Unveiling unique alternative splicing responses to low temperature in Zoysia japonica through ZjRTD1.0, a high-quality reference transcript dataset.

Inadequate reference databases in RNA-seq analysis can hinder data utilization and interpretation. In this study, we have successfully constructed a high-quality reference transcript dataset, ZjRTD1.0, for Zoysia japonica, a widely-used turfgrass with exceptional tolerance to various abiotic stress, including low temperatures and salinity. This dataset comprises 113,089 transcripts from 57,143 genes. BUSCO analysis demonstrates exceptional completeness (92.4%) in ZjRTD1.0, with reduced proportions of fragmented (3.3%) and missing (4.3%) orthologs compared to prior datasets. ZjRTD1.0 enables more precise analyses, including transcript quantification and alternative splicing assessments using public datasets, which identified a substantial number of differentially expressed transcripts (DETs) and differential alternative splicing (DAS) events, leading to several novel findings on Z. japonica's responses to abiotic stresses. First, spliceosome gene expression influenced alternative splicing significantly under abiotic stress, with a greater impact observed during low-temperature stress. Then, a significant positive correlation was found between the number of differentially expressed genes (DEGs) encoding protein kinases and the frequency of DAS events, suggesting the role of protein phosphorylation in regulating alternative splicing. Additionally, our results suggest possible involvement of serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in generating inclusion/exclusion isoforms under low-temperature stress. Furthermore, our investigation revealed a significantly enhanced overlap between DEGs and differentially alternatively spliced genes (DASGs) in response to low-temperature stress, suggesting a unique co-regulatory mechanism governing transcription and splicing in the context of low-temperature response. In conclusion, we have proven that ZjRTD1.0 will serve as a reliable and useful resource for future transcriptomic analyses in Z. japonica.

Altered serum levels of cytokines in patients with myasthenia gravis.

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by generalized skeletal muscle contraction weakness due to autoantibodies targeting neural-muscular junctions. Here, we investigated the relationship between key cytokines and MG type, disease course, antibodies, and comorbidities. Method: Cytokine levels in serum samples collected from MG (n = 45) and healthy control (HC, n = 38) patients from January 2020 to June 2022 were quantified via flow cytometry. Results: Levels of IL-6 were higher in the MG group versus healthy individuals (p = 0.026) and in patients with generalized versus ocular MG (p = 0.019). IL-6 levels were positively correlated with QMG score. In patients with MG with both AChR and Titin antibodies, serum levels of sFas and granulysin were higher than in those with AChR alone (p = 0.036, and p = 0.028, respectively). LOMG had a reduction in serum levels of IL-2 compared to EOMG (p = 0.036). LOMG patients with diabetes had lower serum levels of IL-2, IL-4, and IFN-γ (p = 0.044, p = 0.038, and p = 0.047, respectively) versus those without diabetes. sFas in the MG with Abnormal thymus were reduced compared to those in MG with Normal thymus (p = 0.008). Conclusions: This study revealed a positive correlation between IL-6 level and MG status. Serum cytokine levels of the AChR + Titin MG group differed from those of the AChR group. LOMG had a lower IL-2 level. Comorbidities affect some cytokines in peripheral blood in MG serum.

Extracellular vesicles encapsulated with caspase-1 inhibitor ameliorate experimental autoimmune myasthenia gravis through targeting macrophages.

Cysteinyl aspartate-specific proteinase-1 (caspase-1) is a multifunctional inflammatory mediator in many inflammation-related diseases. Previous studies show that caspase-1 inhibitors produce effective therapeutic outcomes in a rat model of myasthenia gravis. However, tissue toxicity and unwanted off-target effects are the major disadvantages limiting their clinical application as therapeutic agents. This study shows that dendritic cell-derived extracellular vesicles (EVs) loaded with a caspase-1 inhibitor (EVs-VX-765) are phagocytized mainly by macrophages, and caspase-1 is precisely expressed in macrophages. Furthermore, EVs-VX-765 demonstrates excellent therapeutic effects through a macrophage-dependent mechanism, and it notably inhibits the level of interleukin-1ß and subsequently inhibits Th17 response and germinal center (GC) reactions. In addition, EVs-VX-765 demonstrates better therapeutic effects than routine doses of VX-765, although drug loading is much lower than routine doses, consequently reducing tissue toxicity. In conclusion, this study's findings suggest that EV-mediated delivery of caspase-1 inhibitors is effective for treating myasthenia gravis and is promising for clinical applications.

A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014-2022).

Background: The REFLECT phase-III trial has demonstrated the efficacy of lenvatinib in improving the overall survival of advanced hepatocellular carcinoma (HCC) patients, comparable to sorafenib. The rapidly evolving landscape of hepatocellular carcinoma therapy presents new avenues for lenvatinib. This study aims to provide a scientometric analysis of publications and predict research hotspots in this field. Methods: Relevant publications were sourced from the Web of Science Core Collection (WoSCC) database up until November 2022. The bibliometrix tool in R was employed for scientometric analysis and visualization. Results: A total of 879 publications from 2014 to 2022 were obtained from WoSCC that met the established criteria. These studies involved 4,675 researchers from 40 countries, with an average annual growth rate of 102.5%. The highest number of publications was from Japan, followed by China, Italy, and the United States. The largest proportion of studies, 14.0% (n = 123), was contributed by FUDAN UNIV. The studies were published in 274 journals, with CANCERS (n = 53) being the top journal, followed by FRONTIERS IN ONCOLOGY (n = 51) and HEPATOLOGY RESEARCH (n = 36). The top ten journals accounted for 31.5% of the 879 studies. The most prolific authors were Kudo M (n = 51), Hiraoka A (n = 43), and Tsuji K (n = 38). A total of 1,333 keywords were analyzed, with the present research hotspots being "immune checkpoint inhibitors," "prognosis," and "pd-1." Co-occurrence clustering analysis revealed the top keywords, authors, publications, and journals. Strong collaboration was identified in the field. Conclusion: This scientometric and visual analysis provides a comprehensive summary of the published articles on lenvatinib in HCC during 2014-2022, highlighting the research hotspots, knowledge domain, and frontiers. The results can provide insights into future research directions in this field.

Type 2 diabetes mellitus as a possible risk factor for myasthenia gravis: a case-control study.

Background: A certain number of myasthenia gravis (MG) patients clinically had type 2 diabetes mellitus (T2DM) prior to MG onset, which suggests that the onset of MG may correlate with the history of T2DM. This study aimed to examine the correlation between MG and T2DM. Methods: In a single-center, retrospective, 1:5 matched case-control study, all 118 hospitalized patients with a diagnosis of MG from 8 August 2014 to 22 January 2019 were enrolled. In total, four datasets with different sources of the control group were retrieved from the electronic medical records (EMRs). Data were collected at the individual level. A conditional logistic regression analysis was used to test the risk of MG associated with T2DM. Findings: The risk of MG was significantly associated with T2DM, and there were notable differences by sex and age. Whether compared to the general population, general hospitalized patients without autoimmune diseases (AIDs), or patients with other AIDs except MG, women aged over 50 years with T2DM had an increased risk of MG. The mean onset age of diabetic MG patients was more than that of the non-diabetic MG patients. Interpretation: This study demonstrates that T2DM is strongly associated with the subsequent risk of MG and varies significantly by sex and age. It reveals that diabetic MG may be a unique subtype that is different from the conventional MG subgroup classification. More clinical and immunological features of diabetic MG patients need to be explored in further studies.

Catalytic Asymmetric Diels-Alder Reaction of 2'-Hydroxychalcone as a Dienophile with a VANOL-Borate Ester Complex.

Numerous flavonoid Diels-Alder-type natural products have been isolated and received great attention from the synthetic community. Herein, we reported a catalytic strategy for an asymmetric Diels-Alder reaction of 2'-hydroxychalcone with a range of diene substrates using a chiral ligand-boron Lewis acid complex. This method enables the convenient synthesis of a wide range of cyclohexene skeletons in excellent yields with moderate to good enantioselectivities, which is critical to prepare natural product congeners for further biological studies.

Clinical Characteristics of 606 Patients with Community-Acquired Pyogenic Liver Abscess: A Six-Year Research in Yantai.

Objective: This study was designed to analyze the clinical characteristics, etiological characteristics, drug resistance, and empirical use of antibiotics for community-acquired pyogenic liver abscess (PLA) to provide a basis for rational and effective empirical treatment of PLA in the local area. Methods: The clinical data, etiological characteristics, drug resistance, and empirical anti-infective therapy schemes of 606 patients with PLA were collected and analyzed retrospectively. Results: The included patients were mainly males, with a male-to-female ratio of 1.3:1. The average age of the patients was 60.3 ± 14.1 years. The underlying diseases were diabetes and biliary tract disease, accounting for 38.7% and 22.3%, respectively. The main clinical manifestations were fever (92.9%), abdominal pain (44.7%), and nausea (33.3%). Imaging findings: the proportion of patients with a single lesion was 74.7%, and 67% of the patients had involvement in the right lobe of the liver. The main pathogen was Klebsiella pneumoniae accounted for 74.9% in blood culture and 84.1% in pus culture, mainly extended-spectrum ß-lactamase. In 272 strains negative for extended-spectrum ß-lactamase (ESBLs), 100% were resistant to ampicillin and less than 50% were sensitive to nitrofurantoin. Only 36 ESBL-positive strains had higher than 80% sensitivity to carbapenems, ß-lactamase inhibitor compound, and amikacin. Patients treated with different treatment methods showed significantly different average length of hospital stay (14 [9-21] vs 13 [8-18]). Empirical anti-infective therapy: Beta-lactamase complex, carbapenems, cephalosporins, and quinolones were used in 280 (37.6%), 180 (29.7%), 180 (29.7%), and 147 (24.3%) patients, respectively. Conclusion: Patients with community-acquired PLA in this area are mainly males, and the underlying diseases are mainly diabetes and hepatobiliary system disease. The main clinical manifestation is fever, so patients with fever of unknown cause should pay attention to possible liver abscesses. Based on drug sensitivity tests, the empirical use of antibiotics is somewhat unreasonable.

Diabetes mellitus aggravates humoral immune response in myasthenia gravis by promoting differentiation and activation of circulating Tfh cells.

Myasthenia gravis (MG) is a T-cell-dependent, antibody-mediated autoimmune disease. Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia and emerging evidence indicates its profound impacts on the immune homeostasis. Previous studies and our data showed DM might serve as an independent risk factor of MG, yet the underlying immune and molecular mechanisms remain to be addressed. Our study observed that circulating Tfh (cTfh) cells were increased in MG patients with DM and expressed a high level of ICOS. Besides, positive correlations between activated cTfh cells and plasmablasts were documented. Further studies demonstrated hyperglycemia promoted the differentiation and activation of Tfh cells which, in turn, caused abnormal plasmablasts differentiation and antibody secretion through the mTOR signaling pathway. These results indicated DM might aggravate the aberrant humoral immunity in MG patients by augmenting Tfh cells differentiation and function and tight glycemic control might be beneficial for MG patients with DM.

The role of Gadd45b in neurologic and neuropsychiatric disorders: An overview.

Growth arrest and DNA damage-inducible beta (Gadd45b) is directly intertwined with stress-induced DNA repair, cell cycle arrest, survival, and apoptosis. Previous research on Gadd45b has focused chiefly on non-neuronal cells. Gadd45b is extensively expressed in the nervous system and plays a critical role in epigenetic DNA demethylation, neuroplasticity, and neuroprotection, according to accumulating evidence. This article provided an overview of the preclinical and clinical effects of Gadd45b, as well as its hypothesized mechanisms of action, focusing on major psychosis, depression, autism, stroke, seizure, dementia, Parkinson's disease, and autoimmune diseases of the nervous system.

Solitary necrotic nodules of the liver with "ring"-like calcification: A case report.

BACKGROUND: Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with a complete necrotic core and a clear fibrous capsule containing elastic fibers. We present the case of a patient with a radiographic computed tomography (CT) finding of "ring"-like annular calcification within the lesion and postoperative pathologic diagnosis of necrotic nodules wrapped by dense fibers in liver tissue, as well as the patient's subsequent management and outcome. CASE SUMMARY: A 38-year-old Chinese woman with a history of systemic lupus erythematosus treated with prednisone and hydroxychloroquine, without any symptoms, was found to have hepatic space-occupying lesions by imaging examination at a health examination. A subsequent CT scan suggested a space-occupying lesion of the liver with annular calcification, which was not defined to be benign or malignant. After that, a laparoscopic hepatic space-occupying resection was performed. The postoperative pathological diagnosis was necrotic nodules wrapped by dense fibers in the liver tissue, and the final diagnosis was SNNL. The patient had an uneventful postoperative recovery. CONCLUSION: There is a "ring"-like calcification in SNNL. This patient had a history of systemic lupus erythematosus, without a history of parasite infection, trauma, or tumor. Therefore, whether the etiology and pathological changes of SNNL are related to rheumatic immune diseases remains to be investigated.

Clinical and genetic spectrum of primary ciliary dyskinesia in Chinese patients: a systematic review.

BACKGROUND: Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures. METHODS: We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing. RESULTS: A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced. CONCLUSIONS: Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD. TRIAL REGISTRY: PROSPERO; No.: CRD42021257804; URL: www.crd.york.ac.uk/prospero/.

An ERP study on the influence of mental abacus calculation on subthreshold arithmetic priming in children.

OBJECTIVE: The objective of this study was to investigate the influence of mental abacus calculation training (MACT) on subliminal cognitive processes. METHODS: Twenty children with intensive MACT (MACT group) and 20 children without MACT (non-MACT group) were selected. The two groups of children were matched in age, sex, handedness and academic grade. The participants were tested with subthreshold arithmetic priming task while their neural activities were recorded with a 32-channel electroencephalogram system. RESULTS: We found that MACT changed the subliminal cognitive mechanism of computational processing, speeding up the computation. MACT affected the computational processing mode. Specifically, in the identification stage, both groups of children adopted the visual space processing mode, while in the computing stage, the MACT group adopted a visual space processing mode, but the non-MACT group adopted a semantic processing mode. Moreover, MACT improved children's executive functions. CONCLUSION: These results yielded insights into the effect of early abacus training on children's cognitive processing, providing a theoretical basis for the development and promotion of abacus training.

A Survey of Enhanced Cold Tolerance and Low-Temperature-Induced Anthocyanin Accumulation in a Novel Zoysia japonica Biotype.

Zoysia japonica is a warm-season turfgrass that is extensively used in landscaping, sports fields, and golf courses worldwide. Uncovering the low-temperature response mechanism of Z. japonica can help to accelerate the development of new cold-tolerant cultivars, which could be used to prolong the ornamental and usage duration of turf. A novel Z. japonica biotype, YueNong-9 (YN-9), was collected from northeastern China for this study. Phenotypic measurements, cold-tolerance investigation, and whole-transcriptome surveys were performed on YN-9 and LanYin-3 (LY-3), the most popular Z. japonica cultivar in Southern China. The results indicated the following: YN-9 has longer second and third leaves than LY-3; when exposed to the natural low temperature during winter in Guangzhou, YN-9 accumulated 4.74 times more anthocyanin than LY-3; after cold acclimation and freezing treatment, 83.25 ± 9.55% of YN-9 survived while all LY-3 leaves died, and the dark green color index (DGCI) value of YN-9 was 1.78 times that of LY-3; in YN-9, there was a unique up-regulation of Phenylalanine ammonia-lyase (PAL), Homeobox-leucine Zipper IV (HD-ZIP), and ATP-Binding Cassette transporter B8 (ABCB8) expressions, as well as a unique down-regulation of zinc-regulated transporters and iron-regulated transporter-like proteins (ZIPs) expression, which may promote anthocyanin biosynthesis, transport, and accumulation. In conclusion, YN-9 exhibited enhanced cold tolerance and is thus an excellent candidate for breeding cold-tolerant Z. japonica variety, and its unique low-temperature-induced anthocyanin accumulation and gene responses provide ideas and candidate genes for the study of low-temperature tolerance mechanisms and genetic engineering breeding.

Dianthi herba: a comprehensive review of its botany, traditional use, phytochemistry, and pharmacology.

Dianthi herba (called "Qumai" in Chinese) is the dried aerial part of Dianthus superbus L. and Dianthus chinensis L. The species are mainly distributed in the temperate and warm temperate regions in the northern hemisphere, and some regions in Africa and Oceania, as well as South America. However, the distribution pattern of Dianthi herba has not been reviewed. In this review, we summarize the research progress on the botany, traditional use, phytochemistry, pharmacology, toxicology, and clinical applications of Dianthi herba. Approximately 194 chemical compounds have been identified and isolated from Dianthi herba, the most important being triterpenoid saponins, flavonoids, and volatile oil compounds. These compounds possess antiviral, anticancer, antioxidant, and antimicrobial properties, inter alia. Further studies should be carried out on Dianthi herba to elucidate more of its active principles and their mechanisms of action.

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity.

BACKGROUND: Diabetes mellitus (DM) is a common concomitant disease of late-onset myasthenia gravis (MG). However, the impacts of DM on the progression of late-onset MG were unclear. METHODS: In this study, we examined the immune response in experimental autoimmune myasthenia gravis (EAMG) rats with DM or not. The phenotype and function of the spleen and lymph nodes were determined by flow cytometry. The serum antibodies, Tfh cells, and germinal center B cells were determined by ELISA and flow cytometry. The roles of advanced glycation end products (AGEs) in regulating Tfh cells were further explored in vitro by co-culture assays. RESULTS: Our results indicated clinical scores of EAMG rats were worse in diabetes rats compared to control, which was due to the increased production of anti-R97-116 antibody and antibody-secreting cells. Furthermore, diabetes induced a significant upregulation of Tfh cells and the subtypes of Tfh1 and Tfh17 cells to provide assistance for antibody production. The total percentages of B cells were increased with an activated statue of improved expression of costimulatory molecules CD80 and CD86. We found CD4+ T-cell differentiation was shifted from Treg cells towards Th1/Th17 in the DM+EAMG group compared to the EAMG group. In addition, in innate immunity, diabetic EAMG rats displayed more CXCR5 expression on NK cells. However, the expression of CXCR5 on NKT cells was down-regulated with the increased percentages of NKT cells in the DM+EAMG group. Ex vivo studies further indicated that Tfh cells were upregulated by AGEs instead of hyperglycemia. The upregulation was mediated by the existence of B cells, the mechanism of which might be attributed the elevated molecule CD40 on B cells. CONCLUSIONS: Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG rats. Considering the effect of diabetes, therapy in reducing blood glucose levels in MG patients might improve clinical efficacy through suppressing the both innate and adaptive immune responses. Additional studies are needed to confirm the effect of glucose or AGEs reduction to seek treatment for MG.

Prevalence and Clinical Characteristics of Nontuberculous Mycobacteria in Patients with Bronchiectasis: A Systematic Review and Meta-Analysis.

BACKGROUND: Although international bronchiectasis guidelines recommended screening of nontuberculous mycobacteria (NTM) both at initial evaluation and prior to administration of macrolide treatment, data regarding NTM in bronchiectasis remain elusive. OBJECTIVE: To establish the prevalence, species, and clinical features of NTM in adults with bronchiectasis. METHODS: We searched PubMed, Embase, and Web of Science for studies published before April 2020 reporting the prevalence of NTM in adults with bronchiectasis. We only included studies with bronchiectasis confirmed by computed tomography and NTM identified by mycobacteria culture or molecular methods. Random-effects meta-analysis was employed. RESULTS: Of the 2,229 citations identified, 21 studies, including 12,454 bronchiectasis patients were included in the final meta-analysis. The overall pooled prevalence of NTM isolation and pulmonary NTM disease were 7.7% (5.0%-11.7%) (n/N = 2,677/12,454) and 4.1% (1.4%-11.4%) (n/N = 30/559), respectively, with significant heterogeneity (I2 = 97.7%, p < 0.001 and I2 = 79.9%, p = 0.007; respectively). The prevalence of NTM isolation varied significantly among different geographical regions with the highest isolation at 50.0% (47.3%-52.7%) reported in the United States. Mycobacterium avium complex and Mycobacterium abscessus complex accounted for 66 and 16.6% of all species, respectively. Some clinical and radiological differences were noted between patients with and without the presence of NTM isolation although the results are inconsistent. CONCLUSIONS: Heterogeneity in prevalence estimates of NTM isolation indicated that both local surveys to inform development of clinical services tailored to patients with bronchiectasis and population-based studies are needed. The clinical features associated with NTM in bronchiectasis and their incremental utility in studying the association is unknown and merits further investigation.

[Application of remote sensing technology in medicinal plant resources].

The sustainable use of medicinal plants is the foundation of the inheritance of traditional Chinese medicine(TCM) and the acquisition of information on medicinal plants is the basis for the development of TCM. The traditional methods of investigating medicinal plant resources are disadvantageous in strong subjectivity and poor timeliness, making it difficult to real-time monitor medicinal plant resources. In recent years, remote sensing technology has become an important means of obtaining information on medicinal plants. The application of this technology has made up for the shortcomings of traditional methods. The open-access remote sensing data with medium spatial resolution satellites provide an opportunity for extracting information on medicinal plant resources. This study firstly introduced the principles of remote sensing technology, summarized the satellites and the parameters commonly used in the field of medicinal plant resources, and compared the survey methods of remote sensing technology with traditional methods. Secondly, it reviewed the applications of remote sensing technology in the extraction of information on the cultivation of medicinal plants and the common methods for extracting the planting structure information of medicinal plants based on remote sensing technology. Thirdly, the applications of remote sensing technology in the investigation and monitoring of medicinal plants were further analyzed with the research objects divided into wild and cultivated medicinal plants according to the characteristics of the habitats. Finally, it pointed out the key unsolved technical problems in the remote sensing monitoring of medicinal plant resources, and proposed solutions for the intelligent information processing of medicinal plants based on remote sensing big data, which is expected to provide references for the development of remote sensing technology in derivative application in medicinal plant resources.