The Impact of the Composition on the Properties of Simulated Lunar Mare Basalt Fibers.

Lunar mare basalt is recognized as an important in situ resource on the lunar surface. However, the significant compositional variability of lunar mare basalts introduces uncertainties concerning the potential for their use in fabricating fibers and composite materials. This study investigates the impact of different components on the fiber-forming capabilities of mare basalts by simulating the compositions of basalts collected from several well-known lunar missions and then preparing simulated lunar mare basalt fibers. Raman spectroscopy is primarily employed for analysis and characterization, using "peak area normalization" to explore the impact of compositional fluctuations in the simulated lunar mare basalts on the glass network structure. The findings indicate that an increase in the Fe content raises the likelihood of basalt fibers crystallizing. Additionally, Fe3+ is shown to substitute for Si and Al in constructing bridging oxygen bonds in the network structure, albeit reducing the overall polymerization of the network. Meanwhile, Fe2+ acts as a network modifier to enhance the mechanical properties of the fibers.

[Expression and effect of TIGIT in peripheral blood CD56+ T cells of patients with rheumatoid arthritis].

Objective To investigate the proportional change of CD56+ T cells in peripheral blood of patients with rheumatoid arthritis (RA) and the expression of T cell immunoglobulin and immune receptor tyrosine inhibitory motif domain (TIGIT) on the surface of CD56+ T cells, and to explore the effect of TIGIT on CD56+ T cell function in RA. Methods Fifty patients with RA and twenty healthy controls were selected. Flow cytometry was used to determine the proportion of CD56+ T cells in peripheral blood, and the correlation between the resulting cell ratio and clinical indicators of the disease was analyzed. Flow cytometry was used to measure the expression level of TIGIT in peripheral blood CD56+ T cells in RA patients. Density gradient centrifugation was used to isolate peripheral blood mononuclear cells which were subsequently cultured in vitro. The proportion of CD56+ T cells expressing Interferon-γ (IFN-γ) and Interleukin-17A (IL-17A) in peripheral blood of RA patients were measured. The differential expression of IFN-γ and IL-17A in TIGIT- CD56+ T cells and TIGIT+ CD56+ T cells was investigated. The serum IL-17A levels in RA patients were assayed by ELISA. Results Compared with the healthy controls, the proportion of CD56+ T cells in peripheral blood was reduced in RA patients, and the proportion of CD56+ T cells expressing IL-17A was significantly reduced; Serum IL-17A concentration was elevated in RA patients. CD56+ T cells in RA patients were with higher expression of TIGIT molecules, and IFN-γ was mainly derived from TIGIT- CD56+ T cells. There was no significant difference between the proportion of TIGIT- CD56+ T cells and TIGIT+ CD56+ T cells expressing IL-17A. Conclusion Abnormal expression of TIGIT affects cytokine secretion function of CD56+ T cells, which in turn participates in the RA disease progression. And IFN-γ is mainly derived from TIGIT- CD56+ T cells. However, TIGIT may not affect the IL-17A secretion level of CD56+ T cells.

Transcriptomic analysis of wheat reveals possible resistance mechanism mediated by Yr10 to stripe rust.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a catastrophic disease that threatens global wheat yield. Yr10 is a race-specific all-stage disease resistance gene in wheat. However, the resistance mechanism of Yr10 is poorly characterized. Therefore, to elucidate the potential molecular mechanism mediated by Yr10, transcriptomic sequencing was performed at 0, 18, and 48 h post-inoculation (hpi) of compatible wheat Avocet S (AvS) and incompatible near-isogenic line (NIL) AvS + Yr10 inoculated with Pst race CYR32. Respectively, 227, 208, and 4050 differentially expressed genes (DEGs) were identified at 0, 18, and 48 hpi between incompatible and compatible interaction. The response of Yr10 to stripe rust involved various processes and activities, as indicated by the results of Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Specifically, the response included photosynthesis, defense response to fungus, metabolic processes related to salicylic acid (SA) and jasmonic acid (JA), and activities related to reactive oxygen species (ROS). Ten candidate genes were selected for qRT-PCR verification and the results showed that the transcriptomic data was reliable. Through the functional analysis of candidate genes by the virus-induced gene silencing (VIGS) system, it was found that the gene TaHPPD (4-hydroxyphenylpyruvate dioxygenase) negatively regulated the resistance of wheat to stripe rust by affecting SA signaling, pathogenesis-related (PR) gene expression, and ROS clearance. Our study provides insight into Yr10-mediated resistance in wheat.

Human cytomegalovirus UL36 inhibits IRF3-dependent immune signaling to counterbalance its immunoenhancement as apoptotic inhibitor.

Apoptotic inhibition and immune evasion have particular importance to efficient viral infection, while a dilemma often faced by viruses is that inhibiting apoptosis can up-regulate antiviral immune signaling. Herein, we uncovered that in addition to inhibiting caspase-8/extrinsic apoptosis, human cytomegalovirus (HCMV)-encoded UL36 suppresses interferon regulatory factor 3 (IRF3)-dependent immune signaling by directly targeting IRF3 to abrogate IRF3 interaction with stimulator of interferon genes or TANK-binding kinase 1 and inhibit IRF3 phosphorylation/activation. Although UL36-mediated caspase-8/extrinsic apoptosis inhibition enhances immune signaling, the immunosuppressing activity of UL36 counterbalances this immunoenhancing "side effect" undesirable for virus. Furthermore, we used mutational analyses to show that only the wild-type, but not the UL36 mutant losing either inhibitory activity, is sufficient to support effective HCMV replication in cells, showing the functional importance of the dual inhibition by UL36 for the HCMV life cycle. Together, our findings demonstrate a sophisticated mechanism by which HCMV tightly controls innate immune signaling and extrinsic apoptosis for efficient infection.

Renin-angiotensin system inhibitors improve the survival of cholangiocarcinoma: a propensity score-matched cohort study.

BACKGROUND: Hypertension is a risk factor for cholangiocarcinoma (CCA). The effect of anti-hypertensive drugs on the prognosis of CCA is not clear. METHODS: This is a retrospective study of 102 patients (56.9% males, median age 66 years) diagnosed with CCA and hypertension concurrently and received radical surgery (R0), with a median follow-up of 36.7 months. Kaplan-Meier analysis, Cox regressions, and propensity score (PS) matching were applied for statistical analysis. RESULTS: Results of multivariable cox analysis showed that renin-angiotensin system inhibitors (RASis) usage was a protective factor for progression-free survival (PFS) (hazard ratio [HR] = 0.55, 95% confidence interval [95% CI]: 0.32-0.96) and overall survival (OS) (HR = 0.40, 95% CI: 0.20-0.79), respectively. Calcium channel blockers, diuretics, and ß-blockers didn't show significant associations. The association of RASis usage and PFS and OS was derived by PS matching, with a cohort of 28 RASis users and 56 RASis non-users. The median PFS and OS of RASis users (PFS, 17.6 months (9.2-34.4); OS, 24.8 months (16.5-42.3)) were longer than RASis non-users (PFS, 10.5 months (4.1-24.1); OS, 14.6 months (10.6-28.4)). The 1 year, 2 years, and 3 years' survival rates of RASis users (89.1%, 77.0%, and 65.5%) were higher than RASis non-users (70.9%, 54.0%, and 40.0%). CONCLUSIONS: RASis usage improves the survival of patients with CCA and hypertension concurrently.

SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1.

In the past few decades, advances in the outcomes of patients suffering from pancreatic ductal adenocarcinoma (PDAC) have lagged behind these gained in the treatment of many other malignancies. Although the pivotal role of the SUMO pathway in PDAC has been illustrated, the underlying molecule drivers have yet to be fully elucidated. In the present study, we identified SENP3 as a potential suppressor of PDAC progression through an in vivo metastatic model. Further studies revealed that SENP3 inhibited PDAC invasion in a SUMO system dependent fashion. Mechanistically, SENP3 interacted with DKC1 and, as such, catalyzed the deSUMOylation of DKC1, which accepted SUMO3 modifiers at three lysine residues. SENP3-mediated deSUMOylation caused DKC1 instability and disruption of the interaction between snoRNP proteins, which contributed to the impaired migration ability of PDAC. Indeed, overexpression of DKC1 abated the anti-metastasis effect of SENP3, and DKC1 was elevated in PDAC specimens and associated with a poor prognosis in PDAC patients. Collectively, our findings shed light on the essential role of SENP3/DKC1 axis in the progression of PDAC.

Angiotensin receptor blockers retard the progression and fibrosis via inhibiting the viability of AGTR1+ CAFs in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy characterized by massive fibrosis and has ineffective adjuvant therapies. Here, we demonstrate the potential of angiotensin receptor blockers (ARBs) in targeting iCCA. METHODS: Masson's trichrome staining was used to assess the effect of ARBs in iCCA specimens, CCK8 and gel contraction assays in vitro and in xenograft models in vivo. RNA-seq and ATAC-seq were used for mechanistic investigations. RESULTS: Patients with iCCA who were administered ARBs had a better prognosis and a lower proportion of tumour stroma, indicating alleviated fibrosis. The presence of AGTR1, the ARBs receptor, is associated with a poor prognosis of iCCA and is highly expressed in tumour tissues and cancer-associated fibroblasts (CAFs). The ARBs strongly attenuated the viability of AGTR1+ CAFs in vitro and retarded tumour progression and fibrosis in xenograft models of co-cultured CAFs and iCCA cells. Still, they did not have a significant effect on AGTR1- CAFs. Moreover, ARBs decreased the secretion of AGTR1+ CAF-derived MFAP5 via the Hippo pathway, weakened the interaction between CAFs and iCCA cells, and impaired the aggressiveness of iCCA cells by attenuating the activation of the Notch1 pathway in iCCA cells. CONCLUSIONS: ARBs exhibit anti-fibrotic function by inhibiting the viability of AGTR1+ CAFs. These findings support using ARBs as a novel therapeutic option for targeting iCCA.

Growing of fungi on the stored low denatured defatted soybean meals and the hydrolysis of proteins and isoflavone glycosides by fungal enzymes.

Recently, more and more attention has been paid to the effects of fungal contamination and fungal enzymes secreted in raw grain on product quality. As the starting material of protein and active components, the quality of low denatured defatted soybean meals (LDSM) directly determines the qualities of subsequent products. In previous studies, we have revealed that infection with Aspergillus ochraceus protease causes significant hydrolysis of proteins. In this study, growing of fungi on the stored low denatured defatted soybean meals (LDSM) was analyzed by high-throughput sequencing and real-time PCR, which revealed that the abundance of Aspergillus increased significantly after storage. Twenty fungal proteases and 9 fungal glucosidases were found in stored LDSM and zymography showed that the proteases were of serine-type with some cysteine and aspartic activities. Proteolysis of the soybean storage proteins mainly occurred after the hydration of LDSM and the average molecular weight of soy proteins decreased from 57.9 kDa to 30.7 kDa after 60 min's of hydrolysis. Two-dimensional electrophoresis (2-DE) analysis found the polypeptide fragments from soybean 7S and 11S proteins with molecular weight around 10-25 kDa in the hydrated LDSM. Glycosylated isoflavones were hydrolyzed in both dry and hydrated stored LDSM which resulted in significant (p < 0.05) increase in the contents of isoflavone aglycones. This study suggested that fungi contamination be a new factor affecting the properties of LDSM derived soy protein products.

Characterization of proteases from Irpex lacteus grown on minimally denatured soybean meal.

BACKGROUND: Acid and thermal stabilities are important properties for the preparation of acidic protein beverage. It is an important method for enzymatic modification to improve the functional properties of protein. Irpex lacteus protease showed a selective hydrolysis to soy proteins. The purpose of this study was to investigate the mechanism of enzymatic hydrolysis and its effects on acid and thermal stabilities of soy proteins. RESULTS: The I. lacteus protease selectively hydrolyzed the α and α' subunits of the native soybean ß-conglycinin (7S globulin) to produce products that presented as the 55 kDa band upon sodium dodecyl sulfate polyacrylamide gel electrophoresis. The amino acid sequences of 55 kDa polypeptides were analyzed in gel multi-enzyme digestion followed by liquid chromatography-mass spectrometry. By matching the multi-enzyme digestion peptides with the published polypeptide chain sequences of the α and α' subunits, it was confirmed that the 55 kDa polypeptides were formed by eliminating amino acid residues on both sides of the N- and C-terminals. From the published protein structure database (https://www.uniprot.org/), it is known that the cleaved peptide bonds were in extension regions. Non-selective enzyme hydrolysis of both ß-conglycinin (7S globulin) and glycinin (11S globulin), with corresponding drastic increases in the degree of hydrolysis, was observed when the substrates were preheated to the denaturation degree of 40% and above. However, 55 kDa hydrolyzed products and B polypeptides showed some extent of resistance to the proteolysis by I. lacteus protease even if denaturation degree was 100%. Both selective and non-selective hydrolysis of soy proteins by I. lacteus protease improved the acid and heat stabilities under the same hydrolysis conditions (enzyme/substrate ratio, time, and temperature). CONCLUSION: Enzymatic hydrolysis of soybean proteins by the I. lacteus protease can effectively improve the acid and thermal stabilities of proteins. This discovery is significant to avoid aggregation during processing in the beverage industry. In the near future, the protease has potential application value for modification of other proteins. © 2022 Society of Chemical Industry.

Pancreatic ductal adenocarcinoma cells regulated the gemcitabine-resistance function of CAFs by LINC00460.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC-PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull-down, LC-MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine-resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC-PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460.

TLR2 agonist promotes myeloid-derived suppressor cell polarization via Runx1 in hepatocellular carcinoma.

Myeloid-derived suppressor cells (MDSCs) play a critical role in maintaining the tumor immune microenvironment; thus, the promotion of MDSC polarization will improve immunotherapies for cancers. However, the mechanisms involved in controlling MDSC polarization in hepatocellular carcinoma remain largely unclear. In this study, we found that injection of Pam3CSK4 attenuated the process of tumor growth, along with reduction of MDSC and recovery of T cell function. Moreover, Pam3CSK4 promoted MDSC polarization by targeting Runx1. Runx1 inhibitor reversed the therapeutic effect of Pam3CSK4 by increasing tumor size and weight and decreasing the survival rate of tumor mice. In addition, targeting Runx1 reduced the expression of CD11c, F4/80, CD80/CD86 and MHC-II in MDSC after Pam3CSK4 stimulation in vivo and in vitro. MDSC also exhibited consistent changes with increasing reactive oxygen species (ROS) production after Pam3CSK4 and Ro5-3335 treatment. RNA sequence data revealed that tfrc, steap3, and gclm were up-regulated in the Pam3CSK4/Ro5-3335 group compared with Pam3CSK4 treatment alone, suggesting that the regulatory effect of TLR2 and Runx1 on MDSC might act through the ferroptosis pathway. Overall, our study has identified a critical role for TLR2 and Runx1 in regulating the differentiation and function of MDSCs and has provided a new mechanism of controlling MDSC polarization during HCC immunotherapy.

Using Trait-Based Methods to Study the Response of Grassland to Fertilization in the Grassland in Semiarid Areas in the Loess Plateau of China.

Grassland is the dominant vegetation type in the Loess Plateau, and grassland productivity and processes are limited by nitrogen (N) and phosphorus (P). Studies have shown that productivity would change following fertilization in the grassland. The response of productivity to fertilization mainly depends on the dominant species traits. Trait-based methods provide a useful tool for explaining the variations in grassland productivity following fertilization. However, the relative contribution of plant functional traits to grassland productivity under N and P addition in the Loess Plateau is not clear. We measured aboveground biomass (AGB) and leaf N content (LN), leaf P content (LP), leaf N/P ratio (LN/P), specific leaf area (SLA), leaf tissue density (LTD), leaf dry matter content (LDMC), and maximum plant height (Hmax) to study how these plant functional traits regulate the relative biomass of different species and grassland productivity following fertilization. Our results showed, that under different nutrient addition levels, the linkages between plant functional traits and the relative biomass of different species were different. Community AGB was positively related to community-weighted mean LN (CWM_LN), CWM_LN/P, CWM_SLA, and CWM_Hmax, but negatively related to CWM_LTD and CWM_LDMC. Dominant species traits largely determined grassland productivity, in line with the mass ratio hypothesis. These findings further highlight the close linkages between community-level functional traits and grassland productivity. Our study contributes to the mechanisms underlying biodiversity-ecosystem function relationships and has significance for guiding semiarid grassland management.

Xiaoyaosan Exerts Antidepressant-Like Effect by Regulating Autophagy Involves the Expression of GLUT4 in the Mice Hypothalamic Neurons.

Many studies have proven that autophagy plays a pivotal role in the development of depression and it also affects the expression of GLUT4 in the hypothalamus. Xiaoyaosan has been shown to exert antidepressant effects in a variety of ways, but its underlying mechanism by which Xiaoyaosan regulates autophagy as well as GLUT4 in the hypothalamus remains unclear. Thus, in this study, we established a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and set up autophagy blockade as a control to explore whether Xiaoyaosan exerts antidepressant effect by affecting autophagy. We examined the effects of Xiaoyaosan on behaviors exhibited during the open field test, tail suspension test and sucrose preference test, and the changes in autophagy in hypothalamic neurons as well as changes in GLUT4 and the related indicators of glucose metabolism in CUMS-induced depressive mouse model. We found that CUMS- and 3-MA-induced mice exhibited depressive-like behavioral changes, with decreased LC3 expression and increased p62 expression, suggesting decreased levels of autophagy in the mouse hypothalamus. The expression of GLUT4 was also decreased, and it was closely related to the level of autophagy through Rab8 and Rab10. Nevertheless, after the intervention of Xiaoyaosan, the above changes were effectively reversed. These results show that Xiaoyaosan can regulate the autophagy in hypothalamic neurons and the expression of GLUT4 in depressed mice.

Xiaoyaosan Ameliorates Chronic Restraint Stress-Induced Depression-Like Phenotype by Suppressing A2AR Signaling in the Rat Striatum.

Depression is a common mental disorder characterized by pessimism and world-weariness. In our previous study, we found that Xiaoyaosan (XYS) could have antidepressive effects, however the underlying mechanisms remain unclear. Several studies have shown that adenosine A (2 A) receptor (A2AR) in the brain is a key point in the treatment of depression. Our present study aimed to investigate the effects of XYS on A2AR signaling in the striatum of rats exposed to chronic restraint stress (CRS). Ninety-six male Sprague-Dawley rats were randomly divided into 8 groups (control, model, negative control, XYS, A2AR antagonist, A2AR antagonist + XYS, A2AR agonist, A2AR agonist + XYS). The rats in the model group, XYS group, A2AR antagonist group and A2AR antagonist + XYS group were subjected to CRS for 3 h a day. The XYS decoction [2.224 g/(kg·d)] was intragastrical administered by oral gavage to the rats in the negative control group, XYS group, A2AR antagonist + XYS group, and A2AR agonist + XYS group. The rats in the A2AR antagonist group and A2AR antagonist + XYS group were treated with SCH 58261 [0.05 mg/(kg·d)], and the rats in the A2AR agonist and A2AR agonist + XYS group were treated with CGS 21680 [0.1 mg/(kg·d)]. These procedures were performed for 21 consecutive days. Behavioral studies including the open field test, elevated plus maze test, sucrose preference test and forced swimming test, were performed to examine depression-like phenotypes. Then, the effects of XYS on CRS- or A2AR agonist-induced striatal subcellular damage, microglial activation and A2AR signaling changes in the striatum were examined. Here, we report that XYS ameliorates depression-like phenotypes (such as body weight loss as well as depression- and anxiety-like behaviors) and improves synaptic survival and growth in the stratum of the CRS rats. Moreover, XYS reduces A2AR activity and suppresses hyper-activation of striatal microglia. The tissue and cellular effects of XYS were similar to those of the known A2AR antagonists. In conclusion, XYS alleviates depression in the CRS rats via inhibiting A2AR in the striatum.

Intestinal metastasis from choriocarcinoma: a case series and literature review.

BACKGROUND: Gestational choriocarcinoma is a rare trophoblastic tumor that spreads mainly to the lung, liver, and central nervous system. Fewer than 5% of patients present with metastasis to the gastrointestinal system and have a poor prognosis CASE PRESENTATION: We describe four cases of patients with intestinal metastasis from choriocarcinoma who visited the First Affiliated Hospital of Zhejiang University School of Medicine and the First People's Hospital of Hangzhou between April 2012 and October 2019. Four patients presented with gastrointestinal symptoms or developed gastrointestinal symptoms during treatment for choriocarcinoma. Three patients had these intestinal lesions surgically removed, and the postoperative pathology results suggested choriocarcinoma. All patients received multiple chemotherapy regimens during treatment for suboptimal human chorionic gonadotropin (hCG) levels; one patient died 22 months after a definitive diagnosis was made, and the other three patients are still undergoing regular follow-up. CONCLUSION: Given the low incidence of intestinal metastases from choriocarcinoma, the metastatic route of intestinal metastases from choriocarcinoma remains to be elucidated, and diagnosis mainly depends on pathology findings. An effective treatment has not been determined, and surgical excision with chemotherapy is generally accepted.

ACLP promotes activation of cancer-associated fibroblasts and tumor metastasis via ACLP-PPARγ-ACLP feedback loop in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Its fibrotic tumor microenvironment (TME) plays a crucial role in promoting tumor invasion and metastasis, which eventually leads to a dismal 5-year survival rate in PDAC patients. Aortic carboxypeptidase-like protein (ACLP) promotes tissue fibrosis in benign diseases. However, its role in cancer-associated fibrosis remains unelucidated. Here, we show that ACLP was mainly expressed in cancer-associated fibroblasts (CAFs) but not in cancer cells and highly expressed in PDAC tissues. High ACLP expression was correlated with poor overall survival. Moreover, ACLP expression in PDAC patients with liver metastases was higher than that in PDAC patients without liver metastases. By detecting activation marker expression and CAF contractility and motility, we found that ACLP promoted CAF activation in PDAC, leading to TME fibrosis. Furthermore, ACLP-activated CAFs could promote cancer cell invasion in vitro and tumor metastasis in vivo. Mechanistically, ACLP promotes the expressions of MMP1 and MMP3 in CAFs, thus promoting PDAC invasion and metastasis. Intriguingly, we identified an ACLP-PPARγ-ACLP feedback loop in PDAC CAFs. Abatement of this feedback loop might be a promising approach in CAF-targeting PDAC treatment.

Role of Emergency Surgery for Fatal Complications of Gestational Trophoblastic Neoplasia: A Single-Center Experience.

PURPOSE: High-risk gestational trophoblastic neoplasia (GTN) can lead to fatal complications; however, few reports have assessed emergency surgery as a treatment option for such complications. Thus, this study aimed to analyze the clinical features and prognosis of patients with GTN who underwent emergency surgery. PATIENTS AND METHODS: Thirteen patients with high-risk or ultra-high-risk GTN who underwent emergency surgery for fatal complications in the First Affiliated Hospital of Zhejiang University, School of Medicine from 2013 to 2020 were analyzed, and their medical records were reviewed. The patients' characteristics and treatment were evaluated with respect to outcomes. RESULTS: Thirteen patients with GTN who underwent 15 emergency surgical procedures were identified in our center. The mean International Federation of Gynecology and Obstetrics score of these patients was 14.8 (range, 11-19). Of the 13 patients, six underwent brain surgeries, such as tumor resection (n = 5) and conservative surgery (n = 1). All the patients received multi-agent chemotherapy after emergency surgery, and the mean time from emergency surgery to subsequent chemotherapy was 12.7 days. Of the 13 patients, 10 (77%) were cured and disease-free, with a follow-up period ranging from 3 months to 8 years. All the patients (n = 6) who underwent emergency brain surgery survived and achieved complete remission. CONCLUSION: For patients with high-risk GTN with fatal complications, especially brain lesions, emergency surgery combined with subsequent chemotherapy may provide a favorable prognosis.

Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota.

Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1ß and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated anti-inflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

Carabin Deficiency Aggravates Hepatic Ischemia-Reperfusion Injury Through Promoting Neutrophil Trafficking via Ras and Calcineurin Signaling.

Neutrophil infiltration plays an important role in the initial phase of hepatic ischemia and reperfusion injury (HIRI). Despite many different key molecules that have been reported to meditate neutrophil trafficking in HIRI, the mechanism of this process has not been fully elucidated. In this study, we found that Carabin deficiency in myeloid cells (LysMCre : Carabinfl/fl) aggravated IRI-induced hepatic injury and apoptosis through increasing the infiltration of CD11b+Ly6G+ neutrophils. ImmGen Datasets further revealed that Carabin was expressed in bone marrow neutrophils (GM.BM) but was significantly downregulated in thio-induced peripheral neutrophils (GN.Thio.PC), which was consistently verified by comparing GM.BM and liver-infiltrating neutrophils induced by IRI. Mechanistically, up-regulation of Carabin in GM.BM in vitro reduced the expression levels of P-selectin, E-selectin, and αvß3 integrin through inhibiting Ras-ERK and Calcineurin-NFAT signaling. Furthermore, blocking P-selectin, E-selectin, and αvß3 integrin in LysMCre : Carabinfl/fl mice decreased the frequency and number of CD11b+Ly6G+ neutrophils and reversed hepatic ischemia-reperfusion damage. In conclusion, our results provide a new understanding of Carabin, such that it is expressed and functions not only in adaptive immune cells (T and B cells) but also in innate immune cells (neutrophils), contributing to the migration of neutrophils. These findings provide novel and promising therapeutic targets for the prevention of HIRI during liver transplantation or hepatic surgery.

Nitric Oxide Synthase Regulates Gut Microbiota Homeostasis by ERK-NF-κB Pathway in Shrimp.

The gut microbiota is a complex group of microorganisms that is not only closely related to intestinal immunity but also affects the whole immune system of the body. Antimicrobial peptides and reactive oxygen species participate in the regulation of gut microbiota homeostasis in invertebrates. However, it is unclear whether nitric oxide, as a key mediator of immunity that plays important roles in antipathogen activity and immune regulation, participates in the regulation of gut microbiota homeostasis. In this study, we identified a nitric oxide synthase responsible for NO production in the shrimp Marsupenaeus japonicus. The expression of Nos and the NO concentration in the gastrointestinal tract were increased significantly in shrimp orally infected with Vibrio anguillarum. After RNA interference of Nos or treatment with an inhibitor of NOS, L-NMMA, NO production decreased and the gut bacterial load increased significantly in shrimp. Treatment with the NO donor, sodium nitroprusside, increased the NO level and reduced the bacterial load significantly in the shrimp gastrointestinal tract. Mechanistically, V. anguillarum infection increased NO level via upregulation of NOS and induced phosphorylation of ERK. The activated ERK phosphorylated the NF-κB-like transcription factor, dorsal, and caused nuclear translocation of dorsal to increase expression of antimicrobial peptides (AMPs) responsible for bacterial clearance. In summary, as a signaling molecule, NOS-produced NO regulates intestinal microbiota homeostasis by promoting AMP expression against infected pathogens via the ERK-dorsal pathway in shrimp.