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The characteristics of the catalytic hydrogasification of activated carbon/bituminous char/anthracite char with the different catalysts were studied in a pressurized thermogravimetry analysis (PTGA). The GC, BET were used to characterize the physical structure and chemical reaction process of carbon, and the function principle of Co to the carbon-hydrogen reaction was preliminarily obtained. The results show that the catalytic activity of transition metals (Fe, Co, Ni) is significantly higher than that of alkali metals and alkaline earth metals in CCHG process. Transition metal CCHG process exists in low temperature (600−750 ℃) and high temperature (> 800 ℃), the emergence of the low temperature catalytic zone can be attributed to the interaction between the transition metal oxide and carbon, then part of carbon structure is activated. The transition metal is embedded in carbon layer structure, the effects of breaking C-C bond and proving the active hydrogen are more effective. Under the conditions of Co catalyst above 850 ℃ and 1 MPa hydrogen pressure, the hydrogen supply of the catalyst can reach saturation, and the catalytic hydrogasification process of carbon is mainly the catalytic bond breaking reaction induced by temperature. The model carbon with high specific surface area and low density has high CCHG activity with the low catalyst load.

Supplemental material, sj-docx-1-asn-10.1177_17590914231169140 for Activation of the PACAP/PAC1 Signaling Pathway Accelerates the Repair of Impaired Spatial Memory Caused by an Ultradian Light Cycle by Dejiao Xu, Ying Zhang, Jun Feng, Hongyu Fu, Jiayi Li, Wei Wang, Zhen Li, Pingping Zhang, Xinqi Cheng, Liecheng Wang and Juan Cheng in ASN Neuro

What is known and objective Although several clinical trials have compared the clinical efficacy of clomiphene citrate (CC) combined with metformin (MET) in the treatment of women with polycystic ovary syndrome (PCOS), the results are controversial. Therefore, this study was designed to conduct a pooled analysis to evaluate the efficacy of CC combined with MET versus CC in these patients. Methods Computerized searches of the PubMed, Web of Science, Embase and Cochrane Library databases were conducted to identify eligible randomized controlled trials (RCTs) from the data obtained up to June 2021. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias in individual RCTs, and RevMan 5.4 was used for data statistical analysis. Results and discussion A total of 13 RCTs were included in the meta-analysis. These studies involved 1,353 patients, 707 of these were in the combination group and 646 in the monotherapy group. The results indicated a higher clinical pregnancy rate (risk ratio [RR] 1.28, 95% confidence interval [CI] 1.06-1.54, p = 0.01) in the combined group compared to the monotherapy group. However, no significant differences were observed in the ovulation rate (RR 1.13, 95% CI 0.98-1.30, p = 0.10), live birth rate (RR 1.13, 95% CI 0.89-1.42, p = 0.32), multiple pregnancy rate (RR 0.58, 95% CI 0.19-1.73, p = 0.33) and abortion rate (RR 1.26, 95% CI 0.86-1.84, p = 0.23) between the two groups. What is new and conclusion CC combined with MET has an advantage in improving the clinical pregnancy rate compared to CC alone; however, there is no significant difference in the rate of ovulation. For better management of PCOS, a high-quality RCT is needed to demonstrate the safety of the combination.

BACKGROUND: Infantile hemangioma (IHA) is the most common tumor in infancy. We aimed to explore the effect of propranolol on the expression of microRNA (miR)-424 in IHA tissues and XPTS-1 cells, as well as its molecular mechanism of inhibiting XPTS-1 cell activity. METHODS: Tumor tissues and peritumoral tissue were collected from 13 IHA patients in Lishui Municipal Central Hospital. The level of miR-424 were detected using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Cell counting kit-8 (CCK-8) was used to measure XPTS-1 cell viability. Flow cytometry and transwell were used to detect the apoptosis level and invasion ability of XPTS-1 cells. Western blot was used to measure the protein level of vascular endothelial growth factor-A (VEGFA). The luciferase reporter gene assay detected the targeting relationship between miR-424 and VEGFA. RESULTS: Compared with normal tissues and human umbilical vein endothelial cells, the expression level of miR-424 in IHA tissues and XPTS-1 cells was significantly reduced (P

Hypoxia affects proliferation, differentiation, as well as death of cardiomyocyte, and plays an important role in the development of myocardial ischemia. However, the detailed mechanisms through which hypoxia regulates cardiomyocyte ferroptosis have not been explored. In this study, we revealed that hypoxia suppresses the proliferation, migration, and erastin-induced ferroptosis of H9c2 cells. First, we confirmed the upregulation of SENP1 in H9c2 cells cultured under hypoxic conditions. Through adenovirus-mediated SENP1 gene transfection, we demonstrated that SENP1 overexpression could enhance H9c2 cell proliferation and migration while also protecting H9c2 cells from erastin-induced ferroptosis. Furthermore, through immunoprecipitation and western blotting, we confirmed that SENP1 mediated deSUMOylation of HIF-1α and ACSL4 in H9c2 cells. In conclusion, this study describes the underlying mechanism through which hypoxia upregulates SENP1 expression, in turn protecting against ferroptosis via the regulation of HIF-1α and ACSL4 deSUMOylation. Our findings provide a theoretical foundation for the development of novel therapeutics for ischemic heart diseases.

Differentiation therapies with all-trans retinoic acid (ATRA) have been successful in treating acute promyelocytic leukemia, a rare subtype of acute myeloid leukemia (AML). However, their efficacy is limited in the case of other AML subtypes. Here, we show that the combination of ATRA with salt-inducible kinase (SIK) inhibition significantly enhances ATRA-mediated AML differentiation. SIK inhibition augmented the ability of ATRA to induce growth inhibition and G1 cell cycle arrest of AML cells. Moreover, combining ATRA and SIK inhibition synergistically activated the Akt signaling pathway but not the MAPK pathway. Pharmacological blockade of Akt activity suppressed the combination-induced differentiation, indicating an essential role for Akt in the action of the combination treatment. Taken together, our study reveals a novel role for SIK in the regulation of ATRA-mediated AML differentiation, implicating the combination of ATRA and SIK inhibition as a promising approach for future differentiation therapy.

Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. Mutations in the TPMT gene can affect drug activity, which may have adverse effects in humans. Thus, genotyping can help elucidate genetic determinants of drug response to thiopurines and optimize the selection of drug therapies for individual patients, effectively avoiding palindromia during maintenance treatment caused by insufficient dosing and the serious side effects caused by excessive doses. The current available detection methods used for TPMT*3B and TPMT*3C are complex, costly and time-consuming. Therefore, innovative detection methods for TPMT genotyping are urgently required. The aim of the present study was to establish and optimize a simple, specific and timesaving TPMT genotyping method. Using the principles of Web-based Allele-Specific PCR and competitive real-time fluorescent allele-specific PCR (CRAS-PCR), two pairs of Scorpion primers were designed for the detection of TPMT*3B and *3C, respectively, and a mutation in TPMT*3A was inferred based on data from TPMT*3B and *3C. In total, 226 samples from volunteers living in Chongqing were used for CRAS-PCR to detect TPMT*3 mutations. Results showed that nine (3.98%) were mutant (MT) heterozygotes and none were MT homozygotes for TPMT*3C, and no TPMT*3A and TPMT*3B mutations were found. Three TPMT*3C MT heterozygotes were randomly selected for DNA sequencing, and CRAS-PCR results were consistent with the sequencing results. In conclusion, in order to improve simplicity, specificity and efficiency, the present study established and optimized CRAS-PCR assays for commonly found mutant alleles of TPMT*3A (G460A and A719G), TPMT*3B (G460A), and TPMT*3C (A719G).

Background The hand and wrist are most often in contact with electrical currents and thus most vulnerable to severe electrical burns. The treatment of such severe injury via surgical intervention remains a big challenge because of the vast tissue necrosis and the segmental vascular injury. The flow-through lateral-thigh free flap has been used effectively to resurface these defects and to reconstruct segmental vascular defects. Methods Between January 2014 and June 2017, 11 male patients aged 19 to 53 years were admitted to the burn unit of our institution. Each presented with severe electrical burns to the wrist with long segmental vascular injury, and 2 cases suffered from electrical burn on both wrists. After radical debridement, the soft-tissue and segmental artery defects were rebuilt through the application of flow-through lateral-thigh free flap for 1 of the ulnar or radial artery injury (7/12). Ulnar artery defects were rebuilt through the application of flow-through lateral-thigh free flap, and radial artery revascularization was done using a greater saphenous vein graft for both ulnar and radial artery injuries (5/12). Vascular condition was closely monitored throughout the treatment period. Results Forearm amputation was performed in 1 case as a result of distal immediate necrosis postinjury. Successful limb salvage was achieved in the other 12 wrists. Infection beneath the flap occurred in 3 cases but resolved after debridement. Over the course of the 3- to 12-month follow-up period, the free flaps maintained good texture and sharpness, distal circulation of affected limb became well established, and the appearances of the donor sites were acceptable. Conclusions High-voltage electrical burns of the wrist are highly destructive, and sophisticated management of damage requires concomitant vascular reconstruction and soft-tissue coverage. The flow-through anterolateral-thigh flap is an optimal solution for this problem. Emphasis must be placed on the affected blood vessel throughout the treatment period.

Epilepsy is one of the most common diseases of the nervous system. Neuronal apoptosis is closely involved in the development and progression of epilepsy. Triptolide is a widely used immunosuppressive agent in traditional Chinese medicine. However, a neuroprotective role of triptolide in epilepsy has been suggested but not fully explored. To this end, using pentylenetetrazol-induced seizures in rats as a model for epilepsy, we explored the effect of triptolide on seizure and its associated mechanisms. The results showed that triptolide significantly decreased the seizure severity and inhibited the apoptosis of neurons, accompanied by an improvement in the expression of miR-187 in the hippocampus region in pentylenetetrazol-treated rats. The up-regulation of miR-187 expression could inhibit neuronal apoptosis in the hippocampus. Finally, the results showed that miR-187 antagomir significantly reversed the protective effects of triptolide in pentylenetetrazol-treated rats. To the best of our knowledge, this is the first study demonstrating that triptolide inhibits neuronal apoptosis, at least partially, through up-regulating miR-187.

Background Gastric cancer is the third most lethal malignant tumor worldwide. Metastasis has always been a major cause of poor prognosis. Epidemiological evidence shows that the most common sites for metastasis of gastric carcinoma are the liver (48%), peritoneum (32%), lung (15%), and bone (12%); however, subcutaneous metastasis is are and occurs in approximately 0.8% of cases. We report a rare case of armpit subcutaneous metastasis of gastric cancer. The best surgical window was missed, as a result of lacking attention of the mass. Case summary A 69-year-old man who had previously undergone radical gastrectomy and received eight cycles of oral chemotherapy for gastric cancer showed a rapidly growing mass in his the left armpit; within just 3 mo, the mass grew to a size of 6.9 cm × 4.4 cm × 5.7 cm. Color Doppler ultrasonography and Positron emission tomography/computed tomography prompted the possibility of metastasis of the malignancy. Fine needle aspiration biopsy guided by color Doppler ultrasound showed the presence of cancer cells in the mass. Immunohistochemical examination showed CDX-2 (+), PCK (+), CK20 (+), CK7 (-), and TTF (-), which supported the metastasis of gastric cancer. Considering the risk of resection, the patient did not undergo surgical treatment. Conclusion The case indicates that unidentified subcutaneous masses in patients with a history of gastric cancer should be carefully evaluated.

The incidence rate of electrical injury has remained stable, while the absolute case number has increased. Amputations, erosions, occlusions, and delayed blood vessel rupture are the common complications. Ectopic implantation salvage has been performed widely in mechanical trauma patients, to preserve viable or possibly viable tissues and organ, without application in the electrical injury patients to the best of our knowledge. Here, we present a case report involving ectopic implantation salvage of the left thumb before contralateral transplantation to the right hand after high-voltage electrical injury. The patient’s left thumb remained viable despite necrosis of the left forearm at 3 weeks postinjury. After debridement, we implanted the left thumb to his thigh where it was anastomosed to the lateral circumflex femoral artery’s descending branch and great saphenous vein. We replanted the left thumb on the right hand with fixation 6 weeks later. The reassembled right hand remained well-circulated 11 months postreconstruction. We believe this case supports broadening the indication for ectopic implantation salvage surgeries to patients who sustain electrical injuries.

Background: Alcoholic fatty liver disease (AFLD) is the first stage of the alcoholic liver disease course. Yin-Chen-Hao-Tang (YCHT) has a good clinical effect on the treatment of AFLD, but its molecular mechanism has not been elucidated. In this study, we tried to explore the molecular mechanism of YCHT in improving hepatocyte steatosis in AFLD mice through network pharmacology and RNA sequencing (RNA-Seq) transcriptomics. Methods: Network pharmacological methods were used to analyze the potential therapeutic signaling pathways and targets of YCHT on AFLD. Then, the AFLD mice model was induced and YCHT was administered concurrently. Liver injury was measured by serum alanine aminotransferase (ALT) activity and liver tissue H&E staining, and liver steatosis was determined by serum triglyceride (TG) level and liver tissue Oil Red staining. The molecular mechanism of YCHT on prevention and treatment of mice AFLD was investigated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differential expression genes data obtained by liver tissue RNA-Seq. Finally, the key signaling pathway and targets of YCHT on AFLD were verified in the ethanol-induced AFLD hepatocyte model by pathway inhibition experiments.Results: The results of network pharmacology analysis showed that YCHT may exert its pharmacological effect on AFLD through 312 potential targets which are involved in many signaling pathways including the PPAR signaling pathway. AFLD mice experiments results showed that YCHT markedly decreased mice serum ALT activity and serum TG levels. YCHT also significantly improved alcohol-induced hepatic injury and steatosis in mice livers. Furthermore, both KEGG analysis of RNA-Seq and AFLD hepatocyte model experiments showed that the PPAR signaling pathway should be the most relevant pathway of YCHT in the prevention and treatment of AFLD. YCHT could remarkably reduce the expression of PPARγ which is related to the lipogenesis pathway. YCHT also could increase the expression of PPARα which is related to the lipolysis pathway. Conclusions: Our study discovered that PPARγ and PPARα are the key targets and the PPAR signaling pathway is the main signaling pathway for YCHT to prevent and treat AFLD.

Background: Metformin is the first-line drug for type II diabetes, and recent studies indicate that metformin plays an inhibitory role in multiple cancers. Metformin can also enhance the effect of chemotherapy. Although head and neck squamous cell carcinoma cells are sensitive to metformin, the mechanisms related to the metformin response and the chemosensitization effect have not been fully studied. Results: In this study, we aimed to elucidate the molecular mechanisms of metformin in HNSCC by transcriptome analysis and to reveal the underlying mechanisms of the sensitizing effects of metformin by combined online dataset analysis. mRNA sequencing and functional analysis of HNSCC samples after metformin treatment and functional analysis of mRNAs with opposite metformin-induced effects in chemosensitive versus chemoresistant cells revealed the molecular pathways, mainly the base excision repair pathway, by which this small molecule drug sensitizes HNSCC cells to treatment. Conclusions: These findings indicate that metformin exerts a hypersensitization effect by regulating the BER pathway in tumour cells, reducing their self-repair capacity after chemotherapy-induced DNA damage. In addition, the genes identified by transcriptome analysis are candidates for further investigation into the effector targets of metformin in the inhibition of HNSCC and could be applied to improve the treatment in HNSCC patients who develop resistance after advanced chemotherapy.

Li-Ping Zhu,1,&ast; Wei-Lan Yin,2,&ast; Lei Peng,1,&ast; Xiao-Hong Zhou,3 Peng Zhou,1 Shu-Xia Xuan,1 Ying Luo,1 Chen Chen,1 Bin Cheng,1 Jin-Duan Lin,1 Yan-Mei Liu,1 Feng-Jun Tan,4 Wei-Guo Yin1,&ast; 1Department of Molecular Diagnosis Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, Guangdong, People’s Republic of China; 2Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, 421001, Hunan, People’s Republic of China; 3Kingmed Diagnostic Center for Clinical Laboratory, Guangzhou, 510330, Guangdong, People’s Republic of China; 4Department of Otorhinolaryngology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Guo YinDepartment of Molecular Diagnosis Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, No. B24, Xincheng Yinquan Road, Qingcheng District, Qingyuan, 511518, Guangdong, People’s Republic of ChinaTel +86 763 311 3890Email wgy09dr_mn@163.comObjective: This study explored the correlation between myocardial infarction (MI) and the Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene in the Qingyuan area.Methods: The Glu504Lys polymorphism of the ALDH2 gene was analyzed using the polymerase chain reaction and deoxyribonucleic acid microarray analysis for 468 patients diagnosed with MI for the first time and 132 healthy subjects.Results: There was a significant difference in the distribution of the ALDH2 genotype between the MI group and the control group (P = 0.0492), but there was no significant difference in allele frequency between the two groups (P = 0.1363). The clinical data showed that there were statistically significant differences (P < 0.05) in the two groups’ gender and age distributions, rates of diabetes and hypertension, levels of alcohol and tobacco use, serological levels of heart markers, blood lipids and glucose. The subgroup analysis of ALDH2 genotypes found that alcohol consumption, high levels of myoglobin, and low levels of high-density lipoprotein cholesterol were significantly associated with a higher incidence of MI (P < 0.05). After adjusting for gender, hypertension, diabetes, and other related influencing factors, logistic regression analysis showed that the ALDH2 genotype GA/AA was an independent risk factor for MI (P < 0.05, OR = 1.479, 95% CI = 1.003– 2.179).Conclusion: The presence of risk alleles with the genetic effect (ALDH2 genotype GA/AA) is an independent risk factor for MI.Keywords: myocardial infarction, aldehyde dehydrogenase 2, polymorphism

In an effort to develop a new therapy for cancer and to improve antiprogrammed death inhibitor-1 (anti-PD-1) and anticytotoxic T lymphocyte-associated protein (anti-CTLA-4) responses, we have created a telomerase reverse transcriptase promoter-regulated oncolytic adenovirus rAd.sT containing a soluble transforming growth factor receptor II fused with human IgG Fc fragment (sTGFβRIIFc) gene. Infection of breast and renal tumor cells with rAd.sT produced sTGFβRIIFc protein with dose-dependent cytotoxicity. In immunocompetent mouse 4T1 breast tumor model, intratumoral delivery of rAd.sT inhibited both tumor growth and lung metastases. rAd.sT downregulated the expression of several transforming growth factor β (TGFβ) target genes involved in tumor growth and metastases, inhibited Th2 cytokine expression, and induced Th1 cytokines and chemokines, and granzyme B and perforin expression. rAd.sT treatment also increased the percentage of CD8(+) T lymphocytes, promoted the generation of CD4(+) T memory cells, reduced regulatory T lymphocytes (Tregs), and reduced bone marrow-derived suppressor cells. Importantly, rAd.sT treatment increased the percentage of CD4(+) T lymphocytes, and promoted differentiation and maturation of antigen-presenting dendritic cells in the spleen. In the immunocompetent mouse Renca renal tumor model, similar therapeutic effects and immune activation results were observed. In the 4T1 mammary tumor model, rAd.sT improved the inhibition of tumor growth and lung and liver metastases by anti-PD-1 and anti-CTLA-4 antibodies. Analysis of the human breast and kidney tumors showed that a significant number of tumor tissues expressed high levels of TGFβ and TGFβ-inducible genes. Therefore, rAd.sT could be a potential enhancer of anti-PD-1 and anti-CTLA-4 therapy for treating breast and kidney cancers.

Objective Tiopronin is an antioxidant. This study investigated the protective effect of tiopronin on oxidative stress in patients with severe burns. Method Patients aged between 16 and 65 years old with >30% body surface area burns admitted to our burn unit from July 2011 to September 2016 were randomly divided into 3 groups: group A treated with tiopronin (15 mg/kg. 24 hrs), group B with vitamin C (792 mg/kg. 24 hrs), the other group with standard treatment (group C). All 3 groups also received standard treatment. Blood superoxide dismutase (SOD), malondialdehyde (MDA), and the biochemical indexes of liver, kidney, and heart were determined before treatment and 24 and 48 hrs after treatment. Samples from 8 normal healthy adult volunteers were also measured. The resuscitation fluid volume requirement for the first 24 hrs was calculated for 3 groups. Results The serum levels of MDA and the biochemical indexes in severely burned patients were higher than those in healthy volunteers (P

Ionic liquids (IL) have emerged as the next-generation "green" solvent that can replace traditional organic solvent due to properties such as high thermal stability and no vapour pressure. However, their increased usage inevitably allows them to find their way into the environment. The objective of this study was to evaluate the role of autotrophic ammonia-oxidising bacteria (AOB) in the potential removal of 1-dodecylpyridinium chloride ([DPy]+Cl) in both short- and long-term studies. In short-term batch experiments, it was observed that a notable amount of [DPy]+ can be removed by the AOB culture with the removal mechanism being biodegradation and absorption, with the latter playing a greater role. It was also found that [DPy]+ can be released back into the liquid phase when AOB's preferred substrate, NH3, was present. In the long-term study, [DPy]+Cl was successfully biodegraded and a total of nine transformation products were identified. The biodegradation pathway was also proposed. This study demonstrated that [DPy]+Cl can be biological transformed by enriched AOB culture and the accumulation of the by-product did not show long-term negative impact on AOB activities. Nanyang Technological University This study received funding support from the Nanyang Technological University start-up grant—anticipating and mitigating challenges in enhanced biotreatment processes—enhancement and global warming.

Background The gene transduction efficiency of adenovirus to hematopoietic cells, especially T lymphocytes, is needed to be improved. The purpose of this study is to improve the transduction efficiency of T lymphocytes by using fiber-modified human adenovirus 5 (HAdV-5) vectors. Results Four fiber-modified human adenovirus 5 (HAdV-5) vectors were investigated to transduce hematopoietic cells. F35-EG or F11p-EG were HAdV-35 or HAdV-11p fiber pseudotyped HAdV-5, and HR-EG or CR-EG vectors were generated by incorporating RGD motif to the HI loop or to the C-terminus of F11p-EG fiber. All vectors could transduce more than 90% of K562 or Jurkat cells at an multiplicity of infection (MOI) of 500 viral particle per cell (vp/cell). All vectors except HR-EG could transduce nearly 90% cord blood CD34+ cells or 80% primary human T cells at the MOI of 1000, and F11p-EG showed slight superiority to F35-EG and CR-EG. Adenoviral vectors transduced CD4+ T cells a little more efficiently than they did to CD8+ T cells. These vectors showed no cytotoxicity at an MOI as high as 1000 vp/cell because the infected and uninfected T cells retained the same CD4/CD8 ratio and cell growth rate. Conclusions HAdV-11p fiber pseudotyped HAdV-5 could effectively transduce human T cells when human EF1a promoter was used to control the expression of transgene, suggesting its possible application in T cell immunocellular therapy.

Background The prognostic value of Ki-67 expression in colorectal cancer patients was controversial. Therefore, this meta analysis was conducted to ascertain the prognostic value of Ki-67 expression in colorectal cancer patients. Methods The electronic databases, including EMBASE, PubMed, Cochrane Library and Web of Knowledge database, were searched from January 1970 to July 2017. The pooled hazard ratios and 95% confidence intervals were calculated to evaluate the prognostic value of Ki-67 expression for colorectal cancer patients. Results Totally 34 eligible studies and 6180 colorectal cancer patients were included in the present meta analysis. The pooled hazard ratios were 1.54(95% CI 1.17–2.02, P = 0.005) for overall survival and 1.43(1.12–1.83, P = 0.008) for disease free survival in univariate analysis. After adjustment of other prognostic factors, the pooled HR was 1.50(95% CI 1.02–2.22, P = 0.03) for overall survival in multivariate analysis. Conclusion The present meta analysis demonstrated that high Ki-67 expression is significantly correlated with poor overall survival and disease free survival, indicating that high Ki-67 expression may serve as a valuable predictive method for poor prognosis of colorectal cancer patients.

The majority of advanced breast cancer patients develop distal metastasis, including lung and bone metastasis. However, effective therapeutic strategies to prevent metastasis are still lacking. Decorin is a natural inhibitor of transforming growth factor β, which plays a pivotal role in tumor metastasis. An oncolytic adenovirus expressing decorin, rAd.DCN, has been developed previously. In an immune-competent breast tumor (4T1) model, intratumoral (i.t.) as well as intravenous (i.v.) delivery of rAd.DCN inhibited growth of orthotopic tumors and spontaneous lung metastasis. It was shown that i.t. delivery of rAd.DCN produced higher levels of transgene expression and evoked stronger oncolysis of the tumors compared to i.v. delivery. However, i.v. delivery resulted in higher amount of virus accumulation in the lungs and produced stronger responses to prevent tumor lung metastasis. Oncolytic adenovirus-mediated decorin expression in the tumors downregulated the decorin target genes and decreased epithelial mesenchymal transition markers. Decorin expression in lung tissues also increased Th1 cytokine expression, such as interleukin (IL)-2, IL-12, and tumor necrosis factor α, and decreased Th2 cytokines, such as transforming growth factor β and IL-6. Moreover, rAd.DCN treatment induced strong systemic inflammatory responses and upregulated CD8+ T lymphocytes. In conclusion, rAd.DCN inhibits tumor growth and lung metastasis of breast cancer via regulating wnt/β-catenin, vascular endothelial growth factor (VEGF), and Met pathways, and modulating the antitumor inflammatory and immune responses. Considering that i.v. delivery was much more effective in preventing lung metastasis, systemic delivery of rAd.DCN might be a promising strategy to treat breast cancer lung metastasis.

BACKGROUND This study observed the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) and discusses the risk factors of ISR based on clinical data, coronary angiography, and stent features, to provide a theoretical basis for the prevention and treatment of ISR. MATERIAL AND METHODS We selected 1132 cases who received stent implantation at the Shaanxi People's Hospital from June 2014 to June 2016 and were followed up by coronary angiography within 1 year. Based on coronary angiography, the cases were divided into ISR and non-ISR groups. ISR was defined as a reduction in lumen diameter by over 50% after PCI. The ISR group consisted of 93 cases and the non-ISR group consisted of 1039 cases. Medical history, biochemical indicators, features of coronary artery lesions, and stent status were analyzed retrospectively. Risk factors of ISR were identified by univariate and multivariate logistic regression analyses. RESULTS Among 1132 cases, 93 cases had ISR, with the overall incidence of 8.21%. Univariate and multivariate logistic regression analyses indicated that postoperative hypersensitive C-reactive protein (hs-CRP) levels (OR=2.309, 1.579-3.375 mg/L), postoperative homocysteine (HCY) levels (OR=2.202, 1.268-3.826 μmol/L), history of diabetes (OR=1.955,1.272-3.003), coronary bifurcation lesions (OR=3.785, 2.246-6.377), and stent length (OR=1.269, 1.179-1.365 mm) were independent risk factors of ISR after PCI (P

As a common factor of both type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS), circulating microparticles (MPs) may provide a link between these two diseases. The present study compared the content and function of MPs from patients with ACS with or without T2DM. MPs from healthy subjects (n=20), patients with ACS (n=24), patients with T2DM (n=20) and patients with combined ACS and T2DM (n=24) were obtained. After incubating rat thoracic tissue with MPs, the effect of MPs on endothelial‑dependent vasodilatation, expression of caveolin‑1 and endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS at the S1177 and T495 sites and its association with heat shock protein 90 (Hsp90), and the generation of NO and superoxide anion (O2˙‑) were determined. MP concentrations were higher in patients with T2DM and patients with ACS with or without T2DM than in healthy subjects. Moreover, MPs from patients with T2DM or ACS led to impairment in endothelial‑dependent vasodilatation, decreased expression of NO, as well as eNOS and its phosphorylation at Ser1177 and association with Hsp90, but increased eNOS phosphorylation at T495, caveolin‑1 expression and O2˙‑ generation. These effects were strengthened by MPs from patients with ACS combined with T2DM. T2DM not only increased MP content but also resulted in greater vascular impairment effects in ACS. These results may provide novel insight into the treatment of patients with ACS and T2DM.

In recent years, the human gut microbiome has been recognised to play a pivotal role in the health of the host. Intestinal homeostasis relies on this intricate and complex relationship between the gut microbiota and the human host. While much effort and attention has been placed on the characterization of the organisms that inhabit the gut microbiome, the complex molecular cross-talk between the microbiota could also exert an effect on gastrointestinal conditions. Blastocystis is a single-cell eukaryotic parasite of emerging interest, as its beneficial or pathogenic role in the microbiota has been a subject of contention even to-date. In this study, we assessed the function of the Blastocystis tryptophanase gene (BhTnaA), which was acquired by horizontal gene transfer and likely to be of bacterial origin within Blastocystis. Bioinformatic analysis and phylogenetic reconstruction revealed distinct divergence of BhTnaA versus known bacterial homologs. Despite sharing high homology with the E. coli tryptophanase gene, we show that Blastocystis does not readily convert tryptophan into indole. Instead, BhTnaA preferentially catalyzes the conversion of indole to tryptophan. We also show a direct link between E. coli and Blastocystis tryptophan metabolism: In the presence of E. coli, Blastocystis ST7 is less able to metabolise indole to tryptophan. This study examines the potential for functional variation in horizontally-acquired genes relative to their canonical counterparts, and identifies Blastocystis as a possible producer of tryptophan within the gut., Author summary Blastocystis is a genus of microscopic parasites able to infect the human colon. Whether it plays a role in disease has been a topic of debate in the scientific community since its discovery. Some evidence links infection with the parasite to an increase in biodiversity in gut bacteria, which is associated improvements in health. Other evidence links Blastocystis to symptoms of the common gut disease irritable bowel syndrome, or IBS. This study shows that Blastocystis interacts with the amino acid tryptophan in an unexpected manner, which may shed light how it might cause disease. We show that it uses an enzyme known as tryptophanase in reverse–in other organisms, tryptophanase converts tryptophan into another molecule known as indole, while Blastocystis converts indole to tryptophan. Cells in the gut called enterochromaffin cells convert tryptophan into the neurotransmitter serotonin. This molecule can influence the behaviour of the gut, and has been linked to symptoms of IBS. We believe that, under some circumstances, an infection with Blastocystis may cause an increase in tryptophan in the gut, which is then converted to serotonin. The excess serotonin would then cause symptoms of the disease.

Background This study aims to screen the male human papillomavirus (HPV) infection status and genotyping in Qingcheng District, Qingyuan City, Guangdong Province, China to provide a reference basis for formulating prevention strategies for HPV infection. Methods The present study collected urethral epithelium or scraped penile epidermis from high-risk male patients in Qingyuan People's Hospital during the last five years, extracted DNA fragments using the boiling method, and detected 23 types of HPV genotypes by PCR-reverse blot hybridization. Results The positive detection rate was 54.31% of 1044 males with high risk of HPV (567/1044). Among these males, the positive detection rate of HPV was the highest in patients initially diagnosed with warts, and the rate was 66.47%. Five main HPV types are identified as follows: HPV6 18.87% (197/1044), HPV11 10.25% (107/1044), HPV52 8.81% (92/1044), HPV16 6.90% (72/1044), and HPV51 5.08% (53/1044). Among these HPV-infected patients, single infection mainly by low-risk HPV6 and HPV11 accounted for 56.61% (321/567); high- and low-risk combined HPV co-infections accounted for 29.10% (165/567). The HPV infected patients was mainly between 21 and 40 years old, and the HPV infection rate was higher with increased age. Conclusions The HPV infection rate in the Qingyuan area is higher than in other areas and the main infection is single infection. Furthermore, HPV52, HPV16, and HPV51 are the main high-risk infection types, while HPV6 and HPV11 are the main low-risk infection types.

Most prostate carcinomas require androgen stimulation to grow, and for nearly 70 years, androgen ablation therapy has been one of the central therapeutic strategies against advanced prostate cancer. Although most tumours initially respond to this therapy, some will be acquired resistant and progress to metastatic castration-resistant (mCRPC) disease which clinically tends to progress more rapidly than earlier disease manifestations. The underlying molecular biology of mCRPC is highly complex, and numerous mechanisms have been proposed that promote and retain androgen independence. In various clinical and preclinical data explored, the nature of intracellular signalling pathways mediating mitogenic acquired resistant effects of GPCRs in prostate cancer is poorly defined. G-protein-coupled receptor kinase 2 (GRK2) contributes to the modulation of basic cellular functions-such as cell proliferation, survival or motility-and is involved in metabolic homeostasis, inflammation or angiogenic processes. Moreover, altered GRK2 levels are starting to be reported in different tumoural contexts and shown to promote breast tumourigenesis or to trigger the tumoural angiogenic switch. Thus, we are exploring recent findings that present unexpected opportunities to interfere with major tumourigenic signals by manipulating GPCR-mediated pathways.

Adrenocorticotropic hormone (ACTH) is an old medicine derived from porcine pituitary gland that has been marketed for more than 60 years. In this study, we present a recombinant approach to produce ACTH in Escherichia coli (E. coli). The SUMO-tagged fusion protein was cloned and expressed after induction with isopropyl-β- d -thiogalactopyranoside (IPTG) at 25 °C for 8 h. The fusion protein was extracted and purified by anion exchange chromatography, and the SUMO tag was subsequently removed by digestion with ubiquitin-like protease 1 (ULP1). Approximately 95.3 mg of recombinant ACTH with 94.2% purity was obtained after cation exchange purification performed on a 5 mL column, from 286 mL fermentation broth based on the amount of pellets homogenized. The molecular mass of the recombinant ACTH was confirmed by mass spectrometry to equal 4567.32 Da.

Downregulation of the sprouty‑related EVH1 domain protein 2 (Spred2) is closely associated with highly metastatic phenotypes in various tumors. However, the roles of Spred2 in the development and progression of colorectal cancer (CRC) are still largely unexplored. As anticipated, Spred2 expression was significantly downregulated in clinical tumor tissues. To restore Spred2 levels, Ad.Spred2, an adenoviral vector expressing Spred2, was transduced into CRC cells. It was revealed that Ad.Spred2 inhibited the proliferation and decreased the survival and migration of SW480 cells. Epithelial‑mesenchymal transition (EMT) is an essential event during tumor metastasis to distant sites. It was revealed that Ad.Spred2 markedly inhibited EMT by promoting F‑actin reorganization, upregulating E‑cadherin levels and reducing vimentin protein expression. Notably, extracellular‑regulated kinase (ERK) signaling inhibition by PD98059 induced similar effects on EMT in CRC cells, indicating that Ad.Spred2 regulated EMT in CRC cells in an ERK‑dependent manner. Transforming growth factor β (TGF‑β), a well‑known inducer of EMT, increased E‑cadherin expression, decreased vimentin expression and promoted migration in CRC cells. However, neither Ad.Spred2 nor PD98059 had an obvious effect on the expression of SMAD2/3 or SMAD4 in SW480 cells, indicating that Ad.Spred2 inhibited EMT in a SMAD‑independent manner. Notably, Ad.Spred2 transduction downregulated SAMD2/3 and SMAD4 levels in HCT116 cells in an ERK‑independent manner. It was speculated that Ad.Spred2 inhibited the EMT of HCT116 cells by both blocking ERK signaling and reducing SMAD signaling. It was concluded that Spred2 inhibited EMT in CRC cells by interfering with ERK signaling, with or without reduced SMAD signaling. Therefore, the introduction of the clinical application of Spred2 has great potential for development as a gene therapy approach for CRC.

Objective: To explore discrepancy in CT manifestations of coronavirus disease 2019 (COVID-19) in patients outside Wuhan between cases with a history of exposure to Wuhan and with the second-generation infection.Methods: Twenty-two patients with confirmed COVID-19 from two hospitals in Nanchong outside Wuhan were enrolled. All patients underwent initial and follow-up computed tomography after admission, and were divided into two groups. Group A and B were composed of 15 patients with a history of exposure to Wuhan and 7 with the second-generation infection in Nanchong, respectively. Initial CT features including extent score and density score between groups were statistically compared.Results: All patients in group A had abnormal CT findings while 3 of 7 patients in group B had. Patients with abnormal CT findings were more frequent in group A than in group B (P < 0.05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%) and 4 (57.1%) had pure GGO, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of ≥5 were more frequent in group A than in group B (Ps < 0.01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up CT.Conclusion: The COVID-19 in patients with a history of exposure to Wuhan can be severer than with the second-generation infection on CT.

Purpose To evaluate the possible roles of miR-34a expression in thyroid lesions, to unravel the correlation between fluorodeoxyglucose (FDG) uptake and miR-34a expression and moreover, to discover the underlying mechanisms by which miR-34a regulates FDG avidity. Methods We retrospectively reviewed 75 patients with pathology-confirmed thyroid diseases who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) within 3 months before undergoing thyroid surgery and miR-34a analysis from June 2012 to July 2017. 18F-FDG uptake of thyroid lesions was also analyzed semiquantitatively using maximum standardized uptake value (SUVmax). The association between miR-34a expression and clinicopathological variables (age, sex, TNM stage, histopathology, lesion numbers, location and 18F-FDG avidity) was investigated. When there were multiple lesions in thyroid bed, only the one with the highest 18F-FDG uptake was analyzed. Next, we inhibited the miR-34a expression in TPC-1 cells and detected the expression of glucose transporter 1 (GLUT1) mRNA and protein. Results In the patients cohort, miR-34a was upregulated in those with malignant thyroid diseases compared with benign lesions. The expression of miR-34a was associated with tumor stages, histopathological types and SUVmax. There was an inverse relationship between miR-34a expression and SUVmax in patients with thyroid diseases (Spearman correlation coefficient = -0.553, P < 0.0001). With an SUVmax of 4.3 as the threshold, sensitivity and specificity of the prediction of miR-34a expression (low or high) were 70% and 94.3%, respectively. The area under the receiver operating characteristic curve was 0.843 (95% confidence interval: 0.749, 0.936; P = 0.001). Inhibiting miR-34a in TPC-1 cells significantly increased GLUT1 mRNA and protein expression. Conclusion miR-34a expression was upregulated in thyroid lesions, negatively correlated with SUVmax and can be predicted by FDG SUVmax. In addition, miR-34a may regulate FDG avidity via targeting GLUT1.

In this work, a novel Mo1−xS2 (Mo1−xS2/TiO2) with controllable Mo vacancies was successfully synthesized by simple NaBH4 treatment, which exhibits significantly enhanced hydrogen evolution reaction (HER) activity with lower overpotential and smaller Tafel slope in alkaline electrolyte. Compared with pure TiO2 or MoS2/TiO2, the H2 release rate of Mo1−xS2/TiO2 heterostructure photocatalyst was significantly increased when Mo1−xS2 serves as a co-catalyst. At optimal molar ratio of 2.5:1 Mo1−xS2/TiO2, the H2 release rate achieves 1561 μmol g−1 h−1 in triethanolamine solution, which is approximately 5.3 and 2.7 times of pure TiO2 and MoS2/TiO2, respectively. Through electrochemical analysis and first-principle density functional theory calculations, the faster separation and transfer of photogenerated electron and holes as well as higher HER activity improve the efficiency of photocatalytic hydrogen production. This work opens a new doorway for utilization of defective 2D sheet materials towards solar to H2 conversion.

Although the biomedical sciences have achieved tremendous success in developing novel approaches to managing prostate cancer, this disease remains one of the major health concerns among men worldwide. Liposomal formulations of single drugs have shown promising results in cancer treatment; however, the use of multi drugs has shown a better therapeutic index than individual drugs. The identification of cancer-specific receptors has added value to design targeted drug delivering nanocarriers. We have developed genistein and plumbagin co-encapsulating liposomes (∼120 nm) with PSMA specific antibodies to target prostate cancer cells selectively in this work. These liposomes showed >90 % decrease in PSMA expressing prostate cancer cell proliferation without any appreciable toxicity to healthy cells and human red blood cells. Release of plumbagin and genistein was found to decrease the expression of PI3/AKT3 signaling proteins and Glut-1 receptors (inhibited glucose uptake and metabolism), respectively. The decrease in migration potential of cells and induced apoptosis established the observed anti-proliferative effect in prostate cancer cell lines. The discussed strategy of developing novel, non-toxic, and PSMA specific antibody conjugated liposomes carrying genistein and plumbagin drugs may also be used for encapsulating other drugs and inhibit the growth of different types of cancers.

Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children. Forty-eight patients with PNS suffering from their first attack prior to GC treatment were chosen as subjects. They were divided into two groups, those who had steroid-sensitive nephrotic syndrome (SSNS; n = 25) and those with steroid-resistant NS (SRNS; n = 23), according to their response to a 6-week course of oral prednisone. Twenty healthy children from the Physical Examination Center in the hospital served as the control group; Peripheral blood was collected at different time points prior to GC treatment and after regular therapy. RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA) techniques were adopted to analyze HDAC2 mRNA, protein expression, and activity, respectively, in peripheral blood lymphocytes. The level of interleukin-8 (IL-8) in serum was measured by an ELISA. Prior to GC treatment, HDAC2 expression level and activity were lower in the SRNS group than in the SSNS and control group. A statistically significant difference in HDAC2 expression and activity were observed after GC treatment between these groups, with HDAC2 expression and activity lower in the SRNS group than in the SSNS and control groups. In the SSNS group, the expression and activity of HDAC2 were higher following GC treatment than prior to GC treatment. There was a clear difference in HDAC2 expression and activity of SRNS at the different time points. No statistically significant difference was found between the two groups. The pre-treatment and post-treatment serum IL-8 levels in the SRNS group were significantly higher than those in the SSNS group. HDAC2 from children with PNS before GC treatment and after regular therapy for 6 weeks was negatively correlated with serum IL-8 level. The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS.

In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA), were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while there were increased Met and VEGFA levels. To develop a novel therapy for CRC, rAd.DCN.GM, an oncolytic adenovirus encoding decorin and granulocyte macrophage colony stimulating factor (GM-CSF), has been created. Several therapeutic strategies expressing GM-CSF have been employed in clinical trials for treating metastatic colorectal cancer. In this study, infection of CRC cells with rAd.DCN.GM expressed decorin and GM-CSF, and produced cytotoxicity. In murine CT26 xenografts, rAd.DCN.GM and control adenoviruses were administrated intratumorally on days 7 and 10, and tumor volumes were monitored over time. The study showed that rAd.DCN.GM inhibited the tumor growth and lung metastases significantly. rAd.DCN.GM induced apoptosis, inhibited proliferation, and downregulated angiogenesis and epithelial mesenchymal transition markers in the tumors. On day 12 and day 29, the immune-activation in the peripheral blood, tumors, and spleens were analyzed. rAd.DCN.GM increased CD8

A new family of octanuclear Cu–Ln complexes, [Cu6Ln2(tea)2{(py)2CO2}3Cl6]·xH2O (Ln = Dy (1), Tb (2), Ho (3), Er (4), Gd (5); x = 1 for 1, 3 and 5, x = 0 for 2 and x = 7 for 4; (py)2CO2H2 = the gem-diol form of di-2-pyridyl ketone, teaH3 = triethanolamine), has been synthesized and characterized by single-crystal X-ray diffraction, elemental analyses, IR and magnetic properties. These complexes are all isostructural and were obtained by following a self-assembly reaction involving CuCl2·2H2O, Ln(NO3)3·6H2O, di-2-pyridyl ketone, triethanolamine and triethylamine in acetonitrile at room temperature. Single-crystal X-ray diffraction analyses indicate that the LnIII ions in these complexes are seven-coordinate, which is rare in 3d–4f complexes and 4f complexes. The geometries of LnIII in these complexes severely deviate from capped octahedrons. Moreover, coordination sites of Ln were occupied by two (py)2CO22− and one tea3− ligands, without the presence of coordinated solvent molecules such as H2O and small anions such as NO3− ions, which is also rare in 4f ions complexes. The direct-current magnetic susceptibilities show that the ferromagnetic coupling interactions between CuII and Ln ions are presented by fitting the data of 1/χMversus T using the Curie–Weiss law and fitting the data of χMT versus T of 5 (Gd) using PHI program. AC magnetic measurements of 1–5 without dc field and 2000 Oe dc fields show no temperature- and frequency-dependent signals, which may be due to the low symmetry of the coordination configuration of Ln in these complexes.

Abnormal pulmonary arterial vascular smooth muscle cells (PASMCs) proliferation is critical pathological feature of pulmonary vascular remodeling that acts as driving force in the initiation and development of pulmonary arterial hypertension (PAH), ultimately leading to pulmonary hypertension. Aloperine is a main active alkaloid extracted from the traditional Chinese herbal Sophora alopecuroides and possesses outstanding antioxidation and anti-inflammatory effects. Our group found Aloperine has protective effects on monocroline-induced pulmonary hypertension in rats by inhibiting oxidative stress in previous researches. However, the anti-inflammation effects of Aloperine on PAH remain unclear. Therefore, to further explore whether the beneficial role of Aloperine on PAH was connected with its anti-inflammatory effects, we performed experiments in vitro. Aloperine significantly inhibited the proliferation and DNA synthesis of human pulmonary artery smooth muscle cells (HPASMCs) induced by platelet-derived growth factor-BB, blocked progression through G0/G1to S phase of the cell cycle and promoted total ratio of apoptosis. In summary, these results suggested that Aloperine negatively regulated nuclear factor-κB signaling pathway activity to exert protective effects on PAH and suppressed HPASMCs proliferation therefore has a potential value in the treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.

An antibody-free immunoassay that makes use of a boronate affinity molecularly imprinted polymer (MIP) and surface enhanced Raman scattering (SERS) tags is described. It was applied to the specific determination of the carcinoembryonic antigen (CEA) in human serum. For the preparation of the boronate affinity array, a polymer capable of adsorbing glycoproteins was first synthesized on the surface of a glass slide with four spots using 4-vinylbenzeneboronic acid (VPBA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and ethylene glycol and cyclohexanol as porogens. The surface of the VPBA-Co-EGDMA can bind target glycoproteins. After specific capture of the glycoprotein, a “MIP-target glycoprotein-SERS tag” sandwich structure was formed by covalent interaction between the SERS nanotag (consisting of gold nanoparticles and 4-mercaptophenylboronic acid [MPBA]). CEA can be quantified in spiked serum with a detection limit of 0.1 ng·mL−1 via the specific Raman band at 1098 cm−1.

Ionic liquids (ILs) have attracted attention in recent years due to their “greener” properties compared to conventional organic solvents. However, they may still pose a risk to the environment as their toxicity is not fully understood. Bioremediation of such ILs can be an economically and environmentally friendly approach. Therefore, this study aims to examine the interaction of three ILs (1-dodecylpyridnium chloride [DPy] + Cl, 1-Butyl-3-methylimidazolium chloride [BMIm] + Cl, and 1-Carbamoylmethyl pyridinium chloride [CMPy] + Cl) at different concentrations with an enriched ammonia oxidising bacteria (AOB) culture, and investigate their effects on the ammonia oxidation rate (AOR) as well as their removal and transformation. The results indicated that the longer chain IL [DPy] + Cl had a negative effect on the AOR while [BMIm] + Cl and [CMPy] + Cl enhanced the AOR. However, the IL removal rates displayed the opposite results as [DPy] + Cl was observed with the highest removal. It was found that biosorption played a major role in [DPy] + Cl removal. Biotransformation products for each IL were identified and their pathways were proposed. This study demonstrated that although longer chain ILs have a greater degree of removal, and they are also more toxic to AOB at higher concentration.

More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.

Background Drug resistance frequently led to the failure of chemotherapy for malignant cancers, hence causing cancer relapse. Thus, understanding mechanism of drug resistance in cancer is vital to improve the treatment efficacy. Here, we aim to evaluate the association between SMAD4 expression and the drug resistance in cancers by performing a meta-analysis. Method Relevant studies detecting SMAD4 expression in cancer patients treated with chemo-drugs up till December 2020 were systematically searched in four common scientific databases using selected keywords. The pooled hazard ratio (HR) was the ratio of hazard rate between SMAD4neg population vs SMAD4pos population. The HRs and risk ratios (RRs) with 95% confidence intervals (CIs) were used to explore the association between SMAD4 expression losses with drug resistance in cancers. Result After an initial screening according to the inclusion and exclusion criteria, eleven studies were included in the meta-analysis. There were a total of 2092 patients from all the included studies in this analysis. Results obtained indicated that loss of SMAD4 expression was significantly correlated with drug resistance with pooled HRs (95% CI) of 1.23 (1.01–1.45), metastasis with pooled RRs (95% CI) of 1.10 (0.97–1.25) and recurrence with pooled RRs (95% CI) of 1.32 (1.06–1.64). In the subgroup analysis, cancer type, drug type, sample size and antibody brand did not affect the significance of association between loss of SMAD4 expression and drug resistance. In addition, there was no evidence of publication bias as suggested by Begg’s test. Conclusion Findings from our meta-analysis demonstrated that loss of SMAD4 expression was correlated with drug resistance, metastasis and recurrence. Therefore, SMAD4 expression could be potentially used as a molecular marker for cancer resistance.

Kinesin spindle protein (KSP) is a microtubule-associated motor protein that is specifically expressed by mitosis cells. It is highly expressed in various types of tumors including hematomalignances and solid tumors. Chemical KSP inhibition has become a novel strategy in the development of anticancer drugs. SB743921 is a selective inhibitor for KSP, which is a mitotic protein essential for cell-cycle progression. Although SB743921 has shown antitumor activities for several types of cancers and entered into clinical trials, its therapeutic effects on breast cancer and mechanisms have not been explored. In this study, we tested the antitumor activity of SB743921 in breast cancer cell lines and partly elucidated its mechanisms. KSP and denticleless E3 ubiquitin–protein ligase homolog (DTL) are overexpressed in breast cancer cells compared with no-cancer tissues. Chemical inhibition of KSP by SB743921 not only reduces proliferation but also induces cell-cycle arrest and leads to apoptosis in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 breast cancer cell lines with SB743921 results in decreased ability of colony formation in culture. SB743921 treatment also causes a KSP accumulation in protein level that is associated with cell arrest. Furthermore, we showed that SB743921 treatment significantly reduces the expression of bcl-2 and cell cycle-related protein DTL, and upregulates p53 and caspase-3 in breast cancer cells. Taken together, these data indicated that SB743921 can be expected to be a novel treatment agent for breast cancers.

Liposarcoma(LPS) is the most common type of soft tissue sarcoma accounting for 20 % of all adult sarcomas. However, the molecular pathogenesis of this malignancy is still poorly understood. Here, we showed that GPS2 expression was downregulated in LPS and correlated with the prognosis of this disease. In vitro study showed that knockdown of GPS2 resulted in enhanced proliferation and migration of LPS cell line SW872, without significant influence of cell death. Conclusively, our results suggest that GPS2 may act as a tumor suppressor in LPS and serve as a potential prognosis marker for this disease.

To observe the effect of acupuncture on gastric motility, plasma motilin and serum gastrin in patients with diabetic gastroparesis (DGP) and evaluate its clinical efficacy. A total of 100 eligible cases were randomly allocated into an acupuncture group (n=50) and a control group (n=50). Patients in the acupuncture group were treated by needling Zhongwan (CV 12), Zusanli (ST 36) and Neiguan (PC 6), whereas patients in the control group were treated with oral administration of Domperidone. The clinical efficacies of the two groups were compared; and changes in gastric motility, plasma motilin and serum gastrin in both groups were observed before and after treatment. After treatment, the symptom scores, gastric motility and contents of plasma motilin and serum gastrin were significantly improved in both groups (P