Cell dehydration enables massive production of engineered membrane vesicles with therapeutic functions.

Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.

Type III fetal redundancy of the foramen ovale flap mimics hemodynamic changes of mitral stenosis.

Type III redundancy of the foramen ovale flap (RFOF) mimics hemodynamic changes of mitral stenosis(MS), which has not been particularly highlighted in previous literature but carries a favorable prognosis.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Non-invasive anticipation of infusion taste in fine-manipulated green teas through hyperspectral appearance analysis guided by ECG content.

The high catechin content in summer-to-autumn tea leaves often results in strong, unpleasant tastes, leading to significant resource waste and economic losses due to lignification of unpicked leaves. This study aims to improve the taste quality of summer-to-autumn green teas by combining fine manipulation techniques with hyperspectral observation. Fine manipulation notably enhanced infusion taste quality, particularly in astringency and its aftertaste (aftertasteA). Using Partial Least Squares Discriminant Analysis (PLSDA) on hyperspectral data, 100% prediction accuracy was achieved for dry tea appearance in the near-infrared spectrum. Astringency and aftertasteA correlated with hyperspectral data, allowing precise estimation with over 90% accuracy in both visible and near-infrared spectrums. Epicatechin gallate (ECG) emerged as a key taste compound, enabling non-invasive taste prediction. Practical applications in processing and quality control are demonstrated by the derived equations (Astringency = -0.88 × ECG + 45.401, AftertasteA = -0.353 × ECG + 18.609), highlighting ECG's role in shaping green tea taste profiles.

Efficacy of acupoint injection in the treatment of chronic eczema and its influence on peripheral blood T cells.

BACKGROUND: Chronic eczema significantly impacts daily life, social interactions, and quality of life; however, no curative treatment has been identified. AIM: To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells. METHODS: Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group (n = 40), which received conventional Western medicine treatment, or an observation group (n = 40), which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide. Response and adverse reaction rates, as well as differences in the levels of serum cytokines IFN-γ, IL-2, IL-4, and IL-10 before and after treatment were investigated. RESULTS: No difference in overall response rates were found between the observation and control groups (100% vs 90%, respectively; P > 0.05); however, the observation group had a higher marked response rate than the control group (87.5% vs 52.5%; P < 0.05). Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment (P < 0.05), particularly in the observation group (P < 0.05). The observation group had an adverse reaction rate of 2.5% (1/40), which did not differ significantly from that of the control group (P > 0.05). The observation group exhibited higher post-treatment INF-γ and IL-2 but lower IL-4 levels than the control group (P < 0.05); however, no significant inter-group difference was observed in post-treatment IL-10 levels (P > 0.05). CONCLUSION: Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema. Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels, inhibition of inflammatory reactions, and mitigation of immune imbalance.

NAT1 inhibits liver metastasis of colorectal cancer by regulating EMT and glycolysis.

Metastasis is the primary cause of cancer-related deaths, and colorectal cancer (CRC) liver metastasis is a major poor prognostic factor in CRC. NAT1 (N-acetyltransferase 1) plays a crucial role in the invasive and metastatic processes of colorectal cancer. The role and molecular mechanism of NAT1 on tumor cells were verified by establishing a cell model of overexpression and knockdown of NAT1, and further verified by establishing a liver metastasis model of colorectal cancer for animal experiments. In vivo and in vitro experiments have demonstrated that overexpression of NAT1 reduces the ability of metastasis and invasion of colorectal cancer cells. NAT1 overexpression inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing the EMT (epithelial-mesenchymal transition) process and glycolytic ability of tumor cells. Additionally, decreased glycolytic ability results in reduced VEGF (Vascular endothelial growth factor) expression in colorectal cancer cells. The decreased VEGF expression leads to decreased angiogenesis and vascular permeability in liver metastases, ultimately reducing the occurrence of liver metastasis. Our findings highlight that overexpression of NAT1 significantly inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing EMT, glycolytic ability, and VEGF expression in colorectal cancer cells, collectively preventing the development of liver metastasis.

Developing preclinical dog models for reconstructive severed spinal cord continuity via spinal cord fusion technique.

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Quantum dots as advanced nanomaterials for food quality and safety applications: A comprehensive review and future perspectives.

The importance of food quality and safety lies in ensuring the best product quality to meet consumer demands and public health. Advanced technologies play a crucial role in minimizing the risk of foodborne illnesses, contamination, drug residue, and other potential hazards in food. Significant materials and technological advancements have been made throughout the food supply chain. Among them, quantum dots (QDs), as a class of advanced nanomaterials with unique physicochemical properties, are progressively demonstrating their value in the field of food quality and safety. This review aims to explore cutting-edge research on the different applications of QDs in food quality and safety, including encapsulation of bioactive compounds, detection of food analytes, food preservation and packaging, and intelligent food freshness indicators. Moreover, the modification strategies and potential toxicities of diverse QDs are outlined, which can affect performance and hinder applications in the food industry. The findings suggested that QDs are mainly used in analyte detection and active/intelligent food packaging. Various food analytes can be detected using QD-based sensors, including heavy metal ions, pesticides, antibiotics, microorganisms, additives, and functional components. Moreover, QD incorporation aided in improving the antibacterial and antioxidant activities of film/coatings, resulting in extended shelf life for packaged food. Finally, the perspectives and critical challenges for the productivity, toxicity, and practical application of QDs are also summarized. By consolidating these essential aspects into this review, the way for developing high-performance QD-based nanomaterials is presented for researchers and food technologists to better capitalize upon this technology in food applications.

Association of air temperature exposure during pregnancy with risk of preeclampsia in Guangzhou, China.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome.

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Application of"Spinal cord fusion" in spinal cord injury repair and its neurological mechanism.

Spinal cord injury (SCI) is a severely disabling and catastrophic condition that poses significant global clinical challenges. The difficulty of SCI repair results from the distinctive pathophysiological mechanisms, which are characterised by limited regenerative capacity and inadequate neuroplasticity of the spinal cord. Additionally, the formation of cystic cavities and astrocytic scars after SCI further obstructs both the ascending and descending neural conduction pathways. Consequently, the urgent challenge in post-SCI recovery lies in repairing the damaged spinal cord to reconstruct a functional and intact neural conduction circuit. In recent years, significant advancements in biological tissue engineering technology and novel therapies have resulted in a transformative shift in the field of SCI repair. Currently, SCI treatment primarily involves drug therapy, stem cell therapy, the use of biological materials, growth factors, and other approaches. This paper comprehensively reviews the progress in SCI research over the years, with a particular focus on the concept of "Spinal Cord Fusion" as a promising technique for SCI reconstruction. By discussing this important research progress and the neurological mechanisms involved, our aim is to help solve the problem of SCI repair as soon as possible and to bring new breakthroughs in the treatment of paraplegia after SCI.

Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

The Therapeutic Effect of Buyang Huanwu Decoction on Mild Cognitive Impairment (MCI) in Patients with Diabetes.

OBJECTIVE: This study aims to comprehensively verify the efficacy of Buyang Huanwu Decoction in improving cognitive function in patients with diabetes. METHODS: Patients clinically diagnosed with mild cognitive impairment (MCI) assigned to either the placebo group or the Buyang Huanwu Decoction group. After strict screening and exclusions, a total of 156 participants completed the clinical trial, with 76 in the placebo group and 80 in the Buyang Huanwu Decoction group. RESULTS: After treatment, Buyang Huanwu Decoction group showed higher Mini-Mental State Examination and Montreal Cognitive Assessment scores compared to placebo (p < 0.05). Memory and Executive Screening, Boston Naming Test, and Animal Fluency Test scores were also higher in the treatment group (p < 0.05). No significant differences were found in DST and CDT scores (p > 0.05). Trail Making Test scores were lower in the treatment group (p < 0.05). No significant difference was observed between the two groups in terms of complications (p > 0.05). CONCLUSION: Patients receiving Buyang Huanwu Decoction treatment demonstrated improvement in cognitive function, showing positive effects and providing preliminary evidence for the role of Buyang Huanwu Decoction in improving cognitive function in patients with diabetes. This suggests its potential for clinical application and further promotion.

Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.

Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes, but its pathogenesis has not been clearly elucidated. Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression. Therefore, in the present study, we analyzed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance (NGT) throughout the three trimesters. We found that the variation trends of 38 metabolites were significantly different during GDM development. Specifically, longitudinal analyses revealed that cysteine (Cys) levels significantly decreased over the course of GDM progression. Further study showed that Cys alleviated GDM in female mice at gestational day 14.5 possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis. Taken together, these findings suggest that the Cys metabolic pathway might play a crucial role in GDM and that Cys supplementation represents a potential new treatment strategy for GDM patients.

Multidisciplinary management based on clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage: A randomized controlled trial.

OBJECTIVE: To explore the effectiveness of multidisciplinary management based on a clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage (HICH). METHODS: A total of 124 patients with HICH admitted to our hospital between February 2021 and June 2023 were selected as research subjects in this randomized, controlled, unblinded study. They were divided into Control-group and Study-group using a random number table method, with 62 cases in each group. The Control-group received routine care and the Study-group adopted a multidisciplinary management approach based on the clinical nursing pathway model. A multidisciplinary intervention group including 1 attending physician, 1 psychotherapist, 1 nutritionist, 1 rehabilitation specialist, and 4 responsible nurses was constructed. From preoperative to postoperative day, patients were provided with psychological intervention, health education, respiratory tract management, and specific care for patients who were restless. One to 3 days after operation, the patients and their family members were guided in basic postoperative care and nutrition care. From the 4th day after surgery to the 1st day before discharge, patients were guided for rehabilitation exercises. Patients also received discharge advices upon discharge. Activities of daily living, neurological function, stress response indicators, incidence of complications, and nursing satisfaction before and after the intervention were compared between the 2 groups. RESULTS: After the intervention, the activities of daily living and neurological function of the 2 groups were significantly improved compared to before the intervention, and the Study-group was significantly higher than the Control-group (P < .05). After intervention, the levels of stress response indicators in both groups significantly decreased compared to before the intervention, and the Study-group was significantly lower than the Control-group (P < .05). The incidence of complications in the Study-group (3.23%) was lower than that in the Control-group (15.00%) (P < .05). Nursing satisfaction in the Study-group (95.16%) was higher than that in the Control-group (83.33%) (P < .05). CONCLUSIONS: Our findings indicate that adopting a multidisciplinary management approach based on clinical nursing pathways to intervene in patients with HICH can reduce stress response levels, reduce the risk of complications, and facilitate the recovery of neurological function and activities of daily living with high patient satisfaction.

Novel automated antifungal susceptibility testing system for yeasts based on dual-detection algorithm of turbidimetry and colorimetry.

Introduction. The increasing prevalence and growing resistance of fungi present a significant peril to public health. There are only four classes of antifungal medicines available today, and few candidates are in clinical trials.Hypothesis/Gap Statement. Rapid and sensitive diagnostic techniques are lacking for most fungal pathogens, and those that do exist are expensive or hard to obtain.Aim. This study aimed to evaluate the feasibility of a novel automated antifungal susceptibility testing system, Fungus AST, in comparison to the broth microdilution method (BMD) recommended by the Clinical and Laboratory Standards Institute (CLSI).Methodology. A total of 101 clinical Candida spp. isolates were collected from the Zengcheng Branch of Nanfang Hospital and subjected to antifungal susceptibility testing. Antifungal susceptibility was assessed using the Fungus AST method and the BMD.Results. In this study, we introduce a novel automated antifungal susceptibility testing system, Fungus AST, which detects the turbidity and/or colour intensity of microdilution wells using a four-wavelength detection technology in real time and is designed to match the growth characteristics of strains over time. Based on our analysis, all reportable ranges of Fungus AST were suitable for clinical fungal isolates in PR China. Within ±twofold dilutions, reproducibility was 100 %. Considering the BMD as a referenced method, ten antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B, 5-flucytosine and nystatin) showed an essential agreement of >95 %. The category agreement of five antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole and voriconazole) was excellent at >90 %. One Candida albicans isolate and voriconazole showed a major error (ME) (1.7 %), and no other ME or very ME agents were found.Conclusion. Given the above, it can be argued that the utilization of Fungus AST is a discretionary automated approach. More improvements are needed in Fungus AST compared to the BMD system for a wider range of clinical isolates, including different types of fungi.

Presenilin 1 Is a Therapeutic Target in Pulmonary Hypertension and Promotes Vascular Remodeling.

Small muscular pulmonary artery remodeling is a dominant feature of pulmonary arterial hypertension (PAH). PSEN1 affects angiogenesis, cancer, and Alzheimer's disease. We aimed to determine the role of PSEN1 in the pathogenesis of vascular remodeling in pulmonary hypertension (PH). Hemodynamics and vascular remodeling in the Psen1-knockin and smooth muscle-specific Psen1-knockout mice were assessed. The functional partners of PSEN1 were predicted by bioinformatics analysis and biochemical experiments. The therapeutic effect of PH was evaluated by administration of the PSEN1-specific inhibitor ELN318463. We discovered that both the mRNA and protein levels of PSEN1 were increased over time in hypoxic rats, monocrotaline rats, and Su5416/hypoxia mice. Psen1 transgenic mice were highly susceptible to PH, whereas smooth muscle-specific Psen1-knockout mice were resistant to hypoxic PH. STRING analysis showed that Notch1/2/3, ß-catenin, Cadherin-1, DNER (delta/notch-like epidermal growth factor-related receptor), TMP10, and ERBB4 appeared to be highly correlated with PSEN1. Immunoprecipitation confirmed that PSEN1 interacts with ß-catenin and DNER, and these interactions were suppressed by the catalytic PSEN1 mutations D257A, D385A, and C410Y. PSEN1 was found to mediate the nuclear translocation of the Notch1 intracellular domains and activated RBP-Jκ. Octaarginine-coated liposome-mediated pharmacological inhibition of PSEN1 significantly prevented and reversed the pathological process in hypoxic and monocrotaline-induced PH. PSEN1 essentially drives the pathogenesis of PAH and interacted with the noncanonical Notch ligand DNER. PSEN1 can be used as a promising molecular target for treating PAH. PSEN1 inhibitor ELN318463 can prevent and reverse the progression of PH and can be developed as a potential anti-PAH drug.

A systemic lupus erythematosus patient with persistent elevated conjugated bilirubin as the initial symptom: A case report.

RATIONALE: While some systemic lupus erythematosus (SLE) patients may experience varying degrees of liver function abnormalities, only a small portion of these cases have clinical significance, and the majority of patients typically exhibit low levels of serum bilirubin. However, in this article, we present a case of a middle-aged female patient with SLE who exhibited persistent skin jaundice as her initial symptom, offering a fresh perspective on diagnosing and treating patients who exhibit unexplained liver dysfunction and SLE combined with liver injury. PATIENT CONCERNS: A 45-year-old woman was initially admitted to the hospital due to yellowing of the skin and sclera, and her symptoms did not improve significantly during treatment. The results were abnormal after relevant immunological tests. DIAGNOSES: Persistent non-conjugated bilirubin elevation due to lupus hepatitis. INTERVENTIONS: The use of methylprednisolone sodium succinate (40 mg/Qd) and mycophenolate mofetil (0.75 g/d) suppressed immunity, polyolefin choline (20 mL/d) and glutathione (0.6 g/Qd) improved liver function, and nutritional support therapy. OUTCOMES: After 2 weeks of treatment, a significant decrease in the yellow skin and sclera of the patient was observed. LESSONS: Most clinicians overlook that liver function abnormalities are the main manifestation of SLE, resulting in many patients not receiving timely treatment. This study highlights the importance that SLE is also a cause of abnormal liver function.

Ethanolamine as a biomarker and biomarker-based therapy for diabetic retinopathy in glucose-well-controlled diabetic patients.

Diabetic retinopathy (DR) is the leading cause of blindness among the working-age population. Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%, there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-well-controlled diabetic patients (GW-DR). In this study, we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period. The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline, all of whom consistently maintained hemoglobin A1c (HbA1c) levels below 7% without experiencing hypoglycemia. Within this cohort of 71 individuals, 21 subsequently experienced new-onset GW-DR, resulting in an incidence rate of 29.6%. In the validation cohort, we also observed a significant GW-DR incidence rate of 17.9%. Employing targeted metabolomics, we investigated the metabolic characteristics of serum in GW-DR, revealing a significant association between lower levels of ethanolamine and GW-DR risk. This association was corroborated in the validation cohort, exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c, with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts, respectively. Furthermore, in a streptozotocin (STZ)-induced diabetic rat model, ethanolamine attenuated diabetic retinal inflammation, accompanied by suppression of microglial diacylglycerol (DAG)-dependent protein kinase C (PKC) pathway activation. In conclusion, we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.

Crude Lipopeptides Produced by Bacillus amyloliquefaciens Could Control the Growth of Alternaria alternata and Production of Alternaria Toxins in Processing Tomato.

Alternaria spp. and its toxins are the main contaminants in processing tomato. Based on our earlier research, the current study looked into the anti-fungal capacity of crude lipopeptides from B. amyloliquefaciens XJ-BV2007 against A. alternata. We found that the crude lipopeptides significantly inhibited A. alternata growth and reduced tomato black spot disease incidence. SEM analysis found that the crude lipopeptides could change the morphology of mycelium and spores of A. alternata. Four main Alternaria toxins were detected using UPLC-MS/MS, and the findings demonstrated that the crude lipopeptides could lessen the accumulation of Alternaria toxins in vivo and in vitro. Meanwhile, under the stress of crude lipopeptides, the expression of critical biosynthetic genes responsible for TeA, AOH, and AME was substantially down-regulated. The inhibitory mechanism of the crude lipopeptides was demonstrated to be the disruption of the mycelial structure of A. alternata, as well as the integrity and permeability of the membrane of A. alternata sporocytes. Taken together, crude lipopeptides extracted from B. amyloliquefaciens XJ-BV2007 are an effective biological agent for controlling tomato black spot disease and Alternaria toxins contamination.