The interaction effect of pre-pregnancy body mass index and maternal age on the risk of pregnancy complications in twin pregnancies after assisted reproductive technology.

OBJECTIVE: The widespread use of assisted reproductive technology (ART) has led to an increased twin pregnancy rate and increased risk of pregnancy complications. Pre-pregnancy body mass index (BMI) and maternal age are both risk factors for pregnancy complications. This study aimed to explore whether there is an interaction effect between pre-pregnancy BMI and maternal age on pregnancy complications in women with twin pregnancies after ART. METHODS: Data of 445,750 women with twin pregnancies after ART were extracted from the National Vital Statistics System (NVSS) database in 2016-2021 in this retrospective cohort study. Univariate and multivariate logistic regression analyses were used to explore (1) the associations between pre-pregnancy BMI, maternal age, and total pregnancy complications; (2) interaction effect between pre-pregnancy BMI and maternal age on total pregnancy complications; and (3) this interaction effect in parity, race, gestational weight gain (GWG), and preterm birth subgroups. The evaluation indexes were odds ratios (ORs), relative excess risk of interaction (RERI), attributable proportions of interaction (AP), and synergy index (S) with 95% confidence intervals (CIs). RESULTS: A total of 6,827 women had pregnancy complications. After adjusting for the covariates, compared with women had non-AMA and pre-pregnancy BMI <25 kg/m2, higher maternal age combined with higher pre-pregnancy BMI was associated with higher odds of total pregnancy complications [OR = 2.16, 95%CI: (1.98-2.36)]. The RERI (95% CI) was 0.22 (0.04-0.41), AP (95% CI) was 0.10 (0.02-0.19), and S (95% CI) was 1.24 (1.03-1.49). Subgroup analysis results indicated that the potential additive effect between pre-pregnancy BMI and maternal age on total pregnancy complications was also found in women with different race, multipara/unipara, GWG levels, or preterm births/non-preterm births (all p < 0.05). CONCLUSION: Pre-pregnancy BMI and maternal age may have an additive effect on the odds of pregnancy-related complications in women with twin pregnancy after ART.

The callus formation capacity of strawberry leaf explant is modulated by DNA methylation.

Shoot regeneration from leaf tissue requires de-differentiation of cells from a highly differentiated state into an active dividing state, but how this physiological transition occurs and is regulated especially at epigenetic level remains obscure. Here we have characterized the DNA methylome represented by 5-methylcytosine (5mC) in leaf and the callus tissue derived from the leaf explant of woodland strawberry Fragaria vesca. We detected an overall increase of DNA methylation and distinct 5mC enrichment patterns in the CG, CHG and CHH sequence contexts in genetic and transposable elements. Our analyses revealed an intricate relation between DNA methylation and gene expression levels in leaf or leaf-derived callus. However, when considering the genes involved in callus formation and shoot regeneration, e.g. FvePLT3/7, FveWIND3, FveWIND4, FveLOG4 and FveIAA14, their dynamic transcription levels were associated with the differentially methylated regions located in the promoters or gene bodies, indicating a regulatory role of DNA methylation in the transcriptional regulation of pluripotency acquisition in strawberry. Furthermore, application of a DNA methyltransferase inhibitor 5'-azacytidine (5'-Aza) hampered both callus formation and shoot regeneration from the leaf explant. We further showed that 5'-Aza down-regulated the genes involved in cell wall integrity, such as expansin, pectin lyase and pectin methylesterase genes, suggesting an essential role of cell wall metabolism during callus formation. This study reveals the contribution of DNA methylation in callus formation capacity and will provide a basis for developing a strategy to improve shoot regeneration for basic and applied research applications.

Characterization of expansin genes and their transcriptional regulation by histone modifications in strawberry.

MAIN CONCLUSION: The possible candidate expansin genes, which may be important for strawberry fruit softening, have been identified in the diploid woodland strawberry Fragaria vesca and the octoploid cultivated strawberry Fragaria × ananassa and their transcriptional regulation by histone modifications has been studied. Softening process greatly affects fruit texture and shelf life. Expansins (EXPs) are a group of structural proteins participating in cell wall loosening, which break the hydrogen bonding between cellulose microfibrils and hemicelluloses. However, our knowledge on how EXP genes are regulated in fruit ripening, especially in non-climacteric fleshy fruits, is limited. Here, we have identified the EXP genes in both the octoploid cultivated strawberry (Fragaria × ananassa) and one of its diploid progenitor species, woodland strawberry (Fragaria vesca). We found that EXP proteins in F. × ananassa were structurally more divergent than the ones in F. vesca. Transcriptome data suggested that FaEXP88, FaEXP114, FveEXP11 and FveEXP33 were the four candidate EXP genes more likely involved in fruit softening, whose transcript levels dramatically increased when firmness decreased during fruit maturation. Phylogenetic analyses showed that those candidate genes were closely clustered, indicating the presence of homoeolog expression dominance in the EXP gene family in strawberry. Moreover, we have performed chromatin immunoprecipitation (ChIP) experiments to investigate the distribution of histone modifications along the promoters and genic regions of the EXP genes in F. vesca. ChIP data revealed that the transcript levels of EXP genes were highly correlated with the enrichment of H3K9/K14 acetylation and H3K27 tri-methylation. Collectively, this study identifies the key EXP genes involved in strawberry fruit softening and reveals a regulatory role of histone modifications in their transcriptional regulation, which would facilitate functional studies of the EXP genes in the ripening of non-climacteric fruits.

Iron oxide nanoparticle targeted chemo-immunotherapy for triple negative breast cancer.

Triple negative breast cancer is difficult to treat effectively, due to its aggressiveness, drug resistance, and lack of the receptors required for hormonal therapy, particularly at the metastatic stage. Here, we report the development and evaluation of a multifunctional nanoparticle formulation containing an iron oxide core that can deliver doxorubicin, a cytotoxic agent, and polyinosinic:polycytidylic acid (Poly IC), a TLR3 agonist, in a targeted and simultaneous fashion to both breast cancer and dendritic cells. Endoglin-binding peptide (EBP) is used to target both TNBC cells and vasculature epithelia. The nanoparticle demonstrates favorable physicochemical properties and a tumor-specific targeting profile. The nanoparticle induces tumor apoptosis through multiple mechanisms including direct tumor cell killing, dendritic cell-initiated innate and T cell-mediated adaptive immune responses. The nanoparticle markedly inhibits tumor growth and metastasis and substantially extends survival in an aggressive and drug-resistant metastatic mouse model of triple negative breast cancer (TNBC). This study points to a promising platform that may substantially improve the therapeutic efficacy for treating metastatic TNBC.

How does nitrate regulate plant senescence?

Nitrogen is an essential macronutrient for plant growth and development and plays an important role in the whole life process of plants. Nitrogen is an important component of amino acids, chlorophyll, plant hormones and secondary metabolites. Nitrogen deficiency leads to early senescence in plants, which is accompanied by changes in gene expression, metabolism, growth, development, and physiological and biochemical traits, which ensures efficient nitrogen recycling and enhances the plant's tolerance to low nitrogen. Therefore, it is very important to understand the adaptation mechanisms of plants under nitrogen deficiency for the efficient utilization of nitrogen and gene regulation. With the popularization of molecular biology, bioinformatics and transgenic technology, the metabolic pathways of nitrogen-deficient plants have been verified, and important progress has been made. However, how the responses of plants to nitrogen deficiency affect the biological processes of the plants is not well understood. The current research also cannot completely explain how the metabolic pathways identified show other reactions or phenotypes through interactions or cascades after nitrogen inhibition. Nitrate is the main form of nitrogen absorption. In this review, we discuss the role of nitrate in plant senescence. Understanding how nitrate inhibition affects nitrate absorption, transport, and assimilation; chlorophyll synthesis; photosynthesis; anthocyanin synthesis; and plant hormone synthesis is key to sustainable agriculture.

Application of lung ultrasonography in critically ill patients with COVID-19.

PURPOSE: Lung ultrasonography (LU) is useful to assess lung lesions and variations at bedside. To investigate the results of LU in severe and critical patients with coronavirus disease 2019 (COVID-19), we performed a single-institution study to evaluate the related lung lesions and variations, and prophylactic strategies, in a large referral and treatment center. METHODS: We included 91 adult patients with severe and critical COVID-19, namely 62 males and 29 females, with an average age of 59 ± 11 years, who underwent LU. We collected the following patient information: sex, age, days in hospital, and days in ICU. In the ultrasound examinations, we recorded the presence of discrete B lines, confluent B lines, consolidation, pleural thickening, pleural effusion, and pneumothorax (PTX). RESULTS: Among the 91 severe and critical patients, 59 cases had scattered B lines, 56 cases had confluent B lines, 58 cases had alveolar-interstitial syndrome (AIS), 48 cases had lung consolidation, six cases had pleural thickening, 39 cases had pleural effusion (average depth of the pleural effusion: 1.0 ± 1.5 cm), and 20 patients developed PTX. In the Cox multivariate analysis, there were significant differences in age, hospitalization days, ICU days, and lung consolidation. CONCLUSION: Lung ultrasonography performed at the bedside can detect lung diseases, such as B lines, PTX, pulmonary edema, lung consolidation, pleural effusion, and variations of these findings. Our findings support the use of LU and measurements for estimating factors, and monitoring response to therapy in severe and critical COVID-19 patients.

Identification and characterization of cherry (Cerasus pseudocerasus G. Don) genes responding to parthenocarpy induced by GA3 through transcriptome analysis.

BACKGROUND: Fruit set after successful pollination is key for the production of sweet cherries, and a low fruit-setting rate is the main problem in production of this crop. As gibberellin treatment can directly induce parthenogenesis and satisfy the hormone requirement during fruit growth and development, such treatment is an important strategy for improving the fruit-setting rate of sweet cherries. Previous studies have mainly focused on physiological aspects, such as fruit quality, fruit size, and anatomical structure, whereas the molecular mechanism remains clear. RESULTS: In this study, we analyzed the transcriptome of 'Meizao' sweet cherry fruit treated with gibberellin during the anthesis and hard-core periods to identify genes associated with parthenocarpic fruit set. A total of 25,341 genes were identified at the anthesis and hard-core stages, 765 (681 upregulated, 84 downregulated) and 186 (141 upregulated, 45 downregulated) of which were significant differentially expressed genes (DEGs) at the anthesis and the hard-core stages after gibberellin 3 (GA3) treatment, respectively. Based on DEGs between the control and GA3 treatments, the GA3 response mainly involves parthenocarpic fruit set and cell division. Exogenous gibberellin stimulated sweet cherry fruit parthenocarpy and enlargement, as verified by qRT-PCR results of related genes as well as the parthenocarpic fruit set and fruit size. Based on our research and previous studies in Arabidopsis thaliana, we identified key genes associated with parthenocarpic fruit set and cell division. Interestingly, we observed patterns among sweet cherry fruit setting-related DEGs, especially those associated with hormone balance, cytoskeleton formation and cell wall modification. CONCLUSIONS: Overall, the result provides a possible molecular mechanism regulating parthenocarpic fruit set that will be important for basic research and industrial development of sweet cherries.

Efficacy and Safety of Nalbuphine for Post-operative Analgesia ：a Meta-analysis / 中国药房

OBJECTIVE： To evaluate the efficacy and safety of nalbuphine for postoperative analgesia systematically， and to provide evidence-based reference in clinic. METHODS： Retrieved from Embase， Medline， PubMed， CNKI， VIP and Wanfang database， RCTs about nalbuphine hydrochloride （trial group） vs. other analgesics （control group） for postoperative analgesia were collected. After literature screening， data extraction and literature quality evaluation with modified Jadad scale， Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS： A total of 10 RCTs were included， involving 796 patients. Results of Meta-analysis showed that there was no statistical significance in satisfaction rate of analgesia [OR＝1.11，95％CI（0.70，1.74），P＝0.66]， the incidence of nausea [OR＝1.20，95％CI（0.79，1.83），P＝0.39]， vomiting [OR＝1.02，95％CI（0.69，1.50），P＝0.92] or narcolepsy [OR＝1.32，95％CI（0.47，3.76），P＝0.06] between 2 groups. The incidence of pruritus [OR＝0.29，95％CI（0.14，0.58），P＝0.000 6]， respiratory depression [OR＝0.21，95％CI（0.08，0.58），P＝0.003] and uroschesis [OR＝0.05，95％CI（0.01，0.37），P＝0.004] in trial group were significantly lower than control group. CONCLUSIONS： Nalbuphine has better efficacy and safety for postoperative analgesia.

Characterization of MK8(H2) from Rhodococcus sp. B7740 and Its Potential Antiglycation Capacity Measurements.

Menaquinone (MK) has an important role in human metabolism as an essential vitamin (VK2), which is mainly produced through the fermentation of microorganisms. MK8(H2) was identified to be the main menaquinone from Rhodococcus sp. B7740, a bacterium isolated from the arctic ocean. In this work, MK8(H2) (purity: 99.75%) was collected through a convenient and economic extraction process followed by high-speed countercurrent chromatography (HSCCC) purification. Additionally, high-resolution mass spectrometry (HRMS) was performed for further identification and the hydrogenation position of MK8(H2) (terminal unit) was determined using nuclear magnetic resonance (NMR) for the first time. MK8(H2) showed a superior antioxidant effect and antiglycation capacity compared with ubiquinone Q10 and MK4. High-performance liquid chromatography⁻mass spectrometer (HPLC-MS/MS) and molecular docking showed the fine interaction between MK8(H2) with methylglyoxal (MGO) and bull serum albumin (BSA), respectively. These properties make MK8(H2) a promising natural active ingredient with future food and medicine applications.

Chemical constituents from Euphorbia helioscopia / 中草药

Objective: To investigate the chemical constituents from Euphorbia helioscopia. Methods: The compounds were isolated and purified using macroporous resin, silica gel colimu, ODS, MCI gel and Sephadex LH-20, and their structures were elucidated on the basis of spectral data and physicochemical properties. Results: Sixteen compounds were isolated from 95% ethyl alcohol extract from the whole arial of E. helioscopia and identified as four terpenoides: helioscopinolide E (1), ent-kaurane-3-oxo-16β-17-diol (2), oleanolic acid (3), betulinic acid (4); six phenolics: benzoic acid (5), ethyl gallate (6), 3, 3', 4, 4'-tetrahydroxy diphenyl (7), brevifolin (8), 6-hydroxy-7, 8-methylenedioxy coumarin (9), 3, 3'-di-O-methylellagic acid (10); and five phenolics: apigenin (11), chrysoeriol (12), hyperin (13), naringenin-7-O-β-D-glucoside (14), cannabisci-trin (15), and 3β-hydroxy-cholesta-5-ene (16). Conclusion: Compounds 7-10 and 12 are isolated from this genus for the first time. Compounds 2-5 and 14-15 are isolated from this plant for the first time.

Apolipoprotein M increases the expression of vitamin D receptor mRNA in colorectal cancer cells detected with duplex fluorescence reverse transcription-quantitative polymerase chain reaction.

Apolipoprotein M (ApoM) and the vitamin D receptor (VDR) are apolipoproteins predominantly presenting in high-density lipoprotein (HDL) and a karyophilic protein belonging to the steroid­thyroid receptor superfamily, respectively. Previous studies have demonstrated that ApoM and VDR are associated with cholesterol metabolism, immune and colorectal cancer regulation. In order to investigate whether ApoM affected the expression of VDR in colorectal cancer cells, a single­tube duplex fluorescence reverse transcription­quantitative polymerase chain reaction (RT­qPCR) system was developed to simultaneously detect the mRNA levels of VDR and GAPDH in HT­29 cells overexpressing ApoM. The results demonstrated that the amplification products were confirmed as the specific fragment of VDR/GAPDH using the DNA sequencing instrument. The sensitivity, linear range, correlation coefficient, amplification efficiency, intra­assay and inter­assay coefficients of variation were 40 copies/µl, 4.00x101­4.00x105 copies/µl, 0.999, 92.42%, 0.09­0.34% and 0.32­0.65% for VDR, and 40 copies/µl, 4.00x101­4.00x105 copies/µl, 0.999, 98.07%, 0.19­0.43% and 0.40­0.75% for GAPDH, respectively. The results indicated that the expression of VDR mRNA was significantly higher in HT­29 cells overexpressing ApoM, compared with the negative control group (P<0.05). In conclusion, the current study successfully developed the single­tube duplex RT­qPCR to simultaneously detect VDR and GAPDH expression in colorectal cancer cells. The methodology results demonstrated that the duplex RT­qPCR system with high sensitivity and specificity could ensure the objectivity and credibility of the detection. The present study confirmed that ApoM significantly increased the expression of VDR in HT­29 cells. In addition, it was hypothesized that ApoM may be involved in antineoplastic activity via the upregulation of VDR expression, which may provide novel directions for the investigation of ApoM in cancer.

Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1ß, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. STATEMENT OF SIGNIFICANCE: Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature. Current scaffolds often focus on providing sufficient mechanical support or bio-mimetic structure to promote cartilage repair. Thus, silk has been adopted and investigated broadly. However, inflammation is one of the most important factors in OA. But few scaffolds for cartilage repair reported anti-inflammation property. Meanwhile, chondroitin sulfate (CS) is a glycosaminoglycan present in the natural cartilage ECM, and has exhibited a number of useful biological properties including anti-inflammatory activity. Thus, we designed this silk-CS scaffold and proved that this scaffold exhibited good anti-inflammatory effects both in vitro and in vivo, promoted the repair of articular cartilage defect in animal model.

17ß-estradiol regulates the expression of apolipoprotein M through estrogen receptor α-specific binding motif in its promoter.

BACKGROUND: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression. RESULTS: Our results demonstrated either free 17ß-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to -1575 bp (-GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region. CONCULSION: In summary, the present study indicates that 17ß-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.

Method of bubble under water capsulorhexis in small incision used in mature cataract operation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe application of underwater bubble method capsulorhexis overmature period to improve the small incision cataract surgery, so as to explore the clinical value of the surgical method. ● METHODS: From Jul. 2012 to Mar. 2016 at the grassroots of blindness 58 people fail in the 66 eyes overmature period of cataract were randomly divided into underwent capsulorhexis by underwater bubble method to improve the small incision cataract surgery group ( 36 eyes of 30 cases ) and conventional viscoelastic agent underwent capsulorhexis small incision cataract surgery group (30 eyes of 28 cases). ● RESULTS: A total of 66 eyes in success rate of continuous circular capsulorhexis: 92% ( 33/36 eyes ) of underwater bubble method, method of viscoelastic agent only 40% ( 12/30 eyes ) . Two groups of cases of postoperative corneal endothelial cell density are compared with preoperative significantly reduced, no significant statistical difference between the two groups(P>0. 05). ● CONCLUSION: Underwater bubble method capsulorhexis difficult to overmature period of cataract surgery capsulorhexis solution is a better way.

Prognostic value of right ventricular end-diastolic diameter in patients with chronic systolic heart failure / 中华老年医学杂志

Objective To investigate the prognostic value of right ventricular end-diastolic diameter (RVDD) in patients with chronic systolic heart failure (CHF).Methods A retrospective study was conducted with clinical data of inpatients from 12 third-grade class-A hospitals of Hubei Province between 2000 to 2010,followed up by phone calls.Based on RVDD,patients diagnosed with chronic systolic CHF were divided into four groups:＞38 mm,31-38 mm,25-30 mm and ＜25 mm groups;based on prognosis,patients were divided into the death group and the survival group.Of the death group,patients were further divided into the heart failure death subgroup and the sudden cardiac death subgroup.Single-factor and multi-factor Cox survival analyses were conducted to analyze the relationships between RVDD and mortality,including all-cause mortality,CHF mortality and sudden cardiac death (SCD).Results A total of 16681 patients were enrolled in this study.They were followed up for 1-4 years,during which 6453 died.Multivariate Cox survival analysis showed that the mortality risk for patients with RVDD between 25-30 mm,between 31-38 mm,and ＞38 mm groups was 1.87,2.41,3.95 times that for patients with RVDD＜25 mm,respectively (95％CI:1.64-2.13,2.06-2.80,3.61-4.32,all P＜0.01).The risk of sudden cardiac death for patients with RVDD＞38mm was 3.82 times that for patients with RVDD＜25 mm (95％CI:2.27-5.94,P＜0.01).The areas under the ROC curve for death by the best prediction model alone and RVDD combined with the best respectively.RVDD increased the areas under the ROC curve for all cause mortality,CHF mortality and sudden cardiac death.The best prediction model combined with RVDD could discriminate between total mortality,heart failure mortality and sudden cardiac death for patients with different causes of death in multivariate analysis.Conclusions RVDD has a predictive value in the prognosis of patients with chronic systolic heart failure.RVDD increases the sensitivity and specificity of the best prediction model for total mortality prediction in patients with chronic systolic heart failure.RVDD increases the sensitivity and specificity of the best prediction model to discriminate between all-cause mortality,heart failure mortality and sudden cardiac death in patients with different causes of death.RVDD＞38 mm can serve as an indicator for the assessment of sudden cardiac death in CHF patients.

The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel.

Degradation of proteoglycan is the key early event in the development of osteoarthritis (OA). The aggrecanase ADAMTS-5 has been identified as the major enzyme responsible for the degradation and thus is an attractive therapeutic target for OA. However, currently there is no report on using an ADAMTS-5 inhibition strategy for OA treatment. The present study aimed to investigate the synergic effect of combining an ADAMTS-5 inhibitor (114810) with a hyaluronic acid hydrogel (HAX) for OA therapeutics. Two OA models were induced by surgically creating an osteochondral defect or removing the anterior cruciate ligament (ACL) in Sprague-Dawley rats. Human OA cartilage was obtained from total joint replacement patients. Both human and rat OA cartilage showed marked proteoglycan loss with significantly increased ADAMTS-5 expression. The effectiveness of ADAMTS-5 inhibition by 114810 was confirmed by a cartilage explants assay in vitro, which showed that the 114810 halted the aggrecanase-mediated (374)ARGS neoepitope released from aggrecan induced by IL-1ß stimulation. The in vivo effect of ADAMTS-5 inhibition was assessed by the articular injection of HAX with 114810 into OA knee joints. Evaluated eight weeks after injection, 114810 with HAX significantly promoted the in vivo cartilage healing in the osteochondral defect model, and prevented the progression of degenerative changes in the ACL model. Our results confirmed that ADAMTS-5 is an effective target for OA treatment, and the intra-articular injection of an ADAMTS-5 inhibitor within HAX gel could be a promising strategy for OA treatment.

Visual detection of biological thiols based on lightening quantum dot-TiO2 composites.

The quenched fluorescence of quantum dots (QDs) attached to TiO2 nanoparticles was selectively switched on by biothiols through ligand replacement, which makes it feasible for facilely sensing biothiols based on the fluorescence turn on mechanism. The present sensor exhibited excellent selectivity and high sensitivity. Furthermore, a novel fluorescent indicating paper was constructed by immobilizing the probe on filter paper to visually detect biothiols in which only a UV lamp was used.

Quantum dots-based ratiometric fluorescence probe for mercuric ions in biological fluids.

Fluorescence analysis by means of a single fluorescence signal output usually leads to the signal fluctuation caused by various external factors. Ratiometric fluorescence probes that can significantly eliminate the external effects by self-calibration of two different emission bands are preferable for the detection of real samples. In this work, we designed a dual-emission quantum dots (QDs) nanocomposite as a ratiometric probe for the visual detection of Hg(2+). The dual-emission QDs nanocomposite consists of two differently sized CdTe/CdS QDs. The red-emitting larger sized CdTe/CdS QDs embeded in silica nanoparticles are insensitive to Hg(2+), while the green-emitting smaller sized ones are covalently conjugated onto the silica nanoparticles surface and sensitive to Hg(2+). The addition of Hg(2+) can only quench green fluorescence in the dual-emission QDs nanocomposites, which triggers the change of fluorescence intensity ratio of two different emission wavelengths and hence induces the evolution of fluorescence color of the probe solution with variation of Hg(2+) concentration. Based on this feature, the dual-emission QDs nanocomposites can be used to develop a ratiometric fluorescence probe for the visual detection of Hg(2+). Under the optimized conditions, the ratiometric fluorescence QDs probe shows a linear relationship between fluorescence intensity ratio and Hg(2+) concentration in the range of 5-300 nM. The detection limit of this probe was found to be 3.1 nM. This ratiometric assay also exhibits a high selectivity and it has been successfully used in the determination of Hg(2+) content in fetal bovine serum and human urine.

Adenosine capped QDs based fluorescent sensor for detection of dopamine with high selectivity and sensitivity.

Facile detection of dopamine (DA) in biological samples for diagnostics remains a challenge. This paper reported an effective fluorescent sensor based on adenosine capped CdSe/ZnS quantum dots (A-QDs) for highly sensitive detection of DA in human urine samples. In this assay, adenosine serves as a capping ligand or stabilizer for QDs to render high-quality QDs dispersed in water, and as a receptor for DA to attach DA onto the surface of A-QDs. DA molecules can bind to A-QDs via non-covalent bonding, leading to the fluorescence quenching of A-QDs due to electron transfer. The A-QDs based fluorescence probe showed a limit of detection (LOD) of ca. 29.3 nM for DA detection. This facile method exhibited high selectivity and anti-interference in the presence of amino acid, ascorbic acid (AA), uric acid (UA) and glucide with 100-fold higher concentration in PBS solution. Furthermore, it was also successfully used in the detection of DA in the human urine samples with quantitative recoveries (94.80-103.40%).

Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression.

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models.