Search

Xue-Qing Guan, Lin Guan, Gong Cheng, Zhi-Jun Sun, Chuan-He Wang Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of ChinaCorrespondence: Zhi-Jun Sun; Chuan-He Wang, Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China, Tel/Fax +86 18940251218 ; Tel/Fax +86 18940252598, Email sunzhijunszj8@126.com; chuanhewangwch@126.comAim: In this study, the predictive value of soluble growth stimulation expressed gene 2 protein (sST2) for long-term clinical outcomes in patients with acute heart failure (AHF) is assessed. In addition, the influence of a history of myocardial infarction on the levels of sST2 in patients with HF, as well as its impact on outcome events, is explored. We also aim to establish a specific standard for sST2 levels in this subgroup.Methods: We conducted an ambispective cohort study involving hospitalized patients with AHF, measuring their sST2 levels and following their progress over three years. The primary endpoint was major adverse cardiovascular events (MACEs), encompassing heart failure readmission and all-cause mortality over three years. Cox regression analysis was used to evaluate the prognostic significance of sST2 levels, along with a subgroup analysis using propensity score matching (PSM) to adjust for confounding variables. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal sST2 threshold using Youden’s J statistics, and a sensitivity analysis included Kaplan–Meier survival curves.Results: The study included 149 patients with a median age of 68 years, of whom 57% were male. Both univariate and multivariate Cox regression analyses confirmed sST2 as an independent predictor of MACEs. Post-PSM analysis, 124 samples were grouped by MI history ROC curve analysis revealed an area under the curve of 0.726 for predicting MACEs in patients with MI, demonstrating a significant predictive value for sST2 levels above 34 ng/mL, which correlated with increased readmission and mortality rates. In contrast, sST2 levels in patients without MI history showed no significant predictive relevance.Conclusion: sST2 has significant long-term predictive value for clinical outcomes in patients with AHF, particularly for those with a prior MI history, indicating a need for heightened clinical attention and thorough follow-up to mitigate long-term adverse cardiovascular outcomes.Keywords: Acute heart failure, myocardial infarction, soluble growth-stimulated expression gene 2, ventricular remodeling

Mengya Dong,1 Chenyuan Liang,1 Gong Cheng2 1Department of Cardiovascular Medicine, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Department of Cardiovascular Medicine, Honghui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Gong Cheng, Department of Cardiovascular Medicine, Honghui Hospital, Xi’an Jiaotong University, 555 East Youyi Road, Xi’an, Shaanxi, 710054, People’s Republic of China, Tel +86– 18629529996, Email Xianchenggong@163.comObjective: A new approach called the loop technique has been proven safe and effective for repeated intraoperative transvenous left ventricular (LV) lead dislocations during cardiac resynchronization therapy (CRT) in a 3-year follow-up. This study aimed to report on the 5-year safety and effectiveness of the loop technique.Methods: This study was a prospective cohort study. Forty-four patients who underwent CRT device implantation at the Cardiology Department of Shaanxi Provincial People’s Hospital between January 2013 and June 2019 were included. Data on patient demographics, medical history, laboratory test results, and echocardiography images at admission were collected. The loop technique was performed with repeated intraoperative dislocations of the LV lead. The intraoperative CRT parameters were also recorded. All patients were followed for 5 years. Several auxiliary examinations were performed during follow-up.Results: The 44 patients were divided into the traditional operation group (n=36, 81.8%) and loop technique group (n=8, 18.2%). The baseline patient characteristics were almost balanced. During the 5-year follow-up, 8 (22.2%) patients in the traditional operation group and 2 (25.0%) patients in the loop technique group died. No lead dislocation or other complications related to CRT were observed. There were no significant differences in mortality rate (P=0.87), cardiac function (P=0.56), echocardiographic indices, threshold (P=0.58), or impedance (P=0.22) of the LV lead. There were no significant differences in the threshold and impedance between postoperative, 3-year, and 5-year follow-ups in the loop technique group (P=0.53).Conclusion: The loop technique is an ideal solution for repeated intraoperative LV lead dislocation during CRT implantation.Keywords: loop technique, new technique, cardiac resynchronization therapy, left ventricular lead, repeated intraoperative dislocations

Huaqiao Tang,1,* Liying Dong,1,* Xue Xia,1,* Xinling Chen,1 Meichen Ren,1 Gang Shu,1 Hualin Fu,1 Juchun Lin,1 Ling Zhao,1 Li Zhang,2 Guoqiang Cheng,2 Xianxiang Wang,3 Wei Zhang1 1College of Veterinary, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China; 2Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, People’s Republic of China; 3College of Science, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang, Email Zhangwei26510c@126.comIntroduction: Chrysin has a wide range of biological activities, but its poor bioavailability greatly limits its use. Here, we attempted to prepare casein (cas)-based nanoparticles to promote the biotransfer of chrysin, which demonstrated better bioavailability and anti-infection activity compared to free chrysin.Methods: Cas-based chrysin nanoparticles were prepared and characterized, and most of the preparation process was optimized. Then, the in vitro and in vivo release characteristics were studied, and anti-pulmonary infection activity was evaluated.Results: The constructed chrysin-cas nanoparticles exhibited nearly spherical morphology with particle size and ζ potential of 225.3 nm and − 33 mV, respectively. These nanoparticles showed high encapsulation efficiency and drug-loading capacity of 79.84% ± 1.81% and 11.56% ± 0.28%, respectively. In vitro release studies highlighted a significant improvement in the release profile of the chrysin-cas nanoparticles (CCPs). In vivo experiments revealed that the relative oral bioavailability of CCPs was approximately 2.01 times higher than that of the free chrysin suspension. Further investigations indicated that CCPs effectively attenuated pulmonary infections caused by Acinetobacter baumannii by mitigating oxidative stress and reducing pro-inflammatory cytokines levels, and the efficacy was better than that of the free chrysin suspension.Conclusion: The findings underscore the advantageous bioavailability of CCPs and their protective effects against pulmonary infections. Such advancements position CCPs as a promising pharmaceutical agent and candidate for future therapeutic drug innovations.Keywords: chrysin, nanoparticles, Acinetobacter baumannii, casein

Yongjun Huang,1,* Yong Chen,2,* Guoyun Cheng,1,* Wenqiang Li,3 Hongan Zhang,1,4 Chaoqun Yu,1 Jia Fang,1 Jieyi Zuo,1 Ying Li,1 Lei Xu,1 Dawei Sun1 1Department of Orthopedics, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 2Department of Orthopedics, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, People’s Hospital, Qingyuan, 511518, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 4The Second Clinical School of Medicine, Southern Medical University, Guangzhou, 510260, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Xu; Dawei Sun, Department of Orthopedics, Guangdong Second Provincial General Hospital, 11th Floor, Building 3, No. 466, Xingang Middle Road, Guangzhou, Guangdong Province, 510317, People’s Republic of China, Email orthoxl@163.com; sundw@gd2h.org.cnBackground: As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public.Methods: Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings.Results: The introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days).Conclusion: Experiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair. Keywords: TA/Cu2+ nanoparticles, carboxymethyl chitosan, wound dressing, antioxidant activity

Yang Zhou, Yongxiang Ge, Jian Liu, Weijian Shen, Hailiang Gu, Guochang Cheng Department of Hernia and Pediatric Surgery, Taizhou People’s Hospital, Taizhou Clinical Medical School of Nanjing Medical University, Taizhou City, Jiangsu Province, 225300, People’s Republic of ChinaCorrespondence: Guochang Cheng, Email chengguochang@hotmail.comBackground: Postoperative seroma is the most common minor complication after inguinal hernia repair surgery and can have negative consequences. The objective of this study was to identify potential risk factors for postoperative seroma.Methods: This study consecutively included 354 elderly patients with inguinal hernia who underwent laparoscopic Transabdominal preperitoneal Patch Plasty (TAPP). Seroma diagnosis was conducted by the same experienced surgeon based on the physical examinations combined with ultrasound. Risk factors for seroma were identified through univariate analysis and subsequently included in the binary multivariate logistic regression model.Results: A total of 40 patients experienced postoperative complications of seroma, with an incidence rate of 11.3% (40/354). The binary logistic regression analysis revealed that obesity (OR: 2.98, 95% CI: 1.20– 7.41, P = 0.018), disease duration ≥ 4.5 years (OR: 4.88, 95% CI: 2.14– 11.18, P < 0.001), albumin-fibrinogen ratio (AFR) level < 9.25 (OR: 6.13, 95% CI: 2.00– 18.76, P = 0.001), and modified frailty index (mFI) score ≥ 0.225 (OR: 6.38, 95% CI: 2.69– 15.10, P < 0.001) were four independent risk factors for postoperative seroma.Conclusion: Obesity, prolonged disease duration, decreased AFR level, and increased mFI score independently predict postoperative seroma after laparoscopic TAPP.Keywords: inguinal hernia, Transabdominal preperitoneal Patch Plasty, modified frailty index, albumin-fibrinogen ratio, risk factor

Xue-Qing Guan,1 Chuan-He Wang,1 Peng Cheng,1 Ling-Yu Fu,2 Qi-Jun Wu,3– 5 Gong Cheng,1 Lin Guan,1 Zhi-Jun Sun1 1Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China; 2Department of Clinical Epidemiology and Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, 110021, People’s Republic of China; 3Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China; 4Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China; 5Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of ChinaCorrespondence: Zhi-Jun Sun, Department of Cardiology, Shengjing Hospital of China Medical University, No. 39 of Huaxiang Road, Tiexi District, Shenyang, 110021, People’s Republic of China, Tel +86 02496615, Email sunzhijunszj8@126.comAbstract: Although empagliflozin has been recommended for individuals with heart failure, its effects on heart failure with preserved ejection fraction (HFpEF) remain uncertain from a physiopathological standpoint. The metabolites produced by gut microbiota have been shown to have a crucial role in the development of heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT2) have been shown to change the make-up of the gut microbiota in rodent studies. There is mixed evidence from similar studies investigating whether or not SGLT2 can affect the microbiota in the human gut. This trial is a pragmatic, randomized, open-label controlled study with empagliflozin as an intervention. We will enroll 100 patients with HFpEF and randomly assign them to one of two groups to receive either empagliflozin or a placebo. Patients in the Empagliflozin group will be given 10 mg of the drug daily, while those in the Control group will not be given empagliflozin or any other SGLT2. The purpose of the trial is to validate the changes that occur in gut microbiota in patients with HFpEF who take empagliflozin and to investigate the function of gut microbiota and their metabolites in the process.Keywords: derived metabolite, gut microbiota, heart failure, HF, myocardial fibrosis, SGLT2, short-chain fatty acids, SCFAs, sodium-glucose cotransporter-2 inhibitor

Yumin Chen,1 Wei Xiong,2,3 Ying Zhang,1 Xue Bai,1 Guoliang Cheng,1 Yifan Zhang,1 Rui Chen,1 Yinghui Guo,1 Hui Kong,1 Yue Zhang,4 Huihua Qu,5 Yan Zhao1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Institutes of Health Research, Mayinglong Pharmaceutical Group Co., Ltd, Wuhan, Hubei, People’s Republic of China; 4School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Centre of Scientific Experiment, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaHuihua QuCentre of Scientific Experiment, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Email quhuihuadr@163.comCorrespondence: Yan Zhao, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Email zhaoyandr@163.comBackground: At present, people are susceptible to developing depression and anxiety disorders in response to stress. However, there is no specific medicine for anxiety. Os Draconis (OD, named “Long gu” in Chinese) are fossilized bones that have been used in traditional Chinese medicine to treat neurological diseases for thousands of years. Thus, we conducted this study to determine the biological basis for the anxiolytic effect of OD.Methods: In this study, novel carbon dots (OD-CDs) from OD decoctions were discovered and separated. OD-CDs were anatomized using nanomaterials characterization methods to characterize the morphological structure, optical properties, and functional group properties. Four behavioural tests were conducted to observe the behavioural activities of mice, including the open field test (OFT), light/dark box test (LDT), elevated plus maze test (EPMT), and novelty-suppressed feeding test (NSFT), to determine its anxiolytic effects. Moreover, we assessed the possible mechanisms of the OD-CDs by detecting hormones associated with the hypothalamic-pituitary-adrenal (HPA) axis.Results: OD-CDs were spherical and monodispersed with a narrow size distribution between 1 and 5 nm and had a yield of 3.67%. OD-CDs increased the activity time of mice in the central zone in the OFT. The mice in the experimental group showed more frequent activity in the light compartment and the open arms, in LDT and EPMT, respectively. In addition, OD-CDs shortened the feeding latency in the NSFT. Furthermore, the results after OD-CDs intervention showed a significant increase in serum serotonin (5-HT) and norepinephrine (NE). In addition, the concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ATCH), and corticosterone (CORT) were decreased.Conclusion: These results demonstrate a definite anxiolytic effect of OD-CDs and reveal the possible mechanism of action of OD-CDs’ anxiolytic effect, which supports the research of OD for neurological disorders and a promising new trend of therapeutic approach and drug development.Graphical Abstract: Keywords: Os Draconis, carbon dots, anti-anxiety, HPA axis

Gong Cheng,1 Ji Zhang,2 Shuo Jia,2 Panpan Feng,3 Fengjun Chang,1 Li Yan,1 Pranay Gupta,4 Haoyu Wu1 1Department of Cardiology, Shaanxi Provincial People’s Hospital, Xian, 710068, People’s Republic of China; 2Department of Emergency, Shaanxi Provincial People’s Hospital, Xian, 710068, People’s Republic of China; 3Department of General Medicine, Shaanxi Provincial People’s Hospital, Xian, 710068, People’s Republic of China; 4Department of Pharmacology, Institut Teknologi Bandung, Bandung, Jawa Barat, IndonesiaCorrespondence: Gong Cheng, Department of Cardiology, Shaanxi Provincial People’s Hospital, Xian, 710068, People’s Republic of China, Tel +8618729529996, Email shanxichenggong@sina.comBackground: Myocardial ischemic/reperfusion (I/R) injury is a key prognostic factor after the myocardial infarction. However, at the time of reperfusion, the myocardial tissue has undergone for the necrosis and initiated the induction of oxidative stress and inflammation. The current study was to scrutinize the cardioprotective effect of gossypin against ISO-induced I/R injury in myocardial tissue and explore the possible underlying mechanism.Methods: Sprague Dawley (SD) was used in the current protocol and ISO was used for induction the I/R in rat. The rats were divided into different groups and received the oral administration of gossypin treatment before the reperfusion. The body weight, heart weight and heart body weight ratio were estimated. The antioxidant, cardiac injury parameters, inflammatory cytokines, inflammatory mediators, gut microbiota and lipid parameters were estimated. At the end, heart tissue histopathological study was carried out.Results: ISO-induced I/R rats received the gossypin treatment significantly (P < 0.001) enhanced the body weight and decreased the heart weight, along with suppressed the infarct size. Gossypin treatment significantly (P < 0.001) reduced the level of heart parameters, such as creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (CTn-I) and cardiac troponin T (CTn-T) in the serum. Gossypin treatment significantly (P < 0.001) altered the cardiac function, hepatic, antioxidant, inflammatory cytokines and inflammatory mediators. Gossypin significantly (P < 0.001) suppressed the MMP-2 and MMP-9 in ISO-induced I/R rats. Gossypin treatment considerably alleviated the gut dysbiosis through altered Firmicutes to Bacteroidetes (F/B) ratio and also maintained the relative abundance of Butyricicoccus, Clostridium IV, Akkermansia, Roseburia and Clostridium XIVs.Conclusion: Based on result, we can conclude that gossypin is an alternative drug for the treatment of ISO-induced I/R in rats via alteration of oxidative stress, inflammatory reaction and gut microbiota.Keywords: gossypin, ischemia-reperfusion, gut microbiota, inflammatory, antioxidant

Guilan Cheng,1,&ast; Dingxi Wang,1,&ast; Ping Zhu,2 Ziqi Lin,2 Shichao Zhu,3 Juan Li,1 Linqian Li,1 Yipeng Zhang,4 Guixiang Li1 1Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Infection Control, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Information Centre, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guixiang Li, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37 Wainan Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel +86 18980601726, Email liguixiang@wchscu.cnBackground: There are few published reports describing the clinical characteristics of acute pancreatitis (AP) patients with multidrug-resistant organism (MDRO) infection.Methods: This was a retrospective analysis of AP patients with MDRO infection in West China Hospital between July 2015 and June 2020. Basic clinical data, disease progression states, and prognoses of the MDRO and non-MDRO infection groups were compared and analyzed. Logistic regression analysis was performed to explore the related risk factors for MDRO infection. The prognoses of different MDRO infection types were compared.Results: In total, 9812 AP patients were included, 2436 (24.83%) of whom had healthcare-associated infections (641 [26.31%] MDRO infections and 1795 [73.69%] non-MDRO infections). The main MDRO strain was carbapenem-resistant Acinetobacter baumannii (CRAB) (400/62.40%). The rate of discharge against doctor’s advice, mortality, hospitalization expenses, and hospitalization days was higher in the MDRO infection group than in the noninfection group. By logistic regression analysis, the independent risk factors associated with MDRO infection included male sex (OR 1.36, 95% CI 1.09∼ 1.70), severity (OR 1.40, 95% CI 1.10∼ 1.78), ICU referral (OR 2.48, 95% CI 1.79∼ 3.44), abdominal puncture (OR 2.78, 95% CI 1.93∼ 4.02), fiberoptic bronchoscopy (OR 1.95, CI 1.35∼ 2.81), and PICC/CVC placement (OR 1.48, CI 1.06∼ 2.06). Compared with biliary and hypertriglyceridemia (HTG) (OR 0.94, 95% CI 0.73∼ 1.23), alcohol (OR 0.30, 95% CI 0.19∼ 0.47) and other etiologies (OR 0.58, 95% CI 0.41∼ 0.81) conferred a lower risk of MDRO infection. The carbapenem-resistant Klebsiella pneumoniae (CRKP) infection rate was highest in the patients who died.Conclusion: The CRAB proportion was highest in AP patients with MDRO infection. MDRO infection is related to many factors, has a poor prognosis, and increases the patient burden. CRKP infection is directly related to poor prognosis.Keywords: acute pancreatitis, multidrug-resistant organisms, infection

Yusheng Zhao,1 Yue Zhang,2 Hui Kong,1 Guoliang Cheng,1 Huihua Qu,3 Yan Zhao1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Centre of Scientific Experiment, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of ChinaCorrespondence: Huihua Qu; Yan Zhao Tel +86 10 6428 6705Fax +86 1 6428 6821Email quhuihuadr@163.com; zhaoyandr@163.comIntroduction: The charcoal processed product of Armeniacae Semen Amarum (ASA), ASA Carbonisata (ASAC), has long been used for its anti-inflammatory effects. However, the material basis and mechanism of action of ASAC remain unclear.Aim: To explore the anti-inflammatory effects of Armeniacae Semen Amarum Carbonisata-derived carbon dots (ASAC-CDs).Methods: The physicochemical properties of ASAC-CDs including morphology, optical properties, functional groups were characterized by a series of methods, mainly including electron microscopy, optical technology and X-ray photoelectron spectroscopy. The anti-inflammatory effect of ASAC-CDs was evaluated and confirmed using acute lung injury (ALI) induced by lipopolysaccharides (LPS) in rats.Results: The ASAC-CDs ranged from 1.5 to 5.5 nm in diameter, with a quantum yield of 3.17%. ASAC-CDs alleviated LPS-induced inflammation, as demonstrated by reducing the levels of IL-6, IL-1β and TNF-α and increasing the contents of IL-10 in rat serum. More interestingly, ASAC-CDs reduce the content of MDA and MPO and increase the activity of SOD and the content of GSH, indicating the antioxidant activity of ASAC-CDs.Conclusion: These results demonstrate the remarkable anti-inflammatory effects of ASAC-CDs against ALI induced by LPS, which provide an important basis for the application of ASAC-CDs in clinical anti-pneumonia, and lay an experimental foundation for the research and development of novel nano-drugs.Keywords: Armeniacae Semen Amarum Carbonisata, carbon dots, lipopolysaccharide, anti-inflammatory

Jie Hu,1,* Juan Luo,1,* Meiling Zhang,1 Jiashu Wu,1 Yue Zhang,2 Hui Kong,1 Huihua Qu,3 Guoliang Cheng,4 Yan Zhao1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2School of Life Science, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, 276000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan ZhaoSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of ChinaTel +86 010-62486705Email zhaoyandr@bucm.edu.cnGuoliang ChengState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., No. 209 Hong Qi Lu, Lanshan District, Linyi, 276000, Shandong Province, People’s Republic of ChinaTel +86 18905391156Email 18905391156@163.comAim: To explore the effects of Radix Sophorae Flavescentis carbonisata-based carbon dots (RSFC-CDs) on an ethanol-induced acute gastric ulcer rat model.Methods: The structure, optical properties, functional groups and elemental composition of RSFC-CDs synthesized by one-step pyrolysis were characterized. The gastric protective effects of RSFC-CDs were evaluated and confirmed by applying a rat model of ethanol-induced acute gastric ulcers. The underlying mechanisms were investigated through the nuclear factor-kappa B (NF-κB) signalling pathway and oxidative stress.Results: RSFC-CDs with a diameter ranging from 2– 3 nm mainly showed gastric protective effects by reducing the levels of NF-κB, tumour necrosis factor-α (TNF-α), interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) to inhibit ethanol-induced inflammation and oxidative stress.Conclusion: RSFC-CDs have anti-inflammatory and anti-oxidative effects, making them promising for application in ethanol-induced gastric injury.Keywords: carbon dots, Radix Sophorae Flavescentis, gastroprotection, anti-inflammatory, antioxidant

Baize Zhang,1 Junhui Wang,1 Zhifei Zhou,2 Xin Ge,1 Geng Cheng,3 Yujiang Chen,1 Xiaojing Wang1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; 2Department of Stomatology, The General Hospital of Tibetan Military Region, Lasha, 850000, People’s Republic of China; 3State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Endodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of ChinaCorrespondence: Xiaojing WangDepartment of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi’an, Shaanxi, 710032, People’s Republic of ChinaTel/Fax +86-29-84776239Email wxjingpd@hotmail.comAbstract: Currently, the common treatment for pulpitis and periapical diseases is root canal treatment. However, the complex variations of root canal system often affect the effect of root canal treatment and even lead to treatment failure. Therefore, it is of great significance for dentists to emphasize the diversity of root canal morphology and to be familiar with the anatomical morphology of root canal to improve the success rate of clinical diagnosis and treatment. We reported a case of an eight-year-old female patient of type V root canal in a young maxillary middle incisor. The young maxillary central incisor was diagnosed with irreversible pulpitis by radiography and CBCT examination. The present case report described the entire treatment procedure of a young maxillary central incisor after trauma, including successive apical examination, CBCT examination and multiple root canal filling, and finally the treatment was completed with the aid of microscope. The root canals were filled with the vertical compression technique. Z350 composite resin was used to repair the tooth. The patient was followed-up at three, six, and 12 months after endodontic treatment. All of the examinations were normal. Finding the anatomical configuration of root canal by various ways will help to improve the success rate of root canal therapy.Keywords: cone-beam computed tomography, CBCT, one root with two root canals, root canal microscope, young maxillary central incisor

Liping Zou, Guiping Cheng, Chengcheng Xu, Heyu Liu, Yingying Wang, Nianyu Li, Xiaorong Fan, Changhong Zhu, Wei Xia Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Wei XiaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86 27 8369 2651Email tjxiawei@hust.edu.cnPurpose: The toxicity of copper nanoparticle (CuNP) exposure in the ovaries has attracted attention recently, but the precise molecular mechanism involved requires further investigation. We investigated the cytotoxicity of CuNPs in ovarian granulosa cells and the protective effect of heme oxygenase 1 (HO-1) against CuNP-induced damage.Methods: Human ovarian granulosa cells (COV434) were treated with CuNPs, and cytotoxicity was evaluated using Cell Counting Kit-8 and flow cytometry assays. Oxidative stress was identified using biochemical markers of oxidation and anti-oxidation. The protein levels of mitogen-activated protein kinase 14 (MAPK14), phospho-MAPK14, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 were measured by immunoblotting. Subsequently, for oxidative stress parameter detection, the cells were pre-treated with hemin to induce HO-1 expression prior to CuNP treatment.Results: Exposure to CuNPs decreased cell viability and the mitochondrial membrane potential, increased the apoptosis rate, and induced oxidative stress. Furthermore, hemin pretreatment induced HO-1 expression in cells, which partially reduced the accumulation of reactive oxygen species induced by CuNPs and increased the levels of antioxidant enzymes.Conclusion: CuNPs exert cytotoxic effects on human ovarian granulosa cells by inducing oxidative stress, and may induce HO-1 expression via the MAPK14-Nrf2 signaling pathway. Moreover, HO-1 protects against oxidative stress induced by CuNPs.Keywords: copper nanoparticles, cytotoxicity, oxidative stress, heme oxygenase 1

Yu-Tao Liu,1 Xue-Zhi Hao,1 De-Ruo Liu,2 Gang Cheng,3 Shu-Cai Zhang,4 Wen-Hua Xiao,5 Yi Hu,6 Jun-Feng Liu,7 Ming He,7 Cui-Min Ding,8 Li Zhang,9 Jun Wang,10 Hui Li,11 Gui-Lan Dong,12 Xiu-Yi Zhi,13 Jian Li,14 Yuan-Kai Shi1 1Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of General Thoracic Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Medical Oncology, Beijing Hospital, Beijing, People’s Republic of China; 4Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, People’s Republic of China; 6Department of Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 7Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 8Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 9Department of Respiratory Medicine, Peking Union Medical College Hospital, Affiliated to Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 10Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, People’s Republic of China; 11Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China; 12Department of Radiotherapy and Chemotherapy, Tangshan People’s Hospital, Tangshan, Hebei, People’s Republic of China; 13Department of Thoracic Surgery, Xuanwu Hospital of Capital Medical University, Beijing, People’s Republic of China; 14Department of Thoracic Surgery, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yuan-Kai ShiDepartment of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People’s Republic of ChinaTel +86 10 8778 8293Email syuankai@cicams.ac.cnAbstract: The efficacy and possible role of epidermal growth factor receptor tyrosine kinase inhibitors in treating early-stage non-small-cell lung cancer have yet to be established. Therefore, we aimed to explore the efficacy and safety of icotinib in completely resected EGFR-mutant stage II–IIIA lung adenocarcinoma patients who underwent standard chemotherapy. This is a randomised, double-blinded, placebo-controlled, multicentre, Phase III trial. A total of 124 patients aged 18– 75 years who qualified the inclusion criteria were recruited. These patients were randomised (1:1) to receive either icotinib (125 mg 3 times per day) or placebo (the same dosage and frequency) for 36 months, followed by a further 36 months of observational window. The primary endpoint is disease-free survival (DFS), while the secondary endpoints are overall survival, 3-year and 5-year DFS, safety and tolerability of the medication, and health-related quality-of-life. Analyses will be conducted in a full analysis set and a per-protocol set as well. To our knowledge, the present study is the first randomised, double-blinded, placebo-controlled, multicenter trial designed to explore efficacy and safety of icotonib in this population. The results obtained in the near future may provide potential guidance in clinical practice.Trial Registration: This trial was registered on www.ClinicalTrail.gov as NCT02125240.Keywords: EGFR mutation, non-small-cell lung cancer, lung adenocarcinoma, icotinib, adjuvant chemotherapy

Shuwei Wang, Xinru Guo, Wenying Lv, Yanteng Li, Leiming Zhang, Chao Dong, Jianning Zhang, Gang Cheng Department of Neurosurgery, Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, People’s Republic of ChinaCorrespondence: Jianning Zhang; Gang ChengDepartment of Neurosurgery, Sixth Medical Center, Chinese PLA General Hospital, No. 6 Pucheng Road, Beijing 100048, People’s Republic of ChinaTel +86 10-66951351Email jianningz36@aliyun.com; bgsvsaswgxo6@163.comIntroduction: Ribosomal protein SA pseudogene 52 (RPSAP52) has been characterized as an oncogenic lncRNA in pituitary tumors. Analysis of TCGA dataset revealed the upregulation of RPSAP52 in glioblastoma (GBM). We, therefore, investigated the roles of RPSAP52 in GBM.Methods: A total of 50 GBM patients (33 males and 20 females; 54– 75 years; mean age: 61.8± 5.8 years) were selected from the 89 cases of GBM patients. Under the guidance of MRI, brain biopsy was performed to collect GBM tissues from each patient for the diagnosis of GBM. U-373 MG cells were employed and had transient transfections. qRNA, Western blot, and a series of experiments were performed to characterize their associations.Results: The results showed that RPSAP52 was upregulated in GBM patients, and its high expression levels predicted poor survival. In GBM tissues, expression levels of RPSAP52 were significantly and positively correlated with that of TGF-β 1. In GBM tissues, RPSAP52 positively regulated the expression of TGF-β 1. Cell stemness assay showed that, compared to C and NC groups, overexpression of RPSAP52 and TGF-β 1 led to increased, while silencing of RPSAP52 led to decreased CD133+ cells. Overexpression of TGF-β 1 attenuated the effects of RPSAP52 siRNA silencing.Conclusion: Therefore, RPSAP52 upregulates TGF-β 1 to increase cancer cell stemness and predict postoperative survival in GBM.Keywords: glioblastoma, RPSAP52, TGF-β 1, survival, stemness

Chenghui Zhang,1,2,* Qing Ou,1,* Yan Gu,1,* Gaiping Cheng,3 Rong Du,1,2 Li Yuan,1 Ruth LM Cordiner,4 Deying Kang,5 Jiaying Zhang,6 Qiaorong Huang,7 Chuan Yu,8 Li Kang,9 Xuan Wang,4,10 Xin Sun,5 Xianming Mo,7 Haoming Tian,1 Ewan R Pearson,4 Wentong Meng,7 Sheyu Li1,4 1Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Endocrinology and Metabolism, Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region, Chengdu 610041, People’s Republic of China; 3Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 4Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UK; 5Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 6Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 7Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 8Department of Health-Related Social and Behavioral Science, West China School of Public Health, Sichuan University, Chengdu 610041, People’s Republic of China; 9Division of Systems Medicine, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UK; 10Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Uppsala 75123, Sweden*These authors contributed equally to this workCorrespondence: Sheyu LiDepartment of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu 610041, ChinaTel +86-13194874843Fax +86-28-85422982Email lisheyu@gmail.comWentong MengLaboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan 610041, People’s Republic of ChinaTel +86-18980601256Fax +86-28-85422982Email mwentong@sina.comAim: To investigate the count of circulating tissue factor-positive (TF+) procoagulant microparticles (MPs) in patients with type 1 diabetes mellitus (T1DM).Methods: This case-control study included patients with T1DM and age and sex-matched healthy volunteers. The counts of phosphatidylserine-positive (PS+) MPs and TF+PS+MPs and the subgroups derived from different cell types were measured in the peripheral blood sample of the two groups using multicolor flow cytometric assay. We compared the counts of each MP between groups as well as the ratio of the TF+PS+MPs and PS+MPs (TF+PS+MPs/PS+MPs).Results: We recruited 36 patients with T1DM and 36 matched healthy controls. Compared with healthy volunteers, PS+MPs, TF+PS+MPs and TF+PS+MPs/PS+MPs were elevated in patients with T1DM (PS+MPs: 1078.5 ± 158.08 vs 686.84 ± 122.04/μL, P

Qianzi Che,1 Ying Yang,2 Guanliang Cheng,2 Jia Jia,2 Fangfang Fan,2 Jianping Li,2 Yong Huo,2 Dafang Chen,1 Yan Zhang21Department of Epidemiology & Biostatistics, Peking University Health Science Center, Beijing, People’s Republic of China; 2Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaBackground: Type 2 diabetes (T2DM), hypertension and kidney dysfunction are known risk factors for cardiovascular disease, but their combined effect on carotid plaque remains uncertain. This study aims to assess the associations between T2DM, hypertension, kidney dysfunction and carotid plaque, and further explore the combined effect of three diseases.Patients and methods: We conducted a cross-sectional analysis among 3,815 community-dwelling adults in a Chinese atherosclerosis cohort. Estimated glomerular filtration rate (eGFR), hypertension and T2DM were evaluated as risk factors for carotid plaque. The presence, number and total area of carotid plaques were also assessed. Using logistic model, mutinomial logistic model and generalized linear regression model, the relationship between risk factors and carotid plaque was examined.Results: T2DM, hypertension, decreased GFR, and, inversely, eGFR, were independently associated with the presence, number and total area of carotid plaque. Stratified analysis by T2DM and hypertension showed T2DM attenuated the association between eGFR change and carotid plaque. There was a cumulative relationship between three risk factors and carotid plaque burden. The OR for the number of plaques was 1.0 (reference), 1.55 to 2.03, 1.94 to 3.14, and 3.69 (all P

Guangyan Cheng,1 Fei Liu,1 Xinyu Niu,1 Qigen Fang2 1Department of Oral Medicine, Stomatology Center, The First affiliated hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Head Neck and Thyroid, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China Background: To analyze the value of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in the survival of patients with parotid cancer.Methods: In total, 249 patients were enrolled. Information including age, sex, pretreatment NLR, and pathologic variables such as, tumor stage, intraparotid node (IPN) metastasis, and follow-up findings was extracted and analyzed.Results: IPN metastasis was noted in 45 (18.1%) patients, and the mean NLR was 2.48, with a range from 1.5 to 6.1. The NLR was significantly associated with tumor stage, disease stage, and disease grade. A total of 73 patients died of the disease, and the 10 -year disease-specific survival (DSS) rate was 62%. In patients with an NLR

Ana Alves-Pinto,1 Stefan Ehrlich,2 Gordon Cheng,2 Varvara Turova,1 Tobias Blumenstein,1 Renée Lampe1 1Research Unit of the Buhl-Strohmaier Foundation for Paediatric Neuroorthopaedics and Cerebral Palsy, Department of Orthopaedics, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; 2Chair for Cognitive Systems, Department of Electrical and Computer Engineering, Technical University of Munich, Munich, Germany Abstract: Playing a musical instrument demands the integration of sensory and perceptual information with motor processes in order to produce a harmonic musical piece. The diversity of brain mechanisms involved and the joyful character of playing an instrument make musical instrument training a potential vehicle for neurorehabilitation of motor skills in patients with cerebral palsy (CP). This clinical condition is characterized by motor impairments that can affect, among others, manual function, and limit severely the execution of basic daily activities. In this study, adolescents and adult patients with CP, as well as a group of typically developing children learned to play piano for 4 consecutive weeks, having completed a total of 8 hours of training. For ten of the participants, learning was supported by a special technical system aimed at helping people with sensorimotor deficits to better discriminate fingers and orient themselves along the piano keyboard. Potential effects of piano training were assessed with tests of finger tapping at the piano and tests of perception of vibratory stimulation of fingers, and by measuring neuronal correlates of motor learning in the absence of and after piano training. Results were highly variable especially among participants with CP. Nevertheless, a significant effect of training on the ability to perceive the localization of vibrations over fingers was found. No effects of training on the performance of simple finger tapping sequences at the piano or on motor-associated brain responses were registered. Longer periods of training are likely required to produce detectable changes. Keywords: music, neurorehabilitation, sensorimotor, integration, alpha event-related desynchronization

Yi Liu,1 Hongyu Piao,1 Ying Gao,1 Caihong Xu,2 Ye Tian,1 Lihong Wang,1 Jinwen Liu,1 Bo Tang,1 Meijuan Zou,1 Gang Cheng1 1Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Food Science, Shenyang Normal University, Shenyang, Liaoning Province, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN38), an active metabolite of irinotecan (CPT-11), is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OH)SN38 and chitosan-(C20-OH)SN38) to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OH)SN38 (CS-(10s)SN38) and chitosan-(C20-OH)SN38 (CS-(20s)SN38) were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC)0–24 of SN38 after intravenously administering CS-(10s)SN38 and CS-(20s)SN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P

Gang Cheng,1,2 Yiyan He,1 Li Xie,1 Yu Nie,1 Bin He,1 Zhirong Zhang,2 Zhongwei Gu11National Engineering Research Center for Biomaterials, 2Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of ChinaBackground: The reduction-sensitive cationic polymer is a promising nonviral carrier for gene delivery. Until now, disulfide bonds have been the only golden standard for its design. The aim of this research was to develop a novel reduction-responsive cationic polymer as a gene carrier.Methods: Polycationic carriers were synthesized by addition of branched oligoethylenimine 800 Da (OEI800) via an active ester containing diselenide bonds. Disulfide bonds cross-linked with OEI800-SSx and monoselenide bonds linked with OEI800-Sex were synthesized and compared. Their molecular weights and degradation properties were determined using gel permeation chromatography. Changes in particle size, morphology, and DNA binding were investigated by dynamic light scattering, transmission electron microscopy, and electrophoresis assay in a reduction environment. Cytotoxicity and transfection in vitro were evaluated in a murine melanoma cell line (B16F10) and a human cervical epithelial carcinoma cell line (HeLa), while intracellular degradation and dissociation with DNA were studied by confocal laser scanning microscopy with FITC-labeled OEI800 derivatives and Cy5-labeled DNA.Results: Diselenide-conjugated OEI800 (OEI800-Se Sex) polymer carriers of high molecular weight were successfully synthesized. After compacting with DNA, the OEI800-SeSex polymers formed nanoparticles with an average size of 140 nm at an adequate C/P ratio. OEI800-Se Sex showed reduction-responsive degradation properties similar to those of the OEI800-SSx via gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. OEI800-SeSex showed much lower cytotoxicity than PEI25k, and significantly higher transfection efficiency than OEI800 in both B16F10 and HeLa cells. Transfection of luciferase in the OEI800-SeSex group was comparable with that of standard PEI25k and traditional reduction-sensitive polymer OEI800-SSx groups. Furthermore, intracellular degradation of OEI800-SeSex and dissociation with DNA were also confirmed by confocal laser scanning microscopy.Conclusion: The OEI800-SeSex obtained was able to bind plasmid DNA efficiently to yield nanosized particles and had reduction sensitivity which is as efficient as that for OEI800-SSx. In vitro experiments confirmed its low cytotoxicity and high transfection ability. Diselenide bonds can be used as effective and novel reduction-sensitive linkages for gene delivery.Keywords: diselenide, oligoethylenimine, reduction-sensitive, gene carriers

Xianting Ding1, David Jesse Sanchez2,3, Arash Shahangian2, Ibrahim Al-Shyoukh1,4, Genhong Cheng2, Chih-Ming Ho11Department of Mechanical and Aerospace Engineering, UCLA, Los Angeles, CA, USA; 2Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA; 4Molecular and Medical Pharmacology Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, USABackground: Infectious diseases cause many molecular assemblies and pathways within cellular signaling networks to function aberrantly. The most effective way to treat complex, diseased cellular networks is to apply multiple drugs that attack the problem from many fronts. However, determining the optimal combination of several drugs at specific dosages to reach an endpoint objective is a daunting task.Methods: In this study, we applied an experimental feedback system control (FSC) method and rapidly identified optimal drug combinations that inhibit herpes simplex virus-1 infection, by only testing less than 0.1% of the total possible drug combinations.Results: Using antiviral efficacy as the criterion, FSC quickly identified a highly efficacious drug cocktail. This cocktail contained high dose ribavirin. Ribavirin, while being an effective antiviral drug, often induces toxic side effects that are not desirable in a therapeutic drug combination. To screen for less toxic drug combinations, we applied a second FSC search in cascade and used both high antiviral efficacy and low toxicity as criteria. Surprisingly, the new drug combination eliminated the need for ribavirin, but still blocked viral infection in nearly 100% of cases.Conclusion: This cascade search provides a versatile platform for rapid discovery of new drug combinations that satisfy multiple criteria.Keywords: drug combination, HSV-1, combinatorial drug optimization, feedback system control, FSC, drug screening

The pump user demands for specification along with noise and vibration magnitude for extreme operating conditions apart from best efficiency flow. In order to predict the noise level in pumps, the entire unit of pump has to be considered for acoustic evaluation. Hence, the full three dimensional model of vertical inline pump which consists of inlet pipe, impeller, and volute casing is considered for detailing the flow induced noise using Lighthill analogy. The performance characteristics of pump are well matched between experimental and computational results and the overall sound power level at best efficiency flow using computation was compared with empirical relations and found to be agreed well. The streamline patterns along the inlet pipe shows the effects of recirculation and return flow at partload condition and confirm that the utilization of flow passage is not well streamlined even for nominal flow rate. Further, the detailed study of inlet pipe cross sections reveals the nature of different noise sources such as dipole and quadrupole sound levels along with Proudman source power level. The intensity of turbulence and vortices in flow passage is predicted well using quadrupole source and Proudman sound power levels.

Refractive index changes in a-SiO2 consist of positive index variations or regular nanoscale patterns. We spectroscopically reveal the electronic and structural transformation of glass in the self-organized structures, indicating bond breaking and oxygen deficiency. We equally propose a method of real time control of nanogratings formation under the action of ultra -short laser pulse with variable envelopes. Application as polarizing optical devices is discussed.

Ionic liquid (IL)-based pretreatment makes lignocellulosic biomass more accessible to enzymes and improves enzymatic digestibility. However, the ILs left in biomass slurry after pretreatment could inhibit activity of enzymes and microbial fermentation. Therefore, it is necessary to develop robust host strains that are IL-tolerant. In this study, we characterized IL tolerance and biofuel production of adapted Escherichia coli obtained by adaptive laboratory evolution (ALE). We found that IL-tolerant E. coli obtained via ALE by 1-butyl-3-methylimidazolium chloride ([C 4 C 1 Im]Cl) showed improved growth in the presence of four ILs, [C 4 C 1 Im]Cl, 1-ethyl-3-methylimidazolium chloride ([C 2 C 1 Im]Cl), 1-butyl-3-methylimidazolium acetate ([C 4 C 1 Im][OAc]), and 1-ethyl-3-methylimidazolium acetate ([C 2 C 1 Im][OAc]) compared to that of the parent strain. The growth of adapted strain E. coli MG1655-A1 was even promoted by [C 4 C 1 Im]Cl and [C 2 C 1 Im]Cl of certain concentrations. The adapted strains were further transformed by introducing mevalonate-based metabolic pathway and they showed significantly increased isoprenol titer compared to parent strain E. coli MG1655. Furthermore, they were shown to use [C 4 C 1 Im][OAc] and [C 2 C 1 Im][OAc] as carbon sources and assimilate the acetate ions. These results indicated that ALE provided promising host strains for one-pot biofuel production.

A high heat transfer rate and excellent heat transfer uniformity are crucial to the physical tempering manufacturing of glass. In the current study, numerical simulations were conducted to evaluate the influence of nozzle shape (circular, square, or triangular) on the transient heat transfer rate and uniformity during jet impingement heating using a square-array configuration at low nozzle-to-plate distances. The Reynolds number (Re) was varied between 2000 and 10000, the nozzle-to-plate distance to nozzle diameter ratio (H/D) was varied between 0.2 and 2, and the nozzle-to-nozzle spacing to nozzle diameter ratio (S/D) was set to values of 4, 5, and 7. The properties of heat transfer rate and uniformity are evaluated by the surface Nusselt number distribution, the average Nusselt number, and the coefficient of variation of temperature. The results revealed that a higher heat transfer rate and good heat transfer uniformity could be obtained only at H/D = 0.2 or 2. Furthermore, square and triangular nozzles afforded superior heat transfer rates and uniformity to the corresponding circular nozzles in specific jet configurations. Moreover, at low H/D values, non-circular nozzles can obtain a higher local maximum Nusselt number than circular nozzles, and significant axis switching occurs around the impingement hole in the center of the jet impingement wall. [ABSTRACT FROM AUTHOR]