Search

Aim: To characterize the N 6 -methyladenosine (m 6 A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC)., Methods: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m 6 A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m 6 A-lncRNAs., Results: Large amount of m 6 A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair., Conclusion: Our results for the first time present an overview of the m 6 A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC., Competing Interests: Conflicts of Interest: Ye HF, None; Zhang X, None; Zhao ZN, None; Zheng C, None; Fei P, None; Xu Y, None; Lyu J, None; Chen JL, None; Guo XX, None; Zhu H, None; Zhao PQ, None., (International Journal of Ophthalmology Press.)

Purpose: To explore the effects of personalized oral stents in intensity-modulated radiation therapy (IMRT) treatment., Methods: Totally 108 patients with nasopharyngeal carcinoma treated with IMRT at Nanjing Gaochun People's Hospital from January 2021 to December 2023 were selected. Using a random number table method, the patients were divided into experimental group (n=54) using personalized oral stents and control group (n=54) using simple mouthpieces. The dosimetry of clinical target volumes (CTV), normal oral tissues, conformity index (CI), homogeneity index (HI), pain level evaluated by visual analogue scale(VAS ), grades of oral mucositis, xerostomia scores, taste scores, oral health impact profile (OHIP) scores and incidence of complications(dental caries, xerostomia, taste disorders, oral candidiasis, osteomyelitis of the jaw) were compared between the two groups. SPSS 23.0 software package was used for statistical analysis., Results: There was no significant difference between the two groups in average received dose and CI, HI values on CTV and the tongue(P＞0.05); however, the experimental group showed a lower average received dose on the mandible, mandibular teeth, and bilateral parotid glands compared to the control group(P＜0.05). After treatment, the experimental group had significantly lower scores in VAS, grades of oral mucositis, xerostomia evaluation, OHIP and frequency of complications (P＜0.05). The taste scores in the experimental group were significantly higher than that in the control group (P＜0.05)., Conclusions: Personalized oral stents significantly reduce the radiation dose to oral sites in IMRT treatment, decrease pain and other oral complications, and improve patients' quality of life.

A study was conducted on rural women of childbearing age aged 20-49 who underwent the National Free Preconception Health Examination Project (NFPHEP)in Yunnan Province from 2013 to 2019. Descriptive analysis was conducted to determine the negative rate of IgG antibodies against the rubella virus and its differences among various socio-demographic characteristics. Among the 1 511 203 study subjects, the negative rate of IgG antibodies against the rubella virus was 24.36%. Only 2.64% of the population had received rubella virus vaccine. The negative rate of IgG antibodies among rural childbearing-age women in the preconception period in Yunnan Province decreased with age and educational level ( P t rend <0.001). The negative rate of IgG antibodies in ethnic minority women of childbearing age in the preconception period (25.19%) was higher than that of Han women (23.88%). Among the 22 ethnic groups with over 1 000 participants, the negative rates of IgG antibodies in women of childbearing age from the Blang (32.85%), Bouyei (31.03%), Zhuang (31.01%), and Miao (30.70%) ethnic groups were higher than those of women from other ethnic groups. Among the 16 states (cities) in Yunnan Province, the negative rate of IgG antibodies in pregnant women of childbearing age in Wenshan Zhuang and Miao Autonomous Prefecture (38.06%) and Lincang City (32.63%) was higher than that in other states (cities). The negative rate of serum IgG antibodies in women who reported having received rubella virus vaccine (18.60%) was lower than that in other non-vaccinated populations (24.52%). The proportion of rural women of childbearing age in Yunnan Province who were susceptible to the rubella virus before pregnancy was still high. It is necessary to promote rubella vaccination among people susceptible to rubella, especially pregnant women, to prevent rubella virus infection and reduce the incidence rate and disease burden of rubella people.

Background: Serum creatinine (Cr) and Albumin (Alb) have emerged as prognostic factors for mortality in many diseases including burned patients. However, few studies report the relationship between Cr/Alb ratio and major burned patients. The purpose of this study is to make evaluation of efficacy of Cr/Alb ratio in predicting 28-day mortality in major burned patients., Method: Based on a local largest tertiary hospital in South of China, we retrospectively analyzed data of 174 patients with total burn area surface (TBSA) ≥ 30% from January 2010 to December 2022. Receiver operating characteristic curve (ROC), logistic analysis, and Kaplan-Meier analysis were performed to evaluate the association between Cr/Alb ratio and 28-day mortality. Integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to estimate the improvements in new model performance., Results: 28-day mortality rate was 13.2% (23/174) in burned patients. Cr/Alb on admission at level of 3.340μmol/g showed the best discrimination between survivors and non-survivors after admission at 28 days. The result of multivariate logistic analysis suggested that age (OR, 1.058 [95%CI 1.016-1.102]; p = 0.006), higher FTSA (OR, 1.036 [95%CI 1.010-1.062]; p = 0.006), and higher level of Cr/Alb ratio (OR, 6.923 [95CI% 1.743-27.498]; p = 0.006) were independently associated with 28 day-mortality. A regression model was constructed by logit(p) = 0.057 *Age + 0.035 *FTBA + 1.935 * Cr/Alb - 6.822. The model showed a better discrimination and risk reclassification compared with ABSI and rBaux score., Conclusions: High Cr/Alb ratio at admission is a herald of poor outcome. The model generated from multivariate analysis could serve as an alternative prediction tool among major burned patients., Competing Interests: Conflict of interest statement We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases that regulate multiple physiological processes. Aberrant activation of FGFR2 and FGFR3 has been linked to the pathogenesis of many tumor types, including cholangiocarcinoma and bladder cancer. Current therapies targeting the FGFR2/3 pathway exploiting small-molecule kinase inhibitors are associated with adverse events due to undesirable inhibition of FGFR1 and FGFR4. Isoform-specific FGFR2 and FGFR3 inhibitors that spare FGFR1 and FGFR4 could offer a favorable toxicity profile and improved therapeutic window to current treatments. Herein we disclose the discovery of dual FGFR2/FGFR3 inhibitors exploiting scaffold repurposing of a previously reported ALK2 tool compound. Structure-based drug design and structure-activity relationship studies were employed to identify selective and orally bioavailable inhibitors with equipotent activity toward wild-type kinases and a clinically observed gatekeeper mutant., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

The participants in this study were 20-49 years old rural childbearing age people who received the National Free Preconception Health Examination Project (NFPHEP) in Yunnan Province during 2013 to 2019. The proportion of ABO and RhD blood groups among different ethnic groups and different areas were calculated. The proportion of 2 748 131 participants with blood group A phenotype was highest (32.60%), followed by O (30.60%), B (27.33%) and AB (9.47%). In the RhD blood system, the proportion of the RhD positivity (RhD+) and RhD negativity (RhD-) group were 99.29% and 0.71% respectively. The proportions blood groups were significantly different among ethnic groups and areas (all P <0.001). Among 18 ethnic groups with more than 3 000 participants, Yao (42.75%), Bouyei (40.58%) and Dai (40.37%) ethnic groups had higher proportion of blood group O phenotype than other ethnic groups. Wa ethnic groups had highest proportion of the A (40.15%) and AB phenotypes (11.23%). Miao ethnic group (34.70%) and Lahu ethnic group (34.42%) had higher proportion of blood group B phenotype than other ethnic groups. Wa ethnic group had the highest proportion of RhD-group (1.88%). In all 16 prefectures of Yunnan, the proportion of blood group O phenotype was highest in Xishuangbanna Dai Autonomous Prefecture (40.27%). Baoshan city (36.39%), Lincang city (36.22%) and Dali Bai autonomous prefecture (36.06%) had higher proportion of blood group A phenotype than other regions. Diqing Tibetan Autonomous Prefecture (30.83%) and Qujing city (30.48%) had higher proportion of blood group B phenotype than other areas, while Zhaotong city had a highest proportion of blood group AB phenotype (11.19%). The proportion of RhD-group was highest in Honghe hani and Yi nationality autonomous prefecture(1.37%). The A RhD+(39.36%), A RhD-(0.78%), AB RhD+(11.03%), AB RhD-(0.20%) and O RhD-(0.48%) blood groups were higher proportion in Wa ethnic group than in other ethnic groups ( P <0.001).

Herein we report the discovery of a novel biaryl amide series as selective inhibitors of hematopoietic protein kinase 1 (HPK1). Structure-activity relationship development, aided by molecular modeling, identified indazole 5b as a core for further exploration because of its outstanding enzymatic and cellular potency coupled with encouraging kinome selectivity. Late-stage manipulation of the right-hand aryl and amine moieties surmounted issues of selectivity over TRKA, MAP4K2, and STK4 as well as generating compounds with balanced in vitro ADME profiles and promising pharmacokinetics., Competing Interests: The authors declare the following competing financial interest(s): All of the authors are current or former employees of Incyte Corporation., (© 2022 American Chemical Society.)

In spite of the great success of immune checkpoint inhibitors in immune-oncology therapy, an urgent need still exists to identify alternative approaches to broaden the scope of therapeutic coverage. Hematopoietic progenitor kinase 1 (HPK1), also known as MAP4K1, functions as a negative regulator of activation signals generated by the T cell antigen receptor. Herein we report the discovery of novel pyrazolopyridine derivatives as selective inhibitors of HPK1. The structure-activity relationship campaign led to the discovery of compound 16 , which has shown promising enzymatic and cellular potency with encouraging kinome selectivity. The outstanding pharmacokinetic profiles of 16 in rats and monkeys supported further evaluations of its efficacy and safety in preclinical models., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

Objective: To determine the prevalence, epidemiological characteristics, and related factors of syphilis infection among rural childbearing age people to promote medical interventions on pre-pregnancy aristogenesis and syphilis infection in Yunnan province. Methods: The subjects in this study were 18-49-year-old rural couples of childbearing age from the National Free Preconception Health Examination Project in Yunnan province during 2013-2017. The descriptive study was carried out to determine the positive rate of Treponema pallidum specific antibody (TPsAb) and related sociodemographic characteristics. Results: The overall positive rate of TPsAb was 0.38% (8 204/2 160 455) in 2 160 455 rural childbearing age people in Yunnan. The positive rate of TPsAb was 0.39% (4 019/1 040 981) in men,higher than that in women (0.37%,4 185/1 119 474). The positive rate of TPsAb was highest in the age group 45-49 years (0.70%,158/22 511). The positive rate of TP antibody in the minority ethnic groups and Han ethnic groups appeared the same (0.38%). However,the highest positive rate of TPsAb was 0.77% (461/60 153) in Hani ethnic group among all the 17 minority ethnic groups. People with education level of primary education had the highest anti-TP positive rate (0.54%,2 327/431 275). The positive rate of TPsAb appeared the highest in Zhaotong (0.73%, 2 049/281 614) area among all the 16 prefectures of the province. The positive rate of TPsAb in the population from the impoverished regions (0.50%,2 963/590 039) was higher than in other disadvantaged areas (0.34%, 3 115/929 368) or areas with average income (0.33%,2 126/641 048). Significant differences appeared in the positive rate of TPsAb among populations of different ages, ethnic, education level, and economic level groups (trend χ 2 test, P <0.001). Conclusions: The positive rate of TP antibody in rural childbearing age people in Yunnan was related to multi factors,including sex,age,ethnic group,education level,area, residence, and local economic situation. The positive rate of TPsAb was higher in men than in women. And people with elder age, lower education level, being Hani or Lahu ethnic group, and Zhaotong areas had higher TPsAb positive rates and higher syphilis infection risk.

Parameterizing an effective water model is a challenging issue because of the difficulty in maintaining a comprehensive balance among the diverse physical properties of water with a limited number of parameters. The advancement in machine learning provides a promising path to search for a reliable set of parameters. Based on the TIP4P water model, hence, about 6000 molecular dynamics (MD) simulations for pure water at 1 atm and in the range of 273-373 K are conducted here as the training data. The back-propagation (BP) neural network is then utilized to construct an efficient mapping between the model parameters and four crucial physical properties of water, including the density, vaporization enthalpy, self-diffusion coefficient and viscosity. Without additional time-consuming MD simulations, this mapping operation could result in sufficient and accurate data for high-population genetic algorithm (GA) to optimize the model parameters as much as possible. Based on the proposed parameterizing strategy, TIP4P-BG (a conventional four-site water model) and TIP4P-BGT (an advanced model with temperature-dependent parameters) are established. Both the water models exhibit excellent performance with a reasonable balance among the four crucial physical properties. The relevant mean absolute percentage errors are 3.53% and 3.08%, respectively. Further calculations on the temperature of maximum density, isothermal compressibility, thermal expansion coefficient, radial distribution function and surface tension are also performed and the resulting values are in good agreement with the experimental values. Through this water modeling example, the potential of the proposed data-driven machine learning procedure has been demonstrated for parameterizing a MD-based material model.

Objective: To explore the current status of HBV infection before pregnancy among rural childbearing age people in Yunnan province, find out the population at high risk and areas with high incidence and provide evidence for promoting pre-pregnancy aristogenesis and medical interventions for prevention of HBV infection. Methods: The subjects in the study were rural childbearing age people aged 18-49 who received the national free pre pregnancy eugenic health examination in Yunnan province during 2013-2017. Descriptive analysis was conducted for HBsAg positive rate and its difference among various characteristics. The SPSS 22.0 software was used for statistical analysis. Results: A total of 2 180 841 rural childbearing age people were surveyed, the HBsAg positive rate before pregnancy was 3.13%(68 314/2 180 841) in Yunnan. And the HBsAg positive rate was 3.56% (37 694/1 057 376) in men, higher than that in women (2.73%, 30 620/1 123 465). The HBsAg positive rate was highest in age group 41-49 years (3.77%, 3 126/82 931). The HBsAg positive rate was higher in minority ethnic group (3.77%, 27 974/742 518) than in Han ethnicity group (2.81%, 40 024/1 425 870). Moreover, the highest HBsAg positive rate of was 8.20%(851/10 378) in Yao ethnic group. The people with education level of primary education had the highest HBsAg positive rate (3.97%, 17 294/435 219). The HBsAg positive rate was highest in Xishuangbanna Dai autonomous prefecture (6.65%, 3 875/58 232) in Yunnan. Moreover, the HBsAg positive population in severe poor area (3.32%, 19 755/595 665) was higher than those in less poor area (3.17%, 29 750/939 101) or normal areas (2.91%, 18 809/646 075). There was significant difference in HBsAg positive rate among populations in different age groups, ethnic groups, education level groups, areas and economic level groups ( P <0.001). Conclusions: The HBsAg positive rate in rural childbearing age people in Yunnan was related to multi factors, including sex, age, ethnic group, education level, area and economic development level. The HBsAg positive rate was higher in men, older age and lower education level, minority ethnic group (especially in Yao ethnic group), from Xishuangbanna prefecture and the poor living conditions in childbearing age population.

Photocatalytic hydrogen evolution from pure water is successfully realized by using interstitial P-doped CdS with rich S vacancies (CdS-P) as the photocatalyst in the absence of any electron sacrificial agents. Through interstitial P doping, the impurity level of S vacancies is located near the Fermi level and becomes an effective electron trap level in CdS-P, which can change dynamic properties of photogenerated electrons and thus prolong their lifetimes. The long-lived photogenerated electrons are able to reach the surface active sites to initiate an efficient photocatalytic redox reaction. Moreover, the photocatalytic activity of CdS-P can be further improved through the loading of CoP as a cocatalyst., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To determine whether the immunopotentiator chitosan oligosaccharide(COS)can recover the reproductive functions of pathological ovarian recession mice and improvetheir immunity., Methods: Forty-three fertile female mice (at around 2 months),in addition to a normal control group ( n =8), injected intraperitoneally with busulfan and cyclophosphamide to construct premature ovarian failure mod-els. Three of them were used to test whether the infertility model was constructed successfully by HE staining. Then the models were randomly divided into four groups ( n =8) and treated with different dosages of COS by gavage, after which compared different groups' organ ratios (the weight of immune organs and ovary/body weight), ovarian follicles and peritoneal macrophages' phagocytosis as well as estragon(E 2 ) and pro-gesterone(P) levels in peripheral blood. In addition, we measured the expression dynamics of the ovarian protein reproductive cell marker mouse vasa homolog(MVH), germ stem cell marker OCT-4 in ovarian surface epithelium (OSE) and part of immune factors including tumor necrosis factor (TNF-α),interleukin-2(IL-2)as well as IL-6 to analyze the correlativity between germline stem cells marker dynamics and im-mune factors expression changes., Results: With increasing dosages of COS, organ ratios of ovaries, thymus and spleen both went up syn-chronously; The whole number of follicles and every stages of follicles are all presenting with progressive tendency; E 2 level in peripheral blood ascends, however, progesterone level declined relatively; Neutral red experiment revealed the phagocytosis ability of peritoneal macrophages became stronger with increasing dosages of COS; the results of Western blot had shown that no matter the expression level of germ stem cells marker or immune factors were all presenting increasing tendency, which means that the expression level dynamics of germ stem cell marker has a positive correlation with immune factors expression changes. The results were statistically significant., Conclusions: COS could improve the immunity of mice with pathological ovarian recession and at the same time it would promote the proliferation and differentiation of female germ line stem cells (FGSCs), and then helped saving ovarian functionsto some extent.

The effects of water filling and electric field on the mechanical property of carbon nanotubes (CNTs) are investigated with molecular dynamics simulations. The simulation results indicate that the water filling and electric field could enhance the elastic modulus but reduce the Poisson's ratio of the CNTs. As for the buckling behaviors, a significant enhancement could be observed in the yield stress and average post-buckling stress of the CNTs. In particular, the enhancement in the yield stress induced by the water filling and electric field could be even higher than that resulted from the solid filling. Moreover, a transition mechanism from the rod instability to shell buckling is shown to explain the nonmonotonic variation of yield stress, and the critical diameter can be tuned through filling the water molecules and applying the electric field. The present findings provide a valuable route for the optimized design and application of the nanoscale functional devices based on the water-filled CNTs.

Based on atomistic simulations, the elastic moduli and vibration behaviors of fivefold twinned copper nanowires are investigated in this paper. Simulation results show that the elastic (i.e., Young's and shear) moduli exhibit size dependence due to the surface effect. The effective Young's modulus is found to decrease slightly whereas the effective shear modulus increases slightly with the increase in the wire radius. Both moduli tend to approach certain values at a larger radius and can be suitably described by core-shell composite structure models. Furthermore, we show by comparing simulation results and continuum predictions that, provided the effective Young's and shear moduli are used, classic elastic theory can be applied to describe the small-amplitude vibration of fivefold twinned copper nanowires. Moreover, for the transverse vibration, the Timoshenko beam model is more suitable because shear deformation becomes apparent.

Purpose: To report the clinical findings of three cases with ultra-late postoperative capsular block syndrome (CBS) by Pentacam Scheimpflug imaging., Methods: Case series., Results: Three cases of ultra-late postoperative CBS are presented., Discussion: This report highlights the importance of conducting Pentacam Scheimpflug imaging in late CBS. Each case either enhanced our understanding or improved our differential diagnosis of late CBS.

Purpose: To identify proteins interacting with alpha A-crystallin (CRYAA) and to investigate the potential role that these protein interactions play in the function of CRYAA using a human proteome (HuProt) microarray., Methods: The active full-length CRYAA protein corresponding to amino acids 1-173 of CRYAA was recombined. A HuProt microarray composed of 17,225 human full-length proteins with N-terminal glutathione S-transferase (GST) tags was used to identify protein-protein interactions. The probes were considered detectable when the signal to noise ratio (SNR) was over 1.2. The identified proteins were subjected to subsequent bioinformatics analysis using the DAVID database., Results: The HuProt microarray results showed that the signals of 343 proteins were higher in the recombinant CRYAA group than in the control group. The SNR of 127 proteins was ≥ 1.2. The SNR of the following eight proteins was > 3.0: hematopoietic cell-specific Lyn substrate 1 (HCLS1), Kelch domain-containing 6 (KLHDC6), sarcoglycan delta (SGCD), KIAA1706 protein (KIAA1706), RNA guanylyltransferase and 5'-phosphatase (RNGTT), chromosome 10 open reading frame 57 (C10orf57), chromosome 9 open reading frame 52 (C9orf52), and plasminogen activator, urokinase receptor (PLAUR). The bioinformatics analysis revealed 127 proteins associated with phosphoproteins, alternative splicing, acetylation, DNA binding, the nuclear lumen, ribonucleotide binding, the cell cycle, WD40 repeats, protein transport, transcription factor activity, GTP binding, and cellular response to stress. Functional annotation clustering showed that they belong to cell cycle, organelle or nuclear lumen, protein transport, and DNA binding and repair clusters. CRYAA interacted with these proteins to maintain their solubility and decrease the accumulation of denatured target proteins. The protein-protein interactions may help CRYAA carry out multifaceted functions., Conclusions: One-hundred and twenty-seven of 17,225 human full-length proteins were identified that interact with CRYAA. The advent of microarray analysis enables a better understanding of the functions of CRYAA as a molecular chaperone.

Objective: To explore the safety and effectiveness of endoscopic mucosal resection (EMR) in the treatment of colorectal polyps., Method: EMR was applied in the treatment of colorectal polyps., Results: A total of 3578 polyps in 2609 patients were all completely resected except 2 cases and the integrated rate of samples was 99.6%. Intra- and post-operation complications occurred in 22 cases(0.8%), including 7 intraoperative bleeding, 5 postoperative bleeding, and 10 thermal burn, which were cured by symptomatic treatment. A total of 1530 (58.6%) cases were followed-up with 3-12 months and no relapse was found in former place of excision., Conclusion: EMR can be applied in resection of colorectal polyps effectively and safely.

Researches on lens proteomics are becoming prevalent in recent years. Characterized by their high resolution and efficiency, proteomics approaches provide reliable methodological support for lenses proteomic research, which demonstrates a new orientation for revealing the mechanism of cataractogenesis. This review outlines the separation, identification and some novel approaches of proteomic techniques applied in recent lenses proteomic research.

The mutual effects of two crucial features of carbon nanotubes (CNTs) (surface and confinement) on the temperature-dependent water diffusion are studied through molecular dynamics simulations. A two-stage diffusion mechanism is detected in the CNTs of diameter smaller than 12.2 Å, which becomes obscure as the temperature increases. This peculiar phenomenon can be ascribed to the cooperation of the small confinement and the periodic surface. The diffusion coefficient of the confined water exhibits a nonmonotonic dependence on the confinement size and an unexpected increase inside the large CNTs (compared to that of bulk water). These anomalous behaviors can be attributed to the competition of the smooth surface and the small confinement. Considering the mutual effects, an empirical formula is proposed on the basis of two groups of numerical examples, whose results indicate that the confinement effect will dominate over the surface effect until the CNT diameter increases up to ~16 Å, whereas thereafter the surface effect becomes dominant and finally both of them vanish gradually.

Background: Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies., Methods/principal Findings: We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84-7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR=3.23, 95% CI: 0.63-16.47). Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO(3) in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice., Conclusions: Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.

Objective: To investigate the antimicrobial resistance of community respiratory pathogens isolated in China., Methods: The strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from patients with community-acquired respiratory tract infections at 14 Chinese hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey the susceptibility of 14 antibiotics against these strains. These antibiotics included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor, cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin, tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT)., Results: A total of 1870 strains were collected including S. pneumoniae (n = 997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n = 198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP) were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%, 9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6% respectively. 36.9% of S. pneumoniae strains isolated from or= 92.9%., Conclusions: Antimicrobial resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from children < or = 6 years old is higher than other age groups. Amoxicillin-clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain highly active against common community respiratory pathogens.

This study investigated the emissions of criteria air pollutants (carbon monoxide [CO], hydrocarbons [HCs], and oxides of nitrogen [NOx]) from motorcycle exhaust at cold- and hot-start driving cycles on a chassis dynamometer. Seven four-stroke carburetors and two fuel-injection motorcycles were tested. As expected, the emission factors (g/km) of CO and HCs increased during cold-start driving. The ratio of emission factors (g/km) for cold- and hot-start driving cycles ranged from 1.1-1.5 (for CO) to 1.2-2.8 (for HCs). However, the difference of NOx emissions between the cold- and hot-start cycles was not pronounced. Further, the cold-/hot-start ratios of CO and HCs from 50-cm3 motorcycles were higher than those of 100- and 125-cm3 motorcycles; however, the carbon dioxide (CO2) emission was the lowest for the four-stroke motorcycles. High engine temperature and poor combustion efficiency of smaller cylinder-capacity motorcycles may contribute a significant amount of exhaust emission. Additionally, the fuel-base emission factor (g/L-fuel) ratios were low compared with the distance-base emission factor (g/km) in cold- and hot-start driving. This indicates that the effect of catalyst efficiency was greater than the effect of fuel combustion in the tested motorcycles. A comparison of emission ratios of motorcycles and passenger cars shows that the warm-up may be more important for cars, especially under low-temperature conditions. However, the motorcycle contributes a large proportion of CO and HC emissions in many Asian counties. The difference between cold- and hot-start emissions may affect inventory

Based on the basic concepts of differential geometry in analyzing environmental data and establishing related models, the methodology for differential geometry expression and analysis of pollutants concentration in terrestrial environment was presented. As a kind of regionalized variables, the spatial distribution pattern of the pollutants concentration was transformed into 3-dimension form, and fitted with conicoid. This approach made it possible to analyze the quantitative relationships between the regionalized variables and their spatial structural attributes. For illustration purpose, several sorts of typical space fabrics, such as convexity, concavity, ridge, ravine, saddle, and slope, were calculated and characterized. It was suggested that this approach was feasible for analyzing the regionalized variables of pollutants concentration in terrestrial environment.

Multilocus sequence typing (MLST) data have revealed many insights into the global epidemiology of Staphylococcus aureus but, with notable exceptions such as Japan, the evidence from most Asian countries is currently limited. Here we have applied MLST to 132 hospital-acquired meticillin-resistant Staphylococcus aureus (HA-MRSA) isolates collected in mainland China in 2002. In all, 102 isolates were recovered from a single tertiary hospital in Guangzhou, South China, and the remaining 30 isolates were recovered from six metropolitan tertiary hospitals from geographically diverse districts corresponding to a total area of more than 2 million km2. The data reveal a striking predominance throughout mainland China of a single clonal lineage, ST 239, which accounts for 97% of the 132 isolates. These data support more limited evidence from previous studies suggesting the widespread predominance of ST 239 throughout hospitals in China, a pattern which possibly extends to the whole of continental Asia. Staphylococcal chromosome cassette mec (SCCmec) typing confirmed the homogeneity of the ST 239 isolates, with the vast majority corresponding to the Hungarian clone (ST 239-III).

Objective: To investigate the antimicrobial resistance among the nosocomial gram-negative pathogens from 15 teaching hospitals located in different areas in China in 2005., Methods: A total of 1927 non-repetitive nosocomial gram-negative pathogens were collected from 15 teaching hospitals in different areas in China and sent to the central lab for reidentification and susceptibility testing. The levels of minimal inhibitory concentration (MIC) of 18 antimicrobial agents were determined by agar dilution method. WHONET 5.4 software was used to analyze the data., Results: The strains of Escherichia coli, Klebsiella pneumoniae, and Proteous mirabilis isolates that did not produce extended spectrum beta lactamases (ESBLs) showed high sensitivity to beta-lactams. The antibiotics with a susceptibility rates over 80% against the strains of Entorobacter cloacae, Enterobacter aerogene, Citrobacter spp, Serratia spp, and Proteous vulgaris producing AmpC enzyme included meropenem, imipenem, and piperacillin-tazobactam, and these 3 drugs showed a susceptibility rate of more than 80% against the ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Other antimicrobial agents showing a relatively high activity against Enterobacter spp, Citrobacter spp, Serratia spp and Proteous vulgaris included cefepime (67.3% - 100%), amikacin (67.3% - 95.2%), ceftazidime (52.9% - 100%) and cefoperazone-sulbactam (51.9% - 100%). The susceptibility rate of fluoroquinolones was 34.8% - 36.1% against non-ESBL-producing Escherichia coli and was 13.4% - 17.1% against ESBL-producing isolates. The most active agent against Pseudomonas aeruginosa was polymyxin B (95.6%). The agents with the activity rates of 70% - 80% included meropenem, imipenem, amikacin, and piperacillin-tazobactam. The antibiotic with a high susceptible rate against Acinetobacter baumannii was polymyxin B (98.3%), followed by imipenem (80.8%), meropenem (76.2%), and minocycline (67.4%). The susceptible rates of other agents were all below 60%. The agents with relatively high activity against Stenotrophomonas maltophilia included minocycline (85%), levofloxacin (82.5%), and trimethoprim-sulfamethoxazole (77.5%). The agents with a relatively high activity against Burkholderia cepacia included minocycline (77.2%) and meropenem (61.4%)., Conclusion: Carbapenem, piperacillin-tazobactam, amikacin and cefepime remained relatively high activity against nosocomial Enterobacteriaceae, Non-fermenting pathogens have lower susceptibility to the antimicrobial agents than before.

This paper revaluated the situation of cadmium (Cd) pollution in rice field soils of Zhangshi irrigation area in Shenyang. The results indicated that the soil Cd pollution of test area was still quite serious. The Cd content in brown rice samples ranged from 0.435 to 0.855 mg x kg(-1), which exceeded the national criteria for food sanitation in China, and increased by 335%-755% compared with that 20 years ago. Brown rice Cd had a significant negative correlation with soil pH, and a positive correlation with soil available Cd. The decrease of soil pH induced more soil Cd transformed into available Cd which occupied 22.8%-52.0% of the total Cd and was easy to be absorbed by rice plant, inducing the Cd in brown rice exceeded national criteria. The pollutant Cd could transfer along with surface runoff, ground water and flying dust, making the pollution extend gradually.

Preparation of a poly (gamma-glutamic acid)-cisplatin conjugate was introduced and its in vitro antitumor effect was investigated. Poly (gamma-glutamic acids) was obtained by using fermentation methods. The hydrolyzed small molecular weight of poly (gamma-glutamic acids) was prepared by acid hydrolysis. The interaction between poly (gamma-glutamic acids) -cisplatin conjugate (PGA-CDDP) and DNA was investigated by PCR model. MTT assay was used to investigate the in vitro anticancer activity of the conjugate. Apoptosis assay of the conjugate was investigated by FCM assay and the in vivo toxicity was also proceeded. The results showed that the poly (gamma-glutamic acids) -cisplatin conjugate was obtained successfully and its yield is 10% - 12%. It has obvious antitumor effects on human liver tumor BEL7404 cells, human lung tumor H446 cells and human colon tumor RKO cells. At the same time, it also has apoptosis effects on the three kinds of tumor cell lines. The in vivo toxicity of PGA-CDDP was examined in normal mice and the results showed that the in vivo toxicity of this conjugate was significantly lower than that of free CDDP. In conclusion, the poly (gamma-glutamic acids) -cisplatin conjuate could be used as a potential clinic antitumor drug. The poly (gamma-glutamic acids) obtained by fermentation can be used as a valuable drug carrier system.

The series of trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines have been widely investigated as opioid receptor antagonists. One of our research goals was to explore the bioactive conformation of the N-phenethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine derivative 3, prototypical mu-opioid antagonist in this series. In this effort, the rotational degrees of freedom of the N-substituent of 3 were limited by incorporation of an ethylene bridge between the piperidine 2- or 6-position of 3 and the benzylic position of the N-phenethyl moiety. The overall modification led to a novel series of fused bicyclic derivatives of the octahydroquinolizine chemical class, conformationally restricted analogue of 3. The constrained analogues 6 and 9 showed high affinity toward the mu-opioid receptor. Compound 6 was found to be a mu-opioid antagonist, whereas the constrained analogue 9 displayed potent mu-agonist activity in vitro. This study provides additional information about the molecular determinants for mu recognition, the structural features affecting ligand binding, and the structure function relationships.

Objective: To determine the prevalence and genotypes of TEM- and SHV-type beta-lactamase-producing Klebsiella pneumoniae in Guangzhou area., Methods: Genotype determination of TEM- and SHV-type beta-lactamases were performed by PCR amplification followed by denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing among 57 strain of klebsiella pneumonia obtained from the hospitals in Guangzhou., Results: The genes bla(TEM) and bla(SHV) were amplified from all strains. TEM-116 type ESBLs were found in 56.14% (32/57) of the isolates. SHV-12 (n = 19), -11 (n = 11), -2a (n = 6), -28 (n = 4), -26 (n = 1), -33 (n = 1) and five novel SHV-type beta-lactamases were identified among the SHV-type beta-lactamases. These novel enzymes were designated from SHV-64, -65, -66, -67 and SHV-69, which derived from SHV-1 beta-lactamase or SHV-12 ESBL. A total of 94.74% of the isolates (54/57) produced both TEM- and SHV-type beta-lactamases simultaneously, in which 13.0% were TEM-116 and SHV-12 (n = 12)., Conclusion: TEM-116 and SHV-12 are the predominant TEM- and SHV-type genotypes of Klebsiella pneumoniae producing beta-lactamases in Guangzhou. This area is confronted with the prevalence of the phenotypes of Klebsiella pneumoniae that simultaneously produce TEM- and SHV-type beta-lactamases.

Structure-activity relationships at the 2alpha-position of the piperidine ring of the trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine mu-opioid antagonist series were investigated. This study showed that only small linear alkyl groups (methyl, propyl) are tolerated at the 2alpha-position of the piperidine ring of this series.

Light-activated gene expression systems hold promise as new tools for studying spatial and temporal gene patterning in multicellular systems. Photo-caged forms of nuclear receptor agonists have recently been shown to mediate photo-dependent transcription in mammalian cells, however, because intracellularly released agonists can rapidly diffuse out of cells, the photo-initiated transcription response is only transient and limited to only a few hours in reported examples. Herein we describe a photo-caged thyroid hormone receptor agonist that provides a robust 36 h transcription response to a single irradiation event. These findings are in contrast to a closely related system, which uses a caged retinoic acid receptor agonist, which provides only a short transcription response. Comparison of the two systems, show that the duration of transcription response is not controlled by the rate of diffusion of free ligand out of the cell, but perhaps by the duration of ligand-induced transcription/stability of the active transcription complex.

An efficient solid-phase synthesis of mono-N-substituted piperazines is presented. The key transformation involves a selective borane amide bond reduction in the presence of a carbamate resin linkage. This synthetic route takes advantage of the large diverse pool of commercially available carboxylic acids, acid chlorides, and sulfonyl chlorides. The solid-phase approach facilitates parallel processing by eliminating the need for column chromatography after each synthetic step. The N-monosubstituted piperazines were shown to react with polymeric activated tetrafluorophenol (TFP) reagents to generate arrays of amides and sulfonamides in good purity for biological testing.

A temperature-constrained cascade-correlation network (TCCCN) was used to identify ultraviolet (UV) spectra of organic environmental pollutants. Library search for UV spectra is more difficult than that for infrared (IR) spectra, because the UV spectra overlap more severely than IR spectra. Besides, drift and noise in the measurement will have significant effect on UV library spectra search. Therefore, neural networks with fuzzy output should be a better alternative for the library search. The TCCCN is different from the commonly used BP networks in architecture. The processing units in the TCCCN are connected in a cascade mode, and a temperature constraint is introduced. Therefore, the TCCCN can reduce overtraining and fast training speed. TCCCN was used for library search of UV spectra in the present work and the effects of network parameters and noise were investigated. Results showed that better results were obtained with the TCCCN than with conventional correlation method.

The highly selective I1-PBS imidazoline analogue PMS 952 has been selected to study the incidence of intramolecular hydrogen bond and molecular flexibility on its biological activity. On one hand, the weak energy difference between three calculated conformers does not support the stabilization of one conformer by an internal hydrogen bond. The 3-D electrostatic map confirms this feature and the solvent effect does not significantly modify the relative energy of these conformers. On the other hand, the conformational spaces of the neutral and ionized forms present a great number of equilibrium structures, in a short energetic range (20 Kcal). The results are representative of an exceptional conformational flexibility due to a cooperative effect between several parts of the molecule.

A three-year prospective study was carried out in 283 postmenopausal women to evaluate the effects of a long-acting estriol derivative-nylestriol. The women were randomly assigned into 3 groups: group A (136 cases, nylestriol 2 mg/2 wk), group B (97, nylestriol 1 mg/2 wk) and group C (50, placebo/2wk). LDL-C decreased and HDL-C increased after 3 months of medication (P < 0.05), but TC and TG not significantly changed in any group (P > 0.05). No changes of lipids were found in group C (P > 0.05). Serum ALP, Ca/Cr and Hpr/Cr in fasting urine decreased in 3 months in both group A and B (P < 0.05), but not in group C (P > 0.05). Forearm bone mineral content loss was restrained in groups A and B (P > 0.05), but decreased markedly in group C (P < 0.01). The Kupperman index scores decreased by about 50% after 3 months and 80% in 12 months in groups A and B. Nylestriol induced mild stimulatory effect on the uterine endometrium, and addition of 6 mg of provera daily for 7-10 days every 6 months is recommended. Nylestriol exhibited no obvious effect on the breast. This study demonstrated that nylestriol can be used as an effective and acceptable estrogen replacement therapy for postmenopausal women.

A prospective double-blind study was carried out in 136 women 0.5 to 21 years since menopause (YSM) in order to demonstrate the effects of a long-acting estriol derivative-Nylestriol (CEE3) on bone loss and lipoprotein lipids. They were orally administered at 2 mg of CEE3 or placebo every 2 weeks. Among 90 subjects who finished 1 year of medication, 49 received CEE3 and 41 placebo. The results were: 1. Serum ALP, Ca/Cr and Hop/Cr in fasting urine decreased in 3 months (P < 0.05); 2. Menopause-related reduction of forearm bone density was restrained; 3. LDL-C decreased in 3 months and HDL-C increased in 6 months (P < 0.05), with no significant changes in TC and TG; 4. Side effects were mild. 1/3 of those with intact uterus had spotting and another 1/3 had moderate withdrawal bleeding after the addition of medroxyprogesterone acetate at the end of 12 months of CEE3 therapy. This study demonstrates that CEE3 is effective and acceptable for preventing osteoporosis and lipoprotein lipids disorder in postmenopausal women. Long-term application awaits further studies.