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BackgroundHepatic fibrosis and its associated consequences continue to pose a substantial global health challenge. Developing novel approaches to hepatic fibrosis management and prevention is critically necessary. Radix Paeoniae Alba (RPA) is widely used in Traditional Chinese Medicine (TCM) to treat various diseases. Our earlier research found that a bioactive component of RPA had a dose-dependent effect on anti-allergic asthma. RPA reduces allergic asthma by slowing the hepatic wind, according to “Treatise on Febrile Diseases”. However, this bioactive fraction’s pharmacological effects and mechanisms on the liver are unknown.AimThis study examined the bioactive fraction MP-40, the methanol extract of RPA (MRPA), on bile duct ligation (BDL) for its anti-hepatic fibrosis activity and potential mechanisms.MethodsFirst, the effectiveness of MP-40 in treating BDL-induced hepatic fibrosis in mice and rats was evaluated through survival rates, ALT, AST HYP, and pathological changes. Molecular assays were performed using in vitro cultures of HSC-T6 activation. The expression of α-SMA and Collagen I evaluated fibro-tropic factors with HSC activation. Furthermore, the levels of pyroptosis were assessed by examining the expression of the pyroptosis-related proteins, including NLRP3, Cleaved Caspase-1, GSDMD-N, and 1L-1β. Additionally, the effective constituents of MP-40 were identified by extraction, separation, and identification. Finally, PF and TGG, as the delegate compounds of MP-40, were tested to confirm their inhibition effects on HSC-T6 activation.ResultsThe findings demonstrated that MP-40 and MRPA could lower ALT, AST, and HYP levels, boost survival rates, and reduce liver damage in BDL mice and rats. Furthermore, MP-40 outperforms MRPA. MP-40 was proven to drastically diminish fibrotic α-SMA and Collagen I. The expression of pyroptosis-related proteins NLRP3, Cleaved Caspase-1, TGF-β1, GSDMD-N, and 1L-1β decreased. MP-40 inhibited the synthesis of pyroptosis-related proteins more effectively than MCC950 (an NLRP3-specific inhibitor). Monoterpene glycosides and tannins were shown to be the most potent MP-40 components. Finally, the delegate compounds MP-40, PF, and TGG were shown to have substantial inhibitory effects on HSC-T6 activation.ConclusionThe results proved that MP-40 alleviates BDL-induced cholestatic hepatic fibrosis by inhibiting NLRP3-mediated pyroptosis. PF and TGG play a role in treating BDL-induced cholestatic hepatic fibrosis in MP-40.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. Methods Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. Results We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. Conclusion PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.

Phytophthora sojae (Kauffman and Gerdemann) is an oomycete pathogen that threatens soybean (Glycine max L.) production worldwide. The development of soybean cultivars with resistance to this pathogen is of paramount importance for the sustainable management of the disease. The objective of this study was to identify genomic regions associated with resistance to P. sojae isolate 40468 through genome-wide association analyses of 983 soybean germplasms. To elucidate the genetic basis of resistance, three statistical models were employed: the compressed mixed linear model (CMLM), Bayesian-information and linkage disequilibrium iteratively nested keyway (BLINK), and fixed and random model circulating probability unification (FarmCPU). The three models consistently identified a genomic region (3.8–5.3 Mbp) on chromosome 3, which has been previously identified as an Rps cluster. A total of 18 single nucleotide polymorphisms demonstrated high statistical significance across all three models, which were distributed in eight linkage disequilibrium (LD) blocks within the aforementioned interval. Of the eight, LD3-2 exhibited the discernible segregation of phenotypic reactions by haplotype. Specifically, over 93% of accessions with haplotypes LD3-2-F or LD3-2-G displayed resistance, whereas over 91% with LD3-2-A, LD3-2-C, or LD3-2-D exhibited susceptibility. Furthermore, the BLINK and FarmCPU models identified new genomic variations significantly associated with the resistance on several other chromosomes, indicating that the resistance observed in this panel was due to the presence of different alleles of multiple Rps genes. These findings underscore the necessity for robust statistical models to accurately detect true marker–trait associations and provide valuable insights into soybean genetics and breeding.

IntroductionPholiota nameko is a widely consumed edible fungus. This study focuses on two crucial developmental stages of Pholiota nameko, namely, mycelium and ascospores. The objectives of this research were to investigate changes in microbial diversity and community structure during the growth of Pholiota nameko and to analyze the adaptability of the dominant strains to their respective habitats through metabolic.MethodsSpecifically, we conducted second-generation sequencing of the 16S rRNA gene (Illumina) on samples obtained from these stages. In addition, we isolated and characterized endophytes present in Pholiota nameko, focusing on examining the impact of dominant endophyte genera on autolysis. We also conducted a metabolic pathway analysis.Results and discussionThe results unveiled 578,414 valid sequences of Pholiota nameko endophytic fungi. At the phylum level, the dominant taxa were Basidiomycota, Ascomycota, Zoopagomycota, and Mucoromycota. At the genus level, the dominant taxa observed were Pholiota, Inocybe, Fusarium, and Hortiboletus. For endophytic bacteria, we obtained 458,475 valid sequences. The dominant phyla were Proteobacteria, TM6, Firmicutes, and Bacteroidetes, while the dominant genera were Edaphobacter, Xanthomonas, Burkholderia, and Pseudomonas. Moreover, we identified the isolated strains in Pholiota nameko using 16S rDNA, and most of them were found to belong to the genus Pseudomonas, with Pseudomonas putida being the most prevalent strain. The findings revealed that the Pseudomonas putida strain has the ability to slow down the breakdown of soluble proteins and partially suppress the metabolic processes that generate superoxide anion radicals in Pholiota nameko, thereby reducing autolysis. Additionally, our results demonstrated that molybdenum enzyme-mediated anaerobic oxidative phosphorylation reactions were the primary energy metabolism pathway in the Pseudomonas putida strain. This suggests that the molybdenum cofactor synthesis pathway might be the main mechanism through which Pholiota nameko adapts to its complex and diverse habitats.

Abstract Background Immune inflammatory responses play an important role in spinal cord injury (SCI); however, the beneficial and detrimental effects remain controversial. Many studies have described the role of neutrophils, macrophages, and T lymphocytes in immune inflammatory responses after SCI, although little is known about the role of B lymphocytes, and immunosuppression can easily occur after SCI. Methods A mouse model of SCI was established, and HE staining and Nissl staining were performed to observe the pathological changes. The size and morphology of the spleen were examined, and the effects of SCI on spleen function and B cell levels were detected by flow cytometry and ELISA. To explore the specific mechanism of immunosuppression after SCI, B cells from the spleens of SCI model mice were isolated using magnetic beads and analyzed by 4D label-free quantitative proteomics. The level of inflammatory cytokines and iron ions were measured, and the expression of proteins related to the Tom20 pathway was quantified by western blotting. To clarify the relationship between iron ions and B cell pyroptosis after SCI, we used FeSO4 and CCCP, which induce oxidative stress to stimulate SCI, to interfere with B cell processes. siRNA transfection to knock down Tom20 (Tom20-KD) in B cells and human B lymphocytoma cell was used to verify the key role of Tom20. To further explore the effect of iron ions on SCI, we used deferoxamine (DFO) and iron dextran (ID) to interfere with SCI processes in mice. The level of iron ions in splenic B cells and the expression of proteins related to the Tom20–Bax–caspase–gasdermin E (GSDME) pathway were analyzed. Results SCI could damage spleen function and lead to a decrease in B cell levels; SCI upregulated the expression of Tom20 protein in the mitochondria of B cells; SCI could regulate the concentration of iron ions and activate the Tom20–Bax–caspase–GSDME pathway to induce B cell pyroptosis. Iron ions aggravated CCCP-induced B cell pyroptosis and human B lymphocytoma pyroptosis by activating the Tom20–Bax–caspase–GSDME pathway. DFO could reduce inflammation and promote repair after SCI by inhibiting Tom20–Bax–caspase–GSDME-induced B cell pyroptosis. Conclusions Iron overload activates the Tom20–Bax–caspase–GSDME pathway after SCI, induces B cell pyroptosis, promotes inflammation, and aggravates the changes caused by SCI. This may represent a novel mechanism through which the immune inflammatory response is induced after SCI and may provide a new key target for the treatment of SCI.

With low gluten wheat flour as main raw material, Cordyceps militaris egg rolls were made by adding C. militaris powder, egg liquid, yellow cream and white granulated sugar, etc. Methods: Box-Behnken multiple regression model was constructed through single factor test and response surface methodology to optimize the formula of C. militaris egg rolls. Texture parameters were determined by TMS-PRO texture analyzer, and product performance indexes were determined according to the national food safety standards. Results：The optimum formula for egg rolls was as follows, C. militaris powder 6%, egg liquid 25%, white granulated sugar 30%, and yellow cream 37% based on the total amount of low gluten wheat flour. Under the optimal conditions, the sensory score of C. militaris egg rolls was up to 91.0 points. All the performance indexes were in line with the national safety standards, and had good water and oil retention. The hardness of C. militaris egg rolls was 34.03±0.49 N, adhesion was −1.34±0.01 N·s, the cohesiveness was 0.13±0.01 mJ, mastication was 3.36±0.23 N, the elasticity was 0.76±0.01 mm. Conclusion：Compared with the whole powder egg rolls, C. militaris egg rolls had better nutritional values with characteristics of high protein, high fat, high cordycepin, high water holding capacity and low oil holding capacity.

ObjectiveThis aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs.MethodsA total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0.ResultsSomatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions.ConclusionThis study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.

In traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement’s substance is unclear. Differences in quality are intimately correlated with a plant’s metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments.

BackgroundCircular RNAs (circRNAs) are types of endogenous noncoding RNAs produced by selective splicing that are expressed highly specifically in various organisms and tissues and have numerous clinical implications in the regulation of cancer development and progression. Since circRNA is resistant to digestion by ribonucleases and has a long half-life, there is increasing evidence that circRNA can be used as an ideal candidate biomarker for the early diagnosis and prognosis of tumors. In this study, we aimed to reveal the diagnostic and prognostic value of circRNA in human pancreatic cancer (PC).MethodsA systematic search for publications from inception to 22 July 2022 was conducted on Embase, PubMed, Web of Science (WOS), and the Cochrane Library databases. Available studies that correlated circRNA expression in tissue or serum with the clinicopathological, diagnostic, and prognostic values of PC patients were enrolled. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to evaluate clinical pathological characteristics. Area under the curve (AUC), sensitivity, and specificity were adopted to assess diagnostic value. Hazard ratios (HRs) were utilized to assess disease-free survival (DFS) and overall survival (OS).ResultsThis meta-analysis enrolled 32 eligible studies, including six on diagnosis and 21 on prognosis, which accounted for 2,396 cases from 245 references. For clinical parameters, high expression of carcinogenic circRNA was significantly associated with degree of differentiation (OR = 1.85, 95% CI = 1.47–2.34), TNM stage (OR = 0.46, 95% CI = 0.35–0.62), lymph node metastasis (OR = 0.39, 95% CI = 0.32–0.48), and distant metastasis (OR = 0.26, 95% CI = 0.13–0.51). As for clinical diagnostic utility, circRNA could discriminate patients with pancreatic cancer from controls, with an AUC of 0.86 (95% CI: 0.82–0.88), a relatively high sensitivity of 84%, and a specificity of 80% in tissue. In terms of prognostic significance, carcinogenic circRNA was correlated with poor OS (HR = 2.00, 95% CI: 1.76–2.26) and DFS (HR = 1.96, 95% CI: 1.47–2.62).ConclusionIn summary, this study demonstrated that circRNA may act as a significant diagnostic and prognostic biomarker for pancreatic cancer.

Mushroom dietary fiber is a type of bioactive macromolecule derived from the mycelia, fruiting bodies, or sclerotia of edible or medicinal fungi. The use of mushroom dietary fiber as a prebiotic has recently gained significant attention for providing health benefits to the host by promoting the growth of beneficial microorganisms; therefore, mushroom dietary fiber has promising prospects for application in the functional food industry and in drug development. This review summarizes methods for the preparation and modification of mushroom dietary fiber, its degradation and metabolism in the intestine, its impact on the gut microbiota community, and the generation of short-chain fatty acids (SCFAs); this review also systematically summarizes the beneficial effects of mushroom dietary fiber on host health. Overall, this review aims to provide theoretical guidance and a fresh perspective for the prebiotic application of mushroom dietary fiber in the development of new functional foods and drugs.

The non-metallic inclusions in steel mainly come from the deoxidization process of molten steel. Based on the different deoxidization processes of GCr15 bearing steel produced by a domestic steel plant, the single deoxidization curves of Al, Si, and Mn and the compound deoxidization curves of Al-Si and Si-Mn under pure molten iron and GCr15 bearing steel production conditions were calculated with the FactSage 8.1 thermodynamic software. The results show that the deoxidization curves under the two conditions are quite different. At the same time, the Al-Ti deoxidation equilibrium curve under the condition of GCr15 bearing steel was calculated. It was found that when [Ti] < 0.0015% in the steel, the equilibrium deoxidation product was Al2O3, and no titanium oxide was generated. Finally, a thermodynamic calculation and analysis of the effect of rare-earth Ce content on the modification of inclusions in GCr15 bearing steel were carried out. The results showed that when T = 1873 K, the rare-earth Ce treatment of aluminum deoxidized the GCr15 bearing steel; when [Al] = 0.015%, Al2O3 inclusions increased with the increase in [Ce] content, and the evolution path was Al11O18Ce→CeAlO3→Ce2O3. When [Si] = 0.28%, [O] > 50 ppm, and CeCrO3 and [O] 0.012% appeared. CeS inclusions appeared in the steel, and the final equilibrium product was CeS + Ce2O3. When [Ce] < 0.012%, CeS was not produced in the steel, and only Ce2O3 existed.

Abstract Background Increasing studies focused on the regulatory roles of circular RNAs (circRNAs) in diverse cancers. This study was to evaluate the function and mechanism of circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) in esophageal cancer (EC). Methods The circ-SFMBT2, microRNA-107 (miR-107) and solute-linked carrier family A1 member 5 (SLC1A5) levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay and EdU assay. Cell apoptosis and invasion were detected by flow cytometry and transwell assay. Glutamine metabolism was assessed by the corresponding kits for glutamine consumption, α-ketoglutarate production and glutamate production. Western blot was used for protein quantification. The binding analysis was performed using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays. The functional research of circ-SFMBT2 in vivo was performed by xenograft tumor assay. Exosomes were identified by morphological observation and protein detection. Results Circ-SFMBT2 was overexpressed in EC samples and cells. Circ-SFMBT2 downregulation inhibited EC cell proliferation, invasion and glutamine metabolism. Circ-SFMBT2 targeted miR-107 and the regulation of circ-SFMBT2 was achieved by sponging miR-107. SLC1A5 was a target of miR-107, and it worked as an oncogene in EC cells. MiR-107 retarded the EC progression by downregulating SLC1A5. Circ-SFMBT2 could affect the SLC1A5 expression by targeting miR-107. Circ-SFMBT2 regulated EC progression in vivo by miR-107/SLC1A5 axis. Circ-SFMBT2 was transferred by exosomes in EC cells. Conclusion These results suggested that circ-SFMBT2 upregulated the SLC1A5 expression to promote the malignant development of EC by serving as a miR-107 sponge.

Volatile organoamines exist widely in various industrial and commercial products. The chronic and prolonged exposure to amines can compromise human health and cause even the risk of serious illness. Herein, the aggregation of ZnO decorated with g-C3N4 (ZOCN) is synthesized and it can serve as enhanced sensitive sensor for the detection of dimethylamine (DMA). The structure, morphology, composition and band structure of the materials are characterized by various analytical techniques. The results show that, controllable additions of g-C3N4 affect self-assemble of nanoparticles and aggregation structure, even energy band, as confirmed by DFT calculation. Notably, the formed heterojunction is conductive to electron transfer and adsorption of more O2 molecules to form reactive oxygen species, thereby promoting the reaction between oxygen and DMA and leading to high sensitivity to DMA with a detection limit of 920 ppb and about 2.5 times higher sensitivity than pristine ZnO. ZOCN-based sensor shows a high selectivity to DMA, a fast response time (1 s) and a fast recovery time (40 s) to various concentrations of gas phase DMA at low temperatures. Additionally, the sensor exhibits a linear relationship between the response and concentration of DMA vapor in a wide concentration range, a characteristic that is desirable for quantitative analysis in gas sensors.

Summary: The formation of thermodynamically accessible metallacycle is crucial to achieve site-selective C–H bond activation. Here, we report an isocyanide-bridging C–H activation through the formation of a five-membered palladacycle. As such, a proximal C–H bond in aldehyde moiety is activated selectively. The subsequent palladium shift and intramolecular C=N bond insertion construct a valuable isoindolinone framework. Compared with conventional isocyanide-promoted C–H bond activation, both carbon and nitrogen atoms in isocyanide are engaged in new bond formations. Notably, three types of isoindolinones can be obtained selectively by variations of the reaction conditions. Mechanistic studies shed light on the reaction pathways. Moreover, the synthetic potential of current methodology is demonstrated by providing concise routes to key intermediates of indoprofen, indobufen, aristolactams, lennoxamine, and falipamil.

Volatile organoamines are important industrial raw materials and chemicals. Long-term exposure to amines could be harmful to human health and even cause serious pollution. In this study, SnO2 decorated g-C3N4 material was fabricated and used as a sensor material for the detection of ethanolamine (EA). The structures, morphology, surface chemical states, and band structure were characterized, and gas sensing was studied. The results showed that SnO2 nanoparticles were dispersed on g-C3N4, and band structure was dependent on g-C3N4 doping. Notably, the interface heterojunction was conducive to electron transferring and O2 molecule adsorption; the formed reactive oxygen species enhanced the reaction between oxygen and EA, thus leading to high sensitivity to EA. This composite exhibited a high response that was 2.6 times higher than that of pure SnO2, and the detection limit reached 294 ppb. A g-C3N4/SnO2-based sensor displayed a high selectivity to EA with a fast response time (1 s) and recovery time (20 s) at low operating temperatures. In particular, this sensor exhibited a linear relationship between the response and concentration, which is required for quantitative analysis.

Pleomorphic adenoma gene like-2 (PLAGL2) has been implicated in the development and progression of diverse malignancies, including glioblastoma. An increasing number of studies have reported that dysregulated expression of PLAGL2 is a common phenomenon in different malignancies. However, the mechanism and biological functions of PLAGL2 in patients with high-grade glioma (HGG) remain unclear. In addition, the expression and clinical significance of PLAGL2 in HGG have not yet been reported. Herein, we investigated the expression patterns and prognostic values of PLAGL2 in patients with HGG by using various databases, including Tumor Immune Estimation Resource 2.0 (TIMER2.0), GENT2, ONCOMINE, GEPIA, Human Protein Atlas, and Gene Expression Omnibus datasets. In the present study, we analyzed the relationship between PLAGL2 mRNA expression and clinical parameters in 184 HGG cases and found that PLAGL2 presented positively high expression and was relevant to poor prognosis. Immunohistochemistry analysis confirmed the overexpression of PLAGL2 protein, which is mainly expressed in the nucleus of glioma. Additionally, a high level of expression of the PLAGL2 gene was associated with lower survival in progression-free survival and overall survival in GBM patients. The correlation analysis between PLAGL2 and immune infiltration related to the abundance of B cells, CD8+ T cells, CD4+ T cells, macrophages, DCs, and neutrophils was also performed using TIMER2.0. GSEA results showed that high PLAGL2 expression was associated with cell migration, proliferation, actin cytoskeletal, and angiogenesis. To sum up, our findings indicated that PLAGL2 could serve as an independent prognostic biomarker and might be a potential therapeutic target for HGG, which should be further investigated.

Soybean [Glycine max (L.) Merr.] is an economically important crop with high protein and oil contents. A range of biotic stresses constantly threaten soybean production and lead to decreases in yield and quality, but bacterial pustule caused by Xanthomonas citri pv. glycines (Xcg) is one of the most destructive diseases affecting worldwide soybean production. This review provides an extensive summary of multidisciplinary research on the soybean–Xcg interaction. First, we introduce general biological features of the causal agent Xcg as well as symptoms of the bacterial pustule disease it causes. Second, we review the geographic distribution of and genetic changes in the Xcg population over time, based on molecular evidence from recent studies. Third, we integrate several published studies to identify resistance loci against Xcg using bi-parental mapping populations and collections of germplasm along with genetic sources and molecular markers associated with resistance. Fourth, we summarize the molecular interactions between soybean and Xcg. Lastly, we discuss perspectives on future genomic research and breeding for improved resistance to Xcg in soybean.

Digestive diseases have become an important source of morbidity and mortality. The considerable financial and health burdens caused by digestive diseases confirm the importance of extensive research to better understand and treat these diseases. The development of reliable preclinical models is essential for understanding the pathogenesis of digestive diseases and developing treatment and prevention methods. However, traditional established cell lines and animal models still have many limitations in the study of the digestive system. Conditional reprogramming (CR) cell culture is a newly developed primary technology that uses irradiated Swiss-3T3-J2 mouse fibroblast cells and the Rho-associated kinase (ROCK) inhibitor Y-27632 to rapidly and efficiently generate many cells from diseased and normal tissues. CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and recapitulate the histological and genomic features of the original tissue. Moreover, after removing these conditions, the phenotype was completely reversible. Therefore, CR technology may represent an ideal model to study digestive system diseases, to test drug sensitivity, to perform gene profile analysis, and to undertake xenograft research and regenerative medicine. Indeed, together with organoid cultures, CR technology has been recognized as one of the key new technologies by NIH precision oncology and also used for NCI human cancer model initiatives (HCMI) program with ATCC. In this article, we review studies that use CR technology to conduct research on diseases of the digestive system.

Background: The main reason for esophageal squamous cell carcinoma (ESCC) treatment failure is metastasis. Little is known about the mechanisms involved in the metastasis of ESCC, and there is a lack of effective therapeutic targets. In our previous study, we found that patients with high levels of BC200 tended to have poor prognoses.Methods: First, we applied qRT-PCR to detect the expression level of BC200 in normal esophageal squamous epithelial cells and ESCC cells with different degrees of differentiation ability. Then, we changed BC200 expression by transfecting constructed lentiviruses that included BC200 shRNA (LV-BC200-shRNA, KD), negative control (CON053, NC), or BC200 gene (LV-BC200, BC200) to create BC200-deficient cell models in KYSE410 and KYSE70 cells and BC200 overexpression cell models in EC9706 cells and verified the transfection effect by qRT-PCR. Then, we examined cell migration by wound healing assay, invasion by Transwell assay, and proliferation by MTT assay and examined the metastasis ability in a xenograft mouse model. Gene expression profiling was performed to screen a panel of mRNAs following inhibition of BC200 expression. We then used ingenuity pathway analysis (IPA) to analyze the functions of the changed molecules and their interactions. The results from the microarray were validated by qRT-PCR and Western blotting.Results: In this study, we found that the expression of BC200 in poorly differentiated cell lines was significantly higher than that in well-differentiated cell lines. BC200 can significantly promote the migration and invasion but not the proliferation ability of ESCC cells in vitro and BC200 shRNA can significantly suppress tumor metastasis in vivo. Our genome-wide expression profile chip showed 406 differentially expressed genes, with 91 upregulated genes and 315 downregulated genes. The upstream regulator analysis showed that ATF4 was predicted to be strongly inhibited and 21 genes were consistently inhibited by this gene. Our qRT-PCR and Western blotting data also identified the reduced expression of ATF4 and some selected downstream genes, such as SNAIL2, GADD45A, and PSAT1, as a consequence of downregulating BC200 expression in ESCC.Conclusion: Our data showed that BC200 promoted the metastasis of ESCC cells and could regulate the expression of ATF4 and its downstream genes.

Abstract Background SKA1, an important mitosis protein, has been indicated in the initiation and progression of several malignancies. However, its clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated. Methods mRNA expression of SKA1 was examined in 126 HCC and paired non-neoplastic tissues using real-time PCR and validated in The Cancer Genome Atlas (TCGA) database. SKA1 protein expression was detected using immunohistochemistry in the 126 HCC tissues and its associations with clinicopathological parameters and prognosis were analyzed. Hierarchical cluster analysis and gene set enrichment analysis (GSEA) were performed in selected Gene Expression Omnibus data sets. Results SKA1 mRNA expression was significantly elevated in HCC tissues from both local hospital and TCGA database. Immunohistochemistry revealed that increased SKA1 expression was present in 65 of the 126 cases and was significantly associated with higher serum alpha-fetoprotein concentration, larger tumor size and higher TNM stage. Patients with positive SKA1 expression showed significantly worse overall and relapse-free survival. Multivariate Cox regression analysis revealed that SKA1 was an independent predictor of patient prognosis. Gene expression profiling analysis of public data showed that high-SKA1 expression HCC tissues had similar gene expression profiles with fetal liver tissues. Moreover, GSEA showed that genes up-regulated in high SKA1 HCC subgroup were significantly enriched in cell cycle pathway, while genes down-regulated were significantly enriched in apoptosis pathway. Conclusions Our findings indicate that the oncofetal gene SKA1 might be involved in the progression of the HCC and could serve as a prognostic marker for HCC.

Abstract Background Opacification of hydrophobic and hydrophilic intraocular lenses (IOLs) has been reported. Herein, we report a case of spontaneous resolution of opacification following acute clouding of a trifocal IOL, which consisted of hydrophilic acrylic material (25%) with hydrophobic surface properties, occurring in a cold region in the winter season. Case presentation A young adult with bilateral radiation cataract underwent phacoemulsification using a femtosecond laser and implantation of a trifocal IOL. The trifocal IOL was delivered to the operating theatre 30 min before the surgery. The outside temperature was approximately − 7 °C. The IOL package was warmed using a radiator at approximately 35 °C for 15 min. After the optical region was implanted in the eye, cloudiness was observed, which persisted throughout the operation. Complete clearing of the IOL was apparent after three postoperative hours. Conclusion In this case, rapid opacification and clearing of the IOL suggested an acute and transient process. IOLs should be stored and shipped at a constant temperature, and sudden temperature fluctuations should be avoided, especially in the colder seasons.

B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV) domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers.

Tumors are one of the diseases that seriously endanger human life and health. The existing treatments can cause side effects and drug resistance. The anti-cancer potential of medicinal mushrooms has attracted much attention due to their safety and efficacy. Understanding the research hotspots and trends in this field provides ideas and basis for Mycomedicine to treat tumors. The English literatures related to the antitumor effects of Mycomedicine were searched through Web of Science (WOS), PubMed (PM), and Elsevier ScienceDirect (SD) from January 1, 2012 to December 31, 2021. CiteSpace and VOSviewer were used to analyze and display the high frequency ranking of literatures, author collaboration view, keyword co-occurrence and clustering, and the network of issuing institutions and the number of articles issued. After screening, a total of 5,342 English literatures were included in the analysis. The most popular antitumor bacteriophages were Ganoderma lucidum, Poria, Morus alba, and Cordyceps sinensis. The high-frequency keywords were "Ganoderma lucidum triterpenoid", "Ganoderma lucidum acid", and "Biological activity". The related literature focused on the basic research of the extraction and structural properties of the active substances of edible and medicinal mushrooms and the anti-tumor mechanism of the mushroom components. Compared with traditional anticancer therapies, Mycomedicine demonstrated higher safety and multi-target pharmacological efficacy. The Mycomedicine activity analysis, reagent development, and antitumor mechanism research would become the main trend of future development in this field. [ABSTRACT FROM AUTHOR]