Epilepsy Treatment and Diagnosis Enhanced by Current Nanomaterial Innovations: A Comprehensive Review.

Epilepsy is a complex disease in the brain. Complete control of seizure has always been a challenge in epilepsy treatment. Currently, clinical management primarily involves pharmacological and surgical interventions, with the former being the preferred approach. However, antiepileptic drugs often exhibit low bioavailability due to inherent limitations such as poor water solubility and difficulty penetrating the blood-brain barrier (BBB). These issues significantly reduce the drugs' effectiveness and limit their clinical application in epilepsy treatment. Additionally, the diagnostic accuracy of current imaging techniques and electroencephalography (EEG) for epilepsy is suboptimal, often failing to precisely localize epileptogenic tissues. Accurate diagnosis is critical for the surgical management of epilepsy. Thus, there is a pressing need to enhance both the therapeutic outcomes of epilepsy medications and the diagnostic precision of the condition. In recent years, the advancement of nanotechnology in the biomedical sector has led to the development of nanomaterials as drug carriers. These materials are designed to improve drug bioavailability and targeting by leveraging their large specific surface area, facile surface modification, ability to cross the BBB, and high biocompatibility. Furthermore, nanomaterials have been utilized as contrast agents in imaging and as materials for EEG electrodes, enhancing the accuracy of epilepsy diagnoses. This review provides a comprehensive examination of current research on nanomaterials in the treatment and diagnosis of epilepsy, offering new strategies and directions for future investigation.

Construction and Application of Autonomy Theory of Rehabilitation Program for Bronchiectasis Patients.

Objective: The autonomy theory holds that the autonomy of individuals in the rehabilitation process is crucial to the success of rehabilitation. To explore the use of autonomous rehabilitation programs in patients with bronchiectasis, This study was conducted through the construction of a stable family rehabilitation program for bronchiectasis patients and the application of patients self-determination theory. To further explore the value of autonomy theory in rehabilitation therapy. Method: The experimental group used self-determination theory as the guide for intervention on the basis of the control groups. The two groups of observation indexes included St. George's Respiratory Questionnaire, FEV1 and FEV1 values, lung capacity, V25, V50, maximal ventilation, compliance questionnaire, anxiety self-assessment scale, and depression self-assessment scale. Results: (1) The lung capacity of the experimental group patients (3.01 ± 0.82) L was higher than that of the control group (2.86 ± 0.36) L, and the V25 value (2.63 ± 0.31) L/s, V50 value (4.31 ± 1.01) L/s, and maximum ventilation volume (71.63 ± 18.35) L/min were all higher than those of the control group, with P < .05; (2) After intervention, the SGRO score of patients in the experimental group (38.66 ± 8.67)score was lower than that of the control group (56.48 ± 9.86)score. The FEV1 score of patients in the experimental group (9.35 ± 2.36)L was higher than that of the control group (1.04 ± 0.29)L. After intervention, the FEV1 score of patients in the experimental group was% (56.83 ± 9.21)% higher than that of the control group (46.37 ± 7.67)%, with P < .05; (3) Comparison of compliance scores between two groups of patients before and after intervention: the experimental group had scores for timed medication (4.89 ± 0.64)score, moderate exercise (4.61 ± 1.04)score, and dietary regulation (4.72 ± 0.87)score after intervention, all of which were higher than those of the control group (P < .05); (4) The comparison of anxiety and depression between two groups of patients showed that the anxiety score (10.16 ± 3.03)score of the experimental group after intervention was lower than that of the control group (13.03 ± 3.67)score, and the depression score (9.35 ± 2.36)score of the experimental group after intervention was lower than that of the control group (12.34 ± 3.01)score, with P < .05. Conclusion: Using the theory of autonomy to construct and apply the rehabilitation program in the home stabilization stage of bronchiectasis patients can improve respiratory and lung function. At the same time, it has a certain degree of promoting effect on improving patients' treatment compliance, and can improve patients' emotional state and reduce the occurrence of anxiety and depression. The results of this study will provide a certain theoretical basis for the construction of the treatment and rehabilitation program of clinically related diseases. In the future clinical treatment, personalized treatment intervention can be carried out according to the autonomy of patients to improve the clinical prognosis.

Effects of airflow superfine pulverization on the structure, functional properties, and flavor quality of wheat bran.

BACKGROUND: Wheat bran (WB) is a byproduct of refined wheat flour production with poor edible taste and low economic value. Herein, the WB was micronized via airflow superfine pulverization (ASP), and the effects of the ASP conditions on its particle size, nutritive compositions, whiteness, hydration characteristics, moisture distribution, microstructure, cation exchange capacity, volatile flavor components, and other characteristics were investigated. RESULTS: Reducing the rotational speed of the ASP screw and increasing the number of pulverizations significantly decreased the median particle size Dx(50) of WB to a minimum of 12.97 ± 0.19 µm (P < 0.05), increased the soluble dietary fiber content from 55.05 ± 2.94 to 106.86 ± 1.60 mg g-1, and improved the whiteness and water solubility index. In addition, the water holding capacity and oil holding capacity were significantly reduced (P < 0.05), while the cation exchange and swelling capacities first increased and then decreased. Up to about 70% of water in WB exists as bound water. As the Dx(50) of WB decreased, the content of bound and immobile water increased, while the free water decreased from 14.37 ± 1.21% to 7.59 ± 1.03%. Furthermore, WB was micronized and the particles became smaller and more evenly distributed. Using gas chromatography-ion mobility spectrometry, a total of 37 volatile compounds in micronized WB (including 10 aldehydes, 9 esters, 7 alcohols, and several acids, furans, ethers, aldehydes, esters, and alcohols) were identified as the main volatile compounds of WB. CONCLUSION: Collectively, ASP improved the physicochemical properties of WB. This study provides theoretical references for the use of ASP to improve the utilization and edibility of WB. © 2024 Society of Chemical Industry.

Visible-light-induced photocatalyst-free cascade cyclization of 3-(2-(ethynyl)phenyl)quinazolinones to sulfonated quinolino[2,1-b]quinazolinones.

A visible-light-induced K2S2O8-promoted cascade sulfonation/cyclization reaction was established using 3-(2-(ethynyl)phenyl)quinazolinones as efficient substrates under mild conditions. A series of sulfonated quinolino[2,1-b]quinazolinones were successfully synthesized under transition-metal- and photocatalyst-free conditions. Notably, this strategy has the advantages of room temperature and simple operation, easy scale-up, and good functional group tolerance.

Age was a protective factor for unexpected malignant diagnoses in patients with vertebral compression fracture.

OBJECTIVE: The purpose was to investigate the risk factors for unexpected malignant diagnoses in patients with vertebral compression fractures (VCF). METHODS: The clinical data were retrospectively collected from 1396 patients who underwent vertebral augmentation and biopsy between 2012 and 2022. According to the imaging results, the preoperative diagnoses were benign VCF (BVCF) in all these cases. Based on the histological findings, the patients were divided into two groups. In group A, unexpected malignant VCF (MVCF) was identified, while benign VCF (BVCF) was verified in group B. Logistic regression analysis was performed to analyze the risk and protective factors for unexpected malignant diagnoses. RESULTS: There were 44 patients in group A and 1352 in group B. The incidence of unexpected MVCF was 3.2 %. Age was significantly lower in group A compared to group B. Additionally, none of the patients in group A were older than 75. Age was associated with unexpected malignant diagnoses, according to the univariate logistic analysis. The multivariate logistic analysis showed that age was a protective factor for unexpected malignant diagnoses (odds ratio = 0.849, 95 % confidence interval: 0.809-0.891, p < 0.01). CONCLUSION: Age was a protective factor for unexpected malignant diagnoses in patients with preoperative diagnosis of BVCF. A routine biopsy is recommended to be performed during vertebral augmentation in young patients without preoperative imaging evidence of MVCF.

Effects of wheat starch content on its flour and frozen dough bread.

The refined wheat flour was mixed with different types of wheat starch in different addition levels, their microstructure, chemical bonds in the dough and baking characteristics of 0-8 weeks frozen dough bread were studied. With the increase of A-Type starch granules and whole wheat starch, the pores of gluten network first decreased and then increased. Conversely, an increase in B-Type starch granules consistently reduced gluten network porosity. With the increase of whole wheat starch, the content of free sulfhydryl group and hydrophobic interaction decreased gradually. Minimal additions of B-Type granules were found to enhance the specific volume of fresh bread, whereas increased quantities improved the specific volume of frozen dough bread. The addition of a small quantity of A- or B-Type granules enhances the freezing stability of bread. This study provides effective information for elucidating the effects of wheat starch on the frozen dough and bread properties in protein-starch matrix.

Antibiofilm Efficacy and Mechanism of the Marine Chlorinated Indole Sesquiterpene Against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) can easily form biofilms on food surfaces, thus leading to cross-contamination, which is difficult to remove. Therefore, there is an urgent need to find alternatives with good antibacterial and antibiofilm effects. In this study, two indole sesquiterpene compounds, xiamycin (1) and chlorinated metabolite chloroxiamycin (2), were isolated from the fermentation liquid of marine Streptomyces sp. NBU3429 for the first time. The chemical structures of the two compounds were characterized by spectroscopic data interpretation, including 1D NMR and HRESIMS analysis. Antimicrobial test showed that chloroxiamycin (2) (minimum inhibitory concentration, MIC = 16 µg/mL) exhibited superior antibacterial activity than xiamycin (1) (MIC = 32 µg/mL) against MRSA ATCC43300. Moreover, compound (2) decreased the biofilm formation rate of MRSA ATCC43300 by 12.7%-84.6% in the concentration range of 32-512 µg/mL, which is relatively stronger than xiamycin (1) (4.1%-49.9%) as well. Antibacterial/antibiofilm mechanism investigation indicated that chloroxiamycin (2) could disrupt the cell wall and membrane of MRSA, inhibiting the production of biofilm extracellular polysaccharides. All these results illustrated that chloroxiamycin (2) is an effective antibacterial/antibiofilm agent, which makes it an attractive candidate for food preservatives.

HER2/PI3K/AKT pathway in HER2-positive breast cancer: A review.

Breast cancer is currently the most commonly occurring cancer globally. Among breast cancer cases, the human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for 15% to 20% and is a crucial focus in the treatment of breast cancer. Common HER2-targeted drugs approved for treating early and/or advanced breast cancer include trastuzumab and pertuzumab, which effectively improve patient prognosis. However, despite treatment, most patients with terminal HER2-positive breast cancer ultimately suffer death from the disease due to primary or acquired drug resistance. The prevalence of aberrantly activated the protein kinase B (AKT) signaling in HER2-positive breast cancer was already observed in previous studies. It is well known that p-AKT expression is linked to an unfavorable prognosis, and the phosphatidylinositol-3-kinase (PI3K)/AKT pathway, as the most common mutated pathway in breast cancer, plays a major role in the mechanism of drug resistance. Therefore, in the current review, we summarize the molecular alterations present in HER2-positive breast cancer, elucidate the relationships between HER2 overexpression and alterations in the PI3K/AKT signaling pathway and the pathways of the alterations in breast cancer, and summarize the resistant mechanism of drugs targeting the HER2-AKT pathway, which will provide an adjunctive therapeutic rationale for subsequent resistance to directed therapy in the future.

Variability in Chromosome 1 of select Moroccan P. teres f. teres isolates enables isolates to overcome a highly effective barley Chromosome 6H source of resistance.

Barley net form net blotch (NFNB) is a destructive foliar disease caused by Pyrenophora teres f. teres. Barley line CIho5791, which harbors the broadly effective chromosome 6H resistance gene Rpt5, displays dominant resistance to P. teres f. teres. To genetically characterize P. teres f. teres avirulence/virulence on the barley line CIho5791, we generated a P. teres f. teres mapping population using a cross between the Moroccan CIho5791-virulent isolate MorSM40-3, and the avirulent reference isolate 0-1. Full genome sequences were generated for 103 progenies. Saturated chromosome-level genetic maps were generated, and quantitative trait locus (QTL) mapping identified two major QTL associated with P. teres f. teres avirulence/virulence on CIho5791. The most significant QTL mapped to chromosome (Ch) 1 where the virulent allele was contributed by MorSM40-3. A second QTL mapped to Ch8; however, this virulent allele was contributed by the avirulent parent 0-1. The Ch1 and Ch8 loci accounted for 27 and 15% of the disease variation, respectively, and the avirulent allele at the Ch1 locus was epistatic over the virulent allele at the Ch8 locus. As a validation, we used a natural P. teres f. teres population in a genome-wide association study that identified the same Ch1 and Ch8 loci. We then generated a new reference quality genome assembly of parental isolate MorSM40-3 with annotation supported by deep transcriptome sequencing of infection time points. The annotation identified candidate genes predicted to encode small, secreted proteins, one or more of which are likely responsible for overcoming the CIho5791 resistance.

Genomic Analysis of Kitasatospora setae to Explore Its Biosynthetic Potential Regarding Secondary Metabolites.

Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their natural products has led to a diminished probability of discovering novel bioactive compounds from this group. Consequently, our research focus has shifted towards less explored actinomycetes, beyond Streptomyces, with particular emphasis on Kitasatospora setae (K. setae). The genome of K. setae was annotated and analyzed through whole-genome sequencing using multiple bio-informatics tools, revealing an 8.6 Mbp genome with a 74.42% G + C content. AntiSMASH analysis identified 40 putative biosynthetic gene clusters (BGCs), approximately half of which were recessive and unknown. Additionally, metabolomic mining utilizing mass spectrometry demonstrated the potential for this rare actinomycete to generate numerous bioactive compounds such as glycosides and macrolides, with bafilomycin being the major compound produced. Collectively, genomics- and metabolomics-based techniques confirmed K. setae's potential as a bioactive secondary metabolite producer that is worthy of further exploration.

Du-moxibustion ameliorates depression-like behavior and neuroinflammation in chronic unpredictable mild stress-induced mice.

BACKGROUND: Neuroinflammation is involved in the advancement of depression. Du-moxibustion can treat depression. Here, we explored whether Du-moxibustion could alleviate neuroglia-associated neuro-inflammatory process in chronic unpredictable mild stress (CUMS) mice. METHODS: C57BL/6J mice were distributed into five groups. Except for the CON group, other four groups underwent CUMS for four consecutive weeks, and Du-moxibustion was given simultaneously after modeling. Behavioral tests were then carried out. Additionally, Western blot was conducted to measure the relative expression levels of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). Immunofluorescence was employed to evaluate the positive cells of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were analyzed using an ELISA assay. RESULTS: We found that CUMS induced depression-like behaviors, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, decreased the time in open arms and prolonged immobility. Furthermore, versus the CON group, the expression of HMGB1, TLR4, MyD88, NF-κB, positive cells of Iba-1, IL-1ß and TNF-α were increased but positive cells of GFAP were decreased in CUMS group. However, the detrimental effects were ameliorated by treatment with CUMS+FLU and CUMS+DM. LIMITATIONS: A shortage of this study is that only CUMS model of depression were used, while other depression model were not included. CONCLUSIONS: Du-moxibustion alleviates depression-like behaviors in CUMS mice mainly by reducing neuroinflammation, which offers novel insights into the potential treatment of depression.

Dynamic event-triggered control for CPSs under QoS-based variable sampling approach.

In this article, a quality of service (QoS) dependent variable sampling dynamic event-triggered control method is designed for a cyber-physical system (CPS) with delays and packets dropout to cope with non-ideal network environments, maintain the desired control performance and improve the communication efficiency. To achieve the variable period sampling, a sampler is designed based on the QoS of the wireless network by using the delta operator discretization method. Then, a variable period sampling scheme for the delta operator system converted from the CPS is designed. Furthermore, a dynamic event-triggered mechanism (DETM) is proposed using the variable period sampling signal, which can reduce event triggered data calculations and increase event triggered intervals. By utilizing the average dwell time (ADT) approach, sufficient conditions contains the explicit variable sampling period are derived for the derived switched CPS. Finally, the effectiveness of the designed method is verified by numerical examples.

Reponses of morphological and biochemical traits of bamboo trees under elevated atmospheric O3 enrichment.

Dwarf bamboo (Indocalamus decorus) is an O3-tolerant plant species. To identify the possible mechanism and response of leaf morphological, antioxidant, and anatomical characteristics to elevated atmospheric O3 (EO3) concentrations, we exposed three-year-old I. decorus seedlings to three O3 levels (low O3-LO: ambient air; medium O3-MO: Ambient air+70 ppb high O3-HO: Ambient air+140 ppb O3) over a growing season using open-top chambers. Leaf shape and stomatal characteristics, and leaf microscopic structure of I. decorus were examined. The results indicated that 1) the stomata O3 flux (Fst) of HO decreased more rapidly under EO3 as the exposure time increased. The foliar O3 injury of HO and MO occurred when AOT40 was 26.62 ppm h and 33.20 ppm h, respectively, 2) under EO3, leaf number, leaf mass per area, leaf area, and stomata length/width all decreased, while leaf thickness, stomatal density, width, and area increased compared to the control, 3) MDA and total soluble protein contents all showed significantly increase under HO (36.57% and 32.77%) and MO(31.91% and 19.52%) while proline contents only increased under HO(33.27%). 4) MO and HO increased bulliform cells numbers in the leaves by 6.28% and 23.01%, respectively. HO reduced the transverse area of bulliform cells by 13.73%, while MO treatments had no effect, and 5) the number of fusoid cells interspace, the transverse area of fusoid cells interspace, and mesophyll thickness of HO significantly increased by 11.16%, 28.58%, and 13.42%, respectively. In conclusion, I. decorus exhibits strong O3 tolerance characteristics, which stem from adaptions in the leaf's morphological, structural, antioxidant, and anatomical features. One critical attribute was the enlargement of the bulliform cell transverse area and the transverse area of fusoid cells interspace that drove this resistance to O3. Local bamboo species with high resistance to O3 pollution thus need to be promoted for sustained productivity and ecosystem services in areas with high O3 pollution.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

The Main Mechanisms of Mesenchymal Stem Cell-Based Treatments against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future. METHODS: Literature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved. RESULTS: Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, anti-inflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on. CONCLUSION: Mesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation.

BACKGROUND: Lipocalin 13 (LCN13) is a member of the lipocalin family that consists of numerous secretory proteins. LCN13 high-expression has been reported to possess anti-obesity and anti-diabetic effects. Although metabolic dysfunction-associated steatotic liver diseases (MASLD) including metabolic dysfunction-associated steatohepatitis (MASH) are frequently associated with obesity and insulin resistance, the functional role of endogenous LCN13 and the therapeutic effect of LCN13 in MASH and related metabolic deterioration have not been evaluated. METHODS: We employed a methionine-choline deficient diet model and MASH cell models to investigate the role of LCN13 in MASH development. We sought to explore the effects of LCN13 on lipid metabolism and inflammation in hepatocytes under PA/OA exposure using Western blotting, real-time RT-PCR, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, oil red O staining. Using RNA sequencing, chromatin immunoprecipitation assay, and luciferase reporter assays to elucidate whether farnesoid X receptor (FXR) regulates human LCN13 transcription as a transcription factor. RESULTS: Our study found that LCN13 was down-regulated in MASH patients, MASH mouse and cell models. LCN13 overexpression in hepatocyte cells significantly inhibited lipid accumulation and inflammation in vitro. Conversely, LCN13 downregulation significantly exacerbated lipid accumulation and inflammatory responses in vivo and in vitro. Mechanistically, we provided the first evidence that LCN13 was transcriptionally activated by FXR, representing a novel direct target gene of FXR. And the key promoter region of LCN13 binds to FXR was also elucidated. We further revealed that LCN13 overexpression via FXR activation ameliorates hepatocellular lipid accumulation and inflammation in vivo and in vitro. Furthermore, LCN13-down-regulated mice exhibited aggravated MASH phenotypes, including increased hepatic lipid accumulation and inflammation. CONCLUSION: Our findings provide new insight regarding the protective role of LCN13 in MASH development and suggest an innovative therapeutic strategy for treating MASH or related metabolic disorders.

CircALMS1 Alleviates Pulmonary Microvascular Endothelial Cell Dysfunction in Pulmonary Hypertension.

BACKGROUND: Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. METHODS AND RESULTS: Deep RNA sequencing and quantitative real-time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P<0.0001). Molecular biology and histopathology experiments were used to elucidate the roles of circALMS1 in regulating PMEC dysfunction among patients with PH. The circALMS1 expression was decreased in the plasma of patients with PH (P=0.0315). Patients with lower circALMS1 levels had higher risk of death (P=0.0006). Moreover, the circALMS1 overexpression of adeno-associated viruses improved right ventricular function and reduced pulmonary vascular remodeling in monocrotaline-PH and sugen/hypoxia-PH rats (P<0.05). Furthermore, circALMS1 overexpression promoted apoptosis and inhibited PMEC proliferation and migration under hypoxia by directly downregulating miR-17-3p (P<0.05). Dual luciferase assay confirmed the direct binding of circALMS1 to miR-17-3p and miR-17-3p binding to its target gene YT521-B homology domain-containing family protein 2 (YTHDF2) (P<0.05). The YTHDF2 levels were also downregulated in hypoxic PMECs (P<0.01). The small interfering RNA YTHDF2 reversed the effects of miR-17-3p inhibitors on PMEC proliferation, migration, and apoptosis. Finally, the results indicated that, although YTHDF2, as an N(6)-methyladenosine reader protein, contributes to the degradation of many circular RNAs, it could not regulate the circALMS1 levels in PMECs (P=0.9721). CONCLUSIONS: Our study sheds new light on circALMS1-regulated dysfunction of PMECs by the miR-17-3p/YTHDF2 pathway under hypoxia and provides insights into the underlying pathogenesis of PH.

Optimal timing for awake prone positioning in Covid-19 patients: Insights from an observational study from two centers.

BACKGROUND: The widespread application and interest in awake prone positioning stems from its ease and availability and its ability to enhance patients' oxygenation. Nevertheless, due to the absence of consensus over the regimen of awake prone positioning, the efficacy of awake prone positioning remains uncertain. OBJECTIVE: To explore the optimal regimen for awake prone positioning, including the timing of initiation, ideal daily duration, and strategies for improving patient comfort and encouraging adherence. DESIGN: Retrospective observational study. SETTING(S): Two university-affiliated hospitals in Shanghai. PARTICIPANTS: Between December 2022 and February 2023, a total of 475 patients with COVID-19-related pneumonia who received awake prone positioning were observed. METHODS: The data were collected from the hospital's electronic medical record system. The differentiation efficiency of peripheral blood oxygen saturation [SpO2]:fractional oxygen concentration in inspired air [FiO2] ratio at first awake prone positioning for different outcomes was tested by the area under the receiver operating characteristic curve. The Cox proportional hazard regression model was used to analyze the relationship between time to occurrence of 28-day outcomes and collected variables. Kaplan-Meier curves were plotted with the percentage of 28-day outcomes according to the SpO2:FiO2 ratio at first awake prone positioning after controlling covariates through Cox regression. RESULTS: The best efficiency in predicting patient outcomes was achieved when the cutoff SpO2:FiO2 ratio at first awake prone positioning was 200. Patients with a reduced SpO2:FiO2 ratio (≤200) experienced more adverse respiratory outcomes (RR = 5.42, 95%CI [3.35, 8.76], p < 0·001) and higher mortality (RR = 16.64, 95%CI [5.53, 50.13], p < 0.001). Patients with a SpO2:FiO2 ratio of ≥200 at first awake prone positioning, longer duration between first awake prone positioning and admission, more awake prone positioning days, and better awake prone positioning completion were significantly protected from 28-day adverse respiratory outcomes and mortality. CONCLUSIONS: Initiating awake prone positioning with a SpO2:FiO2 ratio exceeding 200, increasing the number of awake prone positioning days, prolonging the time between first awake prone positioning and admission, and achieving better completion of awake prone positioning were found to be significantly associated with reduced adverse respiratory outcomes and mortality. REGISTRATION: ClinicalTrials.gov; No.: NCT05795751; URL: www. CLINICALTRIALS: gov.

Economic risks hidden in local water pollution and global markets: A retrospective analysis (1995-2010) and future perspectives on sustainable development goal 6.

Pollution from untreated wastewater discharges depletes clean water supply for humans and the environment. It poses adverse economic impacts by determining agricultural yields, manufacturing productivity, and ecosystem functionality. Current studies mainly focus on quantity-related water scarcity assessment. It is unknown how low water quality amplifies local water stress and induces cascading economic risks globally. In this study, we estimated both quality and quantity-related water scarcity index (WSI), local economic water scarcity risk (WSR), and cascading virtual WSR evident in global trade markets across 40 major economies from 1995 to 2010. We find developing countries, e.g., India and China, witnessed fast growth in both quantity and quality-related WSI. Major developed economies, e.g., the US and Germany, experienced a modest increase in water stress but alleviated quality-related risks. Local economic risk (WSR) grew from $116B to $380B, with quality-related risks rising from 20 % to 30 %. Virtual economic WSR in global supply chains increased from $39B to $160B, with quality-related risks increasing from 19 % to 27 %. China became the top exporter of economic WSR, ranked above the US, France, and Japan, and the second-largest position as an importer, trailing only the US. We finally conducted scenario modeling by 2030, assuming different progresses on SDG 6 targets. The findings suggest that only the most ambitious progress in both water quality enhancement and efficiency improvement helps to alleviate ∼20 % economic WSR globally. Our findings underscore the necessity for strategies that integrate management of untreated wastewater flows, improved water use efficiency, and diversification of supply chain networks to enhance global economic resilience to water challenges in the future.