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Jia-Qi Ning,1,2 Jian-Sheng Luo,1,2 Ling-Ling Ding,2 Yu-Hong Guo,3 Zhuo-Ya Chen,2 Qi Wang,2 Rui-Ling Zhou2 1Department of Anesthesiology, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 3Department of Emergency, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of ChinaCorrespondence: Ling-Ling Ding, Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China, Tel/Fax +86 1087906647, Email dignlilbc@outlook.com; dinglingling301@126.comObjective: This study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes.Methods: Forty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45– 75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists’ physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared.Results: There was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001).Conclusion: Electroacupuncture stimulation can increase rSO2 levels in patients with diabetes.Clinical Registration Number: ChiCTR2100048783 (http://www.chictr.org.cn).Keywords: electroacupuncture, preconditioning, regional cerebral oxygen saturation, diabetes

Xi-Jian Dai,1,2* Chun-Lei Liu,3,4* Ren-Lai Zhou,3 Hong-Han Gong,1 Bin Wu,5 Lei Gao,1 Yi-Xiang J Wang2 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, People’s Republic of China; 3Beijing Key Lab of Applied Experimental Psychology, School of Psychology, and National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, People’s Republic of China; 4School of Education, Qufu Normal University, Qufu, Shandong, People’s Republic of China; 5National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, People’s Republic of China *These authors have contributed equally to this work Objective: The aim of this study is to use resting-state functional connectivity (rsFC) and amplitude of low-frequency fluctuation (ALFF) methods to explore intrinsic default-mode network (DMN) impairment after sleep deprivation (SD) and its relationships with clinical features. Methods: Twelve healthy male subjects underwent resting-state functional magnetic resonance imaging twice: once following rested wakefulness (RW) and the other following 72 hours of total SD. Before the scans, all subjects underwent the attention network test (ANT). The independent component analysis (ICA), rsFC, and ALFF methods were used to examine intrinsic DMN impairment. Receiver operating characteristic (ROC) curve was used to distinguish SD status from RW status. Results: Compared with RW subjects, SD subjects showed a lower accuracy rate (RW =96.83%, SD =77.67%; P

In humans, gut microbiota can determine the health status. The regulatory mechanisms of the gut microbiota in asthma must be elucidated. Although antibiotics (ABXs) can clear infections, they markedly alter the composition and abundance of gut microbiota. The present study used ABX-treated mice to examine the time-dependent effects of ABX administration on the gut microbiota and intestinal mucosal barrier. The mouse asthma model was established using ovalbumin (OVA) and gavaged with an ABX cocktail for different durations (1 or 2 weeks) and stacked sequences. The pathology of the model, model 2, OVA-ABX, OVA-ABX 2, ABX-OVA and ABX-OVA was severe when compared with the control group as evidenced by the following results: i) significantly increased pulmonary and colonic inflammatory cell infiltration; ii) enhanced pause values and iii) OVA-induced immunoglobulin E (IgE) and TGF-β expression levels, and significantly downregulated Tight Junction Protein 1 (TJP1), claudin 1 and Occludin expression levels. Furthermore, the intestinal bacterial load in the OVA-ABX and OVA-ABX 2 groups was significantly lower than that in the ABX-OVA and ABX-OVA 2 groups, respectively. The predominant taxa were as follows: phyla, Firmicutes and Proteobacteria , genera, Escherichia - Shigella , Lactobacillus and Lachnospira . The abundances of Lachnospira and Escherichia - Shigella were correlated with the expression of OVA-induced IgE and TJPs. These findings indicated that ABX administration, which modifies microbiome diversity and bacterial abundance, can disrupt colonic integrity, downregulate TJ proteins, damage the intestinal barrier, enhance enterocyte permeability, and promote the release of inflammatory factors, adversely affecting asthma alleviation and long-term repair., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Xu et al.)

To enhance the anti-HIV-1 efficacy and solubility of our previously documented NNRTI 1, a collection of innovative quinoline-substituted DAPY derivatives were devised using heteroaromatic replacement strategy. The results of biological evaluation revealed that the representative compound 5h possessed the highest inhibitory activity against wild-type HIV-1 and selectivity index (EC 50  = 0.0018 μM, SI > 166667), which were obviously better than that of 1 (EC 50  = 0.00978 μM, SI > 37764), NVP (EC 50  = 0.059 μM, SI > 158), EFV (EC 50  = 0.028 μM, SI > 269), and ETR (EC 50  = 0.0029 μM, SI > 1519). The water solubility of compound 5h was remarkably improved, surpassing that of 1, ETR and RPV. Additionally, this compound exerted significantly enhanced anti-resistance potency, compared to 1, and displayed comparable activity to ETR against WT RT of HIV-1 (IC 50  = 0.011 μM). To elucidate the underlying molecular mechanisms, molecular docking studies were conducted to investigate the crucial interactions between 5h and WT/mutant strains of HIV-1. These findings provide valuable insights and drive further advancements in the development of DAPYs for HIV therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Our recent great interest in developing 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) analogs for HIV therapy identified a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) 3 (EC 50  = 0.01681 μM), but its therapeutic efficacy was limited by its poor anti-resistance potency. This prompted us to search for potential HEPT analogs with broad-spectrum activities, leading to the generation of a series of novel HEPT analogs through exploring the chemical space of the solvent - protein interface. Encouraging improvements in anti-resistance efficacy were observed in some of these analogs, with the most promising compound 7 g being 3 to 26 - fold more potent than 3 against five mutant strains (E138K, Y181C, L100I, K103N, and Y188L). This analog surpassed the activity and selectivity of compound 3 by approximately 2-fold (EC 50  = 0.007468 μM, SI = 4260). Furthermore, it was found to demonstrate feeble inhibition of CYP and hERG in vitro, and no in vivo acute toxicity. This study will further enrich the structure-activity relationships (SARs) of the HEPT scaffold, providing new guidance for the development of NNRTIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Circulating n -3 PUFA, which integrate endogenous and exogenous n -3 PUFA, can be better used to investigate the relationship between n -3 PUFA and disease. However, studies examining the associations between circulating n -3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case–control study aimed to examine the association between serum n -3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n -3 PUFA and total n -3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, P for trend < 0·001) for ALA, 0·57 (0·40, 0·80, P for trend < 0·001) for DPA, 0·48 (0·34, 0·68, P for trend < 0·001) for DHA, 0·39 (0·27, 0·56, P for trend < 0·001) for long-chain n -3 PUFA and 0·31 (0·22, 0·45, P for trend < 0·001) for total n -3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n -3 PUFA and total n -3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n -3 PUFA and total n -3 PUFA were inversely associated with odds of having CRC in Chinese population.

As a new-generation photoelectric material, perovskites have attracted researchers' attention due to their excellent optoelectronic properties. However, the existence of defects inevitably causes structural degradation and restricts their performance, which need to be further improved by post-treatment. At present, post-treatments mostly focus on non-contact treatments, which may constrain the effect since the influence on the perovskites caused by the direct contact is much more straightly. Therefore, we proposed an annealing strategy of straight manipulation in a solvent atmosphere with the assistance of polyimide (PI) tape for the perovskite post-treatment, due to the high heat resistance and less glue residual of this tape. It casts an influence on the perovskite directly, proving the possibility of the straight manipulation by operators, promoting the recrystallization of the perovskite grains and removing the impurity substance. The optimized Pb-free perovskite film exhibits a better X-ray sensitivity of 7.5 × 10 4 μC Gy air -1 cm -2 and a great detection limit of 47 nGy air s -1 , which is comparable to advanced Pb-based perovskite X-ray detectors and all commercial ones. The new annealing strategy provides a facile, effective, and simple method to improve the perovskite quality, exhibiting the potential and harmlessness of the direct contact post-treatment, which paves the way for a broader application of perovskites.

Objective: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI., Methods: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group，with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot., Results: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased( P <0.05), the levels of total protein, IL-1β and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased( P <0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed( P <0.05) in the EA group rather than in the sham-acupoint group., Conclusion: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.

Members of the HEPT class are potential non-nucleoside inhibitors of HIV-1 reverse transcriptase. Our previously disclosed one representative HEPT analog 2 produced potent inhibitory activity against wild-type HIV-1 (EC 50  = 63.0 nM), but its high cytotoxicity and low selectivity index still needs to be improved (CC 50  = 34.0 μM, SI = 565). In this work, a series of novel cyclopropyl-substituted HEPT analogs were developed by substituting a cyclopropyl ring for the isopropyl group at the C-5 position of 2 with the purpose of improving its potency and safety. Of this series, the most potent compound 9h featuring a 2,5-fluoro substitution on the C-6 benzene ring exerted significantly increased inhibitory activity toward wild-type HIV-1 (EC 50  = 0.017 μM), which was 4-fold more active than the lead compound 2. The cytotoxicity of 9h was also reduced with much higher selectivity index (SI > 2328). This compound possessed good pharmacokinetics profiles and potential safety: (1) No obvious in vitro inhibition effect toward CYP enzyme and hERG was observed in 9h; (2) The single-dose acute toxicity test did not induce mice death and obvious pathological damage; (3) Excellent oral bioavailability of 9h (F= 86%) in rats was unveiled. These results provide valuable guidance for further development of HEPT anti-HIV-1 drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Vitamin B 2 is essential for DNA methylation, stability and repair, which may influence the development and pathogenesis of several cancers. However, data regarding the associations of circulating vitamin B 2 with colorectal cancer risk are limited. The purpose of this study was to investigate the associations between serum vitamin B 2 and colorectal cancer risk, particularly among participants with different serum levels of vitamin B 6 or folate. A hospital-based case-control study, including 1009 colorectal cancer cases and 1182 controls matched by age and sex, was conducted in Guangdong Province, China. Vitamin B 2 including riboflavin and flavin mononucleotide (FMN), the vitamin B 6 indicator pyridoxal-5'-phosphate (PLP) and folate in serum samples were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Vitamin B 2 sum was calculated as the sum of riboflavin plus FMN. A significant inverse association was observed between serum FMN, but not serum riboflavin or vitamin B 2 sum, and colorectal cancer risk. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of serum FMN, by comparing the highest with the lowest quartile, was 0.63 (0.46-0.85, P trend = 0.001). Stratified analysis by serum PLP and folate levels indicated that serum FMN was inversely associated with colorectal cancer risk among participants with lower serum PLP or higher folate levels. This study added supporting data to the limited evidence that vitamin B 2 could play a preventive role in colorectal carcinogenesis among the Chinese population, primarily by FMN. Individuals with a lower PLP level or an adequate folate level could be more sensitive to the protective role of vitamin B 2 .

Plant-based diets are associated with a lower risk of colorectal cancer, but the risk might differ by the quality of plant-based diets. This study aimed to investigate the association between different types of plant-based dietary patterns and colorectal cancer risk in the Chinese population. We conducted a case-control study with 2799 eligible colorectal cancer cases and 2799 sex- and age-matched controls in Guangzhou, China. A validated food frequency questionnaire was used to collect dietary data, from which we derived plant-based diet indices, including the plant-based diet index (PDI), the healthy PDI (hPDI), and the unhealthy PDI (uPDI). The PDI, hPDI, and uPDI assess the adherence to overall, healthy, and unhealthy plant-based dietary patterns, respectively. The odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer risk were estimated using unconditional logistic regression models. Higher adherence to the PDI, particularly the hPDI, was associated with a lower risk of colorectal cancer, whereas greater adherence to the uPDI was associated with a higher risk of colorectal cancer. Compared with the lowest quintile, the adjusted ORs in the highest quintile were 0.79 (95% CI: 0.66-0.95) for the PDI, 0.45 (95% CI: 0.38-0.55) for the hPDI, and 1.45 (95% CI: 1.18-1.78) for the hPDI, respectively. In stratified analysis, the inverse association between the PDI and colorectal cancer risk was not observed in women, and the positive association between the uPDI and colorectal cancer risk was not observed in men. In conclusion, these results support recommendations that shifting to a healthy plant-based dietary pattern is important for the prevention of colorectal cancer, particularly in the Chinese population that habitually consumes plant foods.

Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer's disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM., (© 2022. The Author(s).)

Currently, investigations on the microbiota of sports centers and related facilities have been carried out in some countries, which showed that Microsporum gypseum, Trichophyton mentagrophytes and T. tonsurans are important dermatoprotofungi. In China, some research on athletes and sports equipment between the fungal community and public health has made some interesting achievements. However, the bacterial group among them has not been reported. Therefore, The aim of this study was to uncover (I) gymnastic equipment is there potential pathogenic factors and (ii) is there any difference in the biomarker of bacterial in different types of gymnastic room? The samples were collected from the gymnastics halls of one university in western China and main sports equipment, including gymnastics carpets, moving barres, hoops and balls, as well as wall bars, parallel bars and horizontal bars. The 16S rDNA of all the samples was sequenced, and the analyses were performed using FaproTax, Bug base function prediction and Line Discriminant Analysis (LDA) Effect Size. A 16S rDNA sequence analysis revealed abundant bacterial species biodiversity on gymnasts and apparatuses from two gymnastics halls at a university in western China. An analysis using the FaproTax and Bugbase functional prediction platforms showed that there were some opportunistic pathogens on the athletes and equipment from the Rhythmic Gymnastics (RG) and Artistic Gymnastics (AG) halls, such as Staphylococcus and Corynebacteiaceae. Infectious agents associated with cancer induction and development, such as Ruminococcaceae, Veillonellaceae and Moraxellaceae, as well as microbial toxin producers with a potential impact on human health, were also detected. According to a line discriminant analysis (LDA effect size), the bacterial biomarker groups of the two gymnasiums were different at the phylum-genus level: for RG, Erysipelatoclostridium, Lachnospiraceae and Bacteroidales, while for AG, Rhizobiales. Based on the results of the investigation, we suggest that more comprehensive consideration should be given to indoor microbial biodiversity and related public health problems in school gymnasiums., (© 2022. The Author(s).)

Aim: To evaluate the long-term effect of foldable capsular vitreous body (FCVB) in the treatment of severe ocular rupture to provide a practical basis for clinical selection., Methods: A total of 26 patients (26 eyes), 23 men and 3 women, with severe ocular rupture who underwent FCVB implantation between March 2018 and September 2018 were retrospectively analysed. All open ocular wounds located in zone III, with preoperative visual acuity grade IV and above (Snellen less than 4/200). The best corrected visual acuity (BCVA), intraocular pressure (IOP), cornea, anterior chamber, iris, lens, choroid, and retina were evaluated before and after the surgery. The subjective feeling and the location of FCVB were also assessed., Results: The average age of the 26 patients was 36y (20-60y). Postoperative follow-up was from 10 to 14mo. At the end of follow up, BCVA was light perception (LP) in 10 cases, no light perception (NLP) in 13 cases, hand motions (HM) in 3 cases. IOP was 11±5 mm Hg. Corneal degeneration was in 3 cases and corneal endothelial dystrophy was in 7 cases. Shallow anterior chamber was in 8 cases and hyphema was in 8 cases. Organized membrane in the pupil was in 14 cases. Epiphora occurred in 3 cases. FCVB drainage tube exposed in 3 cases. All FCVBs were in their normal location and no rejection occurred., Conclusion: FCVB implantation is a long-term effective treatment and may provide a practical selection for severe ocular rupture., (International Journal of Ophthalmology Press.)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that predominately involves the motor neurons in the brain and spinal cord. The TARDBP gene, encoding TAR DNA-binding protein 43 (TDP-43) protein, has been identified as a major causative gene in ALS. In this study, we screened 275 SALS patients and 20 unrelated FALS probands for TARDBP mutations. We identified three TARDBP mutations in three SALS patients and two TARDBP mutations in two FALS probands, including a previously unreported mutation, p.K176I, in FALS patients consistent with frontotemporal dementia (FTD) and parkinsonism. The p.K176I mutation is the first mutation outside exon 6 of the TARDBP gene manifesting parkinsonism and the first TARDBP mutation manifesting parkinsonism identified in the Chinese population. Our results support that TARDBP mutations are one of the most common changes in both FALS and SALS in China. Patients with TARDBP mutations may have a broad phenotype spectrum of ALS, FTD, and parkinsonism. The TARDBP gene should be included in genetic screening for ALS with FTD, and/or parkinsonism., (Copyright © 2021. Published by Elsevier Inc.)

Objective: LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B . This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on. It has firmly demonstrated through lab experiments either in vivo or in vitro , as well as clinical studies that the over-expression of LAPTM4B-35 can promote cancer growth, metastasis, and multidrug resistance. Specially, the expressive level of LAPTM4B-35 is associa-ted with recurrence of HCC. The aim of this study is to identify the release of LAPTM4B-35 protein from hepatocellular carcinoma into blood of HCC patients and into the medium of cultured HCC cells, and to identify its possible form of LAPTM4B-35 protein existed in blood and cell culture medium, as well as to explore the possibility of LAPTM4B-35 protein as a novel HCC biomarker for diagnosis of HCC and prognosis of HCC patients., Methods: Immunobloting (Western blot) and enzyme-linked immunosorbent assay (ELISA) were used for identification of LAPTM4B-35 protein in the blood of HCC patients and normal individuals. Ultrafiltration and ultracentrifugation were used to isolate and purify exosomes from the culture medium of HCC cells., Results: LAPTM4B-35 protein existed in the blood from HCC patients and normal donors that were demonstrated through Western blot and ELISA. LAPTM4B-35 was also released into the culture medium of HCC cells in the form of exosomes. Preliminary experiments showed that the average and the median of LAPTM4B-35 protein level in the blood of HCC patients ( n =43) were both significantly higher than that in the blood of normal donors ( n =33) through sandwich ELISA., Conclusion: It is promising that the LAPTM4B-35 protein which is released from HCC cells in the form of exosomes into their extraenvironment may be exploited as a novel cancer biomarker for HCC serological diagnosis.

Dairy fat intake has been considered as a risk factor for cardiovascular disease. Rodent models show that trans fatty acids in industrial hydrogenated oil and ruminant milk have different effects on cardiovascular diseases. One of the main reasons is that the distributions of trans fatty acids in triacylglycerols from dairy products and from industrial hydrogenated oil are different, which affects lipid absorption and metabolism. This study investigated the effects of 1,3-olein-2-elaidin (OEO, representing industrial hydrogenated oil triacylglycerols) and 1-vaccenic-2,3-olein (OOV, representing ruminant triacylglycerols in dairy products) on the function of human umbilical vein endothelial cells (HUVEC), including cell viability, lactate dehydrogenase (LDH) exudation rate, and nitric oxide secretory and nitric oxide synthase relative activity. We found that the detrimental effect of OEO on HUVEC was significantly greater than that of OOV. The results also showed that the absorption rate of OEO in HUVEC (78.25%) was significantly greater than that of OOV (63.32%). Mechanistically, based on phospholipidomics analysis, we found that calcium-independent phospholipase A2 (iPLA2) played a key role with regard to the OOV-mediated arachidonic acid (ARA)/COX-2/PG pathway, whereas secretory phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) are responsible for the OEO-mediated ARA/COX-2/PG pathway. Moreover, OEO had a greater effect on the protein expression of COX-2 and PG secretion than OOV. In addition, iPLA2, sPLA2, and cPLA2 could mediate the ARA/CYP4A11 pathway in OOV-treated HUVEC, but only iPLA2 could mediate this pathway in HUVEC treated with OEO. We also found that sPLA2 could mediate the ARA/5-LOX pathway in HUVEC treated with OOV, but none of these 3 forms of PLA2 could mediate this pathway in HUVEC treated with OEO. On the other hand, after OOV treatment, trans-11 C18:1 was converted to beneficial forms of fatty acids in HUVEC, including conjugated linoleic acid (CLA) and trans-9 C16:1. In conclusion, we elucidated the potential mechanisms that might account for the diverse effects of triacylglycerols from industrial hydrogenated oil and ruminant milk on the function of HUVEC., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the epidemiological characteristics and clinical features of patients with fatal coronavirus disease (COVID-19), in order to provide evidence for clinical diagnosis and treatment. Methods: In this retrospective study, we analyzed data on 141 fatal cases of confirmed COVID-19 that occurred among patients in Jinyintan Hospital in Wuhan, China, from January 20 to March 6, 2020. We analyzed their epidemiological characteristics, clinical and radiological features, laboratory results, and treatment. Results: Of the 141 patients (49 females, 92 males), the median age was 77 years (range: 24-92 years). The most likely source of exposure included the Huanan seafood market ( n= 3, 2%), family members ( n= 6, 4%), and hospital-acquired infection ( n= 8, 6%). The remaining 116 patients (72%) had no known source of exposure. Of the patients, 101 (72%) had chronic diseases. The most common comorbidities were hypertension, diabetes and coronary heart disease. The most common clinical manifestations were fever ( n= 121, 85%), dry cough ( n= 77, 54%), shortness of breath ( n= 23, 16%), and chest pain ( n= 15, 10%). Less common clinical manifestations included fatigue ( n= 7, 4%), headache ( n= 3, 2%), disorders of consciousness ( n= 2, 1%), diarrhea ( n= 2, 1%) and lumbago ( n= 1, 0.7%). In terms of laboratory tests, the absolute value of lymphocytes in most patients was reduced ( n= 132, 94%), but C-reactive protein ( n= 141, 100%), procalcitonin( n= 121, 89%), serum amyloid ( n= 140, 99%) were significantly increased. The most common findings on imaging of the lungs were bilateral multiple mottling and ground-glass opacity ( n= 101, 72%), mainly in the lower lobes ( n= 15, 10%), with lesions being more common on the right. Other imaging findings included diffuse consolidation ( n= 4, 3%), ground-glass opacity and consolidation ( n= 20, 14%), and pneumothorax ( n= 1, 0.7%). All patients were treated with antibiotics and antiviral drugs. Other treatments included immunoglobulin ( n= 49, 35%), corticosteroids ( n= 45, 32%), continuous renal replacement therapy ( n= 24, 17%), and extracorporeal membrane oxygenation ( n= 12, 9%). All patients were treated with oxygen therapy. The mode of administration included invasive mechanical ventilation ( n= 61, 43%), noninvasive mechanical ventilation ( n= 65, 46%), and nasal catheter oxygen inhalation ( n= 15, 11%). The direct causes of death were acute respiratory distress syndrome ( n= 90, 64%), multiple organ failure ( n= 24, 17%), sudden cardiac arrest ( n= 11, 8%), viral myocarditis ( n= 8, 5%), acute myocardial infarction ( n= 4, 3%), cerebrovascular accident ( n= 3, 2%), and acute gastrointestinal bleeding ( n= 1, 0.7%). Conclusions: Risk factors for death due to COVID-19 included older age, male sex, and the presence of comorbidities. The most common direct causes of death were acute respiratory distress syndrome, multiple organ failure, sudden cardiac arrest, and viral myocarditis.

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular disease characterized by pulmonary vasculature reconstruction and right ventricular dysfunction. The mortality rate of PAH remains high, although multiple therapeutic strategies have been implemented in clinical practice. These drugs mainly target the endothelin-1, prostacyclin and nitric oxide pathways. Management for PAH treatment includes improving symptoms, enhancing quality of life, and extending survival rate. Existing drugs developed to treat the disease have resulted in enormous economic and healthcare liabilities. The estimated cost for advanced PAH has exceeded $200,000 per year. The pathogenesis of PAH is associated with numerous molecular processes. It mainly includes germline mutation, inflammation, dysfunction of pulmonary arterial endothelial cells, epigenetic modifications, DNA damage, metabolic dysfunction, sex hormone imbalance, and oxidative stress, among others. Findings based on the pathobiology of PAH may have promising therapeutic outcomes. Hence, faced with the challenges of increasing healthcare demands, in this review, we attempted to explore the pathological mechanisms and alternative therapeutic targets, including other auxiliary devices or interventional therapies, in PAH. The article will discuss the potential therapies of PAH in detail, which may require further investigation before implementation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (copyright: © 2020 Xiao et al.)

Recently, the arsenic monolayer has been successfully fabricated by micromechanical stripping. However, it is a non-magnetic semiconductor, including its derivatives. Here, we theoretically explore how to induce magnetism for arsenene armchair nanotubes (AsANTs) with a low-concentration TM (TM = Co, Y, Rh, Ni, Mo, Ru) atom doping, especially focusing on their structural stability, magneto-electronic property, carrier mobility, and strain effects. The high stability of these doped tubes are confirmed by the calculated binding energy and formation energy, as well as Forcite annealing molecular dynamics simulations. The AsANT can act as bandgap narrowed non-magnetic semiconductors or highly spin-polarized magnetic semiconductors (half-semiconductor or bipolar magnetic semiconductor) depending on TM types, suggesting different promising applications such as developing infrared photodetectors with broadband detectionin or spintronic devices. The magnetic thermal stability beyond room temperature is predicted for doped tubes. Furthermore, the carrier mobility of AsANTs can be tuned into a wide region by TM doping, but it is enhanced in most cases. The carrier and spin polarity of mobility can also be clearly observed. Particularly, the applied strain can induce a rich magnetic phase transition among a half-semiconductor, half-metal, bipolar magnetic semiconductor and nonmagnetic state. Furthermore, the presented stepwise change of total magnetic moment between high magnetized and nonmagnetic states is highly desirable for engineering a mechanical switch which can reversibly work between magnetism and demagnetism to control spin-polarized transport by applying strain.

trans fatty acids (TFAs) have been reported to promote vascular diseases mainly by promoting apoptosis and inflammation of vascular endothelial cells. However, it has been reported in recent years that elaidic acid (9t18:1) and vaccenic acid (11t18:1) may have different effects on vascular health. This study investigated the effects of 9t18:1 and 11t18:1 on human umbilical vein endothelial cell (HUVEC) function and the possible mechanism of inflammation by analyzing the changes in the phospholipid composition and the relationship between phospholipase A2 (PLA2) and MAPK pathway. Here we found that the effect of 11t18:1 on cell viability, membrane damage and cellular inflammation was significantly lower than that of 9t18:1 (p < 0.05). And 9t18:1 and 11t18:1 had different effects on phospholipid composition. Both 9t18:1 and 11t18:1 significantly increased the protein expression of PLA2. Moreover, the MAPK pathway regulated the expression of PLA2, inflammatory cytokines and cyclooxygenase-2 (COX-2) and the secretion of prostaglandin E2 (PGE2) in HUVECs induced by 9t18:1 and 11t18:1. In conclusion, 9t18:1 and 11t18:1 activated the MAPK pathway which regulated the expression of PLA2 to cause inflammation in HUVECs.

The monolayer InSe has been successfully fabricated recently and studied intensely. Here, we investigate the geometrical stability and various physical properties such as electronic and magnetic feature, carrier mobility and strain effects for InSe nanoribbons. Our calculations show that armchair nanoribbons, regardless of the bare-edged or H-saturated ones, are semiconductors with an indirect bandgaps, but the bandgap size is increased greatly by H-saturation. Their electron mobility is predicted to be moderately large (from ~10 2 to ~10 3 cm 2 V -1 s -1 ) with the holes being less mobile for wider ribbons, and the carrier polarity phenomenon becomes more prominently for H-saturation. The zigzag InSe nanoribbons are found to be magnetic metals with a bigger magnetic moment and the ferromagnetic ground state at the single edge. The magnetism stems from unpaired electrons at the In-rich edge. More interestingly, it is found that the externally applied mechanical strain can effectively tune the spin polarization efficiency at the Fermi level to two stepwise stages, suggesting that the strain can act as a tool for developing a mechanical switch to control spin-polarized transport under lower bias. The detailed analysis suggests that this strain-tuning mechanism can be attributed to the ionic and covalent bond-configuration competition due to the strain-induced bond-length alterations, which leads to the unpaired electron redistribution in magnetic atoms or vanishing.

Recently, a new type of quasi-1D graphene-like nanoribbons, periodically embedded with four- and eight- membered rings, has been successfully fabricated, and based on this structure, a novel planar 2D carbon allotrope, the so-called the net-Y, has been proposed. Here, we study various nanoribbons derived from such a 2D monolayer focusing on the structure stability, electronic, and transport properties, especially on the physical field coupling effects of electronic behaviors. Very high stability is predicted for various types of nanoribbons by the calculated binding energy and molecular dynamics simulation. Different edge shapes and widths have a significant influence on their electronic properties. Armchair nanoribbons are always semiconductors, and possess a high carrier mobility. After hydrogen termination, some metallic nanoribbons can become semiconductors or quasi-metals with massless Dirac-fermion behavior. In particular, the electronic properties of ribbons can be effectively modulated by applying strain and electric field. The band gap size and the transition from indirect to direct band gap can be realized upon strain or electric field. These flexibly tunable electronic properties for nanoribbons expand their applications in nanoelectronics and optoelectronics.

Background: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism., Methods: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology., Results: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway., Conclusions: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Charcot‑Marie‑Tooth (CMT) disease is a group of motor and sensory neuropathies with a high degree of pathological and genetic heterogenicity. The present study described 2 patients with CMT in a Chinese Han pedigree. The proband exhibited the classic manifestation of CMT with slowly progressing muscular atrophy and weakness. Electrophysiological examination highlighted axonal and demyelinating features. His mother did not have any symptoms, but did exhibit abnormal electrophysiological results. Next‑generation sequencing technology was employed to screen mutations in the genes associated with inherited motor never diseases. A novel mutation, c.528&#95;530delAGT, in the gap junction protein beta 1 (GJB1) gene for CMTX, and a rare variation, c.2369C>T, in the dehydrogenase E1 and transketolase domain containing 1 (DHTKD1) gene for CMT disease type 2Q (CMT2Q), were identified in the proband and his mother. The results were verified by Sanger sequencing. Although the in silico analysis predicted no change in the 3‑dimensional structure, the clinical and electrophysiological presentation in the pedigree and the high evolutionary conservation of the affected amino acid supported the hypothesis that the c.528&#95;530delAGT mutation in the GJB1 gene may be pathogenic in this pedigree. In silico analysis and high evolutionary conservation suggested the pathogenicity of the c.2369C>T mutation in the DHTKD1 gene; however, the clinical and electrophysiological performances of the proband and his mother did not conform to those of CMT2Q caused by the DHTKD1 gene. The present study provided additional information concerning the range of mutations of the GJB1 gene, which facilitated the understanding of the genotype‑phenotype association of CMT.

The diagnosis of PD might be in difficulty, especially in the early stages. Therefore, the identification of novel biomarkers is imperative for the diagnosis and monitoring disease progression in PD. DJ-1 and α-synuclein, are two proteins that are critically involved in the pathogenesis of PD, and they have been examined as disease biomarkers in studies. However, no study exists regarding DJ-1 in plasma neural-derived exosomes. In the present study, the levels of DJ-1 and α-synuclein in plasma neural-derived exosomes were studied together in order to investigate novel biomarkers for PD. DJ-1 and α-synuclein in plasma and plasma neural-derived exosomes of the patients with PD and controls were quantified by ELISAs. The data revealed that the levels of DJ-1 and α-synuclein in plasma neural-derived exosomes and the ratio of plasma neural-derived exosomal DJ-1 to total DJ-1 were significantly higher in patients with PD, compared with controls, while levels of the two proteins in plasma exhibited no difference between the patients with PD and controls. However, no relationship was identified between biomarkers and disease progression. In addition, significant positive correlations between DJ-1 and α-synuclein in plasma neural-derived exosomes were found in the patients with PD and in healthy individuals. We hypothesize that DJ-1 in plasma neural-derived exosomes may be used as a potential biomarker as α-synuclein in PD and they might participate in the mechanism of PD together.

Endothelial inflammation is recognized as the initial stage of a multistep process leading to coronary heart disease (CHD). Recently, the different effects of industrial trans fatty acids (elaidic acid, 9t18:1) and ruminant trans fatty acids (vaccenic acid, 11t18:1) on CHD have been reported in epidemiological and animal studies, however, the mechanism was not fully studied. Therefore, the objective of this study was to explore the underlying mechanism by which 9t18:1 and 11t18:1 affect human umbilical vein endothelial cells (HUVECs) inflammation. We found that 9c11t-CLA modulated the inflammation of HUVECs induced by 9t18:1 and 11t18:1. Fatty acid composition, pro-inflammatory factors, phosphorylation of MAPKs, and the TLR4 level in HUVECs altered by 11t18:1 induction, collectively suggest that the bio-conversion of 11t18:1 to 9c11tCLA might be the cause why 11t18:1 and 9t18:1 have distinct influences on endothelial injuries. It was concluded that it is biosynthesis of 9c11t CLA from11t18:1, and the modulation of TLR4-MAPK pathway by 9c11t CLA, which at least partially account for the slight effect of 11t18:1 on endothelial inflammation.

Objective The optimal plate for fixation of tarsometatarsal joint injuries is controversial. The objective of this study was to compare the biomechanical characteristics between a locking plate and 1/4 tubular plate for first tarsometatarsal joint fracture-dislocation. Method Finite element analysis was used after establishment of a first tarsometatarsal joint fracture-dislocation model. Two implant simulations using a locking plate and five-hole 1/4 tubular plate were designed to simulate fixation of the fracture-dislocation. The displacement of the first tarsometatarsal articular surface and the stress distribution in the implants were calculated. Results A 700-N load was applied to both models. The minimum displacement of the articular surface in the locking plate and 1/4 tubular plate model was 0.6471 mm and 0.3833 mm, respectively. The maximum principal stress in the locking plate and 1/4 tubular plate was 1.212 × 10 3   MPa and 1.107 × 10 3   MPa, respectively. Conclusion Use of a 1/4 tubular plate is recommended for fixation of first tarsometatarsal joint fracture-dislocation after consideration of other factors such as economical issues.

As an important technical reference for efficient prevention and fighting against forest fire, forest fire behavior parameters are mainly obtained from fire behavior simulators in some deve-loped countries. This study selected two simulators, the Farsite from USA and the Prometheus from Canada, which were both widely used in local area. Through comparing simulated results and relative data of the '3·29 Fire' occurred in Anning City, Southwestern China, we tried to evaluate accuracy of the simulators in a quantitative way. The results indicated that, in the simulation of peri-meter, the precision of Farsite under Scott fuel model was the highest, while Prometheus was the lowest, but the difference was not significant. The difference in simulative perimeter between Farsite and Prometheus mainly concentrated in the distribution area of Pinus yunnanensis. In the simulation of rate of spread (ROS), the mean ROS results of Farsite under both fuel models were close to the actual situation, while the results of Prometheus were far away from the actual situation. The diffe-rent simulative area of ROS between Farsite and Prometheus mainly concentrated in the distribution area of P. yunnanensis. In the simulation of fireline intensity (FLI), the mean FLI results of Farsite under both fuel models were similar, and Prometheus obtained significantly different FLI results from Farsite, while the different simulative area of FLI between Farsite and Prometheus mainly concentrated in the distribution area of Quercus.

Recently, studies on the extent to which spaceflight affects the psychology of individuals has received attention. In order to reveal the mental challenges that humans face in space, we need practical viewpoints to integrate the psychological effects, behavior, performance and the environment itself for space exploration. The present review discusses the individual variables related to space psychology and manned spaceflight, in addition to their growing trends. These items include patterns of emotional changes in extreme environments and the approaches to evaluating emotions. Moreover, the review concludes with suggested future research on emotion during spaceflight and its analogs. These data and information are needed to plan for the exploration of the Moon and Mars, along with contributions to the construction of the international space station (ISS) and astronaut training.

Corn seedlings are often harmed by strong wind-sand in the spring in semi-arid wind-sand area of west of Northeast China. In order to understand physiological response mechanisms of the corn seedlings to wind-sand damage, the changes in MDA content, membrane permeability, protective enzymes activities and osmotic regulation substances at 0 (CK) , 6, 9, 12, 15 and 18 m . s-1 wind speed (wind-sand flow strength: 0, 1.00, 28.30, 63.28, 111.82 and 172.93 g . cm-1 . min-1, respectively) for 10 min duration were studied during the spring, 2013 in the Horqin Sand Land of Inner Mongolia. The results showed that effects of wind-sand flow blowing on the RWC of the corn seedling were lighter in the 6-12 m . s-1 treatments, but the RWC decreased by 19.0% and 18.7% in the 15 m . s-1 and 18 m . s-1 treatments compared to the CK, respectively. The MDA content tended to decline with increasing the wind-sand flow strength, and decreased by 35.0% and 39.0% in the 15 m . s-1 and 18 m . s-1 treatments compared to the CK, respectively. The membrane permeability increased significantly with increasing the wind-sand flow strength, and increased by 191.3% and 187.8% in the 15 m . s-1 and 18 m . s-1 treatments compared to the CK, respectively. With the increase of wind-sand flow strength, SOD activities decreased and changes of CAT activities were not significant, only POD activities increased significantly, which played an important role in the process of scavenging reactive oxygen species and protecting cell membrane against damage. For lighter water stress caused, by wind-sand flow blowing, proline and soluble sugar did not play any role in osmotic adjustment, but the proline content increased by 11.4% and 24.5% in the 15 m . s-1 and 18 m . s-1 treatments compared to the CK, respectively, which played an important role in osmotic adjustment.

Mainstream theories about decision-making under risk suggest that risky decisions are made by choosing the option that offers the highest mathematical expectation. The present event-related potentials (ERPs) study investigated the neurocognitive mechanisms underlying risky choice by contrasting a preferential choice task with an expected value choice task. The ERP data revealed that (1) the computational difficulty, which would be expected to influence a compensatory process, affected the slow wave only when participants were forced to choose the option with the highest expectation; and that (2) the difference in the minimum outcome dimension between two options, which would be expected to be influential in a heuristic process, affected the P300 and slow wave when participants were asked to choose the preferred option. Our findings provide neural evidence that preferential choice is not based on an expectation computation and thus raised the question of whether expectation theories can provide an adequate description of individual risky decisions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In 2010-2011, a sand burial experiment was conducted on the Horqin Sand Land of Inner Mongolia to study the growth characteristics and physiological properties of Agriophyllum squarrosum seedlings under different depths of sand burial. The A. squarrosum seedlings had stronger tolerance against sand burial. The seedling growth could be severely inhibited when the burial depth exceeded seedling height, but some seedlings could still be survived when the burial depth exceeded 1.66 times of seedling height. When the burial depth did not exceed the seedling height, the seedling MDA content and membrane permeability had no significant change, but the lipid peroxidation was aggravated and the cell membrane was damaged with increasing burial depth. Under sand burial stress, the seedling SOD and POD activities and proline content increased significantly, while the seedling CAT activity and soluble sugar content deceased. Sand burial decreased the leaf photosynthetic area and damaged cell membrane, inducing the increase of seedling mortality and the inhibition of seedling growth. The increase of SOD and POD activities and proline content played a definite role in reducing the sand burial damage to A. squarrosum seedlings.

Objective: To investigate the effect of recombinant human interleukin-2 (rhIL-2) activated natural killer cells (rhIL-2-NK) on angiogenesis and cardiac function of rats with myocardial infarction (MI)., Methods: Natural killer cells (NKs) were isolated and activated by rhIL-2 in vitro. Untreated NKs were used as the control, the killing capacity of rhIL-2-NK were evaluated with cytotoxicity assay. Cardiac microvascular endothelial cells (CMECs) were cocultured with rhIL-2-NK. One hour after MI, rats were randomly divided into rhIL-2-NK group, NK group and blank control group and NK, rhIL-2-NK and PBS were injected directly in the infracted myocardium. At the 0, 1(st), 3(rd), 5(th), 7(th) and 20(th)th day after MI, the mRNA expression of monocyte chemotactic protein-1 (MCP-1), Tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were was detected by q-PCR essay. At the end of the therapy, the platelet endothelial cell adhesion molecule-1(CD31) and vascular endothelial growth factor (VEGF) were evaluated through immunohistochemical assay, and the cardiac function observed with echocardiography, homodynamic measurements., Results: The NKs were isolated successfully and the CMEC were proliferated remarkably by coculturing with rhIL-2-NK (P < 0.01). The mRNA expression of MCP-1, TNF-α, CD31 and rhIL-2, VEGF were significantly upregulated in rhIL-2-NK group than in the PBS control group (P < 0.01). Four weeks after operation, LVEF was significantly higher in rhIL-2-NK group than in the PBS control group [(77.56 ± 15.67)% vs. (41.47 ± 12.21)%, P < 0.05)] and histomorphology assay revealed that the density of microvascular endothelial (MVD) of rhIL-2-NK group was significantly higher than that of PBS control group (17.35 ± 1.82 vs. 4.76 ± 0.92, P < 0.01)., Conclusions: Myocardial injection of rhIL-2-NK could promote angiogenesis and improve cardiac function in MI rats.

Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The +10+292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells.

The aim of the present study was to establish a minimally invasive H reflex model in mice for the benefit of the research of clinical spinal cord injury and related diseases. Minimally invasive surgery was performed in hind limb of Kunming mouse under light anesthesia. The skin was incised at the point of one-third of the distance from greater trochanter to the base of the cauda. A pair of fine copper conductors were inserted into the shallow muscle using a syringe needle. After the needles were withdrawed, the retained conductors were ligated and fixed with the tissues surrounding the sciatic nerve as the first pair of stimulating electrodes. Another pair of conductors were inserted and fixed in medial malleolus close to the tibial nerve as the second stimulating electrodes. Copper conductor was inserted passing the skin above the proximal end of the metatarsal and fixed as the recording electrode. The reference electrode was placed at the walking pad in the base of the big toe using the same method. Electromyography (EMG) was used to record M and H waves in planta pedis muscles. The stimulus was a square wave with a width of 0.2 ms and frequency of 0.3 Hz. The latency time of the M and H waves which were induced from the two pairs of stimulating electrodes was recorded. Nerve conduction velocity (NCV) was then calculated from the distance between the cathodes of the stimulating electrodes and the latency time difference of M or H waves. The result showed the achievement ratios of H reflex induction were 92.73% and 81.82% in sciatic and tibial nerves, respectively. The latency time of H wave was about 7~10 ms. Motor nerve conduction velocity (MNCV) obtained was (25.84 ± 4.70) m/s (n = 35), while sensory nerve conduction velocity (SNCV) was (31.45 ± 7.30) m/s (n = 35). The method established in the present paper is simple to practice, does slight harm to the animal, and can produce waveforms with little interference. With these advantages, the method can be applied for the study of the latency of H reflex, and it is suitable for the researches which demands good physical condition of experimental animal during H reflex study. This model can also be applied to the detection of SNCV and MNCV.

Background: Lysosome associated protein transmembrane 4 beta (LAPTM4B) was identified first as a novel gene overexpressed in human hepatocellular carcinoma. LAPTM4B*1 and LAPTM4B*2 are two alleles of the gene; they are differentiated at 5'UTR in the first exon. Allele *1 contains only one copy of a 19-bp sequence in the 5'UTR. However, allele *2 contains another identical 19-bp sequence following the first one tightly. In this case-control study, we aimed to identify the relationship between LAPTM4B gene polymorphism and the susceptibility of primary liver cancer., Materials and Methods: The case-control study was conducted in China, including 303 primary liver cancer cases and 515 controls. LAPTM4B gene polymorphism was determined by PCR. Statistical analysis includes odds ratio (OR) and 95% confidence interval (CI) calculations using unconditional logistic regression., Results: We found a significant difference in the frequency of LAPTM4B*2 between cases and controls (P<0.05). Our study showed that LAPTM4B*1/2 and *2/2 were associated with a significantly increased risk of primary liver cancer compared with LAPTM4B*1/1 (OR=1.898, 95% CI=1.387-2.598 and OR=2.483, 95% CI=1.480-4.168, respectively). The genotypes of LAPTM4B in this study have negative correlation with the clinicopathologicals observed., Conclusion: The evidences suggest that gene polymorphism of LAPTM4B may influence the individuals' susceptibility to primary liver cancer and allele *2 being considered as a potential risk factor.

Background: Diabetic kidney disease (DKD) is associated with increased morbidity and mortality, mostly relating to cardiovascular complications. The relevance of inflammation in the pathogenesis of DKD has been investigated in recent years, and it has been shown that inflammatory markers are higher in people with DKD compared with the wider population. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with favourable anti-inflammatory effects and immunoregulatory properties. The anti-inflammatory effects conferred by pentoxifylline may be beneficial in the management of DKD., Objectives: To assess the benefits and harms of pentoxifylline for treating people with DKD., Search Methods: We searched the Cochrane Renal Group's specialised register (January 2012), CENTRAL (Issue 12, 2011), MEDLINE, EMBASE and four Chinese biomedical literature databases (CBM-disc, 1979 to July 2009), Chinese Science and Technique Journals Database (VIP, until July 2009), China National Knowledge Infrastructure (CNKI, until July 2009) and WanFang database (until July 2009)., Selection Criteria: All randomised controlled trials (RCTs) and quasi-RCTs studying the benefits and harms of pentoxifylline for DKD., Data Collection and Analysis: Data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome in sufficiently similar patients. Results of dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Mean differences (MD) were calculated to assess the effects of treatment where outcomes were expressed on continuous scales, and standardised mean differences (SMD) calculated where different scales were used. Data was pooled using the random effects model. Adverse effects were assessed using descriptive techniques and where possible, risk differences (RD) with 95% CI., Main Results: We identified 17 studies that included a total of 991 participants with DKD which met our inclusion criteria. Overall, the methodological quality of included studies was low: 4/17 reported the method of randomisation, 13/17 did not; no study described the method of random allocation; 4/17 studies were considered to be at high risk of bias and 13/17 were considered to have unclear risk for incomplete outcome data reporting; 9/17 studies were at low risk bias and in 8/17 the risk of bias was unclear for selective outcome reporting.Compared with placebo, pentoxifylline significantly reduced serum creatinine (SCr) (MD -0.10 mg/dL, 95% CI -0.17 to -0.03), albuminuria (SMD -2.28, 95% CI -3.85 to -0.70) and overt proteinuria (MD -428.58 µg/min, 95% CI -661.65 to -195.50), but there was no difference in creatinine clearance (CrCl) (MD -5.18 mL/min, 95% CI -15.55 to 5.19). When compared with routine treatment alone, pentoxifylline did not significantly reduce SCr (MD 0.00 mg/dL, 95% CI -0.06 to 0.07) or blood pressure (systolic (SBP): MD -0.28 mm Hg, 95% CI -2.20 to 1.63; diastolic (DBP): MD -0.15 mm Hg, 95% CI -1.44 to 1.14), but did significantly reduce albuminuria (SMD 0.62, 95% CI 0.18 to 1.07) and proteinuria (MD 0.46 g/24 h, 95% CI 0.17 to 0.74). There was no significant difference in SCr (MD 0.00 mg/dL, 95% CI -0.08 to 0.07), albuminuria (MD -8.79 µg/min, 95% CI -27.18 to 9.59), proteinuria (MD -0.01 g/24 h, 95% CI -0.03 to 0.01) or blood pressure (SBP: MD 1.46 mm Hg, 95% CI -0.57 to 3.50; DBP: MD 1.37 mm Hg, 95% CI -0.23 to 2.98) between pentoxifylline and the active comparator (captopril or clonidine/methyldopa) for patients with type 1 and type 2 DKD. CrCl was significantly increased when pentoxifylline was compared to clonidine/methyldopa (MD 10.90 mL/min, 95% CI -1.40 to 20.40) but not with captopril (MD 3.26 mL/min, 95% CI -1.05 to 7.59). No data were available on the incidence of end-stage kidney disease (ESKD), time to ESKD, quality of life, or all-cause mortality. The adverse events of pentoxifylline were mild; no serious adverse events were reported in any of the included studies., Authors' Conclusions: From the available evidence, pentoxifylline seems to offer some beneficial effects in renal function improvement and reduction in albuminuria and proteinuria, with no obvious serious adverse effects for patients with DKD. However, most studies were poorly reported, small, and methodologically flawed. Evidence to support the use of pentoxifylline for DKD was insufficient to develop recommendations for its use in this patient population. Rigorously designed, randomised, multicentre, large scale studies of pentoxifylline for DKD are needed to further assess its therapeutic effects.

This study was aimed to investigate the clinical value of detecting BCR/ABL fusion gene by fluorescence in situ hybridization (FISH). The conventional cytogenetic test and detection of BCR/ABL fusion gene by FISH for bone marrow of patients with newly diagnosed chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, acute lymphocytic leukemia and chronic myelogenous leukemia (CML) after allogeneic hematopoietic stem cell transplantation were carried out. The results showed that (1) out of 46 newly diagnosed as chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, 22 cases were diagnosed as CML, the FISH detection showed all positive (100%), while cytogenetic test showed 86.4% (19/22) positive, in the other 24 patients who were diagnosed as other chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, BCR/ABL fusion gene all were be detected as negative 100% by FISH, while the cytogenetic test of bone marrow in 3 cases supported the diagnosis of CML, and the diagnosis of myelodysplastic disorder in 1 case; (2) in 3 out of 7 acute lymphocytic leukemia cases the BCR/ABL fusion gene could not be detected by FISH; (3) the BCR/ABL fusion gene could be detected by FISH in 2 cases of CML received allogeneic hematopoietic stem cell transplantation, with abnormal threshold 6.5% and 1.2% respectively. It is concluded that the detection of BCR/ABL fusion gene by FISH is sensitive and reliable, which is very important for the diagnosis and differential diagnosis of chronic myeloproliferative disorders, myelodysplastic and myeloproliferative disease, as well as definite diagnosis of Ph(+) acute lymphoblastic leukemia. This method also has an important significance for monitor of minimal residual disease in CML patients received allogeneic hematopoietic stem cell transplantation.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in China. We have previously demonstrated that LAPTM4B-35, encoded by lysosomal protein transmembrane 4 beta gene, is overexpressed in over 80% of HCCs and is a novel-independent prognostic factor for metastasis, recurrence, and postoperative survival in HCC. In this study, we investigated the role of LAPTM4B-35 in malignant transformation and tumorigenesis using L02 cells, a cell line originated from human normal liver cells. Our data show that replication-deficient adenovirus vector-mediated upregulation of LAPTM4B-35 promotes anchorage-independent proliferation and resistance to adriamycin-induced apoptosis. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included the activation of phosphoinositide 3-kinases (PI3K)/serine/threonine protein kinase B (PKB/AKT)/bcl-xL/bcl-2-associated death promoter homolog (Bad) signaling pathway, inhibition of caspase-3 activation, upregulation of Bcl-2, and downregulation of Bax. In addition, upregulation of LAPTM4B-35 in L02 cells resulted in tumorigenesis in 100% (6/6) of inoculated nude mice and accelerated the death of mice with xenografts in vivo. In conclusion, LAPTM4B-35 promotes malignant transformation and tumorigenesis in human liver L02 cell line through promotion of deregulated proliferation and inhibition of apoptosis. These findings suggest that overexpression of LAPTM4B-35 may play a critical role in hepatocarcinogenesis and therefore, may be a therapeutic target for HCC., (Copyright © 2011 Wiley-Liss, Inc.)

A numerical investigation of the effect of grating antireflective layer structure on the photoelectric conversion efficiency of solar cells was carried out by the finite-difference time-domain method. The influence of grating shape, height and the metal film thickness coated on grating surface on energy storage was analyzed in detail. It was found that the comparison between unoptimized and optimized surface grating structure on solar cells shows that the optimization of surface by grating significantly increases the energy storage capability and greatly improves the efficiency, especially of the photoelectric conversion efficiency and energy storage of the triangle grating. As the film thickness increases, energy storage effect increases, while as the film thickness is too thick, energy storage effect becomes lower and lower.

Background: It was shown previously that LAPTM4B promoted growth of gallbladder carcinoma (GBC) cells and predicted poor prognosis in GBC; however, its roles and relative mechanisms in apoptosis of GBC cells remain unknown., Methods: The plasmids, pcDNA3-AE, containing the complete open reading frame of LAPTM4B and Mock (pcDNA3), were transfected transiently into GBC-SD cells, followed by induction of apoptosis by epirubicin. Cell apoptosis was determined by Hoechst 33258 staining, propidium iodide (PI) staining, and Annexin V/PI double staining flow cytometry. Protein expression was detected by immunoblotting., Results: Overexpression of LAPTM4B-35 was observed in cells transfected with pcDNA3-AE. These cells possessed significantly less apoptosis ratios compared with cells transfected with the Mock plasmid, although the values were still greater than those in parent cells. Of the apoptosis-related molecules, expression of Bcl-2 and Bcl-xL was up-regulated in cells transfected with pcDNA3-AE, whereas expressions of Bax, Bid, and cleaved caspase-9 and -3 were down-regulated compared with their expression in other kinds of cells., Conclusion: Our data show that LAPTM4B-35 attenuated epirubicin-induced apoptosis of GBC-SD cells in vitro through a mitochondria-dependent pathway. Therefore, the protein LAPTM4B-35 might be associated with the chemoresistance of GBC., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To investigate whether the fetal immune tolerance induction could replace the HLA typing for hematopoietic stem cell transplantation., Methods: Immune tolerance of SD rats was induced by injecting host Wistar rats peripheral blood mononuclear cells into yolk sac of the embryo, afterward the mature male offsprings were used as donor. The host female recipients received lethal dose irradiation and bone marrow transplantation(BMT). The Wistar rats transplanted with bone marrow from donor and unrelated SD rats as well as the rats which received radiation alone were used as control. The survival, histopathologically GVHD, the mental status, food and water intake, coat characteristics, activities were observed. Forty days after BMT, autologous and allogenous skin transplantation between donor and recipient rats was performed to observe the engraftment of solid organ., Results: The survival of the rats received bone marrow grafts from the immune tolerant donor was significantly longer than that of control groups (30 day survival rates were 86.7%, 6.7%, 0%, and 0% respectively), and there was no histopathologically GVHD observed, while in the sham group, the manifestations of GVHD was clearly visible. The skin engraftment rate between the host and the immune tolerant donor was significantly higher than that among non-related rats (84.6% and 0% respectively)., Conclusion: The induction of immune tolerance in embryo can overcome the HLA barrier and provide a good donor for hematopoietic stem cell and solid organ transplantation.

In this study, an analytical method was developed and used to quantify simultaneously protocatechuic acid, neochlorogenic acid, cryptochlorogenic acid and 1, 3-dicaffeoylquinic acid--four bioactive compounds contained in Fructus Xanthii using UPLC. The contents of four phenolic components of 28 batches of samples collected from different product areas and markets were determined and compared by means of this established method. The mobile phase was composed of methanol and water containing 0.1% phosphoric acid. Chromatography was monitored at dual-wavelengths--220 and 327 nm. Flow rate was 0.4 mL x min(-1) and column temperature was 35 degrees C. The correlation coefficient between concentration and chromatographic peak area of protocatechuic acid, neochlorogenic acid, cryptochlorogenic acid and 1, 3-dicaffeoylquinic acid was over 0.9999 in the range of 0.3570-35.70, 2.500-250.0, 1.060-106.1, 1.010-101.0 microg x mL(-1), respectively. The average recoveries of the four compounds were 97.68%, 99.55%, 97.92% and 100.4%, respectively. In conclusion, the established method can rapidly attain an accurate and reproducible result used to control the quality of Fructus Xanthii.

LAPTM4B (lysosomal protein transmembrane 4 beta) is a newly identified cancer-associated gene. Both of its mRNA and the encoded LAPTM4B-35 protein are significantly upregulated with more than 70% frequency in a wide variety of cancers. The LAPTM4B-35 level in cancer is evidenced to be an independent prognostic factor and its upregulation promotes cell proliferation, migration and invasion, as well as tumorigenesis in nude mice. In contrary, knockdown of LAPTM4B-35 expression by RNA interference (RNAi) reverses all of the above malignant phenotypes. We herein reveal a new role of LAPTM4B-35 in promoting multidrug resistance of cancer cells. Upregulation of LAPTM4B-35 motivates multidrug resistance by enhancement of efflux from cancer cells of a variety of chemodrugs with variant structures and properties, including doxorubicin, paclitaxel and cisplatin through colocalization and interaction of LAPTM4B-35 with multidrug resistance (MDR) 1 (P-glycoprotein, P-gp), and also by activation of PI3K/AKT signaling pathway through interaction of PPRP motif contained in the N-terminus of LAPTM4B-35 with the p85α regulatory subunit of PI3K. The specific inhibitors of PI3K and knockdown of LAPTM4B-35 expression by RNAi eliminate the multidrug resistance effect motivated by upregulation of LAPTM4B-35. In conclusion, LAPTM4B-35 motivates multidrug resistance of cancer cells by promoting drug efflux through colocalization and interaction with P-gp, and anti-apoptosis by activating PI3K/AKT signaling. These findings provide a promising novel strategy for sensitizing chemical therapy of cancers and increasing the chemotherapeutic efficacy through knockdown LAPTM4B-35 expression by RNAi.

Background: Lysosomal protein transmembrane 4 β-35 (LAPTM4B-35), a novel oncoprotein that belongs to the mammalian 4-tetratransmembrane spanning protein superfamily, has been implicated in oncogenesis and cancer progression in several solid malignances. However, the expression of LAPTM4B-35 and its role in endometrial cancer progression remain unknown., Materials and Methods: We investigated the expression of the LAPTM4B-35 protein by immunohistochemistry in 30 normal endometrium specimens and 165 endometrial carcinomas and analyzed its correlation with various clinicopathologic features, including patient outcome., Results: LAPTM4B-35 immunoreactivity was overexpressed in endometrial carcinoma cases compared with normal endometrium (P < 0.001). High LAPTM4B-35 expression was found in 117 (70.91%) of these 165 carcinomas and was positively correlated with the International Federation of Gynecology and Obstetrics stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence, but not with age and histological type. Patients with high LAPTM4B-35 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of LAPTM4B-35 (P = 0.001 and P = 0.002, respectively). Multivariate analysis showed that high LAPTM4B-35 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with endometrial carcinoma (both P = 0.005)., Conclusions: These results showed that high LAPTM4B-35 expression was associated with progression and prognosis of endometrial carcinoma.

Background: The overexpression of LAPTM4B-35 in gallbladder carcinoma (GBC) and its clinicopathologic and prognostic significance have been previously shown. Thus, this gene may play a role in the growth of GBC cells., Methods: The pcDNA3-AE containing the complete open reading frame of LAPTM4B (lysosome-associated protein transmembrane-4beta) and mock (pcDNA3) plasmids were transiently transfected into GBC-SD cells. Cell proliferation, cell cycle distribution, and protein expression were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium assay, flow cytometry, and Western blot, respectively., Results: Cells transfected with pcDNA3-AE revealed accelerated proliferation, less serum dependence, and significant cell cycle progression compared with cells transfected with mock plasmid and parent cells. These phenotypes were accompanied by upregulated expression of C-myc, c-Fos, c-Jun, cyclin D1, and cyclin E and downregulated expression of P16 and P-27., Conclusions: LAPTM4B overexpression promotes the growth of GBC cells in vitro by regulating the expression levels of some proliferation-associated proteins. Therefore, the LAPTM4B gene might be used as a novel therapeutic target of GBC., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background/aims: It was previously established that LAPTM4B-35 highly expressed in gallbladder carcinoma and being of clinicopathological and prognostic significances. However, expression of LAPTM4B gene in gallbladder carcinoma (GBC-SD), a gallbladder carcinoma cell line, and its role in invasive potential remain unclear., Methodology: Expression of LAPTM4B in GBC-SD cells was first detected. Plasmids, pcDNA3-AE (containing complete open reading frame of LAPTM4B) and Mock (pcDNA3), were transiently transfected into GBC-SD cells. Invasive phenotypes (migration and invasion) and relative molecules were then shown by transwell assay, crossing river test and Western blot analysis., Results: Immunocytochemical staining revealed that LAPTM4B-35 positively expressed in cytoplasm of GBC-SD cells. But LAPTM4B-35 expression was obviously weaker in GBC-SD cells than that in BEL-7402 cells (positive control). Besides, cells transfected with pcDNA3-AE presented shorter crossing river time, less migrated and invaded cell numbers, compared with cells transfected with the Mock plasmid and parent cells. Finally, increased expressions of active uPA, MMP-9, pro MMP-2 and active MMP-2 were also observed in cells transfected with pcDNA3-AE., Conclusions: Our data suggested that LAPTM4B expressed in GBC-SD cells at a relatively low level. Forced overexpression of LAPTM4B increased invasive potential of GBC-SD cells, through modulating molecules associated with degradation of extracellular matrix.