Search

Xiaotao Jiang,1,2 Fan Liu,2,3 Peng Liu,1,2 Yanhua Yan,1,2 Shaoyang Lan,1 Kunhai Zhuang,1,4 Yufeng Liu,5 Kailin Jiang,1,2 Yuancheng Huang,1,2 Kechao Nie,1,2 Zhihua Zheng,1,2 Jinglin Pan,6 Junhui Zheng,1,2 Fengbin Liu,1,4 Shijie Xu,5 Peiwu Li,1 Yi Wen1 1Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Zhaoqing Hospital of Chinese Medicine Affiliated to Southern Medical University, Zhaoqing, Guangdong, People’s Republic of China; 4Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 5Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 6Department of Gastroenterology, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Peiwu Li; Yi Wen Email doctorlipw2@163.com; 421491922@qq.comObjective: We aimed to build a ferroptosis-based classifier to characterize the molecular features of gastric cancers (GC) and investigate the relationship between different ferroptosis patterns and GC tumor microenvironment (TME).Methods: Based on the genomic and clinical information from TCGA portal and GEO database, non-negative matrix factorization (NMF) was used to identify ferroptosis subtypes in GC patients. In order to estimate the ferroptosis levels, we established ferroptosis subtype score (FSS) to quantify ferroptosis patterns and ferroptosis potential index (FPI) by principal component analysis (PCA). The correlations of different ferroptosis patterns with TME cell-infiltrating characteristics (including immune cell infiltration, immune checkpoints expression levels, tumor mutational burden (TMB) and immunotherapy response) were systematically analyzed.Results: Two ferroptosis subtypes, C1 (with lower FSS) and C2 (with higher FSS), were determined. C2 displayed a significantly lower FPI than C1. Besides, C2 was associated with diffuse subtype while C1 with intestinal subtype. As for TME characteristics, C2 was in accordance with the immune-excluded phenotype as it showed more active immune and stromal activities but lower TMB, less probability of immunotherapy response and poorer prognosis. C1 was linked to immune-inflamed phenotype as it had lower stromal activities but increased neoantigen load, enhanced response to immunotherapy and relatively better prognosis.Conclusion: The systematic assessment of ferroptosis patterns and ferroptosis levels presented in our study implied that ferroptosis serves as an important factor in the formation of TME, which may expand the understanding of TME and provide a novel perspective for the development of targeted immunotherapeutic strategies for GC patients.Keywords: ferroptosis, gastric cancer, immune cell infiltration, tumor microenvironment, immunotherapy

Shanshan Yuan,1,2,* Wangli Si,2,* Kun Zhuang,2 Yijun Li,2 Yanting Zhang,2 Jiaming Liu,2 Li Yang,3 Xin Zhang2 1Department of Gastroenterology, The Affiliated Xi’an Central Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Gastroenterology, Xi’an Central Hospital, Xi’an, Shaanxi, People’s Republic of China; 3Department of Ultrasonography, The Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li YangDepartment of Ultrasonography, The Affiliated Children’s Hospital of Xi’an Jiaotong University, No. 69, Xijuyuan Lane, Xi’an, Shaanxi, People’s Republic of ChinaTel +86-29-87692073Email liyangscience@21cn.comXin ZhangDepartment of Gastroenterology, Xi’an Central Hospital, No. 161, Xiwu Road, Xi’an, Shaanxi, People’s Republic of ChinaTel +86-29-62812284Email zhangxin_1121@21cn.comBackground: LncRNAs are functional regulators in tumor progression which act by regulating mRNAs in multiple types of cancer. However, the effect of lnc-UCID on hepatocellular carcinoma (HCC) metastasisremains unclear.Methods: Lnc-UCID expression was quantified in HCC tissues and HCC cell lines by qRT-PCR. HCC cell lines with lnc-UCID knockdown were established by lentivirus transduction. The migration and invasion abilities of HCC cells were analyzed by Transwell and wound-healing assays. Protein expression of epithelial–mesenchymal transition (EMT)-related factors was examined by Western blot assay. Dual-luciferase assays and actinomycin D treatment were conducted to explore the relationship between lnc-UCID and Snail mRNA. The direct interaction between lnc-UCID and Snail mRNA was subjected to quantification analysis by biotinylated lnc-UCID pulldown assays. Pearson’s correlation coefficient was used to analyze correlations between lnc-UCID and Snail expression level in clinical samples. Rescue experiments were performed to uncover the role of Snail in the HCC metastasis process.Results: Lnc-UCID was upregulated in human HCC tissues and HCC cell lines. Lnc-UCID promoted the cells’ mobility and invasiveness by enhancing the EMT process of HCC cells. The expression of Snail positively correlated with lnc-UCID abundance, and the interaction between lnc-UCID and Snail mRNA prevented miR-122, miR-203, miR-30b, miR-34a or miR-153 binding to the 3ʹ-UTR of Snail. Transfection of Snail greatly rescued the migration and invasion of HCC cells.Conclusion: Lnc-UCID was upregulated in clinical HCC samples and directly interacted with Snail mRNA to enhance the stability of Snail mRNA, thus promoting the EMT process to accelerate HCC metastasis.Keywords: hepatocellular carcinoma, HCC, long non-coding RNA, lnc-UCID, Snail, metastasis

Jiawei Lv,1 Kai Zhuang,1 Xiyu Jiang,1 Heqing Huang,1,2 Shijian Quan1 1Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, People’s Republic of ChinaCorrespondence: Heqing Huang; Shijian QuanDepartment of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email huangheq@mail.sysu.edu.cn; quansj@gzucm.edu.cnPurpose: Glomerular sclerosis and renal interstitial fibrosis are the most important pathologies in the development of kidney damage under diabetic conditions. Smad3 plays antagonistic roles in high glucose-induced renal tubular fibrosis, which is an important treatment target for diabetic nephropathy (DN). Formononetin (FMN) has multiple effects on diabetic vascular complications including DN. However, whether it plays an anti-fibrosis role by regulating smad3 is unclear. The purpose of this study was to evaluate the renoprotective effect of FMN by suppressing smad3 expression in db/db mice.Methods: FMN was orally administered to db/db mice with a dose of 25 or 50 mg/kg/day for 8 weeks. At the end of the study, serum, urine, and kidney samples were collected for biochemical and pathological examinations. The expressions of proteins and mRNA associated with renal fibrosis were determined by biochemical, histological, immunofluorescence, and real-time PCR analysis.Results: The results showed that FMN substantially improved the glucolipid metabolism, reduced the oxidative stress, and protected renal function in db/db mice. Meanwhile, protein and mRNA expression of smad3 and related regulatory factor of extracellular matrix deposition were significantly suppressed.Conclusion: The present study suggested that FMN has a good renoprotective effect in DN, which plays an anti-fibrosis role in db/db mice by suppressing the expression of smad3.Keywords: formononetin, diabetic nephropathy, db/db mice, renal fibrosis, expression of smad3, antioxidants

Jia Mi,1,* Wenda He,1,* Jiawei Lv,1 Kai Zhuang,1 Heqing Huang,1,2 Shijian Quan1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heqing Huang; Shijian QuanDepartment of School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email Huangheq@mail.sysu.edu.cn quansj@gzucm.edu.cnPurpose: Activation of the hypothalamus-pituitary-adrenal (HPA) axis pathway is closely related to insulin resistance (IR), glucose, and lipid metabolism disorders in type 2 diabetes mellitus (T2DM). Berberine (BBR) has effect on regulating disorder of glucose and lipid metabolism in T2DM. In fact, activation of the HPA axis pathway is closely related to IR, glucose, and lipid metabolism disorders in T2DM. Here, we investigated whether the therapeutic effect of BBR on T2DM rats is acted through the HPA axis pathway. Methods: In this research, we investigated the effects of BBR on the HPA-axis pathway-related indicators and expression of skeletal muscle glucose transporter 4 (GLUT4) in the high-fat diet and streptozotocin-induced T2DM rats, and identify its possible mechanism of improving IR in T2DM.Results: BBR significantly reduced fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol in model rats. It also improved the abnormalities of the high-density lipoprotein cholesterol, the insulin resistance index, the insulin sensitivity index, glucagon, and insulin levels. BBR decreased levels of hypothalamic Orexin-A, the OX2R receptor, the corticotropin-releasing hormone, the pituitary and the plasma adrenocorticotropic hormone, as well as serum and urine corticosterone. At the same time, BBR increased mRNA and protein expressions of GLUT4 in skeletal muscles of model rats as well.Conclusion: Those results suggested that BBR can exert inhibition on the HPA-axis and increased skeletal muscle expression of GLUT4 proteins, which may be one of the important mechanisms in BBR to improve IR and regulating glucose and lipid metabolism in T2DM rats.Keywords: berberine, type 2 diabetes mellitus, insulin resistance, the HPA-axis, GLUT4

Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Abstract Background Glioblastoma (GBM), the most common primary malignant brain tumor, has a poor prognosis, with a median survival of only 14.6 months. The Warburg effect is an abnormal energy metabolism, which is the main cause of the acidic tumor microenvironment. This study explored the role of the Warburg effect in the prognosis and immune microenvironment of GBM. Methods A prognostic risk score model of Warburg effect‐related genes (Warburg effect signature) was constructed using GBM cohort data from The Cancer Genome Atlas. Cox analysis was performed to identify independent prognostic factors. Next, the nomogram was built to predict the prognosis for GBM patients. Finally, the drug sensitivity analysis was utilized to find the drugs that specifically target Warburg effect‐related genes. Results Age, radiotherapy, chemotherapy, and WRGs score were confirmed as independent prognostic factors for GBM by Cox analyses. The C‐index (0.633 for the training set and 0.696 for the validation set) and area under curve (>0.7) indicated that the nomogram exhibited excellent performance. The calibration curve also indicates excellent consistency of the nomogram between predictions and actual observations. In addition, immune microenvironment analysis revealed that patients with high WRGs scores had high immunosuppressive scores, a high abundance of immunosuppressive cells, and a low response to immunotherapy. The Cell Counting Kit‐8 assays showed that the drugs targeting Warburg effect‐related genes could inhibit the GBM cells growth in vitro. Conclusion Our research showed that the Warburg effect is connected with the prognosis and immune microenvironment of GBM. Therefore, targeting Warburg effect‐related genes may provide novel therapeutic options.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Objective: This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase I trial. Methods: A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg. Results: The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95–1.27 h on day 1 and 1.19–1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day. Conclusions: This phase I study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.

Summary: The recycling of spent batteries is an important concern in resource conservation and environmental protection, while it is facing challenges such as insufficient recycling channels, high costs, and technical difficulties. To address these issues, a review of the recycling of spent batteries, emphasizing the importance and potential value of recycling is conducted. Besides, the recycling policies and strategies implemented in representative countries are summarized, providing legal and policy support for the recycling industry. Moreover, a comprehensive classification and comparison of recycling technologies identify the characteristics and current status of different approaches. The integrated recycling technology provides a better recycling performance with zero-pollution recycling of spent battery. Biorecycling technology is expected to gain a broad development prospect in the future owing to the superiority of energy-saving and environmental protection, high recycling efficiency, via microbial degradation, enzymatic degradation, etc. Consequently, as for the existing recycling challenges of waste batteries, developing new recycling technology and perfecting its recycling system is an indispensable guarantee for the sustainable development of waste battery. Meanwhile, theoretical support is offered for the recycling of spent batteries.

New type reactors usually adopt advanced fuel types and more anisotropic fuel arrangements, the neutron spectrum is very different from that of pressurized water reactor, and the neutron anisotropy is stronger. If using the neutron transport theory, although better results can be obtained, the computational efficiency is low. If the traditional diffusion theory is used, the calculation efficiency can be improved, however, the complex neutron energy spectrum and strong neutron anisotropy in the core decrease the calculation accuracy. In this study, the core calculation and analysis method based on quasi-diffusion equation was employed. One of the basic assumptions established by traditional diffusion theory is that the angular flux of neutrons is a first-order function of angle, but the quasi-diffusion equation does not adopt this assumption, and an Eddington factor is used to express product of the angular flux of neutrons and angle vectors. The Eddington factor can describe the anisotropic characteristics that cannot be reflected by traditional diffusion theory, and the form of quasi-diffusion equation is similar to the traditional diffusion equation. Most of the current researches applied the quasi-diffusion equation to accelerate the calculation neutron transport. Due to the computational complexity of the Eddington factor, the studies on the quasi-diffusion equation independently employed to the reactor calculation, especially for the reactor with hexagonal assembly are insufficient. Aiming at the characteristics of nonlinear calculation of the Eddington factor, this study regarded the Eddington factor as a special few-group constant based on “two-step” method, and adopted Monte Carlo code SERPENT of better neutron energy spectrum adaptability to calculate. For three-dimensional multi-group quasi-diffusion equation, based on Galerkin variation principle and Lagrange multiplier method, this study established a functional including the nodal balance relationship and boundary condition in the entire region, and used the Ritz discrete method to expand this functional by orthogonal basis function. Then the response relation between nodal neutron flux density and neutron current was built to solve the quasi-diffusion equation, and a code named VNMQD for reactor core with hexagonal assembly was developed. The VNMQD code was verified by using 3D VVER1000 benchmark, RBWR single assembly problem and 3D BN600 simplified model. The results show that the VNMQD code is developed correctly. For the core with strong anisotropy problem, VNMQD has a great improvement in the calculation accuracy for the effective core multiplication factor and neutron flux density compared with traditional diffusion calculation, and the calculation efficiency of both is similar. VNMQD achieves a balance between calculation accuracy and calculation efficiency.

The rapid development of new energy in the distribution network increases its flexibility while making it more complicated to operate and manage the network. For this reason, a novel flexible switch, which is composed of integrated gate- commutated thyristors (IGCT) and parallel voltage converters, is proposed in this paper. Applying virtual synchronous generator (VSG) control on the parallel voltage converterensures smoothness and steadiness while switching from one feeder to another. Firstly, the proposed flexible switch is compared with the flexible multi-state switch and the mechanical switch on their main characteristics. Then, the operating features of the flexible switch before, during, and after feeder fault are analyzed, as well as its switching logic. Finally, the switching process between different feeders is simulated on a control in-the-loop experiment based on RT-Lab. The voltage and current waveforms are obtained under different operating modes and during flexible switching. The experiment resultsshow that the flexible switch has short-term voltage support capability and does not generate voltage and current impulses during the switching process.

Key points “Target signs” and “lollipop signs” should be recognised in imaging evaluation, raising the possibility of HEHE in the differential diagnosis. Abnormal blood vessels in tumours may have implications for imaging diagnosis. When HEHE is suspected, radiologists should be aware of tumour thrombi in the vena cava. HEHEs always present with a peripheral enhancement of various shapes with centripetal progressive filling.

Abstract Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain tumors, enhanced biological understanding and unexampled innovations in targeted therapies and immunotherapies have considerably improved patients’ prognoses. Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. Previous literature data revealed that several different signaling pathways are dysregulated in brain tumor. Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. This paper began with a brief description of the epidemiology, incidence, risk factors, as well as survival of brain tumors. Next, the major signaling pathways underlying these brain tumors’ pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed. Finally, future perspective and challenges of development of novel therapeutic strategies in brain tumor were emphasized.

SAF2507 duplex stainless steel (DSS) is often used as a structural component in ocean-going vessels and marine petroleum exploitation equipment, which require superior mechanical properties. In this study, we used cold rolling (CR) at room temperature with 55% or 80% deformation amounts and subsequent annealing at 1273 K in 1 min to prepare SAF2507 samples with a heterogeneous structure (HS) that was composed of ferrite and austenite phases with different grain sizes. Compared with the homogeneous structure samples, the yield strength of the HS samples increased, while the ductility did not decrease. The 55%-1273 and 80%-1273 samples exhibited the hetero-zone boundary-affected regions on both sides of the grain boundary, phase boundary, and twin boundary. This resulted in hetero-deformation-induced (HDI) strengthening and strain hardening of samples during tensile deformation, which improved the ultimate tensile strength of the HS samples while maintaining a good uniform elongation. In addition, the heterogeneous structure of DSS had better corrosion resistance than the initial sample of coarse grain (CG) structure; mainly because the HS samples had finer grains and more grain boundaries on the DSS surface than the CG structure, which is conducive to the formation of high-density passivation film on the surface of stainless steel. The current study provides a new method of material selection of some structural components with the demands of high strength and good ductility.

Summary: Inadequate remnant volume and regenerative ability of the liver pose life-threatening risks to patients after partial liver transplantation (PLT) or partial hepatectomy (PHx), while few clinical treatments focus on safely accelerating regeneration. Recently, we discovered that supplementing 5-aminolevulinate (5-ALA) improves liver cold adaptation and functional recovery, leading us to uncover a correlation between 5-ALA metabolic activities and post-PLT recovery. In a mouse 2/3 PHx model, 5-ALA supplements enhanced liver regeneration, promoting infiltration and polarization of anti-inflammatory macrophages via P53 signaling. Intriguingly, chemokine receptor CX3CR1 functions to counterbalance these effects. Genetic ablation or pharmacological inhibition of CX3CR1 (AZD8797; phase II trial candidate) augmented the macrophagic production of insulin-like growth factor 1 (IGF-1) and subsequent hepatocyte growth factor (HGF) production by hepatic stellate cells. Thus, short-term treatments with both 5-ALA and AZD8797 demonstrated pro-regeneration outcomes superior to 5-ALA-only treatments in mice after PHx. Overall, our findings may inspire safe and effective strategies to better treat PLT and PHx patients.

Alloys with a gradient structure (GS) exhibit a superior combination of strength and ductility. However, the effects of treatment temperature and stacking fault energy on the tensile behavior and microstructure evolution of GS alloys have not been systematically investigated. In this study, GS Cu-Al-Zn alloys with different stacking fault energy (SFE, 40/7 mJ/m2) were prepared using surface mechanical attrition treatment (SMAT) at cryogenic and room temperature, respectively. The microstructure results indicate that more stacking faults and deformation twins were activated in the SFE-7 alloys at cryogenic temperature, which led to higher strength compared to that of the alloys SMAT-ed at room temperature. In addition, it was found that the yield strength and hetero-deformation-induced (HDI) stress of the SFE-7 alloy were significantly higher than those of the SFE-40 alloy, resulting in a good combination of strength and ductility. Furthermore, more dispersed strain bands were observed in the SFE-7 sample during whole tensile deformation, which contributes to higher ductility.

BackgroundAs one of the essential nutrients for the human body, minerals participate in various physiological activities of the body and are closely related to many cancers. However, the population study on glioma is not sufficient.ObjectiveThe purpose of this study was to evaluate the relationship between five dietary minerals and glioma.MethodsA total of 506 adult patients with glioma and 506 healthy controls were matched 1:1 according to age (±5 years) and sex. The food intake of the subjects in the past year was collected through the food frequency questionnaire, and the intakes of calcium, magnesium, iron, zinc, and copper in the diet were calculated. The logistic regression model was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for dietary minerals to gliomas.ResultsAfter adjusting for confounders, higher intakes of calcium (OR = 0.65, 95% CI: 0.57–0.74), magnesium (OR = 0.18, 95% CI: 0.11–0.29), iron (OR = 0.04, 95% CI: 0.02–0.11), zinc (OR = 0.62, 95% CI: 0.54–0.73), and copper (OR = 0.22, 95% CI: 0.13–0.39) were associated with a significantly decreased risk of glioma. Similar results were observed in gliomas of different pathological types and pathological grades. The restriction cubic spline function suggested significant linear dose-response relationships between intakes of five minerals and the risk of glioma. When the dietary minerals exceeded a particular intake, the risk of glioma stabilized.ConclusionOur study suggests that higher dietary intakes of calcium, magnesium, iron, zinc, and copper are associated with a decreased risk of glioma. However, the results of this study require further exploration of potential mechanisms in the future better to elucidate the effects of mineral intake on gliomas.

Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are still lacking. Moreover, there is no standard treatment for patients with olfactory neuroblastoma that progressed to leptomeningeal carcinomatosis. Here we report an uncommon case of a 59-year-old woman who was diagnosed with olfactory neuroblastoma and leptomeningeal carcinomatosis. For a direct delivery of the drugs to the tumor, and to avoid the impact of lumbar puncture on the patient’s quality of life, the intravenous chemotherapy plus intrathecal administration of MTX via an Ommaya reservoir was chosen. The results were striking, with the disappearance of tumor cells in the cerebrospinal fluid and the relief of the patient’s symptoms with PR. Our result indicates that chemotherapy via an Ommaya reservoir offers a new potential therapy for patients with meningeal metastases.

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein–protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma.

Micro burner is the fundamental element of a micro energy power system. The performance, output power, and efficiency of the system are directly involved by the combustion stability, efficiency, and temperature distribution of the exterior wall. Owing to the small combustion space of the micro burner and the resident short time of the premixed fuel/air, the fuel is difficult to burn completely, resulting in poor burning efficiency and flame stability. Therefore, the study of micro burner technology is the focus of current research to improve combustion performance. This article introduces the micro power system, micro combustion technology, and combustion status and characteristics, focusing on four kinds of micro combustion technology. The purpose is tantamount to fully understand the current status of micro combustion technology and compare the characteristics of different combustion technologies. For improving output power and efficiency of the power system, the combustion stability and performance are enhanced, which provides theoretical support for the effective realization of micro scale combustion and application.

Abstract In this study, thin-film composite with embedded polyester screen, cellulose triacetate with a cast nonwoven and cellulose triacetate with embedded polyester screen (CTA-ES) was examined as the intermediate membranes in osmotic microbial fuel cells (OsMFCs). The reactors were fed with actual landfill leachate and the performance was studied in two operation modes: active layer facing draw solution and active layer facing feed solution (AL-FS). The OsMFC with CTA-ES exhibited the best energy generation (maximum power density: 0.44 W m− 2) and pollutant removal efficiency (ammonia nitrogen: 70%, total nitrogen: 74%) in the AL-FS mode, which could be ascribed to the lowest internal resistance (237 Ω) and highest microbial richness. Pseudomonas was the highest proportion of microbial in OsMFCs. The result of this study has demonstrated the potential of OsMFCs for landfill leachate treatment.

Abstract Background Systemic cardiac hypoperfusion is a well-acknowledged contributor to ischemic leukoencephalopathy. However, it has remained elusive how atherosclerosis-mediated cardiac remodelling modifies cerebral perfusion homeostasis as well as neuroimaging burden in cerebral small vessel disease (CSVD) development. Methods This retrospective study identified 103 arteriosclerotic CSVD (aCSVD) patients (CSVD burdenlow 0 ~ 1, n = 61 and CSVD burdenhigh 2 ~ 4, n = 42) from Sep. 2017 to Dec. 2019 who underwent transthoracic echocardiography(n = 81), structural magnetic resonance imaging and arterial spin labelling (ASL). Total CSVD burden was graded according to the ordinal “small vessel disease” rating score (0–4). We investigated the univariate and multivariate linear regression of mean deep regional cerebral blood flow (CBF) as well as logistic regression analysis of CSVD burdenhigh. Results Right atrial diameter (B coefficient, − 0.289; 95% CI, − 0.578 to − 0.001; P = 0.049) and left ventricular ejection fraction (B coefficient, 32.555; 95% CI, 7.399 to 57.711; P = 0.012) were independently associated with deep regional CBF in aCSVD patients. Binary logistic regression analysis demonstrated decreased deep regional CBF (OR 0.894; 95% CI 0.811–0.985; P = 0.024) was independently associated with higher CSVD burden after adjusted for clinical confounders. Multivariate receiver operating characteristics curve integrating clinical risk factors, mean deep CBF and echocardiographic parameters showed predictive significance for CSVD burdenhigh diagnosis (area under curve = 84.25, 95% CI 74.86–93.65%, P

Picolinic acid (PA) is a typical mono-carboxylated pyridine derivative produced by human/animals or microorganisms which could be served as nutrients for bacteria. Most Bordetella strains are pathogens causing pertussis or respiratory disease in humans and/or various animals. Previous studies indicated that Bordetella strains harbor the PA degradation pic gene cluster. However, the degradation of PA by Bordetella strains remains unknown. In this study, a reference strain of genus Bordetella, B. bronchiseptica RB50, was investigated. The organization of pic gene cluster of strain RB50 was found to be similar with that of Alcaligenes faecalis, in which the sequence similarities of each Pic proteins are between 60% to 80% except for PicB2 (47% similarity). The 3,6-dihydroxypicolinic acid (3,6DHPA) decarboxylase gene (BB0271, designated as picCRB50) of strain RB50 was synthesized and over-expressed in E. coli BL21(DE3). The PicCRB50 showed 75% amino acid similarities against known PicC from Alcaligenes faecalis. The purified PicCRB50 can efficiently transform 3,6DHPA to 2,5-dihydroxypyridine. The PicCRB50 exhibits optimal activities at pH 7.0, 35 °C, and the Km and kcat values of PicCRB50 for 3,6DHPA were 20.41 ± 2.60 μM and 7.61 ± 0.53 S−1, respectively. The present study provided new insights into the biodegradation of PA by pathogens of Bordetella spp.

Recently, an increasing number of studies have highlighted the role of the cerebellum in language processing. However, the role of neural reorganization within the cerebellum as well as within the cerebrocerebellar system caused by poststroke aphasia remains unknown. To solve this problem, in the present study, we investigated regional alterations of the cerebellum as well as the functional reorganization of the cerebrocerebellar circuit by combining structural and resting-state functional magnetic resonance imaging (fMRI) techniques. Twenty patients diagnosed with aphasia following left-hemispheric stroke and 20 age-matched healthy controls (HCs) were recruited in this study. The Western Aphasia Battery (WAB) test was used to assess the participants’ language ability. Gray matter volume, spontaneous brain activity, functional connectivity, and effective connectivity were examined in each participant. We discovered that gray matter volumes in right cerebellar lobule VI and right Crus I were significantly lower in the patient group, and the brain activity within these regions was significantly correlated with WAB scores. We also discovered decreased functional connectivity within the crossed cerebrocerebellar circuit, which was significantly correlated with WAB scores. Moreover, altered information flow between the cerebellum and the contralateral cerebrum was found. Together, our findings provide evidence for regional alterations within the cerebellum and the reorganization of the cerebrocerebellar system following poststroke aphasia and highlight the important role of the cerebellum in language processing within aphasic individuals after stroke.

Aims To evaluate the effect of ultraviolet ( UV) disinfection on antibiotic-resistant Escherichia coli. Methods and Results Antibiotic-resistant E. coli strains were isolated from a wastewater treatment plant and subjected to UV disinfection. The effect of UV disinfection on the antibiotic resistance profiles and the antibiotic resistance genes ( ARGs) of antibiotic-resistant E. coli was evaluated by a combination of antibiotic susceptibility analysis and molecular methods. Results indicated that multiple-antibiotic-resistant ( MAR) E. coli were more resistant at low UV doses and required a higher UV dose (20 mJ cm−2) to enter the tailing phase compared with those of antibiotic-sensitive E. coli (8 mJ cm−2). UV disinfection caused a selective change in the inhibition zone diameters of surviving antibiotic-resistant E. coli and a slight damage to ARGs. The inhibition zone diameters of the strains resistant to antibiotics were more difficult to alter than those susceptible to antibiotics because of the existence and persistence of corresponding ARGs. Conclusions The resistance of MAR bacteria to UV disinfection at low UV doses and the changes in inhibition zone diameters could potentially contribute to the selection of antibiotic-resistant bacteria in wastewater treatment after UV disinfection. The risk of spread of antibiotic resistance still exists owing to the persistence of ARGs. Significance and Impact of the Study Our study highlights the acquisition of other methods to control the spread of ARGs. [ABSTRACT FROM AUTHOR]