Molecularly specific detection towards trace nitrogen dioxide by utilizing Schottky-junction-based Gas Sensor.

Trace NO2 detection is essential for the production and life, where the sensing strategy is appropriate for rapid detection but lacks molecular specificity. This investigation proposes a sensing mechanism dominated by surface-scattering to achieve the molecularly-specific detection. Two-dimensional Bi2O2Se is firstly fabricated into a Schottky-junction-based gas-sensor. Applied with an alternating excitation, the sensor simultaneously outputs multiple response signals (i.e., resistance, reactance, and the impedance angle). Their response times are shorter than 200 s at room temperature. In NO2 sensing, these responses present the detection limit in ppt range and the sensitivity is up to 16.8 %·ppb-1. This NO2 sensitivity presents orders of magnitude higher than those of the common gases within the exhaled breath. The impedance angle is involved in the principle component analysis together with the other two sensing signals. Twelve kinds of typical gases containing NO2 are acquired with molecular characteristics. The change in dipole moment of the target molecule adsorbed is demonstrated to correlate with the impedance angle via surface scattering. The proposed mechanism is confirmed to output ultra-sensitive sensing responses with the molecular characteristic.

[Factors associated with the care needs of the older adults based on different disability levels].

OBJECTIVE: To identify the factors associated with the care needs of the older adults aged 65-105 by age groups, and to compare these factors across different age groups. METHODS: A total of 12 244 older adults from the Chinese longitudinal healthy longevity survey (CLHLS) conducted in 2018 were included in the analyses. The participants were categorized into three age groups: young-old (aged 65-79), middle-old (aged 80-89), and oldest-old (aged 90-105). The level of disability was measured by the disability index (DI) in four dimensions, reflecting their care needs. Potential factors associated with care needs were selected based on the health ecological model (HEM), including perspectives of personal characteristics, behavioral characteristics, interpersonal network, living and working conditions, and policy environment. Multifactor analysis was performed using multinomial Logistic regression. RESULTS: Among China ' s 12 244 older adults, 43.4% had medium or high care needs. Factors for higher care needs of older adults included higher age, higher number of chronic diseases, no exercise habit, excessive sleep duration (≥9 h/d), depressive tendency, living with children or spouse, and uneducated (all P < 0.05). In addition, the young-old group who were past smokers (OR=2.009, 95% CI: 1.019-3.959), were past drinkers (OR=2.213, 95% CI: 1.141-4.291), and reported self-perceived poverty (OR=2.051, 95% CI: 1.189-3.540), had higher level of care needs. The middle-old group who were female (OR=1.373, 95% CI: 1.038-1.817), never drank alcohol (OR=1.551, 95% CI: 1.059-2.269), and were lack of medical insurance (OR=1.598, 95% CI: 1.053-2.426), and had higher level of care needs. The oldest-old group who were female (medium care needs vs. low care needs: OR=1.412, 95% CI: 1.062-1.878; high care needs vs. low care needs: OR=1.506, 95% CI: 1.137-1.993), reported self-perceived poverty (OR=2.064, 95% CI: 1.282-3.323), and were lack of medical insurance (OR=1.621, 95% CI: 1.148-2.291), and had higher level of care needs. CONCLUSION: The identical factors associated with care needs across different age groups include age, chronic disease, exercise, sleep, depression, living arrangement, and education. Smoking, alcohol consumption, and economic status are specific factors among the young-old group of the older adults, while gender and medical insurance are specific factors among the middle-old and the oldest-old group of the older adults. We recommend conducting prospective cohort studies and intervention studies among specific age groups on the above factors to provide reliable evidence for policy formulation.

HNRNPA2B1 stabilizes NFATC3 levels to potentiate its combined actions with FOSL1 to mediate vasculogenic mimicry in GBM cells.

BACKGROUND: Vasculogenic mimicry (VM) is an enigmatic physiological feature that influences blood supply within glioblastoma (GBM) tumors for their sustained growth. Previous studies identify NFATC3, FOSL1 and HNRNPA2B1 as significant mediators of VEGFR2, a key player in vasculogenesis, and their molecular relationships may be crucial for VM in GBM. AIMS: The aim of this study was to understand how NFATC3, FOSL1 and HNRNPA2B1 collectively influence VM in GBM. METHODS: We have investigated the underlying gene regulatory mechanisms for VM in GBM cell lines U251 and U373 in vitro and in vivo. In vitro cell-based assays were performed to explore the role of NFATC3, FOSL1 and HNRNPA2B1 in GBM cell proliferation, VM and migration, in the context of RNA interference (RNAi)-mediated knockdown alongside corresponding controls. Western blotting and qRT-PCR assays were used to examine VEGFR2 expression levels. CO-IP was employed to detect protein-protein interactions, ChIP was used to detect DNA-protein complexes, and RIP was used to detect RNA-protein complexes. Histochemical staining was used to detect VM tube formation in vivo. RESULTS: Focusing on NFATC3, FOSL1 and HNRNPA2B1, we found each was significantly upregulated in GBM and positively correlated with VM-like cellular behaviors in U251 and U373 cell lines. Knockdown of NFATC3, FOSL1 or HNRNPA2B1 each resulted in decreased levels of VEGFR2, a key growth factor gene that drives VM, as well as the inhibition of proliferation, cell migration and extracorporeal VM activity. Chromatin immunoprecipitation (ChIP) studies and luciferase reporter gene assays revealed that NFATC3 binds to the promoter region of VEGFR2 to enhance VEGFR2 gene expression. Notably, FOSL1 interacts with NFATC3 as a co-factor to potentiate the DNA-binding capacity of NFATC3, resulting in enhanced VM-like cellular behaviors. Also, level of NFATC3 protein in cells was enhanced through HNRNPA2B1 binding of NFATC3 mRNA. Furthermore, RNAi-mediated silencing of NFATC3, FOSL1 and HNRNPA2B1 in GBM cells reduced their capacity for tumor formation and VM-like behaviors in vivo. CONCLUSION: Taken together, our findings identify NFATC3 as an important mediator of GBM tumor growth through its molecular and epistatic interactions with HNRNPA2B1 and FOSL1 to influence VEGFR2 expression and VM-like cellular behaviors.

Anatomical substrates and connectivity for bradykinesia motor features in Parkinson's disease after subthalamic nucleus deep brain stimulation.

Parkinsonian bradykinesia is rated using a composite scale incorporating the slowed frequency of repetitive movements, decrement amplitude and arrhythmicity. Differential localization of these movement components within the basal ganglia will drive the development of more personalized network-targeted symptomatic therapies. In this study, using an optical motion sensor, we evaluated the amplitude and frequency of hand movements during a grasping task with subthalamic nucleus deep brain stimulation 'on' or 'off' in 15 patients with Parkinson's disease. The severity of bradykinesia was assessed blindly using the Unified Parkinson's Disease Rating Part III scale. The volumes of activated tissue of each subject were estimated where changes in amplitude and frequency were mapped to identify distinct anatomical substrates of each component in the subthalamic nucleus. The volumes of activated tissue were used to seed a normative functional connectome to generate connectivity maps associated with amplitude and frequency changes. Deep brain stimulation-induced change in amplitude was negatively correlated with a change in Unified Parkinson's Disease Rating Part III scale for right (r = -0.65, P < 0.05) and left hand grasping scores (r = -0.63, P < 0.05). The change in frequency was negatively correlated with amplitude for both right (r = -0.63, P < 0.05) and left hands (r = -0.57, P < 0.05). The amplitude and frequency changes were represented as a spatial gradient with overlapping and non-overlapping regions spanning the anteromedial-posterolateral axis of the subthalamic nucleus. Whole-brain correlation maps between functional connectivity and motor changes were also inverted between amplitude and frequency changes. Deep brain stimulation-associated changes in frequency and amplitude were topographically and distinctly represented both locally in the subthalamic nucleus and in whole-brain functional connectivity.

Leveraging GPT-4 for food effect summarization to enhance product-specific guidance development via iterative prompting.

Food effect summarization from New Drug Application (NDA) is an essential component of product-specific guidance (PSG) development and assessment, which provides the basis of recommendations for fasting and fed bioequivalence studies to guide the pharmaceutical industry for developing generic drug products. However, manual summarization of food effect from extensive drug application review documents is time-consuming. Therefore, there is a need to develop automated methods to generate food effect summary. Recent advances in natural language processing (NLP), particularly large language models (LLMs) such as ChatGPT and GPT-4, have demonstrated great potential in improving the effectiveness of automated text summarization, but its ability with regard to the accuracy in summarizing food effect for PSG assessment remains unclear. In this study, we introduce a simple yet effective approach,iterative prompting, which allows one to interact with ChatGPT or GPT-4 more effectively and efficiently through multi-turn interaction. Specifically, we propose a three-turn iterative prompting approach to food effect summarization in which the keyword-focused and length-controlled prompts are respectively provided in consecutive turns to refine the quality of the generated summary. We conduct a series of extensive evaluations, ranging from automated metrics to FDA professionals and even evaluation by GPT-4, on 100 NDA review documents selected over the past five years. We observe that the summary quality is progressively improved throughout the iterative prompting process. Moreover, we find that GPT-4 performs better than ChatGPT, as evaluated by FDA professionals (43% vs. 12%) and GPT-4 (64% vs. 35%). Importantly, all the FDA professionals unanimously rated that 85% of the summaries generated by GPT-4 are factually consistent with the golden reference summary, a finding further supported by GPT-4 rating of 72% consistency. Taken together, these results strongly suggest a great potential for GPT-4 to draft food effect summaries that could be reviewed by FDA professionals, thereby improving the efficiency of the PSG assessment cycle and promoting generic drug product development.

Predictive value of ellipsoid zone-related angle parameters in primary surgery of large macular hole: a case control study.

BACKGROUND: To explore the predictive value of Ellipsoid Zone (EZ) -related angle parameters for the outcome of primary macular hole surgery. METHODS: This was a retrospective study. Patients diagnosed with large macular hole (MH) (minimum diameter > 500 µm) between 2018 and 2021 were enrolled. All patients underwent 25-gauge pars plana vitrectomy, internal limiting membrane (ILM) peeling and air tamponade. Spectral-domain OCT (SD-OCT) and best corrected visual acuity (BCVA) were measured in preoperative and 2-week post-operative. Classic and angle related parameters were measured via ImageJ. Angle regularity (AR) were defined as the standard deviation of the angle parameters in vertical and horizontal direction. RESULTS: Seventy-six eyes were included for analysis; 24 eyes showed an unclosed macular hole at the 2-week postoperative and 52 eyes showed a closed hole. Preoperatively, MLD (P < 0.001), BD (P = 0.009) and diameter of EZ/ELM disruption (P = 0.002 and 0.025) in patients failed to close the hole after primary surgery were significantly larger than those succeeded. EZ-MH (P = 0.018), EZ-NFL (P = 0.006), EZ-GCL (P = 0.004), EZ-INL (P = 0.002), EZ-OPL (P = 0.009) and EZ-ONL (P = 0.011) angles were smaller in patients with unclosed hole. AR of the EZ-NFL (P = 0.009), EZ-GCL (P = 0.009), EZ-OPL (P = 0.023), EZ-ONL (P = 0.048) and Basal-NFL (P = 0.030) angles among the unclosed patients were significantly larger than those of the closed group. EZ-NFL (P = 0.015), EZ-GCL (P = 0.004), EZ-INL (P < 0.001), EZ-OPL (P < 0.001), EZ-ONL (P < 0.001), Basal (P = 0.023) and Basal-NFL (P < 0.001) angles of hole-unclosed patients enlarged significantly after the surgery. CONCLUSIONS: Patients with large macular holes and an increased EZ-related angle and angle AR are more likely to experience unsuccessful outcomes following primary MH surgery. Therefore, EZ-related angles hold potential as valuable parameters for predicting the surgical outcome.

Beyond Valence and Arousal: The Role of Age of Acquisition in Emotion Word Recognition.

Although the age of acquisition (AoA) effect has been established in numerous studies, how emotion word processing is modulated by AoA, along with affective factors, such as valence and arousal, is not well understood. Hence, the influence of age of acquisition (AoA), valence, and arousal on Chinese emotion word recognition was investigated through two experiments. Experiment 1 (N = 30) adopted a valence judgment task to explore the roles of valence and AoA in emotion word recognition, whereas Experiment 2 (N = 30) used a lexical decision task to examine AoA and arousal effects. A mixed linear effects model was used to examine the fixed effects of AoA, arousal, and valence and random effects of participants and items. The findings provided confirmation of the effects of AoA, valence, and arousal. Notably, AoA and valence had independent influences on emotion word recognition, as evidenced by longer reaction times for later-acquired words and negative words compared to early-acquired words and positive words (all ps < 0.05). On the other hand, AoA and arousal demonstrated interdependent effects on emotion word recognition. Specifically, a larger AoA effect was observed for low-arousing words (all ps < 0.05), whereas the influence of AoA on high-arousing words was insignificant. These results underscored the significance of AoA in processing emotion words and highlighted the interplay between AoA and arousal. Additionally, it is plausible to suggest that the AoA effect was primarily perceptual rather than semantic in nature.

PharmBERT: a domain-specific BERT model for drug labels.

Human prescription drug labeling contains a summary of the essential scientific information needed for the safe and effective use of the drug and includes the Prescribing Information, FDA-approved patient labeling (Medication Guides, Patient Package Inserts and/or Instructions for Use), and/or carton and container labeling. Drug labeling contains critical information about drug products, such as pharmacokinetics and adverse events. Automatic information extraction from drug labels may facilitate finding the adverse reaction of the drugs or finding the interaction of one drug with another drug. Natural language processing (NLP) techniques, especially recently developed Bidirectional Encoder Representations from Transformers (BERT), have exhibited exceptional merits in text-based information extraction. A common paradigm in training BERT is to pretrain the model on large unlabeled generic language corpora, so that the model learns the distribution of the words in the language, and then fine-tune on a downstream task. In this paper, first, we show the uniqueness of language used in drug labels, which therefore cannot be optimally handled by other BERT models. Then, we present the developed PharmBERT, which is a BERT model specifically pretrained on the drug labels (publicly available at Hugging Face). We demonstrate that our model outperforms the vanilla BERT, ClinicalBERT and BioBERT in multiple NLP tasks in the drug label domain. Moreover, how the domain-specific pretraining has contributed to the superior performance of PharmBERT is demonstrated by analyzing different layers of PharmBERT, and more insight into how it understands different linguistic aspects of the data is gained.

Potential dynamic changes of single-season rice planting suitability across China.

As an important food crop in China, changes in suitable areas for rice planting are critical to agricultural production. In this study, the maximum entropy model (MaxEnt) was utilized to pick the main climatic factors affecting single-season rice planting distribution and project the potential changes under RCP4.5 and RCP8.5 scenarios. It was clear that rice planting distribution was significantly affected by annual total precipitation, the accumulated temperature during a period in which daily temperature was ≥ 10 °C, the moisture index, total precipitation during April-September, and continuous days during the period of daily temperature ≥ 18 °C, with their contribution being 97.6%. There was a continuous decrease in the area of good and high suitability for rice planting projected from 2021-2040 to 2061-2080, with a respective value ranging from 1.49 × 106 km2 to 0.93 × 106 km2 under the RCP4.5 scenario and from 1.42 × 106 km2 to 0.66 × 106 km2 under RCP8.5 scenarios. In 2081-2100, there was a bit increase in the area of good and high suitability under the RCP4.5 scenario. The most significant increases in good and high suitability were detected in Northeast China, while obvious decreases were demonstrated in the Yangtze River Basin which might be exposed to extreme temperature threat. The spatial potential planting center was characterized by the largest planting area in 25°N-37°N and 98°E-134°E. The north boundary and center of rice cultivation arose to 53.5°N and 37.52°N, respectively. These potential distributions for single-season rice under future climate change can provide a theoretical basis for optimizing rice planting layout, improving cultivation, and adjusting variety and management systems in response to climate change.

Anatomical Substrates and Connectivity for Parkinson's Disease Bradykinesia Components after STN-DBS.

Background: Parkinsonian bradykinesia is rated using a composite scale incorporating slowed frequency of repetitive movements, decrement amplitude, and arrhythmicity. Differential localization of these movement components within basal ganglia would drive the development of more personalized network-targeted symptomatic therapies. Methods: Using an optical motion sensor, amplitude and frequency of hand movements during grasping task were evaluated with subthalamic nucleus (STN)-Deep Brain Stimulation (DBS) "on" or "off" in 15 patients with Parkinson's disease (PD). The severity of bradykinesia was assessed blindly using the MDS-UPDRS Part-III scale. Volumes of activated tissue (VAT) of each subject were estimated where changes in amplitude and frequency were mapped to identify distinct anatomical substrates of each component in the STN. VATs were used to seed a normative functional connectome to generate connectivity maps associated with amplitude and frequency changes. Results: STN-DBS-induced change in amplitude was negatively correlated with change in MDS-UPDRS-III right (r = -0.65, p < 0.05) and left hand grasping scores (r = -0.63, p < 0.05). The change in frequency was negatively correlated with amplitude for both right (r = -0.63, p < 0.05) and left hand (r = -0.57, p < 0.05). The amplitude and frequency changes were represented as a spatial gradient with overlapping and non-overlapping regions spanning the dorsolateral-ventromedial axis of the STN. Whole-brain correlation maps between functional connectivity and motor changes were also inverted between amplitude and frequency changes. Conclusion: DBS-associated changes in frequency and amplitude were topographically and distinctly represented both locally in STN and in whole-brain functional connectivity.

Fine-tuning BERT for automatic ADME semantic labeling in FDA drug labeling to enhance product-specific guidance assessment.

Product-specific guidances (PSGs) recommended by the United States Food and Drug Administration (FDA) are instrumental to promote and guide generic drug product development. To assess a PSG, the FDA assessor needs to take extensive time and effort to manually retrieve supportive drug information of absorption, distribution, metabolism, and excretion (ADME) from the reference listed drug labeling. In this work, we leveraged the state-of-the-art pre-trained language models to automatically label the ADME paragraphs in the pharmacokinetics section from the FDA-approved drug labeling to facilitate PSG assessment. We applied a transfer learning approach by fine-tuning the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model to develop a novel application of ADME semantic labeling, which can automatically retrieve ADME paragraphs from drug labeling instead of manual work. We demonstrate that fine-tuning the pre-trained BERT model can outperform conventional machine learning techniques, achieving up to 12.5% absolute F1 improvement. To our knowledge, we were the first to successfully apply BERT to solve the ADME semantic labeling task. We further assessed the relative contribution of pre-training and fine-tuning to the overall performance of the BERT model in the ADME semantic labeling task using a series of analysis methods, such as attention similarity and layer-based ablations. Our analysis revealed that the information learned via fine-tuning is focused on task-specific knowledge in the top layers of the BERT, whereas the benefit from the pre-trained BERT model is from the bottom layers.

Surveillance of the progression and assessment of treatment endpoints for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD) characterized by steatosis-associated inflammation and liver injury. Without effective treatment or management, NASH can have life-threatening outcomes. Evaluation and identification of NASH patients at risk for adverse outcomes are therefore important. Key issues in screening NASH patients are the assessment of advanced fibrosis, differentiation of NASH from simple steatosis, and monitoring of dynamic changes during follow-up and treatment. Currently, NASH staging and evaluation of the effectiveness for drugs still rely on pathological diagnosis, despite sample error issues and the subjectivity associated with liver biopsy. Optimizing the pathological assessment of liver biopsy samples and developing noninvasive surrogate methods for accessible, accurate, and safe evaluation are therefore critical. Although noninvasive methods including elastography, serum soluble biomarkers, and combined models have been implemented in the last decade, noninvasive diagnostic measurements are not widely applied in clinical practice. More work remains to be done in establishing cost-effective strategies both for screening for at-risk NASH patients and identifying changes in disease severity. In this review, we summarize the current state of noninvasive methods for detecting steatosis, steatohepatitis, and fibrosis in patients with NASH, and discuss noninvasive assessments for screening at-risk patients with a focus on the characteristics that should be monitored at follow-up.

Online platforms' framing around vaping.

In this paper, we provide a descriptive overview of how vaping is framed differently between various online platforms (Wikipedia, Quora, Medium, Reddit, Stack Exchange, wikiHow, Facebook, and online news media). We provide an overview of >1 million posts and news articles about vaping to study the differences in framing between online platforms. Findings indicate an inconsistent framing around vaping across platforms. Stakeholders may utilize our findings to intervene around the framing of vaping and may design communications campaigns that improve the way society sees vaping, possibly aiding smoking cessation and reducing youth vaping.

Reversible stability of colloids switched by CO2 based on polyhexamethylene guanidine.

The stability of a colloid, including emulsion and polymer latex, can be destroyed irreversibly by the addition of salt. Using the CO2 stimulus, amines can be converted into organic ammonium salts reversibly, which can access the switching of colloids. Polyhexamethylene guanidine (PHMG), was chosen as a switchable amine. The conductivity of PHMG aqueous solution switched by adding and removing CO2. Surface tension measurements verified that, under CO2, the critical micelle concentration of sodium dodecyl benzene sulfonate (SDBS) decreased from 1.0 × 10-3 to 5.0 × 10-4 M with the addition of PHMG. The crude oil emulsion containing SDBS and PHMG was destroyed and restored reversibly by the treatment with CO2 and N2. The polystyrene latex also occurred an obvious stratification after sparging with CO2 and returned a homogeneous phase upon bubbling N2. This study is intended to pave the way for colloids which has reversible stability in response to CO2 stimulation.

Confining Nano-Fe3O4 in the Superhydrophilic Membrane Skin Layer to Minimize Internal Fouling.

Membrane surface fouling is often reversible as it can be mitigated by enhancing the crossflow shear force. However, membrane internal fouling is often irreversible and thus more challenging. In this study, we developed a new superhydrophilic poly(vinylidene fluoride) (P-PVDF) membrane confined with nano-Fe3O4 in the top skin layer via reverse filtration to reduce internal fouling. The surface of the P-PVDF membrane confined with nano-Fe3O4 had superwetting properties (water contact angle reaching 0° within 1 s), increased roughness (from 182 to 239 nm), and enhanced water affinity. The Fe3O4@P-PVDF membrane surface showed a thicker and enhanced hydration layer, which prevented foulants from approaching membrane surfaces and pores, thereby improving the rejection. For example, when 50 ppm humic acid (HA) solution was used as the feed, the removal efficiency of the Fe3O4@P-PVDF membrane was ∼67%, while the HA removal of the P-PVDF membrane was only ∼20%. The results from the resistance-in-series model showed that nanoconfinement of Fe3O4 in the top skin layer of the membrane allowed foulants to accumulate on the membrane surface (i.e., surface fouling) rather than within the internal pores (i.e., internal fouling). The filtration results under crossflow fouling and cleaning confirmed that the Fe3O4@P-PVDF membrane had higher surface fouling but it was much more reversible and much lower internal fouling compared with the control membrane. Our fouling analysis offers new insights into mass transfer mechanisms of the membrane with a nanoconfinement-enhanced hydration layer. This study provides an effective strategy to develop membranes with low internal fouling propensities.

Therapeutic developments in metabolic dysfunction-associated fatty liver disease.

ABSTRACT: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become one of the most prevalent chronic liver diseases worldwide, bringing risk of multiorgan disfunctions including cardiovascular events, complications of cirrhosis, and even malignance. In terms of health burden management, screening patients with high risk of MAFLD and providing individual comprehensive treatment is critical. Although there are numerous agents entering clinical trials for MAFLD treatment every year, there is still no effective approved drug. The nomenclature of MAFLD highlighted the concomitant metabolic disorders and obesity. MAFLD patients with type 2 diabetes had higher risk of developing liver cirrhosis and cancer, and would benefit from anti-hyperglycemic agents; overweight and obese patients may benefit more from weight loss therapies; for patients with metabolic syndrome, individual comprehensive management is needed to reduce the risk of adverse outcomes. In this review, we introduced the current status and advances of the treatment of MAFLD based on weight loss, improving insulin resistance, and management of cardiometabolic disorders, in order to provide individualized therapy approaches for patients with MAFLD.

Altered expression levels of miR-144-3p and ATP1B2 are associated with schizophrenia.

Objectives: Schizophrenia is a devastating mental disease. Various microRNAs were proven to be associated with schizophrenia. Altered microRNA-144-3p (miR-144-3p) levels were found in various neurological and psychotic disorders. Beta2-subunit of Na(+)/K(+)-ATPase (ATP1B2) regulates neuronal migration and cell growth during brain development through the PI3K/Akt/mTOR pathway. The present study explored the associations of miR-144-3p and ATP1B2 with schizophrenia and their mutual interaction.Methods: A schizophrenic animal model employing repeated MK-801 administration was established and 293 T cells over-expressing miR-144-3p were constructed by lentivirus. The in vitro and in vivo levels of miR-144-3p, ATP1B2, and the PI3K/Akt/mTOR pathway were examined by qRT-PCR and Western Blots. The interaction between miR-144-3p and ATP1B2 was predicted and assessed by using bioinformatic methods and a luciferase reporter gene assay, respectively.Results: MiR-144-3p expression was elevated in the schizophrenic rat hippocampus. ATP1B2 was down-regulated in schizophrenic patients by analysing GEO datasets. Additionally, miR-144-3p can directly bind with ATP1B2. Furthermore, the ATP1B2 expression and PI3K/Akt/mTOR phosphorylation levels were down-regulated in the 293 T cells over-expressing miR-144-3p and schizophrenic rat hippocampus, which could be reversed by risperidone.Conclusions: This study revealed that up-regulated miR-144-3p might be associated with schizophrenia through down-regulating ATP1B2, implicating new targets of schizophrenia treatment.

The burden and sexual dimorphism with nonalcoholic fatty liver disease in Asian children: A systematic review and meta-analysis.

BACKGROUND: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD. CONCLUSIONS: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation.

Current status and challenges in the drug treatment for fibrotic nonalcoholic steatohepatitis.

Currently, nonalcoholic steatohepatitis (NASH) is one of the most common forms of chronic hepatitis, increasing the burden of health care worldwide. In patients with NASH, the fibrosis stage is the most predictive factor of long-term events. However, there are still no drugs approved by the Food and Drug Administration of the United States for treating biopsy-proven NASH with fibrosis or cirrhosis. Although some novel drugs have shown promise in preclinical studies and led to improvement in terms of hepatic fat content and steatohepatitis, a considerable proportion of them have failed to achieve histological endpoints of fibrosis improvement. Due to the large number of NASH patients and adverse clinical outcomes, the search for novel drugs is necessary. In this review, we discuss current definitions for the evaluation of treatment efficacy in fibrosis improvement for NASH patients, and we summarize novel agents in the pipeline from different mechanisms and phases of trial. We also critically review the challenges we face in the development of novel agents for fibrotic NASH and NASH cirrhosis.

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients. METHODS: A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis. RESULTS: Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004-5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083-9.725, p<0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p<0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%). CONCLUSIONS: Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.