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IntroductionCirculating tumor cells (CTCs) have attracted significant interest as a biomarker for cancer diagnosis. In this study, we judiciously constructed a recombinant MUC1-dependent adenovirus (rAdF35-MUC1) that can selectively replicate and overexpress copepod super green fluorescent proteins (copGFP) in MUC1-positive tumor cells to investigate its role in the detection of CTCs.MethodsWe conducted a comparative study between rAdF35-MUC1 and the existing hTERT-dependent adenovirus (rAdF35-hTERT). Breast cancer cell lines and healthy human peripheral blood mononuclear cells (PBMCs) were infected with both viral constructs to evaluate infection efficiency and the incidence of false-positive cells. CTC Model Samples were employed to determine detection rates, and clinical samples from breast cancer patients were analyzed to preliminarily evaluate the efficacy of CTC detection in a clinical context.ResultsIn preclinical and clinical studies, rAdF35-MUC1 exhibited a significantly high detection efficiency for breast cancer cells, outperforming the existing hTERT-dependent adenovirus (rAdF35-hTERT), especially in detecting CTCs at low quantities. Moreover, rAdF35-MUC1 demonstrated reduced incidence of false positives in healthy PBMCs compared to rAdF35-hTERT.ConclusionIn brief, rAdF35-MUC1 emerges as a potent tool for the sensitive and specific identification of CTCs derived from breast cancer patients, holding clinical translation potential for advancing cancer (early) diagnosis, treatment monitoring, and prognosis.

ObjectiveThis study aimed to observe the effect of edaravone dexborneol (EDB) on the incidence of early post-stroke depression (PSD) and explore its inflammatory mechanisms.MethodsA prospective, randomized controlled study was conducted from January 2022 to June 2023, involving patients with acute ischemic stroke (AIS) at the Neurology Department of the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine. The control group received routine treatment, while the experimental group received routine combined EDB treatment. The main outcome measures included PSD incidence, Patient Health Questionnaire (PHQ-9) and Hamilton Depression Scale (HAMD) scores on days 14 and 30, and inflammatory factor levels on day 14.ResultsA total of 93 patients were included in the study, 51 in the experimental group and 42 in the control group. On day 14, the PSD incidence was 13.7% in the experimental group, lower than 31.0% in the control group (95%CI 0.127–0.996; p = 0.044). Compared to the control group, the experimental group showed significantly lower concentrations of pro-inflammatory cytokines IL-1β (95%CI 3.353–5.184), IL-6 (95%CI 2.694–3.426), TNF-α (95%CI 4.985–12.196), IFN-γ (95%CI 0.163–0.451), MCP-1 (95%CI 0.335–0.787), IL-17A (95%CI 0.543–1.024), and IL-23p19 (95%CI 1.677–1.959) (all p

As a newly discovered virus, Decapoda iridovirus 1 (DIV1) can cause a mortality rate of up to 100% in crustaceans, leading to huge economic losses. At present, there is no effective prevention and control measures for this disease. In the present study, the specific primers targeting highly conserved regions of MCP gene were designed, and then a quantitative real-time PCR method was established. The results indicate that DIV1 quantitative real-time PCR established has good specificity and does not cross react with other pathogens including white spot syndrome virus (WSSV), infectious subcutaneous and hematopoietic necrosis virus (IHHNV) and Vibrio parahaemolyticus induced acute hepatopancreatic necrosis disease (VpAHPND). The real-time PCR was capable of detecting DIV1 DNA at a minimum concentration of 10 copies/μL within 34 cycles. The method has good repeatability, with intra group and inter group coefficients of variation both less than 2%. Thirty-two clinical samples were assessed using both the real-time PCR and conventional PCR. The results shown real-time PCR we established are more sensitive than conventional PCR. In conclusion, this method has strong specificity, stable repeatability, and high sensitivity, providing technical support for clinical diagnosis, epidemiology investigation and monitoring of DIV1.

BackgroundImmune checkpoint inhibitors (ICIs) represent a groundbreaking approach to cancer therapy. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have emerged as potential indicators strongly associated with tumor prognosis, albeit their prognostic significance remains contentious. The predictive value of NLR, PLR, LMR in patients with gastric cancer (GC) treated with ICIs has not been fully explored; therefore, we conducted a meta-analysis to examine the potential of inflammatory markers NLR, PLR, and LMR as survival predictors in this population.MethodsA comprehensive search was conducted across PubMed, Embase, Web of Science, and Cochrane databases, with the search cut-off date set as March 2024. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were calculated to assess the prognostic significance of NLR, PLR, and LMR for both progression-free survival (PFS) and overall survival (OS).ResultsFifteen cohort studies involving 1336 gastric cancer patients were finally included in this meta-analysis. The results of the meta-analysis showed that high levels of NLR were associated with poorer OS and PFS in GC patients receiving ICIs, with combined HRs of OS [HR=2.01, 95%CI (1.72,2.34), P

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.

Background: There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma. Methods: A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1). Results: One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%). Conclusions: Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.

Abstract Background Aberrant glycosylation, catalyzed by the specific glycosyltransferase, is one of the dominant features of cancers. Among the glycosyltransferase subfamilies, sialyltransferases (SiaTs) are an essential part which has close linkages with tumor-associated events, such as tumor growth, metastasis and angiogenesis. Considering the relationship between SiaTs and cancer, the current study attempted to establish an effective prognostic model with SiaTs-related genes (SRGs) to predict patients’ outcome and therapeutic responsiveness of bladder cancer. Methods RNA-seq data, clinical information and genomic mutation data were downloaded (TCGA-BLCA and GSE13507 datasets). The comprehensive landscape of the 20 SiaTs was analyzed, and the differentially expressed SiaTs-related genes were screened with “DESeq2” R package. ConsensusClusterPlus was applied for clustering, following with survival analysis with Kaplan–Meier curve. The overall survival related SRGs were determined with univariate Cox proportional hazards regression analysis, and the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to generate a SRGs-related prognostic model. The predictive value was estimated with Kaplan–Meier plot and the receiver operating characteristic (ROC) curve, which was further validated with the constructed nomogram and decision curve. Results In bladder cancer tissues, 17 out of the 20 SiaTs were differentially expressed with CNV changes and somatic mutations. Two SiaTs_Clusters were determined based on the expression of the 20 SiaTs, and two gene_Clusters were identified based on the expression of differentially expressed genes between SiaTs_Clusters. The SRGs-related prognostic model was generated with 7 key genes (CD109, TEAD4, FN1, TM4SF1, CDCA7L, ATOH8 and GZMA), and the accuracy for outcome prediction was validated with ROC curve and a constructed nomogram. The SRGs-related prognostic signature could separate patients into high- and low-risk group, where the high-risk group showed poorer outcome, more abundant immune infiltration, and higher expression of immune checkpoint genes. In addition, the risk score derived from the SRGs-related prognostic model could be utilized as a predictor to evaluate the responsiveness of patients to the medical therapies. Conclusions The SRGs-related prognostic signature could potentially aid in the prediction of the survival outcome and therapy response for patients with bladder cancer, contributing to the development of personalized treatment and appropriate medical decisions.

Abstract Background Endometriosis (EMS) occurs when normal uterine tissue grows outside the uterus and causes chronic pelvic pain and infertility. Endometriosis-associated infertility is thought to be caused by unknown mechanisms. In this study, using necroptosis-related genes, we developed and validated multigene joint signatures to diagnose EMS and explored their biological roles. Methods We downloaded two databases (GSE7305 and GSE1169) from the Gene Expression Omnibus (GEO) database and 630 necroptosis-related genes from the GeneCards and GSEA databases. The limma package in Rsoftware was used to identify differentially expressed genes (DEGs). We interleaved common differentially expressed genes (co-DEGs) and necroptosis-related genes (NRDEGs) in the endometriosis dataset. The DEGs functions were reflected by gene ontology analysis (GO), pathway enrichment analysis, and gene set enrichment analysis (GSEA). We used CIBERSORT to analyze the immune microenvironment differences between EMS patients and controls. Furthermore, a correlation was found between necroptosis-related differentially expressed genes and infiltrating immune cells to better understand the molecular immune mechanism. Results Compared with the control group, this study revealed that 10 NRDEGs were identified in EMS. There were two types of immune cell infiltration abundance (activated NK cells and M2 macrophages) in these two datasets, and the correlation between different groups of samples was statistically significant (P

Abstract Background Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. Methods In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher’s exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. Results The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P

Mucus clearance, epithelium mucosal barrier and P-glycoprotein (P-gp) efflux are the main gastrointestinal barriers that limit the oral delivery of nanoparticles. Inspired by tunable particles surface properties-dependent trans-mucus and trans-mucosal abilities, novel bilayer-functionalized mesoporous silica nanoparticles (MSN) containing D-α-tocopheryl polyethylene glycol succinate (TPGS) and sulfobetaine 12 (SB12) were designed by layer-to-layer assembly. The amino-grafted MSN (MSN-NH2) was firstly functionalized with TPGS as hydrophobic layer (MSN-TPGS), and then SB12 was self-assembled on the hydrophobic surface of MSN-TPGS to generate a neutral and hydrophilic MSN (MSN-TPGS@SB12). Compared with MSN-NH2, MSN-TPGS, and MSN-TPGS@P123, the MSN-TPGS@SB12 possessed “one stone three birds” functions that enhanced mucus penetration, increased trans-mucosal absorption, as well as suppressed P-gp efflux. The pharmacokinetics study demonstrated that the MSN-TPGS@SB12 loading puerarin (MSN-TPGS@SB12-PUE) exhibited much higher bioavailability compared to other PUE-loaded formulations. Furthermore, the MSN-TPGS@SB12-PUE could significantly enhance the anti-inflammatory efficacy of PUE in vitro and in vivo. In summary, bilayer-functionalized MSN-TPGS@SB12 is a promising vehicle for overcoming the multiple gastrointestinal barriers (mucus clearance, intestinal epithelium barrier and P-gp efflux). Meanwhile, this study also provides a better understanding of the importance of tunable surface property of MSN on oral delivery of drugs.

Background and purposeThis study aimed to explore the correlation and causal relationship between fibrinogen, D-dimer, and the severity of cerebral white matter hyperintensity (MMH).MethodsA retrospective analysis of 120 patients with cerebral small vessel disease (CSVD) confirmed by head MRI attending the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine from August 2021 to February 2023 was performed. According to the Fazekas scale score, the patients were divided into 42 cases in the mild group, 44 cases in the moderate group, and 34 cases in the severe group. The levels of fibrinogen and D-dimer were compared among the three groups; the correlations between fibrinogen, D-dimer, and WMH severity were further analyzed; and independent risk factors for WMH severity were explored using the multivariate ordered logistic regression analysis. Furthermore, a two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of fibrinogen and D-dimer on WMH.ResultsAs the severity of WMH increased, the levels of D-dimer and fibrinogen also gradually increased, and the results showed a positive correlational association, with significant differences within the groups (all p

The advancement of molecular pathology techniques has led to the discovery of rare EGFR mutations for targeted therapy in lung cancer. Additionally, a substantial body of evidence indicates a connection between the development of lung cancer and genetic variations in the EGFR gene. Here, we present a case report of a patient with multifocal lung adenocarcinoma who possessed a rare germline mutation, EGFR R776H. An investigation into the family history of the patient exposed the notable incidence of lung adenocarcinoma, indicating a plausible genetic vulnerability to the ailment. To be specific, the patient's older brother and sister both suffered from lung cancer, which underlines the hereditary predisposition. Furthermore, it should be noted that the patient's daughter has inherited the germline mutation and also presented with multiple lung ground-glass nodules, emphasizing the clinical importance of this genetic variation. Following the lobectomy, the patient received treatment with almonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), and at the latest follow-up, the patient has achieved partial remission. This case highlights the significance of taking into account germline possibilities when multiple lesions carry the same mutation. It stresses the importance of acquiring a comprehensive family history and performing genetic testing on leukocytes. Moreover, for the infrequent EGFR R776H mutation, third generation EGFR-TKIs may be a viable option.

Abstract Background Cross‐lineage expression of the myeloid‐associated antigens CD13/CD33 is common in adult B‐lymphoblastic leukemia (B‐ALL) patients, yet its prognostic value is still controversial. Methods We conducted a retrospective study of 1005 de novo adult B‐ALL patients from January 2009 to December 2019 in our hospital. Logistic and Cox regression were used to analyze the prognostic value of CD13/CD33 expression in B‐ALL. A Cox regression model was established to predict overall survival (OS) for B‐ALL patients. Results Of the 1005 B‐ALL patients, 53.7% (n = 540) aberrantly expressed CD13/CD33 (CD13/CD33+). Patients in the CD13/CD33+ group showed a higher incidence of BCR::ABL1 rearrangement and minimal/measurable residual disease (MRD) positivity but similar complete remission rate, relapse‐free survival, mortality, and OS with CD13/CD33‐. CD13/CD33+ patients had a higher risk of MRD positivity than CD13/CD33‐ patients. Notably, CD13/CD33+ patients who underwent tyrosine kinase inhibitor (TKI) therapy had a better long‐term prognosis than those without TKI experience. Sex, group based on CD13/CD33 expression and TKI experience and white blood cell count were variables independently associated with OS. The Cox regression model integrating these three variables showed a moderate performance for OS prediction (C‐index: 0.724). Conclusions In real‐world practice, CD13/CD33 expression can predict the risk of MRD in patients without TKI experience, but has no adverse effect on the prognosis of adult B‐ALL patients. Incorporating CD13/CD33 into the standard antibody panels of B‐ALL diagnosis and MRD measurements can help predict relapse risk and decisions on therapy options.

The seed, a critical organ in higher plants, serves as a primary determinant of agricultural productivity, with its quality directly influencing crop yield. Improper storage conditions can diminish seed vigor, adversely affecting seed germination and seedling establishment. Therefore, understanding the seed-aging process and exploring strategies to enhance seed-aging resistance are paramount. In this study, we observed that seed aging during storage leads to a decline in seed vigor and can coincide with the accumulation of hydrogen peroxide (H2O2) in the radicle, resulting in compromised or uneven germination and asynchronous seedling emergence. We identified the abscisic acid (ABA) catabolism gene, abscisic acid 8′-hydroxylase 2 (OsABA8ox2), as significantly induced by aging treatment. Interestingly, transgenic seeds overexpressing OsABA8ox2 exhibited reduced seed vigor, while gene knockout enhanced seed vigor, suggesting its role as a negative regulator. Similarly, seeds pretreated with ABA or diphenyleneiodonium chloride (DPI, an H2O2 inhibitor) showed increased resistance to aging, with more robust early seedling establishment. Both OsABA8ox2 mutant seeds and seeds pretreated with ABA or DPI displayed lower H2O2 content during aging treatment. Overall, our findings indicate that ABA mitigates rice seed aging by reducing H2O2 accumulation in the radicle. This study offers valuable germplasm resources and presents a novel approach to enhancing seed resistance against aging.

Abstract Background The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (NBS) in eastern coastal areas of China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area. Methods The NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis. Results Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was—IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short‐chain acyl‐CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were—PAH gene for PKU: c.728G > A, c.442‐1G > A, c.611A > G, c.721C > T; PTS gene for non‐classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del. Conclusion This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of China. Implementing NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for NBS to detect IEM.

Decapod iridescent virus 1 (DIV1) has emerged as a novel threat to shrimp farming. The development of a rapid, convenient, and accurate method for diagnosing DIV1 is urgently needed, serving as a key factor in the reduction of the risk of viral outbreaks. This study aimed to develop a new variable antigen receptor (vNAR), derived from shark heavy-chain antibodies, directed against DIV1 for use in detection assays. White-spotted bamboo sharks were immunized with DIV1 virions, and an immune phage-display library was constructed. After three rounds of panning, the lead D02 vNAR was isolated from the library. D02 vNAR was identified to target the viral antigen ORF064L through western blotting, LM-SC/SC, and pull-down analyses. Furthermore, indirect enzyme linked immunosorbent assay (indirect ELISA) and dot-blot assays were developed based on D02 vNAR. The detection limits of the indirect ELISA and dot blot methods were 5 ng/mL and 6.25 ng/spot, respectively. Furthermore, in the indirect ELISA method, a standard curve describing the log concentration of DIV1 versus OD value was established, which was linear in the concentration range of 80–10,240 ng/mL, and the linear regression equation was derived as y = 0.3565x − 0.51601. Furthermore, 300 clinical samples were analyzed by the two methods using quantitative real-time polymerase chain reaction (qRT-PCR) as a reference. Compared to qRT-PCR, the diagnostic sensitivity and specificity of the indirect ELISA and dot blot methods were 96.7 % and 100 % and 93.5 % and 100 %, respectively, demonstrating the practicability and reliability of the vNAR-based indirect ELISA and dot blot methods for the robust detection of DIV1. Overall, this is the first study in which a vNAR has been developed against DIV1. The developed vNAR offers a robust tool with great potential for the diagnosis of DIV1 during shrimp cultivation.

To study the magnetic change mechanism of weakly caking coal during the heating process, the mass magnetic susceptibility of coal samples during the heating process was measured in this paper. Compared with the burnt coal sample after heat treatment at the same temperature, the magnetic change process of coal during heating was divided into four stages. The experiments of programmed temperature rise, industrial analysis and X-ray diffraction of coal were conducted at different stages to explore the key factors that lead to changes in its magnetic properties in different heating stages. The experimental results show that the magnetic susceptibility of the coal sample changes from negative to positive and then slowly rises at room temperature to 200 ℃. The effect on the magnetic properties of the coal at this stage is due to the decrease of the diamagnetic carbon-containing compounds in the coal due to oxidative consumption. At 200 ℃ to 350 ℃, the magnetic susceptibility of the coal sample rises sharply, and the average growth rate is 10 times higher than that of the previous stage. This is because the trace minerals in the coal sample chemically react to produce more magnetic substances. When the temperature exceeds 350 ℃, the magnetic susceptibility begins to decrease rapidly, and the magnetic susceptibility stabilizes near 0 after the temperature is 500 ℃. The possible reason is that with the increase of temperature, the movement of particles inside the mineral intensifies and affects the orderly arrangement of the magnetic domain and magnetic moment. When the temperature rises to the Curie temperature, this influence reaches its limit and the change tends to be stable.

Abstract Volatile oil from traditional Chinese medicine has various biological activities and has pharmacological activities in the central nervous system, digestive system, cardiovascular system, respiratory system, etc. These oils are widely used in clinical practice. However, the development of their clinical applications is restricted due to the disadvantages of volatile oils, such as high stimulation, high volatility and poor stability. To improve the stability of a volatile oil in the preparation process, its volatilization and stable release must be controlled. In this paper, porous starch was used as a solid carrier material, and liquid volatile oil was solidified by physical adsorption. GC–MS was used to determine the chemical constituents of the volatile oil, solidified powder and tablets, and the volatilization rules of 34 chemical constituents were analysed statistically. The solidified volatile oil/porous starch powder was characterized by XRD, TGA and DSC, and the VOCs of the volatile oil before and after solidification were analysed by portable GC–MS. Finally, the stable release of the volatile oil could be optimized by changing the porous starch ratio in the formulation. Volatilization was shown to be closely related to the peak retention time and chemical composition, which was consistent with the theory of flavour. The physical properties and chemical composition of the volatile oil did not change after curing, indicating that the adsorption of the volatile oil by porous starch was physical adsorption. In this paper, the porous starch-solidified volatile oil had a slow-release effect, and the production process is simple, easy to operate, and has high application value.

Abstract Background The influence of external environmental factors on secondary metabolites of medicinal plants has always been studied. However, little is known about the relationships between endophytes and host metabolites, especially the relationship differences between different plant species. Thus, we used high-throughput sequencing methods to compare endophyte diversity from roots of two closely related species, Gentiana officinalis and G. siphonantha, from the same production area, and analyze the association with four secondary metabolites (Gentiopicroside, Loganic acid, Swertiamarine and Sweroside). Results The fungal and bacteria communities’ richness and diversity of G. siphonantha was higher than G. officinalis. Ascomycota and Proteobacteria were dominant fungal and bacterial phylum of the two closely related species. At the genus level, Tetracladium and Cadophora were dominant fungal genus in G. officinalis and G. siphonantha samples, respectively. While Pseudomonas was dominant bacterial genus in two closely related species, with relative abundances were 8.29 and 8.05%, respectively. Spearman analysis showed that the content of loganic acid was significantly positively correlated with endophytic fungi, the content of gentiopicroside, swertiamarine and sweroside were significantly positively correlated with endophytic bacteria in the two related species. PICRUSt and FUNGuild predictive analysis indicated that metabolism and saprotroph was primary function of endophytic bacteria and fungi in the two related species. Conclusion Our results will expand the knowledge on relationships of plant-microbe interactions and offer pivotal information to reveal the role of endophytes in the production of Gentiana plant and its important secondary metabolite.

Abstract Background Perioperative neurocognitive disorders (PND) are common complications of major surgery among elderly patients, remarkably decreasing patients’ life quality. Platelet count has been proved to be an essential factor in inflammation. However, as far as we know, the relationship between platelet count and PND is not clear yet in the orthopedic area. PND could be a long-term disease, which sometimes lasts for several years, and it is meaningful to find a biomarker of PND at the early stage. Thus, we designed this study to find out the association between perioperative platelet count and occurrence of PND, and determine whether preoperative platelet count could be a biomarker of the early stage of PND. Methods A prospective observational study was performed on the patients who would take total knee arthroplasty or total hip arthroplasty. Their peripheral platelets were counted by blood routine examination 1 day before and 3 days after the surgery. And we assessed their neurocognitive functions 1 day before and 3 days after the surgery. These data were recorded and analyzed to find out the relationship between platelet count and the occurrence of PND. Results Eventually, 70 patients finished the whole process, and 14 of them developed PND. The median preoperative platelet count in the PND group was significantly higher than that in the non-PND group (239 vs 168 × 10^9/L, p = 0.009). Preoperative platelet count was an independent risk factor for PND (odds ratio = 1.014, 95% confidence interval [CI] 1.000–1.027, P = 0.043) in the logistic multivariable regression, while the area under the curve of the receiver operating characteristic curve of the prediction model was 0.796 (95% CI 0.676–0.916). Conclusions The higher preoperative and postoperative level of platelet count in the peripheral blood were associated with the early stage of PND, and preoperative platelet count could be a potential predictor of the early stage of PND in patients undergoing major orthopedic surgeries. Trial registration Chinese Clinical Trial Registry: ChiCTR2000033001 , registration date: 17 May 2020.

Objective: Quercetin-3-O-β-D-glucuronide (QG) can alleviate immunological bone marrow failure (BMF) by increasing platelet counts. However, the principal mechanism is less known. This study aimed at deciphering the possible underlying mechanism of QG that is indicated in thrombocytopenic purpura. Methods: In vitro and in vivo experiments were carried out for investigating the mechanism behind QG-facilitated inhibition of mitochondrial pathway-mediated excessive apoptosis of platelets through the phosphatidylinositol-3-kinase (PI3K)/AKT pathway. Results: Our results revealed that QG, the main effective ingredient of Herba Sarcandrae, increases the number of platelets and decreases the expression of Bax, Bad, Bid, and caspase-9 in immunological BMF, indicating the inhibition of mitochondrial pathway-mediated apoptosis. Moreover, we found that the protein and mRNA expressions, as well as the phosphorylated levels of PI3K and AKT, were increased significantly by QG, suggesting the activation of the PI3K/AKT pathway. Furthermore, the inhibition of the PI3K/AKT pathway by LY294002 antagonizes the effects of QG on platelet counts and mitochondrial pathway-mediated apoptosis. Conclusion: We demonstrate that QG inhibits the mitochondria pathway-mediated platelet apoptosis via the PI3K/AKT pathway in immunological BMF. This study thus sheds light on exploring the possible regulatory mechanism of traditional Chinese medicine in the treatment of thrombocytopenia induced by BMF.

Acute respiratory distress syndrome (ARDS) is an acute and diffuse pulmonary inflammation, characterized by severe hypoxic respiratory failure caused by inflammatory tissue damage, which is a common cause of respiratory failure. Currently, there is no treatment available that can prevent or reverse the devastating effects caused by these conditions. The purpose of this study was to determine the effects of WRS on gut microbiota and the potential effect of gut microbiota on the treatment of lung disease by using a staphylococcal enterotoxin B (SEB)-induced ARDS model. The results showed that WRS could significantly reduce the pathological damage to lung and colon tissues and improve the lung and intestinal functions of ARDS mice. WRS was able to improve the level of cytokines in serum and lung tissue. Additionally, WRS could reverse the gut microbiota dysbiosis caused by SEB in ARDS mice. WRS increases the production of short-chain fatty acids (SCFAs) in the gut. This increase in SCFAs may lead to increased migration of SCFAs to the lungs and activation of free fatty acid receptors (FFAR) three and FFAR2 in lung epithelial cells, alleviating the symptoms of ARDS. Interestingly, WRS improves the faecal metabolite profiles in SEB-induced ARDS mice via tryptophan metabolism. On the basis of the component-target-metabolism strategy, baicalin, oroxylin A-7-O-glucuronide and skullcapflavon II were identified as the potential bioactive markers in WRS for the treatment of ARDS. Our study showed that WRS could ameliorate SEB-induced ARDS by regulating the structure of gut microbiota, increasing the production of SCFAs and modifying the faecal metabolite profiles through the lung-gut axis, and providing alternative treatment strategies for lung disease.

Abstract Background Erythropoiesis and iron homeostasis are closely related; anemia due to lower-risk myelodysplastic syndromes (MDS) remains difficult to treat. In the last decade, we have been committed to improving the regulation of iron metabolism using traditional Chinese medicine (TCM). Previous studies have found that the TCM Yi Gong San (YGS) can reduce the expression of transferrin by inhibiting hepcidin overexpression caused by inflammation, promote the outward transfer of intracellular iron, and improve the symptoms of anemia. Here, our study aimed to compare the efficacy of a conventional drug with YGS with that of conventional medicine with placebo to provide a scientific basis for making clinical decisions. Methods A prospective, multicenter, double-blinded, randomized controlled clinical trial will be conducted to evaluate the therapeutic efficacy of conventional medicine combined with YGS with that of conventional medicine alone in the treatment of MDS. A total of 60 patients would be enrolled in this study, with each treatment group (conventional medicine + YGS and conventional medicine + placebo) comprising 30 patients. Oral medication would be administered twice daily for 3 months. All patients would be followed up throughout the 3-month period. The primary outcome was measured by assessing blood hemoglobin level. The secondary outcome was measured by assessing TCM symptom score, iron metabolism, hepcidin levels, and inflammatory factors. Discussion This trial would aim to demonstrate the effectiveness and feasibility of YGS in the treatment of lower-risk MDS anemia, as well as its impact on inflammatory factors and iron metabolism in patients with lower-risk MDS. Trial registration Chinese Clinical Trials Registry ( http://www.chictr.org.cn/ ) ChiCTR1900026774 . Registered on October 21, 2019.

Interferon epsilon (IFN-ε) is a type I IFN. Some biological properties has been identified in many species, such as antiproliferative, anti-tumor, and antiviral effects, of IFN-ε, which are much weaker than those of IFN-α, have also been revealed. It has been shown to play a role in mucosal immunity and bacterial infection and in the prevention of certain sexually transmitted diseases, such as human immunodeficiency virus (HIV). This paper reviews the known activity of IFN-ε, particularly in some viruses. In general, this review provides a better understanding of effective IFN-ε treatment in the future.

Objective: To analyze surveys measuring the prevalence of burnout among Chinese doctors and reveal the overall prevalence, characteristics, timeline, and factors related to burnout. Methods: A comprehensive search was conducted on China National Knowledge Infrastructure, WANFANG, PubMed, EMBASE, PsycINFO and Cochrane Library databases from their inception to 28 February 2021. Random-effects meta-analyses, meta-regression and planned subgroup analyses were performed, and the standardized mean difference was adopted for comparisons between subgroups. Egger’s and Begg’s tests were performed to evaluate publication bias. Heterogeneity across the studies was tested using the I2 statistic. The study protocol was registered on PROSPERO (CRD42018104249). Results: In total, 3,210 records were reviewed; 64 studies including 48,638 Chinese doctors were eligible for meta-analysis. The prevalence of burnout increased continuously from 2008 to 2017 and decreased significantly from 2018 to 2020, a little increase from 2020 to 2021. The overall prevalence of burnout was 75.48% (95% CI, 69.20 to 81.26; I2 = 99.23%, P < 0.001), and high burnout was 9.37% (95% CI, 4.91 to 15.05, I2 = 98.88%, P < 0.001). The prevalence of emotional exhaustion was 48.64% (95% CI, 38.73 to 58.59; I2 = 99.53%, P < 0.001), depersonalization was 54.67% (95% CI, 46.95 to 62.27; I2 = 99.20%, P < 0.001), and reduced personal accomplishment was 66.53% (95% CI, 58.13 to 74.44; I2 = 99.37%, P < 0.001). Gender, marriage, professional title and specialty all influenced burnout. Conclusions: The results showed that the total prevalence of doctor burnout in China is very high. The prevalence of burnout varies by location. Gender, marital status and professional title all affect burnout scores.

Summary: Background: Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC. Methods: This was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0–120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478. Findings: Between Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; P = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25–120 h), 90.6% vs. 75.5%, (P

Objective: To evaluate the efficacy and safety of Morinda officinalis oligosaccharide (MOO) capsules for depressive disorder. Methods: Eight electronic databases were searched for relevant studies from inception to April 19, 2020. Randomized controlled trials comparing MOO capsules with antidepressants were included. Data analysis was conducted using Review Manager 5.3 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and the quality of the studies was evaluated by two researchers using the Grading of Recommendation, Assessment, Development and Evaluations (GRADE) software. Results: Seven studies involving 1,384 participants were included in this study. The effect of MOO capsules for moderate depressive disorder was not different from that of antidepressants (risk ratio [RR] = 0.99, 95%CI 0.92-1.06). Regarding adverse events, no significant difference was found between MOO capsules and antidepressants (RR = 0.84, 95%CI 0.65-1.07). In addition, the quality of evidence related to these adverse events was rated as low. Conclusion: This systematic review suggests that the efficacy of MOO capsules in the treatment of mild to moderate depression is not inferior to that of conventional antidepressants, which may provide a new direction for clinical alternative selection of antidepressants. However, more high-quality research and detailed assessments are needed.

BackgroundmiR-101 is one of the most abundantly expressed microRNA (miRNA) and exerst a critical role in hepatocellular carcinoma (HCC) by targeting to 3’ -untranslated region (UTR) of Girders of actin filaments (CCDC88A) and Vascular endothelial growth factor (VEGF) mRNA, but the underlying molecular mechanism remains to be elucidated. This study aimed to investigate the potential role of CCDC88A on malignancies and stemness by regulating VEGF via miR-101 in HCC.MethodsGene Expression Profiling Interactive Analysis (GEPIA) was employed to analyze the relevance of CCDC88A expression with prognosis in HCC. Tissue slides were performed to confirm the protein level of CCDC88A in HCC. Correlation between CCDC88A and VEGF was transcriptionally and post-transcriptionally detected, followed by evaluation of malignancies.ResultsBy employing Immunohistochemistry, we found CCDC88A protein was upregulated in HCC tissues, which is closely correlated to poor prognosis and survival rate. Employment of GEPIA revealed the positive correlation between CCDC88A and VEGF in HCC, but not in liver tissue. Silencing of CCDC88A in Huh-7 and SK-HEP-1 cells significantly decreased proliferation, cell cycle phases, migration, invasion, colony formation, and tumor formation. Introduction of miR-101 mimics specifically targeting CCDC88A and VEGF decreased protein levels of both CCDC88A and VEGFA. Notably, inhibition of miR-101 reversed the correlation between CCDC88A and VEGFA protein levels, indicating that CCDC88A and VEGF may exert as a miR-101 sponge. The addition of SKLB1002, a VEGFR2 inhibitor inhibited malignant behaviors, which was further inhibited by the introduction of miR-101 mimics, indicating that CCDC88A regulates malignant behaviors partially via regulating VEGF. Moreover, CCDC88A also promotes the stemness of cancer stem-like cells derived from HCC cells depending on VEGF modification.ConclusionTaken together, our findings suggested that the miR-101/CCDC88A/VEGF axis could be a potential therapeutic target of HCC treatment.

BackgroundSarcopenia is an age-related clinical condition and associated with an increased risk of adverse outcomes. However, to date, there is no global standard for the diagnosis of sarcopenia, and fewer serum biomarkers have been suggested for the diagnosis of sarcopenia. It is, thus, important that sarcopenia-related serological diagnostic markers be explored. The present study was based on the Asian Working Group on Sarcopenia 2019 (AWGS 2019) criteria to assess whether aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and fasting insulin*prealbumin (INS*PA) product are diagnostic markers associated with sarcopenia in various ethnic groups in western China.MethodsThis cross-sectional study included 4,099 adults (1,471 men and 2,628 women) from the West China Health and Aging Trend (WCHAT) study. The value of serum biomarkers was based on laboratory data. The accompanying metabolic disorders and the associated parameters were evaluated. Logistic regression analysis was used to explore the association between markers and sarcopenia. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic efficacy of the test in differentiating sarcopenia.ResultsBinary regression analysis showed that high serum AST/ALT (OR = 2.247) and adrenal cortisol (PTC, OR = 1.511), low serum INS*PA (OR = 2.970), free triiodothyronine (FT3, OR = 1.313), 25-OH-VitD (VitD, in male participants, OR = 1.817), and diastolic blood pressure (DBP, in female subjects, OR = 1.250) were independent risk factors for sarcopenia (P

Sepiapterin reductase (Spr) plays an essential role in the biosynthesis of tetrahydrobiopterin (BH4), a key cofactor of multiple enzymes involved in various physiological and immune processes. Suppression of Spr could result in BH4 deficiency-caused diseases in human and murine models. However, information on the biological function of Spr in invertebrates is limited. In this study, two Sprs (CG12116 and Sptr) from Drosophila melanogaster were found to be downregulated in transgenic flies overexpressing white spot syndrome virus (WSSV) immediate-early protein WSV056. CG12116 and Sptr exerted an inhibitory effect on the replication of the Drosophila C virus. A Litopenaeus vannamei Spr (LvSpr) exhibiting similarity of 64.1–67.5% and 57.3–62.2% to that of invertebrate and vertebrate Sprs, respectively, were cloned. L. vannamei challenged with WSSV revealed a significant decrease in LvSpr transcription and Spr activity in hemocytes. In addition, the BH4 co-factored nitric oxide synthase (Nos) activity in shrimp hemocytes was reduced in WSSV-infected and LvSpr knockdown shrimp, suggesting WSSV probably inhibits the LvNos activity through LvSpr downregulation to limit the production of nitric oxide (NO). Knockdown of LvSpr and LvNos caused the reduction in NO level in hemocytes and the increase of viral copy numbers in WSSV-infected shrimp. Supplementation of NO donor DETA/NO or double gene knockdown of WSV056 + LvSpr and WSV056 + LvNos recovered the NO production, whereas the WSSV copy numbers were decreased. Altogether, the findings demonstrated that LvSpr and LvNos could potentially inhibit WSSV. In turn, the virus has evolved to attenuate NO production via LvSpr suppression by WSV056, allowing evasion of host antiviral response to ensure efficient replication.

To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick’s diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.

Kai-Xin-San (KXS) is a classic formula for the treatment of Alzheimer’s disease (AD). KXS has been widely used to treat emotional diseases; however, its active components remain unknown. There have been some reports about the efficacy and metabolic analysis of KXS, which are mainly based on studying normal animals. The current work first established an AD rat model by injecting D-galactose into the abdominal cavity and injecting Aβ25–35 into the hippocampus on both sides, followed by intragastric administration of KXS for a consecutive week; then, the analytical method for ethanol extraction from the serum of normal and model rats was developed using UPLC-LTQ-Orbitrap-MS; finally, the transitional components in the blood were systematically compared and analyzed by multivariate statistical analysis. A total of 36 components of KXS were identified in the rat serum of the normal group, including 24 prototype components (including ginsenosides, triterpenoid acids of Poria cocos, polygala saponins, polygala xanthones and polygala ester) and 13 metabolites (including desugar, hydration and oxidation products of ginsenosides, triterpenoid acid hydroxylation, deoxygenation, demethylation, desaturation, and glycine-conjugated products of Poria cocos). Twenty KXS-relevant components were detected in the rat serum of the model group, including 11 prototypes and 9 metabolites. The normal group and the model group shared 12 common components, including 9 prototypes and 3 metabolites. The intestinal microecological balance of the model rats probably was destroyed, affecting the absorption/metabolism of saponins by the body, which resulted in fewer transitional components in the model group. This study reflected the drug-body interaction from an objective and accurate perspective, offering references and insights for elucidating the basis of active components and mechanism of action of KXS for treating AD.

Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.

Abstract Backgrounds The chemical composition of many essential oils indicates that they have sedative and hypnotic effects, but there is still a lack of systematic studies on the sedative and hypnotic effects of essential oils. In addition, aromatherapy does not seem to have the side effects of many traditional psychotropic substances, which is clearly worthwhile for further clinical and scientific research. The clinical application of essential oils in aromatherapy has received increasing attention, and detailed studies on the pharmacological activities of inhaled essential oils are increasingly needed. Hypothesis/purpose As insomniacs are usually accompanied by symptoms of depression and anxiety of varying degrees, based on the theory of aromatherapy of Traditional Chinese Medicine, this experiment is to study a Compound Anshen essential oil that is compatible with Lavender essential oil, Sweet Orange essential oil, Sandalwood essential oil and other aromatic medicine essential oils with sedative and hypnotic effects, anti-anxiety and anti-depression effects. To study the sedative and hypnotic effects of Compound Anshen essential oil inhaled and the main chemical components of Compound Anshen essential oil, and to compare and analyze the pharmacodynamics of diazepam, a commonly used drug for insomnia. Methods The Open field test and Pentobarbital-induced sleep latency and sleep time experiments were used to analyze and compare the sedative and hypnotic effects of inhaling Compound Anshen essential oil and the administration of diazepam on mice. The changes of 5-HT and GABA in mouse brain were analyzed by Elisa. The main volatile constituents of Compound Anshen essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS). Results Inhalation of Compound Anshen essential oil can significantly reduce the spontaneous activity of mice, reduce latency of sleeping time and prolong duration of sleeping time. The results of enzyme-linked immunosorbent assay showed that Compound Anshen essential oil can increase the content of 5-HT and GABA in mouse brain. The main volatile chemical constituents of the Compound Anshen essential oil are D-limonene (24.07%), Linalool (21.98%), Linalyl acetate (15.37%), α-Pinene (5.39%), and α-Santalol (4.8%). Conclusion The study found that the inhalation of Compound Anshen essential oil has sedative and hypnotic effect. This study provides a theoretical basis for further research and development of the sedative and hypnotic effects of Compound Anshen essential oil based on the theory of aromatherapy.

Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1β on the changes that can promote VM. The evidence for VM stimulated by IL-1β was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-β. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1β treatment. The increase in VM response was observed in IL-1β treated cells under both normoxia and hypoxia. IL-1β also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1β stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1β stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1β may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells.

Dendrimers are used for a variety of applications in medicine but, due to their host–guest and entrapment characteristics, are particularly used for the delivery of genes and drugs. However, dendrimers are intrinsically toxic, thus creating a major limitation for their use in biological systems. To reduce such toxicity, biocompatible dendrimers have been designed and synthesized, and surface engineering has been used to create advantageous changes at the periphery of dendrimers. Although dendrimers have been reviewed previously in the literature, there has yet to be a systematic and comprehensive review of the harmful effects of dendrimers. In this review, we describe the routes of dendrimer exposure and their distribution in vivo. Then, we discuss the toxicity of dendrimers at the organ, cellular, and sub-cellular levels. In this review, we also describe how technology can be used to reduce dendrimer toxicity, by changing their size and surface functionalization, how dendrimers can be combined with other materials to generate a composite formulation, and how dendrimers can be used for the diagnosis of disease. Finally, we discuss future challenges, developments, and research directions in developing biocompatible and safe dendrimers for medical purposes.

In this study, the steam distillation process of volatile oil from Angelicaesinensis Radix was optimized according to the concept of quality-by-design. A homemade glass volatile oil extractor was used to achieve better cooling of the volatile oil. First, the soaking time, distillation time, and liquid–material ratio were identified as potential critical process parameters by consulting the literature. Then, the three parameters were investigated by single factor experiments. The volatile oil yield increased with the extension in the distillation time, and first increased and then decreased with the increase in soaking time and liquid–material ratio. The results confirmed that soaking time, distillation time, and liquid–material ratio were all critical process parameters. The kinetics models of volatile oil distillation from Angelicaesinensis Radix were established. The diffusion model of spherical particle was found to be the best model and indicated that the major resistance of mass transfer was the diffusion of volatile oil from the inside to the surface of the medicinal herb. Furthermore, the Box–Behnken experimental design was used to study the relationship between the three parameters and volatile oil yield. A second-order polynomial model was established, with R2 exceeding 0.99. The design space of the volatile oil yield was calculated by a probability-based method. In the verification experiments, the average volatile oil yield reached 0.711%. The results showed that the model was accurate and the design space was reliable. In this study, 21 chemical constituents of volatile oil from Angelicaesinensis Radix were identified by gas chromatograph-mass spectrometer(GC-MS), accounting for 99.4% of the total volatile oil. It was found that the content of Z-ligustilide was the highest, accounting for 85.4%.

Characterization of the diversified immunoglobulin (Ig) repertoire may provide insight into pathways that shape an efficient antibody (Ab) repertoire for immune response against human immunodeficiency virus (HIV) infection. This study aimed to profile characteristics of the plasmablast repertoire during chronic HIV infection. Ig variable regions of plasmablasts from both chronically HIV-infected donors (HIVDs) previously treated with antiretroviral therapy (ART) and healthy donors (HDs) were amplified by single-cell PCR to establish the basis for further repertoire analysis. We compared the plasmablast repertoires expressed in multiple chronically HIVDs after ART treatment cessation and HDs. We also examined the non-productive repertoire to identify the indication of the immediate products of the rearrangement machinery without an impact of selection during HIV infection. We found multiple differences between the productive repertoires of HIVD and HD subjects, including biased usages of VH3-49, VH1-2, VH3-33, VH3-74, and VH5-51 in VH and D1-7, D1-14, D1-20, and D5-5/18 in D segments in the HIVD group, as well as shorter and preferential glycine usages in CDRH3 regions. Gene selections were also detected in light chains. Notably, differences between productive rearrangements of HIVDs and HDs outnumbered those between productive and non-productive rearrangements within HIVDs. HIV infection may exert a dominant impact on the development of the plasmablast repertoire. The impact of selection is of limited significance in shaping the plasmablast repertoire. Overall, the data indicate that the environment in which the plasmablasts live can affect the distribution of the VH and VL genes in the repertoire and the amino acid compositions of the expressed Abs.