episode drug-naive schizophrenia. SUBJECTS AND METHODS: We searched English database (PubMed, EMBASE, MEDLINE, Cochrane Library databases) and Chinese database (Wan Fang Data, CBM disc, VIP, and CNKI) from their inception until Jul 2018 for case-control studies examining glucose metabolism abnormalities. Measurements, such as fasting plasma glucose levels, fasting plasma insulin levels, insulin resistance and HbA1c levels in first-episode antipsychotic-naive patients were used to test for prediabetes. Standardized/weighted mean differences and 95% confidence intervals were calculated and analyzed. RESULTS: 19 studies (13 in English and 6 in Chinese) consisting of 1065 patients and 873 controls were included. Fasting plasma glucose levels (95% CI; 0.02 to 0.29; P=0.03), 2 h plasma glucose levels after an OGTT (95% CI; 0.63 to 1.2; P<0.00001), fasting plasma insulin levels (95% CI; 0.33 to 0.73; P<0.00001), insulin resistance (95% CI; 0.29 to 0.6; P<0.00001) in patients with first-episode schizophrenia were significant elevated. There was no significant difference in HbA1c level (95% CI; -0.34 to 0.18; P=0.54) in patients with first-episode schizophrenia compared with controls. CONCLUSIONS: This meta-analysis showed that glucose metabolism was impaired in patients with first-episode schizophrenia. Higher quality studies with larger samples are warranted to confirm these findings.

Cadmium stress suppresses lateral root formation by interfering with the root clock.

A biological clock activated by oscillating signals, known as root clock, has been linked to lateral root (LR) formation and is essential for regular LR spacing along the primary root. However, it remains unclear how this internal mechanism is influenced by environmental factors known to affect the LR pattern. Here, we report that excessive cadmium (Cd) inhibits LR formation by disrupting the lateral root cap (LRC)-programmed cell death (PCD)-regulated root clock. Cd restricts the frequency of the oscillating signal rather than its amplitude. This could be attributed to the inhibition on meristematic activity by Cd, which resulted in decreased LRC cell number and LRC-PCD frequency. Genetic evidence further showed that LRC cell number is positively correlated with root resistance to Cd. Our study reveals root cap dynamics as a novel mechanism mediating root responses to Cd, providing insight into the signalling pathways of the root clock responding to environmental cues.