Impact of the ketogenic diet as a dietary approach on cardiovascular disease risk factors: a meta-analysis of randomized clinical trials.

BACKGROUND: Cardiovascular diseases (CVD) remain the leading cause of mortality globally, and the scarcity of scientific evidence regarding the impact of ketogenic diets on CVD risk factors necessitates urgent attention and redress. OBJECTIVES: This meta-analysis evaluates the impact of the ketogenic diet on CVD risk factors compared with control diets through randomized controlled trials (RCTs). METHODS: The study was registered in advance in the PROSPERO database (CRD42023491853). A systematic search was conducted across PubMed, Web of Science, EMBASE, and Cochrane Library to identify relevant RCTs. Fixed and random effects were employed to calculate the mean differences and 95% confidence intervals (CIs) for changes in CVD risk factors pre- and postketogenic diet intervention. RESULTS: A total of 27 RCTs with 1278 participants were analyzed. The ketogenic diet intervention presented increase in total cholesterol (mean differences: 0.36 mmol/L; 95% CI: 0.15, 0.57; I2: 85.1%), low-density lipoprotein cholesterol (mean differences: 0.35 mmol/L; 95% CI: 0.20, 0.50; I2: 73.9%) and high-density lipoprotein cholesterol (mean differences: 0.16 mmol/L; 95% CI: 0.09, 0.23; I2: 86.7%) concentrations. Reductions were observed in the triglyceride (mean differences: -0.20 mmol/L; 95% CI: -0.29, -0.11; I2: 72.2%), blood glucose (mean differences: -0.18 mmol/L; 95% CI: -0.33, -0.02; I2: 76.4%), blood insulin (mean differences: -8.32 pmol/L; 95% CI: -14.52, -2.12; I2: 81.5%), diastolic blood pressure (mean differences: -1.41 mmHg; 95% CI: -2.57, -0.26; I2: 49.1%), weight (mean differences: -2.59 kg; 95% CI: -3.90, -1.28; I2: 87.4%), and body mass index (mean differences: -1.59 kg/m2; 95% CI: -2.32, -0.86; I2: 84.5%) concentrations after implementing ketogenic diets. CONCLUSIONS: Although the ketogenic diet demonstrates benefits in terms of triglyceride, blood pressure, weight, and glycemic control, its impact on CVD risk factors, especially the elevated total cholesterol and low-density lipoprotein cholesterol concentrations, warrants a cautious approach.

Timeframe for Conversion to Psychosis From Individuals at Clinical High-Risk: A Quantile Regression.

BACKGROUND AND HYPOTHESIS: The time taken for an individual who is at the clinical high-risk (CHR) stage to transition to full-blown psychosis may vary from months to years. This temporal aspect, known as the timeframe for conversion to psychosis (TCP), is a crucial but relatively underexplored dimension of psychosis development. STUDY DESIGN: The sample consisted of 145 individuals with CHR who completed a 5-year follow-up with a confirmed transition to psychosis within this period. Clinical variables along with functional variables such as the Global Assessment of Function (GAF) score at baseline (GAF baseline) and GAF-drop from the highest score in the past year. The TCP was defined as the duration from CHR identification to psychosis conversion. Participants were categorized into 3 groups based on TCP: "short" (≤6 months, ≤33.3%), "median" (7-17 months, 33.3%-66.6%), and "long" (≥18 months, ≥66.6%). The quantile regression analysis was applied. STUDY RESULTS: The overall sample had a median TCP of 11 months. Significant differences among the three TCP groups were observed, particularly in GAF-drop (χ2 = 8.806, P = .012), disorganized symptoms (χ2 = 7.071, P = .029), and general symptoms (χ2 = 6.586, P = .037). Greater disorganized symptoms (odds ratio [OR] = 0.824, P = .009) and GAF-drop (OR = 0.867, P = .011) were significantly associated with a shorter TCP, whereas greater general symptoms (OR = 1.198, P = .012) predicted a longer TCP. Quantile regression analysis demonstrated a positive association between TCP and GAF baseline above the 0.7 quantile and a negative association between TCP rank and GAF drop below the 0.5 quantile. CONCLUSIONS: This study underscores the pivotal role of functional characteristics in shaping TCP among individuals with CHR, emphasizing the necessity for a comprehensive consideration of temporal aspects in early prevention efforts.

Prolyl hydroxylase domain enzyme PHD2 inhibits proliferation and metabolism in non-small cell lung cancer cells in HIF-dependent and HIF-independent manners.

Prolyl hydroxylase domain protein 2 (PHD2) is one of the intracellular oxygen sensors that mediates proteasomal degradation of hypoxia-inducible factor (HIF)-α via hydroxylation under normoxic conditions. Because of its canonical function in the hypoxia signaling pathway, PHD2 is generally regarded as a tumor suppressor. However, the effects of PHD2 in tumorigenesis are not entirely dependent on HIF-α. Based on analysis of data from the Cancer Genome Atlas (TCGA) database, we observed that the expression of PHD2 is upregulated in non-small cell lung cancer (NSCLC), which accounts for approximately 80-85% of lung cancers. This suggests that PHD2 may play an important role in NSCLC. However, the function of PHD2 in NSCLC remains largely unknown. In this study, we established PHD2-deficient H1299 cells and PHD2-knockdown A549 cells to investigate the function of PHD2 in NSCLC and found that PHD2 suppresses cell proliferation and metabolism but induces ROS levels in human NSCLC cells. Further results indicated that the function of PHD2 in NSCLC is dependent on its enzymatic activity and partially independent of HIF. Moreover, we performed RNA-sequencing and transcriptomic analysis to explore the underlying mechanisms and identified some potential targets and pathways regulated by PHD2, apart from the canonical HIF-mediated hypoxia signaling pathway. These results provide some clues to uncover novel roles of PHD2 in lung cancer progression.

[Two new glycosides from Hypericum elatoides].

The column chromatography with silica gel, reversed-phase C_(18), and Sephadex LH-20 was employed to separate the methanol extract of the aerial parts of Hypericum elatoides. The compounds were identified by the comprehensive analysis of IR, NMR, and MS data as methyl 8-O-ß-D-glucopyranosyl-(Z)-5-octenoate(1), methyl 3-O-ß-D-glucopyranosyl-4-methylhexanoate(2), byzantionoside B(3), 9-epi-blumenol C glucoside(4), corchoionoside C(5),(6S,9R)-roseoside(6), cis-p-coumaric acid 4-O-ß-D-glucopyranoside(7), trans-p-coumaric acid 4-O-ß-D-glucopyranoside(8), methyl 3-(4-hydroxyphenyl)propanoate(9),(E)-chlorogenic acid methyl ester(10), quercetin-3-O-ß-D-glucopyranoside(11), ß-sitosterol(12), stigmasterol(13), stigmast-4-en-3-one(14), ß-amyrin(15), daucosterol(16), sitoindoside Ⅰ(17), oleic acid(18), methyl α-linolenate(19), trilinolein(20), and cassipourol(21). Among them, compounds 1 and 2 were identified as new glycosides and named hyperelatosides G and H. Compounds 3-5, 7-9, 17, and 20-21 were isolated from the genus Hypericum for the first time. The remaining compounds were isolated from H. elatoides for the first time. The results of biological assays revealed that compound 11 exhibited significant anti-neuroinflammatory activity, and compounds 1, 3, and 19 displayed certain neuroprotective effects.

Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization.

BACKGROUND: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol-induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD. METHODS: Almost 8-12-week-old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg-1·h-1, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y-maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt-like protein 1 (BMAL1), brain-derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme-linked immunosorbent assay detected IL-6, IL-1ß, arginase 1 (Arg1), and IL-10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes. RESULTS: Compared to the control group, the sleep-deprived rats showed poor cognitive performance on both the MWM test and the Y-maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non-rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL-1ß and IL-6 levels, increased BDNF, Arg1, and IL-10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti-inflammatory M2 type. CONCLUSION: Propofol reduces SD-induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.

Distribution of self-reported borderline personality disorder traits symptoms in a large-scale clinical population.

Introduction: Borderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations. Methods: A total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: "F1: Affective Instability and Impulsivity", "F2: Interpersonal Unstable and Extreme Reactions", and "F3: Identity Disturbance". Results: Among 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p<0.001). Discussion: Our study revealed the pervasive presence of BPD traits and symptoms among psychiatric outpatients, exhibiting distinctive distributions across gender, age, and diagnostic categories. These findings emphasize the significance of identifying and addressing BPD pathology in the clinical care of psychiatric outpatients.

Sex-specific comparative outcomes between oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis.

AIMS: Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022. Sex-specific comparative outcomes of stroke/systemic embolism (SE), major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) between oral anticoagulants were pooled using random effects models. P values for interaction were calculated to examine differences in results between sexes. RCTs and observational studies were meta-analysed separately. RESULTS: 5 RCTs and 33 observational studies were included, totalling 1 085 931 women and 1 387 123 men. Meta-analyses showed that for both sexes, DOAC versus warfarin was generally associated with lower risk of stroke/SE, major bleeding and ICH; in DOAC-DOAC comparisons, rivaroxaban versus dabigatran had higher GIB risk. The only sex-specific difference observed was that when compared with warfarin, women had higher GIB risk with rivaroxaban (women: pooled risk ratio (pRR)=1.34, 95% CI=1.18 to 1.51; men: pRR=0.97, 95% CI=0.85 to 1.10; p value for interaction (p for interaction)<0.001) and possibly dabigatran (women: pRR=1.25, 95% CI=0.92 to 1.70; men: pRR=0.83, 95% CI=0.72 to 0.97; p-for-interaction=0.02). The sex difference in GIB remained for rivaroxaban when a Bonferroni-corrected significance level was used (α=0.003). No sex-specific GIB data for apixaban and edoxaban was available for the meta-analysis. CONCLUSIONS: For both sexes, DOACs generally demonstrated favourable effectiveness and safety over warfarin. However, observational data suggested that women may have higher GIB risk with rivaroxaban and possibly dabigatran than warfarin. Further studies are warranted to verify our findings and elucidate sex-specific GIB risk with apixaban and edoxaban, of which the data is currently lacking. PROSPERO REGISTRATION NUMBER: CRD42022325027.

Regioselective fluorination of allenes enabled by I(I)/I(III) catalysis.

The prominence and versatility of propargylic fluorides in medicinal chemistry, coupled with the potency of F/H and F/OH bioisosterism, has created a powerful impetus to develop efficient methods to facilitate their construction. Motivated by the well-established conversion of propargylic alcohols to allenes, an operationally simple, organocatalysis-based strategy to process these abundant unsaturated precursors to propargylic fluorides would be highly enabling: this would consolidate the bioisosteric relationship that connects propargylic alcohols and fluorides. Herein, we describe a highly regioselective fluorination of unactivated allenes based on I(I)/I(III) catalysis in the presence of an inexpensive HF source that serves a dual role as both nucleophile and Brønsted acid activator. This strategy enables a variety of secondary and tertiary propargylic fluorides to be prepared: these motifs are prevalent across the bioactive small molecule spectrum. Facile product derivatisation, concise synthesis of multi-vicinal fluorinated products together with preliminary validation of enantioselective catalysis are disclosed. The expansive potential of this platform is also demonstrated through the highly regioselective organocatalytic oxidation, chlorination and arylation of allenes. It is envisaged that the transformation will find application in molecular design and accelerate the exploration of organofluorine chemical space.

Community Composition and Functional Characterization of Microorganisms in Surface Sediment of the New Britain Trench.

The deep-sea harbors abundant prokaryotic biomass is a major site of organic carbon remineralization and long-term carbon burial in the ocean. Deep-sea trenches are the deepest part of the ocean, and their special geological and morphological features promoting the accumulation of organic matter and active organic carbon turnover. Despite the expanding reports about the organic matter inputs, limited information is known regarding microbial processes in deep-sea trenches. In this study, we investigated the species composition and metabolic potential in surface sediment of the New Britain Trench (NBT), using a metagenomic approach. The predominant microbial taxa in NBT sediment include Proteobacteria, Acidobacteria, Planctomycetes, Actinobacteria and Chloroflexota. The microbial communities showed highly diverse metabolic potentials. Particularly, genes encoding enzymes for degradation of aromatic compounds, as well as those encoding haloalkane dehalogenase and haloacetate dehalogenase were annotated in the NBT surface sediment, which indicate the potential of microorganisms to degrade different types of refractory organic matter. The functional genes encoding enzymes for dissimilatory nitrate reduction, denitrification, and nitrification were also represented in the NBT metagenome. Overall, the microbial communities show high diversity of heterotrophic lineages and metabolic features, supporting their potential contributions in organic carbon metabolism. Meanwhile, Nitrosopumilus, a dominant genus in the surface sediment of the NBT, is a typical ammonia-oxidizing archaea (AOA), with autotrophic CO2 fixation pathways including the 3-hydroxypropionate/4-hydroxybutylate (3HP/4HB) cycle, the reductive TCA (rTCA) cycle. The results demonstrate that autotrophic metabolic processes also play an important role in the surface sediment, by providing newly synthesized organic matter.

Enhancing Air Traffic Control Communication Systems with Integrated Automatic Speech Recognition: Models, Applications and Performance Evaluation.

In air traffic control (ATC), speech communication with radio transmission is the primary way to exchange information between the controller and the pilot. As a result, the integration of automatic speech recognition (ASR) systems holds immense potential for reducing controllers' workload and plays a crucial role in various ATC scenarios, which is particularly significant for ATC research. This article provides a comprehensive review of ASR technology's applications in the ATC communication system. Firstly, it offers a comprehensive overview of current research, including ATC corpora, ASR models, evaluation measures and application scenarios. A more comprehensive and accurate evaluation methodology tailored for ATC is proposed, considering advancements in communication sensing systems and deep learning techniques. This methodology helps researchers in enhancing ASR systems and improving the overall performance of ATC systems. Finally, future research recommendations are identified based on the primary challenges and issues. The authors sincerely hope this work will serve as a clear technical roadmap for ASR endeavors within the ATC domain and make a valuable contribution to the research community.

Filamentation and inhibition of prokaryotic CTP synthase with ligands.

Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic pathogens. Utilizing cryo-electron microscopy, we determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, nicotinamide adenine dinucleotide (NADH), and the covalent inhibitor 6-diazo-5-oxo- l-norleucine (DON), achieving a resolution of 2.9 Å. We constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis, providing an evolutionary perspective on CTPS filament formation. Our computational analysis revealed a solvent-accessible ammonia tunnel upon DON binding. Through comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

Gastric Cancer Assembloids Derived from Patient-Derived Xenografts: A Preclinical Model for Therapeutic Drug Screening.

The construction of reliable preclinical models is crucial for understanding the molecular mechanisms involved in gastric cancer and for advancing precision medicine. Currently, existing in vitro tumor models often do not accurately replicate the human gastric cancer environment and are unsuitable for high-throughput therapeutic drug screening. In this study, droplet microfluidic technology is employed to create novel gastric cancer assembloids by encapsulating patient-derived xenograft gastric cancer cells and patient stromal cells in Gelatin methacryloyl (GelMA)-Gelatin-Matrigel microgels. The usage of GelMA-Gelatin-Matrigel composite hydrogel effectively alleviated cell aggregation and sedimentation during the assembly process, allowing for the handling of large volumes of cell-laden hydrogel and the uniform generation of assembloids in a high-throughput manner. Notably, the patient-derived xenograft assembloids exhibited high consistency with primary tumors at both transcriptomic and histological levels, and can be efficiently scaled up for preclinical drug screening efforts. Furthermore, the drug screening results clearly demonstrated that the in vitro assembloid model closely mirrored in vivo drug responses. Thus, these findings suggest that gastric cancer assembloids, which effectively replicate the in vivo tumor microenvironment, show promise for enabling more precise high-throughput drug screening and predicting the clinical outcomes of various drugs.

Exploring drug repositioning possibilities of kinase inhibitors via molecular simulation.

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

In-situ monitoring of cellular H2O2 within 3D cell clusters using conductive scaffolds.

Accurately monitoring H2O2 concentrations in 3D cell clusters is challenging due to limited diffusion and rapid degradation of H2O2 in the culture medium. Despite the incorporation of three-dimensional cell culture approaches, the detection technology has largely remained as a 2D planar system. In this study, we present a versatile approach of 3D electrochemical sensing utilizing carbon nanotubes as conductive scaffolds for in-situ monitoring of H2O2 in cell clusters. These scaffolds enabled direct contact between H2O2 released from cells and the electrodes, thereby improving sensitivity and ensuring biocompatibility for cell aggregates. The scaffolds exhibited electrocatalytic behavior with a limit of detection of 6.7 nM H2O2. Additionally, the electrochemical responses of cell clusters with the scaffolds exhibited significantly higher current compared to clusters without scaffolds when stimulated with model drugs. This study underscores the potential of conductive scaffolds for real-time monitoring of H2O2 released from cell clusters in 3D microenvironments.

Multifunctional Phosphor with High-Efficient Near-Infrared Emission Based on Antimony-Zinc Halides.

Metal halide-based broadband near-infrared (NIR) luminescent materials face problems such as complicated preparation, high cost, low photoluminescence quantum yield, and high excitation energy. Here, incorporating Sb3+ and Br- into (C20H20P)2ZnCl4 crystals allowed for the achievement of efficient broadband near-infrared emission under 400 nm excitation while maintaining satisfactory environmental and thermal stability. The compounds exhibit a broad range of emission bands from 550 to 1050 nm, with a photoluminescence quantum yield of 93.57%. This is a groundbreaking achievement for organic-inorganic hybrid metal halide NIR luminescent materials. The near-infrared emission is suggested to originate from [SbX5]2-, as supported by the femtosecond transient absorption spectra and density-functional theory calculations. This phosphor-based NIR LEDs successfully demonstrate potential applications in night vision, medical imaging, information encryption, and anticounterfeiting.

An RPA-Assisted CRISPR/Cas12a Assay Combining Fluorescence and Lateral Flow Strips for the Rapid Detection of Enterotoxigenic Bacillus cereus.

Bacillus cereus (B. cereus) is a foodborne pathogen that can produce tripartite enterotoxins, which can cause a variety of diseases after infection. It is critical to rapidly and accurately detect strains with enteropathogenic potential to safeguard human health. In this study, a dual-signal visualized detection platform with fluorescence assay and paper-based lateral flow assay (LFA) based on recombinase polymerase amplification (RPA), CRISPR/Cas12a system, and self-developed CRISPR nucleic acid test strips was constructed for enterotoxigenic B. cereus. The genes that encode two tripartite enterotoxins─nheA, nheB, and nheC for nonhemolytic enterotoxin and hblA, hblC, and hblD for hemolysin BL─were utilized as detection targets. The platform was capable of detecting six enterotoxin genes at the same genomic DNA level. The limits of detection for each gene were 10-3 ng/µL in fluorescence assay and 10-4 ng/µL in LFA. Furthermore, 101-102 CFU/mL of B. cereus in pure culture was detected. Additionally, a smartphone miniprogram could assist in evaluating the results in LFA. The platform demonstrated good utility by detecting B. cereus in food samples, including milk and rice. The results indicate that our RPA-CRISPR/Cas12a dual-signal visualized detection platform can quickly and easily detect B. cereus with three-component enterotoxin-producing potentials. The whole analytic process took less than 60 min without complex operation or expensive equipment.

The cumulative impact of temperature and nitrogen availability on the potential nitrogen fixation and extracellular polymeric substances secretion by Dolichospermum.

Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.

Chromosome-level genome assembly of Cnidium monnieri, a highly demanded traditional Chinese medicine.

Cnidium monnieri, a medicinal herb of the Cnidium genus and the Apiaceae family, is among the most important traditional Chinese medicines and is widely distributed in China. However, to date, no C. monnieri-related genomic information has been described. In this study, we assembled the C. monnieri genome of approximately 1210.23 Mb with a contig N50 of 83.14 Mb. Using PacBio HiFi and Hi-C sequencing data, we successfully anchored 93.86% of the assembled sequences to 10 pseudochromosomes (2n = 20). We predicted a total of 37,460 protein-coding genes, with 97.02% of them being functionally annotated in Non-Redundant, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and other databases. In addition, we identified 2,778 tRNAs, 4,180 rRNAs, 258 miRNAs, and 1,700 snRNAs in the genome. This is the first reported C. monnieri genome. Hopefully, the availability of this chromosome-level reference genome provides a significant basis for upcoming natural product-related biosynthetic pathway assessment in C. monnieri.

Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom-Dominant Psychosis.

Importance: Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge. Objective: To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis. Design, Setting, and Participants: This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023. Exposure: Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD. Main Outcomes and Measures: Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Results: This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002). Conclusions and Relevance: The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

Acupoint catgut embedding attenuates oxidative stress and cognitive impairment in chronic cerebral ischemia by inhibiting the Ang II/AT1R/NOX axis.

Chronic cerebral ischemia (CCI) is a common neurological disorder, characterized by progressive cognitive impairment. Acupoint catgut embedding (ACE) represents a modern acupuncture form that has shown neuroprotective effects; nevertheless, its effects on CCI and the mechanisms remain largely unknown. Here, we aimed to explore the therapeutic action of ACE in CCI-induced cognitive impairment and its mechanisms. The cognitive function of CCI rats was determined using Morris water maze test, and histopathological changes in the brain were assessed through hematoxylin-eosin (HE) staining. To further explore the molecular mechanisms, the expression levels of oxidative stress markers and the Ang II/AT1R/NOX axis-associated molecules in the hippocampus were evaluated using enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry. Here, we observed that ACE treatment alleviated cognitive dysfunction and histopathological injury in CCI rats. Intriguingly, candesartan (an AT1R blocker) enhanced the beneficial effects of ACE on ameliorating cognitive impairment in CCI rats. Mechanistically, ACE treatment blocked the Ang II/AT1R/NOX pathway and subsequently suppressed oxidative stress, thus mitigating cognitive impairment in CCI. Our findings first reveal that ACE treatment could suppress cognitive impairment in CCI, which might be partly due to the suppression of Ang II/AT1R/NOX axis.