Impact of COVID-19 on Chinese urban consumers' food safety knowledge and behavior - A comparative study between pre and post pandemic eras.

The COVID-19 pandemic caused notable changes to the food-related habits of consumers worldwide due to their concerns about the risk of infection and the requirement to follow government mandates. To investigate the impact of the pandemic on Chinese consumers' food safety knowledge, food safety behaviors, and their most recent food poisoning experiences, we compared the results from an online survey (n = 583, Dec 2019) conducted before the pandemic was officially announced with an identical survey (n = 599, Aug 2023) conducted seven months after the Chinese government downgraded restrictions related to COVID-19. Post-pandemic there was a significant decrease in consumers' food safety knowledge and self-reported food safety behaviors and a significant increase in their self-reported experiences of food poisoning. Despite respondents stating that their food safety knowledge and behaviors had improved since the start of the pandemic, the data obtained from the two surveys and the respondents self-reporting of foodborne illness suggest that in fact their safety knowledge and behaviors had decreased. These findings highlight the need to reinforce food safety education and behaviors during times when the food system is disrupted, and consumers are focusing on what they perceive to be more immediate issues.

A review of HSV pathogenesis, vaccine development, and advanced applications.

Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV's sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV's unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons.

Achieving High-Performance Polymer-Wrapper-Free Aligned Carbon Nanotube Field-Effect Transistors Through Degradable Polymer Wrapping and Efficient Removal Techniques.

Semiconducting carbon nanotubes (s-CNTs) have emerged as a promising alternative to traditional silicon for ultrascaled field-effect transistors (FETs), owing to their exceptional properties. Aligned s-CNTs (A-CNTs) are particularly favored for practical applications due to their ability to provide higher driving current and lower contact resistance compared with individual s-CNTs or random networks. Achieving high-semiconducting-purity A-CNTs typically involves conjugated polymer wrapping for selective separation of s-CNTs, followed by self-assembly techniques. However, the presence of the polymer wrapper on A-CNTs can adversely impact electrical contact, gating efficiency, carrier transport, and device-to-device variations, necessitating its complete removal. While various methods have been explored for polymer removal, accurately characterizing the extent of removal remains a challenge. Traditional techniques such as absorption spectroscopy and X-ray photoelectron spectroscopy (XPS) may not accurately depict the remaining polymer content on A-CNTs due to their inherent detection limits. Consequently, the performance of FETs based on pure polymer-wrapper-free A-CNTs is unclear. In this study, we present an approach for preparing high-semiconducting-purity and polymer-wrapper-free A-CNTs using poly[(9,9-dioctylfluorenyl-2,7-dinitrilomethine)-(9,9-dioctylfluorenyl-2,7-dimethine)] (PFO-N-PFO), a degradable polymer, in conjunction with a modified dimension-limited self-alignment process (m-DLSA). Comprehensive transmission electron microscopy (TEM) characterizations, complemented by absorption and XPS characterizations, provide robust evidence of the successful near-complete removal of the polymer wrapper via a cleaning procedure involving acidic degradation, hot solvent rinsing, and vacuum annealing. Furthermore, top-gated FETs based on these high-semiconducting-purity and polymer-wrapper-free A-CNTs exhibit good performance metrics, including an on-current (Ion) of 2.2 mA/µm, peak transconductance (gm) of 1.1 mS/µm, low contact resistance (Rc) of 191 Ω·µm, and negligible hysteresis, representing a significant advancement in the CNT-based FET technology.

Novel antibody-drug conjugates based on DXd-ADC technology.

In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents.

Recent advancements in the small-molecule drugs for hepatocellular carcinoma (HCC): Structure-activity relationships, pharmacological activities, and the clinical trials.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and the sixth leading cause of cancer death worldwide, and it is urgent to find safe and effective drugs for treatment. As an important therapeutic method, small-molecule drugs are continually being updated to achieve improved therapeutic effects. The purpose of this study was to investigate the structural effects of various FDA-listed small-molecule drugs sorafenib, cabozantinib, lenvatinib, and regorafenib on the corresponding HCC targets and possible structural optimization methods, and to explore the mechanism for identifying potential therapeutic drugs that offer better efficacy and fewer side effects. METHODS: The structure-activity relationship, pharmacological actions, and clinical applications of small-molecule drugs were reviewed by referencing MEDLINE, Web of Science, CNKI, and other databases, summarizing and integrating the relevant content. RESULTS: The results showed that small-molecule drugs can inhibit HCC primarily by forming hydrogen bonds with Glu885, Asp1046, and Cys919 on the HCC target. HCC can be targeted by inhibiting the activation of multiple pathways, blocking the conduction of downstream signaling, and reducing the formation of tumor blood vessels. In general, small-molecule drugs primarily target four key receptors in HCC: VEGFR, PDGFR, EGFR, and FGFR, to achieve effective treatment. CONCLUSIONS: By revealing their structure-activity relationships, pharmacological actions, and clinical trials, small-molecule drugs can offer broad prospects for the development of new medications.

Recent advances in anti-inflammation via AMPK activation.

Inflammation is a complex physiological phenomenon, which is the body's defensive response, but abnormal inflammation can have adverse effects, and many diseases are related to the inflammatory response. AMPK, as a key sensor of cellular energy status, plays a crucial role in regulating cellular energy homeostasis and glycolipid metabolism. In recent years, the anti-inflammation effect of AMPK and related signalling cascade has begun to enter everyone's field of vision - not least the impact on metabolic diseases. A great number of studies have shown that anti-inflammatory drugs work through AMPK and related pathways. Herein, this article summarises recent advances in compounds that show anti-inflammatory effects by activating AMPK and attempts to comment on them.

Microbial and Metabolic Profiling of Obese and Lean Luchuan Pigs: Implications for Phenotypic Divergence.

Luchuan (LC) pigs are a Chinese breed renowned for their distinctive black and white coloring, superior meat quality and rapid reproduction, but their growth rate is slow. Over the course of approximately two decades of controlled breeding, the LC pigs maintained at the Shanghai Academy of Agricultural Sciences (Shanghai, China) have diverged into two phenotypes: one characterized by obesity (FLC) and the other by leanness (LLC). Recent studies indicate a correlation between microorganisms and the differentiation of host phenotypes. In this study, we examined the fecal microbiota profiles and serum metabolites of FLC and LLC pigs. The body weight, chest circumference, and alanine aminotransferase and aspartate aminotransferase enzyme activities were increased in the FLC pigs compared to the LLC pigs. Conversely, the levels of the Fusobacterium and Streptococcus genera were lower in the FLC pigs, while the number of Firmicutes, Lactobacillus, Phascolartobacterium, and Rikenellaceae_RC9_gut_group members were higher. A total of 52 metabolites were altered between the two groups, with many playing crucial roles in prolactin signaling, oocyte meiosis, and aldosterone-regulated sodium reabsorption pathways. The correlation analyses demonstrated a significant association between the modified microbiota and metabolites and the phenotypic variations observed in the LC pigs. Specifically, Jeotgalicoccus was positively correlated with the body weight and chest circumference, but was negatively correlated with metabolites such as 2-mercaptobenzothiazole and N1-pyrazin-2-yl-4-chlorobenzamide, which were positively associated with Bacteroides. These results provide compelling evidence for a novel relationship between the gut microbiome and metabolome in the phenotypic differentiation of LC pigs.

Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits. Its complexity stems from genetic predisposition, environmental influences, and metabolic factors. Epigenetic processes govern various cellular functions such as transcription, chromatin structure, and cell division. In NAFLD, these epigenetic tendencies, especially the process of histone methylation, are intricately intertwined with fat accumulation in the liver. Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis. While early-stage NAFLD is reversible, its progression to severe stages becomes almost irreversible. Therefore, early detection and intervention in NAFLD are crucial, and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

Serotonin signaling: a new player and therapeutic target beyond Long-haul coronavirus disease.

During the coronavirus disease 2019 (COVID-19) pandemic, a subset of individuals continues to suffer from symptoms including fatigue, post-exertional malaise, dyspnea, bone loss, and memory and neurocognitive dysfunction for months and even years after infection. This clinical phenomenon has been labeled 'Long-haul COVID' or 'post-acute sequelae of COVID-19 (PASC)'; however, the underlying pathophysiological mechanisms remain unclear. In a recent study published in Cell, Wong et al. revealed that viral infection and type I interferon-driven reduction of peripheral serotonin impaired hippocampal responses and short-term memory through vagal neurons in patients with PASC. Therefore, the study provided novel insights into how serotonin links persistent viral inflammation with the neurocognitive symptoms of Long-haul COVID and actionable therapeutic targets for patients with PASC.

Disparities in awareness and utilisation of National Essential Public Health Services between the floating population and the registered residents: a cross-sectional study in China.

OBJECTIVE: There are differences between the floating population and the registered population in the awareness and use of the National Essential Public Health Services (NEPHS) due to the influence of China's household registration system. The Equalization of Basic Public Health and Family Planning Services (EBPHFPS) policy aims to reduce disparities among populations by enhancing the migrant population's access to basic public health services. The aim of this study is to examine the relationship between the EBPHFPS targeted at the floating population and the disparities in access to and utilisation of NEPHS between registered residents and the floating population. DESIGN: A cross-sectional study. SETTING: 8 cities (regions, autonomous prefectures) in China. PARTICIPANTS: 13 998 floating population and 14 000 registered residents in eight cities (regions, autonomous prefectures) were included in the analysis. OUTCOME MEASURES: Three binomial variables, including awareness of NEPHS, acceptance of health education and establishment of health records, were used as outcome indicators to examine the relationship between the EBPHFPS and the disparities between the floating and registered populations. METHODS: A linear regression model, fairness gap calculation and propensity score matching were used to explore the associations. RESULTS: The areas that implemented EBPHFPS exhibited an 8.3% increase in awareness of the NEPHS (p<0.01) and a 4.0% increase (p<0.05) in the likelihood of individuals having received health education within the previous year compared with the areas without the policy implementation. In contrast to registered residents, however, the floating population still faces significant disparities in NEPHS awareness and utilisation. Compared with areas without the equalisation policy, the inequality of opportunity in health education of the floating population in implementation areas is significantly lower (p<0.01), whereas no significant difference is observed in the inequality of opportunity regarding NEPHS awareness among the floating population (p>0.1). The floating population in the pilot areas of the policy encountered greater disparities in the establishment of health records (p<0.01). CONCLUSIONS: Positive associations between the EBPHFPS policy and NEPHS awareness and utilisation among the floating population were demonstrated to some extent; however, the floating population was still confronted with a degree of inequality of opportunity. The government needs to develop target-oriented policies and a guaranteed mechanism to ensure access to NEPHS among the floating population.

Waste treats waste: Facile fabrication of porous adsorbents from recycled PET and sodium alginate for efficient dye removal.

Dye-contaminated water and waste plastic both pose enormous threats to human health and the ecological environment, and simultaneously solving these two issues in a sustainable and resource-saving way is highly important. In this work, a sodium alginate-polyethylene terephthalate-sodium alginate (SA@PET) composite adsorbent for efficient dye removal is fabricated using wasted PET bottle and marine plant-based SA via simple and energy-efficient nonsolvent-induced phase separation (NIPS) method. Benefiting from its porous structure and the abundant binding sites, SA@PET shows an excellent methylene blue (MB) adsorption capacity of 1081 mg g-1. The Redlich-Peterson model more accurately describes the adsorption behavior, suggesting multiple adsorption mechanisms. In addition to the electrostatic attractions of SA to MB, polar interactions between the PET matrix and MB are also identified as adsorption mechanisms. It is worth mentioning that SA@PET could be recycled 7 times without a serious decrease in performance, and the trifluoroacetic acid-dichloromethane solvent involved in the NIPS process has the possibility of reuse and stepwise recovery. Finally, the discarded adsorbent could be completely degraded under mild conditions. This work provides not only a composite adsorbent with excellent cationic dye removal performance for wastewater treatment, but also an upcycling strategy for waste PET.

A promising therapy for fatty liver disease: PCSK9 inhibitors.

BACKGROUND: Fatty liver disease (FLD) poses a significant global health concern worldwide, with its classification into nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) contingent upon the presence or absence of chronic and excessive alcohol consumption. The absence of specific therapeutic interventions tailored to FLD at various stages of the disease renders its treatment exceptionally arduous. Despite the fact that FLD and hyperlipidemia are intimately associated, there is still debate over how lipid-lowering medications affect FLD. Proprotein Convertase Subtilisin/ Kexin type 9 (PCSK9) is a serine protease predominantly synthesized in the liver, which has a crucial impact on cholesterol homeostasis. Research has confirmed that PCSK9 inhibitors have prominent lipid-lowering properties and substantial clinical effectiveness, thereby justifying the need for additional exploration of their potential role in FLD. PURPOSE: Through a comprehensive literature search, this review is to identify the relationship and related mechanisms between PCSK9, lipid metabolism and FLD. Additionally, it will assess the pharmacological mechanism and applicability of PCSK9 inhibitors (including naturally occurring PCSK9 inhibitors, such as conventional herbal medicines) for the treatment of FLD and serve as a guide for updating the treatment protocol for such conditions. METHODS: A comprehensive literature search was conducted using several electronic databases, including Pubmed, Medline, Embase, CNKI, Wanfang database and ClinicalTrials.gov, from the inception of the database to 30 Jan 2024. Key words used in the literature search were "fatty liver", "hepatic steatosis", "PCSK9", "traditional Chinese medicine", "herb medicine", "botanical medicine", "clinical trial", "vivo", "vitro", linked with AND/OR. Most of the included studies were within five years. RESULTS: PCSK9 participates in the regulation of circulating lipids via both LDLR dependent and independent pathways, and there is a potential association with de novo lipogenesis. Major clinical studies have demonstrated a positive correlation between circulating PCSK9 levels and the severity of NAFLD, with elevated levels of circulating PCSK9 observed in individuals exposed to chronic alcohol. Numerous studies have demonstrated the potential of PCSK9 inhibitors to ameliorate non-alcoholic steatohepatitis (NASH), potentially completely alleviate liver steatosis, and diminish liver impairment. In animal experiments, PCSK9 inhibitors have exhibited efficacy in alleviating alcoholic induced liver lipid accumulation and hepatitis. Traditional Chinese medicine such as berberine, curcumin, resveratrol, piceatannol, sauchinone, lupin, quercetin, salidroside, ginkgolide, tanshinone, lunasin, Capsella bursa-pastoris, gypenosides, and Morus alba leaves are the main natural PCS9 inhibitors. Excitingly, by inhibiting transcription, reducing secretion, direct targeting and other pathways, traditional Chinese medicine exert inhibitory effects on PCSK9, thereby exerting potential FLD therapeutic effects. CONCLUSION: PCSK9 plays an important role in the development of FLD, and PCSK9 inhibitors have demonstrated beneficial effects on lipid regulation and FLD in both preclinical and clinical studies. In addition, some traditional Chinese medicines have improved the disease progression of FLD by inhibiting PCSK9 and anti-inflammatory and antioxidant effects. Consequently, the inhibition of PCSK9 appears to be a promising therapeutic strategy for FLD.

Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor.

INTRODUCTION: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. OBJECTIVE: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. METHODS AND RESULTS: Collecting duct NCOR1 knockout (KO) mice manifested increased BP and aggravated vascular and renal injury in an angiotensin II (Ang II)-induced hypertensive model. KO mice also showed significantly higher BP than littermate control (LC) mice in deoxycorticosterone acetate (DOCA)-salt model. Further study showed that collecting duct NCOR1 deficiency aggravated volume and sodium retention after saline challenge. Among the sodium transporter in the collecting duct, the expression of the three epithelial sodium channel (ENaC) subunits was markedly increased in the renal medulla of KO mice. Consistently, BP in Ang II-infused KO mice decreased significantly to the similar level as those in LC mice after amiloride treatment. ChIP analysis revealed that NCOR1 deficiency increased the enrichment of mineralocorticoid receptor (MR) on the promoters of the three ENaC genes in primary inner medulla collecting duct (IMCD) cells. Co-IP results showed interaction between NCOR1 and MR, and luciferase reporter results demonstrated that NCOR1 inhibited the transcriptional activity of MR. Knockdown of MR eliminated the increased ENaC expression in primary IMCD cells isolated from KO mice. Finally, BP was significantly decreased in Ang II-infused KO mice after treatment of MR antagonist spironolactone and the difference between LC and KO mice was abolished. CONCLUSIONS: NCOR1 interacts with MR to control ENaC activity in the collecting duct and to regulate sodium reabsorption and ultimately BP. Targeting NCOR1 might be a promising tactic to interrupt the volume and sodium retention of the collecting duct in hypertension.

SETDB1: Progress and prospects in cancer treatment potential and inhibitor research.

SET domain bifurcated methyltransferase 1 (SETDB1) serves as a histone lysine methyltransferase, catalyzing the di- and tri-methylation of histone H3K9. Mounting evidence indicates that the abnormal expression or activity of SETDB1, either through amplification or mutation, plays a crucial role in tumorigenesis and progression. This is particularly evident in the context of tumor immune evasion and resistance to immune checkpoint blockade therapy. Furthermore, there is a robust association between SETDB1 dysregulation and an unfavorable prognosis across various types of tumors. The oncogenic role of SETDB1 primarily arises from its methyltransferase function, which contributes to the establishment of a condensed and transcriptionally inactive heterochromatin state. This results in the inactivation of genes that typically hinder cancer development and silencing of retrotransposons that could potentially trigger an immune response. These findings underscore the substantial potential for SETDB1 as an anti-tumor therapeutic target. Nevertheless, despite significant strides in recent years in tumor biology research, challenges persist in SETDB1-targeted therapy. To better facilitate the development of anti-tumor therapy targeting SETDB1, we have conducted a comprehensive review of SETDB1 in this account. We present the structure and function of SETDB1, its role in various tumors and immune regulation, as well as the advancements made in SETDB1 antagonists. Furthermore, we discuss the challenges encountered and provide perspectives for the development of SETDB1-targeted anti-tumor therapy.

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.

Integrative Analysis of N6-methyladenosine RNA modifications related genes and their Influences on Immunoreaction or fibrosis in myocardial infarction.

Increasing studies have shown that N6-methyladenosine (m6A) modification plays an important role in cardiovascular diseases. In this study, we systematically investigated the regulatory mode of m6A genes in myocardial infarction (MI) by combining bioinformatics analysis of clinical samples with animal experiments. We utilized gene expression data of clinical samples from public databases to examine the expression of m6A genes in heart tissues and found a large difference between the healthy control group and MI group. Subsequently, we established an MI diagnosis model based on the differentially expressed m6A genes using the random forest method. Next, unsupervised clustering method was used to classify all MI samples into two clusters, and the differences in immune infiltration and gene expression between different clusters were compared. We found LRPPRC to be the predominant gene in m6A clustering, and it was negatively correlated with immunoreaction. Through GO enrichment analysis, we found that most differentially expressed genes between the two clusters were profibrotic. By means of WGCNA, we inferred that GJA4 might be a core molecule in the m6A regulatory network of MI. This study demonstrates that m6A regulators probably affects the immune-inflammatory response and fibrosis to regulate the process of MI, which provides a potential therapeutic target.

Predictive value of serum MDA and 4-HNE levels on the occurrence of early neurological deterioration after intravenous thrombolysis with rt-PA IVT in patients with acute ischemic stroke.

OBJECTIVE: This study investigated the predictive value of serum MDA and 4-HNE levels on early neurological deterioration (END) after recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. METHODS: This study analyzed 287 AIS patients with standard-dose rt-PA IVT. Clinical baseline and pathological data were recorded before rt-PA IVT, and neurologic deficit was assessed by NIHSS. AIS patients were classified into Non-END and END groups. Serum MDA and 4-HNE levels were determined by ELISA and their correlations with NIHSS scores were evaluated. AIS patients were allocated into groups with high and low MDA or 4-HNE expression, and post-IVT END incidence was compared. Independent risk indexes for post-IVT END and the predictive value of serum MDA+4-HNE levels on post-IVT END were assessed. RESULTS: Serum MDA and 4-HNE were higher in AIS patients with post-IVT END. NIHSS score showed a positive correlation with serum MDA and 4-HNE levels. MDA levels were positively correlated with 4-HNE levels in AIS patients. END after IVT was increased in AIS patients with high MDA/4-HNE expression. FBG, lymphocyte percentage, PLR, NIHSS score, serum MDA, and 4-HNE levels were independent risk factors for END after IVT. The diagnostic efficacy of MDA+4-HNE in assessing post-IVT END in AIS patients (sensitivity 92.00 %, specificity 82.70 %) was higher than MDA or 4-HNE alone. CONCLUSION: Serum MDA and 4-HNE levels were higher in AIS patients with post-IVT END than in those with non-END, and MDA+4-HNE possessed a higher predictive value for post-IVT END in AIS patients.

Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes. We here investigated the role of KDM1A, one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of KDM1A in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the KDM1A can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, KDM1A exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of KDM1A blunted its capability to promote the development of NAFLD. In summary, our study discovered that KDM1A exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. KDM1A might be considered as a potential therapeutic target in this regard.

Service readiness for the management of non-communicable diseases in publicly financed facilities in Malawi: findings from the 2019 Harmonised Health Facility Assessment census survey.

INTRODUCTION: Non-communicable diseases (NCDs) are rising in low-income and middle-income countries, including Malawi. To inform policy-makers and planners on the preparedness of the Malawian healthcare system to respond to NCDs, we estimated NCD service readiness in publicly financed healthcare facilities in Malawi. METHODS: We analysed data from 564 facilities surveyed in the 2019 Harmonised Health Facility Assessment, including 512 primary healthcare (PHC) and 52 secondary and tertiary care (STC) facilities. To characterise service readiness, applying the law of minimum, we estimated the percentage of facilities with functional equipment and unexpired medicines required to provide NCD services. Further, we estimated permanently unavailable items to identify service readiness bottlenecks. RESULTS: Fewer than 40% of PHC facilities were ready to deliver services for each of the 14 NCDs analysed. Insulin and beclomethasone inhalers had the lowest stock levels at PHC facilities (6% and 8%, respectively). Only 17% of rural and community hospitals (RCHs) have liver and kidney diagnostics. STC facilities had varying service readiness, ranging from 27% for managing acute diabetes complications to 94% for chronic type 2 diabetes management. Only 38% of STC facilities were ready to manage chronic heart failure. Oral pain medicines were widely available at all levels of health facilities; however, only 22% of RCHs and 29% of STCs had injectable morphine or pethidine. Beclomethasone was never available at 74% of PHC and 29% of STC facilities. CONCLUSION: Publicly financed facilities in Malawi are generally unprepared to provide NCD services, especially at the PHC level. Targeted investments in PHC can substantially improve service readiness for chronic NCD conditions in local communities and enable STC to respond to acute NCD complications and more complex NCD cases.