The amino acid sensor MetRS is required for methionine-induced milk protein synthesis in a domestic pigeon model.

This study was conducted to investigate whether methionyl-tRNA synthetase (MetRS) is a mediator of Met-induced crop milk protein synthesis via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signalling pathway in breeding pigeons. In Experiment 1, a total of 216 pairs of breeding pigeons were divided into 3 groups (control, Met-deficient, and Met-rescue groups). In Experiments 2 and 3, forty pairs of breeding pigeons from each experiment were allocated into 4 groups. The 2nd experiment included a control group and 3 MetRS inhibitor (REP8839) groups. The 3rd experiment included a Met-deficient group, Met-sufficient group, REP8839 + Met-deficient group, and REP8839 + Met-sufficient group. Experiment 1 showed that Met supplementation increased crop development, crop milk protein synthesis, the protein expression of MetRS and JAK2/STAT5 signalling pathway, and improved squab growth. Experiment 2 showed that crop development, crop milk protein synthesis, and the protein expression of MetRS and the JAK2/STAT5 signalling pathway were decreased, and squab growth was inhibited by the injection of 1.0 mg/kg BW REP8839, which was the selected dose for the 3rd experiment. These results showed that Met supplementation increased crop development, crop milk protein synthesis, and the expression of MetRS and JAK2/STAT5 signalling pathway and rescued squab growth after the injection of REP8839. Moreover, the Co-IP results showed that there was an interaction between MetRS and JAK2. Taken together, these findings indicate that MetRS mediates Met-induced crop milk protein synthesis via the JAK2/STAT5 signalling pathway, resulting in improved squab growth in breeding pigeons.

Injectable self-assembled GDF5-containing dipeptide hydrogels for enhanced tendon repair.

Owing to the tissue characteristics of tendons with few blood vessels and cells, the regeneration and repair of injured tendons can present a considerable challenge, which considerably affects the motor function of limbs and leads to serious physical and mental pain, along with an economic burden on patients. Herein, we designed and fabricated a dipeptide hydrogel (DPH) using polypeptides P11-4 and P11-8. This hydrogel exhibited self-assembly characteristics and could be administered in vitro. To endow the hydrogel with differentiation and regeneration abilities, we added different concentrations of growth differentiation factor 5 (GDF5) to form GDF5@DPH. GDF5@DPH promoted the aggregation and differentiation of tendon stem/progenitor cells and promoted the regeneration and repair of tendon cells and collagen fibers in injured areas. In addition, GDF5@DPH inhibited inflammatory reactions in the injured area. Owing to its injectable properties, DPH can jointly inhibit adhesion and scar hyperplasia between tissues caused by endogenous inflammation and exogenous surgery and can provide a favorable internal environment for the regeneration and repair of the injured area. Overall, the GDF5@DPH system exhibits considerable promise as a novel approach to treating tendon injury.

Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging.

Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with aging. Currently, aging biomarkers are primarily categorized into physiological traits, imaging characteristics, histological features, cellular-level alterations, and molecular-level changes that encompass the secretion of aging-related factors. However, in the context of the musculoskeletal soft tissue system, aging-related biological indicators primarily involve microscopic parameters at the cellular and molecular levels, resulting in inconvenience and uncertainty in the assessment of musculoskeletal soft tissue aging. To identify convenient and effective indicators, we conducted a comprehensive literature review to investigate the correlation between ectopic mineralization and age-related changes in the musculoskeletal soft tissue system. Here, we introduce the concept of ectopic mineralization as a macroscopic, reliable, and convenient biomarker for musculoskeletal soft tissue aging and present novel targets and strategies for the future management of age-related musculoskeletal soft tissue disorders.

Spatial separation of nitrifiers and denitrifiers promotes selection and enrichment of polyhydroxyalkanoates storing mixed cultures fed by crude glycerol and propionate wastewater.

Polyhydroxyalkanoates (PHA) recovery from industrial wastewater has been highlighted as a promising strategy for a circular bioeconomy. However, the high and varying level of nitrogen in wastewater makes enrichment of mixed microbial culture (MMC) low efficiency. In this study, spatial separation of nitrifiers and denitrifiers was adopted by adding biocarriers in MMC and decreasing the sludge retention time (SRT) to accelerate the enrichment of PHA-storing MMC fed by mixed wastewater containing glycerol and propionate. Nitrifiers and denitrifiers were sustained on biocarriers, obtaining a high total inorganic nitrogen removal and allowing a more efficient selective pressure of a high carbon and nitrogen ratio (C/N) under low SRT conditions. The maximum PHA cell content and relative abundance of PHA-storing bacteria were increased to 60.51 % (SRT 6 d) and 49.62 % (SRT 6 d) with the decrease of SRT, respectively. This study demonstrates an efficient way to highly enrich PHA-storing MMC from crude glycerol, which provide a relevant technical support for high-efficiency enrichment of PHA-storing bacteria in low C/N wastewater.

The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis.

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

Targeting Senescent Tendon Stem/Progenitor Cells to Prevent or Treat Age-Related Tendon Disorders.

Age-related tendon disorder, a primary motor system disease, is characterized by biological changes in the tendon tissue due to senescence and seriously affects the quality of life of the elderly. The pathogenesis of this disease is not well-understood. Tendon stem/progenitor cells (TSPCs) exhibit multi-differentiation capacity. These cells are important cellular components of the tendon because of their roles in tendon tissue homeostasis, remodeling, and repair. Previous studies revealed alterations in the biological characteristics and tenogenic differentiation potential of TSPCs in senescent tendon tissue, in turn contributing to insufficient differentiation of TSPCs into tenocytes. Poor tendon repair can result in age-related tendinopathies. Therefore, targeting of senescent TSPCs may restore the tenogenic differentiation potential of these cells and achieve homeostasis of the tendon tissue to prevent or treat age-related tendinopathy. In this review, we summarize the biological characteristics of TSPCs and histopathological changes in age-related tendinopathy, as well as the potential mechanisms through which TSPCs contribute to senescence. This information may promote further exploration of innovative treatment strategies to rescue TSPCs from senescence.

Short report: relationship between self-reported sleep characteristics and falls-associated fractures in elderly individuals: a population-based study.

Currently, the data for effect of sleep on falls-associated fractures in elderly individuals are still limited. This current study was aimed to assess the link between self-reported sleep characteristics and falls-associated fractures in elderly individuals. This study included a total of 20,497 participants from National Health and Nutritional Examination Survey (NHANES) 2005-2008, and 6,174 participants aged 45 years and older were identified. Self-reported sleep characteristics and conditions of falls-associated fractures of individuals were obtained via the method of personal questionnaires. In a total of 610 participants with exact history of fractures, 168 individuals with falls-associated fractures were identified, and the prevalence was 27.5%. The mean age of falls-associated fractures group was (72.1 ± 8.8) years, and the female (P < 0.001) occupied a higher proportion. Factors of living alone (P = 0.003), combined with hypertension (P = 0.003) and osteoporosis (P < 0.001), sleeping less or more (P = 0.009), and frequent snoring (P = 0.007) were linked to falls-associated fractures. Compared with sleep duration of 6 to 8 h/night, sleep duration of ≤4 h/night (odds ratio [OR] 1.858, 95% confidence interval [CI] 1.115-3.094) and of ≥9 h/night (OR 1.932, 95% CI 1.195-3.123) were related to an increased risk of falls-associated fractures. Collectively, our nationwide data noted that sleep characteristics were closely related to falls-associated fractures in elderly individuals, and a longer sleep duration may exhibit a protective effect against the falls-associated fractures, but it should be limited within 9 h/night.

Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function.

Background: Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce. Methods: In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics. Results: Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid). Conclusions: Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future. The translational potential of this article: This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among nurses.

BACKGROUND: The standard of care provided to patients with chronic epilepsy might be affected by clinical nurses' understanding, awareness, and attitudes toward the condition. The objective of this study was to assess the knowledge, awareness, and attitudes toward chronic epilepsy among clinical nurses in the Second Affiliated Hospital of Zhejiang University School of Medicine, China. METHODS: Two hundred and thirty-eight nurses from the neurosurgery, neurology, epilepsy center, other internal medicine and other surgery department working at our hospital participated in this descriptive and cross-sectional study in 2022. The data were collected through an electronic questionnaire, which comprised four domains including demographic and clinical epilepsy-related questions, awareness of epilepsy section, 18 items for knowledge and a 15-item scale for attitudes. Mann-Whitney U tests, Kruskal-Wallis H tests, post hoc analysis, Pearson correlation analysis, and descriptive statistics were used to analyze the non-normal distribution of the dataset. RESULTS: The clinical nurses' average score on the awareness of epilepsy section was 14.93 ± 2.69 (maximum score: 20), the knowledge of epilepsy section scored 15.41 ± 2.30 (maximum score: 18), and the epilepsy attitude section scored 30.65 ± 7.40. The knowledge and awareness accuracy of the responses to the epilepsy-related questions were positively and significantly correlated (r = 0.251, p < 0.001). The multiple linear regression model found that the department (p < 0.001) and rank (p = 0.015) of nurses were independently associated with awareness toward epilepsy. Meanwhile, there was a statistically significant difference between the departments of nurses and accuracy on the Epilepsy Knowledge Scale (H = 18.340, p < 0.001). In addition, 92.77% of nurses agreed that people with chronic epilepsy have the same rights as all people. Unfortunately, over 30% of nurses maintained an uncertain attitude toward the employment, marriage, and emotion related to epilepsy. CONCLUSION: Our findings revealed that nurses had a general awareness and understanding of epilepsy, attitudes toward epilepsy. Specifically, nurses working in the Neurology Department and the Epilepsy Center were predisposed to have a considerably better level of awareness and knowledge of epilepsy. Additionally, as their understanding of epilepsy grew, so did their sensitivity to those who suffer from the condition. The study also recommends that epilepsy experts deliver additional lectures and training sessions to enhance nurses' knowledge of first-aid for seizures.

3D Mapping of the Lateral Malleolus Fractures for Predicting Syndesmotic Injuries in Supination External Rotation Type Ankle Fractures.

Supination external rotation (SER) type ankle fracture is the most common ankle fracture in the Lauge-Hansen classification and is often accompanied with syndesmotic injury. However, the mechanism of this injury is indistinct and a suggestive role can be given by preoperative imaging. This study was to preoperatively predict whether SER type ankle fractures are accompanied with syndesmotic injuries by the means of lateral malleolus fracture mapping. One hundred and forty-eight patients diagnosed with SER type ankle fractures were retrospectively enrolled in this study. The baseline data were collected and computed tomography data were reconstructed in 3-dimensional (3D) model. Patients were divided into stable and unstable groups according to intraoperative Cotton test and whether the inferior tibiofibular screw was placed. All fracture lines were superimposed on the ankle template to create a fracture map, and the data on the fracture map were further measured. Logistic regression was conducted to identify relevant factors and the cutoff values were given using receiver operating characteristic curves. Forty-one patients were enrolled in the unstable group and 107 patients were enrolled in the stable group. The lateral malleolus fracture lines of the unstable group were higher and steeper than that in the stable group on lateral and posterior views. The fracture height of the posterior cortex and peak height were the significant contributing factors, and the cut-off values of posterior cortex, peak height and inclination angle were 40.35 mm (sensitivity: 78%, specificity: 82%), 55.34 mm (sensitivity: 85%, specificity: 70%) and 55.6° (sensitivity: 66%, specificity: 86%), respectively. In general, when the fracture lines of the lateral malleolus were high and steep, it was usually indicative of a syndesmotic injury and can be predicted by the preoperative 3D reconstruction of fracture height of posterior cortex, peak height and inclination angle. If the cut-off values of these indicators are exceeded, the syndesmotic injuries may be presented and need to be verified in the intraoperative Cotton test to decide whether to insert an inferior tibiofibular screw.

Advanced glycation end productions and tendon stem/progenitor cells in pathogenesis of diabetic tendinopathy.

Tendinopathy is a challenging complication observed in patients with diabetes mellitus. Tendinopathy usually leads to chronic pain, limited joint motion, and even ruptured tendons. Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes, including disorganized arrangement of collagen fibers, microtears, calcium nodules, and advanced glycation end product (AGE) deposition. Tendon-derived stem/ progenitor cells (TSPCs) were found to maintain hemostasis and to participate in the reversal of tendinopathy. We also discovered the aberrant osteochondrogenesis of TSPCs in vitro. However, the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear. In this review, we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.

Low dietary choline intake is associated with the risk of osteoporosis in elderly individuals: a population-based study.

Currently, little is known regarding the association between dietary choline intake and osteoporosis in elderly individuals, as well as if such intakes affect bone health and result in fractures. This study was aimed to examine associations between daily dietary choline intake and osteoporosis in elderly individuals. A total of 31 034 participants from the National Health and Nutritional Examination Survey (NHANES) during 2005-2010 were enrolled, and 3179 participants with complete data and aged 65 years and older were identified. Baseline characteristics and dietary intake data were obtained through method of in-home administered questionnaires. Of 3179 individuals with a mean age of 73.7 ± 5.6 years, female (P < 0.001) and non-hispanic white (P < 0.001) occupied a higher proportion in the osteoporosis group. The logistic regression analysis indicated that the prevalence of osteoporosis in three tertile categories with gradually enhanced dietary choline intake was decreased progressively (P for trend <0.001). The restricted cubic spline (RCS) showed that the risk of osteoporosis generally decreased with increasing daily dietary choline intake (P < 0.001), while this trend was not apparent in relation between the daily dietary choline intake and risk of hip fracture (P = 0.592). The receiver operating characteristic (ROC) analysis identified a daily dietary choline intake of 232.1 mg as the optimal cutoff value for predicting osteoporosis. Our nationwide data suggested that a lower level of daily dietary choline intake was positively associated with the increased risk of osteoporosis in the US elderly population.

The modulatory effect and implication of gut microbiota on osteoporosis: from the perspective of "brain-gut-bone" axis.

Osteoporosis (OP) is a kind of systemic metabolic disease characterized by decreased bone mass and destruction of the bone microstructure. In recent years, it has become an expected research trend to explore the cross-linking relationship in the pathogenesis process of OP so as to develop reasonable and effective intervention strategies. With the further development of intestinal microbiology and the profound exploration of the gut microbiota (GM), it has been further revealed that the "brain-gut" axis may be a potential target for the bone, thereby affecting the occurrence and progression of OP. Hence, based on the concept of "brain-gut-bone" axis, we look forward to deeply discussing and summarizing the cross-linking relationship of OP in the next three parts, including the "brain-bone" connection, "gut-bone" connection, and "brain-gut" connection, so as to provide an emerging thought for the prevention strategies and mechanism researches of OP.

Prevalence, Characteristics, and Associated Risk Factors of the Elderly with Hip Fractures: A Cross-Sectional Analysis of NHANES 2005-2010.

OBJECTIVE: This cross-sectional study was aimed to update the assessment of prevalence, characteristics, and risk factors of the elderly with hip fractures in a non-institutionalized American population. METHODS: This current study included a total of 31,034 participants from the existing National Health and Nutritional Examination Survey (NHANES) database from 2005 to 2010, and 4,265 participants aged 65 years and older were ultimately identified. Their condition of hip fractures was determined by method of questionnaires according to the orthopedic surgeons' diagnosis, and related epidemiological and demographic data were further collected. The univariate analysis was used to screen the risk factors of hip fractures in the elderly, and the logistic regression model was established to conduct the multivariate analysis. RESULTS: Of the total 4,265 participants with clear information of hip fractures in elderly, 127 individuals with hip fractures were identified according to results of questionnaires, exhibiting a prevalence of 28.49 per 1,000 (95% confidence interval [CI]=21.38-35.60) for males and 31.03 per 1,000 (95% CI=23.72-38.35) for females. The mean age of the elderly with hip fractures was 77.12±5.88 years and tumble (48.0%) was the primary factor. In univariate analysis, age, race, smoking, drinking alcohol, and combined with osteoporosis were regarded as risk factors. Multivariate analysis showed that age (80 years and older), living alone, smoking, combined with diabetes and osteoporosis were the independent risk factors. CONCLUSION: Our nationwide data indicate the prevalence of hip fractures in the elderly is generally on the rise, and the female occupies a higher proportion. Age (especially aged 80 years and older), race (mainly Non-Hispanic white), smoking, drinking alcohol, living alone, combined with diabetes and osteoporosis may be closely linked to the occurrence of hip fractures in the elderly, although these variables still need to be verified in further prospective investigations.

Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy.

There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus. Diabetic tendinopathy is an important cause of chronic pain, restricted activity, and even tendon rupture in individuals. Tenocytes and tendon stem/progenitor cells (TSPCs) are the dominant cellular components associated with tendon homeostasis, maintenance, remodeling, and repair. Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy. In this review, the biomechanical properties and histopathological changes in diabetic tendons are described. Then, the cellular and molecular alterations in both tenocytes and TSPCs are summarized, and the underlying mechanisms involved are also analyzed. A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.

Tendon stem/progenitor cell ageing: Modulation and rejuvenation.

Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.

[The Anti-virus Effect of AY358935 Gene on Vesicular Stomatitis Virus and the Mechanism Study].

OBJECTIVE: To explore the anti-virus effect of AY358935 gene cloned by our research team on vesicular stomatitis virus (VSV), and studytheanti-virus mechanism. METHODS: HEK293 cells were stably transfected by the AY358935 gene recombinant plasmid pcDNA3.1-AY358935 or pcDNA3.1 blank plasmid respectively. Then VSV was added into the cell wells to infect the above cells at the multiplicity of infection (MOI) of 0.001. The virus titers in the liquid supernatant of the above three groups of cells were detected on different time, and the mortality of cells of each group was tested with trypan blue exclusion test at 24 h post VSV infection. Total RNA was extracted from the cells that stably transfected with target gene for the whole genome-wide cDNA microarray analysis. RESULTS: ① Virus titer:The virus titer in the liquid supernatant of pcDNA-3.1-AY358935 transfection cells group was obviously lower than those in pcDNA-3.1 transfection cell group and blank control cell group at 12 h post infection. The virus titerin the liquid supernatant of three groups were (7.16±2.33)×105 PFU/mL, (6.25±2.05)×106 PFU/mL and (7.75±2.54)×106 PFU/mL respectively at 18 h post infection. At that time, the virus titerin the liquid supernatant of pcDNA3.1-AY358935 group was nearly 10 times lower than those of other two groups (P < 0.01). ②Mortality of cells:The cell mortality of pcDNA3.1-AY358935 group, pcDNA3.1 group and blank group were (35.00±6.68)%, (78.33±15.03)% and (83.34±14.98)% respectively at 24 h post infection.The cell mortality of pcDNA3.1-AY358935 group was significantly decreased comparing with other two groups (P < 0.01). ③Result of genes chip analysis: compared with pcDNA3.1 group, 30 cell genes were up-regulated by more than 3 times in pcDNA3.1-AY358935 group. Among them, the proportion of interferon-activating gene, interferon-effect gene, cytokine and chemokine was 27%, 17%, and 20%, respectively. CONCLUSION: AY358935 gene hasan anti-VSV effect, and its anti-virus mechanism may involve the interferon-associated natural immune response.

[Cohort Study of EGFR-TKIs Combined with Traditional Chinese Medicine and Single EGFR-TKIs for Advanced NSCLC (Non₋small Cell Lung Cancer)].

OBJECTIVE: To explore the curative effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) combined with Traditional Chinese Medicine (TCM) versus single EGFR-TKIs for Advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 59 NSCLC patients with EGFR mutation were divided (2:1) into treatment group and control group. Patients in treatment group (39 cases) take EGFR-TKIs plus TCM and control group (20 cases) take EGFR-TKIs. Analysis the progression-free survival (PFS), disease control rate (DCR) and treatment-related adverse events of two groups. RESULTS: The DCR of the treatment group and control group was 94.1% and 84.2% respectively (P=0.24). In the total population, PFS was 12.1 months in treatment group and 9.1 months in control group [hazard ratio (HR) 0.46; 95%CI 0.23-0.9; P=0.025]. Among patients with exon 19 deletion (19-del), PFS between treatment group and control group was 10.5 months and 9.5 months respectively (P=0.17). For patients with exon Leu858Arg point mutation (L858R), PFS was significantly longer with treatment group than withcontrol group (median 13.2 months vs. 7.8 months; HR 0.32, 95%CI 0.10-0.97; P=0.046). Grade 3-4 treatment-related adverse events were less common withtreatment-group (8.33 %) than control group (15.00%) (P=0.65). CONCLUSION: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM has a certain effect to prolong PFS, especially for the patients with L858R.

Wheat Bax Inhibitor-1 interacts with TaFKBP62 and mediates response to heat stress.

BACKGROUND: Heat stress is a severe environmental stress that affects plant growth and reduces yield. Bax inhibitor-1 (BI-1) is a cytoprotective protein that is involved in the response to biotic and abiotic stresses. The Arabidopsis (Arabidopsis thaliana) BI-1 mutants atbi1-1 and atbi1-2 are hypersensitive to heat stress, and AtBI-1 overexpression rescues thermotolerance deficiency in atbi1 plants. Nevertheless, the mechanism of BI-1 in plant thermotolerance is still unclear. RESULTS: We identified a wheat (Triticum aestivum L.) BI-1 gene, TaBI-1.1, which was highly upregulated in an RNA sequencing (RNA-seq) analysis of heat-treated wheat. The upregulation of TaBI-1.1 under heat stress was further demonstrated by real time quantitative PCR (qRT-PCR) and ß-glucuronidase (GUS) staining. Compared with the wild type Col-0, the atbi1-2 mutant is hypersensitive to heat stress, and constitutive expression of TaBI-1.1 in atbi1-2 (35S::TaBI-1.1/ atbi1-2) rescued the deficiency of atbi1-2 under heat stress. Furthermore, we identified TaFKBP62 as a TaBI-1.1-interacting protein that co-localized with TaBI-1.1 on the endoplasmic reticulum (ER) membrane and enhanced heat stress tolerance. Additionally, HSFA2, HSFB1, ROF1, HSP17.4B, HSP17.6A, HSP17.8, HSP70B, and HSP90.1 expression levels were suppressed in atbi1-2 plants under heat stress. In contrast, 35S::TaBI-1.1/atbi1-2 relieved the inhibitory effect of AtBI-1 loss of function. CONCLUSIONS: TaBI-1.1 interacted with TaFKBP62 and co-localized with TaFKBP62 on the ER membrane. Both TaBI-1.1 and AtBI-1 regulated the expression of heat-responsive genes and were conserved in plant thermotolerance.

The Wheat Bax Inhibitor-1 Protein Interacts with an Aquaporin TaPIP1 and Enhances Disease Resistance in Arabidopsis.

Bax inhibitor-1 (BI-1) is an endoplasmic reticulum (ER)-resident cell death suppressor evolutionarily conserved in eukaryotes. The ability of BI-1 to inhibit the biotic and abiotic stresses have been well-studied in Arabidopsis, while the functions of wheat BI-1 are largely unknown. In this study, the wheat BI-1 gene TaBI-1.1 was isolated by an RNA-seq analysis of Fusarium graminearum (Fg)-treated wheat. TaBI-1.1 expression was induced by a salicylic acid (SA) treatment and down-regulated by an abscisic acid (ABA) treatment. Based on ß-glucuronidase (GUS) staining, TaBI-1.1 was expressed in mature leaves and roots but not in the hypocotyl or young leaves. Constitutive expression of TaBI-1.1 in Arabidopsis enhanced its resistance to Pseudomonas syringae pv. Tomato (Pst) DC3000 infection and induced SA-related gene expression. Additionally, TaBI-1.1 transgenic Arabidopsis exhibited an alleviation of damage caused by high concentrations of SA and decreased the sensitivity to ABA. Consistent with the phenotype, the RNA-seq analysis of 35S::TaBI-1.1 and Col-0 plants showed that TaBI-1.1 was involved in biotic stresses. These results suggested that TaBI-1.1 positively regulates SA signals and plays important roles in the response to biotic stresses. In addition, TaBI-1.1 interacted with the aquaporin TaPIP1, and both them were localized to ER membrane. Furthermore, we demonstrated that TaPIP1 was up-regulated by SA treatment and TaPIP1 transgenic Arabidopsis enhanced the resistance to Pst DC3000 infection. Thus, the interaction between TaBI-1.1 and TaPIP1 on the ER membrane probably occurs in response to SA signals and defense response.