Search

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from the gastrointestinal epithelium. Although the pathogenesis of GIC has not been fully elucidated, angiogenesis is recognized as the key pathological basis for the growth, invasion and metastasis of cancer cells, and GIC angiogenesis is closely related to vascular endothelial growth factor family, hypoxia-inducible factor family, fibroblast growth factor family and matrix metalloproteinase family. Recently, many natural products have shown a wide range of pharmacological biological activities against GIC. In this review, the effects and mechanisms of natural compounds on the angiogenesis of gastric and colorectal cancer were summarized. The results show that some natural compounds, especially gallic catechin gallate, astragaloside and curcumin, can effectively inhibit angiogenesis; the HIF-1α/VEGF, COX-2/PGE2, HGF/c-Met and PI3K/Akt/mTOR are involved in these inhibition effects. This review examines the anti-angiogenesis potential of natural products in the GIC treatment and provides clues to the development of vascular targeted agents.

Background. Radioimmunotherapy has become one of the most promising strategies for cancer treatment. Preclinical and clinical studies have demonstrated that antiangiogenic therapy can improve the efficacy of immunotherapy and sensitize radiotherapy through a variety of mechanisms. However, it is undefined whether angiogenesis inhibitors can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of anlotinib (AL3818) on the combination of radiotherapy and immune checkpoint inhibitors in Lewis lung carcinoma mouse. Methods. C57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control. Immune response and immunophenotyping including the quantification and activation were determined by flow cytometry, multiplex immunofluorescence, and multiplex immunoassay. Results. Triple therapy (radiotherapy combined with anti-PD-L1 and anlotinib) increased tumor-infiltrating lymphocytes and reversed the immunosuppressive effect of radiation on the tumor microenvironment in mouse model. Compared with radioimmunotherapy, the addition of anlotinib also boosted the infiltration of CD8+ T cells and M1 cells and caused a decrease in the number of MDSCs and M2 cells in mice. The levels of IFN-gamma and IL-18 were the highest in the triple therapy group, while the levels of IL-23, IL-13, IL-1 beta, IL-2, IL-6, IL-10, and Arg-1 were significantly reduced. NF-κB, MAPK, and AKT pathways were downregulated in triple therapy compared with radioimmunotherapy. Thus, the tumor immune microenvironment was significantly improved. As a consequence, triple therapy displayed greater benefit in antitumor efficacy. Conclusion. Our findings indicate that anlotinib might be a potential synergistic treatment for radioimmunotherapy to achieve better antitumor efficacy in NSCLC patients by potentiating the tumor immune microenvironment.

Using CdTe QDs and Probe-Cu2+ as signal reporters, a dual-fluorescence, binary-color distance-reading method for PPase analysis was developed; dip-dying and ink-jet printing were used to make test strips for the clinical diagnosis of hyperthyroidism.

Berberis amurensis Rupr. is used to treat cancer as a traditional herbal medicine. Berbamine (BBM) is a natural bisbenzylisoquinoline alkaloid extracted from Berberis amurensis which possesses multiple pharmacological activity including anticancer.To investigate the influence of BBM on the progression of colorectal cancer (CRC) and further explore the underlying mechanism of BBM based on the RTKs/Akt signaling pathway.In vitro, cell viability and colony formation were conducted to detect BBM inhibitory of CRC cell lines. Transwell was detected the ability of migration and invasion by BBM. Apoptosis detection assay, cell cycle assay and the measurement of ROS were detected to confirm the inductive effect of cell apoptosis. RT-qPCR and Western blot to clarify the specific mechanism of anticancer. Finally, we conducted HE staining, Ki67, Tunnel and immunochemistry were confirmed the anti-colorectal cancer activity of BBM from vivo study.We found that BBM could inhibit CRC cell lines growth. Moreover, BBM presented an inhibitory effect the ability of migration and invasion in CRC cells. Furthermore, the occurrence of apoptosis was involved in the anti-colorectal cancer role of BBM. BBM also triggered ROS accumulation in CRC cells that might be a key factor for the inductive effect of BBM in cell apoptosis. Cell cycle assay revealed that BBM induced the arrest of G1-S phase and increased the p21 levels but decreased CyclinE1, CyclinE2, CDK6, CyclinD1. RT-qPCR manifested that the down-regulation effect of BBM on AKT1, EGFR, PDGFRα and FGFR4 genes. The results also showed that BBM could decreased the expression levels of phosphor-AKT, PDGFRα, PDGFRβ, EGFR, FGFR3 and FGFR4 which belong to RTKs family. Consistently, BBM remarkably suppressed tumor xenograft growth in nude mice.Taken together, all the results as presented above suggest that BBM as a novel multitargeted receptor tyrosine kinase inhibitor plays a crucial role in the inhibitory effect of CRC and may be a promising therapeutic agent for the CRC in clinic.

Radiation measurement at underwater environment helps to get a better understanding on sedimentation, geological structure, radiation monitoring, and so on. However, reports about radiation of natural underwater environment are rare, especially in situ gamma radiation measurement. Two gamma spectrometers are going to be used in underwater in situ radiation measurement. Aiming at different scientific goals, the spectrometers can develop multiple kinds of measurements, including dose and energy spectrum of gamma rays. In this article, a compatible data acquisition (DAQ) system is proposed. The DAQ provides features of readout, visualization, data process algorithm, and file input and output. To benefit from high reusability and low coupling, the Model-View-ViewModel (MVVM) pattern is adopted in the DAQ system. With an application layer protocol based on Modbus, the DAQ can be fully compatible with different spectrometers. Besides supporting of real-time control, the DAQ system also provides a way to program the spectrometers to execute an unmanned mission, so that the spectrometers can load a timetable from a built-in flash memory and run automatically.

In this paper, a portable gamma-ray spectrometer for real-time and in-situ gamma-ray detection applications is presented. By combining a quasi-hemispherical CdZnTe (CZT) semiconductor detector and a Geiger-Muller (GM) counter together, a wide dose rate range is achieved, ranging from 0.1 μSv/h to 100 mSv/h with a relative error of less than 10%. The GM counter is used to measure dose rate from 1 mSv/h to 100 mSv/h. With CZT, the spectrometer can provide a high energy resolution spectrum for nuclide identification and a high precision dose rate at low dose rates. The full width half maximum (FWHM) resolution is 2.2% at 662 keV below 70 μSv/h and is better than 3.3% at 3.8 mSv/h. The weight of the spectrometer is 3.2 kg for handheld and the runtime is up to 12 h without charging. For preliminary applications, the spectrometer was used to measure the gamma radiation around the Back-n white neutron beam line at China Spallation Neutron Source and around the steam generator in the nuclear power plant at Daya Bay Nuclear Power Station.

Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.

The Back-n white neutron source at the China Spallation Neutron Source (CSNS) provides neutrons in the continuous energy region from 0.5 eV to 200 MeV. A spectrometer named Light charged Particle Detector Array (LPDA) is designed for the study of (n, lcp) reactions at Back-n. The main detector of the LPDA spectrometer, a 16-unit ΔE-ΔE-E telescope array, is composed of two arrays of 8-unit ΔE-ΔE-E telescope. Each telescope unit consists of a Low-Pressure Multi-Wire Proportional Chamber (LPMWPC), a Si-PIN detector, and a CsI(Tl) scintillator detector. In 2021, a neutron-proton (n-p) scattering reaction cross-section measurement experiment was accomplished as the first experiment of the telescope array. Protons can be clearly identified in the ΔE-E spectrum (LPMWPC + Si-PIN) and the ΔE-E spectrum (Si-PIN + CsI(Tl)). Cross sections of the n-p scattering reaction in the neutron energy range of several MeV are extracted. The ΔE-E method also provides new measurement opportunities for many-body neutron induced light charged-particle emission reactions.

Cancer stem cells (CSCs) are strongly associated with high tumourigenicity, chemotherapy or radiotherapy resistance, and metastasis and recurrence, particularly in colorectal cancer (CRC). Therefore, targeting CSCs may be a promising approach. Recently, discovery and research on phytochemicals that effectively target colorectal CSCs have been gaining popularity because of their broad safety profile and multi-target and multi-pathway modes of action.This review aimed to elucidate and summarise the effects and mechanisms of phytochemicals with potential anti-CSC agents that could contribute to the better management of CRC.We reviewed PubMed, EMBASE, Web of Science, Ovid, ScienceDirect and China National Knowledge Infrastructure databases from the original publication date to March 2022 to review the mechanisms by which phytochemicals inhibit CRC progression by targeting CSCs and their key signalling pathways. Phytochemicals were classified and summarised based on the mechanisms of action.We observed that phytochemicals could affect the biological properties of colorectal CSCs. Phytochemicals significantly inhibit self-renewal, migration, invasion, colony formation, and chemoresistance and induce apoptosis and differentiation of CSCs by regulating the Wnt/β-catenin pathway (e.g., diallyl trisulfide and genistein), the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway (e.g., caffeic acid and piperlongumine), the neurogenic locus notch homolog protein pathway (e.g., honokiol, quercetin, and α-mangostin), the Janus kinase-signal transducer and activator of transcription pathway (e.g., curcumin, morin, and ursolic acid), and other key signalling pathways. It is worth noting that several phytochemicals, such as resveratrol, silibinin, evodiamine, and thymoquinone, highlight multi-target and multi-pathway effects in restraining the malignant biological behaviour of CSCs.This review demonstrates the potential of targeted therapies for colorectal CSCs using phytochemicals. Phytochemicals could serve as novel therapeutic agents for CRC and aid in drug development.

Background: Colorectal cancer, as a general malignancy of the digestive system, has long constituted a threat to the health of the population and the development of the social economy. It has been widely recognized that exploiting a drug with weaken toxic side effects and excellent antitumor activity can be a viable and promising strategy. Nitidine chloride is a typical bioactive base extracted from the dried roots of the Zanthoxylum nitidum (Roxb.) DC, has been clinically evidenced to exhibit robust immune efficacy against several types of tumor cells. However, the underlying function mechanism of the anti-colorectal-cancer effectiveness is still in its exploratory stage and thereby deserves further in-depth investigations.Objective: To examine the anti-cancer activity of Nitidine chloride against colorectal cancer in vitro and in vivo and its mechanism of effect.Methods: In this work, we combined a series of cellular characterization techniques to examine the inhibitory effect of Nitidine chloride (NC) on colorectal cancer cells, including RKO, HCT116 and HT29 cells. In addition, the potential signaling pathways were clarified via transcriptome sequencing technique. Moreover, we proposed a reliable biomedical mechanism towards the inhibition effects of the NC against colorectal cancer on the basis of qRT-PCR and western blot.Results: At first, we examined the toxic effect of NC on several colorectal cancer cells (RKO, HCT116 and HT29), within which the value of IC30 and IC50 were determined to be 2 µM and 3 µM for RKO; 3.5 µM and 5 µM for HCT116; and 6 µM and 10 µM for HT29, respectively. Through transcriptome sequencing, it is acquired that the p53 pathway and downstream signaling was prominently activated, indicating that NC is strongly correlated with cell proliferation and apoptosis. We also reveal that NC was able to suppress malignant behaviors, including proliferation, migration, invasion and tumor formation in RKO, HCT116 and HT29 cells. Besides, NC treatment significantly modified EMT-related hall marker proteins, including E-cadherin, N-cadherin and MMP9, which is indicative of the inhibition of EMT. Furthermore, the IC50 of NC significantly upregulated the pro-apoptosis-related factors, including Bax, Noxa, and caspase-3 and down-regulated the apoptosis-inhibiting factor Bcl2. Conclusion: In conclusion, the above experimental results and data analysis pointed out that colorectal cancer can be considerably suppressed by NC treatment, which effectively activates p53 signaling. Our approach should hold substantial promise for therapeutic applications in the therapy of colorectal cancer.

Objective. Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide. However, the pyroptosis-related lncRNAs of COAD have not been deeply examined and validated. Here, we constructed and validated a risk model on pyroptosis-related lncRNAs in COAD. Methods. The RNA sequencing transcriptome and clinical data of COAD patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed pyroptosis-related mRNAs and mRNA-lncRNA coexpression network were identified. After univariate and multifactorial cox analyses of prognosis-related lncRNAs, a risk model was constructed. Next, we analyzed the differences in immune infiltration, immune checkpoint blockade-, immune checkpoint-, and N6-methyladenosine-related gene expressions between the high- and low-risk groups. RT-qPCR was used to validate the expression of lncRNAs. Result. A risk model was constructed based on 9 pyroptosis-related lncRNAs and separated COAD patients into the high- and low-risk groups. Immune infiltration analysis and immune checkpoint blockade-, immune checkpoint-, and N6-methyladenosine-related genes showed significant differences between the two subgroups. RT-qPCR showed that the 9 pyroptosis-related lncRNAs could be used as prognostic indicators. Conclusion. A novel risk model based on pyroptosis-related lncRNAs was constructed and demonstrated that these lncRNAs might be used as independent prognostic biomarkers. This will also assist shed light on the COAD prognosis and therapy.

Ginsenoside Rg3 (GRg3) is a ginsenoside extracted from Panax ginseng. GRg3 displays multiple pharmacological properties, such as antitumor, anti-inflammatory, antioxidative and antifibrotic properties. However, whether GRg3 inhibits angiogenesis in gastric precancerous lesions (GPLs) and the possible mechanisms remain unknown. GRg3 attenuated gastric intestinal metaplasia and gastric dysplasia, the hallmark of GPL pathology, in rats with MNNG-ammonia compound induced GPLs. Increased CD34+ microvessel density and VEGF expression, which indicate the presence of angiogenesis, were evident in the rats with GPLs. GRg3 administration reduced VEGF protein expression and CD34+ microvessel density. In addition, GRg3 was capable of attenuating microvascular abnormalities. Data analysis revealed that enhanced protein expression of GLUT1, GLUT3 and GLUT4 were present in both human and animal GPL specimens. The administration of GRg3 caused significant decreases in the mRNA and protein expression levels of GLUT1 and GLUT4 in the rats with GPLs. However, the GRg3-treated rats with GPLs did not demonstrate regulatory effects on GLUT3, GLUT6, GLUT10, and GLUT12. Consistent with in vitro results, GRg3 administration significantly reduced the protein expression levels of GLUT1 and GLUT4 in both AGS and HGC-27 human gastric cancer cells in vitro. In conclusion, GRg3 can attenuate angiogenesis and temper microvascular abnormalities in rats with GPLs, which may be associated with its inhibition on the aberrant activation of GLUT1 and GLUT4.

Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression.To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of "inflammation-cancer transformation" and thus blocking GPL to prevent the development of gastric cancer.In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo.The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/β-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/β-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice.Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/β-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL.

Mitochondria are the energy factories of cells with the ability to modulate the cell cycle, cellular differentiation, signal transduction, growth, and apoptosis. Existing drugs targeting mitochondria in cancer treatment have disadvantages of drug resistance and side effects. Phytochemicals, which are widely found in plants, are bioactive compounds that could facilitate the development of new drugs for gastric cancer. Studies have shown that some phytochemicals can suppress the development of gastric cancer.We searched for data from PubMed, China National Knowledge Infrastructure, Web of Science, and Embase databases from initial establishment to December 2021 to review the mechanism by which phytochemicals suppress gastric cancer cell growth by modulating mitochondrial function. Phytochemicals were classified and summarized by their mechanisms of action.Phytochemicals can interfere with mitochondria through several mechanisms to reach the goal of promoting apoptosis in gastric cancer cells. Some phytochemicals, e.g., daidzein and tetrandrine promoted cytochrome c spillover into the cytoplasm by modulating the members of the B-cell lymphoma-2 protein family and induced apoptotic body activity by activating the caspase protein family. Phytochemicals (e.g., celastrol and shikonin) could promote the accumulation of reactive oxygen species and reduce the mitochondrial membrane potential. Several phytochemicals (e.g., berberine and oleanolic acid) activated mitochondrial apoptotic submission via the phosphatidylinositol-3-kinase/Akt signaling pathway, thereby triggering apoptosis in gastric cancer cells. Several well-known phytochemicals that target mitochondria, including berberine, ginsenoside, and baicalein, showed the advantages of multiple targets, high efficacy, and fewer side effects.Phytochemicals could target the mitochondria in the treatment of gastric cancer, providing potential directions and evidence for clinical translation. Drug discovery focused on phytochemicals has great potential to break barriers in cancer treatment.

In the 21st century, the tension between economic growth, resources and the environment in countries around the world is increasing, and the sustainable development of the economy and society is under great pressure. Green development has become the only way for countries to promote sustainable development. Generally, capitalist countries achieve their green development goals through increasingly strict environmental protection regulations, technological upgrading, industrial upgrading and global transfer based on market mechanisms and legal environments. Evidently, this green development strategy relies on the core position of Western countries in the global technological leadership and the global division of labor. However, limited in terms of their economic strength and by technical barriers, how can developing countries, led by China, in the marginal position in the global market competition, carry out green development transformation? In line with the “high-quality development” strategy, governments at all levels in China are actively exploring green development strategies with their own characteristics. Based on the Second Tibetan Plateau Scientific Expedition and Research and the face-to-face interview method, this paper summarizes a new strategy of systematic government-driven green development combining internal and external factors in the underdeveloped areas of inland China, which has gradually formed in the Xining metropolitan area (XMA) in the past 20 years. This strategy has the following characteristics: Firstly, during the period of rapid growth, the XMA areas have promoted each other through new urbanization and new industrialization and jointly promoted the formation of a green development turn in the new era. Secondly, the government is the core actor and driving force of China’s regional green development and has gradually formulated and implemented a series of policy systems during this development. Restricted by local economic backwardness and low industrial profits, the implementation of green government policies tends to be mandatory. The majority of urban residents and rural people support this transformation because they have benefited from the transformation process. Thirdly, this green development strategy is reflected in many aspects, such as industry, ecology, the environment, space and transportation, and is part of a systematic, green-oriented transformation. Fourthly, the advantages of the socialist system with Chinese characteristics are the guarantee of the green development strategy. It is noteworthy that this kind of green development transformation requires a large amount of “additional” investment and the “rapid” upgrade of the industry. Therefore, it requires more time and the understanding and assistance of all sectors of society.

BackgroundCancer stem cells (CSCs) are able to survive after cancer therapies, resulting in tumor progression and recurrence, as is seen in colorectal cancer. Therapies targeting CSCs are regarded as novel and promising strategies for efficiently eradicating tumors. Berberine, an isoquinoline alkaloid extracted from the Chinese herbal medicine Coptis chinensis, was found to have antitumor activities against colorectal cancer, without knowing whether it exerts inhibitory effects on colorectal CSCs and the potential mechanisms.MethodsIn this study, we examined the inhibitory roles of Berberine on CSCs derived from HCT116 and HT29 by culturing in serum-free medium. We also examined the effects of Berberine on m6A methylation via regulating fat mass and obesity-associated protein (FTO), by downregulating β-catenin.ResultsWe examined the effects of Berberine on the tumorigenicity, growth, and stemness of colorectal cancer stem-like cells. The regulatory effect of Berberine on N6-methyladenosine (m6A), an abundant mRNA modification, was also examined. Berberine treatment decreased cell proliferation by decreasing cyclin D1 and increasing p27 and p21 and subsequently induced cell cycle arrest at the G1/G0 phase. Berberine treatment also decreased colony formation and induced apoptosis. Berberine treatment transcriptionally increased FTO and thus decreased m6A methylation, which was reversed by both FTO knockdown and the addition of the FTO inhibitor FB23-2. Berberine induced FTO-related decreases in stemness in HCT116 and HT29 CSCs. Berberine treatment also increased chemosensitivity in CSCs and promoted chemotherapy agent-induced apoptosis. Moreover, we also found that Berberine treatment increased FTO by decreasing β-catenin, which is a negative regulator of FTO.ConclusionsOur observation that Berberine effectively decreased m6A methylation by decreasing β-catenin and subsequently increased FTO suggests a role of Berberine in modulating stemness and malignant behaviors in colorectal CSCs.

Background:Many specific biomarkers and target genes of gastric cancer have been identified, but the research areas on the characterization of epigenetic and transcriptional landscape in the process of gastric carcinogenesis, known as the trilogy from normal mucosa to precancerous lesions and finally to gastric cancer, remains a black box.Results:We performed whole-transcriptome sequencing and ATAC-seq based on human gastric tumours (T), gastric precancerous lesions (P) and normal gastric mucosa (N) and obtained chromatin open regions, circRNAs, lncRNAs, miRNAs, and mRNAs. Subsequently, differential expression analysis was performed on the N, P, and T groups, followed by GO, KEGG, and PPI analyses to investigate cancer-related hub genes (e.g., VEGFA, FN1, CDK1, and MYC) and extracellular matrix related signalling pathways that might serve as potential therapeutic targets in precancerous lesions and early gastric cancer. A core competing endogenous RNA (ceRNA) network was then constructed that contained 17 mRNAs, 11 miRNAs, 11 lncRNAs and two circRNAs, and the RNAs were validated by TCGA database and RT-PCR to prove they play crucial roles in the trilogy of gastric carcinogenesis; notably, hsa-miR-1226-5p, hsa-miR-6720-5p, lncRNA H19, ARID3A and GPR161 were significantly enriched in the complex network, which might be specificity tumour markers. Finally, ROC curve analysis suggested that nine mRNAs and five lncRNAs may be novel biomarkers with clinical implications for the precise diagnosis of early gastric cancer. Survivorship curve analysis further identified four mRNAs and one lncRNA as potential prognostic indicators. Conclusions:These results reveal a panel of premalignant and malignant specific marker genes in the trilogy of gastric carcinogenesis, potentially aiding the early identification of precancerous lesions and early gastric cancer. Meanwhile, the present study identifies the key molecular targets in the dynamic process of gastric carcinogenesis for experimental research on drugs and molecular mechanisms.

Denitrification during composting is a hidden danger that causes environmental pollution risk and aromatic humic substance damage, which needs to be better regulate urgently. In this study, two denitrification regulation methods, moisture and biochar amendment, were conducted during chicken manure composting. Denitrification performance data showed two regulation methods obviously reduced NO3−-N, NO2−-N and N2 contents. Humic substance increased by 25.3 % and 29.1 % under two regulations. Microbiological analysis indicated that two regulation methods could decreasing denitrifying functional microbes with aroma degradation capability. Subsequently, denitrification gene narG, nirS, nosZ were significantly inhibited (p

The aim of this study was to evaluate nitrogen pollution risks from distinct materials composting with the discrepancy of component, including chicken manure, municipal solid and straw waste (CM, MSW, SW). Results showed total nitrogen maximum mean concentrations were observed in CM (39.57 g/kg). Pollution risks in CM were continuous, while MSW and SW mainly concentrated during heating phases. Microbial analysis confirmed that pollution risks from ammonification and nitrification were more prevalent in CM. The risks of pollution caused by nitrate reduction accompanied N2O were the most serious in MSW. The multifunctional nitrogen-related microbes Pseudomonas and Bacillus were affected by microenvironments and contributed to different pollution risks. Furthermore, PICRUSt analysis identified the “inferred” key genes (pmoC-amoC, nrfH, nifD etc.) related to nitrogen pollution risks. This study evaluated nitrogen pollution risks and proposed the future directions, providing theoretical basis and feasible optimization measures for the mitigation of nitrogen pollution during composting.

Hypertrophic pulmonary osteoarthropathy (HPOA), mainly manifested clubbing, is rare in patients with esophageal sarcomatoid carcinoma. We herein describe a 48-year-old Chinese man whose advanced sarcomatoid carcinoma was diagnosed while examining his symptoms of HPOA. The patient had no opportunity of surgery after surgical evaluation. Chemoradiation, including 5 cycles of chemotherapy (Paclitaxel liposome 60 mg day 1 and nedaplatin 30 mg day 1, q1w) and 6MV-X/VMAT-95%PGTV 59.92 Gy/2.14 Gy/28 F and 95%PTV 50.4 Gy/1.8 Gy/28 F, and subsequent 6 cycles of chemotherapy (paclitaxel liposome 210 mg day 1 and nedaplatin 50 mg day 1, 60 mg day 2, q3w) shrank the tumor and the condition of the patient became stable without clubbing remission or exacerbation. No medical case report found in a PubMed search in the indexed English-language literature in the past 20 years, though there are some reports of HPOA combined with other pathologic types of esophageal carcinoma. The patient's condition was effectively controlled by chemotherapy and radiotherapy and showed stable disease. However, the five-year survival rate of advanced esophageal carcinoma patients is very low with low life quality, and the adverse reactions also contribute to low life quality. The purpose of this report is to present the feature and our treatment for primary esophageal sarcomatoid carcinoma with HPOA, which could be helpful for further understanding of the disease and clinical decision making. Moreover, this article also reviews esophageal carcinoma with HPOA and sarcomatoid carcinoma in the esophagus. We look forward to the breakthrough of immunotherapy and molecular targeting therapy to improve the situation.

The aims of this article were to study the effect of Fenton pretreatment and bacterial inoculation on cellulose-degrading genes and fungal communities during rice straw composting. The rice straw was pretreated by Fenton reactions and functional bacterial agents were then inoculated during the cooling phase of composting. Three treatment groups were carried out, the control (CK), Fenton pretreatment (FeW) and Fenton pretreatment and bacterial inoculation (FeWI). The results indicated that Fenton pretreatment and bacterial inoculation changed the fungal communities composition and increased fungal diversity, leading to changes in the cellulose-degrading genes. In addition, a network analysis showed that in the FeWI treatment, the fungi from modules 1, 5 and 8 were core hosts of the cellulose-degrading genes driving the cellulosic degradation. Moreover, Fenton pretreatment and bacterial inoculation changed the core module fungal communities and strengthened the correlation between the core fungi and the cellulose-degrading genes, thereby promoting cellulosic degradation. Based on redundancy and structural equation model analyses, the NH4+-N, TOC, pH and Shannon index were important factors influencing the variations in the cellulose-degrading genes. This study provides a foundation for cellulosic degradation during cellulosic waste composting.

The aim of this study was to clarify the aromatic cleavage pathways and microbes involved in the adverse effect of nitrate on aromatic compounds humic substances during sludge composting. Results showed that the functional microbes involved in aromatic compounds humic substances precursors (catechol, tyrosine, tryptophan and phenylalanine) cleavage pathways significantly enriched after nitrate addition. Linear regression analysis showed that aromatic-ring cleavage functional microbes exhibited significant negative correlation with aromatic humic substances (p 0.05). Furthermore, network analysis indicated that most of microbial communities prefer cooperative with aromatic-ring cleavage functional microbes. Structural equation model further revealed that composting microenvironment drove aromatic-ring cleavage functional microbes activities, resulting in the biodegradation of complex aromatic compounds. This study parsed the effect of a negative factor on aromatic compounds humic substances from an opposing perspective. Properly controlling nitrate concentration and aromatic-ring cleavage functional microbes involved in precursors cleavage was suggested to the practice of composting.

Breast and colonic carcinomas are two main origins of metastatic liver cancer. Chemotherapy, which introduces various anticancer drugs such as paclitaxel, is an important cure for patients who are not suitable for surgery and transcatheter hepatic arterial chemoembolization. However, the poor water solubility and serious side effects have limited the use of paclitaxel. Nanoparticles are promising carriers for paclitaxel to overcome these limitations. Besides, relatively consistent drug absorption by peritoneum into the liver through the portal system can be obtained if paclitaxel is given through intraperitoneum, which is beneficial to the therapy of metastatic liver cancer. In this study, we used our newly synthetic copolymer thermogels, PDLLA-PEG-PDLLA hydrogel as a carrier of paclitaxel-loaded nanoparticles. This novel injectable thermosensitive hydrogel is able to transfer into physically cross-linked non-flowing gel structure in body temperature with acceptable biocompatibility and biodegradability. The results showed that paclitaxel nanoparticle carried by PDLLA-PEG-PDLLA gel illustrated good liver metastatic cancer suppression efficacy. We also discussed the alterations of inflammatory cells (MDSCs and TAMs) and several inflammatory factors during the treatments. Nano-PTX-GEL led to more obvious reduction of infiltration of MDSCs in metastatic liver cancers, compared with free paclitaxel and Nano-PTX treated groups. In addition, we revealed that free paclitaxel treatment resulted in higher levels of IL-6, IL-10, PDL-1, TGF-β1, TNF-α and VEGF, while the expression levels of these inflammatory factors were much lower in the other two groups, especially in the Nano-PTX-GEL treated groups. These results suggested that utilization of PDLLA-PEG-PDLLA hydrogel as a carrier for paclitaxel could reduce inflammatory reaction induced by paclitaxel in liver metastatic cancers treatment. Besides, in this study, we used a simpler method to build liver metastatic cancer model through surgery, which can control the bias of results.