CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

Engineered Living Bacteriophage-Enabled Self-Adjuvanting Hydrogel for Remodeling Tumor Microenvironment and Cancer Therapy.

Due to the complexity and heterogeneity in the tumor microenvironment, the efficacy of breast cancer treatment has been significantly impeded. Here, we established a living system using an engineered M13 bacteriophage through chemical cross-linking and biomineralization to remodel the tumor microenvironment. Chemically cross-linking of the engineered bacteriophage gel (M13 Gel) could in situ synthesize photothermal palladium nanoparticles (PdNPs) on the pVIII capsid protein to obtain M13@Pd Gel. In addition, NLG919 was further loaded into a gel to form (M13@Pd/NLG gel) for down-regulating the expression of tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Both in vitro and in vivo studies showed that the M13 bacteriophage served not only as a cargo-loaded device but also as a self-immune adjuvant, which induced the immunogenic death of tumor cells effectively and down-regulated IDO1 expression. Such a bioactive gel system constructed by natural living materials could reverse immunosuppression and significantly improve the anti-breast cancer response.

Structural Insights into the Stability and Recognition Mechanism of the Antiquinalphos Nanobody for the Detection of Quinalphos in Foods.

Nanobodies (Nbs) have great potential in immunoassays due to their exceptional physicochemical properties. With the immortal nature of Nbs and the ability to manipulate their structures using protein engineering, it will become increasingly valuable to understand what structural features of Nbs drive high stability, affinity, and selectivity. Here, we employed an anti-quinalphos Nb as a model to illustrate the structural basis of Nbs' distinctive physicochemical properties and the recognition mechanism. The results indicated that the Nb-11A-ligand complexes exhibit a "tunnel" binding mode formed by CDR1, CDR2, and FR3. The orientation and hydrophobicity of small ligands are the primary determinants of their diverse affinities to Nb-11A. In addition, the primary factors contributing to Nb-11A's limited stability at high temperatures and in organic solvents are the rearrangement of the hydrogen bonding network and the enlargement of the binding cavity. Importantly, Ala 97 and Ala 34 at the active cavity's bottom and Arg 29 and Leu 73 at its entrance play vital roles in hapten recognition, which were further confirmed by mutant Nb-F3. Thus, our findings contribute to a deeper understanding of the recognition and stability mechanisms of anti-hapten Nbs and shed new light on the rational design of novel haptens and directed evolution to produce high-performance antibodies.

Genome-wide identification and characterization analysis of RWP-RK family genes reveal their role in flowering time of Chrysanthemum lavandulifolium.

BACKGROUND: RWP-RKs are plant specific transcription factors, which are widely distributed in plants in the form of polygenic families and play key role in nitrogen absorption and utilization, and are crucial to plant growth and development. However, the genome-wide identification and function of RWP-RK in Compositae plants are widely unknown. RESULTS: In this study, 101 RWP-RKs in Chrysanthemum lavandulifolium were identified and tandem repeat was an important way for the expansion of RWP-RKs in Compositae species. 101 RWP-RKs contain 38 NIN-like proteins (NLPs) and 31 RWP- RK domain proteins (RKDs), as well as 32 specific expansion members. qRT-PCR results showed that 7 ClNLPs in leaves were up-regulated at the floral transition stage, 10 ClNLPs were negatively regulated by low nitrate conditions, and 3 of them were up-regulated by optimal nitrate conditions. In addition, the flowering time of Chrysanthemum lavandulifolium was advanced under optimal nitrate conditions, the expression level of Cryptochromes (ClCRYs), phytochrome C (ClPHYC) and the floral integration genes GIGANTEA (ClGI), CONSTANS-LIKE (ClCOL1, ClCOL4, ClCOL5), FLOWERING LOCUS T (ClFT), FLOWERING LOCUS C (ClFLC), SUPPRESSOR OF OVER-EXPRESSION OF CONSTANS 1 (ClSOC1) also were up-regulated. The expression level of ClCRY1a, ClCRY1c, ClCRY2a and ClCRY2c in the vegetative growth stage induced by optimal nitrate reached the expression level induced by short-day in the reproductive growth stage, which supplemented the induction effect of short-day on the transcription level of floral-related genes in advance. CONCLUSIONS: It was speculated that ClNLPs may act on the photoperiodic pathway under optimal nitrate environment, and ultimately regulate the flowering time by up-regulating the transcription level of ClCRYs. These results provide new perspective for exploring the mechanism of nitrate/nitrogen affecting flowering in higher plants.

MiRNAs regulate cell communication in osteogenesis-angiogenesis coupling during bone regeneration.

Bone regeneration is a complex process that requires not only the participation of multiple cell types, but also signal communication between cells. The two basic processes of osteogenesis and angiogenesis are closely related to bone regeneration and bone homeostasis. H-type vessels are a subtype of bone vessels characterized by high expression of CD31 and EMCN. These vessels play a key role in the regulation of bone regeneration and are important mediators of coupling between osteogenesis and angiogenesis. Molecular regulation between different cell types is important for coordination of osteogenesis and angiogenesis that promotes bone regeneration. MiRNAs are small non-coding RNAs that predominantly regulate gene expression at the post-transcriptional level and are closely related to cell communication. Specifically, miRNAs transduce external stimuli through various cell signaling pathways and cause a series of physiological and pathological effects. They are also deeply involved in the bone repair process. This review focuses on three signaling pathways related to osteogenesis-angiogenesis coupling, as well as the miRNAs involved in these pathways. Elucidation of the molecular mechanisms governing osteogenesis and angiogenesis is of great significance for bone regeneration.

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and has no safe and effective drug for treatment. We have previously reported the function of blueberry, but the effective monomer and related molecular mechanism remain unclear. METHODS: The monomer of blueberry was examined by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The NASH cell model was constructed by exposing HepG2 cells to free fatty acids. The NASH mouse model was induced by a high-fat diet for 12 weeks. NASH cell and mouse models were treated with different concentrations of blueberry monomers. The molecular mechanism was studied by Oil Red O staining, ELISA, enzyme activity, haematoxylin-eosin (H&E) staining, immunohistochemistry, immunofluorescence, western blot, RNA sequencing, and qRT-PCR. RESULTS: We identified one of the main monomer of blueberry as tectorigenin (TEC). Cyanidin-3-O glucoside (C3G) and TEC could significantly inhibit the formation of lipid droplets in steatosis hepatocytes, and the effect of TEC on the formation of lipid droplets was significantly higher than that of C3G. TEC can promote cell proliferation and inhibit the release of inflammatory mediators in NASH cell model. Additionally, TEC administration provided a protective role against high-fat diets induced lipid damage, and suppressed lipid accumulation. In NASH mouse model, TEC can activate autophagy, inhibit pyroptosis and the release of inflammatory mediators. In NASH cell model, TEC inhibited pyroptosis by stimulating autophagy. Then, small RNA sequencing revealed that TEC up-regulated the expression of tRF-47-58ZZJQJYSWRYVMMV5BO (tRF-47). The knockdown of tRF-47 blunted the beneficial effects of TEC on NASH in vitro, including inhibition of autophagy, activation of pyroptosis and release of inflammatory factors. Similarly, suppression of tRF-47 promoted the lipid injury and lipid deposition in vivo. CONCLUSIONS: These results demonstrated that tRF-47-mediated autophagy and pyroptosis plays a vital role in the function of TEC to treat NASH, suggesting that TEC may be a promising drug for the treatment of NASH.

Clinical characteristics of catheter-related infection in patients with chronic renal failure End Stage Renal failure undergoing semi-permanent catheter placement during maintenance hemodialysis through tunnelled cuffed hemodialysis catheter.

Objective: To analysis the relevant infections and risk factors of patients undergoing hemodialysis semi-permanent catheter (tunneled cuffed) placement during for maintenance hemodialysis. Methods: A total of 158 patients with chronic renal failure (CRF) End stage renal failure (ESRF) treated in our hospital from September 2018 to September 2021 were retrospectively analyzed. All the patients underwent semi-permanent catheter placement during maintenance hemodialysis. The occurrence of catheter-related infections in the patients were recorded. The patients with catheter-related infections were included in the infection group, and the others without infection in the non-infection group. The differences in hypertension, gender, diabetes, age, catheter indwelling time and dialysis time between the two groups were analyzed, and the distribution of pathogens in the patients with infections was analyzed. Results: The patients were followed up for 13 to 36 months, with an average of (22.18 ± 6.09) months. Among the 158 patients who underwent going semi-permanent catheter placement, 42 (26.58%) presented semi-permanent catheter-related infections, including four cases of catheter-related bacteremia, 16 cases of tunnel infection and 22 cases of catheter exit-site infection. Among total of 42 strains of pathogens were isolated from the 42 patients with catheter-related infections, including 243 strains of Gram-positive cocci were identified in 24/42(57.14%), and 163 strains of Gram-negative bacilli were identified 16/42(38.10%) and one starin of fungus was identified in 2/42 patients. Statistically significant differences were found in dialysis duration time, hypoalbuminemia, average mean age, diabetes and catheter indwelling time between patients with and without catheter-related infections (P < 0.05). Hypoalbuminemia, catheter indwelling time and diabetes were risk factors for catheter-related infections (P < 0.05). Conclusions: Patients with ESRF CRF are at risk and prone to catheter-related infections during hemodialysis using catheter, mainly tunnel infection and catheter exit-site infection. Gram-positive cocci are the main pathogens. Hypoalbuminemia, too long catheter indwelling time and diabetes are the risk factors for infections.

A Strategy Based on the Enzyme-Catalyzed Polymerization Reaction of Asp-Phe-Tyr Tripeptide for Cancer Immunotherapy.

Immunotherapy has provided a promising strategy for the treatment of cancers. However, even in tumors with high antigen burdens, the systemic inhibition of the antigen presentation still greatly restricts the application of immunotherapy. Here, we construct a tumor protein-engineering system based on the functional tripeptide, Asp-Phe-Tyr (DFY), which can automatically collect and deliver immunogenetic tumor proteins from targeted cells to immune cells. Through a tyrosinase-catalyzed polymerization, the DFY tripeptide selectively accumulates in tyrosinase high-expressed melanoma cells. Then quinone-rich intermediates are covalently linked with tumor-specific proteins by Michael addition and form tumor protein-carried microfibers that could be engulfed by antigen-presenting cells and exhibited tumor antigenic properties for boosting immune effect. In melanoma cells with deficient antigen presentation, this system can successfully enrich and transport tumor antigen-containing proteins to immune cells. Furthermore, in the in vivo study on murine melanoma, the transdermal delivery of the DFY tripeptide suppressed the tumor growth and the postsurgery recurrence. Our findings provide an avenue for the regulation of the immune system on an organism by taking advantage of certain polymerization reactions by virtue of chemical biology.

Risk factors for acute stroke-associated pneumonia and prediction of neutrophil-to-lymphocyte ratios.

OBJECTIVES: This study aimed to analyze the risk factors for stroke-associated pneumonia (SAP) and assess the predictive effect of neutrophil-to-lymphocyte ratio (NLR) on acute SAP. METHODS: The study included acute stroke patients from April 2018 to June 2019. These patients were divided into the SAP and Non-SAP groups. The patients' history of chronic diseases was assessed, including history of hypertension, diabetes, hyperlipidemia, chronic lung disease, and current smoking status. The clinical characteristics of all studied cases were recorded, including the initial stroke type (cerebral infarction or cerebral hemorrhage), National Institute of Health Stroke Scale (NIHSS) score, indwelling nasogastric tubes, stroke-associated pneumonia within 7 days of hospitalization, and length of hospitalization. The study also recorded the laboratory testing data, including fasting blood glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, glycosylated hemoglobin, and high-sensitivity C-reactive protein (hsCRP) as well as white blood cell (WBC), neutrophil, and lymphocyte counts. SPSS 19.0 was used for statistical analysis. RESULTS: A total of 328 eligible acute stroke patients were included. Among all participants, SAP occurred in 64 (19.5%) patients. In the SAP group, the patients were older, the proportion of cerebral hemorrhage was higher, the NIHSS score was higher, and more patients had nasogastric tubes (P < 0.05). Concomitantly, the blood glucose, hsCRP, WBC count, neutrophil count, and NLR of the SAP group were significantly higher than those of the Non-SAP group, whereas the lymphocyte count was significantly lower than that of the Non-SAP group (P < 0.05). Multivariable analysis of Binary Logistic regression revealed that stroke type (cerebral hemorrhage), indwelling gastric tube, and NLR were independent risk factors for SAP. Receiver operating characteristic curve analysis demonstrated that the area under the curve for the NLR's ability to predict SAP was 0.861. The optimal cutoff threshold, sensitivity, and specificity were 3.745, 0.891, and 0.727, respectively. CONCLUSIONS: The risk factors for SAP were multifaceted. Cerebral hemorrhage, indwelling nasogastric tube, and high NLR were independent risk factors. An early NLR had a predictive effect on the occurrence of SAP in patients with acute stroke.

Temporal Trends in the Risk Factors and Clinical Characteristics of Ischemic Stroke in Young Adults.

OBJECTIVES: This study aimed to analyze the risk factors of ischemic stroke in young adults of different ages; explore the changes in these risk factors with time; analyze the clinical characteristics of ischemic stroke in young adults; and assess how to better prevent ischemic stroke in young adults. METHODS: All patients with ischemic stroke who presented to the Department of Emergency Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School were enrolled. The data of patients aged 18-50 years were retrospectively evaluated for two periods, January-December 2008 and January-December 2018. Additionally, we collected the data of patients aged 51-90 years with ischemic stroke in the same ward in 2018. The subjects were divided into three groups: ischemic stroke in young people in 2008 ("Youth 2008"), ischemic stroke in young people in 2018 ("Youth 2018"), and ischemic stroke in elderly people in 2018 ("Senior 2018"). Risk factors, clinical characteristics and test indices were recorded and analyzed statistically. RESULTS: The "Youth 2008" group included 28 patients-19 males (67.9%) and 9 females (31.2%) with a male-to-female ratio of 2.11:1. The "Youth 2018" group included 23 patients-20 males (87.0%) and 3 females (13.0%) with a male-to-female ratio of 6.67:1. The "Senior 2018" group included 210 patients-150 males (71.4%) and 60 females (28.6%) with a male-to-female ratio of 2.50:1. The risk factors in "Youth 2018" were higher than those in "Youth 2008" in terms of hypertension, hyperglycemia, and hypercholesterolemia without significant difference. Smoking and hypertrophic cardiomyopathy were significantly increased (P < 0.05) in this population. Smoking, hypercholesterolemia, and hypertrophic cardiomyopathy were more prevalent among the "Youth 2018" group than among the "Senior 2018" group, whereas carotid plaques, hypertension, and atrial fibrillation were less common in the younger group (P < 0.05). There was no significant difference between the younger and older groups in terms of thrombolysis rate, cerebral infarction type, and complications, except pulmonary infections (P < 0.05). CONCLUSIONS: There was no significant change in the main risk factors of ischemic stroke in young adults during the 10-year period. Traditional risk factors-smoking and hypertrophic cardiomyopathy-were still common but with a significantly greater prevalence, whereas carotid plaques, hypertension, and atrial fibrillation had become less common. The clinical characteristics, other than pulmonary infection, were not significantly different between the younger and older patients with ischemic stroke.

Distribution and Risk Assessment of Antibiotics in a Typical River in North China Plain.

We evaluated the occurrence and distribution of 12 antibiotics from the sulfonamide (SAs), fluoroquinolone (FQs) and tetracycline (TCs) groups in the Weihe River, North China. The total antibiotic concentrations in surface water, pore water, and sediment samples ranged from 11.1 to 173.1 ng/L, 5.8 to 103.9 ng/L, and 9.5 to 153.4 µg/kg, respectively. The values of the sediment-water partitioning coefficient in the Weihe River varied widely, from not detected to 943, 2213, and 2405 L/kg for SAs, FQs, and TCs, respectively. The values of the partitioning coefficients between sediment and surface water were generally lower than those between sediment and pore water, which indicated ongoing inputs to the water. The risk assessment showed that there were relatively high ecological risks to aquatic algae in this area from sulfamethoxazole, norfloxacin, tetracycline, ofloxacin, and ciprofloxacin.

Increased ratio of neutrophil elastase to α1-antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis.

An imbalance between neutrophil elastase (NE) and its inhibitor α1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.

Multiplex-PCR for Identification of Two Species in Genus Hishimonus (Hemiptera: Cicadellidae) in Jujube Orchards.

The insect family Cicadellidae includes economically important vectors of plant pathogens. Hishimonus sellatus (Uhler) transmits jujube witches'-broom (JWB). Currently, H. sellatus and Hishimonus lamellatus Cai et Kuoh are observed to co-occur at the same locality on jujube. H. lamellatus is now suspected to be a JWB vector. As such, correct identification of Hishimonus species present in vineyards is essential for epidemiological surveys. However, traditional identification of Hishimonus by morphology is limited to the adult male. We provide a comprehensive description of morphological and molecular tools for discriminating between H. sellatus and H. lamellatus, for use in identification and monitoring of the two Hishimonus species and studies of their plant hosts. A rapid and inexpensive method is introduced to identify H. sellatus and H. lamellatus occurring in jujube orchards. This method is based on amplification of mitochondrial cytochrome oxidase I (COI) gene, using PCR with multiplexed, species-specific primers. The reliability of this new method has been tested on different populations from different sites in Beijing region of China.

Effect of piglitazone and metformin on retinol-binding protein-4 and adiponectin in patients with type 2 diabetes mellitus complicated with non-alcohol fatty acid liver diseases.

OBJECTIVE: To compare the effects of piglitazone and metformin on retinol-binding protein-4 (RBP-4) and adiponcetin (APN) in patients with type 2 diabetes mellitus (T2DM) complicated with Non alcohol fatty acid liver disease (NAFLD). METHODS: Totally 60 T2DM patients complicated with NAFLD were equally and randomly divided into pioglitazone group and metform group. The levels of biochemical indicators including body mass index (BMI), glucose hemoglobin A1C (GHbA1C), insulin resistance (HOMA-IR), fasting blood glucose (FBG), fasting insulin (FIns), and serum triglycerides (TG) as well as serum RBP-4 and APN level were measured pre-treatment and 12 weeks after treatments. RESULTS: After 12 weeks of treaments, BMI, FBG, HOMA-IR, GHbA1C, FIns, and TG decreased (all P<0.05) in both piglitazone group and metform group. APN increased (all P<0.05) in both groups. RBP-4 decreased (P<0.05) in piglitazone group. Compare with the metform group, the levels of RBP-4, FIns ,and HOMA-IR decreased and BMI increased in piglitazone group (P<0.05). CONCLUSION: Piglitazone is superior to metoform in decreasing RBP-4 level and HOMA-IR in patients with T2DM complicated with NAFLD.

Mitochondrial dysfunction: A promising therapeutic target for liver diseases.

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy, which is mainly produced by the mitochondria. Liver tissues of patients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mitochondrial lesions, mitochondrial DNA damage, disturbed mitochondrial dynamics, and compromised ATP production. Overproduction of mitochondrial reactive oxygen species induces oxidative damage to mitochondrial proteins and mitochondrial DNA, decreases mitochondrial membrane potential, triggers hepatocyte inflammation, and promotes programmed cell death, all of which impair liver function. Mitochondrial DNA may be a potential novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus. We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases, such as hepatocellular carcinoma, viral hepatitis, drug-induced liver injury, alcoholic liver disease, and non-alcoholic fatty liver disease. This review also discusses mitochondrion-centric therapies for treating liver diseases.

cla-miR164-NO APICAL MERISTEM (ClNAM) regulates the inflorescence architecture development of Chrysanthemum lavandulifolium.

Chrysanthemum × morifolium has great ornamental and economic value on account of its exquisite capitulum. However, previous studies have mainly focused on the corolla morphology of the capitulum. Such an approach cannot explain the variable inflorescence architecture of the chrysanthemum. Previous research from our group has shown that NO APICAL MERISTEM (ClNAM) is likely to function as a hub gene in capitulum architecture in the early development stage. In the present study, ClNAM was used to investigate the function of these boundary genes in the capitulum architecture of Chrysanthemum lavandulifolium, a closely related species of C. × morifolium in the genus. Modification of ClNAM in C. lavandulifolium resulted in an advanced initiation of the floral primordium at the capitulum. As a result, the receptacle morphology was altered and the number of florets decreased. The ray floret corolla was shortened, but the disc floret was elongated. The number of capitula increased significantly, arranged in more densely compounded corymbose synflorescences. The yeast and luciferase reporter system revealed that ClAP1, ClRCD2, and ClLBD18 target and activate ClNAM. Subsequently, ClNAM targets and activates ClCUC2a/c, which regulates the initiation of floral and inflorescence in C. lavandulifolium. ClNAM was also targeted and cleaved by cla-miR164 in this process. In conclusion, this study established a boundary gene regulatory network with cla-miR164-ClNAM as the hub. This network not only influences the architecture of capitulum, but also affects compound corymbose synflorescences of the C. lavandulifolium. These results provide new insights into the mechanisms regulating inflorescence architecture in chrysanthemum.

Generation of transgene-free induced pluripotent stem cells with non-viral methods.

Induced pluripotent stem (iPS) cells were originally generated from mouse fibroblasts by enforced expression of Yamanaka factors (Oct3/4, Sox2, Klf4, and c-Myc). The technique was quickly reproduced with human fibroblasts or mesenchymal stem cells. Although having been showed therapeutic potential in animal models of sickle cell anemia and Parkinson's disease, iPS cells generated by viral methods do not suit all the clinical applications. Various non-viral methods have appeared in recent years for application of iPS cells in cell transplantation therapy. These methods mainly include DNA vector-based approaches, transfection of mRNA, and transduction of reprogramming proteins. This review summarized these non-viral methods and compare the advantages, disadvantages, efficiency, and safety of these methods.

Diagnostic value of visceral adiposity index in chronic kidney disease: a meta-analysis.

AIMS: Several studies have revealed inconsistencies about the predictive properties of visceral adiposity index (VAI) in identifying chronic kidney disease (CKD). To date, it is unclear whether the VAI is a valuable diagnostic tool for CKD. This study intended to evaluate the predictive properties of the VAI in identifying CKD. METHODS: The PubMed, Embase, Web of Science, and Cochrane databases were searched for all studies that met our criteria from the earliest available article until November 2022. Articles were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The heterogeneity was explored with the Cochran Q test and I2 test. Publication bias was detected using Deek's Funnel plot. Review Manager 5.3, Meta-disc 1.4, and STATA 15.0 were used for our study. RESULTS: Seven studies involving 65,504 participants met our selection criteria and were therefore included in the analysis. Pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.67 (95%CI: 0.54-0.77), 0.75 (95%CI: 0.65-0.83), 2.7 (95%CI: 1.7-4.2), 0.44 (95%CI: 0.29-0.66), 6 (95%CI:3.00-14.00) and 0.77 (95%CI: 0.74-0.81), respectively. Subgroup analysis indicated that mean age of subjects was the potential source of heterogeneity. The Fagan diagram found that the predictive properties of CKD were 73% when the pretest probability was set to 50%. CONCLUSIONS: The VAI is a valuable agent in predicting CKD and may be helpful in the detection of CKD. More studies are needed for further validation.

Non-coding RNAs regulate the BMP/Smad pathway during osteogenic differentiation of stem cells.

MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are involved in the regulation of bone metabolism. The BMP/Smad pathway is a key signaling pathway for classical regulation of osteogenic differentiation. Non-coding RNAs (ncRNAs) and the BMP/Smad pathway both have important roles for osteogenic differentiation of stem cells, bone regeneration, and development of bone diseases. There is increasing evidence that ncRNAs interact with the BMP/Smad pathway to regulate not only osteogenic differentiation of stem cells but also progression of bone diseases, such as osteoporosis (OP), myeloma, and osteonecrosis of the femoral head (ONFH), by controlling the expression of bone disease-related genes. Therefore, ncRNAs that interact with BMP/Smad pathway molecules are potential targets for bone regeneration as well as bone disease diagnosis, prevention, and treatment. However, despite extensive studies on ncRNAs associated with the BMP/Smad pathway and osteogenic differentiation of stem cells, there is a lack of comparability. Moreover, some bone disease-associated ncRNAs with low abundance can be difficult to detect and there is a lack of mature delivery systems for their stable translocation to target sites, thus limiting their application. In this review, we summarize the research progress on interactions between ncRNAs and the BMP/Smad pathway during osteogenic differentiation of various stem cells and in the regulation of bone regeneration and bone diseases.

Genome-wide identification of the MIKCc-type MADS-box gene family in Chrysanthemum lavandulifolium reveals their roles in the capitulum development.

Chrysanthemum ×morifolium is well known throughout the world for its diverse and exquisite flower types. However, due to the complicated genetic background of C. ×morifolium, it is difficult to understand the molecular mechanism of its flower development. And it limits the molecular breeding of improving chrysanthemum flower types. C. ×morifolium has the typical radial capitulum, and many researches showed that the members of the MIKCc-type MADS box gene family play a key role in the formation and development of the capitulum. However, it has been difficult to isolate the important MIKCc and investigate their roles in this process due to the lack of genomic information in chrysanthemum. Here, we identified MIKCc-type MADS box genes at whole genome-wide level in C. lavandulifolium, a diploid species closely related to C. ×morifolium, and investigated their roles in capitulum development by gene expression pattern analysis and protein interaction analysis. A total of 40 ClMIKCc were identified and were phylogenetically grouped into 12 clades. Members of all clades showed different enriched expression patterns during capitulum formation. We speculate that the E-class genes in C. lavandulifolium underwent subfunctionalization because they have a significantly expanded, more diverse expression patterns, and specifically tissue expression than AtSEPs. Meanwhile, we detected the C-class expressed in disc floret corolla, which could be the clue to explore the morphological differences between disc and ray floret corolla. In addition, the potential roles of some MIKCcs in complex inflorescence formation were explored by comparing the number and phylogenetic relationship of MIKCc subfamily members in Asteraceae with different capitulum types. Members of the FLC branch in Asteraceae were found to be possibly related to the differentiation and development of the ray floret.