Clinical diagnosis and treatment of 37 cases of gallbladder neuroendocrine carcinoma.

OBJECTIVE: This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). METHODS: Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. RESULTS: Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89-30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61-7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67-43.33 months) for Group 3 (n = 4), and 19 months (range 7.89-30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). CONCLUSION: Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.

Tumor Necrosis Factor Alpha-Induced Protein-3 Inhibits the Activation of Hepatic Stellate Cells by Regulating the p65 Molecule in the NF-κB Signaling Pathway.

Tumor necrosis factor alpha-induced protein-3, also called A20, is a zinc-finger protein that participates in various inflammatory responses; however, the putative relationship between A20 and hepatic fibrosis remains unelucidated. Therefore, we investigated the role and mechanism of action of A20 in activating hepatic stellate cells (HSC) during the progression of hepatic fibrosis. Cell counting kit-8 (CCK8), colony growth, transwell assays, cell cycle analysis, and apoptosis assays were performed to explore the effect of A20 on cell function in vitro. An interspecies intravenous injection of the adeno-associated virus was used to assess the in vivo role of A20. The regulation of A20 on p65 was detected using mass spectrometry and immunoprecipitation. Our findings revealed that A20 was highly expressed in the liver tissues of patients with hepatic fibrosis and that the expression level of A20 in the liver tissue was closely correlated with the stage of liver fibrosis. In the LX-2 cell line, the downregulation of A20 upregulated the expression of fibrosis-related proteins and increased the expression of inflammatory factors, indicating the activation of HSC and vice versa. In addition, overexpression of A20 in mice reduced the degree of liver fibrosis in thioacetamide model mice. Finally, co-immunoprecipitation demonstrated that A20 could interact with p65. Hence, A20 inhibits HSC activation by binding to p65.

Screening of high-efficiency nitrogen-fixing bacteria from the traditional Chinese medicine plant Astragalus mongolicus and its effect on plant growth promotion and bacterial communities in the rhizosphere.

BACKGROUND: Astragalus mongolicus Bunge is used in traditional Chinese medicine and is thus cultivated in bulk. The cultivation of A. mongolicus requires a large amount of nitrogen fertilizer, increasing the planting cost of medicinal materials and polluting the environment. Isolation and screening of plant growth-promoting rhizobacteria (PGPR) and exploring the nitrogen fixation potential of A. mongolicus rhizosphere microorganisms would effectively reduce the production cost of A. mongolicus. RESULTS: This study used A. mongolicus roots and rhizosphere soil samples from Longxi County of Gansu Province, Jingle County, and Hunyuan County of Shanxi Province, China, to isolate and identify nitrogen-fixing bacteria. Through nitrogen fixation efficiency test, single strain inoculation test, and plant growth-promoting characteristics, three strains, Bacillus sp. J1, Arthrobacter sp. J2, and Bacillus sp. G4 were selected from 86 strains of potential nitrogen-fixing bacteria, which were the most effective in promoting the A. mongolicus growth and increasing the nitrogen, phosphorus, and potassium content in plants. The antagonistic test showed that these bacteria could grow smoothly under the co-culture conditions. The J1, J2, and G4 strains were used in a mixed inoculum and found to enhance the biomass of A. mongolicus plants and the accumulation of the main medicinal components in the field experiment. Mixed bacterial agent inoculation also increased bacterial diversity and changed the structure of the bacterial community in rhizosphere soil. Meanwhile, the relative abundance of Proteobacteria increased significantly after inoculation, suggesting that Proteobacteria play an important role in plant growth promotion. CONCLUSIONS: These findings indicate that specific and efficient PGPRs have a significant promoting effect on the growth of A. mongolicus, while also having a positive impact on the structure of the host rhizosphere bacteria community. This study provides a basis for developing a nitrogen-fixing bacterial fertilizer and improving the ecological planting efficiency of A. mongolicus.

CandiHap: a haplotype analysis toolkit for natural variation study.

Haplotype blocks greatly assist association-based mapping of casual candidate genes by significantly reducing genotyping effort. The gene haplotype could be used to evaluate variants of affected traits captured from the gene region. While there is a rising interest in gene haplotypes, much of the corresponding analysis was carried out manually. CandiHap allows rapid and robust haplotype analysis and candidate identification preselection of candidate causal single-nucleotide polymorphisms and InDels from Sanger or next-generation sequencing data. Investigators can use CandiHap to specify a gene or linkage sites based on genome-wide association studies and explore favorable haplotypes of candidate genes for target traits. CandiHap can be run on computers with Windows, Mac, or UNIX platforms in a graphical user interface or command line, and applied to any species, such as plant, animal, and microbial. The CandiHap software, user manual, and example datasets are freely available at BioCode (https://ngdc.cncb.ac.cn/biocode/tools/BT007080) or GitHub (https://github.com/xukaili/CandiHap). Supplementary information: The online version contains supplementary material available at 10.1007/s11032-023-01366-4.

Effect of accessory hepatic artery reconstruction on prognosis in orthotopic liver transplantation: a single center experience.

BACKGROUND: In orthotopic liver transplantation (OLT), preserving an aberrant hepatic artery (AHA) can increase the number of arterial anastomoses and may lead to arterial-related complications. AHA includes accessory hepatic artery and replaced hepatic artery. Herein, the purpose of our research is to evaluate the requirement for accessory anastomosis in OLT. METHODS: We retrospectively reviewed a total of 95 patients who underwent OLT in our hospital between April 2020 and December 2022. We found seven cases of donor livers with accessory HA. The method of arterial anastomosis and details of the diagnosis and treatment of complications were collated. RESULTS: Among 95 consecutive patients with OLT, complications occurred in two of seven patients-patient 2 had an accessory right hepatic artery, while patient 5 had an accessory left hepatic artery. Patient 2 showed bile leakage leading to rupture and bleeding of the accessory HA anastomosis after OLT, and was treated with interventional coil embolization. In patient 5, hepatic artery thrombosis and accessory HA occlusion were treated with embolization and thrombolysis of the splenic artery and left gastric artery. During the intervention, we also found that the internal hepatic artery and accessory HA had communicating branches. After treatment, both patients remain healthy with no complications such as liver necrosis or liver abscess. CONCLUSION: An AHA can be ligated when assessed as an accessory artery. This can reduce the incidence of arterial complications, contribute to the perioperative management of liver transplantation (LT) patients, and improve the prognosis of LT.

A Localization and Mapping Algorithm Based on Improved LVI-SAM for Vehicles in Field Environments.

Quickly grasping the surrounding environment's information and the location of the vehicle is the key to achieving automatic driving. However, accurate and robust localization and mapping are still challenging for field vehicles and robots due to the characteristics of emptiness, terrain changeability, and Global Navigation Satellite System (GNSS)-denied in complex field environments. In this study, an LVI-SAM-based lidar, inertial, and visual fusion using simultaneous localization and mapping (SLAM) algorithm was proposed to solve the problem of localization and mapping for vehicles in such open, bumpy, and Global Positioning System (GPS)-denied field environments. In this method, a joint lidar front end of pose estimation and correction was designed using the Super4PCS, Iterative Closest Point (ICP), and Normal Distributions Transform (NDT) algorithms and their variants. The algorithm can balance localization accuracy and real-time performance by carrying out lower-frequency pose correction based on higher-frequency pose estimation. Experimental results from the complex field environment show that, compared with LVI-SAM, the proposed method can reduce the translational error of localization by about 4.7% and create a three-dimensional point cloud map of the environment in real time, realizing the high-precision and high-robustness localization and mapping of the vehicle in complex field environments.

Efficacy and safety of maintenance immune checkpoint inhibitors with or without pemetrexed in advanced non-squamous non-small cell lung cancer: a retrospective study.

BACKGROUND: Advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients without driver gene mutations are usually treated with immune checkpoint inhibitors (ICIs) plus pemetrexed as maintenance therapy after first-line ICIs plus 4-6 cycles of pemetrexed/platinum. Some patients in the real world receive ICIs monotherapy as maintenance therapy. No clinical study has compared the efficacy and safety of ICIs with or without pemetrexed as maintenance therapy. METHODS: We performed a retrospective study analyzing clinical data of patients with NS-NSCLC who were diagnosed in Zhejiang Cancer Hospital from September 2018 to May 2021 and received maintenance therapy after 4-6 cycles of ICIs plus pemetrexed/platinum. Patients were divided into ICIs plus pemetrexed group and ICIs monotherapy group. Progression Free Survival 1 (PFS1) and PFS2, defined as the interval from the date of initial treatment and maintenance therapy to the date of systemic progression/death or the last follow-up, respectively. RESULTS: A total of 120 patients received ICIs with or without pemetrexed as maintenance therapy. Eighty-two patients received ICIs plus pemetrexed as maintenance therapy, and 38 patients received ICIs monotherapy. There were no statistically significant difference in median PFS1 between the ICIs monotherapy group and ICIs plus pemetrexed group (12.00 months vs. 12.07 months, P = 0.979). Among patients with PD-L1 TPS < 1%, the median PFS1 was worse with ICIs monotherapy (9.50 months vs. 14.20 months, P = 0.039). Among patients with PD-L1 TPS ≥50% or 1-49%, the median PFS1 in both groups was not statistically significant (P = 0.866, P = 0.589, respectively). Results for median PFS2 were similar to median PFS1, with statistically significantly different only in patients with PD-L1 TPS < 1% (P = 0.008). The 2-year survival rates of the two groups were similar (66.7% vs. 69.5%, P = 0.812). The incidence of fatigue was significantly higher in the ICIs plus pemetrexed group (P = 0.023). CONCLUSIONS: ICIs with or without pemetrexed can be used as maintenance therapy after first-line ICIs plus 4-6 cycles of pemetrexed/platinum in patients with advanced NS-NSCLC based on PD-L1 expression.

Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research.

OBJECTIVE: To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels. METHODS: The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction. RESULTS: In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012-0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132-0.926]). CONCLUSIONS: Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Regional assemblages shaped by historical and contemporary factors: Evidence from a species-rich insect group.

Understanding diversity patterns requires accounting for the roles of both historical and contemporary factors in the assembly of communities. Here, we compared diversity patterns of two moth assemblages sampled from Taihang and Yanshan mountains in Northern China and performed ancestral range reconstructions using the Multi-State Speciation and Extinction model, to track the origins of these patterns. Further, we estimated diversification rates of the two moth assemblages and explored the effects of contemporary ecological factors. From 7,788 specimens we identified 835 species belonging to 23 families, using both DNA barcode analysis and morphology. Moths in Yanshan mountains showed higher species diversity than in Taihang mountains. Ancestral range analysis indicated Yanshan as the origin, with significant historical dispersals from Yanshan to Taihang. Asymmetrical diversification, population expansion, along with frequent and considerable gene flow were detected between communities. Moreover, dispersal limitation or the joint effect of environment filtering and dispersal limitation were inferred as main driving forces shaping current diversity patterns. In summary, we demonstrate that a multiscale (community, population and species level) analysis incorporating both historical and contemporary factors can be useful in delineating factors contributing to community assembly and patterning in diversity.

Effect of anesthesia strategy during endovascular therapy on 90-day outcomes in acute basilar artery occlusion: a retrospective observational study.

BACKGROUND AND OBJECTIVE: The research on the effect of anesthesia on endovascular therapy (EVT) of acute ischemic stroke is mainly focused on the anterior circulation, and little is known about the data of basilar artery occlusion (BAO). This study aims to investigate the association of anesthesia strategy with 90-day clinical outcomes of patients with acute BAO treated with EVT. METHODS: We reviewed our prospectively collected data from the endovascular treatment database at the Beijing Tiantan Hospital. This included patients with acute BAO who had a documented 90-day modified Rankin Scale (mRS) score from January 2012 to July 2018. Options for EVT included general anesthesia (GA) and conscious sedation (CS) performed by an anesthesia care team in the institution. The recommendation of anesthesia for patients was a joint decision between anesthesiologist and neurointerventionalist according to a pre-designed scheme. Patients who required tracheal intubation for airway protection prior to EVT were excluded. The clinical outcomes we observed were functional independence (mRS ≤2), favorable outcome (mRS ≤3), and mortality at 90 days after the procedure. Univariate and multivariable logistic regression analyses were used to explore the relationship between anesthesia methods and 90-day outcomes. RESULTS: A total of 187 patients with BAO were treated by EVT in this study. Nine cases requiring emergent intubation prior to EVT were excluded. 139 patients (78.1%) underwent GA and 39 patients (21.9%) underwent CS. In univariate analysis, GA was associated with less functional independence [odds ratio (OR), 0.28; 95% confidence interval (CI), 0.13-0.59] and less favorable outcome (OR, 0.23; 95% CI, 0.10-0.52) than was CS. After adjusting for potential confounders, multivariable analysis showed that there were still significant differences between GA and CS in functional independence (OR, 0.31; 95%CI, 0.10-0.97) and favorable outcome (OR, 0.24; 95%CI, 0.07-0.75). CONCLUSION: Our retrospective analysis suggested that the anesthesia strategy may affect outcome, in which general anesthesia may result in less favorable outcomes. Nevertheless, future multicenter randomized controlled trials are needed to confirm our findings.

SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma.

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.

Loss of FOXF2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma Patients.

BACKGROUND: FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown. METHODS: Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes. RESULTS: FOXF2 downregulation was observed in HCC tissues (p < 0.001) compared with peritumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (p = 0.023 and 0.006, respectively) in patients with HCC. RNAi-mediated silencing of the FOXF2 gene in the MHCC-97H cell line significantly promoted proliferation and anti-apoptosis. CONCLUSIONS: The results of the present study indicate that FOXF2 may serve as a prognostic biomarker for HCC and may be a promising target in the treatment of patients with HCC.

Loss of CD155 expression predicts poor prognosis in hepatocellular carcinoma.

AIMS: CD155 is an important ligand in triggering tumour rejection by immune cells. However, the expression of CD155 and its clinical significance in hepatocellular carcinoma (HCC) remains unknown. METHODS AND RESULTS: We examined the expression level of CD155 in 174 HCC tissue samples by immunohistochemical staining and in HCC cell lines by flow cytometry; 63.8% (111 of 174) of HCC tissue samples showed negative CD155 expression. When compared with adjacent peritumour tissues, HCC tissues exhibited a significantly lower expression of CD155 (P < 0.001). Flow cytometry analysis indicated that HCC cell lines had low levels of CD155 expression. Moreover, negative CD155 expression was associated significantly with higher serum α-fetoprotein level (P = 0.016) and a higher incidence of portal vein tumour thrombus (P = 0.050). Importantly, patients with positive CD155 expression had better overall survival after surgery than those with negative CD155 expression (P = 0.005). Furthermore, Cox regression analyses showed that CD155 expression was an independent prognostic factor for HCC (P = 0.049). CONCLUSIONS: Our findings suggest that loss of CD155 expression may play an important role in the immune escape of HCC cells and thus CD155 may serve as a prognostic marker as well as a potential therapeutic target for HCC.

Nuclear factor-κB activation inhibitor attenuates ischemia reperfusion injury and inhibits Hmgb1 expression.

OBJECTIVE AND DESIGN: To investigate the effects of nuclear factor-κB activation inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on cardiac ischemia reperfusion injury in a transplantation model. METHODS: Hearts of C57BL/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. Some mice were administrated intraperitoneally with DHMEQ (8 mg/kg) 1 h before reperfusion. For inhibition of Hmgb1, mice were treated with glycyrrhizin at 250 mg/kg prior to reperfusion. RESULTS: DHMEQ decreased cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by DHMEQ treatment. Cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts with DHMEQ treatment (IR+DHMEQ: 58.6 ± 5.75 ml/min; IR: 25.9 ± 4.1 ml/min; P < 0.05). Furthermore, DHMEQ suppressed high mobility group protein (Hmgb1) expression. And the Caspase 3 activity, the number of TUNEL-positive cardiomyocytes and infiltrated neutrophil in cardiac allograft were markedly decreased with Hmgb1 inhibitor treatment. CONCLUSIONS: Nuclear factor-κB activation inhibitor DHMEQ attenuates ischemia reperfusion injury in a cardiac transplantation model and it may be a suitable agent for the protection of the cardiac against ischemia reperfusion injury.

Integrated Transcriptomics and Metabolomics Analysis Reveals the Effects of Cutting on the Synthesis of Flavonoids and Saponins in Chinese Herbal Medicine Astragalus mongholious.

Astragali Radix, derived from the roots of Astragalus mongholicus, is a traditional Chinese medicine containing flavonoids and saponins as its key ingredients. With a shortage in the wild sources of the herbal plant, it is especially important to explore a cultivation mode for A. mongholicus for medicinal purposes. Cutting, a physical environmental stress method, was used in this study with the objective of improving the quality of this herbal legume. We found that cutting of the top 1/3 of the aboveground part of A. mongholicus during the fruiting period resulted in a significant increase in the content of flavonoids and saponins, as well as in root growth, including length, diameter, and dry weight. Furthermore, the leaves were sampled and analyzed using a combined transcriptome and metabolome analysis approach at five different time points after the treatment. Sixteen differentially expressed unigenes (DEGs) involved in the biosynthesis of flavonoids were identified; these were found to stimulate the synthesis of flavonoids such as formononetin and calycosin-7-O-ß-D-glucoside. Moreover, we identified 10 DEGs that were associated with the biosynthesis of saponins, including astragaloside IV and soyasaponin I, and found that they only regulated the mevalonic acid (MVA) pathway. These findings provide new insights into cultivating high-quality A. mongholicus, which could potentially alleviate the scarcity of this valuable medicinal plant.

Integration of Transcriptomics and WGCNA to Characterize Trichoderma harzianum-Induced Systemic Resistance in Astragalus mongholicus for Defense against Fusarium solani.

Beneficial fungi of the genus Trichoderma are among the most widespread biocontrol agents that induce a plant's defense response against pathogens. Fusarium solani is one of the main pathogens that can negatively affect Astragalus mongholicus production and quality. To investigate the impact of Trichoderma harzianum on Astragalus mongholicus defense responses to Fusarium solani, A. mongholicus roots under T. harzianum + F. solani (T + F) treatment and F. solani (F) treatment were sampled and subjected to transcriptomic analysis. A differential expression analysis revealed that 6361 differentially expressed genes (DEGs) responded to T. harzianum induction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the 6361 DEGs revealed that the genes significantly clustered into resistance-related pathways, such as the plant-pathogen interaction pathway, phenylpropanoid biosynthesis pathway, flavonoid biosynthesis pathway, isoflavonoid biosynthesis pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and plant hormone signal transduction pathway. Pathway analysis revealed that the PR1, formononetin biosynthesis, biochanin A biosynthesis, and CHIB, ROS production, and HSP90 may be upregulated by T. harzianum and play important roles in disease resistance. Our study further revealed that the H2O2 content was significantly increased by T. harzianum induction. Formononetin and biochanin A had the potential to suppress F. solani. Weighted gene coexpression network analysis (WGCNA) revealed one module, including 58 DEGs associated with T. harzianum induction. One core hub gene, RPS25, was found to be upregulated by T. harzianum, SA (salicylic acid) and ETH (ethephon). Overall, our data indicate that T. harzianum can induce induced systemic resistance (ISR) and systemic acquired resistance (SAR) in A. mongholicus. The results of this study lay a foundation for a further understanding of the molecular mechanism by which T. harzianum induces resistance in A. mongholicus.

Key genes and immune pathways in T-cell mediated rejection post-liver transplantation identified via integrated RNA-seq and machine learning.

Liver transplantation is the definitive treatment for end-stage liver disease, yet T-cell mediated rejection (TCMR) remains a major challenge. This study aims to identify key genes associated with TCMR and their potential biological processes and mechanisms. The GSE145780 dataset was subjected to differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms to pinpoint key genes associated with TCMR. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and regulatory networks were constructed to ascertain the biological relevance of these genes. Expression validation was performed using single-cell RNA-seq (scRNA-seq) data and liver biopsy tissues from patients. We identified 5 key genes (ITGB2, FCER1G, IL-18, GBP1, and CD53) that are associated with immunological functions, such as chemotactic activity, antigen processing, and T cell differentiation. GSEA highlighted enrichment in chemokine signaling and antigen presentation pathways. A lncRNA-miRNA-mRNA network was delineated, and drug target prediction yielded 26 potential drugs. Evaluation of expression levels in non-rejection (NR) and TCMR groups exhibited significant disparities in T cells and myeloid cells. Tissue analyses from patients corroborated the upregulation of GBP1, IL-18, CD53, and FCER1G in TCMR cases. Through comprehensive analysis, this research has identified 4 genes intimately connected with TCMR following liver transplantation, shedding light on the underlying immune activation pathways and suggesting putative targets for therapeutic intervention.

A novel selenium analog of HDACi-based twin drug induces apoptosis and cell cycle arrest via CDC25A to improve prostate cancer therapy.

Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. Methods: The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. Results: SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both in vitro and in vivo. Our findings provide an important theoretical basis for clinical prostate cancer treatment. Conclusions: Our in vivo and in vitro results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS).

BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Risk factors of postoperative cerebral hyperperfusion syndrome and its relationship with clinical prognosis in adult patients with moyamoya disease.

BACKGROUND: To investigate the incidence, risk factors, and clinical prognosis of cerebral hyperperfusion syndrome (CHS) after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis (STA-MCA/EDAS) in adult patients with moyamoya disease (MMD). METHODS: The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed. According to CHS diagnosis, MMD patients were divided into CHS and non-CHS group. Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed. RESULTS: A total of 12 patients (7.5%) developed postoperative CHS, of which 4 patients (2.5%) presented with cerebral hemorrhage. Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere (OR = 3.04, 95% CI = 1.02-9.03, P = 0.046) and left operated hemisphere (OR = 5.16, 95% CI = 1.09-21.34, P = 0.041) were independent risk factors for CHS. The other variables, such as age, gender, presentation, hypertension, diabetes, smoking, mean mRS score on admission, modified Suzuki stage and pre-infarction stage on surgical hemisphere, and bypass patency, had no association with postoperative CHS (P > 0.05). At final follow-up with average 38 months, there were 18 out of 133 patients (13.5%, 4.91% per person year) presented with newly developed complications. There was no significant difference between newly developed complications, mean mRS scores, and Kaplan-Meier curve of stroke-free survival in patients with and without CHS (P > 0.05). CONCLUSION: The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS, which could not affect the clinical prognosis if treated timely and properly. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.