Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS: A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS: On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION: Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.

Screening optimal DC-targeting peptide to enhance the immune efficacy of recombinant Lactobacillus expressing RHDV VP60.

Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.

The safety and feasibility assessment of overlap esophagojejunostomy with self-pulling and latter transection technique in totally laparoscopic total gastrectomy.

BACKGROUND: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT. METHODS: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676). CONCLUSION: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration.

A review on triterpenoid and triterpenoid saponins from Xanthoceras sorbifolium Bung.

Xanthoceras sorbifolium Bunge, also known as Tu-Mu-Gua and Wen-Dan-Ge-Zi, has several applications. Clinical data and experimental studies have shown anti-tumor, anti-inflammatory, anti-bacterial, and anti-oxidant properties of Xanthoceras sorbifolium Bunge that inhibits prostate hyperplasia, lowers blood pressure and lipid level, and treats enuresis and urinary incontinence. It also has neuroprotective effects and can treat Alzheimer's disease and Parkinson's syndrome. The research on the chemical composition and pharmacological effects of Xanthoceras sorbifolium Bunge has been increasing. Triterpenoid and triterpenoid saponins are the main constituents in Xanthoceras sorbifolium Bunge and exhibit biological activities. In this review, we summarized the research progress on triterpenoids and their glycosides in Xanthoceras sorbifolia, including the chemical constituents, pharmacological activities, and biogenic pathways of triterpenoid mother nucleus. The results would provide a reference for further research and development of triterpenoids and their glycosides in Xanthoceras sorbifolia.

[Effects of BMAL2 on Aerobic Glycolysis and Cell Proliferation in Acute Myeloid Leukemia Cells].

OBJECTIVE: To explore the expression of basic helix-loop-helix ARNT like 2 (BMAL2) in acute myeloid leukemia (AML) patients and its correlation with prognosis, and analyze its effects on the aerobic glycolysis and proliferation of AML cells. METHODS: The expressions of BMAL2 in bone marrow mononuclear cells (BMMCs) of AML patients and normal control group were detected by RT-qPCR. The correlation of BMAL2 expression with prognosis of AML patients was analyzed using public database of National Center for Biotechnology Information (NCBI). The interfering in BMAL2 expression of HL-60 and Kasumi-1 cells was performed using lentiviral vector-mediated shRNA. Cell glucose metabolism and proliferation were detected by using glucose uptake experiment, lactate content test, CCK-8 assay and cell colony formation test. RESULTS: The expression level of BMAL2 mRNA in BMMCs of AML patients was significantly higher than normal control group (P < 0.01). The overall survival time of AML patients with high expression of BMAL2 was significantly shorter than those with low expression of BMAL2 (P < 0.05). Knockdown of BMAL2 significantly reduced glucose uptake and lactate production in AML cell line HL-60 and Kasumi-1 cells. The results of RT-PCR and Western blot showed that BMAL2 promoted aerobic glycolysis by enhancing the expression of HIF1A in AML cells, thereby promoting cell proliferation. CONCLUSION: BMAL2 is highly expressed in AML patients, and promotes aerobic glycolysis by enhancing the expression of HIF1A, thereby promoting cell proliferation.

Influence of GPRC5A-Regulated ABCB1 Expression on Lung Adenocarcinoma Proliferation.

Objective Aberrant expression of ATP binding cassette subfamily B member 1 (ABCB1) plays a key role in several cancers. However, influence of G protein coupled receptor family C group 5 type A (GPRC5A)-regulated ABCB1 expression on lung adenocarcinoma proliferation remains unclear. Therefore, this study investigated the effect of GPRC5A regulated ABCB1 expression on the proliferation of lung adenocarcinoma. Methods ABCB1 expressions in lung adenocarcinoma cell lines, human lung adenocarcinoma tissues, and tracheal epithelial cells and lung tissues of GPRC5A knockout mice and wild-type mice were analyzed with RT-PCR, Western blot, or immunohistochemical analysis. Cell counting kit-8 assay was performed to analyze the sensitivity of tracheal epithelial cells from GPRC5A knockout mice to chemotherapeutic agents. Subcutaneous tumor formation assay was performed to confirm whether down-regulation of ABCB1 could inhibit the proliferation of lung adenocarcinoma in vivo. To verify the potential regulatory relationship between GPRC5A and ABCB1, immunofluorescence and immunoprecipitation assays were performed. Results ABCB1 expression was up-regulated in lung adenocarcinoma cell lines and human lung adenocarcinoma tissues. ABCB1 expression in the tracheal epithelial cells and lung tissues of GPRC5Adeficient mice was higher than that in the wild type mice. Tracheal epithelial cells of GPRC5A knockout mice were much more sensitive to tariquidar and doxorubicin than those of GPRC5A wild type mice. Accordingly, 28 days after injection of the transplanted cells, the volume and weight of lung tumor in ABCB1knockout cell-transplanted GPRC5A-/-C57BL/6 mice were significantly smaller than those in wild type cell-transplanted mice (P= 0.0043, P= 0.0060). Furthermore, immunofluorescence and immunoprecipitation assays showed that GPRC5A regulated ABCB1 expression by direct binding.Conclusion GPRC5A reduces lung adenocarcinoma proliferation via inhibiting ABCB1 expression. The pathway by which GPRC5A regulates ABCB1 expression needs to be investigated.

Role of STAT3 in cancer cell epithelial­mesenchymal transition (Review).

Since its discovery, the role of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in both normal physiology and the pathology of numerous diseases, including cancer, has been extensively studied. STAT3 is aberrantly activated in different types of cancer, fulfilling a critical role in cancer progression. The biological process, epithelial­mesenchymal transition (EMT), is indispensable for embryonic morphogenesis. During the development of cancer, EMT is hijacked to confer motility, tumor cell stemness, drug resistance and adaptation to changes in the microenvironment. The aim of the present review was to outline recent advances in knowledge of the role of STAT3 in EMT, which may contribute to the understanding of the function of STAT3 in EMT in various types of cancer. Delineating the underlying mechanisms associated with the STAT3­EMT signaling axis may generate novel diagnostic and therapeutic options for cancer treatment.

Immunoprotection of FliBc chimeric fiber2 fusion proteins targeting dendritic cells against Fowl adenovirus serotype 4 infection.

Hepatitis-hydropericardium syndrome (HHS) is a highly fatal disease in chickens caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4), which has severe economic consequences. The fiber2 protein exhibits excellent potential as a candidate for a subunit vaccination against FAdV-4. Despite having a high safety profile, subunit vaccines have low immunogenicity due to their lack of infectivity, which leads to low levels of immune response. As a vaccine adjuvant, Salmonella flagellin possesses the potential to augment the immunological response to vaccinations. Additionally, a crucial strategy for enhancing vaccine efficacy is efficient presentation of immune antigens to dendritic cells (DC) for targeted vaccination. In this study, we designed FAdV-4-fiber2 protein, and a recombinant protein called FliBc-fiber2-SP which based on FAdV-4-fiber2 protein, was generated using the gene sequence FliBc, which retains only the conserved sequence at the amino and carboxyl termini of the flagellin B subunit, and a short peptide SPHLHTSSPWER (SP), which targets chicken bone marrow-derived DC. They were separately administered via intramuscular injection to 14-day-old specific pathogen-free (SPF) chickens, and their immunogenicity was compared. At 21 d postvaccination (dpv), it was found that the FliBc-fiber2-SP recombinant protein elicited significantly higher levels of IgG antibodies and conferred a vaccine protection rate of up to 100% compared to its counterpart fiber2 protein. These results suggest that the DC-targeted peptide fusion strategy for flagellin chimeric antigen construction can effectively enhance the immune protective efficacy of antigen proteins.

Disseminated Talaromyces marneffei infection associated with haemophagocytic syndrome in an HIV-negative patient in northern China: a case report.

BACKGROUND: Talaromyces marneffei is endemic to eastern India, Southeast Asia, and Guangdong and Guangxi provinces in China. It is common in immunocompromised individuals, especially in HIV-infected patients. CASE PRESENTATION: A 66-year-old male who had a history of hypertension and resided in Shandong Province (Northern China) was admitted for recurrent fever for one month. The patient had recurrent fever, multiple lymphadenopathies, hepatosplenomegaly, a back rash, and a progressive decrease in white blood cells and platelets. Talaromyces marneffei was isolated from peripheral blood and bone marrow after admission, and suspected fungal cells were found via lymph node pathology. The patient's infection secondary to haemophagocytic syndrome continued to worsen despite antifungal, anti-inflammatory, and symptomatic treatment, leading to death due to multiple-organ failure. CONCLUSION: Although rare, infection due to Talaromyces marneffei in HIV-negative patients has been increasing in recent years, and we should be vigilant about "new" infections in nonendemic areas.

Hsa-miR-877-5p Expression in Acute Ischemic Stroke Based on Bioinformatics Analysis and Clinical Validation.

Inflammation and immunity play important roles in the pathogenesis of ischemic stroke. This study aimed to explore key regulatory genes in acute ischemic stroke (AIS) and their underlying mechanisms to provide new research targets for the diagnosis and treatment of ischemic stroke. We searched for differentially expressed mRNAs and miRNAs in patients with AIS and healthy populations in GEO databases, constructed a miRNA-mRNA network, and screened key miRNAs using least absolute shrinkage and selection operator regression and the support vector machine-recursive feature elimination model. Correlations between key miRNAs and infiltrating immune cells and inflammatory factors were analyzed using CIBERSORT and immunoassays and verified using clinical experiments. Bioinformatics analysis identified hsa-miR-877-5p as a key regulatory miRNA in AIS that can modulate immune and inflammatory responses. In clinical studies, it was verified by quantitative PCR analysis that the expression of hsa-miR-877-5p in the blood of AIS patients was higher than that of the healthy group. Then, enzyme-linked immunosorbent assay revealed that the expression of IL-23 and TNF-α related to inflammation in AIS patients was higher than that of the healthy. Quantitative PCR further found that the relative mRNA expression of IL-23, CXCR3, and TNF-α in AIS group was higher than that of the healthy group. This study may provide a basis for a more comprehensive understanding of the potential mechanism of the occurrence and development of AIS, and hsa-miR-877-5p and its downstream effectors IL-23, CXCR3, and TNF-α may be potential intervention targets in AIS.

Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin-dendritic Cell-OX40 Ligand Axis in a Mouse Model.

Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)-dendritic cell (DC)-OX40L axis was investigated. A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively. Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased. Amygdalin thus regulates the Th1/Th2 balance through the TSLP-DC-OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments.

Crosstalk of nervous and immune systems in pancreatic cancer.

Pancreatic cancer is a highly malignant tumor known for its extremely low survival rate. The combination of genetic disorders within pancreatic cells and the tumor microenvironment contributes to the emergence and progression of this devastating disease. Extensive research has shed light on the nature of the microenvironmental cells surrounding the pancreatic cancer, including peripheral nerves and immune cells. Peripheral nerves release neuropeptides that directly target pancreatic cancer cells in a paracrine manner, while immune cells play a crucial role in eliminating cancer cells that have not evaded the immune response. Recent studies have revealed the intricate interplay between the nervous and immune systems in homeostatic condition as well as in cancer development. In this review, we aim to summarize the function of nerves in pancreatic cancer, emphasizing the significance to investigate the neural-immune crosstalk during the advancement of this malignant cancer.

Application of traditional Chinese medicine acupoint needle embedding combined with emotional nursing in patients with gynecological malignant tumors.

BACKGROUND: Few relevant literature reports on applying acupoint press-needle embedding combined with emotional nursing in patients with a gynecological malignant tumor. AIM: To explore the effect of traditional Chinese medicine acupoint needle embedding combined with emotional nursing on chemotherapy-related nausea and vomiting (CINV), cancer-related fatigue (CRF) and psychological state in patients with gynecological malignant tumors. METHODS: Retrospective analysis of the clinical information of 84 patients with gynecological malignant tumors treated in our hospital from August 2020 to December 2022 Led to the development of an observation group (n = 42) and a control group (n = 42) based on various nursing approaches. Ondansetron hydrochloride injection was administered to the individuals in the control group. However, the observation group received emotional nursing based on the control group and acupoint press-needle embedding of traditional Chinese medicine. Patients in both groups received the chemotherapy regimen of paclitaxel liposome + carbo-platin/ cisplatin. For four weeks, both groups intervened. The CINV grade, quality of life, CRF, psychological status and sleep quality scores of the two groups before and after intervention were compared. RESULTS: After intervention, the degree of CINV in the observation group was significantly better than that in the control group. After intervention, the scores of each dimension and total score of FLIE scale were significantly higher than those in the control group. After intervention, the scores of each dimension and total score of Piper Fatigue Scale were significantly lower than those in the control group (P < 0.05). After intervention, the scores of avoidance and yield dimensions in the observation group were significantly lower than those in the control group, and the scores of confrontation dimension were significantly higher than those in the control group (P < 0.05). After intervention, the sleep quality score of the observation group was significantly lower than that of the control group, and the Karnofsky Performance Status scale score was significantly higher than that of the control group (P < 0.05). CONCLUSION: The acupuncture point needle embedding of traditional Chinese medicine combined with emotional nursing can further reduce the incidence of chemotherapy-related nausea and vomiting in patients with gynecological malignant tumors, improve the quality of life and the degree of CRF, alleviate the bad psychological state, adopt a positive way to face the disease and treatment, and improve the quality of sleep and quality of life.

Two pyrrole acids isolated from Phyllanthus emblica L. and their bioactivities.

An undescribed pyrrole acid, 1-(4'-methoxy-4'-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.

Novel Platelet Function Analyzer 200 Predicts Blood Transfusion After Elective Cardiac Surgery in Patients Suspended on Dual Antiplatelet Therapy.

The value of platelet function test in timing of cardiac surgery remains uncertain. Researches on correlation between Platelet Function Analyzer 200 (PFA-200) and bleeding after elective cardiac surgery are still inadequate. The objective of this study was to investigate the predictive value of PFA-200 in blood transfusion after cardiac surgery. A total of 71 patients on aspirin and P2Y12 receptor inhibitors undergoing cardiac surgery in Fuwai Hospital were enrolled. Platelet function after discontinuing of antiplatelet drugs was assessed by PFA-200 using closure time (CT). PFA-200 results before surgery were included in the statistics. The primary endpoint was postoperative blood transfusion. Seventeen patients (21.9%) received blood transfusion after cardiac surgery. The preoperative PFA-200 CT value in the transfused group was significantly higher than that in the non-transfused group (147.24 ± 85.54 s vs 98.06 ± 61.59 s, P = .011). Using 106 seconds as the dividing point, the incidence of blood transfusion in the elevated PFA-200 (CT > 106 s) group was significantly higher than those in normal PFA-200 (CT ≤ 106 s) group (10/24 patients, 41.9% vs 7/47 patients, 14.7%, P = .012). Multivariate logistic regression analysis showed that PFA-200 CT value > 106 s was an independent predictor of postoperative blood transfusion (OR: 4.05, 95%CI: 1.19-13.86, P = .026). The platelet function test PFA-200 had a predictive value for postoperative blood transfusion in elective cardiac surgery and had a promising prospect in the timing of cardiac surgery.

Ethyl caffeate attefnuates Aß-induced toxicity in Caenorhabditis elegans AD models via the insulin/insulin-like growth factor-1 signaling pathway.

The pathogenesis of Alzheimer's disease (AD), a multifactorial progressive neurodegenerative disease associated with aging, is unclear. Ethyl caffeate is a plant polyphenol that has been reported to have neuroprotective effects, but the mechanisms by which it acts are unclear. In this study, for the first time, we investigated the molecular mechanism of its anti-AD properties using the Caernorhabditis elegans model. The results of our experiments showed that ethyl caffeate delayed the paralysis symptoms of CL4176 to a different extent and reduced the exogenous 5-hydroxytryptophan-induced paralysis phenotype. Further studies revealed that ethyl caffeate lowered Aß plaques and depressed the expression of Aß monomers and oligomers, but did not influence the mRNA levels of Aß. Moreover, it was able to bring paraquat-induced ROS levels down to near-standard conditions. Real-time quantitative PCR experiment showed a significant upregulation of the transcript abundance of daf-16, skn-1 and hsf-1, key factors associated with the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway (IIS), and their downstream genes sod-3, gst-4 and hsp-16.2. It was further shown that ethyl caffeate activated the translocation of DAF-16 and SKN-1 from the cytoplasm to the nucleus and enhanced the expression of sod-3::GFP, gst-4::GFP and hsp-16.2::GFP in transgenic nematodes. This meant that the protection against Aß toxicity by ethyl caffeate may be partly through the IIS signaling pathway. In addition, ethyl caffeate suppressed the aggregation of polyglutamine proteins in AM141, which indicated a potential protective effect against neurodegenerative diseases based on abnormal folding and aggregation of amyloid proteins. Taken together, ethyl caffeate is expected to develop as a potential drug for the management of AD.

Preventive effect of LCZ696 on hypoxic pulmonary hypertension in rats via regulating the PI3K/AKT signaling pathway.

Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic drugs are lacking. This study investigated the effects and underlying mechanisms of LCZ696 treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or sildenafil. The mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and immunofluorescence staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. Western blotting was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary vascular remodeling, pulmonary arteriomyosis, and pulmonary artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.

[Effect of a Novel Dihydroartemisinin Dimer Containing Nitrogen Atoms SM 1044 on Apoptosis of Human Leukemia Cell Line NB4-R1].

OBJECTIVE: To investigate the effect of a water-soluble novel dihydroartemisinin dimer containing nitrogen atoms SM 1044 on the apoptosis of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanism. METHODS: The effects of SM 1044 on cell apoptosis, mitochondrial transmembrane potential, and the level of reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of apoptosis-related proteins were determined by Western blot. The effects of SM 1044 on MAPK (ERK, JNK) signaling pathway, PML/RARα fusion protein, and expressions of apoptosis-related proteins were detected by Western blot. RESULTS: SM 1044 could significantly induce apoptosis and the loss of mitochondrial transmembrane potential in NB4-R1 cells, and activate apoptosis-related proteins caspase-3, caspase-8, caspase-9 and poly (ADP-ribose) polymerase (PARP). SM 1044 could also induce NB4-R1 cells to produce ROS. Western blot showed that SM 1044 activated the phosphorylation of MAPK (ERK, JNK) signaling pathway and down-regulated the expression of PML/RARα fusion protein. CONCLUSION: SM 1044 can induce apoptosis of ATRA resistant APL NB4-R1 cells, which may be related to ROS/ERK and ROS/JNK signaling pathway, and can also induce by down-regulating PML/RARα fusion protein.

Acid and alkali-resistant fabric-based triboelectric nanogenerator for self-powered intelligent monitoring of protective clothing in highly corrosive environments.

The corrosion of materials severely limits the application scenarios of triboelectric nanogenerators (TENGs), especially in laboratories, chemical plants and other fields where leakage of chemically corrosive solutions is common. Here, we demonstrate a chemical-resistant triboelectric nanogenerator (CR-TENG) based on polysulfonamide (PSA) and polytetrafluoroethylene (PTFE) non-woven fabrics. The CR-TENG can stably harvest biological motion energy and perform intelligent safety protection monitoring in a strong corrosive environment. After treatment with strong acid and alkali solution for 7 days, the fabric morphology, diameter, tensile properties and output of CR-TENG are not affected, showing high reliability. CR-TENG integrated into protective equipment can detect the working status of protective equipment in real time, monitor whether it is damaged, and provide protection for wearers working in high-risk situations. In addition, the nonwoven-based CR-TENG has better wearing comfort and is promising for self-powered sensing in harsh environments.

Highly oxygenated germacrane-type sesquiterpenoids from the whole plant of Salvia cavaleriei H.Lév. and their biological activities.

The entire plant Salvia cavaleriei H.Lév. (Lamiaceae) is used as a traditional Chinese herbal medicine. Its leaves are edible, and the flowers can be soaked in water to make a health-care tea. In an effort to find natural bioactive chemical components, twelve undescribed germacrane-type sesquiterpenoids, salcavalins A-L, were isolated from the whole plant of S. cavaleriei and were identified as analogs. This is the first study to isolate highly oxygenated germacrane-type sesquiterpenoids from this plant. The structures of these undescribed compounds were elucidated by various spectroscopic methods, and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation and electronic circular dichroism calculations. The biological activity of these undescribed compounds on the production of tumor necrosis factor-alpha in lipopolysaccharide induced NR8383 cells was evaluated, and salcavalins I and K showed anti-inflammatory activity to some extent. Salcavalins A-C, F and L were found to be neuroprotective with antiparkinsonic potential in a nematode (Caenorhabditis elegans) model. In addition, salcavalins F and I displayed marked phytotoxic activity against radish seeds at a low concentration of 50 ppm. Our findings provide scientific justification to show that bioactive sesquiterpenoids from the edible herb have anti-inflammatory in vitro, neuroprotective and phytotoxic activities.