Design, Synthesis, Biological Evaluation, and Molecular Modeling of 2-Difluoromethylbenzimidazole Derivatives as Potential PI3Kα Inhibitors.

PI3Kα is one of the potential targets for novel anticancer drugs. In this study, a series of 2-difluoromethylbenzimidazole derivatives were studied based on the combination of molecular modeling techniques 3D-QSAR, molecular docking, and molecular dynamics. The results showed that the best comparative molecular field analysis (CoMFA) model had q2 = 0.797 and r2 = 0.996 and the best comparative molecular similarity indices analysis (CoMSIA) model had q2 = 0.567 and r2 = 0.960. It was indicated that these 3D-QSAR models have good verification and excellent prediction capabilities. The binding mode of the compound 29 and 4YKN was explored using molecular docking and a molecular dynamics simulation. Ultimately, five new PI3Kα inhibitors were designed and screened by these models. Then, two of them (86, 87) were selected to be synthesized and biologically evaluated, with a satisfying result (22.8 nM for 86 and 33.6 nM for 87).

Antimicrobial activity and stability of protonectin with D-amino acid substitutions.

The misuse and overuse of antibiotics result in the emergence of resistant bacteria and fungi, which make an urgent need of the new antimicrobial agents. Nowadays, antimicrobial peptides have attracted great attention of researchers. However, the low physiological stability in biological system limits the application of naturally occurring antimicrobial peptides as novel therapeutics. In the present study, we synthesized derivatives of protonectin by substituting all the amino acid residues or the cationic lysine residue with the corresponding D-amino acids. Both the D-enantiomer of protonectin (D-prt) and D-Lys-protonectin (D-Lys-prt) exhibited strong antimicrobial activity against bacteria and fungi. Moreover, D-prt showed strong stability against trypsin, chymotrypsin and the human serum, while D-Lys-prt only showed strong stability against trypsin. Circular dichroism analysis revealed that D-Lys-prt still kept typical α-helical structure in the membrane mimicking environment, while D-prt showed left hand α-helical structure. In addition, propidium iodide uptake assay and bacteria and fungi killing experiments indicated that all D-amino acid substitution or partially D-amino acid substitution analogs could disrupt the integrity of membrane and lead the cell death. In summary, these findings suggested that D-prt and D-Lys-prt might be promising candidate antibiotic agents for therapeutic application against resistant bacteria and fungi infection. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS production in yeast cells.

Candidiasis is often observed in immunocompromised patients and is the 4th most common cause of bloodstream infections. However, antifungals are limited, so novel antifungal agents are urgently needed. Antimicrobial peptides (AMPs) are considered as potential alternatives of conventional antibiotics. In the present study, antimicrobial peptide protonectin was chemically synthesized and its antifungal activity and mode of action were studied. Our results showed that protonectin has potent antifungal activity and fungicidal activity against the tested fungi cells. Its action mode involved the disruption of the membrane integrity and the inducing of the production of cellular ROS. Furthermore, protonectin could inhibit the formation of biofilm and kill the adherent fungi cells. In conclusion, with the increase of fungal infection, protonectin may offer a new strategy and be considered as a potential therapeutic agent against fungal disease.

Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option.

Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with single oral metformin in a randomized controlled trial (RCT). METHODS: A total of 132 patients with T2DM were enrolled in the study, who only took metformin (500-1000 mg/day) for at least three months and with inadequate glycemic control (7.0% ≤ hemoglobin A1c ≤ 9.0% ) in the past three months. The patients stopped taking metformin with lifestyle interventions for three weeks, and 105 patients qualified for the program. They were randomly divided into the Sancai powder group and the metformin group (1500 mg/day). The follow-up period was for 12 weeks. Comparisons of several variables were analyzed. RESULTS: No significant differences were found between the two groups in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and 2 h post-meal glucose (2hPG), although they had decreased significantly (P < 0.01). Homeostasis model assessment of beta cell function index was significantly improved in Sancai powder group (P < 0.01), and there were significant differences in the changes of homeostasis model assessment of insulin resistance and insulin sensitivity index in the two groups (P < 0.05). Sancai powder significantly reduced triglyceride level (P < 0.05), although there was no significant difference in the body weight and body mass index in the two groups. CONCLUSION: In this 12-week study, Sancai powder could significantly reduce hemoglobin A1c, FPG and 2hPG levels, improved beta-cell function and insulin resistance of the T2DM inadequately controlled with metformin.

[Traditional Chinese Medicine Treatment of Gouty Arthritis Based on Syndrome Differentiation].

OBJECTIVE: To observe the clinical effect and safety of traditional Chinese medicine (TCM) treatment in gouty arthritis (GA) based on syndrome differentiation. METHODS: 81 patients of GA were enrolled from August 2013 to August 2014. They were divided into syndrome differentiation treatment group (27 cases), disease differentiation treatment group (27 cases) and basic treatment group (27 cases). The patients in syndrome differentiation treatment group were given corresponding TCM drug granules prescription by dialectical syndromes classification. The patients in disease differentiation treatment group were given TCM drug granules prescription. The patients in basic treatment group.were only given Diclofenac Sodium sustained-release tablets in acute phase, and Benzbromarone tablets in chronic phase. After 12 weeks treatments, all the patients received the measurements of serum uric acid (SUA), serum creatinine (SCr), blood urea nitrogen (BUN), triacylglycerol (TG), cholesterol (TC). The clinical efficacy, recurrence rate and adverse reactions were recorded and analyzed. RESULTS: Syndrome differentiation treatment group achieved higher clinical efficacy than basic treatment group and disease differentiation treatment group (P<0. 05). Moreover, syndrome differentiation treatment were superior to disease differentiation treatment in improving of recurrence rate (P<0. 05). There were no obvious adverse reactions occurred. There were no clinical significant changes in blood, urine routine analysis, and electrocardiogram examination before and 3 months after the treatments. CONCLUSION: The treatment of TCM in patients with GA based on syndrome differentiation showed definite therapeutic effects.

Causal Associations Between Gut Microbiota, Gut Microbiota-Derived Metabolites, and Alzheimer's Disease: A Multivariable Mendelian Randomization Study.

Background: Multiple studies have demonstrated that the gut microbiome is closely related to the onset of Alzheimer's disease, but the causal relationship between the gut microbiome and AD, as well as potential mediating factors, have not been fully explored. Objective: Our aim is to validate the causal relationship between the gut microbiome and the onset of AD and determine the key mechanism by which the gut microbiome mediates AD through blood metabolites using Mendelian randomization (MR) analysis methods. Methods: We first conducted bidirectional and mediating MR analyses using gut microbiota, blood amino acid metabolites, and AD-related single nucleotide polymorphisms as research data. In the analysis process, the inverse variance-weighted average method was mainly used as the primary method, with other methods serving as supplementary evidence. Results: Ultimately, we found that six types of gut bacteria and two blood amino acid metabolites have a causal effect on AD. Subsequent mediation analysis proved that decreased glutamine concentration mediates the negative causal effect of Holdemanella bacteria on AD (mediation ratio of 14.5%), and increased serum alanine concentration mediates the positive causal effect of Parabacteroide bacteria on AD (mediation ratio of 9.4%). Conclusions: Our study demonstrates the causality of Holdemanella and Parabacteroides bacteria in the onset of AD and suggests that the reduced glutamine and increased alanine serums concentration may be key nodes in mediating this effect.

Enhancement of membrane B7-H3 costimulatory molecule but reduction of its soluble form in multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system mediated by T cells. B7-H3 plays a diverse role in regulating T cell responses. However, its expression and clinical significance in MS are not well known. This study analyzed the expression of membrane B7-H3 (mB7-H3) and levels of soluble B7-H3 (sB7-H3) in MS patients to determine its clinical significance. METHODS: Peripheral blood (PB) or cerebrospinal fluid (CSF) samples from healthy controls, other noninflammatory neurological disorders, viral encephalitis, and MS patients were collected. Expression of mB7-H3 on immune cells was detected by flow cytometry. Levels of sB7-H3 in serum or CSF samples were measured by ELISA. RESULTS: mB7-H3 expression was up-regulated in CSF from MS patients compared to PB (p<0.001). However, serum or CSF levels of sB7-H3 in MS patients were significantly lower than those in controls (p<0.05). Relapsing-MS patients had higher CSF mB7-H3 expression than the remitting subgroup. Relapsing-MS patients had decreased serum and CSF sB7-H3 levels compared with the remitting subgroup. Neurological deficits showed negative correlations with serum or CSF sB7-H3 levels, but a positive correlation with CSF mB7-H3 expression. Methylprednisolone therapy significantly elevated sB7-H3 levels and reduced mB7-H3 expression compared with pre-therapy levels. sB7-H3 levels did not correlate with mB7-H3 expression. CONCLUSIONS: We demonstrated enhanced mB7-H3 expression and reduced sB7-H3 levels in MS patients which correlated with the clinical characteristics of MS patients. These results suggest that B7-H3 may be a promising biomarker and associated with the pathogenesis of MS.

The effectiveness of shockwave therapy on patellar tendinopathy, Achilles tendinopathy, and plantar fasciitis: a systematic review and meta-analysis.

Background: Tendinopathy is a growing global concern affecting many people, like athletes, workers, and the elderly. Despite its commonality among the sporting population, there is no practical clinical guideline for patellar tendinopathy (PT). Furthermore, there is conflicting evidence between clinical guidelines on shockwave therapy's application and clinical utility for Achilles tendinopathy (AT) and plantar fasciitis (PF). Thus, our aim of this study is to evaluate the evidence for shockwave therapy; to provide a Grading of Recommendation, Assessment, Development and Evaluation (GRADE) level of the evidence and effectiveness of shockwave therapy for patellar tendinopathy, Achilles tendinopathy, and Plantar fasciitis. Method: Medical Literature Analysis and Retrieval System Online (Medline), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro) and China National Knowledge Infrastructure database (CNKI) were searched to find relevant studies published before December 14th, 2022. Results: Our study showed that for PT in the short term, extracorporeal shockwave therapy (ESWT) or ESWT + eccentric exercise (EE) has a negligible effect on pain and function compared to a placebo or placebo + EE. On the contrary, ESWT significantly affects pain compared to conservative treatment (CT). For AT, ESWT has a small inconclusive effect on pain and function in the short term compared to EE. On the other hand, a placebo outperformed ESWT in improving function for AT but not pain outcomes. PF showed that ESWT significantly affects short- and long-term pain and function. When ESWT was compared to other interventions such as low laser therapy (LLLT), corticosteroid injection (CSI), or CT, there was a small inconclusive effect on pain and function in the short term. Conclusion: There is low-moderate evidence that ESWT has a negligible effect on pain and function for PT and AT. However, high-quality evidence suggests ESWT has a large effect on pain and function for PF. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396835, identifier CRD42023396835.

Tuning ice nucleation with pH-modulated Fe3+ cross-linked hydrogel surfaces.

Ice nucleation plays a vital function in various fields. In this study, we prepared hydrogel surfaces with different cross-linkages by pH-modulating the coordination pattern of Fe3+ and catechol. We found that the ice nucleation temperature decreases with increasing cross-linkages. Further analysis shows that the hydrogel surfaces with different cross-linking degrees could achieve the regulation of ice nucleation by modulating the interfacial water. Our study elucidates the mechanism of ice nucleation regulated by interfacial water in soft matter and proposes a new method for preparing ice nucleation-regulated material.

[Retracted] Astragaloside IV inhibits oxidized low­density lipoprotein­induced endothelial damage via upregulation of miR­140­3p.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the ß­actin control western blotting data featured in Fig. 3E were strikingly similar to data appearing in different form in another article by different authors. Upon asking the authors to explain this phenomenon, they were unable to provide the raw data for this experiment. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 847­856, 2019; DOI: 10.3892/ijmm.2019.4257].

Effects of strength training on functional ambulation following knee replacement: a systematic review, meta-analysis, and meta-regression.

Strength training is recommended by the American Physical Therapy Association to improve muscle strength, mobility, and balance following knee replacement. Few studies have focused on the direct effects of strength training on functional ambulation, and potential dose-response relationships between strength training parameters and the effect remain unclear. The aim of this systematic review, meta-analysis, and meta-regression was to evaluate the effects of strength training on functional ambulation following knee replacement (KR). We also aimed to explore potential dose-response relationships between strength training parameters and performance in functional ambulation. A systematic literature search of eight online databases was performed on March 12, 2023, for randomized controlled trials evaluating the effects of strength training on functional ambulation by six-minute walk test (6MWT) or timed-up and go test (TUG) after KR. Data were pooled by random-effect meta-analyses and presented as weighted mean difference (WMD). A random-effect meta-regression was performed for four predetermined training parameters, namely, duration (weeks), frequency (sessions per week), volume (time per session), and initial time (after surgery) separately to explore dose-response relationships with WMD. Fourteen trials encompassing 956 participants were included in our study. Meta-analyses showed an improvement in 6MWT performance after strength training (WMD: 32.15, 95% CI 19.44-44.85) and a decrease in time to complete TUG (WMD: - 1.92, 95% CI - 3.43 to - 0.41). Meta-regression revealed a dose-response relationship only between volume and 6MWT, with a decreasing trend (P = 0.019, 95% CI - 1.63 to - 0.20). Increasing trends of improvement in 6MWT and TUG were observed with increasing training duration and frequency. A slight decreasing trend of improvement was observed in 6MWT with postponed initial time, while an opposite trend was observed in TUG. Based on existing studies, moderate-certainty evidence suggests that strength training could increase 6MWT distance, and low-certainty evidence shows that strength training could decrease the time to complete TUG after KR. Meta-regression results only suggested a dose-response relationship between volume and 6MWT with a decreasing trend.Registration: PROSPERO: CRD42022329006.

High-quality genome of a pioneer mangrove Laguncularia racemosa explains its advantages for intertidal zone reforestation.

Ecological restoration of mangrove ecosystems that became susceptible to recent habitat perturbations is crucial for tropical coast conservation. The white mangrove Laguncularia racemosa, a pioneer species inhabiting intertidal environments of the Atlantic East Pacific (AEP) region, has been used for reforestation in China for decades. However, the molecular mechanisms underlying its fast growth and high adaptive potential remain unknown. Using PacBio single-molecule real-time sequencing, we completed a high-quality L. racemosa genome assembly covering 1105 Mb with scaffold N50 of 3.46 Mb. Genomic phylogeny shows that L. racemosa invaded intertidal zones during a period of global warming. Multi-level genomic convergence analyses between L. racemosa and three native dominant mangrove clades show that they experienced convergent changes in genes involved in nutrient absorption and high salinity tolerance. This may explain successful L. racemosa adaptation to stressful intertidal environments after introduction. Without recent whole-genome duplications or activated transposable elements, L. racemosa has retained many tandem gene duplications. Some of them are involved in auxin biosynthesis, intense light stress and cold stress response pathways, associated with L. racemosa's ability to grow fast under high light or cold conditions when used for reforestation. In summary, our study identifies shared mechanisms of intertidal environmental adaptation and unique genetic changes underlying fast growth in mangrove-unfavourable conditions and sheds light on the molecular mechanisms of the white mangrove utility in ecological restoration.

Exosomes in malignant pleural effusion from lung cancer patients impaired the cytotoxicity of double-negative T cells.

CD3+CD4-CD8- double-negative T (DNT) cells are new weapons in cancer immunotherapy. Here, we explored DNT cells in malignant pleural effusions (MPEs) from lung cancer patients. DNT cells, especially TCRαß+CD56- DNT cells, were increased in MPE from lung cancer patients. DNT cells highly expressed PD-1, TRAIL, NKG2D and DNAM-1. In contrast, FasL was barely detected in DNT cells. Compared with non-MPE cells, MPE-derived DNT cells expressed much higher levels of PD-1 and TRAIL. DNT cells from healthy peripheral blood donors potentially killed lung cancers, which was decreased by MPE supernatant. Exosomes from MPE supernatant expressed PD-1 and CEACAM1 and impaired the cytotoxicity of DNT cells. Blocking PD-1 and TIM3 rescued the cytotoxicity of DNT cells treated with MPE-derived exosomes. Overall, we demonstrated that the frequency of DNT cells in MPE from lung cancer patients was increased and that MPE-derived exosomes impaired the cytotoxicity of DNT cells via the PD-1/PD-L1 and CEACAM1/TIM3 pathways.

World Health Organization survey on the level of integration of traditional Chinese medicine in Chinese health system rehabilitation services.

Background: To meet the growing global demand for rehabilitation services, the World Health Organization (WHO) launched Rehabilitation 2030. This study was commissioned by the WHO to investigate the integration degree of traditional Chinese medicine (TCM) in Chinese health system rehabilitation services and the demand for TCM rehabilitation in China. Methods: Twenty TCM rehabilitation experts and relevant government administrators were invited to complete the questionnaire between September 2019 and January 2022. The development of traditional, complementary, and integrative medicine (TCI) rehabilitation in China was assessed primarily based on six different health system components. Results: 26 policies, regulations, and national strategic plans related to TCI rehabilitation were issued by relevant government departments since 2002; notably, 14 policies related to TCI rehabilitation development were intensively introduced from 2016 to 2021. These policies cover the three main areas of financing, infrastructure development, and service delivery. The National Administration of Traditional Chinese Medicine's investment in TCM clinical capacity infrastructure and scientific research in 2019-2021 increased by 66% compared to 2010-2012, and the average number of TCM hospitals with rehabilitation departments in 2020 increased by 6.5% compared to 2018. The proportion of community health service centers providing TCM services in primary medical and health institutions has increased by 30.8% over the past 10 years. Conclusion: Long-term continuous policies, substantial financial investment, and expansion of the scope of TCI rehabilitation services in primary care institutions have effectively contributed to the rapid development of TCI rehabilitation. However, human resources and financing mechanisms for TCI rehabilitation need further improvement.

Bending modulus of the rippled graphene: the role of thickness.

Bending modulus is a key parameter to characterize the stiffness of materials. Commonly, it is believed that the bending modulus is closely related to the thickness as described by the thin plate theory. However, the thin plate theory fails in multilayer van der Waals materials like multilayer graphene, suggesting a more complex relationship between the bending modulus and thickness. Here, rippled graphene structures containing non-hexagonal carbon rings with different thicknesses are constructed to study the thickness-dependent bending modulus by the first-principles calculations. It is found that the bending modulus of rippled graphene depends on several factors, such as geometry, bending curvature, and thickness. Particularly, for the egg-tray graphene structures with similar structural pattern and bending curvature, i.e., eliminating the effects of structural pattern and bending curvature, the bending modulus could show a linear relationship to the thickness. Moreover, this linear relationship is very robust even in the case of changing the thickness through heteroatom doping.

Traditional Chinese Medicine and Sarcopenia: A Systematic Review.

Sarcopenia has become a key challenge for healthy aging in older adults. However, it remains unclear whether traditional Chinese medicine can effectively treat sarcopenia. This systematic review analyzes the current evidence for the effect of traditional Chinese medicine (TCM) on sarcopenia. We searched for articles regarding sarcopenia treated by TCM in Cochrane library, PubMed, SinoMed, Web of Science, Embase, and the China National Knowledge Infrastructure (from inception until 10 December 2021). Two researchers independently screened the literature in accordance with the inclusion and exclusion criteria designed by PICOS principles. The risk of bias was assessed by the Cochrane Risk of Bias (ROB) tool. The quality of evidence was assessed by the grading of recommendations, assessment, development, and evaluation (GRADE). Participants' characteristics, interventions, and the relevant results of the included studies were extracted and synthesized in a narrative way. The total number of participants in the 21 included studies was 1,330. Most of the studies evaluated physical function (n = 20) and muscle strength (n = 18), and a small number of studies (n = 6) assessed muscle mass. Overall, it was found that TCM had a positive impact on muscle strength (grip strength, chair stand test) and physical function (6-m walking speed, timed up and go test, sit and reach) in patients with sarcopenia, inconsistent evidence of effects on muscle mass. However, the small sample size of the included studies led to imprecision in the results, and the presence of blinding of the studies, allocation concealment, and unreasonable problems with the control group design made the results low grade. Among these results, the quality of evidence for grip strength (n = 10) was of medium grade, and the quality of evidence related to the remaining indicators was of low grade. This systematic review showed that traditional Chinese Qigong exercises and Chinese herbal medicine have a positive and important effect on physical performance and muscle strength in older adults with sarcopenia. Future high-quality multicenter randomized controlled trials (RCTs) with large samples are needed to determinate whether acupuncture and other therapies are effective in treating sarcopenia.

MiR-181c sensitizes ovarian cancer cells to paclitaxel by targeting GRP78 through the PI3K/Akt pathway.

Primary cytoreductive surgery with platinum-taxane-based chemotherapy is the standard treatment for ovarian cancer (OC) patients; however, resistance to chemotherapy is a contributing factor to OC mortality. Paclitaxel (PTX), the most widely used taxane, has become the first-line drug against OC. The molecular mechanism of PTX resistance is different from that of platinum-based agents and is still not completely elucidated. Our previous study showed that glucose-regulated protein 78 (GRP78) is involved in the resistance of OC cells to PTX. However, little is known regarding endogenous inhibitors of this gene. MicroRNAs (miRNAs) play critical roles in the regulation of gene expression; therefore, we sought to identify miRNA(s) with potential to target GRP78 under the hypothesis that miRNA(s) could serve as potential therapeutic targets. Here, we show that miR-181c, predicted to target GRP78, was downregulated in PTX-resistant OC cells and tissues. MiR-181c downregulated GRP78 expression and induced apoptosis by directly targeting its 3'-untranslated region (UTR). Overexpression of miR-181c sensitized resistant OC to PTX by inhibiting the PI3K/Akt pathway in vitro and in vivo. Taken together, our findings indicate that the delivery of miR-181c can efficiently suppress GRP78 expression and GRP78-mediated PTX resistance in OC and suggest that this strategy has therapeutic potential.

Ditangquan exercises based on safe-landing strategies prevent falls and injury among older individuals with sarcopenia.

Background: Sarcopenia is the age-related loss of skeletal muscle mass and function; it is a risk factor for falls among older individuals. Few studies have focused on training such individuals to adopt a safe-landing strategy that would protect them from fall-related injuries. Ditangquan is a traditional Chinese martial art comprising movements that conform to the principles of safe landing. This study aims to investigate the effectiveness of Ditangquan in preventing fall-related injuries among older individuals with sarcopenia. Methods: A total of 70 participants (21 males and 49 females with sarcopenia) between 60 and 80 years of age were recruited from three local communities and randomly assigned to the Ditangquan exercise group (DG) or the control group (CG) in a 1:1 ratio. Three times a week for 24 weeks, both the DG and CG received an hour of conventional exercise and an hour of Ditangquan exercise based on safe landing. Primary outcomes were the modified falls efficacy scale (MFES), the number of falls, and fall injuries; the secondary outcome was the Timed Up & Go (TUG) test. Results: The DG had significantly fewer falls (1 vs. 8, P = 0.028) and fall injuries (0 vs. 6, P = 0.025) than the CG. Furthermore, at the end of the study, the DG had a significantly improved MFES (mean difference: 32.17 scores; 95% CI: 21.32, 43.02; P <0.001) and TUGT (mean difference: -4.94 s; 95% CI: -7.95, -1.93; P = 0.002) as compared with the CG. Conclusion: Ditangquan exercise based on the safe-landing strategy effectively improves the functional mobility of the elderly, reduces the occurrence of falls and injuries, and increases the individual's confidence in preventing falls.

Genome-Wide Characterization and Expression Analysis of the HD-ZIP Gene Family in Response to Salt Stress in Pepper.

HD-ZIP is a unique type of transcription factor in plants, which are closely linked to the regulation of plant growth and development, the response to abiotic stress, and disease resistance. However, there is little known about the HD-ZIP gene family of pepper. In this study, 40 HD-ZIP family members were analyzed in the pepper genome. The analysis indicated that the introns number of Ca-HD-ZIP varied from 1 to 17; the number of amino acids was between 119 and 841; the theoretical isoelectric point was between 4.54 and 9.85; the molecular weight was between 14.04 and 92.56; most of them were unstable proteins. The phylogenetic tree divided CaHD-ZIP into 4 subfamilies; 40 CaHD-ZIP genes were located on different chromosomes, and all of them contained the motif 1; two pairs of CaHD-ZIP parallel genes of six paralogism genes were fragment duplications which occurred in 58.28~88.24 million years ago. There were multiple pressure-related action elements upstream of the start codon of the HD-Z-IP family. Protein interaction network proved to be coexpression phenomenon between ATML1 (CaH-DZ22, CaHDZ32) and At4g048909 (CaHDZ12, CaHDZ31), and three regions of them were highly homology. The expression level of CaHD-ZIP gene was different with tissues and developmental stages, which suggested that CaHD-ZIP may be involved in biological functions during pepper progress. In addition, Pepper HD-ZIP I and II genes played a major role in salt stress. CaHDZ03, CaHDZ 10, CaHDZ17, CaHDZ25, CaHDZ34, and CaHDZ35 were significantly induced in response to salt stress. Notably, the expression of CaHDZ07, CaHDZ17, CaHDZ26, and CaHDZ30, homologs of Arabidopsis AtHB12 and AtHB7 genes, was significantly upregulated by salt stresses. CaHDZ03 possesses two closely linked ABA action elements, and its expression level increased significantly at 4 h under salt stress. qRT-P-CR and transcription analysis showed that the expression of CaHDZ03 and CaHDZ10 was upregulated under short-term salt stress, but CaHDZ10 was downregulated with long-term salt stress, which provided a theoretical basis for research the function of Ca-HDZIP in response to abiotic stress.