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Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on‐target off‐tumor toxicity limits Ab‐based therapeutics. Cluster of differentiation 147 (CD147) is a tumor‐associated membrane antigen overexpressed in cancer cells. Ab‐based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia‐activation strategies, we developed a conditional Ab‐dependent cellular cytotoxicity (ADCC)‐enhanced humanized anti‐CD147 Ab, HcHAb18‐azo‐PEG5000 (HAP18). Afucosylated ADCC‐enhanced HcHAb18 Ab was produced by a fed‐batch cell culture system. Azobenzene (Azo)‐linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia‐responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement‐dependent cytotoxicity, and Ab‐dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor‐inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia‐activated ADCC‐enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti‐CD147 Ab drugs. [ABSTRACT FROM AUTHOR]

Background: Chloroquine (CQ) is an antimalarial drug that was first synthesized by Hans Andersag, a German scientist, in 1934. Chloroquine has been widely researched and used over the years. The rapid development in the fields of modern science and technology has also contributed to the increase in interest in chloroquine. Hence, it is necessary to comprehensively summarize the research trends to understand the breakthroughs made in the field. Methods: The required data was compiled by analyzing the Web of Science Core Collection (WoSCC) database. The search period for studying global research trends in chloroquine research was set from 2012 to 2021 to ensure a comprehensive analysis over an extended timeframe. Data retrieval was performed on April 4, 2022, focusing on articles and reviews published in English. The retrieval words were: (TS = (chloroquine)) OR (TS = (aralen)). A total of 1,091 reviews and 7,259 articles were retrieved and analyzed. The data obtained from WoSCC was captured and analyzed using VOS viewer (version 1.6.16) and Citesspace (version 5.8.R5). Results: The number of literature reports on chloroquine published in the past 10 years has shown an annual increase. Among the countries, the United States has contributed the highest number of papers and ranks first in terms of both H-index and citation count. The League of European Research Universities is one of the largest research-focused university networks, and Malaria Journal stands out as a prominent journal publishing articles relevant to the field of study. A paper authored by Gautret and Philippe in 2020 achieved the highest citation score globally. The biosynthesis of chloroquine, mechanisms of drug resistance, and drug combinations are receiving growing attention. Conclusion: The research area of chloroquine has been significantly influenced by the American and China. The progress of chloroquine research is further propelled by fruitful collaborations among various countries. Researchers have extensively studied the anti-malarial effect, drug resistance mechanism, and autophagy of chloroquine for the development of a treatment method for COVID-19 based on chloroquine. Bibliometric analysis can be employed to identify hotspots, new directions, and frontiers in the field of chloroquine research. [ABSTRACT FROM AUTHOR]

Atractylodes chinensis has a high medicinal value and is widely cultivated. However, root rot disease seriously affects the yield and quality of A. chinensis. To develop green and safe pesticides, the inhibitory effect of essential oils (EOs) of three Labiatae plants on the pathogenic fungi that causes root rot disease in Atractylodes chinensis was investigated. The results showed that the Origanum vulgare EO and Thymus mongolicus EO exhibited strong inhibitory effects on Fusarium oxysporum, Fusarium solani, and Fusarium redolens, with 100% inhibition rate. The low MIC values of EOs and their main components against the three pathogenic fungi indicated that all of them showed strong fungicidal effects. The MIC values of O. vulgare EO against F. oxysporum, F. solani, and F. redolens were 2.60 mg/mL, 3.13 mg/mL, and 1.56 mg/mL, respectively. Analyses using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the O. vulgare EO severely damaged the cell wall and cell membrane of mycelial cells. The O. vulgare EO increased cell permeability, leading to a large leakage of cell contents (DNA and proteins). In addition, O. vulgare EO inhibited F. oxysporum by inducing ROS production and reducing the amount of intracellular GSH, leading to a large accumulation of ROS. This study showed that plant EOs have excellent fungicidal activity and can be used as novel natural and environmentally friendly pesticides for the control of root rot in A. chinensis. [ABSTRACT FROM AUTHOR]

With traditional Chinese medicine playing an increasingly important role in human society, the scarcity of wild resources has become a key constraint to the development of the industry. For this study, optimized maximum entropy models were employed to predict the patterns and changes in potentially suitable distribution areas for Thesium chinense Turcz. in China, in the present (1970–2000) and future (2050s, 2070s, and 2090s) under multiple climate scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The results showed that the predicted regions of high, medium, and low potential fitness zones were 6.19 × 104, 150.99 × 104, and 155.61 × 104 km2. The highly suitable areas were primarily found in Shandong and Shanxi Provinces. Furthermore, we found its relatively stable habitat was mainly distributed across South Central Shanxi, Eastern Gansu, and Midwest Guizhou. An analysis of the transfer of masses revealed that the potential habitat of the plant migrated in a northwesterly direction under various climatic conditions. [ABSTRACT FROM AUTHOR]

Background: Neurogenic limb deformity disorder (NLDD) refers to limb deformity disorders caused by various neurogenic disorders. However, there are no studies to systematically summarize and analyze these diseases in China, and we first proposed the concept of NLDD. We describe the epidemiological characteristics of NLDD in China based on the largest case database of limb orthopedics in China. Methods: This study analyzed parameters from the Qin Sihe Orthopedic Surgery Case Data (QSHOSCD). The database is based on the Rehabilitation Hospital affiliated to National Research Center for Rehabilitation, which has collected nearly 37,000 patients to date and includes a wide variety of limb deformities. The types of diseases are summarized and classified for all patients studied. Statistical analysis was based on the type of etiology, age, regional distribution, and historical surgical volume. Partial outcomes were statistically analyzed separately by common diseases (polio and cerebral palsy) and rare diseases (37 other diseases). Results: From 1979 to 2019, 30,194 patients with NLDD were treated surgically for 39 neurogenic disorders. The male to female ratio was 1.48:1, the mean age was 19.65 years, and most patients (82.38%) were aged between 6 and 30 years. Patients included from 32 provinces and cities across China, mainly concentrated in populous central provinces and Heilongjiang Province. The peak of annual surgical procedures was from 1988 to 1994, and the number of annual surgical procedures for common diseases gradually decreased from 1994 onwards, but the trending is opposite for rare diseases. Conclusions: This study is the first to demonstrate the disease types, population characteristics and incidence trends of NLDD in China. It suggests that the prevention and treatment of NLDD should focus on the adolescent population and enhance the treatment of neurogenic diseases that cause limb deformities. The growth and adaption of the Ilizarov technique and its practice in Chinese orthopedic benefits the treatment of neurogenic limb deformity disorders. [ABSTRACT FROM AUTHOR]

Eucommia ulmoides, a single extant species of Eucommiaceae, is a perennial deciduous tree distributed across central China. The bark of E. ulmoides is rich in chlorogenic acid and flavonoids that possesses high medicinal value, whereas its leaves and seeds contain abundant Eucommia ulmoides gum (EUG), which is a unique strategic resource in China that can be used as a substitute for natural rubber. Under the background of global warming, the evaluation of habitat suitability is of great significance for the protection and management of E. ulmoides. For this study, maximum entropy (MaxEnt) modeling was employed to simulate the potentially suitable region for E. ulmoides over four periods (current, 2050s, 2070s, and 2090s) under four climate change scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5), as well as to analyze changes in the spatial patterns of E. ulmoides and the essential environmental factors affecting the growth and distribution of E. ulmoides. The results revealed that the current potentially suitable region for E. ulmoides was 211.14 × 104 km2, which accounted for 21.99% of China's territory. The low impact areas for E. ulmoides were distributed in Guizhou, Zhejiang, Sichuan, eastern Chongqing, southern Shaanxi, western Hubei, eastern Shandong, southern Anhui, southern Gansu, and northern Yunnan Provinces. The key bioclimatic variables affecting the distribution of E. ulmoides were mean diurnal range and mean temperature of the coldest quarter, with their contribution rates of 53.8% and 41.4%, respectively. Furthermore, core distributional shift analysis indicated that the center of the potentially suitable regions of E. ulmoides exhibited a general trend of shifting to the northwest and high latitudes. Finally, conservation strategies are proposed, such as the establishment of ex situ protection sites and germplasm resource collection. Future researchers can conduct further studies by integrating the quality of E. ulmoide herbs and environmental variables. In this study, for technical reasons, we only considered the effect of climate on species distribution without considering other biotic and abiotic factors, which can be further addressed by future researchers. [ABSTRACT FROM AUTHOR]

Objective: To provide the current research progress, hotspots, and emerging trends for AI in liver cancer, we have compiled a relative comprehensive and quantitative report on the research of liver disease using artificial intelligence by employing bibliometrics in this study. Methods: In this study, the Web of Science Core Collection (WoSCC) database was used to perform systematic searches using keywords and a manual screening strategy, VOSviewer was used to analyze the degree of cooperation between countries/regions and institutions, as well as the co-occurrence of cooperation between authors and cited authors. Citespace was applied to generate a dual map to analyze the relationship of citing journals and citied journals and conduct a strong citation bursts ranking analysis of references. Online SRplot was used for indepth keyword analysis and Microsoft Excel 2019 was used to collect the targeted variables from retrieved articles. Results: 1724 papers were collected in this study, including 1547 original articles and 177 reviews. The study of AI in liver cancer mostly began from 2003 and has developed rapidly from 2017. China has the largest number of publications, and the United States has the highest H-index and total citation counts. The top three most productive institutions are the League of European Research Universities, Sun Yat Sen University, and Zhejiang University. Jasjit S. Suri and Frontiers in Oncology are the most published author and journal, respectively. Keyword analysis showed that in addition to the research on liver cancer, research on liver cirrhosis, fatty liver disease, and liver fibrosis were also common. Computed tomography was the most used diagnostic tool, followed by ultrasound and magnetic resonance imaging. The diagnosis and differential diagnosis of liver cancer are currently the most widely adopted research goals, and comprehensive analyses of multi-type data and postoperative analysis of patients with advanced liver cancer are rare. The use of convolutional neural networks is the main technical method used in studies of AI on liver cancer. Conclusion: AI has undergone rapid development and has a wide application in the diagnosis and treatment of liver diseases, especially in China. Imaging is an indispensable tool in this filed. Mmulti-type data fusion analysis and development of multimodal treatment plans for liver cancer could become the major trend of future research in AI in liver cancer. [ABSTRACT FROM AUTHOR]

Importance: Blood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment. Objective: This study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients. Design, Setting, and Participants: This study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment (n = 1,479) or docetaxel single-agent treatment (n = 707). BCT was conducted at three time points: pre-treatment (T1), the first day of treatment cycle 3 (T2), and first day of treatment cycle 5 (T3). Univariate and multivariate Cox regression analyses were conducted to identify early BCT biomarkers to predict atezolizumab treatment outcomes in NSCLC patients. Main Outcomes and Measures: Overall survival (OS) was used as the primary end point, whereas progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST), clinical benefit (CB), and objective response rate (ORR) were used as secondary end points. Results: The BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at time point T3 and neutrophil-to-monocyte ratio (NMR) at time point T2 with absolute cutoff values of NLR_T3 = 5, PLR_T3 = 180, and NMR_T2 = 6 were identified as strong predictive biomarkers for atezolizumab (Ate)-treated NSCLC patients in comparison with docetaxel (Dtx)-treated patients regarding OS (BCTscore low risk: HR Ate vs. Dtx = 1.54 (95% CI: 1.04-2.27), P = 0.031; high risk: HR Ate vs. Dtx = 0.84 (95% CI: 0.62-1.12), P = 0.235). The identified BCTscore model showed better OS AUC in the OAK (AUC12month = 0.696), BIRCH (AUC12month = 0.672) and POPLAR+FIR studies (AUC12month=0.727) than that of each of the three single BCT biomarkers. Conclusion and Relevance: The BCTscore model is a valid predictive and prognostic biomarker for early survival prediction in atezolizumab-treated NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Development of severe immune-related adverse events (irAEs) is a major predicament to stop treatment with immune checkpoint inhibitors, even though tumor progression is suppressed. However, no effective early phase biomarker has been established to predict irAE until now. Method: This study retrospectively used the data of four international, multi-center clinical trials to investigate the application of blood test biomarkers to predict irAEs in atezolizumab-treated advanced non-small cell lung cancer (NSCLC) patients. Seven machine learning methods were exploited to dissect the importance score of 21 blood test biomarkers after 1,000 simulations by the training cohort consisting of 80%, 70%, and 60% of the combined cohort with 1,320 eligible patients. Results: XGBoost and LASSO exhibited the best performance in this study with relatively higher consistency between the training and test cohorts. The best area under the curve (AUC) was obtained by a 10-biomarker panel using the XGBoost method for the 8:2 training:test cohort ratio (training cohort AUC = 0.692, test cohort AUC = 0.681). This panel could be further narrowed down to a three-biomarker panel consisting of C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), and thyroid-stimulating hormone (TSH) with a small median AUC difference using the XGBoost method [for the 8:2 training:test cohort ratio, training cohort AUC difference = -0.035 (p < 0.0001), and test cohort AUC difference = 0.001 (p=0.965)]. Conclusion: Blood test biomarkers currently do not have sufficient predictive power to predict irAE development in atezolizumab-treated advanced NSCLC patients. Nevertheless, biomarkers related to adaptive immunity and liver or thyroid dysfunction warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the evolution of Ilizarov technology in China, highlight important milestones, introduce the atmosphere of the era concerning the first uses and development of this technology, and share Chinese modification and experience in this field.Method: A thorough interview with senior ASAMI members of China and literature search and physical books in libraries was undertaken to summarize the history of Ilizarov technology in China.Results: The formal development of Ilizarov technology began when professor Ilizarov himself came to Beijing (1991) and gave a speech. In the following 31 years, his technology was rapidly developed through China, with many symposiums held and associations established including ASAMI China (2003) and ILLRS China (2015). Today, Ilizarov technology has become the main treatment of complex fractures, defects, nonunion, infections, deformities, and chronic ischemic ulcers of the limbs. In those years, Chinese scholars also developed some special treatment methods and made many modifications to Ilizarov external fixators.Conclusion: Ilizarov technology has developed in China for 31 years. It revolutionized the treatment of complex limb traumas, deformities, and diseases. In the treatment of millions of patients, Chinese scholars had many unique experiences and made modifications to this technology which is worthy to share with the world. [ABSTRACT FROM AUTHOR]

Leiodontium geminoserratum S. He & Chantanaorr. (Hypnaceae), a new species from Thailand, is described herein based on distinctive morphological features. The new species resembles L. gracile Broth. from China and Nepal, but differs most notably in having moderately complanate leafy stems and branches, prorate laminal cells, doubly serrate basal leaf margin, and axillary hairs with a globose distal cell. A full description and photographs of the new species are provided. [ABSTRACT FROM AUTHOR]

Background: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli–caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. Methods: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. Results: Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk (< 10% mortality, 0–1 points), medium risk (10–20% mortality, 2 points), and high risk (> 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer–Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P < 0.01). Conclusions: Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality. [ABSTRACT FROM AUTHOR]

The basic fibroblast growth factor (bFGF) plays an important role in the wound repair process. However, lacking of better biomaterials to carry bFGF still is a challenge in skin repair and regeneration. In this study, the human-like collagen (HLC) cross-linked with transglutaminase (TG) to fabricate a HLC/TG hydrogel to load bFGF. The physical properties of hydrogel, such as interior structure, mechanical property, were characterized in vitro using scanning electron microscopy (SEM), rheometer. Then, the effects of the HLC/TG hydrogel on the bFGF and cell attachmentwere evaluated, and the results showed that the HLC/TG hydrogel has good biocompatibility towards bFGF and cells. Finally, skin wound healing test was performed for the evaluation of HLC/TG hydrogels with bFGF in a mouse model. All results of macroscopic and microscopic analysis indicated that not only our HLC/TG hydrogel provide a delivery of growth factors, but also the HLC/TG hydrogel with bFGF achieving better skin regeneration in the structure and function. [ABSTRACT FROM AUTHOR]

Background: Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is one of the main antimicrobial-resistant pathogens. Little data are available on how biofilm formation (BF) contributes to EC-caused bloodstream infection (BSI) in cancer patients. This study investigated the impact of BF on clinical outcomes of cancer patients with EC-caused BSI. Methods: Clinical outcome and microbiological characteristics including the presence of bla genes in ESBL-EC isolates were retrospectively collected from BSI cancer patients. Patients infected with ESBL-EC were compared with patients infected with third-generation cephalosporin-susceptible strains. Survival curves were generated by Kaplan–Meier analysis and the survival difference was assessed by the log-rank test. Risk factors for ESBL-EC infection, predictors of mortality, and outcome differences were determined by multivariate logistic regression and Cox regression analysis, respectively. Results: A high prevalence of ESBL-EC with dominant blaCTX-M-15, blaCTX-M-15 plus blaTEM-52 genotype was found in BSI cancer patients. Independent risk factors for infection with ESBL-EC were cephalosporins, chemotherapy, and BF. Metastasis, ICU admission, BF-positive ESBL-EC, organ failure, and the presence of septic shock were revealed as predictors for mortality. The ESBL characteristic was associated with the BF phenotype, and the overall mortality was significantly higher in cancer patients with BF-positive ESBL-EC-caused BSI. Conclusion: blaCTX-M-15 type ESBL-EC is highly endemic among cancer patients with BSI. BF is associated with multi-drug resistance by ESBL-EC and is also an independent risk factor of mortality for cancer patients with BSI. Our findings suggest that the combination of BF-positive ESBL-EC isolates with other appropriate laboratory indicators might benefit infection control and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) is difficult to treat. The present study explored the efficacy of (liraglutide) Lira in treating T2DM complicated with NAFLD. A total of 127 patients suffering from T2DM complicated with NAFLD were enrolled in the present study, and randomly assigned to a Lira group (liraglutide injection: 0.6–1.2 mg/day, 12 weeks, n=52) or a Metformin (Met) group (oral metformin: 1000–1500 mg/day, 12 weeks, n=75). During the treatment phase, the values for fasting plasma glucose (FPG), 2 h plasma glucose (2hPG), glycated hemoglobin (HbA1c), aspartate aminotransferase (AST)/alanine aminotransferase (ALT), and adiponectin (APN) decreased in both the Lira and Met groups, and the levels of Δ2hPG, ΔAST/ALT, and ΔAPN in the Lira group were significantly lower than those in the Met group. The values for total cholesterol (TC), triglycerides (TG), low-and high-density lipoproteins (LDL and HDL), ALT, AST, weight, body mass index (BMI), waist to hip ratio (WHR), and C-reactive protein were markedly increased in both groups, and levels of ΔAST, ΔALT, Δweight, ΔBMI, ΔWHR, and ΔCRP (C-reactive protein) in the Lira group were significantly higher than those in the Met group. An analysis of treatment efficacy showed that liraglutide was better than metformin in its ability to significantly decrease the ALT levels in patients with combined T2DM and NAFLD. Furthermore, liraglutide was more effective than metformin at ameliorating the severity of T2DM complicated with NAFLD, and produced its effects by alleviating liver inflammation and improving liver function. [ABSTRACT FROM AUTHOR]

Background: The dosage of herb ultrafine particle (UFP) depended on the increased level of its dissolution, toxicity, and efficacy. Objective: The dissolution, antibacterial activity, and cytotoxicity of Coptidis rhizoma (CR) UFP were compared with those of traditional decoction (TD). Materials and Methods: The dissolution of berberine (BBR) of CR TD and UFP was determined by high-performance liquid chromatography. The antibacterial activity of CR extract was assayed by plate-hole diffusion and broth dilution method; the inhibitory effect of rat serums against bacteria growth was evaluated after orally given CR UFP or TD extract. The cytotoxicity of CR extract was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay. Results: The dissolution amount of BBR from CR UFP increased 6-8-folds in comparison to TD at 2 min, the accumulative amount of BBR in both UFP and TD group increased in a time-dependent manner. The minimal inhibitory concentrations and minimal bactericidal concentrations of CR UFP extract decreased to 1/2~1/4 of those of TD extract. The inhibitory effect of rat serums against bacteria growth decreased time-dependently, and no statistical difference was observed between two groups at each time point. The 50% cytotoxic concentrations of UFP extract increased 1.66~1.97 fold than those of TD. Conclusions: The antibacterial activity and cytotoxicity of CR UFP increased in a dissolution-effect manner in vitro, the increased level of cytotoxicity was lower than that of antibacterial activity, and the inhibitory effect of rat serums containing drugs of UFP group did not improve. [ABSTRACT FROM AUTHOR]

Numerous randomized controlled trials (RCTs) of acupuncture have been conducted in recent years. The results of several studies implied that acupuncture was only a powerful placebo; however, certain studies demonstrated that verum acupuncture had a greater effect than placebo and the mechanisms between a verum acupuncture group and a placebo/sham group were different. Researchers attempted to investigate the inherent factors that may potentially influence the results of trials. Certain problems observed in acupuncture RCTs also occurred in RCTs in other fields, including insufficient sample size, high dropout rates, inadequate follow-up and randomization. The study of acupuncture is so complex that specific methodological challenges are raised, which are frequently overlooked, including sham interventions, blinding, powerful placebo effects (even stronger than an inert pill) and variations in acupuncture administration. The aforementioned problems may contribute to bias, and researchers systematically attempt to solve these problems. The present review aimed to suggest techniques to design high-quality studies, minimize the placebo effect and optimize acupuncture administration in acupuncture studies. If these problems are addressed, then the results of acupuncture studies may be different. [ABSTRACT FROM AUTHOR]

Background: Recent experiments have demonstrated that different needling manipulations may induce variable effects via diverse physiological mechanisms. A previous study indicated that needling at Fengchi (GB 20) improved cerebral blood flow in patients with vertigo induced by posterior circulation ischemia (PCI). In this study, we aim to explore the quantity-effect relationship and the physiological mechanisms underlying different acupuncture manipulations in PCI patients with vertigo. Methods/Design: We propose a pragmatic randomized and controlled trial. All participants, outcome assessors, and statisticians will be blinded. A total of 144 eligible participants will be randomized into one of four treatment groups receiving acupuncture at Fengchi (GB 20) with different one-minute manipulation parameters. Group 1 will receive twirling at a frequency of 60 times per minute toward the contralateral outer canthus at a depth of 0.5 to 0.8 cun. Group 2 will receive twirling at a frequency of 60 times per minute toward the Adam's apple at a depth of 0.5 to 0.8 cun. Group 3 will receive twirling at a frequency of 120 times per minute toward the contralateral outer canthus at a depth of 0.5 to 0.8 cun. Group 4 will receive twirling at a frequency of120 times per minute toward the Adam's apple at a depth of 0.5 to 0.8 cun. Additional points will be added based on individualized pattern diagnoses. The participants will receive 14 acupuncture sessions over 3 to 4 weeks. The subjects will be assessed at two time points: baseline and post-treatment. The primary outcome measurements will include subjective measurements (Vertebrobasilar System Ischemic Neurological Impairment Scale, UCLA Dizziness Questionnaire, Activities of Daily Living Scale, and Psychological and Social Adaptation Scale) and objective measurements (Transcranial Doppler, carotid ultrasonography and changes in cerebral oxygenation) to reduce bias arising from the placebo effect. We will use metabolomics to investigate the mechanisms underlying the different manipulation parameters. Discussion: This trial aims to explore the quantity-effect relationship between different acupuncture manipulations and their clinical effects. The results from this study may help explain the contradictory results found in acupuncture studies that practice different manipulations. [ABSTRACT FROM AUTHOR]

The taxonomic position of Sinocalliergon Sakurai (originally described in the Amblystegiaceae) is re-evaluated, based on examination of the type specimens. The monotypic genus is considered synonymous with Barbula Hedw. (Pottiaceae, Bryopsida), and the appropriate new combination, B. satoi (Sakurai) S. He, is made. The name S. satoi Sakurai is lectotypified. [ABSTRACT FROM AUTHOR]

The systematic position of the genus Bryhnia Kaurin has been problematic and remains unsettled. A phylogenetic analysis of Bryhnia and closely related genera, based on the nuclear marker ITS1–5·8S–ITS2 and the plastid markers rpl16, trnG, and trnL–F, was carried out to clarify their relationships and systematic positions. The phylogenetic trees generated from Maximum parsimony and Bayesian analyses show that Bryhnia s.s., represented by B. novae-angliae (Sull. & Lesq.) Grout, B. hultenii E.B.Bartram, and B. scabrida (Lindb.) Kaurin, forms a maximally supported clade nested within Brachythecium Schimp. ‘Bryhnia scabrida’ sensu is Bryhnia brachycladula Cardot, and together they form a monophyletic group with Eurhynchiadelphus eustegia (Besch.) Ignatov & Huttunen and Myuroclada maximowiczii (G.G.Borshch.) Steere & W.B.Schofield. We propose the inclusion of the species currently recognized in Bryhnia in Brachythecium, with the transfer of Bryhnia brachycladula to the genus Myuroclada Besch. Bryhnia brachycladula is further treated as a synonym of the new combination, Myuroclada longiramea (Müll.Hal.) M.Li, Y.F.Wang, M.S.Ignatov & S.Huttunen. [ABSTRACT FROM AUTHOR]

Identification of the gene(s) responsible for flowering time in Arabidopsis has significant implications. We used the T-DNA insertion library of Arabidopsis thaliana to screen an early-flowering mutant that exhibits accelerated flowering under short-day conditions. AP22.65, a novel flowering-time gene in that species, was isolated and identified via genome-walking and bioinformatics analysis. The flowering time of AP22.65-complementing plants was similar to that of the Col-0 wild type (WT). Conversely, its overexpression delayed flowering. Consistent with this phenotype, expression of AP22.65 was decreased in the ap22.65-1 mutant, recovered in AP22.65-complementing plants, and increased in AP22.65-overexpressing plants. Compared with the WT, expression levels of critical genes in different flowering pathways, i.e., SPY, FLC, GI, CO, FT, and LFY, were down-regulated in loss-of-function mutants. Expression of AP22.65 was distributed in flowers, siliques, rosette leaves, and whole seedlings. Therefore, this gene may be a negative regulator of Arabidopsis flowering. [ABSTRACT FROM AUTHOR]

CD147 is a transmembrane glycoprotein overexpressed in human hepatocellular carcinoma (HCC) which could promote HCC progression and metastasis. Promoter methylation is one of the most important processes in gene regulation. In this study, we aim to investigate CD147 promoter methylation status and the correlation with clinicopathological features and prognosis in HCC. CD147 promoter methylation statuses and expression levels in normal and HCC cell lines and 54 paired HCC and adjacent non-tumour (ANT) tissues were, respectively, examined by bisulphite genomic sequencing, methylation-specific PCR, real-time RT-PCR, Western blot and immunohistochemistry. The correlations of promoter methylation statuses with CD147 expression level and the clinicopathological features were statistically analysed in HCC patients. Significantly higher expression of CD147 and significantly lower promoter methylation level were observed in HCC cell lines compared to normal cell lines and tissues control. In vivo and in vitro analysis indicated that demethylation with 5-Aza-2′-deoxycytidine led to increased CD147 expression through enhancing Sp1 binding affinity, and methylation with methyltransferase reduced CD147 transcriptional activity through interfering Sp1 binding. CD147 promoter methylation level in HCC tissues (22.22%) was lower than that in ANT tissues (46.30%; P < 0.05). Within HCC tissues, a significant inverse correlation was observed between CD147 expression and methylation level ( r=−0.615). Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1% versus 58.3%; P < 0.05) and death rate (83.3% versus 50.0%; P < 0.05) than patients with methylated CD147 promoter. In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients. [ABSTRACT FROM AUTHOR]

An increased understanding of cellular uptake mechanisms of macromolecules remains an important challenge in cell biology with implications for viral infection and macromolecular drug delivery. Here, we report a strategy based on antibody-conjugated magnetic nanoparticles for the isolation of endocytic vesicles induced by heparan sulfate proteoglycans (HSPGs). key cell-surface receptors of macromolecular delivery. We provide evidence for a role of the glucose-regulated protein (GRP)75/PBP74/mtHSPlOlmortalin (hereafter termed "GRP75") in HSPG-mediated endocytosis of macromolecules. GRP75 was found to be a functional constituent of intracellular vesicles of a nonclathrin-, noncaveolindependent pathway that was sensitive to membrane cholesterol depletion and that showed colocalization with the membrane raft marker cholera toxin subunit B. We further demonstrate a functional role of the RhoA GTPase family member CDC42 in this transport pathway; however, the small GTPase dynamin appeared not to be involved. Interestingly, we provide evidence of a functional role of GRP75 using RNAi-mediated down-regulation of GRP75 and GRP75-blocking.antibodies, both of which inhibited macromolecular endocytosis. We conclude that GRP7S, a chaperone protein classically found in the endoplasmic reticulum and mitochondria, is a functional constituent of noncaveolar, membrane raft-associated endocytic vesicles. Our data provide proof of principle of a strategy that should be generally applicable in the molecular characterization of selected endocytic pathways involved in macromolecular uptake by mammalian cells. [ABSTRACT FROM AUTHOR]

HAb18G/CD147, a member of the immunoglobulin family enriched on the surface of tumor cells, is reported to be correlated with invasion, metastasis, growth, and survival of malignant cells. Here, we found that annexin II, a 36-kDa Ca2+- and phospholipid-binding protein and in vivo substrate for tyrosine kinase and PKC, is a new interaction protein of HAb18G/CD147 in human hepatocellular carcinoma (HCC) cells. In the present study, we explored the unclear role of annxin II in HCC invasion and migration and the interaction effects between HAb18G/CD147 and annexin II. Our data show that downregulation of annexin II in HCC cells significantly decreased the secretion of MMP, migration ability, and invasive potential, and affected the cytoskeleton rearrangement of tumor cells. The MMP-2 level and invasive potential of HCC cells were regulated by both annexin II and HAb18G/CD147. Also, interaction effects exist between the two molecules in tumor progression, including MMP-2 production, migration, and invasion. These results suggest that annexin II promotes the invasion and migration of HCC cells in vitro, and annexin II and HAb18G/CD147 interact with each other in the same signal transduction pathway working as a functional complex in tumor progression. ( Cancer Sci 2009) [ABSTRACT FROM AUTHOR]

Macromitrium cavaleriei Cardot & Thér. in Thér. is a little known Chinese moss of the family Orthotrichaceae. The species, which, forms dense mats with creeping stems, varies much in its branch leaf shape and in the laminal cell papillosity of the branch and perichaetial leaves. In the present paper, Macromitrium cavaleriei is re-evaluated taxonomically, including the new synonymizations of M. gebaueri Broth., M. sinense E. B. Bartram, M. syntrichophyllum Thér. & P. de la Varde, and M. syntrichophyllum var. longisetum Thér. & Reimers from China. The synonymizations extend the distribution of M. cavaleriei from Guizhou to 15 provinces and one municipality, mainly in the area to the South of the Yangtze River, Southwest China, and Taiwan. Additionally, M. cavaleriei is reported as new to the moss flora of Japan. [ABSTRACT FROM AUTHOR]

The HAMA response is a major challenge when murine antibodies are repeatedly administered for antibody directed enzyme prodrug therapy in vivo. In this study we have achieved humanization of the anti-γ-seminoprotein E4B7 murine mAb by guided selection. Using optimal Ig Fab primers, human Fd and CL gene repertoires were amplified by RT-PCR from PBMCs of prostate cancer patients. The human Lc gene repertoire was first paired with the murine Fd gene of E4B7 mAb to construct a pComb3X hybrid Fab display library. This hybrid library was screened with purified γ-seminoprotein antigen. The human Fd gene repertoire was then paired with the selected human Lc to construct a fully human Fab library. After four more rounds of panning, completely human Fab antibodies specific for γ-seminoprotein were selected and further identified. First, using the E4B7 Fd gene as a template, light chain shuffling was achieved by panning the hybrid library. Then, using the selected Lc as a template, a human Fab antibody against γ-seminoprotein was produced through heavy chain Fd shuffling. Western blotting, ELISA, and flow cytometry results demonstrated that the resulting human Fab antibody resembled the parental E4B7 mAb in that they both recognized the same epitope with similar affinities. Fluorescent cell staining and immunohistochemistry analysis further confirmed that this newly constructed human anti-γ-seminoprotein Fab antibody indeed specifically bound prostate cancer cells and tissue. Through guided-selection, we successfully produced a human anti-γ-seminoprotein Fab antibody. This work lays the foundation for optimal antibody-directed enzyme prodrug therapy of prostate cancer using a fully human Fab antibody. [ABSTRACT FROM AUTHOR]

A new idea is proposed by the PKU group to improve the magnetic properties of the Type-II superconductor niobium. Rare earth elements like scandium and yttrium are doped into ingot niobium during the smelting processes. A series of experiments have been done since 2010. The preliminary testing results show that the magnetic properties of niobium materials have changed with different doping elements and proportions while the superconductive transition temperature does not change very much. This method may increase the superheating magnetic field of niobium so as to improve the performance of the niobium cavity, which is a key component of SRF accelerators. A Tesla-type single-cell cavity made of scandium-doped niobium is being fabricated. [ABSTRACT FROM AUTHOR]