STMHCpan, an accurate Star-Transformer-based extensible framework for predicting MHC I allele binding peptides.

Peptide-major histocompatibility complex I (MHC I) binding affinity prediction is crucial for vaccine development, but existing methods face limitations such as small datasets, model overfitting due to excessive parameters and suboptimal performance. Here, we present STMHCPan (STAR-MHCPan), an open-source package based on the Star-Transformer model, for MHC I binding peptide prediction. Our approach introduces an attention mechanism to improve the deep learning network architecture and performance in antigen prediction. Compared with classical deep learning algorithms, STMHCPan exhibits improved performance with fewer parameters in receptor affinity training. Furthermore, STMHCPan outperforms existing ligand benchmark datasets identified by mass spectrometry. It can also handle peptides of arbitrary length and is highly scalable for predicting T-cell responses. Our software is freely available for use, training and extension through Github (https://github.com/Luckysoutheast/STMHCPan.git).

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Diabetic nephropathy (DN) is a common complication of diabetes and a leading cause of end-stage renal disease. Transforming growth factor-ß1 (TGF-ß1)/SMAD signaling activation plays an important role in the onset and progression of DN. Reported findings suggest that the activation of TGF-ß1 (including the latent form, the active form, and the receptors) and its downstream signaling proteins (SMAD3, SMAD7, etc.) plays a critical role in DN. In addition, TGF-ß1/SMAD signaling may mediate the pathogenesis and progression of DN via various microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Emerging evidence shows that TGF-ß1, SMAD3, and SMAD7 are the main signaling proteins that contribute to the development of DN, and that they can be potential targets for the treatment of DN. However, recent clinical trials have shown that the anti-TGF-ß1 monoclonal antibody treatment fails to effectively alleviate DN, which suggests that upstream inhibition of TGF-ß1/SMAD signaling does not alleviate clinical symptoms and that this may be related to the fact that TGF-ß1/SMAD has multiple biological effects. Targeted inhibition of the downstream TGF-ß1 signaling (e.g., SMAD3 and SMAD7) may be an effective approach to attenuate DN. This article discussed the current understanding of the molecular mechanisms and potential targets for the treatment and prevention of DN by focusing on TGF-ß1/SMAD signaling.

Effect of Herbs on Postoperative Intestinal Obstruction: A Case Report.

Postoperative intestinal obstruction is one of the most common and challenging complications after patients receive pelvic or abdominal surgery. The effectiveness of conventional therapies is varied and they are associated with a high recurrence rate. Traditional Chinese Medicine can be beneficial in the treatment of intestinal obstruction. In this case, a 65-year-old woman had progressively increasing abdominal pain, distension, and constipation following total hip replacement surgery. The patient was diagnosed with partial intestinal obstruction and was treated for 6 days without success using conventional Western medicine, including Enema Glycerini and Sodium Phosphates Rectal Solution. We received a request from the surgical department for a Chinese medicine consultation. Two doses of modified Dachengqi Decoction herbal formula were prescribed for the patient. The patient had her first flatus and defecation within 2 hours after ingestion of the first dose of herbal medicine and subsequently all of the symptoms were relieved. The patient was soon discharged without any further complications; a 5-year follow-up indicated that the patient had no recurrence of intestinal obstruction. This case is the first to report the effect of a Chinese herbal decoction in achieving remission of intestinal obstruction with only 1 dose. Large scale randomized controlled trials are warranted to confirm our findings.

Dose-response association of diabetic kidney disease with routine clinical parameters in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain. Methods: In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148). Findings: This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m2 increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I2 = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I2 = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I2 = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I2 = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I2 = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I2 = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years. Interpretation: BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD. Funding: Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.

Molecular Evolutionary Landscape of the Immune Microenvironment of Head and Neck Cancer.

Head and neck cancer is a highly heterogeneous malignant tumor. Numerous studies have shown that the immune microenvironment of head and neck cancer has a significant impact on its occurrence and development, as well as its prognosis. However, there have been fewer studies related to the accurate immunophenotyping of head and neck cancer. In this study, we used gene expression profile information and clinical information from the TCGA-HNSC cohort (502 samples) and the GSE655858 cohort (270 samples) to identify and independently validate three immune subtypes (Cluster1-Cluster3) with different immune-related molecular profiles and clinical outcomes. Cluster2, which is mainly dominated by B-lymphocyte infiltration, was found to have the best prognosis. In addition, a support vector machine (SVM)-based classifier was constructed, which could accurately classify HNSC based on 19 genes. Furthermore, the results of the prognostic analysis showed activation of antibody-secreting B-lymphocyte function, which showed a good prognostic effect in all three immune subtypes of HNSC. Finally, the immune evolutionary landscape of HNSC was constructed in an attempt to explain the evolutionary pattern of the immune subtypes of HNSC. In summary, we provide a conceptual framework for understanding the tumor immune microenvironment in HNSC and demonstrate the importance of immune infiltration of B lymphocytes in HNSC. Further research is needed to assess the importance of these immunophenotypes in combination drug therapy and to provide a basis for screening appropriate patients for immunotherapy.

Roles and crosstalks of macrophages in diabetic nephropathy.

Diabetic nephropathy (DN) is the most common chronic kidney disease. Accumulation of glucose and metabolites activates resident macrophages in kidneys. Resident macrophages play diverse roles on diabetic kidney injuries by releasing cytokines/chemokines, recruiting peripheral monocytes/macrophages, enhancing renal cell injuries (podocytes, mesangial cells, endothelial cells and tubular epithelial cells), and macrophage-myofibroblast transition. The differentiation and cross-talks of macrophages ultimately result renal inflammation and fibrosis in DN. Emerging evidence shows that targeting macrophages by suppressing macrophage activation/transition, and macrophages-cell interactions may be a promising approach to attenuate DN. In the review, we summarized the diverse roles of macrophages and the cross-talks to other cells in DN, and highlighted the therapeutic potentials by targeting macrophages.

Qili Qiangxin capsules for chronic heart failure: A GRADE-assessed clinical evidence and preclinical mechanism.

Introduction: Chronic heart failure (CHF) has become an increasing concern with the aging of the population. This study aims to evaluate the effectiveness and safety of Qili Qiangxin capsules (QLQX) for CHF. Methods: A systematic review and meta-analysis on clinical studies was conducted. The mechanisms of preclinical studies were summarized. Results: We searched six electronic databases by 20 July 2022, and finally, 7 preclinical experiments (PEs) and 24 randomized controlled trials were included. The risk of bias was accessed by the SYRCLE and RoB 2.0 tool, respectively. PEs indicated that QLQX suppresses myocardial apoptosis, inhibits renin-angiotensin-aldosterone system activation, improves water retention, and enhances cardiocyte remodeling. In clinical studies, compared with routine treatment, QLQX could improve the indicators: clinical efficacy rate (RR = 1.16, 95% CI [1.12, 1.22], GRADE: moderate), left ventricular end-diastolic dimension (SMD = -1.04, 95% CI [-1.39, -0.70], GRADE: low), left ventricular ejection fraction (SMD = 1.20, 95% CI [0.97, 1.43], GRADE: moderate), 6-minute walk distance (SMD = 1.55, 95% CI [0.89, 2.21], GRADE: low), brain natriuretic peptide (SMD = -0.78, 95% CI [-1.06, -0.51], GRADE: low), N-terminal pro-brain natriuretic peptide (SMD = -2.15, 95% CI [-3.60, -0.71], GRADE: low), and adverse events (RR = 0.46, 95% CI [0.25, 0.87], GRADE: low). Discussion: In summary, QLQX exerts a potential mechanism of utility on myocardial apoptosis and cardiac function and has noteworthy clinical adjuvant efficacy and safety in patients with CHF. Systematic review registration: https://www.crd.york.ac.uk/prospero/.

Gold@silver nanodumbbell based inter-nanogap aptasensor for the surface enhanced Raman spectroscopy determination of ochratoxin A.

Here, a plasmonic nanogap structure was fabricated with its specific surface enhanced Raman spectroscopy (SERS) effect to construct an aptasensor for the sensitive detection of ochratoxin A (OTA). Gold nanorod (AuNR) were synthesized first by seed-mediated method. Then, silver was reduced and grown on its surface. In the presence of glycine, Ag0 was preferred to grow at both ends of AuNR to form gold@silver nanodumbbell (Au@AgND). The thiolated OTA aptamer and its complementary sequence were modified on Au@AgND respectively using Ag-SH bond. Under the base complementary pairing principle, Au@AgND assembly formed with certain inter distances. The inter-nanogap structure generated more hot spots which enhanced the Raman signal of 4-hydroxybenzoic acid (4-MBA) immobilized on Au@AgND. When OTA was present, the aptamer preferentially combined to OTA and the Au@AgND assembly disintegrated. Thus, the SERS signal of 4-MBA decreased. Under the optimal conditions, the OTA concentrations were inversely proportional to SERS signal. The linear range was 0.01 ng/mL-50 ng/mL and the limit of detection (LOD) was 0.007 ng/mL. The method can be successfully applied to the detection of real sample (beer/peanut oil).

Remission of new-onset type 2 diabetes mellitus in an adolescent using an integrative medicine approach: A case report.

Among adolescents, the incidence of type 2 diabetes mellitus (T2DM) has recently increased. A 12-year-old Chinese boy with a one-year history of hyperphagia presented to our clinic. The patient was diagnosed with T2DM one month prior to visiting the clinic and reported undergoing no pharmacologic treatment. Using an integrative medicine approach, including Chinese herbal decoction, berberine hydrochloride tablets, physical exercise and diet control, the patient's fasting blood glucose (FBG) decreased from 8.3 mmol/L to 5.5 mmol/L. Additionally, his glycated haemoglobin decreased from 12.9% to 6.1%, indicating that without any Western medicine intervention his diabetes has been reversed after six months of treatment. His FBG remained normal, and nine months after completion of treatment it was 4.9 mmol/L. A potential mechanism in this response may be related to improved insulin resistance and ß-cell function, as indicated by observed changes in homeostasis model assessment of insulin resistance and ß-cell function. Further, weight loss may also have contributed to the effectiveness of the treatment. This case study is the first to present the innovative approach of integrative medicine to achieve remission of new-onset adolescent T2DM.

Epigenetics and Inflammation in Diabetic Nephropathy.

Diabetic nephropathy (DN) leads to high morbidity and disability. Inflammation plays a critical role in the pathogenesis of DN, which involves renal cells and immune cells, the microenvironment, as well as extrinsic factors, such as hyperglycemia, chemokines, cytokines, and growth factors. Epigenetic modifications usually regulate gene expression via DNA methylation, histone modification, and non-coding RNAs without altering the DNA sequence. During the past years, numerous studies have been published to reveal the mechanisms of epigenetic modifications that regulate inflammation in DN. This review aimed to summarize the latest evidence on the interplay of epigenetics and inflammation in DN, and highlight the potential targets for treatment and diagnosis of DN.

Recent achievements in exosomal biomarkers detection by nanomaterials-based optical biosensors - A review.

Exosomal biomarkers including tumor-derived exosomes, exosomal surface proteins and exosomal nucleic acids have emerged as one of the most important and general cancer biomarkers in modern biomedical science. These indicators can provide momentous biological information for early diagnosis and treatment of cancer. Recently, numerous studies have been conducted to design biosensors for exosomal biomarkers detection and profiling with high sensitivity and strong applied ability. Among these biosensors, nanomaterial-based optical biosensors are prospective future platforms for rapid and cost-effective detection of exosomal biomarkers. Firstly, we have focused on the progress and advancements in different optical-transducing approaches (Surface-Enhanced Raman Scattering, Surface Plasmon Resonance, Colorimetry, Immunochromatographic assay, Chemiluminescence, Electrochemiluminescence, and fluorescence) for detecting and profiling exosomal biomarkers. Additionally, we have summarized strengths and drawbacks of each strategy. Finally, challenges and future outlooks in developing efficient nanomaterial-based optical biosensor systems for exosomal tumor biomarkers detection have been discussed. The review will exhibit an overview of this field and provide meaningful information for scientific researchers.

The effectiveness of Baduanjin exercise for hypertension: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hypertension, a major risk factor of cardiovascular mortality, is a critical issue for public health. Although Baduanjin (Eight Brocades, EB), a traditional Chinese exercise, might influence blood pressure, glucose, and lipid status, the magnitude of true effects and subgroup differences remains unclear. Therefore, we performed a systematic review of relevant randomized controlled trials (RCTs) to evaluate the effect of EB on patient-important outcomes. METHODS: We systematically searched PubMed, the Cochrane Library, Web of Science, and Chinese databases since inception until March 30, 2020. Meta-analysis was carried out using "meta" package in R 3.4.3 software. A prespecified subgroup analysis was done according to the type of comparisons between groups, and the credibility of significant subgroup effects (P < 0.05) were accessed using a five-criteria list. A GRADE evidence profile was constructed to illustrate the certainty of evidence. RESULTS: Our meta-analysis, including 14 eligible trials with 1058 patients, showed that compared with routine treatment or health education as control groups, the mean difference (MD) in systolic blood pressure (SBP) of the EB groups was - 8.52 mmHg (95%CI:[- 10.65, - 6.40], P < 0.01) and diastolic blood pressure (DBP) was - 4.65 mmHg (95%CI: [- 6.55, - 2.74], P < 0.01). For blood pressure, the evidence was, however, of low certainty because of risk of bias and inconsistency, and for the outcomes of most interest to patients (cardiovascular morbidity and mortality directly), of very low certainty (measurement of surrogate only). Subgroup analysis showed there was no significant interaction effect between different type of comparisons (SBP P = 0.15; DBP P = 0.37), so it could be easily attributed to chance. CONCLUSION: Regularly EB exercising may be helpful to control blood pressure, but the evidence is only low certainty for blood pressure and very low certainty for cardiovascular morbidity and mortality. Rigorously designed RCTs that carry out longer follow-up and address patient-important outcomes remain warranted. TRIAL REGISTRATION: PROSPERO Registration number: CRD42018095854 .

Nanogapped Au(core) @ Au-Ag(shell) structures coupled with Fe3O4 magnetic nanoparticles for the detection of Ochratoxin A.

Contamination of mycotoxins has been a general problem of food safety and afflicts people all around the world. Ochratoxin A (OTA), an abundant and representative food-contaminating mycotoxin, has a detrimental effect on our health. Herein, an ultrasensitive surface-enhanced Raman scattering (SERS) aptasensor was fabricated for OTA detection. Au(core)@Au-Ag(shell) nanogapped nanostructures (Au@Au-Ag NNSs) were coupled with Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) by OTA aptamer and its complementary DNA sequence. The distance between two nanoparticles become far away in presence of the OTA due to the affinity of aptamer. This effect can obviously bring about the change of Raman intensity which can be used for the detection of OTA. Compared with pure metal nanoparticles, Au@Au-Ag NNSs can effectively enhance the Raman intensity of Raman signal molecule (4-MBA) via the ultrasmall nanogap, which contribute to the sensitivity of the sensor system. Additionally, the utilization of Fe3O4 MNPs offers a green, economical and facile technology to capture targets from solution. The specially modified aptamer and its complementary strand establish a bridge connecting between Au@Au-Ag NNSs and Fe3O4 MNPs. In this study, OTA concentration with a linear range of 0.01-50 ng mL-1 and the limit of detection (LOD) was as low as 0.004 ng mL-1. The proposed SERS aptasensor can combine both of these above type of materials and provide a rapid, sensitive, and low-cost methodology for numerous future applications of point-of-care diagnostics.

Recyclable (Fe3O4-NaYF4:Yb,Tm)@TiO2 nanocomposites with near-infrared enhanced photocatalytic activity.

Herein, the design and synthesis of a multifunctional (Fe3O4-NaYF4:Yb,Tm)@TiO2 photocatalyst through a facile sol-gel process combined with electrostatic self-assembly has been reported. Particularly, as an upconversion sensor, NaYF4:Yb,Tm nanoparticles have the ability to convert near-infrared (NIR) light into ultraviolet (UV) emissions, so that the catalytic body TiO2 can indirectly utilize the NIR part of sunlight but not UV light. The excellent photocatalytic activity of the hybrid samples is evaluated using a model of the degradation of methylene blue (MB). Most importantly, the obtained materials exhibit remarkable magnetic properties because of the addition of a magnetic component (Fe3O4), therefore, the photocatalysts possess desired recyclability and reusability, which is significant for actual applications. Finally, the possible photocatalysis mechanism of the nanohybrids is discussed and hydroxyl radicals (OH˙) are confirmed as the main reactive species.