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Understanding and monitoring life history traits is often important in endangered species conservation. Populations of the endangered mussel Cumberlandian combshell Epioblasma brevidens have continued to decline in the Powell River, USA. Understanding and modeling mussel growth is critical for effective reintroduction of this endangered species. In this study, 2 yr old E. brevidens that were produced in our laboratory were released to the Powell River in 2009 to augment this declining population. A mark-recapture monitoring approach using passive integrated transponder (PIT) tags was used to assess the survival and growth of the released mussels. Hierarchical Bayesian growth models incorporating individual growth variations, periodic growth and growth cessations, along with multiple release occasions were developed and compared to the classic von Bertalanffy growth model. Our results showed that the hierarchical model that incorporated individual growth variation gave the best estimates of model parameters, yielding the lowest deviance information criterion value. Mussels exhibited different growth rates (K), including 0.015, 0.026, 0.110 and 0.050 (moñ1), corresponding to the duration of laboratory culture (ages 2, 3 and 4 yr old) and a growth cessation (GC) for 5.98 mo, respectively. The other parameters of asymptotic length (L∞) and age at zero length (t0) were 51.36 mm and -0.648 mo. The flexible structure of Bayesian hierarchical models allowed us to examine growth characteristics of E. brevidens in a changing environment to better understand the details of its growth and lifespan, thus providing useful data for conservation management.

Jian-Jun Wu,1 Ping-An Zhang,1 Ming-Zhe Chen,2 Yi Zhang,1 Wei-Sha Du,1 Xiao-Ning Li,1 Guo-Chao Ji,1 Liang-Duo Jiang,3 Yang Jiao,4,* Xin Li5,* 1Respiratory Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Infectious Disease Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 3Respiratory Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Respiratory Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Glaucoma Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Li, Glaucoma Department, Eye Hospital, China academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email doudou8295@163.comBackground: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear.Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained.Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated.Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated.Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.Keywords: COPD, GC, GEO database, miRNA-mRNA, DEMs, DEGs

Abstract The basis for our understanding of quantum magnetism has been the study of elegantly simple model systems. However, even for the antiferromagnetic honeycomb lattice with isotropic spin interactions–one of the simplest model systems–a detailed understanding of quantum effects is still lacking. Here, using inelastic neutron scattering measurements of the honeycomb lattice material YbCl3, we elucidate how quantum effects renormalize the single-magnon and multimagnon excitations and how this renormalization can be tuned and ultimately driven to the classical limit by applying a magnetic field. Additionally, our work reveals that the quantum effects tuned by the magnetic field not only renormalize the magnetic excitations but also induce a distinctive sharp feature inside the multimagnon continuum. From a more general perspective, this result demonstrates that structures within magnetic continua can occur over a wide experimental parameter space and can be used as a reliable means of identifying quantum phenomena.

Ziting Qu,1,&ast; Yanxun Han,2,&ast; Qingbo Zhu,1,&ast; Wenxi Ding,1 Yuyan Wang,1 Yan Zhang,1 Wei Wei,1 Yu Lei,1 Min Li,1 Yang Jiao,1 Kangsheng Gu,1,&ast; Yiyin Zhang1,&ast; 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kangsheng Gu; Yiyin Zhang, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Email gukangsheng@ahmu.edu.cn; zhangyiyin@ahmu.edu.cnBackground: Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients’ prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis.Methods: We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO–Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis.Results: Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p< 0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006).Conclusion: Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.Keywords: NETs, gastric cancer, gene signature, tumor microenvironment, prognosis

Lanthanide binding tags (LBTs) have been engineered onto the cell surface of E. coli to enhance biosorption and recovery of rare earth elements (REEs). The protonation behavior of the bacterial surfaces before and after LBT-display was compared by modeling acid-base titration data. A multiple discrete site, constant capacitance surface complexation model was constructed to examine rare earth (Tb) binding to cell surface functional groups, comparing wild type and LBT-engineered surfaces. Our acid-base titrations show similar pKa values between the two strains, suggesting induction of LBTs does not significantly alter cell surface protonation behavior. Tb sorption onto the wild type cell surface can be captured by a one-site carboxyl model. The LBT strain exhibited a higher metal loading that can be explained by the increase of sorption sites in the form of lanthanide binding tags. Furthermore, carboxyl site concentrations between wild type and LBT-induced cells were statistically indistinguishable. We thus attribute the engineered strains’ increase in Tb adsorption capacity and affinity to the addition of lanthanide binding tags to the cell surface. The Tb stability constant with the LBT site is two orders of magnitude higher than that with the carboxyl functional group. As a result, at low metal loading 10 μM, a more abundant but low affinity functional group becomes the main source of adsorption that results in an overall higher sorption capacity. This work demonstrates how surface complexation modeling can be implemented for bacterial surfaces engineered with a known protein tag to optimize REE recovery from fluids with variable pH and metal loadings.

Xiaoyang Qi,1,2 Xugang Li,2 Yuwen Jiao,1 Shuai Chen,1 Peng Song,1 Zhifen Qian,1 Liming Tang1 1Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Orthopaedics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Liming TangDepartment of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, No. 68, Gehu Middle Road, Changzhou, 213000, Jiangsu, People’s Republic of China, Tel +86-13506112690, Email drtangliming@163.comPurpose: Sleeve gastrectomy (SG) is the most currently popular operation for obesity and related metabolic disorders. The aim of this study was to compare the effect of antrum preservation SG (AP-SG) and antrum resection SG (AR-SG) on the body composition, glycemic control and bone mineral density (BMD) in mice.Methods: Sham, AP-SG and AR-SG operation were performed on obese and T2D C57BL/6J mice (8 in each group). Body weight, food intake, and fasting glucose (FG) levels were measured at the 0, 2, 4, 6 and 8 weeks post-operatively. Oral glucose tolerance test (OGTT) was performed preoperatively and at the eighth postoperative week. The body fat content and total body BMD were evaluated by dual-energy x-ray absorptiometry. After being euthanized, the femurs were harvested and analyzed by micro-CT.Results: The improvements in body weight, food intake, FG, glycemic control and body fat were statistically significant following AP-SG and AR-SG. Both AP-SG and AR-SG groups decreased total body BMD and regional BMD in the distal femur compared to the sham group. No significant difference of FG was observed in AP-SG and AR-SG group postoperatively, but AR-SG showed significantly superior OGTT glucose AUC than AP-SG. Except for a lower BMD, AR-SG achieved superior outcomes in body fat and glycemic control than AP-SG.Conclusion: Antrum resection SG shows a lower percentage of body fat and better glycemic control than antrum preservation SG. However, antrum resection SG has a higher risk of having a lower bone mass. Further human clinical trials are needed to confirm this finding.Keywords: sleeve gastrectomy, antrum preservation, antrum resection, body fat, bone mineral density

In this study, we focus on the development of key processes towards wafer-scale 3-dimentional/vertical (3D) integration of Indium-Phosphide (InP) photonic membranes on InP electronics via adhesive bonding. First, we identified the most critical steps and optimized them to achieve high thermal and mechanical compatibility of components for the co-integration process. Next, we developed a strategy for InP-to-InP wafer bonding with high topology tolerance, and introduced hard benzocyclobutene (BCB) anchors to preserve the alignment and BCB thickness uniformity after bonding. The resulting bond layer is homogeneous in terms of physical and mechanical properties. Finally, we developed a novel method to selectively remove the InP substrate from the photonics side via wet etching while protecting the electronics carrier wafer with hermetic multi-layer coatings. The investigation of these key steps is essential for scalable 3D integration of photonics and electronics at ultra short distances (< $15 ~\mu \text{m}$). [ABSTRACT FROM AUTHOR]

Natural methyl chloride (CH3Cl) and methyl bromide (CH3Br) emissions from coastal marsh ecosystems may constitute a significant proportion of stratospheric chlorine and bromine, which catalyze ozone depletion. Current inventories involve substantial uncertainties associated with upscaling plot-scale footprints (i.e., ≤1 m2). Here we present net ecosystem flux measurements of methyl halides from a brackish tidal marsh on the west coast of the United States between April 2016 and June 2017 using the relaxed eddy accumulation method. The measurement footprint encompasses a large part of the studied tidal marsh, including roughly 20 vascular plant species, open water, and soil surfaces. On the annual scale, ecosystem methyl halide emissions showed the strongest relationships to temperature and the growth cycle of halophyte vegetation, whereas on diurnal time scales, fluxes correlated the most with evapotranspiration. The maximum seasonal emissions occurred during the flowering season of Lepidium latifolium (perennial pepperweed), one of the most abundant halophytes on site. The maximum hourly emissions of 111 μg CH3Cl · m−2 s· hr−1 and 38 μg CH3Br · m−2 · hr−1 were observed during a heat wave in early June. Annually integrated emissions were 135 mg/m2 for CH3Cl and 21 mg/m2 for CH3Br, scaling up to 621 and 96 kg over the entire marsh. We provide a global salt marsh emission inventory that takes into account the spatial distribution of salt marshes in different climate zones, yielding a global salt marsh source of 31 Gg/year CH3Cl (range: 10 to 77) and 3 Gg/year CH3Br (range: 1 to 8).

The current uncertainty in the global supply of rare earth elements (REEs) necessitates the development of novel extraction technologies that utilize a variety of REE source materials. Herein, we examined the techno-economic performance of integrating a biosorption approach into a large-scale process for producing salable total rare earth oxides (TREOs) from various feedstocks. An airlift bioreactor is proposed to carry out a biosorption process mediated by bioengineered rare earth-adsorbing bacteria. Techno-economic assessments were compared for three distinctive categories of REE feedstocks requiring different pre-processing steps. Key parameters identified that affect profitability include REE concentration, composition of the feedstock, and costs of feedstock pretreatment and waste management. Among the 11 specific feedstocks investigated, coal ash from the Appalachian Basin was projected to be the most profitable, largely due to its high-value REE content. Its cost breakdown includes pre-processing (leaching primarily, 77.1%), biosorption (19.4%), and oxalic acid precipitation and TREO roasting (3.5%). Surprisingly, biosorption from the high-grade Bull Hill REE ore is less profitable due to high material cost and low production revenue. Overall, our results confirmed that the application of biosorption to low-grade feedstocks for REE recovery is economically viable.

Yilan Xing,1,2 Shishun Fu,3 Meng Li,3 Xiaofen Ma,3 Mengchen Liu,3 Xintong Liu,2 Yan Huang,2 Guang Xu,2 Yonggang Jiao,2 Hong Wu,2 Guihua Jiang,1,3 Junzhang Tian1,3 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Neurology of Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 3Department of Medical Imaging of Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Junzhang Tian; Guihua JiangDepartment of Medical Imaging of Guangdong Second Provincial General Hospital, No. 466, Xingang Road, Guangzhou, People’s Republic of ChinaTel +86 20 89168701; +86 18620120333Email tianjunzhang2015@163.com; GH.jiang2002@163.comPurpose: The aim of this study was to compare regional homogeneity (ReHo) changes in Parkinson’s disease mild cognitive impairment (PD-MCI) patients with respect to normal controls (NC) and those with cognitively normal PD (PD-CN). Further, the study investigated the relationship between ReHo changes in PD patients and neuropsychological variation.Patients and Methods: Thirty PD-MCI, 19 PD-CN, and 21 NC subjects were enrolled. Resting state functional magnetic resonance imaging data of all subjects were collected, and regional brain activity was measured for ReHo. Analysis of covariance for ReHo was determined between the PD-MCI, PD-CN, and NC groups. Spearman rank correlations were assessed using the ReHo maps and data from the neuropsychological tests.Results: In comparison with NC, PD-CN patients showed significantly higher ReHo values in the right middle frontal gyrus (MFG) and lower ReHo values in the left supramarginal gyrus, bilateral inferior parietal lobule (IPL), and the right postcentral gyrus (PCG). In comparison with PD-CN patients, PD-MCI patients displayed significantly higher ReHo values in the right PCG, left middle occipital gyrus (MOG) and IPL. No significant correlation between ReHo indices and the neuropsychological scales was observed.Conclusion: Our finding revealed that decreases in ReHo in the default mode network (DMN) may appear before PD-related cognitive impairment. In order to preserve executive attention capacity, ReHo in the right MFG in PD patients lacking cognition impairment increased for compensation. PD-MCI showed increased ReHo in the left MOG, which might have been caused by visual and visual-spatial dysfunction, and increased ReHo in the left IPL, which might reflect network disturbance and induce cognition deficits.Keywords: Parkinson’s disease, mild cognitive impairment, ReHo, fMRI, DMN

Yang Jiao,1,* Chen Fang,1,* Yuchen Yang,2 Lin Shao,2 Yi Huang,1 Qinying Sun,1 Yuchao Dong1 1Pulmonary and Critical Care Medicine, Changhai Hospital, The Naval Medical University, Guangzhou, People’s Republic of China; 2Burning Rock Biotech, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuchao Dong; Qinying SunPulmonary and Critical Care Medicine, Changhai Hospital, The Naval Medical University, #168 Changhai Road, Yangpu District, Shanghai, 200433, People’s Republic of ChinaEmail dongyc1020@aliyun.com; sqy20031@163.comAbstract: MET exon 14 skipping variants have been identified as a novel type of oncogenic driver mutations in non-small-cell lung cancer (NSCLC), while the germline MET mutation, especially germline MET exon 14 skipping mutation rarely occurred in NSCLC. Herein, we present the first case of a 33-year-old NSCLC patient with a germline MET exon 14 skipping mutation, who also harbored a somatic EGFR exon 20 insertion. The patient was initially diagnosed with a stage IIB adenosquamous carcinoma. He underwent a thoracoscopic radical resection followed by four cycles of adjuvant chemotherapy but relapsed 2 months after completing the chemotherapy. Afatinib was then prescribed but disease progressed immediately. Subsequently, he received anlotinib but did not respond and died a month later with an overall survival of 9 months. Our case may provide an evidence for the pathogenicity of germline MET exon 14 skipping mutation in NSCLC and suggest it as an adverse prognostic factor.Keywords: MET exon 14 skipping mutation, rare germline mutation, next-generation sequencing, NGS, lung adenosquamous carcinoma, rapid disease progression

There is a great interest in generating high-power hard X-ray Free Electron Laser (FEL) in the terawatt (TW) level that can enable coherent diffraction imaging of complex molecules like proteins and probe fundamental high-field physics. A feasibility study of producing such X-ray pulses was carried out employing a configuration beginning with a Self-Amplified Spontaneous Emission FEL, followed by a “self-seeding” crystal monochromator generating a fully coherent seed, and finishing with a long tapered undulator where the coherent seed recombines with the electron bunch and is amplified to high power. The undulator tapering profile, the phase advance in the undulator break sections, the quadrupole focusing strength, etc. are parameters to be optimized. A Genetic Algorithm (GA) is adopted for this multi-dimensional optimization. Concrete examples are given for LINAC Coherent Light Source (LCLS) and LCLS-II-type systems. Analytical estimate is also developed to cross check the simulation and optimization results as a quick and complimentary tool.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity. [ABSTRACT FROM AUTHOR]

Dandan Zheng,1,2,* Chengwei Jiang,3,* Ning Yan,2 Yayun Miao,2 Keren Wang,2 Ge Gao,3 Yan Jiao,4 Xiangkai Zhang,2 Miao He,5 Zhaoying Yang2 1Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, People’s Republic of China; 2Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 3Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 5Department of Anesthesia, The Second Hospital of Jilin University, Changchun, Jilin 130022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Miao HeDepartment of Anesthesia, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, Jilin 130022, People’s Republic of ChinaEmail hemiao@jlu.edu.cnZhaoying YangDepartment of Breast Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, People’s Republic of ChinaEmail zyyang@jlu.edu.cnBackground: Wntless (Wls) is an essential protein that is necessary for the secretion of Wnt proteins. While numerous researches have demonstrated that aberrations in Wnt/β-catenin expression lead to tumorigenesis and progression in many cancer types, the effects of Wls in breast cancer (BC) are less studied.Methods: The mRNA and protein expression of Wls in BC cell lines were detected by RT-qPCR and Western blot; the protein expression of patient samples was detected by immunohistochemistry (IHC). The associations between Wls expression and clinicopathological factors as well as survival time, including overall survival (OS) and disease-free survival (DFS) were analyzed. Bioinformatics analysis was used to reveal the correlation between Wls genes and associated genes or pathways.Results: Wls was overexpressed in BC cell lines and tissues. The expression level of Wls was significantly correlated with tumor size, estrogen receptor (ER), progesterone receptor (PR), Ki-67, molecular classification, and follow-up status. Spearman correlation analysis showed that Wls protein expression was negatively correlated with ER and PR, which was confirmed by bioinformatics analysis in mRNA level. However, there were positive relationships with MBNG (modified Black’s nuclear grade), tumor size, Ki-67, molecular classification, follow-up, and vital status. Univariate and multivariate analysis showed that Wls was an independent prognostic factor for OS and DFS in BC patients. Moreover, Wls was a significant prognostic indicator of OS and DFS in a hormone receptor-positive (HR+) subgroup. GSEA showed that estrogen and androgen response, as well as epithelial-mesenchymal transition pathways, were up-regulated in the Wls high-expression group.Conclusion: Overexpression of Wls is a significant marker of worse prognosis in BC and might play a crucial role in the HR+ subgroup.Keywords: wntless, estrogen receptor, progesterone receptor, androgen receptor, breast cancer, prognosis

Yanqing Li,1 Huining Tian,2 Haoge Luo,1 Jiaying Fu,1 Yan Jiao,3 Yang Li1 1Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2College of Translational Medicine, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Yang LiDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaTel +86 185 4311 2059Fax +86 431 8561 9101Email ygli136@163.comPurpose: Ovarian cancer (OC) has the highest mortality among gynecological malignancies. Therefore, it is urgent to explore prognostic biomarkers to improve the survival of OC patients. One of the most prominent metabolic characteristics of cancer is effective glycolysis. Hexokinase 1 (HK1), as the first rate-limiting enzyme in glycolysis, is closely related to cancer progression. However, the role of HK1 in OC remains unclear.Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression of HK1 in OC patients. The chi-squared test was performed to examine the correlations between HK1 and patients’ clinical characteristics. Survival analyses were undertaken to determine the relationship between HK1 and patient survival, while the univariate/multivariate Cox model was used to evaluate the role of HK1 in patient prognosis. Gene Set Enrichment Analysis (GSEA) was performed to ascertain the related signaling pathways of HK1. RT-qPCR was implemented to validate the mRNA expression of HK1 in OC cells. MTT was used to detect cell viability after adding 2DG and knocking down HK1 in OC cells. HK1 protein expression was examined by Western blotting. Glucose uptake, lactate production, and ATP assays were undertaken following knockdown of HK1 in OC cells. Colony formation assays were performed to determine OC cell proliferation after HK1 knockdown. Transwell and wound healing assays were carried out to detect the invasion and migration of OC cells after HK1 knockdown.Results: We found that HK1 expression was increased in OC tissues and cells, and HK1 was related to the clinical characteristics of OC patients. Survival analysis revealed that OC patients in the HK1 overexpression group had poor survival. Moreover, univariant/multivariate analyses showed that HK1 may be an independent biomarker for the poor prognosis of OC patients. OC cell viability and proliferation decreased after knockdown of HK1. Consistently, glucose uptake, lactic acid production, ATP production, invasion, and migration were also decreased. Finally, GSEA enrichment analysis and Western blotting showed that HK1 was involved in MAPK/ERK signaling.Conclusion: HK1 may be a biomarker for the poor prognosis of OC patients and a potential therapeutic target.Keywords: HK1, ovarian cancer, prognosis, glycolysis

Yao Yao,* Qian Xu,* Liyong Yan, Yan Jiao, Qingqi Su, Xiaoguang Li, Cong Liu, Feng Zhao Department of Stomatology, Central Hospital of Taian, Taian, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Zhao Tel +86-538-6298546Email zxyyzhaofeng@163.comBackground: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cavity cancers, and the 5-year survival rate for OSCC patients remains unsatisfactory. MiRNA-128/miRNA-142 has been reported to work as a tumor suppressor in diverse tumors. However, the biological function of miR-128/miR-142 in OSCC is still unknown.Methods: The expression of miR-128/miR-142 and homeobox A10 (HOXA10) in OSCC tissues and cells was measured by quantitative real-time polymerase chain reaction (RT-qPCR). The effects of miR-128/miR-142 or HOXA10 on proliferation, migration, invasion and apoptosis were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), transwell and flow cytometry assays, respectively. The expression levels of epithelial–mesenchymal transition (EMT)-associated proteins (E-cadherin, N-cadherin and Vimentin), proliferation-associated protein ki-67 and HOXA10 were detected by Western blot assay. The interaction between HOXA10 and miR-128/miR-142 was predicted by TargetScan, and then confirmed by dual-luciferase reporter assay.Results: MiR-128/miR-142 was downregulated in OSCC tissues and cells. Overexpression of miR-128/miR-142 inhibited proliferation, migration, invasion and EMT and induced apoptosis in OSCC cells. HOXA10 as the target of miR-128/miR-142 was verified in OSCC cells. Knockdown of HOXA10 also repressed proliferation, migration, invasion and EMT and boosted apoptosis in OSCC cells. Upregulation of miR-128/miR-142 hindered the expression level of HOXA10, while introduction of HOXA10 weakened the effect.Conclusion: MiR-128/miR-142 suppressed OSCC tumorigenesis and metastasis by targeting HOXA10, providing a new promising therapeutic approach for OSCC patient diagnosis and treatment.Keywords: miR-128, miR-142, oral squamous cell carcinoma, HOXA10, tumorigenesis, EMT

Huining Tian,1 Xiaoyu Zhu,2 You Lv,1 Yan Jiao,3 Guixia Wang1 1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 2Department of Nephrology, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of ChinaCorrespondence: Guixia WangDepartment of Endocrinology and Metabolism, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun 130021, Jilin, People’s Republic of ChinaTel +86 158 0438 1103Fax +86 431 8878 6259Email gwang168@jlu.edu.cnYan JiaoDepartment of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun 130021, Jilin, People’s Republic of ChinaTel/ Fax +86 13843101157Email lagelangri1@126.comAbstract: Hepatocellular carcinoma (HCC) is a tumor that exhibits glucometabolic reprogramming, with a high incidence and poor prognosis. Usually, HCC is not discovered until an advanced stage. Sorafenib is almost the only drug that is effective at treating advanced HCC, and promising metabolism-related therapeutic targets of HCC are urgently needed. The “Warburg effect” illustrates that tumor cells tend to choose aerobic glycolysis over oxidative phosphorylation (OXPHOS), which is closely related to the features of the tumor microenvironment (TME). The HCC microenvironment consists of hypoxia, acidosis and immune suppression, and contributes to tumor glycolysis. In turn, the glycolysis of the tumor aggravates hypoxia, acidosis and immune suppression, and leads to tumor proliferation, angiogenesis, epithelial–mesenchymal transition (EMT), invasion and metastasis. In 2017, a mechanism underlying the effects of gluconeogenesis on inhibiting glycolysis and blockading HCC progression was proposed. Treating HCC by increasing gluconeogenesis has attracted increasing attention from scientists, but few articles have summarized it. In this review, we discuss the mechanisms associated with the TME, glycolysis and gluconeogenesis and the current treatments for HCC. We believe that a treatment combination of sorafenib with TME improvement and/or anti-Warburg therapies will set the trend of advanced HCC therapy in the future.Keywords: hepatocellular carcinoma, tumor microenvironment, glycolysis, gluconeogenesis, Warburg effect