Comprehensive molecular evolutionary analysis of small heat shock proteins in five diploid Gossypium species.

The small heat shock proteins (sHSPs) are important components in plant growth and development, and stress response. However, a systematical understanding of the sHSP family is yet to be reported in five diploid Gossypium species. In this study, 34 GlsHSPs, 36 GrsHSPs, 37 GtsHSPs, 37 GasHSPs, and 38 GhesHSPs were identified in Gossypium longicalyx, Gossypium raimondii, Gossypium turneri, Gossypium arboreum, and Gossypium herbaceum, respectively. These sHSP members can be clustered into 10 subfamilies. Different subfamilies had different member numbers, motif distributions, gene structures, gene duplication events, gene loss numbers, and cis-regulatory elements. Besides, the paleohexaploidization event in cotton ancestor led to expanding the sHSP members and it was also inherited by five diploid Gossypium species. After the cotton ancestor divergence, the sHSP members had the relatively conserved evolution in five diploid Gossypium species. The comprehensive evolutionary history of the sHSP family was revealed in five diploid Gossypium species. Furthermore, several GasHSPs and GhesHSPs were important candidates in plant growth and development, and stress response. These current findings can provide valuable information for the molecular evolution and further functional research of the sHSP family in cotton.

DFT Study of Functional Reduction of CO2 with BH3NMe3: The Real Role of Organic Catalyst TBD.

The detailed mechanism of transition metal-free-catalyzed monomethylation of 2-naphthyl acetonitrile (1a) with CO2 in the presence of triazabicyclodecene (TBD) and BH3NMe3 was investigated using density functional theory. The C-methylation process proved to generate formaldehyde followed by the formation of the product via an alcohol rather than a methoxyborane intermediate. During the reaction, CO2 is activated to form the TBD-CO2 adduct and BH3NMe3 is changed into TBD-BH2 (IM2) in the presence of TBD. IM2 plays a real reducing role within the system due to the unique coordination capability of the B atom. In addition to enhancing the nucleophilicity of 1a through deprotonation by tBuOK, our research also indicates that the generated tBuOH not only assists in proton transfer to generate an alcohol intermediate but also promotes the regeneration of TBD.

A mutation in CsGME encoding GDP-mannose 3,5-epimerase results in little and wrinkled leaf in cucumber.

KEY MESSAGE: Map-based cloning revealed that a mutation in a highly conserved amino acid of the CsGME gene encoding GDP-mannose 3,5-epimerase, causes the phenotype of little and wrinkled leaves in cucumbers. Leaf size is a critical determinant of plant architecture in cucumbers, yet only a few genes associated with this trait have been mapped or cloned. Here, we identified and characterized a mutant with little and wrinkled leaves, named lwl-1. Genetic analysis revealed that the phenotype of the lwl-1 was controlled by a single recessive gene. Through map-based cloning, the lwl-1 locus was narrowed down to a 12.22-kb region exclusively containing one fully annotated gene CsGME (CsaV3_2G004170). CsGME encodes GDP-mannose 3,5-epimerase, which is involved in the synthesis of ascorbic acid (ASA) and one of the components of pectin, RG-II. Whole-length sequencing of the 12.22 kb DNA fragment revealed the presence of only a non-synonymous mutation located in the sixth exon of CsGME in lwl-1, resulting in an amino acid alteration from Pro363 to Leu363. This mutation was unique among 118 inbred lines from cucumber natural populations. CsGME expression significantly reduced in various organs of lwl-1, accompanied by a significant decrease in ASA and pectin content in leaves. Both CsGME and Csgme proteins were localized to the cytoplasm. The mutant phenotype exhibited partial recovery after the application of exogenous boric acid. Silencing CsGME in cucumber through VIGS confirmed its role as the causal gene for lwl-1. Transcriptome profiling revealed that CsGME greatly affected the expression of genes related to the cell division process and cell plate formation. This study represents the first report to characterize and clone the CsGME in cucumber, indicating its crucial role in regulating leaf size and development.

Recent advances in nanomaterial-driven strategies for diagnosis and therapy of vascular anomalies.

Nanotechnology has demonstrated immense potential in various fields, especially in biomedical field. Among these domains, the development of nanotechnology for diagnosing and treating vascular anomalies has garnered significant attention. Vascular anomalies refer to structural and functional anomalies within the vascular system, which can result in conditions such as vascular malformations and tumors. These anomalies can significantly impact the quality of life of patients and pose significant health concerns. Nanoscale contrast agents have been developed for targeted imaging of blood vessels, enabling more precise identification and characterization of vascular anomalies. These contrast agents can be designed to bind specifically to abnormal blood vessels, providing healthcare professionals with a clearer view of the affected areas. More importantly, nanotechnology also offers promising solutions for targeted therapeutic interventions. Nanoparticles can be engineered to deliver drugs directly to the site of vascular anomalies, maximizing therapeutic effects while minimizing side effects on healthy tissues. Meanwhile, by incorporating functional components into nanoparticles, such as photosensitizers, nanotechnology enables innovative treatment modalities such as photothermal therapy and photodynamic therapy. This review focuses on the applications and potential of nanotechnology in the imaging and therapy of vascular anomalies, as well as discusses the present challenges and future directions.

A simulation-based comparison of centralized and point-of-care supply chain strategies for autologous cell therapy.

BACKGROUND AIMS: The selection between centralized and point-of-care (POC) manufacturing supply-chain network design is a crucial consideration in the autologous cell therapy (AuCT) industry, as each approach offers its advantages and disadvantages. METHODS: This study uses a simulation-based approach to compare and examine the two strategies using the supply chain for chimeric antigen receptor T-cell therapy manufacturing as an exemplar. When does it make sense to use one manufacturing strategy over another? Currently, major manufacturers in the AuCT industry use centralized supply-chain strategies predominantly in practice. The simulation results explain the reasons for this choice. To enhance the competitiveness of the POC strategy, two operation rules are proposed and tested with the simulation. The study uses key performance indicators such as cost, fulfillment time, service level, and resource utilization to provide generic guidelines based on the findings. RESULTS: The results have revealed that (i) the centralized supply-chain strategy has a significant advantage at current demand levels of a few thousand products per year; (ii) "optimal capacity" exists for the POC strategy that minimizes the cost of goods and (iii) allowing part-time labor and order transshipment can significantly increase the competitiveness of the POC strategy. CONCLUSIONS: This study may be useful in helping commercial manufacturers make informed decisions about their manufacturing approach to enhance their competitiveness in the market and to ensure a high level of patient benefit.

His bundle pacing versus right ventricular pacing: A comparative study.

BACKGROUND: Pacing is the most effective and dependable method for treating complete atrioventricular block (AVB). OBJECTIVE: The purpose of this study is to investigate the use of His bundle pacing (HBP) in patients with atrioventricular block. METHODS: Patients who underwent HBP or right ventricular pacing (RVP) were enrolled and divided into two groups: the HBP group and the RVP group, respectively. We compared baseline clinical data, fluoroscopy duration, operation duration, pacing electrode parameters during the operation or follow-up, baseline QRS duration, and pacing QRS duration. RESULTS: HBP was attempted in 48 patients and was successful in 34 patients who were included in the HBP group. In addition, 30 RVP patients were included in the RVP group. Fluoroscopy duration and operation duration were significantly longer in the HBP group compared to the RVP group. Compared to the RVP group, the HBP group had a higher pacing threshold, a lower R wave amplitude, and a shorter pacing QRS duration. At 6 months of follow-up, the pacing threshold remained higher, the R wave amplitude was significantly lower, and the end-diastolic diameter of the left ventricle was smaller in the HBP group. CONCLUSION: HBP was safe and effective for atrioventricular block despite the longer fluoroscopy and operation duration in the HBP group when compared to the RVP group.

FAP promotes metastasis and chemoresistance via regulating YAP1 and macrophages in mucinous colorectal adenocarcinoma.

Mucinous colorectal adenocarcinoma (MC) is less likely to respond to chemotherapy and is associated with poorer prognosis compared with non-MC (NMC). Fibroblast activation protein (FAP) was found and validated to be upregulated in MC patients and was negatively correlated with prognosis and therapeutic outcomes in colorectal cancer (CRC) patients who were treated with adjuvant chemotherapy. Overexpression of FAP promoted CRC cell growth, invasion and metastasis, and enhanced chemoresistance. Myosin phosphatase Rho-interacting protein (MPRIP) was identified as a direct interacting protein of FAP. FAP may influence the efficiency of chemotherapy and prognosis by promoting the crucial functions of CRC and inducing tumor-associated macrophages (TAMs) recruitment and M2 polarization through regulating theRas Homolog Family Member/Hippo/Yes-associated protein (Rho/Hippo/YAP) signaling pathway. Knockdown of FAP could reverse tumorigenicity and chemoresistance in CRC cells. Thus, FAP may serve as a marker for prognosis and therapeutic outcome, as well as a potential therapeutic target to overcome chemoresistance in MC patients.

Conserved and divergent evolution of the bZIP transcription factor in five diploid Gossypium species.

MAIN CONCLUSION: 495 bZIP members with 12 subfamilies were identified in the five diploid cottons. Segmental duplication events in cotton ancestor might have led to primary expansion of the cotton bZIP members. The basic leucine zipper (bZIP) transcription factor is one of the largest and most diverse families in plants. The evolutionary history of the bZIP family is still unclear in cotton. In this study, a total of 495 bZIP members were identified in five diploid Gossypium species, including 100 members in Gossypium arboreum, 104 members in Gossypium herbaceum, 95 members in Gossypium raimondii, 96 members in Gossypium longicalyx, and 100 members in Gossypium turneri. The bZIP members could be divided into 12 subfamilies with biased gene proportions, gene structures, conserved motifs, expansion rates, gene loss rates, and cis-regulatory elements. A total of 239 duplication events were identified in the five Gossypium species, and mainly occurred in their common ancestor. Furthermore, some GabZIPs and GhebZIPs could be regarded as important candidates in cotton breeding. The bZIP members had a conserved and divergent evolution in the five diploid Gossypium species. The current study laid an important foundation on the evolutionary history of the bZIP family in cotton.

LGR4 cooperates with PrPc to endow the stemness of colorectal cancer stem cells contributing to tumorigenesis and liver metastasis.

Cancer stem cells (CSCs) are a subpopulation of cancer cells that drive tumour progression and metastasis. Anti-CSC strategies represent new targets for cancer therapies. However, CSCs are highly plastic and heterogeneous, making validation and targeting difficult without bona fide markers that define their identity, especially in a clinical setting. Here, we report that a leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) cooperates with CD44 and PrPc; the latter contributes significantly to metastatic capacity and defines the stemness characteristics of colorectal CSCs. CD44+PrPc+LGR4+ cells effectively developed into organoids and, when transplanted, generated orthotopic and metastatic tumours. Importantly, targeting LGR4 and PrPc with lentiviral shRNAs inhibited organoid development and the growth of orthotopic tumours by inhibiting Wnt/ß-catenin signalling. Thus, our study offers a novel therapeutic strategy that simultaneously targets CSC stemness and metastatic properties.

Analysis of the clinical effect of the concept of "shoulder preservation" in the treatment of proximal humeral fractures: a retrospective cohort study of 66 patients.

BACKGROUND: The three- and four-part fractures of the proximal humerus are often combined with rotator cuff injury, and shoulder joint replacement is often selected clinically. The concept of "shoulder preservation" can greatly restore the function of the shoulder joint through internal fixation of the proximal humerus fracture and rotator cuff suture. This study investigated the clinical effect of the concept of "shoulder preservation" in the treatment of three- and four-part fractures of the proximal humerus. METHODS: We conducted a retrospective analysis of 66 patients with proximal humeral fractures (PHFs) who were treated at the Affiliated Hospital of Qinghai University between 2016 and 2019. The patients were divided into 3 groups according to the Neer fracture classification system, and the fracture healing time of the 3 groups was compared. A visual analog scale (VAS) was used to evaluate the pain, and the Neer score was used to evaluate shoulder joint function. RESULTS: The operations were successfully completed and the 3 groups of patients were compared in pairs. All incisions healed by first intention after operation, and no early complications occurred. The average follow-up time was 18 months. All fractures had healed. The VAS score of the 3 groups of patients was 1.5±0.5 at 1 month after operation and 1.0±0.5 at the final follow-up, which was significantly improved compared with preoperative scores, although the difference was not statistically significant (P>0.05). The Neer scores of the first group of patients at 1, 3, and 9 months postsurgery were higher than those of the second and third groups, and the difference was statistically significant (P<0.05). There was no significant difference among the 3 groups in Neer score 12 months after the operation (P>0.05). CONCLUSIONS: Proximal humeral internal locking osteosynthesis system (PHILOS) fixation + rotator cuff suture is a reliable treatment method involving a simple operation, firm fixation, and good postoperative recovery. It can restore shoulder joint function to the greatest extent, but it also has some shortcomings, including slow recovery time.

The efficacy of Chinese herbal medicine Buyang Huanwu Decoction combined with acupuncture to treat sequela of apoplexy: A protocol for systematic review and meta-analysis.

BACKGROUND: Stroke is a common disease in neurology, patients often have different degrees of sequelae, which affect the patient's quality of life. We conducted a protocol for systematic review and meta-analysis to assess the efficacy of Buyang Huanwu Decoction combined with acupuncture for the treatment of stroke sequelae. METHODS: The current protocol is prepared in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols statement guideline. Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, and Cochrane Library were searched in August 2021 by 2 independent reviewers. The risk of bias assessment of the included studies was performed by 2 authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We will perform meta-analysis using STATA 11.0 (http://www.stata.com; Stata Corporation, College Station, TX). RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. CONCLUSION: Buyang Huanwu Decoction combined with acupuncture seems to be an effective therapy to ameliorate the clinical symptoms of stroke sequelae. In order to further determine the effectiveness and safety of Buyang Huanwu Decoction combined with acupuncture in treating stroke sequelae, more multicenter and prospective randomized controlled trials must be carried out.

The efficacy of Tai Chi for intervention treatment of myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: This protocol for systematic review and meta-analysis aims at assessing the clinical evidence regarding the efficacy of Tai Chi interventions in patients with myocardial infarction (MI). METHODS: Literature retrieval will use the Cochrane Library, Web of Science, PubMed, Embase, Allied and Complementary Medicine Database, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and Ongoing Clinical Trials Database. Our search strategy was based on a string of text words, Medical Subject Headings, and subject headings indicative of Tai Chi. The search strings included: tai chi chuan, taiji, and taiji quan interventions in myocardial infarction; MI infarcts; myocardial infarcts; myocardial; coronary artery disease; coronary arteriosclerosis; acute coronary syndromes; and coronary syndromes. Quality assessment of the included studies was evaluated using the Cochrane risk of bias assessment tool. Statistical analyses were performed using RevMan 5.4 software. RESULTS: The findings of this study will be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide reliable evidence regarding the efficacy of Tai Chi in patients with MI and provide up-to-date evidence for its application.

Long non-coding RNA CRNDE regulates the growth and migration of prostate cancer cells by targeting microRNA-146a-5p.

The function of lncRNA CRNDE and its role in prostate cancer (PC) remains unclear. The aim of this study was to determine the expression level of lncRNA CRNDE in PC tissues and to elucidate its role in PC. The expression levels of lncRNA CRNDE were measured by quantitative reverse transcription polymerase chain reaction. The role of lncRNA CRNDE in PC cells was studied using loss-of-function assays in vitro. Cell proliferation, migration, invasion, and apoptosis were assessed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing, and transwell chamber assays. A luciferase reporter assay was used to characterize the interaction between lncRNA CRNDE and miR-146a-5p. In PC tissues, the expression level of lncRNA CRNDE was upregulated. Moreover, knockdown of lncRNA CRNDE suppressed PC cell proliferation and migration and induced apoptosis in vitro. miR-146a-5p was verified as a direct target of lncRNA CRNDE. Moreover, the inhibition of miR-146a-5p partially counteracted the effects of lncRNA CRNDE on PC cell proliferation, migration, and invasion. In conclusion, lncRNA CRNDE may serve as a cancer promoter in PC by targeting miR-146a-5p. Therefore, lncRNA CRNDE could be a promising target for the clinical treatment of PC.

Rhizospheric pathogen proliferation and ROS production are associated with premature senescence of the osvha-a1 rice mutant.

Root-pathogen interactions influence premature senescence in rice, however, few studies have addressed the underlying mechanism. In this study, when premature senescence significantly occurred in the osvha-a1 mutant (loss of tonoplast H+-ATPase activity), the relative abundance of rhizospheric bacterial communities was similar between the mutant and its wild type, while the fungi in the rhizosphere of the osvha-a1 mutant significantly differed from the wild type. Furthermore, one key fungal strain in the rhizospheric soil of the osvha-a1 mutant, Gibberella intermedia, increased substantially during the late growing phase, resulting in severe accumulation of reactive oxygen species (ROS). By contrast, the wild type showed much lower levels of ROS when infected by G. intermedia. Using high performance liquid chromatography, sugars in root exudates were identified to be different between osvha-a1 mutant and the wild type. G. intermedia could use mannose and rhamnose in root exudates from the mutant more efficiently than any other sugar. Finally, antagonistic bacteria could be employed for limiting the proliferation of G. intermedia in the rhizosphere, thereby alleviating the early senescent phenotypes of the osvha-a1 mutant, and improving grain yield.

Genome-wide identification and molecular evolution analysis of the heat shock transcription factor (HSF) gene family in four diploid and two allopolyploid Gossypium species.

Heat shock transcription factors (HSFs) can regulate plant development and stress response. The comprehensive evolutionary history of the HSF family remains elusive in cotton. In this study, each cotton species had 78 members in Gossypium barbadense and Gossypium hirsutum. The diploid species had 39 GaHSFs in Gossypium arboreum, 31 GrHSFs in Gossypium raimondii, 34 GtHSFs in Gossypium turneri, and 34 GlHSFs in Gossypium longicalyx. The HSF family in cotton can be classified into three subfamilies, with seven groups in subfamily A and five groups in subfamily B. Different groups exhibited distinct gene proportions, conserved motifs, gene structures, expansion rates, gene loss rates, and cis-regulatory elements. The paleohexaploidization event led to the expansion of the HSF family in cotton, and the gene duplication events in six Gossypium species were inherited from their common ancestor. The HSF family in diploid species had a divergent evolutionary history, whereas two cultivated tetraploids presented a highly conserved evolution of the HSF family. The HSF members in At and Dt subgenomes of the cultivated tetraploids showed a different evolution from their corresponding diploid donors. Some HSF members were regarded as key candidates for regulating cotton development and stress response. This study provided the comprehensive information on the evolutionary history of the HSF family in cotton.

A Homotypic Membrane-Camouflaged Biomimetic Nanoplatform with Gold Nanocrystals for Synergistic Photothermal/Starvation/Immunotherapy.

Although photothermal therapy (PTT) has great potential for tumor inhibition, this single mode of action frequently encounters recurrence and metastasis, highlighting the urgent need for developing combination therapy. Inspired by established evidence that PTT could induce efficient immunogenic cell death (ICD), we here developed a versatile biomimetic nanoplatform (denoted as AuDRM) for the synergism of photothermal/starvation/immunotherapy against cancer. Specifically, dendritic mesoporous silica nanoparticles (NPs) were successfully constructed followed by the in situ synthesis of Au NPs in the mesopores. Afterward, a hybrid membrane was coated to facilitate the loading of R837. Upon efficient accumulation in the tumor tissue by homotypic targeting, the pH-sensitive membrane could be jettisoned to ensure the exposure of Au NPs for starvation therapy and the effective release of the immunostimulator R837 for enhancement of immunotherapy. Except for the PTT-mediated tumor ablation, the induction of ICD coupled with the release of tumor antigens could work synergistically with the immunostimulator R837 for inhibiting the primary tumor as well as the metastasis and induce a long-term immune memory effect for tumor inhibition via a vaccine-like function. Thus, this study paves the way for high-performance tumor ablation by the synergism of photothermal/starvation/immunotherapy.

Comparative Study on Iron Content Detection by Energy Spectral CT and MRI in MDS Patients.

Objective: The purpose of this study was to identify the difference between dual energy spectral computed tomography (DECT) and magnetic resonance imaging (MRI) used to detect liver/cardiac iron content in Myelodysplastic syndrome (MDS) patients with differently adjusted serum ferritin (ASF) levels. Method: Liver and cardiac iron content were detected by DECT and MRI. Patients were divided into different subgroups according to the level of ASF. The receiver operating characteristic curve (ROC) analysis was applied in each subgroup. The correlation between iron content detected by DECT/MRI and ASF was analyzed in each subgroup. Result: ROC curves showed that liver virtual iron content (LVIC) Az was significantly less than liver iron concentration (LIC) Az in the subgroup with ASF < 1,000 ng/ml. There was no significant difference between LVIC Az and LIC Az in the subgroup with 1,000 ≤ ASF < 2,500 ng/ml and 2,500 ≤ ASF < 5,000 ng/ml. LVIC Az was significantly higher than LIC Az in the subgroup with ASF <5,000 and 5,000 ≤ ASF ng/ml. In patients undergoing DECT and MRI examination on the same day, ASF was significantly correlated with LVIC, whereas no significant correlation was observed between ASF and LIC. After removing the data of ASF > 5,000 mg/L in LIC, LIC became correlated with ASF. There was no significant difference between the subgroup with 2,500 ≤ ASF < 5,000 ng/ml and 5,000 ng/ml ≤ ASF in LIC expression. Furthermore, both LIC and liver VIC had significant correlations with ASF in patients with ASF < 2,500 ng/ml, while LVIC was still correlated with ASF, LIC was not correlated with ASF in patients with 2,500 ng/ml ≤ ASF. Moreover, neither cardiac VIC nor myocardial iron content (MIC) were correlated with ASF in these subgroups. Conclusion: MRI and DECT were complementary to each other in liver iron detection. In MDS patients with high iron content, such as ASF ≥ 5,000 ng/ml, DECT was more reliable than the MRI in the assessment of iron content. But in patients with low iron content, such as ASF < 1,000 ng/ml, MRI is more reliable than DECT. Therefore, for the sake of more accurately evaluating the iron content, the appropriate detection method can be selected according to ASF.

MiR-105 enhances osteogenic differentiation of hADSCs via the targeted regulation of SOX9.

OBJECTIVE: To investigate whether miR-105 can regulate the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) by targeting SOX9. METHODS: The hADSCs were grouped for subsequent transfection and induction of osteogenic differentiation as follows: control, miR-NC, miR-105 mimics, miR-105 inhibitors, SOX9, SOX9 siRNA, miR-105 mimics + SOX9 and miR-105 inhibitors + SOX9 siRNA groups. Next, hADSCs were stained for alkaline phosphatase (ALP), and Alizarin Red S staining (ARS) was performed. Osteogenic differentiation-related genes and miR-105 expression were assessed by qRT-PCR, while SOX9 protein expression was determined by Western blotting. RESULTS: MiR-105 expression was increased and SOX9 protein expression was decreased during the osteogenic differentiation of hADSCs. A dual-luciferase reporter assay confirmed SOX9 to be a target gene of miR-105. Compared with the control group, the miR-105 mimics and SOX9 siRNA groups had elevated BMP2, OPN, OCN, BSP, Osx and Runx2 mRNA expression with reduced SOX9 expression, as well as increased ARS intensity and ALP activity. After transfection of miR-105 inhibitors/SOX9 into hADSCs, the results were the opposite. Overexpressing SOX9 reversed the effect of miR-105 in promoting the osteogenic differentiation of hADSCs. CONCLUSION: MiR-105 could target SOX9 to improve the expression of osteogenic differentiation genes and thus enhance the osteogenic differentiation of hADSCs.

Influence of non-enzymatic glycation on the mechanical properties of cortical bone.

Poor bone quality induced by non-enzymatic glycation (NEG) of bone tissue in patients with type 2 diabetes mellitus (T2DM) is regarded as the major factor of bone fragility and affecting bone mechanical properties. A comprehensive and systemic mechanical investigation for evaluating the effect of NEG on bone was still lacking. In order to provide additional information for the bone quality of T2DM, the effects of NEG on mechanical properties of cortical bone were investigated in terms of elastoplasticity, fracture toughness and viscoelasticity. All samples of cortical bone, including the samples of strength test (n = 20), fracture toughness test (n = 40, quasi-static and fall-like conditions with displacement rates of 10-3 mm/s and 10 mm/s, respectively) and stress relaxation test (n = 20), were harvested from bovine tibiae. The samples of each test were equally divided into incubated-control group and ribose-incubated group. All mechanical tests were performed after incubating all samples for 15 days. Post-yield strain (p = 0.014), post-yield energy (p < 0.0001) and damage fraction (p = 0.040) of ribose-incubated group were significantly lower than those of incubated-control group, but secant modulus (p = 0.029) of ribose-incubated group was significantly higher than that of incubated-control group. In quasi-static condition, the plastic contribution Jpl of fracture toughness (p = 0.043) of ribose-incubated group was significantly lower than that of incubated-control group. In fall-like condition, there were no differences in Jpl, elastic contribution Jel and J-integral in both two groups. The quasi-static Jel (p < 0.0001, p < 0.0001) of incubated-control and ribose-incubated groups and J-integral (p = 0.007) of incubated-control group were all significantly higher than those of fall-like condition. In stress relaxation test, initial modulus E0 (p = 0.040) and equilibrium modulus (p = 0.029) of ribose-incubated group were significantly higher than those of incubated-control group. Reductions of relaxation modulus, which were the differences between two adjacent time points within 700 s-3000 s for ribose-incubated group, were significantly lower than those of incubated-control group. NEG could decrease the post-yield properties and quasi-static facture toughness of cortical bone, especially the plastic contribution of quasi-static fracture toughness. It could also decrease the viscoelasticity of cortical bone. The present study confirmed the negative effects of NEG on the mechanical properties of cortical bone in terms of elastoplasticity, fracture toughness and viscoelasticity, but NEG had no significant effect on the fracture toughness of cortical bone at fall-like loading. These results provided more evidence for increased fragility of cortical bone in patients with T2DM.

Bone marrow mesenchymal stem cells-derived exosomal microRNA-19b-1-5p reduces proliferation and raises apoptosis of bladder cancer cells via targeting ABL2.

BACKGROUND: Exosomes are involved in intercellular communication via specialized molecular cargo, such as microRNAs (miRNAs). However, the mechanisms underlying exosomal miR-19b-1-5p in bladder cancer remain largely unknown, thus, we aim to investigate the effect of exosomal miR-19b-1-5p on bladder cancer with the involvement of non-receptor protein tyrosine kinase Arg (ABL2). METHODS: miR-19b-1-5p and ABL2 expression were tested in bladder cancer. miR-19b-1-5p inhibition/elevation assays were conducted to determine its role in bladder cancer. Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). Exosomes and T24 cells were co-cultured to verify their function in biological characteristics of bladder cancer cells. RESULTS: miR-19b-1-5p was down-regulated while ABL2 was upregulated in bladder cancer. Exosomal miR-19b-1-5p suppressed malignant behaviors of bladder cancer cells, and also inhibited tumor growth in vivo. Up-regulated ABL2 mitigated the effects of miR-19b-1-5p up-regulation on bladder cancer cells. CONCLUSION: BMSCs-derived exosomal miR-19b-1-5p suppresses bladder cancer growth via decreasing ABL2.