Near-Infrared Dual-Modal Sensing of Force and Temperature in Total Knee Replacement Using Mechanoluminescent Phosphor of Sr3Sn2O7: Nd, Yb.

Knee replacement surgery confronts challenges including patient dissatisfaction and the necessity for secondary procedures. A key requirement lies in dual-modal measurement of force and temperature of artificial joints during postoperative monitoring. Here, a novel non-toxic near-infrared (NIR) phosphor Sr3Sn2O7:Nd, Yb, is designed to realize the dual-modal measurement. The strategy is to entail phonon-assisted upconversion luminescence (UCL) and trap-controlled mechanoluminescence (ML) in a single phosphor well within the NIR biological transmission window. The phosphor is embedded in medical bone cement forming a smart joint in total knee replacements illustrated as a proof-of-concept. The sensing device can be charged in vitro by a commercial X-ray source with a safe dose rate for ML, and excited by a low power 980 nm laser for UCL. It attains impressive force and temperature sensing capabilities, exhibiting a force resolution of 0.5% per 10 N, force detection threshold of 15 N, and a relative temperature sensitive of up to 1.3% K-1 at 309 K. The stability against humidity and thermal shock together with the robustness of the device are attested. This work introduces a novel methodological paradigm, paving the way for innovative research to enhance the functionality of artificial tissues and joints in living organisms.

Clinical features and diagnostic approaches for abdominal tuberculosis: five-year experience from a non-tuberculosis-designated hospital in China.

BACKGROUND AND PURPOSE: abdominal tuberculosis (TB) is a common form of extrapulmonary TB but it is still a diagnostic dilemma in clinical practice. This study aimed to highlight the clinical features and diagnostic approaches for abdominal TB. METHODS: seventy cases of diagnosed abdominal TB were retrospectively collected between August 1st, 2015 and June 30th, 2020. They were classified as peritoneal TB, lymph node TB, gastrointestinal TB, visceral TB or mixed TB. RESULTS: eighteen patients were diagnosed with peritoneal TB, nine with lymph node TB, five with gastrointestinal TB, two with visceral TB and 36 with mixed TB. More than 65 % of the patients had tuberculosis of other sites except the abdomen. The median diagnosis time was 60 days. Ascites (58.6 %), abdominal distension (48.6 %), weight loss (44.3 %) and fever (42.9 %) were the most common symptoms. The overall microbiological and histological detection rates were 70.0 % and 38.6 %, respectively. The non-ascite samples yielded a higher microbiological confirmation rate (63.6 %) than the total samples (40.8 %). Diagnosis was confirmed histologically in 18 patients (69.2 %). Forty-five cases (64.3 %) were clinically diagnosed. Invasive procedures such as surgery (6/7), percutaneous biopsy (7/7) and endoscopy in lymph node TB (4/5) had high confirmation rates. CONCLUSIONS: the diagnosis of abdominal TB should be reached by a combination of clinical, laboratory, radiological, microbiological and pathological findings.

[Effects of different field processing methods on volatile components of Chuanxiong Rhizoma: an exploration based on headspace gas chromatography-mass spectrometry].

The volatile oil of Chuanxiong Rhizoma(CX) is known as an effective fraction. In order to seek a suitable method for processing CX and its decoction pieces, this study selected 16 volatile components as indices to investigate how different processing methods such as washing/without washing, sun-drying, baking, oven-drying and far-infrared drying at different temperatures affected the quality of CX and its decoction pieces(fresh CX was partially dried, cut into pieces, and then dried) by headspace gas chromatography-mass spectrometry(GC-MS), cluster analysis, principal component analysis and comprehensive weighted scoring. The results showed that the rapid washing before processing did not deteriorate the volatile components of CX. Considering the practical condition of production area, oven-drying was believed to be more suitable than sun-drying, baking, and far-infrared drying. The CX decoction pieces with a thickness of 0.3-0.4 cm were recommended to be oven-dried at 50 ℃. The integrated processing(partial drying, cutting into pieces, and drying) did not cause a significant loss of volatile components. For the fresh CX, the oven-drying at 60 ℃ is preferred. The temperature should not exceed 60 ℃, and drying below 60 ℃ will prolong the processing time, which will produce an unfavorable effect on volatile components. This study has provided the scientific evidence for field processing of CX, which is conducive to realizing the normalization and standardization of CX processing in the production area and stabilizing the quality of CX and its decoction pieces.

Study on corrosion behavior of X80 steel under stripping coating by sulfate reducing bacteria.

BACKGROUND: At present, microorganism has been considered as important factors that threaten to buried pipelines with disbonded coatings. Aiming at the problem of unknown corrosion mechanism of sulfate-reducing bacteria (SRB), a series of studies have been carried out in this paper. Spectrophotometer and fluorescent labeling technology are used to study the growth and attachment of SRB in the simulated soil solution. The corrosion behavior of X80 pipeline steel with or without SRB was researched by electrochemical methods such as open circuit potential, dynamic potential polarization curve, and electrochemical impedance spectroscopy. The microscopic morphology of the corrosion products on the surface was observed with a scanning electron microscope (SEM), and the element content of the corrosion products on the surface of the sample after corrosion was observed using X-ray energy spectrum (EDS) analysis. RESULTS: The results showed that the growth and reproduction of SRB caused the pH of the soil simulated solution to increase, which may promote the corrosion of X80 steel. In addition, the cathode reaction of X80 steel in a sterile environment is the reduction of H+, and the main corrosion product is iron oxide. When the soil simulation solution contains SRB, the cathodic reaction is controlled by both H+ reduction and sulfide depolarization reactions, and FeS appears in the corrosion products. CONCLUSION: Although the life cycle of SRB is only about 14 days, the corrosion of X80 steel is greatly promoted by SRB, and even causes corrosion perforation, which will bring huge economic losses and serious safety hazards.

Effects of electrostatic interactions on global folding and local conformational dynamics of a multidomain Y-family DNA polymerase.

The Y-family DNA polymerases specialize in translesion DNA synthesis, which is essential for replicating damaged DNA. The Y-family polymerases, which are made up of four stable domains, exhibit extensive distributions of charged residues, and are responsible for the tight formation of the protein-DNA complex. However, it is still unclear how the electrostatic interactions influence the conformational dynamics of the polymerases. Here, we focus on the case of a prototype Y-family DNA polymerase, Dpo4. Using coarse-grained models including a salt-dependent electrostatic potential, we investigate the effects of the electrostatic interactions on the folding process of Dpo4. Our simulations show that strong electrostatic interactions result in a three-state folding of Dpo4, consistent with the experimental observations. This folding process exhibits low cooperativity led by low salt concentration, where the individual domains fold one by one through one single pathway. Since the refined folding order of domains in multidomain proteins can shrink the configurational space, we suggest that the electrostatic interactions facilitate the Dpo4 folding. In addition, we study the local conformational dynamics of Dpo4 in terms of fluctuation and frustration analyses. We show that the electrostatic interactions can exaggerate the local conformational properties, which are in favor of the large-scale conformational transition of Dpo4 during the functional DNA binding. Our results underline the importance of electrostatic interactions in the conformational dynamics of Dpo4 at both the global and local scale, providing useful guidance in protein engineering at the multidomain level.

Semi-Synthesis of C-Ring Cyclopropyl Analogues of Fraxinellone and Their Insecticidal Activity Against Mythimna separata Walker.

Fraxinellone (1) is a naturally occurring degraded limonoid isolated from Meliaceae and Rutaceae plants. As a potential natural-product-based insecticidal agent, fraxinellone has been structurally modified to improve its activity. Furan ring of fraxinellone is critical in exhibiting its insecticidal activity, but with few modifications. Herein, C-ring-modified cyclopropyl analogues were semi-synthesized by Rh(II)-catalyzed cyclopropanation. The structures of the target compounds were well characterized by NMR and HRMS. The precise three-dimensional structural information of 3a was established by X-ray crystallography. Their insecticidal activity was evaluated against Mythimna separata Walker by a leaf-dipping method. Compound 3c exhibited stronger insecticidal activity than 1 and toosendanin against M. separata with teratogenic symptoms during the different periods, implying that cyclopropanation of the furan ring could strengthen the insecticidal activity of fraxinellone.

[Clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine (draft version for comments)].

By referring to the standards and procedures of WHQ Handbook for Guideline Development, under the guidance of relevant laws, regulations, and technical documents, in line with the principle of "evidence-based, consensus-based, experience-based", and based on the best available evidences, fully combined with expert experience and patient preferences, we summarized eight clinical questions in this paper: can traditional Chinese medicine(TCM) treatment improve the clinical symptoms and the degree of dyspnea in patients with stable chronic obstructive pulmonary disease(COPD) Can TCM treatment reduce the number of exacerbations in patients with stable COPD? Can TCM treatment improve the exercise tolerance of patients with stable COPD? Can TCM treatment improve the quality of life of patients with stable COPD? Can TCM treatment delay the decline of lung function in patients with stable COPD? Can TCM treatment improve anxiety and depression in patients with stable COPD? Does the point application therapy benefit patients with stable COPD? Can non-pharmacological treatment benefit patients with stable COPD? Based on these eight clinical problems, the cha-racteristics of TCM itself, and actual clinical situation, the recommendations of TCM to treat the stable COPD were formed in this guideline, with intention to provide advice and guidance to clinicians in the use of TCM to treat stable COPD, to relieve symptoms, improve exercise tolerance, improve health status, prevent disease progression, prevent and treat exacerbations, and improve clinical efficacy. Due to the influence of the user's region, nationality, race and other factors, the implementation of this guideline should be based on the actual situations.

[Editorial explanation for clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine].

As an important auxiliary document in the process of guideline development, the editorial explanation is the extension and complement to the content of the guideline, a basis for fully understanding the technical content of the guideline, an indispensable document for the guideline's traceability. The project team of this guideline, while formulating the Clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine(draft version for comments), also has written the corresponding editorial explanation. In order to enable the relevant medical workers to more accurately understand and apply the guideline, but also to provide readers with a more in-depth understanding of the reasons and processes for the development of the guideline, the paper will give a detailed introduction to the compilation process about the guideline, includes: work overview(project background, task source, drafting and collaboration unit, project team members and their division of labor), main technical content(the basis and principles of guideline development, technical route), main compilation process(the establishment of project team, the formulation of the guideline plan, the project approval and the registration of research programme, the construction of clinical issues and the selection of outcome indicators, evidence search screening and synthesis, evidence evaluation and grading, the formation of recommendations, the writing of exposure draft, external review and self-assessment, etc), expert consensus implementation requirements and measure suggestions(promotion and implementation measures, and post-effect evaluation), other issues need to be explained and so on.

[Systematic review and Meta-analysis on efficacy and safety of Liujunzi Decoction combined with Western medicine for stable chronic obstructive pulmonary disease].

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

[Systematic review and Meta-analysis on efficacy and safety of Buzhong Yiqi Decoction for stable chronic obstructive pulmonary disease].

To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

[Analysis of acupoint selection of plaster therapy in treatment of stable chronic obstructive pulmonary disease based on data mining].

This article analyze acupoint selection and characteristics of plaster therapy for stable chronic obstructive pulmonary di-sease(COPD) by data mining. The CNKI, VIP, CBM, WanFang, PubMed, EMbase, Cochrane Library were retrieved for collecting clinical studies of plaster therapy for stable COPD. After literature screening, a total of 46 systematic reviews were included. Frequency statistics, cluster analysis, and Apriori correlation analysis were used to analyze the pattern and characteristics of plaster therapy for stable COPD. The result showed that the main acupoints for stable COPD were BL13, Dingchuan, CV22, BL23 and BL20. The acupoints used are mainly concentrated on the chest and back. The most frequently used meridian is the bladder meridian. Analysis of the acupoints yielded 27 correlation rules. And cluster analysis grouped the high frequency acupoints into 5 categories. The results of the study showed that the current choice of acupoints is rather concentrated. "Local acupuncture points" and "matching points with front and back" were the main acupoint selection rules. The choice of acupuncture points reflected the traditional Chinese medicine treatment principle of strengthening healthy Qi to eliminate pathogenic factor, treating both manifestation and root cause of disease, and preventing measure taken after the occurrence of disease.

[Framework construction and standardization practice of standard system for Sichuan Dao-di herbs].

Dao-di herbs is one of the characteristics of traditional Chinese medicine different from other ethnic medicine. Sichuan province is rich in varieties and resources of Dao-di herbs, and its development scale and benefits are not obvious in recent decades due to the lag of standards behind the development of the times and objective needs. From the point of view of the whole process and the whole industrial chain, the significance of standardization system for quality assurance, healthy development of the industry, and development of the industry of Sichuan Dao-di herbs are presented in this paper. At present, Sichuan has made every effort to promote the construction and practice of the standardization system for Sichuan Dao-di herbs, to promote the rapid and high-quality development of Dao-di herbs industry in Sichuan.

[Dao-di herbs pharmacology and new ideas of Dao-di herbs standard construction].

Guided by the basic theory of traditional Chinese medicine and using modern scientific methods, Dao-di herbs pharmacology studies the nature, performance, interaction with the body and its clinical application.It is a bridge between the basic research and clinical application of Dao-di herbs. It can objectively describe the law of efficacy of Dao-di herbs, scientifically explain the mechanism of efficacy of Dao-di herbs, explore and establish the standards and methods of Dao-di herbs based on biological effect and clinical efficacy, and provide scientific basis for the special properties, pharmacology and clinical value of Dao-di herbs.Furthermore, we put forward a new idea of building the standard of Dao-di herbs based on the curative effect rather than the origin.The Dao-di herbs standard should come from the systematic research of traditional Dao-di herbs producing areas and form a new characteristic system, through the extraction of environmental, genetic, character, chemical, pharmacological and other characteristics.This standard originates from the tradition, but it is higher than the tradition. It may not have the origin meaning of strict administrative division, but it can better reflect the pharmacological characteristics and excellent clinical value of Dao-di herbs.

Comparison of Th17 cells mediated immunological response among asthmatic children with or without allergic rhinitis.

OBJECTIVE: To investigate whether there were differences in Th17 cells mediated immunological responses among asthmatics with or without allergic rhinitis. METHODS: A case-control comparison was conducted in a cohort of 67 children with asthma (AS), 50 children with allergic rhinitis (AR), 52 children with both AS and AR (ASR), 25 infectious rhinitis (IR), and 55 healthy controls (HC). The percentages of circulating Th17 cells were determined by flow cytometry. The Th2- and Th17-related cytokines in plasma and culture supernatants were measured by enzyme-linked immunosorbent assay. The effect of proinflammation cytokine IL-17E on Th2 cytokines production from human T helper (Th) lymphocytes was analyzed. RESULTS: (1) A inter-group comparison revealed that Th17 cells levels were highest in ASR group [(0.89% ± 0.27) %], following by AS group [(0.82 ± 0.29) %] and AR group[(0.78 ± 0.17) %] (P < 0.05). (2) After in-vitro stimulation with house dust mite (HDM) antigen, the levels of IL-4 and IL-17E in culture supernatants of PBMCs from allergic children (AS group, AR group and ASR group) were significantly enhanced. (3) The release of Th2 cytokines from IL-17E treated Th cells of allergic children (AS group, AR group and ASR group) were significantly induced, no similar result was observed in IR group and HC group. CONCLUSIONonclusion: Our findings preliminarily revealed that Th17 cell and its related cytokines might be involved in pathogenesis of airway inflammation diseases, and also presenting varying immunological characteristics among asthmatic children with or without allergic rhinitis.

[Study on dynamic changes of chemical constituents during different drying processes of Salvia miltiorrhiza].

There is no consensus on the drying methods of Salvia miltiorrhiza in ancient and modern times,especially on the content of phenolic acid in fresh S. miltiorrhiza. In order to further explore the content of main components in fresh S. miltiorrhiza and study the dynamic changes during the drying process,the content of main components was used as the index in this study to evaluate the processing method,drying method,correlation between dehydration rate and component content for fresh S. miltiorrhiza. In addition,the sealed and unsealed parallel control groups were set to carry out verification test during the drying process. UPLC method was used for determination of seven main components including rosmarinic acid,lithosperic acid,salvianolic acid B,cryptotanshinone,tanshinoneⅠ,methylene salianolate and tanshinone ⅡAin S. miltiorrhiza. The results showed that the fresh S. miltiorrhiza contained low levels of phenolic acid,and the content of phenolic acid increased significantly with the increase of dehydration rate during drying process,while the change of tanshinone was not obvious. In the comparison of three drying methods,we found that drying at 50 ℃ was better than drying in the sun,and drying in the sun was superior to drying in the shade. So,drying at 50 ℃ was the best drying method. The correlation between dehydration and phenolic acid content of S. miltiorrhiza was analyzed by verification test and SPSS software,which further proved that the dehydration rate was significantly positively correlated with the content of phenolic acid components. This study provides reference for the production processing and drying methods of S. miltiorrhiza medicinal materials,which is of great significance for improving the quality of S. miltiorrhiza.

[Generalized science of Chinese material medica-from preventive treatment of disease to Chinese medicine health industry].

Based on the systematic summary of the results of the fourth general survey of traditional Chinese medicine resources, the cultivation of large varieties of Chinese material medica and the latest research on health industrial development, the novel concepts and scientific connotations of generalized science of Chinese material medica are put forward, and the basic ideas and methods of a new Chinese medicine academic system, the cultivation system of large varieties of Chinese medicinal materials and the application system of the large health industry are constructed. This kind of generalized science of Chinese material medica, rooted in the traditional Chinese culture and the theory of "preventive treatment of disease", can avoid the narrow prospect induced by the increasing specialization and refinement of knowledge of science of Chinese material medica. It will play an important role in the modernization, industrialization, internationalization of traditional Chinese medicine.

Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions.

[3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc)3 mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47µM, and compound 5p exhibted highest activity on HeLa cells with IC50 vaule of 2.32µM. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochemistry studies and cell cycle distribution analysis indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, molecular docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin.

Coupling of lever arm swing and biased Brownian motion in actomyosin.

An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5-11 nm displacement due to the biased Brownian motion and the 3-5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family.

[Sporadic cutaneous infections due to nontuberculous mycobacteria: a retrospective study of 37 cases].

OBJECTIVE: To study the clinical and pathological characteristics of sporadic cutaneous infections due to nontuberculous mycobacteria (NTM), and investigate the diagnostic criteria and therapeutic principal. METHODS: Totally 37 cases of sporadic cutaneous infections due to NTM were confirmed in the Department of Dermatology, Peking University People's Hospital from January 2000 to March 2014. The microbiologic and clinical data were reviewed, and their skin biopsy specimens were reassessed. RESULTS: Of all the 37 patients, 30 cases were Mycobacterium marinum infection, 6 were Mycobacterium abscessus infection, and one was Mycobacterium chelonea and Mycobacterium fortuitum infection. Identification of mycobacterial species by analysis of hsp65 gene in tissue DNA was more sensitive than traditional bacterial culture. The most common risk factors were traumatic injuries (21 of 37) and aquarium or fish-related job (21 of 37). One case of Mycobacterium abscessus infection occurred after autologous fat filling. Nodule and plaque were most common lesions in Mycobacterium marinum infection. Twenty-four of the 30 cases of Mycobacterium marinum infection presented with multiple lesions or sporotrichoid spread lesions. Ulceration, papules, abscess, and purulent discharge were observed in cases of Mycobacterium abscessus infection. Infective granuloma was most common histopathological appearance. For the treatment of Mycobacterium marinum infection, rifampin, ethambutol, and clarithromycin were commonly used (combination of two antibiotics, or three antibiotics), with the cure rate 90.00%. Four of the six Mycobacterium abscessus infections cases were cured, and one patient died. CONCLUSION: The most common species of sporadic cutaneous infections due to NTM is Mycobacterium marinum. Traumatic injuries, aquarium or fish-related job, and cosmetic surgeries are common risk factors. Mycobacterium marinum infection often presents with nodules, plaques, and sometimes sporotrichoid spread lesions. Lesions of Mycobacterium abscessus infection may vary. Pathological changes were not species specific, final diagnosis must be made depending on the identification of the microorganism. For the treatment of Mycobacterium marinum infection, excellent outcomes can be achieved by the combination of rifampin and ethambutol, and the combination of clarithromycin and rifampin or ethambutoland. Treatment regimens of Mycobacterium abscessus infection should be decided according to the results of antibiotic susceptibility testing.

Conformational flexibility of loops of myosin enhances the global bias in the actin-myosin interaction landscape.

A long-standing controversy on the mechanism of an actomyosin motor is the role of the Brownian motion of the myosin head in force generation. In order to shed light on this problem, we calculate free-energy landscapes of interaction between an actin filament and the head (S1) of myosin II by using a coarse-grained model of actomyosin. The results show that the free-energy landscape has a global gradient toward the strong-binding site on actin filament, which explains the biased Brownian motion of myosin S1 observed in a single-molecule experiment [Kitamura et al., Nature, 1999, 397, 129 and Biophysics, 2005, 1, 1]. The distinct global gradient in the landscape is brought about only when the conformation of loop 2 at the actin interface of myosin S1 is flexible. The conformational flexibility of loop 3 also contributes to the gradient in the landscape by compensating the role of loop 2. Though the structure of loop 2 is expanded in the weak-binding state, loop 2 shows the larger fluctuation of compaction and expansion due to the actin-myosin interactions as myosin S1 moves toward the strong-binding site on actin filament. Hence, the increase in the compaction-expansion fluctuation of loop 2, the stronger binding of myosin to actin, and the biased Brownian motion of myosin S1 are coupled with each other and should take place in a concurrent way. This predicted coupling should provide opportunities to further test the hypothesis of the biased Brownian motion in actomyosin.