The clinicopathological features and possible physiological mechanisms of only the EGFR-T790M primary mutation in patients with lung adenocarcinoma.

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) patients can be complicated by the presence of the EGFR-T790M mutation. Although primary or secondary EGFR-T790M mutations have been extensively studied worldwide, there are few reports on the clinicopathological characteristics and physiological mechanisms of lung adenocarcinoma (LUAD) with only the EGFR-T790M primary mutation. METHODS: The clinical data of all LUAD patients with only the EGFR-T790M primary mutation were collected. Immunohistochemical staining was performed on cell cycle-related proteins, targeted therapy indicators, and prognosis-related proteins in the specimens obtained from puncture biopsies or surgeries. OBJECTIVES: The aim of this study is to analyze the clinicopathological features and possible physiological mechanisms of only the EGFR-T790M primary mutation in LUAD, and to offer recommendations for clinical management. RESULTS: Two patients who have only the T790M de novo mutation were both female (2/12,928, 0.02%). ß-catenin and Cyclin D1 were both highly expressed. In case 1, IHC results showed a positive Ki67 and mutant P53 and there was a significant increase in serum CYFRA 21-1. Third-generation of EGFR TKIs resulted in a partial response (PR) time of less than 8 months in case 1. In case 2, the patient underwent surgical resection and adjuvant chemotherapy, resulting in a progression-free survival (PFS) time of 25 months. CONCLUSION: The results suggest that abnormal activation of the Wnt signaling pathway may be specifically associated with the EGFR-T790M primary mutation in LUAD. Furthermore, it has been observed that patients with significant Ki67, mutant P53, and CYFRA 21-1 expression tend to have a poor prognosis.

Cribiform and intraductal carcinoma in hereditary prostate cancer: clinical and pathological analysis of 20 cases.

Cribiform and intraductal carcinoma are patterns of aggressive prostate carcinoma. This study investigated the clinical and pathological features of hereditary prostate cancer. Twenty cases of hereditary prostate cancer from 11 family lines treated at the First Affiliated Hospital of Zhejiang University School of Medicine between 2016-2022 were included to summarize the clinical and pathological features by analyzing clinical information including follow up the survival of the patients and pathological features. Of the 20 hereditary prostate cancer cases, 19 were radical prostate specimens and 1 was a biopsy specimen. The mean age at diagnosis of the patients was 67.55 years and the mean PSA was 15.44 ng/ml, of which 10 cases had PSA ≥ 10 ng/ml and 5 cases had PSA ≥ 20 ng/ml. Of the 19 radical prostate specimens, Gleason cribriform pattern (Gleason grade 4) of PCa is observed in 15 cases (78.95%), and intraductal carcinoma, usually a rare form, is seen in 9 cases (47.3%). Two cases demonstrated pelvic lymph node metastasis, and 7 cases (35%) belonged to high-risk or very high-risk PCa. One case (5.26%) showed partial deletion of expression of RB1, and 13 cases (68.42%) showed deletion of expression of PTEN. Follow-up was 4-90 months, 2 cases had biochemical recurrence and 1 case died from prostate cancer. The mean age at diagnosis of this group of patients with hereditary prostate cancer was 67.55 years, the mean preoperative PSA was 15.44 ng/ml, and their histomorphology was characterized by a high percentage of intraductal carcinoma and cribriform pattern of the prostate.

Celastrol inhibits mouse B16-F10 melanoma cell survival by regulating the PI3K/AKT/mTOR signaling pathway and repressing HIF-1α expression.

OBJECTIVE: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. METHODS: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. RESULTS: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. CONCLUSION: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.

Insights into the alleviation of cadmium toxicity in rice by nano-zinc and Serendipita indica: Modulation of stress-responsive gene expression and antioxidant defense system activation.

The adversities of cadmium (Cd) contamination are quite distinguished among other heavy metals (HMs), and so is the efficacy of zinc (Zn) nutrition in mitigating Cd toxicity. Rice (Oryza sativa) crop, known for its ability to absorb HMs, inadvertently facilitates the bioaccumulation of Cd, posing a significant risk to both the plant itself and to humans consuming its edible parts, and damaging the environment as well. The use of nanoparticles, such as nano-zinc oxide (nZnO), to improve the nutritional quality of crops and combat the harmful effects of HMs, have gained substantial attention among scientists and farmers. While previous studies have explored the individual effects of nZnO or Serendipita indica (referred to as S.i) on Cd toxicity, the synergistic action of these two agents has not been thoroughly investigated. Therefore, the gift of nature, i.e., S. indica, was incorporated alongside nZnO (50 mg L-1) against Cd stress (15 µM L-1) and their alliance manifested as phenotypic level modifications in two rice genotypes (Heizhan43; Hz43 and Yinni801; Yi801). Antioxidant activities were enhanced, specifically peroxidase (61.5 and 122.5% in Yi801 and Hz43 roots, respectively), leading to a significant decrease in oxidative burst; moreover, Cd translocation was reduced (85% for Yi801 and 65.5% for Hz43 compared to Cd alone treatment). Microstructural study showed a decrease in number of vacuoles and starch granules with ameliorative treatments. Overall, plants treated with nZnO displayed gene expression pattern (particularly of ZIP genes), different from the ones with alone or combined S.i and Cd. Inferentially, the integration of nZnO and S.i holds great promise as an effective strategy for alleviating Cd toxicity in rice plants. By immobilizing Cd ions in the soil and promoting their detoxification, this novel approach contributes to environmental restoration and ensures food safety worldwide.

Application of enhanced recovery after surgery during the perioperative period in children with Meckel's diverticulum-a single-center prospective clinical trial.

Background: Enhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD. Methods: A prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate. Results: A total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups. Conclusions: In this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.

Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Somatic mutations that affect early genetic progression and immune microenvironment in gastric carcinoma.

Gastric carcinoma (GC) is a high heterogeneity and malignant tumor with a poor prognosis. The current implementation of immunotherapy in GC is limited due to the insufficient exploration of immune-related mutations and speculated early mutation events. Therefore, we performed whole-exome sequencing on 40 patients with GC to explore their genetic characteristics, shedding light on the order of genetic events, somatic mutations impacting the immune microenvironment, and potential biomarkers for immunotherapy. Regarding genetic events, TP53 disruptions were identified as frequent and early events in GC progression, often occurring alongside other gene mutations. The mutations occurring in GANS, SMAD4, and POLE were early independent events. Patients harboring CSMD3, FAT4, FLG, KMT2C, LRP1B, MUC5B, MUC16, PLEC, RNF43, SYNE1, TP53, TTN, XIRP2, and ZFHX4 mutations tended to have decreased B cells, T cells, macrophage, neutrophil, and dendritic cells infiltration, except for the ARID1A gene mutations. We also found patients with microsatellite instability-high tumors had higher homologous recombination deficiency (HRD) scores. HRD showed a positive correlation with tumor mutational burden, which might serve as indirect evidence supporting the potential of HRD as a biomarker for GC. These findings highlighted GC's high heterogeneity and complexity and provided valuable insights into the somatic mutations that affect early genetic progression and immune microenvironment.

Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication.

Shwachman Diamond syndrome (SDS) is a rare autosomal recessive genetic disorder and due to its complex and varied clinical manifestations, diagnosis is often delayed. The purpose of this study was to investigate the clinical manifestations and genetic characteristics of SDS in Chinese patients, in order to increase pediatricians' awareness of SDS and to allow early diagnosis. We conducted a search to identify patients presenting SBDS gene pathogenic variant in two Chinese academic databases. We analyzed and summarized the epidemiology, clinical features, gene pathogenic variants, and key points in the diagnosis and treatment of SDS. We reviewed the clinical data of 39 children with SDS from previously published articles. The interval from the onset of the first symptoms to diagnosis was very long for most of our patients. The age of presentation ranged from 1 day to 10 years (median: 3 months). However, the age of diagnosis was significantly delayed, ranging from 1 month to 14 years (median: 14 months). Hematological abnormalities were the most common presentation, 89.7% (35/39) at the beginning and 94.9% (37/39) at diagnosis of SDS. Diarrhea was the second most common clinical abnormality at the time of diagnosis. 59% (23/39) of patients had a typical history of persistent chronic diarrhea. Furthermore, hepatic enlargement or elevation of transaminase occurred in 15 cases (38.5%). 56.4% patients (22/39) had a short stature, and 17.9% (7/39) patients showed developmental delay. Additionally, twenty patients had compound heterozygous pathogenic variants of c.258 + 2T > C and c.183_ 184TA > CT. Children with SDS in China had high incidence rates of chronic diarrhea, cytopenia, short stature, and liver damage. Furthermore, SBDS c.258 + 2T > C and c.183_ 184TA > CT were the most common pathogenic variants in patients with SDS. The diagnosis of SDS can be delayed if the clinical phenotype is not recognized by the health care provider.

Structural Characterization and Physiological Role of Bombyx mori Fibroinase in the Silk Gland Development.

Silkworm is a highly valuable insect that produces silk through secretion by a silk gland. Within this gland, a type of cathepsin L protease called Fibroinase was identified as an enzyme for hydrolyzing the primary components of silk, including fibroin and sericin. Here, we determined the crystal structure of Fibroinase fromBombyx mori at a resolution of 1.56 Å. Comparative structural analysis revealed that Fibroinase adopted a similar structural pattern with papain-type cathepsin, consisting of an N-terminal domain and a C-terminal domain. The interface between the domains forms a substrate-binding cleft, where the E64 inhibitor noncovalently binds in a novel manner. Additionally, computational simulations combined with biochemical analysis allowed us to define the binding mode and inhibition mechanism of physiological inhibitor Bombyx cysteine protease inhibitor (BCPI) with Fibroinase. Moreover, the expression profiles and RNA interference of Fibroinase indicated its critical role in removing silk proteins in the silk gland lumen and the destruction of silk gland tissue during the larval-pupal metamorphosis. These findings enhance our understanding of the structural and biochemical features of Fibroinase and its inhibitors, while also providing evidence for the physiological role of Fibroinase in silk gland development.

Genetic evidence strengthens the bidirectional connection between oral health status and psychiatric disorders: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies cannot accurately infer the causal associations between oral health status and psychiatric disorders. METHODS: We conducted univariate and multivariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with eight oral health statuses (periodontitis, DMFS, Nteeth, toothache, loose teeth, painful gums, bleeding gums, and mouth ulcers) and four psychiatric disorders (Schizophrenia, Major Depressive Disorder (MDD), anxiety and stress-related disorder (ASRD), and Bipolar Disorder (BIP)) as instrumental variables. Genetic data were sourced from the Gene-lifestyle interactions in dental endpoints (GLIDE), UK Biobank, Psychiatric Genomics Consortium (PGC), and Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The inverse variance-weighted (IVW) approach, supported by a comprehensive sensitivity analysis, was employed. RESULTS: Genetically predicted mouth ulcers were significantly linked to higher MDD (OR = 2.17, 95 % CI: 1.33--3.54, P< 0.01) and BIP risks (OR = 2.25, 95 % CI: 1.22-4.15, P = 0.01). BIP heightened bleeding gums risk (OR = 1.01, 95 % CI: 1.00-1.01, P < 0.01). These associations were adjusted for smoking status and alcohol consumption. Painful gums were significantly associated with MDD risk (OR = 96.48, 95 % CI: 2.66-3495.28, P = 0.01), while MDD raised periodontitis risk (OR = 2.15, 95 % CI: 1.24-3.75, P = 0.01), both confounded by smoking and alcohol. Relatively small effects between several variables, while others could not withstand correction for multiple tests. LIMITATIONS: The sample size and limitation to European populations limits the study generalizability. CONCLUSIONS: This study provide evidence of possible causal relationships between several oral health conditions and mental illness. Focusing on oral health and valuing mental health are important for each other and overall health.

Soil warming affects sap flow and stomatal gas exchange through altering functional traits in a subtropical forest.

Climate warming influences the structure and function of ecosystems. However, the mechanisms of plant water use and gas exchange responses to climate warming have been less studied, especially from the perspective of different functional traits. We conducted a field experiment to investigate how soil warming (+2 °C) affects sap flow and stomatal gas exchange through plant functional traits and nutrient characteristics in a subtropical forest. We measured stomatal gas exchange of trees (Acacia auriculiformis and Schima superba) and shrubs (Castanea henryi and Psychotria asiatica), and monitored long-term sap flow of both tree species. Besides, plant leaf nutrient contents, functional traits, and soil nutrients were also studied. It is demonstrated that soil warming significantly increased maximum sap flow density (Js_max, 35.1 %) and whole-tree transpiration (EL, 46.0 %) of A. auriculiformis, but decreased those of S. superba (15.6 % and 14.9 %, respectively). Warming increased the photosynthetic rate of P. asiatica (18.0 %) and water use efficiency of S. superba (47.2 %). Leaf nutrients and stomatal anatomical characteristics of shrubs were less affected by soil warming. Soil warming increased (+42.7 %) leaf K content of A. auriculiformis in dry season. Decomposition of soil total carbon, total nitrogen, and available nitrogen was accelerated under soil warming, and soil exchangeable Ca2+ and Mg2+ were decreased. Trees changed stomatal and anatomic traits to adapt to soil warming, while shrubs altered leaf water content and specific leaf area under soil warming. Warming had a greater effect on sap flow of trees, as well as on their leaf gas exchange (total effect: -0.27) than on that of shrubs (total effect: 0.06). In summary, our results suggest that the combination of functional and nutrient traits can help to better understand plant water use and gas exchange responses under climate warming.

Kisspeptin prevents pregnancy loss by modulating the immune microenvironment at the maternal-fetal interface in recurrent spontaneous abortion.

PROBLEM: Immune factors are crucial in the development of recurrent spontaneous abortion (RSA). This study aimed to investigate whether kisspeptin regulates immune cells at the maternal-fetal interface and whether G protein-coupled receptor 54 (GPR54) is involved in this process, through which it contributes to the pathogenesis of RSA. METHOD OF STUDY: Normal pregnancy (NP) (CBA/J × BALB/c) and RSA (CBA/J × DBA/2) mouse models were established. NP mice received tail vein injections of PBS and KP234 (blocker of kisspeptin receptor), whereas RSA mice received PBS and KP10 (active fragment of kisspeptin). The changes in immune cells in mouse spleen and uterus were assessed using flow cytometry and immunofluorescence. The expression of critical cytokines was examined by flow cytometry, ELISA, Western blotting, and qPCR. Immunofluorescence was employed to detect the coexpression of FOXP3 and GPR54. RESULTS: The findings revealed that the proportion of Treg cells, MDSCs, and M2 macrophages in RSA mice was lower than that in NP mice, but it increased following the tail vein injection of KP10. Conversely, the proportion of these cells was reduced in NP mice after the injection of KP234. However, the trend of γδT cell proportion change is contrary to these cells. Furthermore, FOXP3 and GPR54 were coexpressed in mouse spleen and uterus Treg cells as well as in the human decidua samples. CONCLUSION: Our results suggest that kisspeptin potentially participates in the pathogenesis of RSA by influencing immune cell subsets at the maternal-fetal interface, including Treg cells, MDSC cells, γδT cells, and M2 macrophages.

Hypolipidemic and Antithrombotic Effect of 6'-O-Caffeoylarbutin from Vaccinium dunalianum Based on Zebrafish Model, Network Pharmacology, and Molecular Docking.

Vaccinium dunalianum leaf buds make one of the most commonly used herbal teas of the Yi people in China, which is used to treat articular rheumatism, relax tendons, and stimulates blood circulation in the body. In addition, 6'-O-caffeoylarbutin (CA) is a standardized extract of V. dunalianum, which has been found in dried leaf buds, reaching levels of up to 31.76%. Because of the uncommon phenomenon, it is suggested that CA may have a potential therapeutic role in hyperlipidemia and thrombosis. This study was designed to study the efficacy of CA on treating hyperlipidemia and thrombosis and the possible mechanisms behind these effects. Hyperlipidemia and thrombosis zebrafish models were treated with CA to observe variations of the integrated optical density within the vessels and the intensity of erythrocyte staining within the hearts. The possible mechanisms were explored using network pharmacology and molecular docking. The results demonstrate that CA exhibits an excellent hypolipidemic effect on zebrafish at concentrations ranging from 3.0 to 30.0 µg/mL and shows thrombosis inhibitory activity in zebrafish at a concentration of 30.0 µg/mL, with an inhibition rate of 44%. Moreover, network pharmacological research shows that MMP9, RELA, MMP2, PRKCA, HSP90AA1, and APP are major targets of CA for therapy of hyperlipidemia and thrombosis, and may relate to pathways in cancer, chemical carcinogenesis-receptor activation, estrogen signaling pathway, and the AGE-RAGE signaling pathway in diabetic complications.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification.

Objective: This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue. Methods: A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis. Results: Six potential active components, namely quercetin, ß-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment. Conclusion: Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase.

Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production. Inhibiting its activity can reduce skin pigmentation. Hydroquinone is an efficient inhibitor of tyrosinase, but its safety has been a subject of debate. In this research, a scaffold hybridization strategy was employed to synthesize a series of hydroquinone-benzoyl ester analogs (3a-3g). The synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase (mTyr). The results revealed that these hydroquinone-benzoyl ester analogs exhibited inhibitory activity against mTyr, with compounds 3a-3e displaying higher activity, with compound 3b demonstrating the highest potency (IC50 = 0.18 ± 0.06 µM). Kinetic studies demonstrated that the inhibition of mTyr by compounds 3a-3e was reversible, although their inhibition mechanisms varied. Compounds 3a and 3c exhibited non-competitive inhibition, while 3b displayed mixed inhibition, and 3d and 3e showed competitive inhibition. UV spectroscopy analysis indicated that none of these compounds chelated with copper ions in the active center of the enzyme. Molecular docking simulations and molecular dynamics studies revealed that compounds 3a-3e could access the active pocket of mTyr and interact with amino acid residues in the active site. These interactions influenced the conformational flexibility of the receptor protein, subsequently affecting substrate-enzyme binding and reducing enzyme catalytic activity, in line with experimental findings. Furthermore, in vitro melanoma cytotoxicity assay of compound 3b demonstrated its higher toxicity to A375 cells, while displaying low toxicity to HaCaT cells, with a dose-dependent effect. These results provide a theoretical foundation and practical basis for the development of novel tyrosinase inhibitors.

Ultrasound Imaging of Tumor Vascular CD93 with MMRN2 Modified Microbubbles for Immune Microenvironment Prediction.

Vascular microenvironment is found to be closely related to immunotherapy efficacy. Identification and ultrasound imaging of the unique vascular characteristics, able to predict immune microenvironment, is important for immunotherapy decision-making. Herein, it is proved that high CD93 expression in the tumor vessels is closely related to the poor immune response of prostate cancer. For ultrasound molecular imaging of CD93, CD93-targeted microbubbles (MBs) consist a gaseous core and the MMRN2 (Multimerin-2) containing cell membrane (CM) /lipid hybrid membrane is then synthesized. In vitro and in vivo assays demonstrate that these MBs can recognize CD93 efficiently and then accumulate within tumor regions highly expressing CD93. Contrast-enhanced ultrasound (CEUS) imaging with CD93-targeted MBs demonstrates that targeted ultrasound intensity is negatively related to inflammatory tumor immune microenvironment (TIME) and cytotoxic T cell infiltration. Together, endothelial expression of CD93 in tumor is a unique predictor of immunosuppressive microenvironment and CD93-targeted MBs have a great potential to evaluate tumor immune status.

Rapid detection of human adenovirus subgroup B using recombinase polymerase amplification assay.

Human adenovirus subgroup B (HAdV B) is one of the major pathogens of human respiratory virus infections, which has considerable transmission and morbidity in a variety of populations. Therefore, rapid and specific detection of HAdV B in clinical samples is essential for diagnosis. This study aimed to develop a product for rapid nucleic acid detection of HAdV B using recombinase polymerase amplification assay (RPA) and validate the performance of this method by using clinical samples. Results showed that this method achieved a lower limit of detection (LOD) of 10 copies/µL and had no cross-reactivity with other adenovirus subgroups or respiratory pathogens. In addition to high sensitivity, it can be completed within 30 min at 40 °C. There is no need to perform nucleic acid extraction on clinical samples. Taking qPCR as the gold standard, the RPA assay possessed a high concordance (Cohen's kappa, 0.896; 95% CI 0.808-0.984; P < 0.001), with a sensitivity of 87.80% and a specificity of 100.00%. The RPA assay developed in this study provided a simple and highly specific method, making it an important tool for rapid adenovirus nucleic acid detection and facilitating large-scale population screening in resource-limited settings.

Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Diagnosis and Prognosis of Thyroid Cancer by Immune-related Genes.

BACKGROUND: Thyroid carcinoma (THCA) is the most common malignant endocrine tumor with low mortality and a relatively good prognosis. Immune genes have attracted much attention as molecular markers of THCA prognosis and potential targets of immunotherapy. METHODS: Our study analyzed the transcriptome and clinical data of immune-related genes (IRGs) of THCA in gene expression omnibus, the cancer genome atlas-THCA, and ImmPort databases. By univariate Cox regression analysis, 15 genes were significantly correlated with the survival of patients with THCA. Five IRGs ( NMU, UBE2C, CDKN2A, COL19A1, and GPM6A ) were selected by LASSO regression analysis as independent prognostic factors to construct a disease-free survival-related prognostic risk model. RESULTS: Kaplan-Meier survival analysis showed that there was a significant difference in disease-free survival between high and low-risk groups. The higher the risk score, the worse the survival of patients. Clinical correlation analysis showed that age and Stage stage of patients were correlated with risk score ( P < 0.05). Quantitative real-time polymerase chain reaction confirmed that there were differences in the expression of 5 IRGs between tumor tissues and normal thyroid tissues. Spearman correlation analysis indicated that the relative expression levels of NMU, CDKN2A, UBE2C, COL19A1 , and GPM6A were positively correlated with programmed death-ligand 1 and recombinant a disintegrin and metalloproteinase with thrombospondin 1. CONCLUSION: Based on the bioinformatics method, we constructed a prognosis evaluation model and risk score system of IRGs in THCA, which provided a reference for predicting the prognosis of patients with THCA.