The conserved domain database in 2023.

NLM's conserved domain database (CDD) is a collection of protein domain and protein family models constructed as multiple sequence alignments. Its main purpose is to provide annotation for protein and translated nucleotide sequences with the location of domain footprints and associated functional sites, and to define protein domain architecture as a basis for assigning gene product names and putative/predicted function. CDD has been available publicly for over 20 years and has grown substantially during that time. Maintaining an archive of pre-computed annotation continues to be a challenge and has slowed down the cadence of CDD releases. CDD curation staff builds hierarchical classifications of large protein domain families, adds models for novel domain families via surveillance of the protein 'dark matter' that currently lacks annotation, and now spends considerable effort on providing names and attribution for conserved domain architectures. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

Amino acids and their roles in tumor immunotherapy of breast cancer.

Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple-negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune-suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor-specific or oncogene-dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

Exoskeleton-Assisted Anthropomorphic Movement Training for the Upper Limb After Stroke: The EAMT Randomized Trial.

BACKGROUND: Robot-assisted arm training is generally delivered in the robot-like manner of planar or mechanical 3-dimensional movements. It remains unclear whether integrating upper extremity (UE) natural coordinated patterns into a robotic exoskeleton can improve outcomes. The study aimed to compare conventional therapist-mediated training to the practice of human-like gross movements derived from 5 typical UE functional activities managed with exoskeletal assistance as needed for patients after stroke. METHODS: In this randomized, single-blind, noninferiority trial, patients with moderate-to-severe UE motor impairment due to subacute stroke were randomly assigned (1:1) to receive 20 sessions of 45-minute exoskeleton-assisted anthropomorphic movement training or conventional therapy. Treatment allocation was masked from independent assessors, but not from patients or investigators. The primary outcome was the change in the Fugl-Meyer Assessment for Upper Extremity from baseline to 4 weeks against a prespecified noninferiority margin of 4 points. Superiority would be tested if noninferiority was demonstrated. Post hoc subgroup analyses of baseline characteristics were performed for the primary outcome. RESULTS: Between June 2020 and August 2021, totally 80 inpatients (67 [83.8%] males; age, 51.9±9.9 years; days since stroke onset, 54.6±38.0) were enrolled, randomly assigned to the intervention, and included in the intention-to-treat analysis. The mean Fugl-Meyer Assessment for Upper Extremity change in exoskeleton-assisted anthropomorphic movement training (14.73 points; [95% CI, 11.43-18.02]) was higher than that of conventional therapy (9.90 points; [95% CI, 8.15-11.65]) at 4 weeks (adjusted difference, 4.51 points [95% CI, 1.13-7.90]). Moreover, post hoc analysis favored the patient subgroup (Fugl-Meyer Assessment for Upper Extremity score, 23-38 points) with moderately severe motor impairment. CONCLUSIONS: Exoskeleton-assisted anthropomorphic movement training appears to be effective for patients with subacute stroke through repetitive practice of human-like movements. Although the results indicate a positive sign for exoskeleton-assisted anthropomorphic movement training, further investigations into the long-term effects and paradigm optimization are warranted. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100044078.

Neutrophils in triple-negative breast cancer: an underestimated player with increasingly recognized importance.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with limited therapeutic options readily available. Immunotherapy such as immune checkpoint inhibition has been investigated in TNBC but still encounters low overall response. Neutrophils, the most abundant leukocytes in the body, are increasingly recognized as an active cancer-modulating entity. In the bloodstream, neutrophils escort circulating tumor cells to promote their survival and stimulate their proliferation and metastasis. In the tumor microenvironment, neutrophils modulate the immune milieu through polarization between the anti-tumor and the pro-tumor phenotypes. Through a comprehensive review of recently published literature, it is evident that neutrophils are an important player in TNBC immunobiology and can be used as an important prognostic marker of TNBC. Particularly, in their pro-tumor form, neutrophils facilitate TNBC metastasis through formation of neutrophil extracellular traps and the pre-metastatic niche. These findings will help advance the potential utilization of neutrophils as a therapeutic target in TNBC.

Association of BMAL1 clock gene polymorphisms with fasting glucose in children.

BACKGROUND: The brain and muscle Arnt-like protein-1 (BMAL1) gene is an important circadian clock gene and previous studies have found that certain polymorphisms are associated with type 2 diabetes in adults. However, it remains unknown if such polymorphisms can affect fasting glucose in children and if other factors modify the associations. METHODS: A school-based cross-sectional study with 947 Chinese children was conducted. A multivariable linear regression model was used to analyze the association between BMAL1 gene polymorphisms and fasting glucose level. RESULTS: After adjusting for age, sex, body mass index (BMI), physical activity, and unhealthy diet, GG genotype carriers of BMAL1 rs3789327 had higher fasting glucose than AA/GA genotype carriers (b = 0.101, SE = 0.050, P = 0.045). Adjusting for the same confounders, rs3816358 was shown to be significantly associated with fasting glucose (b = 0.060, SE = 0.028, P = 0.032). Furthermore, a significant interaction between rs3789327 and nutritional status on fasting glucose was identified (Pinteraction = 0.009); rs3789327 was associated with fasting glucose in the overweight/obese subgroup (b = 0.353, SE = 0.126, P = 0.006), but not in non-overweight/non-obese children. CONCLUSIONS: BMAL1 polymorphisms were significantly associated with the fasting glucose level in children. Additionally, the observed interaction between nutritional status and BMAL1 supports promoting an optimal BMI in children genetically predisposed to higher glucose level. IMPACT: Polymorphisms in the essential circadian clock gene BMAL1 were associated with fasting blood glucose levels in children. Additionally, there was a significant interaction between nutritional status and BMAL1 affecting fasting glucose levels. BMAL1 rs3789327 was associated with fasting glucose only in overweight/obese children. This finding could bring novel insights into mechanisms by which nutritional status influences fasting glucose in children.

RefSeq: expanding the Prokaryotic Genome Annotation Pipeline reach with protein family model curation.

The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) contains nearly 200 000 bacterial and archaeal genomes and 150 million proteins with up-to-date annotation. Changes in the Prokaryotic Genome Annotation Pipeline (PGAP) since 2018 have resulted in a substantial reduction in spurious annotation. The hierarchical collection of protein family models (PFMs) used by PGAP as evidence for structural and functional annotation was expanded to over 35 000 protein profile hidden Markov models (HMMs), 12 300 BlastRules and 36 000 curated CDD architectures. As a result, >122 million or 79% of RefSeq proteins are now named based on a match to a curated PFM. Gene symbols, Enzyme Commission numbers or supporting publication attributes are available on over 40% of the PFMs and are inherited by the proteins and features they name, facilitating multi-genome analyses and connections to the literature. In adherence with the principles of FAIR (findable, accessible, interoperable, reusable), the PFMs are available in the Protein Family Models Entrez database to any user. Finally, the reference and representative genome set, a taxonomically diverse subset of RefSeq prokaryotic genomes, is now recalculated regularly and available for download and homology searches with BLAST. RefSeq is found at https://www.ncbi.nlm.nih.gov/refseq/.

A telerehabilitation programme in post-discharge COVID-19 patients (TERECO): a randomised controlled trial.

OBJECTIVES: To investigate superiority of a telerehabilitation programme for COVID-19 (TERECO) over no rehabilitation with regard to exercise capacity, lower limb muscle strength (LMS), pulmonary function, health-related quality of life (HRQOL) and dyspnoea. DESIGN: Parallel-group randomised controlled trial with 1:1 block randomisation. SETTING: Three major hospitals from Jiangsu and Hubei provinces, China. PARTICIPANTS: 120 formerly hospitalised COVID-19 survivors with remaining dyspnoea complaints were randomised with 61 allocated to control and 59 to TERECO. INTERVENTION: Unsupervised home-based 6-week exercise programme comprising breathing control and thoracic expansion, aerobic exercise and LMS exercise, delivered via smartphone, and remotely monitored with heart rate telemetry. OUTCOMES: Primary outcome was 6 min walking distance (6MWD) in metres. Secondary outcomes were squat time in seconds; pulmonary function assessed by spirometry; HRQOL measured with Short Form Health Survey-12 (SF-12) and mMRC-dyspnoea. Outcomes were assessed at 6 weeks (post-treatment) and 28 weeks (follow-up). RESULTS: Adjusted between-group difference in change in 6MWD was 65.45 m (95% CI 43.8 to 87.1; p<0.001) at post-treatment and 68.62 m (95% CI 46.39 to 90.85; p<0.001) at follow-up. Treatment effects for LMS were 20.12 s (95% CI 12.34 to 27.9; p<0.001) post-treatment and 22.23 s (95% CI 14.24 to 30.21; p<0.001) at follow-up. No group differences were found for lung function except post-treatment maximum voluntary ventilation. Increase in SF-12 physical component was greater in the TERECO group with treatment effects estimated as 3.79 (95% CI 1.24 to 6.35; p=0.004) at post-treatment and 2.69 (95% CI 0.06 to 5.32; p=0.045) at follow-up. CONCLUSIONS: This trial demonstrated superiority of TERECO over no rehabilitation for 6MWD, LMS, and physical HRQOL. TRIAL REGISTRATION NUMBER: ChiCTR2000031834.

Lovastatin enhances chemosensitivity of paclitaxel-resistant prostate cancer cells through inhibition of CYP2C8.

Chemotherapy is the mainstay of treatment for prostate cancer, with paclitaxel being commonly used for hormone-resistant prostate cancer. However, drug resistance often develops and leads to treatment failure in a variety of prostate cancer patients. Therefore, it is necessary to enhance the sensitivity of prostate cancer to chemotherapy. Lovastatin (LV) is a natural compound extracted from Monascus-fermented foods and is an inhibitor of HMG-CoA reductase (HMGCR), which has been approved by the FDA for hyperlipidemia treatment. We have previously found that LV could inhibit the proliferation of refractory cancer cells. Up to now, the effect of LV on chemosensitization and the mechanisms involved have not been evaluated in drug-resistant prostate cancer. In this study, we used prostate cancer cell line PC3 and its paclitaxel-resistant counterpart PC3-TxR as the cell model. Alamar Blue cell viability assay showed that LV and paclitaxel each conferred concentration-dependent inhibition of PC3-TxR cells. When paclitaxel was combined with LV, the proliferation of PC3-TxR cells was synergistically inhibited, as demonstrated by combination index <1. Moreover, colony formation decreased while apoptosis increased in paclitaxel plus LV group compared with paclitaxel alone group. Quantitative RT-PCR showed that the combination of paclitaxel and LV could significantly reduce the expression of CYP2C8, an important drug-metabolizing enzyme. Bioinformatics analysis from the TCGA database showed that CYP2C8 expression was negatively correlated with progression-free survival (PFS) in prostate cancer patients. Our results suggest that LV might increase the sensitivity of resistant prostate cancer cells to paclitaxel through inhibition of CYP2C8 and could be utilized as a chemosensitizer for paclitaxel-resistant prostate cancer cells.

Early life exposure to the Chinese Famine of 1959 - 1961 is an independent risk factor of adulthood elevated homocysteine, hyperuricemia, high LDL, and hypertension.

Famine exposure in early life was associated with cardiovascular diseases in later life. Whether biochemical surrogates of cardiovascular diseases, such as homocysteine and uric acid, are also associated with famine exposure is unknown so far. Data were derived from a population-based cross-sectional study in the Hunan Province of China, which was heavily affected by the Famine in 1959 - 1961. A total of 1,150 adults born between 1952 and 1964 were selected, and 5 cohorts were defined: no exposure, fetal, early childhood, mid-childhood, and late childhood exposure. Compared with the no-famine exposure group, participants exposed to famine in their fetal period had a higher risk of high homocysteine in adulthood with OR of 2.21 (95% CI: 1.01 - 4.83), whereas famine exposures in early, mid, or late childhood were not significantly associated with high homocysteine in adulthood. Similarly, participants in the fetal famine exposure group had a 1.59-fold higher risk of hyperuricemia (OR = 2.59, 95% CI: 1.07 - 5.30) and a 2.03-fold higher risk of high low-density lipoprotein cholesterol (LDL) (OR = 0.03, 95% CI: 1.35 - 6.78) in adulthood compared to those without famine exposure, respectively. We furthermore conducted a meta-analysis including 16 studies regarding the association between fetal famine exposure and adulthood hypertension, including our study. The meta-analysis, including 34,804, subjects showed that fetal famine exposure is associated with a higher risk of adulthood hypertension (OR = 1.22, 95% CI: 1.07 - 1.40). Taken together, fetal famine exposure is related to higher odds of cardio-metabolic risk factors, such as high homocysteine, hyperuricemia, and LDL as well as hypertension, suggesting that undernutrition during fetal life may affect metabolism of homocysteine, uric acid, and LDL in adulthood.

CDD/SPARCLE: the conserved domain database in 2020.

As NLM's Conserved Domain Database (CDD) enters its 20th year of operations as a publicly available resource, CDD curation staff continues to develop hierarchical classifications of widely distributed protein domain families, and to record conserved sites associated with molecular function, so that they can be mapped onto user queries in support of hypothesis-driven biomolecular research. CDD offers both an archive of pre-computed domain annotations as well as live search services for both single protein or nucleotide queries and larger sets of protein query sequences. CDD staff has continued to characterize protein families via conserved domain architectures and has built up a significant corpus of curated domain architectures in support of naming bacterial proteins in RefSeq. These architecture definitions are available via SPARCLE, the Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

[Associations between birth outcomes with blood pressure level and risk of high blood pressure in childhood].

OBJECTIVE: To explore the associations between birth outcomes and blood pressure, and study the sex dimorphism of these associations. METHODS: With a multistage cluster random sampling method, 62 168 children were recruited in seven provinces of China in September of 2013, with 32 064 boys and 30 104 girls, median age of 10.74 years and mean birth weight of 3.3 kg, 49 843 single birth(97%), 1339 twin(2.6%), 180 triplet or more(0.4%). Questionnaire investigation and physical examination were conducted in the present study. Weight, height and blood pressure were measured in the physical examination. Demographic characteristics, birth outcomes(including birth weight and number of births), dietary behavior, physical activities were measured by questionnaire. The widely used age-, gender-and height-specific high blood pressure standard developed by American CDC was used for the present study. Multivariate linear and logistic regression analysis were conducted to study the associations between birth outcomes and blood pressure level or high blood pressure(HBP), and also sex dimorphism of these associations was explored. RESULTS: A total of 5933 children were categorized as having high blood pressure in the 62 168 participants(9.5%). With stratified analyses by birth weight category, only in the low-birth-weight strata birth weight was significantly inversely associated with systolic blood pressure(SBP) and diastolic blood pressure(DBP) with potential covariates adjusted(SBP: b=-1.628, 95%CI-2.571--0.685, P=0.001; DBP: b=-1.463, 95%CI-2.186--0.740, P<0.001). While compared with the non-low birth weight children, low birth weight was not associated with higher risk of HBP(P>0.05). Compared with those boys born as singleton, boys born as one of the twins have a 36.4% higher risk of HBP(OR=1.364, 95%CI 1.049-1.774), while in girls no such significant association was found. Additionally, compared with a term birth, overdue birth and preterm birth was not associated with higher risk of HBP(P>0.05). CONCLUSION: Birth weight and singleton or not were associated with childhood blood pressure levels and higher risk of high blood pressure, and some associations were sex specific. Gender differences should be paid attention to in the prevention and control of high blood pressure in children and adolescents in the future, and the prevention and control should be focused on low-birth weight children or twin boys.

RefSeq: an update on prokaryotic genome annotation and curation.

The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) provides annotation for over 95 000 prokaryotic genomes that meet standards for sequence quality, completeness, and freedom from contamination. Genomes are annotated by a single Prokaryotic Genome Annotation Pipeline (PGAP) to provide users with a resource that is as consistent and accurate as possible. Notable recent changes include the development of a hierarchical evidence scheme, a new focus on curating annotation evidence sources, the addition and curation of protein profile hidden Markov models (HMMs), release of an updated pipeline (PGAP-4), and comprehensive re-annotation of RefSeq prokaryotic genomes. Antimicrobial resistance proteins have been reannotated comprehensively, improved structural annotation of insertion sequence transposases and selenoproteins is provided, curated complex domain architectures have given upgraded names to millions of multidomain proteins, and we introduce a new kind of annotation rule-BlastRules. Continual curation of supporting evidence, and propagation of improved names onto RefSeq proteins ensures that the functional annotation of genomes is kept current. An increasing share of our annotation now derives from HMMs and other sets of annotation rules that are portable by nature, and available for download and for reuse by other investigators. RefSeq is found at https://www.ncbi.nlm.nih.gov/refseq/.

CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.

NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBI's Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

[Changes of the nutritional status of children and adolescents aged 7-17 years of Tujia ethnic minority in Hunan Province from 2010 to 2014].

OBJECTIVE: To understand the change of nutritional status of children and adolescents aged 7-17 years from Tujia ethnic minority in Hunan Province, and to provide evidence for the prevention and control policy making of improving the population's nutritional status. METHODS: A total of 4676 children and adolescents aged 7-17 years from Tujia ethnic minority in Hunan Province were included(2310 in year 2010, 2366 in year 2014), sample were recruited in the 2010 and 2014 Chinese National Survey on Students' Constitution and Health. The nutritional status of wasting and stunting was defined by a national malnutrition screening standard(WS/T 456-2014), overweight and obesity were defined by the body mass index percentile criteria developed by Chinese Working Group on Obesity for Children(WGOC). RESULTS: From 2010 to 2014, the obesity prevalence of Tujia children and adolescents from Hunan increased obviously from 3.1% to 5.7%, and the prevalence of wasting also increased, from 7.8% to 10.5%. The trend analysis of stunting showed that the stunting prevalence decreased significantly from 8.4% in 2010 to 3.5% in 2014. CONCLUSION: The stunting issue in Tujia children and adolescents has improved a lot from 2010 to 2014. But the prevalence of stunting is still high, and there is a dual burden of malnutrition and overnutrition.

[Influencing factors of the amount of drinking water by Changsha college students: a multilevel model analysis].

OBJECTIVE: To investigate the amount of water intake and the influencing factors of daily water intake of Changsha undergraduates. METHODS: From December 2014 to January 2015, we investigated 1000 undergraduates in 4 colleges of Changsha through questionnaire and cup measurement. Total of 1000 undergraduates were selected by multistage random sampling method. Multi-level analysis were used to analyze the characteristics and influencing factors of daily water intake. RESULTS: The median of total daily water intake was 2803 mL, daily direct water intake was 1983 mL, and indirect water intake was 757 mL. The median of daily water intake in spring or autumn of undergraduates was 2656 mL, 3480 mL in summer and 2236 mL in winter. With multilevel analysis, we found that sex, BMI and status of smoking or alcohol drinking influencing the water intake of undergraduates. CONCLUSION: The daily water drink of undergraduates is influenced by sex, BMI and smoking and alcohol drinking. Therefore, these influencing factors should be comprehensively considered when making environmental risk evaluation through water intake.

CDD: NCBI's conserved domain database.

NCBI's CDD, the Conserved Domain Database, enters its 15(th) year as a public resource for the annotation of proteins with the location of conserved domain footprints. Going forward, we strive to improve the coverage and consistency of domain annotation provided by CDD. We maintain a live search system as well as an archive of pre-computed domain annotation for sequences tracked in NCBI's Entrez protein database, which can be retrieved for single sequences or in bulk. We also maintain import procedures so that CDD contains domain models and domain definitions provided by several collections available in the public domain, as well as those produced by an in-house curation effort. The curation effort aims at increasing coverage and providing finer-grained classifications of common protein domains, for which a wealth of functional and structural data has become available. CDD curation generates alignment models of representative sequence fragments, which are in agreement with domain boundaries as observed in protein 3D structure, and which model the structurally conserved cores of domain families as well as annotate conserved features. CDD can be accessed at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

Does the addition of specific acupuncture to standard swallowing training improve outcomes in patients with dysphagia after stroke? a randomized controlled trial.

OBJECTIVE: To assess the effect of adding acupuncture to standard swallowing training for patients with dysphagia after stroke. DESIGN: Single-blind randomized controlled trial. SETTING: Inpatient and outpatient clinics. SUBJECTS: A total of 124 patients with dysphagia after stroke were randomly divided into two groups: acupuncture and control. INTERVENTIONS: The acupuncture group received standard swallowing training and acupuncture treatment. In comparison, the control group only received standard swallowing training. Participants in both groups received six days of therapy per week for a four-week period. MAIN MEASURES: The primary outcome measures included the Standardized Swallowing Assessment and the Dysphagia Outcome Severity Scale. The secondary outcome measures included the Modified Barthel Index and Swallowing-Related Quality of Life, which were assessed before and after the four-week therapy period. RESULTS: A total of 120 dysphagic subjects completed the study (60 in acupuncture group and 60 in control group). Significant differences existed in the Standardized Swallowing Assessment, Dysphagia Outcome Severity Scale, Modified Barthel Index, and Swallowing-Related Quality of Life scores of each group after the treatment (P < 0.01). After the four-week treatment, the Standardized Swallowing Assessment (mean difference - 2.9; 95% confidence interval (CI) - 5.0 to - 0.81; P < 0.01), Dysphagia Outcome Severity Scale (mean difference 2.3; 95% CI 0.7 to 1.2; P < 0.01), Modified Barthel Index (mean difference 17.2; 95% CI 2.6 to 9.3; P < 0.05) and Swallowing-Related Quality of Life scores (mean difference 31.4; 95% CI 3.2 to 11.4; P < 0.01) showed more significant improvement in the acupuncture group than the control group. CONCLUSIONS: Acupuncture combined with the standard swallowing training may be beneficial for dysphagic patients after stroke.

CDD: conserved domains and protein three-dimensional structure.

CDD, the Conserved Domain Database, is part of NCBI's Entrez query and retrieval system and is also accessible via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. CDD provides annotation of protein sequences with the location of conserved domain footprints and functional sites inferred from these footprints. Pre-computed annotation is available via Entrez, and interactive search services accept single protein or nucleotide queries, as well as batch submissions of protein query sequences, utilizing RPS-BLAST to rapidly identify putative matches. CDD incorporates several protein domain and full-length protein model collections, and maintains an active curation effort that aims at providing fine grained classifications for major and well-characterized protein domain families, as supported by available protein three-dimensional (3D) structure and the published literature. To this date, the majority of protein 3D structures are represented by models tracked by CDD, and CDD curators are characterizing novel families that emerge from protein structure determination efforts.

Effect of combined low-frequency repetitive transcranial magnetic stimulation and virtual reality training on upper limb function in subacute stroke: a double-blind randomized controlled trail.

The effect of combined low-frequency repetitive transcranial magnetic stimulation (LF rTMS) and virtual reality (VR) training in patients after stroke was assessed. In a double-blind randomized controlled trial, 112 patients with hemiplegia after stroke were randomly divided into two groups: experimental and control. In experimental group, the patients received LF rTMS and VR training treatment, and those in control group received sham rTMS and VR training treatment. Participants in both groups received therapy of 6 days per week for 4 weeks. The primary endpoint including the upper limb motor function test of Fugl-meyer assessment (U-FMA) and wolf motor function test (WMFT), and the secondary endpoint including modified Barthel index (MBI) and 36-item Short Form Health Survey Questionnaire (SF-36) were assessed before and 4 weeks after treatment. Totally, 108 subjects completed the study (55 in experimental group and 53 in control group respectively). After 4-week treatment, the U-FMA scores [mean difference of 13.2, 95% confidence interval (CI) 3.6 to 22.7, P<0.01], WMFT scores (mean difference of 2.9, 95% CI 2.7 to 12.3, P<0.01), and MBI scores (mean difference 16.1, 95% CI 3.8 to 9.4, P<0.05) were significantly increased in the experimental group as compared with the control group. The results suggested the combined use of LF rTMS with VR training could effectively improve the upper limb function, the living activity, and the quality of life in patients with hemiplegia following subacute stroke, which may provide a better rehabilitation treatment for subacute stroke.

Association of cardiopulmonary health effects with source-appointed ambient fine particulate in Beijing, China: a combined analysis from the Healthy Volunteer Natural Relocation (HVNR) study.

Previous studies have associated ambient particulate chemical constituents with adverse cardiopulmonary health effects. However, specific pollution sources behind the cardiopulmonary health effects of ambient particles are uncertain. We examined the cardiopulmonary health effects of fine particles (PM2.5) from different pollution sources in Beijing, China, among a panel of 40 healthy university students. Study subjects were repeatedly examined for a series of cardiopulmonary health indicators during three 2-month-long study periods (suburban period, urban period 1, and urban period 2) in 2010-2011 before and after relocating from a suburban campus to an urban campus with changing air pollution levels and contents. Daily ambient PM2.5 mass samples were collected over the study and measured for 29 chemical constituents in the laboratory. Source appointment for ambient PM2.5 was performed using Positive Matrix Factorization, and mixed-effects models were used to estimate the cardiopulmonary effects associated with source-specific PM2.5 concentrations. Seven PM2.5 sources were identified as traffic emissions (12.0%), coal combustion (22.0%), secondary sulfate/nitrate (30.2%), metallurgical emission (0.4%), dust/soil (12.4%), industry (6.9%), and secondary organic aerosol (9.9%). Ambient PM2.5 in the suburban campus had larger contributions from secondary sulfate/nitrate (41.8% vs. 22.9%-26.0%) and metallurgical emission (0.7% vs. 0.3%) as compared to that in the urban campus), whereas PM2.5 in the urban campus had larger contributions from traffic emissions (13.0%-16.3% vs. 5.1%), coal combustion (21.0%-30.7% vs. 10.7%), and secondary organic aerosol (9.7%-12.0% vs. 8.7%) as compared to that in the suburban campus. Potential key sources were identified for PM2.5 effects on inflammatory biomarkers (secondary sulfate/nitrate and dust/soil), blood pressure (coal combustion and metallurgical emission), and pulmonary function (dust/soil and industry). Analyses using another source appointment tool Unmix yielded a similar pattern of source contributions and associated health effects. In conclusion, ambient PM2.5 in Beijing suburban and urban areas has two distinct patterns of source contributions, and PM2.5 from different sources may play important roles on different aspects of PM2.5-related cardiopulmonary health effects.