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Semen Lepidii is the dried and mature seeds of the cruciferous plant of Descurainia Sophia or Lepidium Apetalum, being a widely-used traditional Chinese medicine for various pharmacological effects, such as antibacterial, antitumor, diuretic and improving immune function. However, the chemical components of Semen Ledidii from different regions have not been clear, limiting the further application of this herb medicine in clinic. Therefore, in this study, a method of ultra-performance liquid chromatography-electrostatic Orbital ion trap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) was developed to identify the chemical components of the three Semen Lepidii, namely Descurainia Sophia 1 (DS1), Descurainia Sophia 2 (DS2) and Lepidium Apetalum (LA) from different regions, and to study the fragmentation pathways of the identified components. The methanol-water (70:30, V/V) extract of the three mashed powder samples was separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm×1.7 μm), and infused into high mass resolution Orbitrap mass spectrometer for analyzing under positive and negative ion modes. MS/MS data were acquired with a Full MS/dd-MS2 mode, and the chromatographic peaks were aligned and extracted by using Compound Discoverer (CD) software. Then, the accurate mass informations of the precursor and fragment ions were matched to the databases in the CD platform for identification of components in the samples, and studied the fragmentation pathways of identified compounds. A total of 39 compounds are identified in DS1, including alkaloids, flavonoids, cardiac glycosides, amides, organic acids, amino acids, and others. This method was used to analyze methanol-water extract of DS2 and LA, 37 compounds are identified in DS2, including 10 compounds which are not identified in DS1, and 42 compounds are identified in LA, including 7 compounds which are not identified in both DS1 and DS2. The results indicated that the chemical components of Semen Lepidii originated from different regions are remarkably different and may act as medicine in various ways. This study provides a fundamental for further studying the molecular mechanism of pharmacological effects of Semen Lepdii, which can promote its clinical application.

The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies. To address this issue, a therapeutic cocktail could be an effective countermeasure. In the present study, we isolated a fully human neutralizing antibody, JS026, from a convalescent patient. The comparative analysis revealed that JS026 binding to SARS-CoV-2-RBD mainly located between epitopes for class 2 and class 3 mAbs as opposed to that of class 1 (etesevimab) antibodies. A cocktail of etesevimab and JS026 increased neutralizing efficacy against both wild-type SARS-CoV-2 and the recent emergence of Alpha, Beta, Gamma, and Delta variants. JS026 and the cocktail reduced virus titers in the infected lungs of hACE2 transgenic mice and relieved pathological changes. These findings would benefit antibody-based therapeutic countermeasures in the treatment of COVID-19.

Strophanthidin (SPTD), one of the cardiac glycosides, is refined from traditional Chinese medicines such as Semen Lepidii and Antiaris toxicaria, and was initially used for the treatment of heart failure disease in clinic. Recently, SPTD has been shown to be a potential anticancer agent, but the underlying mechanism of action is poorly understood. Herein, we explored the molecular mechanism by which SPTD exerts anticancer effects in A549 human lung adenocarcinoma cells by means of mass spectrometry-based quantitative proteomics in combination with bioinformatics analysis. We revealed that SPTD promoted the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2, or DR5) in A549 cells to activate caspase 3/6/8, in particular caspase 3. Consequently, the activated caspases elevated the expression level of apoptotic chromatin condensation inducer in the nucleus (ACIN1) and prelamin-A/C (LMNA), ultimately inducing apoptosis via cooperation with the SPTD-induced overexpressed barrier-to-autointegration factor 1 (Banf1). Moreover, the SPTD-induced DEPs interacted with each other to downregulate the p38 MAPK/ERK signaling, contributing to the SPTD inhibition of the growth of A549 cells. Additionally, the downregulation of collagen COL1A5 by SPTD was another anticancer benefit of SPTD through the modulation of the cell microenvironment.

ObjectiveThe present study aimed to predict myocardial ischemia in coronary heart disease (CHD) patients based on the radiologic features of coronary computed tomography angiography (CCTA) combined with clinical factors.MethodsThe imaging and clinical data of 110 patients who underwent CCTA scan before DSA or FFR examination in Changzhou Second People’s Hospital, Nanjing Medical University (90 patients), and The First Affiliated Hospital of Soochow University (20 patients) from March 2018 to January 2022 were retrospectively analyzed. According to the digital subtraction angiography (DSA) and fractional flow reserve (FFR) results, all patients were assigned to myocardial ischemia (n = 58) and normal myocardial blood supply (n = 52) groups. All patients were further categorized into training (n = 64) and internal validation (n = 26) sets at a ratio of 7:3, and the patients from second site were used as external validation. Clinical indicators of patients were collected, the left ventricular myocardium were segmented from CCTA images using CQK software, and the radiomics features were extracted using pyradiomics software. Independent prediction models and combined prediction models were established. The predictive performance of the model was assessed by calibration curve analysis, receiver operating characteristic (ROC) curve and decision curve analysis.ResultsThe combined model consisted of one important clinical factor and eight selected radiomic features. The area under the ROC curve (AUC) of radiomic model was 0.826 in training set, and 0.744 in the internal validation set. For the combined model, the AUCs were 0.873, 0.810, 0.800 in the training, internal validation, and external validation sets, respectively. The calibration curves demonstrated that the probability of myocardial ischemia predicted by the combined model was in good agreement with the observed values in both training and validation sets. The decision curve was within the threshold range of 0.1–1, and the clinical value of nomogram was higher than that of clinical model.ConclusionThe radiomic characteristics of CCTA combined with clinical factors have a good clinical value in predicting myocardial ischemia in CHD patients.

Polycystic ovary syndrome (PCOS) and periodontal disease (PDD) share common risk factors. The bidirectional interaction between PCOS and PDD has been reported, but until now, the underlying molecular mechanisms remain unclear. Endocrine disorders including hyperandrogenism (HA) and insulin resistance (IR) in PCOS disturb the oral microbial composition and increase the abundance of periodontal pathogens. Additionally, PCOS has a detrimental effect on the periodontal supportive tissues, including gingiva, periodontal ligament, and alveolar bone. Systemic low-grade inflammation status, especially obesity, persistent immune imbalance, and oxidative stress induced by PCOS exacerbate the progression of PDD. Simultaneously, PDD might increase the risk of PCOS through disturbing the gut microbiota composition and inducing low-grade inflammation and oxidative stress. In addition, genetic or epigenetic predisposition and lower socioeconomic status are the common risk factors for both diseases. In this review, we will present the latest evidence of the bidirectional association between PCOS and PDD from epidemiological, mechanistic, and interventional studies. A deep understanding on their bidirectional association will be beneficial to provide novel strategies for the treatment of PCOS and PDD.

Increasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer’s disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD within the inflammatory aspect. The hippocampus of CP model mice and controls were collected, and changes in protein expression were evaluated using two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis combined with liquid chromatography tandem mass spectrometry. A total of 15 differentially expressed proteins were identified in CP model mice, as compared with the controls. Among them, S100-A9, transthyretin, Cofilin 2, peroxiredoxin 2, and lipocalin-2 were validated by Western blot according to their dual function both in inflammation and AD. Based on 2D-DIGE analysis, CP animal model had higher levels of S100-A9, Cofilin 2, peroxiredoxin 2, and lipocalin-2 compared to controls. The level of Cofilin 2, one of the well-established proteins in the pathology of AD, was strongly correlated with the time course of CP pathology, indicating a specific molecular correlation between CP and AD. Moreover, the in vivo results showed the level of Cofilin 2 increased significantly along with a prominent increase of the phosphorylation of protein phosphatase 2 (PP2A) and tau protein in the cell lysates of Porphyromonas gingivalis (P.g-LPS)-treated SK-N-SH APPwt cells. Cofilin 2 inhibition resulted in a sharp decrease in PP2A dependent of tau phosphorylation. Furthermore, tumor growth factor (TGF)-β1 was one of the most important inflammatory cytokines for the Pg-LPS-induced Cofilin 2 upregulation in SK-N-SH APPwt cells. These results showed inflammation served as the bond between CP and AD, whereas inflammatory related proteins could be the key linkers between the two diseases. Determining the association between CP and AD at the molecular mechanism will not only hold the direct evidence of the association between the two diseases but also provide a new way of preventing and treating AD: the effective prevention and treatment of CP could serve as a useful method to alleviate the development of AD.

Gibberellins (GAs) promote secondary cell wall (SCW) development in plants, but the underlying molecular mechanism is still to be elucidated. Here, we employed a new system, the first internode of cotton, and the virus-induced gene silencing method to address this problem. We found that knocking down major DELLA genes via VIGS phenocopied GA treatment and significantly enhanced SCW formation in the xylem and phloem of cotton stems. Cotton DELLA proteins were found to interact with a wide range of SCW-related NAC proteins, and virus-induced gene silencing of these NAC genes inhibited SCW development with downregulated biosynthesis and deposition of lignin. The findings indicated a framework for the GA regulation of SCW formation; that is, the interactions between DELLA and NAC proteins mediated GA signaling to regulate SCW formation in cotton stems.

Entrapped air in the chambers of a T-girder bridge generates a considerably large vertical force which is harmful to the safety of the bridge superstructure. The contribution of the entrapped air is not considered when calculating flood force in the related specifications, and also it has not been taken into account by researchers. Two-dimensional, scaled-down models at a 1:40 scale are selected as the research object. Analytical and numerical methods are employed to investigate the contribution of entrapped air in T-girder chambers to flood forces. Results show that the entrapped air in the rear chambers could escape easier than that in the front chambers and the compressibility of entrapped air has a small influence on drag force and vertical force (generated by dynamic pressure) coefficients, but it reduces the buoyancy of the T-girder. Considering the entrapped air compressibility and entrapped air escape, the calculation method of the buoyancy of entrapped air is proposed to improve the precision of the existing flood force calculation method.

While Brain-derived Neurotrophic Factor (BDNF) has long been implicated in treating neurological diseases, recombinant BDNF protein has failed in multiple clinical trials. In addition to its unstable and adhesive nature, BDNF can activate p75NTR, a receptor mediating cellular functions opposite to those of TrkB. We have now identified TrkB agonistic antibodies (TrkB-agoAbs) with several properties superior to BDNF: They exhibit blood half-life of days instead of hours, diffuse centimeters in neural tissues instead millimeters, and bind and activate TrkB, but not p75NTR. In addition, TrkB-agoAbs elicit much longer TrkB activation, reduced TrkB internalization and less intracellular degradation, compared with BDNF. More importantly, some of these TrkB-agoAbs bind TrkB epitopes distinct from that by BDNF, and work cooperatively with endogenous BDNF. Unlike BDNF, the TrkB-agoAbs exhibit a half-life of days/weeks and diffused readily in nerve tissues. We tested one of TrkB-agoAbs further and showed that it enhanced motoneuron survival in the spinal-root avulsion model for motoneuron degeneration in vivo. Thus, TrkB-agoAbs are promising drug candidates for the treatment of neural injury.

A numerical analysis of the chemical non-equilibrium phenomena in a scramjet nozzle has been performed using CHEMKIN software. Different operating conditions of the Hyshot scramjet nozzle were simulated and analyzed. Three chemical status, frozen flow, equilibrium flow, and non-equilibrium flow, were tested and compared to demonstrate the chemical reaction effect on nozzle flow field. The real non-equilibrium flow simulation result is between those of the two limiting cases: frozen flow and equilibrium flow, and is closer to that of frozen flow. With complete combustion condition at nozzle inlet, the radical recombination reaction releases tremendous amount of heat and this heat is mainly used to increases gas temperature and has only slight increasing effect on thrust. With incomplete combustion condition at nozzle inlet, both combustion reaction and radical recombination occur in the nozzle, the effect of reaction heat release on thrust depends on the degree of combustion completeness at nozzle inlet, it could increase thrust tremendously compared to frozen flow.

Basic/helix-loop-helix (bHLH) proteins comprise one of the largest transcription factor families and play important roles in diverse cellular and molecular processes. Comprehensive analyses of the composition and evolution of the bHLH family in cotton are essential to elucidate their functions and the molecular basis of cotton development. By searching bHLH homologous genes in sequenced diploid cotton genomes (Gossypium raimondii and G. arboreum), a set of cotton bHLH reference genes containing 289 paralogs were identified and named as GobHLH001-289. Based on their phylogenetic relationships, these cotton bHLH proteins were clustered into 27 subfamilies. Compared to those in Arabidopsis and cacao, cotton bHLH proteins generally increased in number, but unevenly in different subfamilies. To further uncover evolutionary changes of bHLH genes during tetraploidization of cotton, all genes of S5a and S5b subfamilies in upland cotton and its diploid progenitors were cloned and compared, and their transcript profiles were determined in upland cotton. A total of 10 genes of S5a and S5b subfamilies (doubled from A- and D-genome progenitors) maintained in tetraploid cottons. The major sequence changes in upland cotton included a 15-bp in-frame deletion in GhbHLH130D and a long terminal repeat retrotransposon inserted in GhbHLH062A, which eliminated GhbHLH062A expression in various tissues. The S5a and S5b bHLH genes of A and D genomes (except GobHLH062) showed similar transcription patterns in various tissues including roots, stems, leaves, petals, ovules, and fibers, while the A- and D-genome genes of GobHLH110 and GobHLH130 displayed clearly different transcript profiles during fiber development. In total, this study represented a genome-wide analysis of cotton bHLH family, and revealed significant changes in sequence and expression of these genes in tetraploid cottons, which paved the way for further functional analyses of bHLH genes in the cotton genus.

BackgroundThe current national burden of emergency general surgery (EGS) illnesses and the extent of surgeon involvement in the care of these patients remain largely unknown. To inform needs assessments, research, and education, we sought to: (1) translate previously developed International Classification of Diseases (ICD), 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes representing EGS conditions to ICD 10th Revision, CM (ICD-10-CM) codes and (2) determine the national burden of and assess surgeon involvement across EGS conditions.MethodsWe converted ICD-9-CM codes to candidate ICD-10-CM codes using General Equivalence Mappings then iteratively refined the code list. We used National Inpatient Sample 2016 to 2017 data to develop a national estimate of the burden of EGS disease. To evaluate surgeon involvement, using Wisconsin Hospital Association discharge data (January 1, 2016 to June 30, 2018), we selected adult urgent/emergent encounters with an EGS condition as the principal diagnosis. Surgeon involvement was defined as a surgeon being either the attending provider or procedural physician.ResultsFour hundred and eighty-five ICD-9-CM codes mapped to 1,696 ICD-10-CM codes. The final list contained 985 ICD-10-CM codes. Nationally, there were 2,977,843 adult patient encounters with an ICD-10-CM EGS diagnosis. Of 94,903 EGS patients in the Wisconsin Hospital Association data set, most encounters were inpatient as compared with observation (75,878 [80.0%] vs. 19,025 [20.0%]). There were 57,780 patients (60.9%) that underwent any procedure. Among all Wisconsin EGS patients, most had no surgeon involvement (64.9% [n = 61,616]). Of the seven most common EGS diagnoses, surgeon involvement was highest for appendicitis (96.0%) and biliary tract disease (77.1%). For the other five most common conditions (skin/soft tissue infections, gastrointestinal hemorrhage, intestinal obstruction/ileus, pancreatitis, diverticular disease), surgeons were involved in roughly 20% of patient care episodes.ConclusionSurgeon involvement for EGS conditions ranges from highly likely (appendicitis) to relatively unlikely (skin/soft tissue infections). The wide range in surgeon involvement underscores the importance of multidisciplinary collaboration in the care of EGS patients.Level of evidencePrognostic/epidemiological, Level III.