The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia.

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Serotonin syndrome caused by escitalopram in Parkinson's disease psychosis: a case report.

BACKGROUND: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning. CASE PRESENTATION: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition. CONCLUSIONS: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

Potential Roles of the GRF Transcription Factors in Sorghum Internodes during Post-Reproductive Stages.

Growth-regulating factor (GRF) is a plant-specific family of transcription factors crucial for meristem development and plant growth. Sorghum (Sorghum bicolor L. Moench) is a cereal species widely used for food, feed and fuel. While sorghum stems are important biomass components, the regulation of stem development and the carbohydrate composition of the stem tissues remain largely unknown. Here, we identified 11 SbGRF-encoding genes and found the SbGRF expansion driven by whole-genome duplication events. By comparative analyses of GRFs between rice and sorghum, we demonstrated the divergence of whole-genome duplication (WGD)-derived OsGRFs and SbGRFs. A comparison of SbGRFs' expression profiles supports that the WGD-duplicated OsGRFs and SbGRFs experienced distinct evolutionary trajectories, possibly leading to diverged functions. RNA-seq analysis of the internode tissues identified several SbGRFs involved in internode elongation, maturation and cell wall metabolism. We constructed co-expression networks with the RNA-seq data of sorghum internodes. Network analysis discovered that SbGRF1, 5 and 7 could be involved in the down-regulation of the biosynthesis of cell wall components, while SbGRF4, 6, 8 and 9 could be associated with the regulation of cell wall loosening, reassembly and/or starch biosynthesis. In summary, our genome-wide analysis of SbGRFs reveals the distinct evolutionary trajectories of WGD-derived SbGRF pairs. Importantly, expression analyses highlight previously unknown functions of several SbGRFs in internode elongation, maturation and the potential involvement in the metabolism of the cell wall and starch during post-anthesis stages.

Application of Difluoromethyl Isosteres in the Design of Pesticide Active Molecules.

Difluoromethyl (CF2H) groups have been found in many listed pesticides due to their unique physical and chemical properties and outstanding biological activity. In pesticide molecules, compared with the drastic changes brought by trifluoromethyl, difluoromethyl usually moderately regulates the metabolic stability, lipophilicity, bioavailability, and binding affinity of compounds. Therefore, difluoromethylation has become an effective means to modify the biological activity of pesticide molecules. This paper reviews the representative literatures and patents containing difluoromethyl groups in the past 10 years, and introduces the research progress. The aim is to provide an effective reference value for the study of difluoromethyl in pesticides.

The effect of self-rated health on depressive symptoms in Chinese older adults: The mediating role of social participation and spouse health.

This study investigates the relationship between self-rated health, social participation, spouse health, and depressive symptoms in older adults. It also analyzed the moderating effects of gender, drinking, visual function, diet, quality of life, and economic level on the model. We analyzed data from 5119 participants aged 60 and above, from the CLHLS. We used a partial least squares structural equation model to explore the correlation between self-rated health, spouse health, social participation, and depressive symptoms. Self-rated health was significantly correlated with spouse health, social participation, and depressive symptoms (P < 0.001). Social participation (ß=-0.034) and spouse health (ß=-0.029) were mediators of self-rated health to depressive symptoms. In addition, gender, drinking, visual function, diet, quality of life, and economic level were mediated factors. This study provides evidence that self-rated health has direct or indirect associations with depressive symptoms in older people, with social participation and spouse health playing a crucial mediating role.

Associations between abnormal sleep behavior and indoor environmental risk factors among children with a chronic cough in Wuxi, China: a cross-sectional study.

BACKGROUND: Indoor environmental factors, such as pet ownership, presence of cockroaches, mattress quality, fuel usage (gas or electricity), use of biomass for cooking and heating, exposure to tobacco smoke or household molds can significantly affect the sleep quality of children with chronic cough. However, data regarding the effects of indoor environmental conditions on sleep in this population are limited. This study aimed to assess the prevalence of abnormal sleep behaviors and to establish associations between indoor environmental factors and sleep behaviors among children with chronic cough in Wuxi, China. METHODS: A cross-sectional design was employed in this study, involving children aged 3-18 years. Data on sociodemographic factors, allergies, home environmental exposures, and sleep characteristics of the participants were collected using paper-based questionnaires. The association between indoor environmental factors and sleep behaviors in children with chronic cough was analyzed using logistic regression models. RESULTS: The findings demonstrated that the prevalence of chronic cough among children in Wuxi was 15.50%. The chronic cough group exhibited a significantly higher incidence of eczema, wheezing, rhinitis, food allergy, and nasosinusitis than the non-chronic cough group. In addition, children with chronic cough also tended to have a family history of sleep disorders and adenoid hypertrophy (P < 0.01). After adjusting for confounding factors, a significant association was observed between bruxism (teeth grinding) and chronic cough (sometimes: odds ratio [OR] = 1.04; confidence interval [CI] = 1.01-1.08; always: OR = 1.11; CI = 1.04-1.19; P < 0.01). Among children with chronic cough, recent home decoration was associated with sleepwalking (OR = 1.04; CI = 1.00-1.07; P < 0.05), mold exposure was associated with bruxism (OR = 1.15; CI = 1.0-1.31; P < 0.05), and carpet use at home was associated with apnea (OR = 1.09; CI = 1.02-1.17; P < 0.05), twitching during sleep (OR = 1.13; CI = 1.00-1.27; P < 0.01) and morning headache (OR = 1.14; CI = 1.05-1.23; P < 0.01). CONCLUSION: Children with chronic cough are more prone to some abnormal sleep behaviors than children without chronic cough. Household decoration within a year, household mold exposure, and carpet use were all significantly positively associated with abnormal sleep behaviors in children with chronic cough. Our study provides novel insights into the impact of the indoor environment on children's sleep and the occurrence of chronic cough, offering guidance for tailored health promotion programs for families.

Factors associated with an inconclusive result from commercial homologous recombination deficiency testing in ovarian cancer.

INTRODUCTION: Homologous recombination deficiency (HRD) testing is used to determine the appropriateness of poly ADP-ribose polymerase inhibitors for patients with epithelial ovarian cancer and no germline/somatic BRCA1/2 alterations. Myriad MyChoice CDx reports a genomic instability score (GIS) to quantify the level of HRD, with a positive score defined as ≥42. The authors sought to define factors associated with obtaining an inconclusive HRD test result. METHODS: GIS was retrieved for patients at their institution with epithelial ovarian cancer without germline/somatic BRCA1/2 deleterious alterations who underwent HRD testing from April 2020-August 2023. Clinical data were abstracted from the medical record. RESULTS: Of 477 HRD test results identified, 57 (12%) were inconclusive. High-grade serous ovarian cancers had higher GIS than other histologic types (median 29 vs. 21, p < .001). Most HRD cases were of high-grade serous histology; no cases with clear cell or endometrioid histology were HRD-positive. On univariate analysis, interval versus primary cytoreductive surgery, other specimen sources versus surgical specimens, and chemotherapy exposure were risk factors for inconclusive HRD testing. On multivariable analysis, chemotherapy exposure, and tissue source were associated with an inconclusive test result, with surgical specimens more likely to yield a conclusive result than other sources (biopsy, cytology, other). Age, stage, self-reported race, and histology were not associated with an inconclusive result. CONCLUSIONS: Surgical tissue was more likely to yield a conclusive HRD test result versus other sources of epithelial ovarian cancer tissue acquisition. When feasible, laparoscopic biopsy before initiation of neoadjuvant chemotherapy may increase the likelihood of obtaining interpretable HRD test results.

First Report of Fusarium avenaceum Causing Root Rot of Raspberry (Rubus corchorifolius) in China.

Raspberry (Rubus corchorifolius) plants hold historical, economic, and medicinal importance in China (Yang et al. 2022). Raspberries are cultivated to generate income for local farmers in Lintao County, Dingxi City, Gansu Province. However, farmers encountered challenges due to raspberry plants exhibiting root rot disease, resulting in plant death. During a thorough field survey conducted in June 2022, symptoms ranging from leaf yellowing and wilting to necrotic lesions and root rots were observed, where approximately 30% of raspberry plants were affected. Five diseased and healthy plants were collected from the farmers' fields in Lintao (35.53oN, 103.84oE) for pathogen identification. Symptomatic and asymptomatic root tissues were surface sterilized with 75% ethanol for 30 s and 3% NaOCl for 5 min, followed by three rinses in sterile water. Small pieces (0.5 × 0.5 cm) were cut and incubated on potato dextrose agar (PDA) plates at 25°C for 7-10 days. Twenty-two pure Fusarium isolates, which displayed four distinct colony groups morphologically, were obtained. Pathogenicity tests on isolates RB10, RB1, RB30, and RB23, representing each colony group, revealed that RB10 exhibited symptoms similar to those observed in the field. The RB10 strain produced yellowish-white to greyish-white colonies on PDA and was then cultured in a carboxymethylcellulose (CMC) broth for enhanced conidia production (Zhang et al. 2020). Macroconidia were sickle-shaped or slightly curved, with three to five septa (19.2 to 38.5 x 3.1 to 5.8 µm, n =40). Microconidia were oval to ellipsoidal, non-septate or featuring 1 to 2 septa (4.8 to 10.5 x 2.1 to 5.2 µm, n=20). These morphological features indicated the isolate was similar to Fusarium avenaceum (Leslie and Summerell, 2006). For further identification of the strains, genomic regions (ITS-rDNA, TEF-1α, and RPB2) were amplified and sequenced using specific primers ITS1/ITS4, EF-1/EF-2, and 5f2/7cr, respectively (O'Donnell et al. 2010; Uwaremwe et al. 2021; Zarrin et al. 2016). PCR BLASTn queries of NCBI GenBank revealed a 99.8% (522 bp), 99.4% (355 bp) and 99.6% (985 bp) homology with F. avenaceum (MZ724839.1, MN271631.1, and MK185026.1), respectively. Sequences were deposited in GenBank (ITS, OR735571; TEF-1α, PP216660; RPB2, PP857820). One-year-old raspberry seedlings were planted in pots with a sterile soil mix (2:2:1 v/v ratio of soil, peat, and vermiculite) under controlled greenhouse conditions (23-26°C, 16h light/8h dark). A month post-planting, taproots were wounded in six pots and inoculated with 20 ml of conidia suspension (106 conidia/ml), while the other six pots were maintained as controls. After 14 days, RB10-infected plants showed symptoms similar to field observations, while controls remained healthy. The experiment was conducted twice, and re-isolation confirmed both the pathogenicity and identity of the pathogen. In the concatenated phylogenetic tree of ITS, TEF-1α and RPB2, strain RB10 was clustered with the F. avenaceum representative strains KG502, KG431 and F094. Studies revealed F. avenaceum varied pathogenicity across plants (Bugingo, 2022; Moparthi et al. 2020& 2024; Yli-Mattila et al. 2018), and it has been reported to induce raspberry fruit rot (Wang et al. 2017). However, no previous reports linked this fungus to raspberry root rot. This report is crucial for understanding the impact of root rot disease on raspberry cultivation and developing effective management strategies.

Dynamic functional connectivity and gene expression correlates in temporal lobe epilepsy: insights from hidden markov models.

BACKGROUD: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. RESULTS: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function. CONCLUSIONS: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE.

Choice intention for the national volume-based procurement drug and its associated factors: a cross-sectional study on patients with late-life depression in China.

BACKGROUND: The national volume-based procurement (NVBP) policy has significantly decreased prices and increased the accessibility of NVBP drugs. Nevertheless, issues such as heightened adverse reactions and suboptimal efficacy have arisen. Concerns regarding the quality of low-cost medications and the absence of long-term research have been widely recognized. This has led to caution among patients with late-life depression (LLD) due to their delicate health and the severity of their condition. This study evaluated the choice intention for NVBP drugs and associated factors in older patients with LLD. METHODS: A weighted sample of 408 participants between December 2022 and March 2023 were included. Data were collected via face-to-face interviews and questionnaires. To identify significant associated factors of choice intention, a multilevel logistic regression model was employed. RESULTS: Over half (53.68%) of older patients with LLD intended to choose NVBP drugs. Associated factors included self-assessed poor economy, higher out-of-pocket expenses, monthly household income exceeding CNY 6000, absence of other non-communicable chronic diseases, ordinary registration, urban employee medical insurance, no requirements for brand-name drugs, adverse reactions after using NVBP drugs, and rejection of physicians' recommendation for NVBP drugs. The interaction effect between the real economic condition and patients self-assessed economy significantly influences choice intention for NVBP drugs. Among 124 patients with self-assessed poor economy, 75 showed a higher intention to use NVBP drugs. In these patients, age, medical insurance reimbursement, and brand awareness were significantly associated with choice intention. CONCLUSION: Economic factors, physical conditions, medical needs, and physician recommendations significantly influenced the choice intention for NVBP drugs. The choice intention can be improved by strengthening physician-patient communication, increasing the scope and proportion of medical insurance reimbursement, improving substitution studies, and conducting post-marketing re-evaluations of NVBP drugs.

Postoperative delayed gastric emptying: may gut microbiota play a role?

Postoperative delayed gastric emptying is a prevalent complication following surgical procedures, imposing heavy physical and financial burdens on patients. However, current treatment options remain suboptimal. In recent years, an increasing number of studies have highlighted that the gut microbiota and its metabolites are closely associated with postoperative complications. Various factors can disrupt the gut microbiome after surgery. This review discusses the potential mechanisms by which the gut microbiota and their metabolites may contribute to the pathogenesis of postoperative delayed gastric emptying. However, the current knowledge base is limited in terms of fully understanding the exact mechanisms involved. It is therefore evident that further research is required to fully elucidate the role of the gut microbiome in postoperative delayed gastric emptying, with the aim of uncovering new possibilities for preventive measures and therapeutic treatments.

Pulmonary artery smooth muscle cell pyroptosis promotes the proliferation of PASMCs by paracrine IL­1ß and IL­18 in monocrotaline­induced pulmonary arterial hypertensive rats.

Pulmonary arterial hypertension (PAH) is a common vascular disease, and pulmonary vascular remodeling is a pivotal pathophysiological mechanism of PAH. Major pathological changes of pulmonary arterial remodeling, including proliferation, hypertrophy and enhanced secretory activity, can occur in pulmonary artery smooth muscle cells (PASMCs). Multiple active factors and cytokines play important roles in PAH. However, the regulatory mechanisms of the active factors and cytokines in PAH remain unclear. The present study aimed to reveal the crucial role of PASMC pyroptosis in PAH and to elucidate the intrinsic mechanisms. To establish the PAH rat models, Sprague-Dawley rats were injected intraperitoneally with monocrotaline (MCT) at a dose of 60 mg/kg. The expression of proteins and interleukins were detected by western blotting and ELISA assay. The results indicated that the pyroptosis of PASMCs is significantly increased in MCT-induced PAH rats. Notably, pyroptotic PASMCs can secret IL-1ß and IL-18 to promote the proliferation of PASMCs. On this basis, inhibiting the secretion of IL-1ß and IL-18 can markedly inhibit PASMC proliferation. Collectively, the findings of the present study indicate a critical role for PASMC pyroptosis in MCT-induced PAH rats, prompting a new preventive and therapeutic strategy for PAH.

Transport and spatio-temporal conversion of sugar facilitate the formation of spatial gradients of starch in wheat caryopses.

Wheat grain starch content displays large variations within different pearling fractions, which affecting the processing quality of corresponding flour, while the underlying mechanism on starch gradient formation is unclear. Here, we show that wheat caryopses acquire sugar through the transfer of cells (TCs), inner endosperm (IE), outer endosperm (OE), and finally aleurone (AL) via micro positron emission tomography-computed tomography (PET-CT). To obtain integrated information on spatial transcript distributions, developing caryopses are laser microdissected into AL, OE, IE, and TC. Most genes encoding carbohydrate transporters are upregulated or specifically expressed, and sugar metabolites are more highly enriched in the TC group than in the AL group, in line with the PET-CT results. Genes encoding enzymes in sucrose metabolism, such as sucrose synthase, beta-fructofuranosidase, glucose-1-phosphate adenylyltransferase show significantly lower expression in AL than in OE and IE, indicating that substrate supply is crucial for the formation of starch gradients. Furthermore, the low expressions of gene encoding starch synthase contribute to low starch content in AL. Our results imply that transcriptional regulation represents an important means of impacting starch distribution in wheat grains and suggests breeding targets for enhancing specially pearled wheat with higher quality.

Associations between type 2 diabetes mellitus and risk of falls among community-dwelling elderly people in Guangzhou, China: a prospective cohort study.

BACKGROUND: Several studies have demonstrated that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of falls compared to those without T2DM, which may lead to disability and a lower quality of life. While, limited prospective studies have quantified the associations in southern China. We conducted a longitudinal cohort study to quantify the associations between T2DM and falls and investigate the risk factors of falls among community-dwelling elderly people in Guangzhou, China. METHODS: The population-based study included 8800 residents aged 65 and over in 11 counties of Guangzhou at baseline in 2020 and then prospectively followed up through 2022. Of 6169 participants had complete follow-up and were included in the present study. A fall event was identified by self-reported. The Cox regression was applied to quantify the associations between T2DM and falls, and hazard ratios (HRs) were calculated to the factors associated with falls among participants. RESULTS: The median follow-up time for participants was 2.42 years. During the follow-up period, the incidence of falls among all participants was 21.96%. After adjusting for covariates in Cox regression models, T2DM remained a significant risk factor for falls, with HR of 1.781 (95% CI: 1.600-1.983) in the unadjusted covariates model and 1.757 (1.577-1.957) in the adjusted covariates model. Female (1.286, 1.136-1.457), older age (≥ 80: 1.448, 1.214-1.729), single marital status (1.239, 1.039-1.477), lower education level (primary school and below: 1.619, 1.004-1.361), hypertension (1.149, 1.026-1.286) and stroke (1.619, 1.176-2.228) were associated with a higher risk of falls, whereas everyday physical exercise (0.793, 0.686-0.918) was associated with a lower risk of falls. CONCLUSION: Falls are common, with risks between T2DM and falls quantified and several factors investigated in the longitudinal cohort study among community-dwelling elderly people in Guangzhou, China. Targeted action on the risk factors may reduce the burden of falls in elderly people with T2DM in the future.

A transcription factor of SHI family AaSHI1 activates artemisinin biosynthesis genes in Artemisia annua.

BACKGROUND: Transcription factors (TFs) of plant-specific SHORT INTERNODES (SHI) family play a significant role in regulating development and metabolism in plants. In Artemisia annua, various TFs from different families have been discovered to regulate the accumulation of artemisinin. However, specific members of the SHI family in A. annua (AaSHIs) have not been identified to regulate the biosynthesis of artemisinin. RESULTS: We found five AaSHI genes (AaSHI1 to AaSHI5) in the A. annua genome. The expression levels of AaSHI1, AaSHI2, AaSHI3 and AaSHI4 genes were higher in trichomes and young leaves, also induced by light and decreased when the plants were subjected to dark treatment. The expression pattern of these four AaSHI genes was consistent with the expression pattern of four structural genes of artemisinin biosynthesis and their specific regulatory factors. Dual-luciferase reporter assays, yeast one-hybrid assays, and transient transformation in A. annua provided the evidence that AaSHI1 could directly bind to the promoters of structural genes AaADS and AaCYP71AV1, and positively regulate their expressions. This study has presented candidate genes, with AaSHI1 in particular, that can be considered for the metabolic engineering of artemisinin biosynthesis in A. annua. CONCLUSIONS: Overall, a genome-wide analysis of the AaSHI TF family of A. annua was conducted. Five AaSHIs were identified in A. annua genome. Among the identified AaSHIs, AaSHI1 was found to be localized to the nucleus and activate the expression of structural genes of artemisinin biosynthesis including AaADS and AaCYP71AV1. These results indicated that AaSHI1 had positive roles in modulating artemisinin biosynthesis, providing candidate genes for obtaining high-quality new A. annua germplasms.

Genipin promotes the apoptosis and autophagy of neuroblastoma cells by suppressing the PI3K/AKT/mTOR pathway.

This study investigated the underlying function and mechanism of genipin in neuroblastoma (NB). Using flow cytometry analysis and cytotoxicity tests, in vitro studies were conducted to assess the effects of genipin on the SK-N-SH cell line. The mechanism of action of genipin was explored through immunofluorescence staining, Western blotting, and caspase-3 activity assays. In addition, we also created a xenograft tumour model to investigate the effects of genipin in vivo. This research confirmed that genipin suppressed cell viability, induced apoptosis, and promoted autophagy, processes that are likely linked to the inhibition of the PI3K/AKT/mTOR signalling pathway. Autophagy inhibition increases the sensitivity of SK-N-SH cells to genipin. Furthermore, combination treatment with a PI3K inhibitor enhanced the therapeutic efficacy of genipin. These results highlight the potential of genipin as a candidate drug for the treatment of NB.

Multi-omics analysis reveals the effects of three application modes of plant growth promoting microbes biofertilizer on potato (Solanum tuberosum L.) growth under alkaline loess conditions.

Potato is an important crop due to its high contents of starch, protein, and various vitamins and minerals. Biofertilizers are composed of plant growth promoting microbes (PGPMs) which are essential for improving the growth and resistance of potato. However, little information has focused on the modes of inoculation of biofertilizers on plant growth and microecology. This study aims to reveal the response mechanism of the potato to three modes of inoculation of biofertilizers all containing PGPM Bacillus amyloliquefaciens EZ99, i.e. scattered mode of 5 kg/ha biofertilizer (M5), soaking seed tubers with dissolved 5 kg/ha biofertilizer (MZG), and scattered mode of 3 kg/ha biofertilizer + 2 kg/ha sucrose (MY34) in alkaline loess field through multi-omics analysis of transcriptome, metabolome and microbiome. The physiological result revealed that two application modes of equal amount of biofertilizer M5 and MZG significantly improved the growth and yield of potatoes. Furthermore, the transcriptome of potato exhibited sets of differentially expressed genes enriched in photosynthesis, sugar metabolism, and phenylpropanoid biosynthesis among the three modes, with the M5 mode exhibiting overall up-regulation of 828 genes. Based on the untargeted metabolomic analysis of potato tuber, M5 mode significantly accumulated sucrose, while MZG and MY34 mode significantly accumulated the stress metabolites euchrenone b6 and mannobiose, respectively. Besides, the microbial structure of potato rhizosphere showed that the diversity of bacteria and fungi was similar in all soils, but their abundances varied significantly. Specifically, beneficial Penicillium was enriched in M5 and MZG soils, whereas MY34 soil accumulated potential pathogens Plectosphaerella and saccharophilic Mortierella. Collectively, these e findings highlight that MZG is the most effective mode to promote potato growth and stimulate rhizosphere effect. The present study not only encourages sustainable agriculture through agroecological practices, but also provides broad prospects for the application of PGPM biofertilizer in staple foods.

Extraocular muscle volume on time-of-flight magnetic resonance angiography in patients with myasthenia gravis.

INTRODUCTION/AIMS: Despite being a prominent feature of myasthenia gravis (MG), extraocular muscle (EOM) has received little attention in clinical research. The aim of this study was to examine EOM volume in patients with MG and controls using time-of-flight magnetic resonance angiography (TOF-MRA). METHODS: EOM volumes (overall and individual rectus muscles) were calculated using TOF-MRA images and compared between MG patients (including subgroups) and controls. The correlation between EOM volume and disease duration was examined. Predictive equations for the selected parameters were developed using multiple linear regression analysis. RESULTS: EOM volume was lower in MG patients than controls, especially in MG patients with ophthalmoparesis (MG-O). MG-O exhibited a moderate negative correlation between EOM volume and disease duration. Multiple linear regression showed that disease duration and EOM status (ophthalmoparesis or not) account for 48.4% of EOM volume. DISCUSSION: Patients with MG show atrophy of the EOMs, especially those with ophthalmoparesis and long disease duration.

ChatGPT compared to national guidelines for management of ovarian cancer: Did ChatGPT get it right? - A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: We evaluated the performance of a chatbot compared to the National Comprehensive Cancer Network (NCCN) Guidelines for the management of ovarian cancer. METHODS: Using NCCN Guidelines, we generated 10 questions and answers regarding management of ovarian cancer at a single point in time. Questions were thematically divided into risk factors, surgical management, medical management, and surveillance. We asked ChatGPT (GPT-4) to provide responses without prompting (unprompted GPT) and with prompt engineering (prompted GPT). Responses were blinded and evaluated for accuracy and completeness by 5 gynecologic oncologists. A score of 0 was defined as inaccurate, 1 as accurate and incomplete, and 2 as accurate and complete. Evaluations were compared among NCCN, unprompted GPT, and prompted GPT answers. RESULTS: Overall, 48% of responses from NCCN, 64% from unprompted GPT, and 66% from prompted GPT were accurate and complete. The percentage of accurate but incomplete responses was higher for NCCN vs GPT-4. The percentage of accurate and complete scores for questions regarding risk factors, surgical management, and surveillance was higher for GPT-4 vs NCCN; however, for questions regarding medical management, the percentage was lower for GPT-4 vs NCCN. Overall, 14% of responses from unprompted GPT, 12% from prompted GPT, and 10% from NCCN were inaccurate. CONCLUSIONS: GPT-4 provided accurate and complete responses at a single point in time to a limited set of questions regarding ovarian cancer, with best performance in areas of risk factors, surgical management, and surveillance. Occasional inaccuracies, however, should limit unsupervised use of chatbots at this time.