A general therapeutic strategy to treat breast cancer is attractive as different subtypes of breast cancers often exhibit distinct response to existing cancer therapeutics. To this end, we prepare a ...catalyst couple of glucose oxidase (GOx) and gallic acid-ferrous (GA-Fe) nanocomplexes, a type of near-infrared (NIR) absorbing Fenton catalyst, to enable NIR-trigger in-situ gelation and enhanced chemodynamic/starvation therapy that appears to be effective for different types of breast cancer cells. In this system, GOx is mixed with GA-Fe in a solution of N,N-dimethylacrylamide (DMAA) and poly (ethylene glycol) double acrylate (PEGDA). Upon intratumoral injection and NIR laser exposure, such GA-Fe show rapid temperature increase, which would simultaneously increase the catalytic efficiencies of GA-Fe and GOx. The cascade production of hydroxyl radicals (•OH) from glucose is then initiated to enable polymerization of DMAA and PEGDA to form a hydrogel at the injection site within the tumor. The continuous production of cytotoxic •OH together with glucose depletion by the intratumorally fixed catalyst couple would further confer effective destruction of breast cancer tumors by such chemodynamic/starvation therapy. Our work presents a hydrogel-based therapeutic strategy for local treatment of solid tumors with high tumor destruction efficacy and low systemic toxicity.
Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative ...determination method is not accurate enough.
We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis.
The DLRN showed good discrimination of the number of LNM on all cohorts overall C-indexes (95% confidence interval): 0.821 (0.785–0.858) in the primary cohort, 0.797 (0.771–0.823) in the external validation cohorts, and 0.822 (0.756–0.887) in the international validation cohort. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271).
A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.
•Evaluation of the lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC).•Deep leaning radiomic nomogram (DLRN) based on CT images can preoperatively determine the number of LNM in LAGC.•DLRN is significantly superior to the routinely used clinical N stages, tumor size, and clinical model.•DLRN is significantly associated with the overall survival of LAGC.
Tuning the metal insulator transition (MIT) behavior of VO2 film through the interfacial strain is effective for practical applications. However, the mechanism for strain-modulated MIT is still under ...debate. Here we directly record the strain dynamics of ultrathin VO2 film on TiO2 substrate and reveal the intrinsic modulation process by means of synchrotron radiation and first-principles calculations. It is observed that the MIT process of the obtained VO2 films can be modulated continuously via the interfacial strain. The relationship between the phase transition temperature and the strain evolution is established from the initial film growth. From the interfacial strain dynamics and theoretical calculations, we claim that the electronic orbital occupancy is strongly affected by the interfacial strain, which changes also the electron–electron correlation and controls the phase transition temperature. These findings open the possibility of an active tuning of phase transition for the thin VO2 film through the interfacial lattice engineering.
The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. ...However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.
Background
Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important ...role. The aim of this study was to evaluate whether postoperative infective complications influence long‐term survival after liver resection for hepatocellular carcinoma (HCC).
Methods
Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence‐free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection.
Results
Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021).
Conclusion
Postoperative infective complications decreased long‐term OS and RFS in patients treated with liver resection for HCC.
From a multi‐institutional database, 2442 patients who underwent resection with curative intent for hepatocellular carcinoma between 2003 and 2016 were analysed retrospectively. Among them, 332 patients (13·6 per cent) had postoperative infective complications within 30 days after surgery. Multivariable Cox regression revealed that postoperative infective complications decreased long‐term overall and recurrence‐free survival after liver resection for hepatocellular carcinoma.
Complications decrease long‐term overall survival
The commercial production of coalbed methane (CBM) in China has made significant achievements. To further improve the production of CBM and realize its development, it is necessary to establish a ...unique, high-efficiency CBM production method that considers the characteristics of coal reservoirs in China. This paper presents the current status of China’s CBM exploitation over the past 15 years from three aspects: reservoir characteristics, production mode, and exploitation technology. The achievements, in terms of exploration and development of CBM resources in China, were summarized. The CBM reservoirs in China are characterized by high coal rank, low permeability, high gas content, and low reservoir pressure gradient. Strategic measures for coal and CBM co-mining were proposed creatively as “Huainan”, “Jincheng”, and “Songzao” modes. CBM production enhancement measures have achieved significant innovations and breakthroughs in drilling and completion technologies and reservoir reconstruction, effectively reducing development costs and increasing single well production. Finally, based on existing basic research, this study proposes efficient CBM exploitation technologies suitable for the characteristics of CBM reservoirs in China. In particular, the uniform permeability enhancement measures of hydraulic grid slotting and fracturing have the advantages of safety, high efficiency, economy, feasibility, and broad application prospects under complex mining conditions. It is of great strategic significance to improve the CBM recovery rate and optimize China’s energy structure.
Prostate cancer cells escape growth inhibition from transforming growth factor β (TGFβ) by downregulating TGFβ receptors. However, the mechanism by which cancer cells downregulate TGFβ receptors in ...prostate is not clear. Here, we showed that coordinated action of miR-21 and androgen receptor (AR) signaling had a critical role in inhibiting TGFβ receptor II (TGFBR2) expression in prostate cancer cells. Our results revealed that miR-21 suppresses TGFBR2 levels by binding to its 3'-UTR and AR signaling further potentiates this effect in both untransformed and transformed human prostate epithelial cells as well as in human prostate cancers. Analysis of primary prostate cancers showed that increased miR-21/AR expression parallel a significantly reduced expression of TGFBR2. Manipulation of androgen signaling or the expression levels of AR or miR-21 negatively altered TGFBR2 expression in untransformed and transformed human prostate epithelial cells, human prostate cancer xenografts and mouse prostate glands. Importantly, we demonstrated that miR-21 and AR regulated each other's expression resulting in a positive feedback loop. Our results indicated that miR-21/AR mediate its tumor-promoting function by attenuating TGFβ-mediated Smad2/3 activation, cell growth inhibition, cell migration and apoptosis. Together, these results suggest that the AR and miR-21 axis exerts its oncogenic effects in prostate tumors by downregulating TGFBR2, hence inhibiting the tumor-suppressive activity of TGFβ pathway. Targeting miR-21 alone or in combination with AR may restore the tumor inhibitory activity of TGFβ in prostate cancer.
Purpose
The purpose of this study was to explore the outcomes and risk factors for hepatitis B virus (HBV) reactivation after kidney transplantation in occult HBV carriers, who are hepatitis B ...surface antigen (HBsAg) seronegative and hepatitis B core antibody (HBcAb) seropositive before kidney transplantation.
Methods
We retrospectively analyzed 322 occult HBV carriers who received kidney transplantation in our hospital from January 1998 to June 2008. HBsAg and HBV DNA were routinely checked for diagnosis of HBV reactivation.
Results
Our results showed that 15 cases (4.7%) of occult HBV carriers had HBV reactivation after kidney transplantation. Kaplan–Meier analysis showed that 1‐, 3‐, 5‐, and 10‐year patient survival was 86.7%, 79.4%, 72.2%, and 65.0%, respectively, in the HBV reactivation group, and was 96.1%, 93.8%, 91.5%, and 84.5%, respectively, in the non‐HBV reactivation group (log‐rank 4.12, P = 0.042). Graft survival showed no difference between these 2 groups (P > 0.05). The incidences of impairment of liver function, liver function failure, hepatocellular carcinoma, and acute rejection were significantly higher in the HBV reactivation group compared with the non‐HBV reactivation group (P < 0.05). Logistic multivariate analysis showed that older age (>60 years) and using anti‐T‐cell antibodies were independent risk factors for HBV reactivation after kidney transplantation, while being hepatitis B surface antibody (HBsAb) seropositive and using lamivudine prophylaxis could protect occult HBV carriers from HBV reactivation after kidney transplantation (P < 0.05).
Conclusion
In conclusion, our data showed that HBV reactivation may diminish the patient survival but not graft survival. Older age and anti‐T‐cell antibodies may increase the risk of HBV reactivation, whereas lamivudine prophylaxis may prevent HBV reactivation after kidney transplantation.
Charge transport across metal-molecule interfaces has an important role in organic electronics. Typically, chemical link groups such as thiols or amines are used to bind organic molecules to metal ...electrodes in single-molecule circuits, with these groups controlling both the physical structure and the electronic coupling at the interface. Direct metal-carbon coupling has been shown through C60, benzene and π-stacked benzene, but ideally the carbon backbone of the molecule should be covalently bonded to the electrode without intervening link groups. Here, we demonstrate a method to create junctions with such contacts. Trimethyl tin (SnMe(3))-terminated polymethylene chains are used to form single-molecule junctions with a break-junction technique. Gold atoms at the electrode displace the SnMe(3) linkers, leading to the formation of direct Au-C bonded single-molecule junctions with a conductance that is ∼100 times larger than analogous alkanes with most other terminations. The conductance of these Au-C bonded alkanes decreases exponentially with molecular length, with a decay constant of 0.97 per methylene, consistent with a non-resonant transport mechanism. Control experiments and ab initio calculations show that high conductances are achieved because a covalent Au-C sigma (σ) bond is formed. This offers a new method for making reproducible and highly conducting metal-organic contacts.
In China, ethnic minorities often live in frontier areas and have a relatively small population size, and tremendous social transitions have enlarged the gap between eastern and western China, with ...western China being home to 44 ethnic minority groups. These three disadvantages have health impacts. Examining ethnicity and health inequality in the context of western China is therefore essential.
This paper is based on data from the 2010 China Survey of Social Change (CSSC2010), which was conducted in 12 provinces, autonomous regions and province-level municipalities in western China and had a sample size of 10,819. We examined self-rated health and disparities in self-rated health between ethnic minorities and Han Chinese in the context of western China. Self-rated health was coded as poor or good, and ethnicity was coded as ethnic minority or Han Chinese. Ethnic differences in self-rated health was examined by using binary logistic regression. Associations among sociodemographic variables, SES variable, health behaviour variable, health problem variables and self-rated health were also explored.
Fourteen percent of respondents reported their health to be poor. A total of 15.75% of ethnic minorities and 13.43% of Han Chinese respondents reported their health to be poor, indicating a difference in self-rated health between ethnic minorities and Han Chinese. Age, gender, marital status, education, alcohol, and health problems were the main factors that affected differences in self-rated health.
In western China, there were obvious ethnic disparities in self-rated health. Elderly ethnic minorities, non-partnered ethnic minorities, ethnic minorities with an educational level lower than middle school, and ethnic minorities with chronic disease had higher odds of poor self-rated health.
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