Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

Risk factors for recurrent wheezing after bronchiolitis.

BACKGROUND: This study aimed to determine whether there was an association between certain factors in patients with bronchiolitis and recurrent wheezing in childhood. METHOD: In 2021 we tracked children hospitalized for bronchiolitis at Chengdu Women's and Children's Central Hospital in 2017. The patients were classified into recurrent wheezing group (RWG) and non-recurrent wheezing group (NRWG). Possible risk factors including maternal age, school-age siblings, allergic history, atopic dermatitis, allergic rhinitis, atopic family history, severity of the condition, duration of hospitalization, nasopharyngeal secretions culture, blood eosinophil counts, FeNO and skin prick test were compared between the two groups. Continuous variables were analyzed by independent sample t-test for normal distribution and Mann-Whitney U-test for non-normal distribution. Categorical variables were tested using chi-square tests. Multifactor analysis was conducted by stepwise logistics regression analysis. RESULTS: In total 167 participants were included, of which 26 and 141 were in RWG and NRWG respectively. In RWG children represented higher maternal age (P = 0.02) and greater probability of allergic history, atopic dermatitis, allergic rhinitis, atopic family history (odds ratio [OR] = 4.0,3.7, 7.8, 10.9 respectively, P < 0.01). However, school-age siblings, severity of the condition, duration of hospitalization, blood eosinophil counts, fractional exhaled nitric oxide and skin prick test results seemed unrelated to recurrent wheezing. In the subgroup analysis of nasopharyngeal secretion culture, there were more Moraxella catarrhalis-positive in RWG(P = 0.043). Atopic dermatitis, allergic rhinitis and atopic family history were identified as independent risk factors for recurrent wheezing. CONCLUSION: Some children with bronchiolitis will develop recurrent wheezing, and the risk factors are allergic history, Moraxella catarrhalis infection or colonization, atopic dermatitis, allergic rhinitis and atopic family history; the latter three are independent risk factors.

[Influencing factors of poor treatment adherence in uncontrolled asthma patients in China].

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.

[Construction of TRAF6 ubiquitin site 331 mutant colorectal cancer cell stable line and its effect on biological behavior of colorectal cancer cells].

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.

[Influence factors of poor efficacy after flap repair operation in patients with pressure ulcers].

Objective: To investigate the influence factors of poor efficacy after flap repair operation in patients with pressure ulcers. Methods: The retrospective case series study was conducted. From January 2011 to June 2021, 125 patients with stage Ⅲ and Ⅳ pressure ulcers treated in Hainan General Hospital met the inclusion criteria. There were 82 males and 43 females, aged 15-90 (57±20) years. According to the postoperative effects, the patients were divided into poor efficacy group (47 cases) and good efficacy group (78 cases). The clinical data of patients in the two groups were collected, including the age, gender, location, stage, size, and bone exposure of pressure ulcers, preoperative microorganism culture results of wound exudate sample, whether combined with osteomyelitis, diabetes, lower limb paroxysmal myospasm, and gatism or not, the number of surgical debridement combined with negative-pressure wound therapy, type of surgical flap, postoperative position, and preoperative albumin, leukocyte, C-reactive protein (CRP), and hemoglobin. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The binary multivariate logistic regression analysis was conducted to screen the independent risk factors influencing the poor efficacy after flap repair operation in 125 patients with stage Ⅲ and Ⅳ pressure ulcers. Results: The ratio of patients with lower limb paroxysmal myospasm in poor efficacy group was 22/47, which was significantly higher than 3/78 in good efficacy group (χ2=33.83, P<0.01). The preoperative hemoglobin level of patients in poor efficacy group was (102±17) g/L, which was significantly lower than (113±20) g/L in good efficacy group (t=-3.24, P<0.01). The preoperative CRP level of patients was 39.1 (14.1, 91.6) mg/L in poor efficacy group, which was significantly higher than 15.3 (6.6, 42.0) mg/L in good efficacy group (Z=-3.04, P<0.01). There were no statistically significant differences in other indexes between patients in the two groups (P>0.05). Multivariate logistic regression analysis showed that age, lower limb paroxysmal myospasm, and preoperative hemoglobin level were the independent risk factors for poor efficacy after flap repair operation in patients with pressure ulcers (with odds ratios of 1.03, 40.69, and 0.97, 95% confidence intervals of 1.00-1.06, 9.18-180.39, and 0.95-1.00, respectively, P<0.05 or P<0.01). Conclusions: Poor efficacy after flap repair operation in patients with pressure ulcers is affected by many factors, among which the age, lower limb paroxysmal myospasm, and preoperative hemoglobin level are the independent risk factors.

[Clinical efficacy and safety of transvaginal pelvic floor reconstruction with TiLOOP mesh].

Objective: To evaluate the short-term clinical efficacy and safety of transvaginal pelvic floor reconstruction with TiLOOP mesh, a titanized polypropylene lightweight mesh. Methods: From November 2017 to July 2019, 50 patients underwent surgery, who were with anterior vaginal prolapse stage Ⅲ-Ⅳ and (or) apical prolapse and posterior vaginal prolapse (stage Ⅰ-Ⅱ); 37 patients underwent self-cut TiLOOP mesh and 13 patients underwent pre-cut mesh-kit procedure. The subjective and objective parameters (including surgical success) of them were evaluated. Results: The mean follow-up time was (18±6) months. The overall surgical success rate was 90% (45/50). Prolapse recurrence rates were isolated anterior 2% (1/50), isolated apical 2% (1/50) and isolated posterior 6% (3/50). None of recurrent patients underwent re-treatment, including either surgery or use of a pessary at last follow-up. According to patient global impression of improvement (PGI-I), 46 patients (92%, 46/50) were very much better, and 4 patients (8%, 4/50) were much better. After the operation, pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire-short form 7 (PFIQ-7) scores were significantly lower than those before operation (all P<0.05); pelvic organ prolapse-urinary incontinence sexual questionnaire 12 (PISQ-12) score was no significant difference before and after operation (P>0.05), but without dyspareunia. The vaginal mesh erosion rate was 12% (6/50) and the stress urinary incontinence was observed in 2 cases (4%, 2/47). Conclusion: Transvaginal pelvic floor reconstruction with TiLOOP mesh is a safe and effective surgery, short-term efficacy is acceptable, how to reduce the mesh erosion still need to be explored.

SCH58261, the antagonist of adenosine A2A receptor, alleviates cadmium-induced preeclampsia via sirtiun-1/hypoxia-inducible factor-1α pathway in rats.

OBJECTIVE: To identify the role of adenosine A2A receptor (A2AR) in cadmium-induced preeclampsia (PE) rats and the potential molecular mechanism. PATIENTS AND METHODS: The expression of A2AR in placentae obtained from PE women and normal pregnant (NP) women were measured. The pregnant rats were randomly divided into four groups, including NP rats, PE rats, SCH+NP rats, and SCH+PE rats. The 0.125 mg/kg/d CdCl2 was used to establish a PE rat model in PE and SCH+PE rats. SCH58261 was used as the specific antagonist of A2AR with a concentration of 0.2 mg/kg in SCH+NP and SCH+PE rats. The conditions of mother, foetus, and placenta were tested. The placental expression of A2AR, sirtuin-1 (sirt1), and Hypoxia-Inducible Factor-1α (HIF-1α) was measured by Western blot (WB) and immunohistochemistry (IHC) staining. RESULTS: A2AR and HIF-1α increased, and sirt1 decreased in placenta in both PE women and cadmium-induced PE rats. After treatment with SCH58261, the sirt1 increased and HIF-1a decreased in cadmium-induced PE rats along with the amelioration of maternal outcomes, foetal and placental growth. CONCLUSIONS: This paper firstly revealed that placental A2AR mediated cadmium-induced PE, and A2AR suppression could attenuate placental impairment by acting on the expression of sirt1 and sirt1-mediated regulation of HIF-1α.

Additively manufactured biomedical Ti-Nb-Ta-Zr lattices with tunable Young's modulus: Mechanical property, biocompatibility, and proteomics analysis.

Some ß-Ti alloys, such as Ti-Nb-Ta-Zr (TNTZ) alloys, exhibit a low Young's modulus and excellent biocompatibility. These alloys are promising new generation biomedical implant materials. Selective laser melting (SLM) can further enable customer-specific manufacturing of ß-Ti alloys to satisfy the ever-increasing need for enhanced biomedical products. In this study, we quantitatively determined the relationships between porosity, yield strength, and Young's modulus of SLM-prepared TNTZ lattices. The study constitutes a critical step toward understanding the behavior of the lattice and eventually enables tuning the Young's modulus to match that of human bones. Fatigue properties were also investigated on as-printed lattices in terms of the stress limit. The biocompatibility study included a routine evaluation of the relative cell growth rate and a proteomics analysis using a common mouse fibroblast cell line, L929. The results indicated that the as-printed TNTZ samples exhibited evidence of protein proliferation of the L929 cells, particularly P06733, and that those proteins are responsible for biological processes and molecular functions. They in turn may have promoted cell regeneration, cell motility, and protein binding, which at least partially explains the good biocompatibility of the as-printed TNTZ at the protein level. The study highlights the promising applications of additively manufactured TNTZ as a bone-replacing material from mechanical and biocompatibility perspectives.

[Evaluation of potential renal acid load for estimating the health effects of drinking water].

There is a lack of a reliable comprehensive evaluation indicator to access the health effects of drinking water. In recent years, scholars established an indicator to evaluate the comprehensive effect of drinking water on the body's acid-base balance. This indicator came from the potential renal acid load (PRAL) of food and named the potential renal acid load of drinking water. It included several typical anions and cations which are widely found in drinking water. This article reviewed the application, advantages, and disadvantages of PRAL in accessing the effect of drinking water on body acidbase metabolism.

[The blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing].

Objective: To explore the blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing. Methods: A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q1-Q4 groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results: The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) µg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q1 group, the OR (95%CI) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q3 group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI) value of high long term memory (LTM) scores in Q4 group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose-response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion: The blood lead level of school-age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long-term memory ability.

Crystalline characteristics of annealed AlN films by pulsed laser treatment for solidly mounted resonator applications.

AlN films were deposited on Si substrates using a reactive RF magnetron sputtering process and then the films were annealed by using different laser powers and wavelengths (355 nm, 532 nm and 1064 nm). For all three laser systems, the (002) peak intensity was obviously improved following laser irradiation. The improvement in the crystalline property was particularly obtained in the AlN film processed at 355 nm. In particular, given the use of the optimal laser power (0.025 W), the (002) peak intensity was 58.7% higher than that of the as-deposited film. The resonant frequency and 3 dB bandwidth of a SMR filter with an unprocessed AlN film were found to be 2850 MHz and 227.81 MHz, respectively. Following laser treatment with a wavelength of 1064 nm and a power of 0.25 W, the resonant frequency changed from 2850 to 2858 MHz. Moreover, 3 dB bandwidth changed from 227.81 to 202.49 MHz and the return loss of the filter reduced from 17.28 to 16.48 dB. Overall, the results thus show that the frequency response of the SMR filter can be adjusted and the return loss reduced by means of laser treatment with an appropriate wavelength.

Effects of porcine epidemic diarrhea virus infection on tight junction protein gene expression and morphology of the intestinal mucosa in pigs.

Tight junction proteins are important for the maintenance and repair of the intestinal mucosal barrier. The present study investigated relationships among tight junction protein gene expression, porcine epidemic diarrhea virus (PEDV) infection, and intestinal mucosal morphology in piglets. We compared the expression of six tight junction proteins (ZO-1, ZO-2, Occludin, Claudin-1, Claudin-4, and Claudin-5) between seven-day-old piglets infected with PEDV and normal piglets, as well as in PEDV-infected porcine intestinal epithelial cells (IPEC-J2). We also evaluated differences in mucosal morphology between PEDV-infected and normal piglets. The expression of six tight junction protein genes was lower in PEDV-infected piglets than in the normal animals. The expression of ZO-1, ZO-2, Occludin, and Claudin-4 in the intestine tissue was significantly lower (p⟨0.05) in PEDV-infected than in normal piglets. The expression of Claudin-5 in the jejunum was significantly lower in PEDV-infected piglets than in the normal animals (p⟨0.01). The expression of Claudin-1 and Claudin-5 genes in the ileum was significantly higher in PEDV-infected piglets than in normal piglets (p⟨0.01). Morphologically, the intestinal mucosa in PEDV-infected piglets exhibited clear pathological changes, including breakage and shedding of intestinal villi. In PEDV-infected IPEC-J2 cells, the mRNA expression of the six tight junction proteins showed a downward trend; in particular, the expression of the Occludin and Claudin-4 genes was significantly lower (p⟨0.01). These data suggest that the expression of these six tight junction proteins, especially Occludin and Claudin-4, plays an important role in maintaining the integrity of the intestinal mucosal barrier and resistance to PEDV infection in piglets.

[Association of maternal nocturnal sleep throughout pregnancy with the early nocturnal sleep of infants].

Objective: To investigate the association between maternal nocturnal sleep during pregnancy and their infants' nocturnal sleep patterns in early infancy by establishing a birth cohort. Methods: In this prospective study,healthy pregnant women and their infants were recruited in Chongqing Health Center for Women and Children from September 2013 to January 2014. A total of 40 healthy pregnant women and their infants were enrolled, and 34 pairs (85%) completed the whole survey. Actiwatch, wearing on the mother's wrist or infant's ankle,was used to monitor nighttime sleep at home for 7 times in total,with 7 consecutive days for each monitoring course. Pregnant women were monitored at 16, 24, 32 weeks gestational age, and were required to finish Pittsburgh Sleep Quality Index (PSQI) scale at the end of each monitoring. Their infants were initially monitored at 14 days after birth, followed by 1(st), 2(nd), and 3(rd) month after birth,with sleep diary recorded by parents. Pearson correlation analysis and multivariate linear regression were used to investigate the potential correlation between these two sleep patterns. Results: The average nocturnal sleep time was (465±53) min throughout pregnancy, with increased trend in the latency of maternal nighttime sleep onset ((30±15), (34±29), (38±30) min) while decreasing of average sleep efficiency ((85±5)%, (84±8)%, (83±8)%). The longest night sleep duration decreased from (382±74) min in the first trimester to (330±83) min in the third trimester (F=4.932, P<0.05), while awakening time after sleep onset (WASO) correspondingly increased from (27±22) min to (53±25) min (F=12.605, P<0.05). In terms of infants, the latency of nighttime sleep onset decreased from (43±33) min on the 14th day to (20±29) min at 3-month of age (t=3.281, P=0.002), while the longest nighttime sleep duration increased from (20±62) min to (265±140) min (t=3.867, P<0.01); meanwhile, the total nocturnal sleep time and the sleep efficiency increased from (373±126) min and (63±28)% to (431±103) min and (75±16)%, respectively (t=2.362, P=0.024; t=2.418, P=0.039, respectively). After adjusting for maternal age and body mass index (BMI), parental educational level and family income, maternal mood, exposure to tobacco and alcohol during pregnancy, method of delivery, as well as infants' gender, feeding patterns and gestational weeks, the regression analysis showed that the total nocturnal sleep time and the longest nighttime sleep duration during pregnancy were positively correlated with the corresponding parameters of their infants at the age of 3 months (B=0.541, 95%CI 0.168-0.914, t=2.882, P=0.005; B=0.310, 95%CI 0.035-0.586, t=2.240, P=0.027, respectively). Conclusions: The total nocturnal sleep time and the longest nighttime sleep duration during pregnancy are positively correlated with the corresponding parameters of their infants in early infancy. Paying more attention to improve maternal sleep quality may facilitate their infants to establish sleep-wake patterns early.

Paraneoplastic Cerebellar Degeneration in Nasopharyngeal Carcinoma: a Unique Association.

Paraneoplastic cerebellar degeneration (PCD) is a rare disorder that is associated with lung or gynecological malignancies and Hodgkin lymphoma. Neurologic symptoms are commonly the initial presenting sign leading to the diagnosis of an underlying malignancy. We are presenting an Asian male with progressive lower extremity weakness with EBV-positive nasopharyngeal carcinoma (NPC) and anti-Yo antibodies. Peculiarly, transient diffuse leptomeningeal enhancement is seen on MR imaging. This is the first report of PCD associated with NPC and thus illustrates that PCD embodies a boarder set of disease than previously described.

No high Tibetan Plateau until the Neogene.

The Late Paleogene surface height and paleoenvironment for the core area of the Qinghai-Tibetan Plateau (QTP) remain critically unresolved. Here, we report the discovery of the youngest well-preserved fossil palm leaves from Tibet. They were recovered from the Late Paleogene (Chattian), ca. 25.5 ± 0.5 million years, paleolake sediments within the Lunpola Basin (32.033°N, 89.767°E), central QTP at a present elevation of 4655 m. The anatomy of palms renders them intrinsically susceptible to freezing, imposing upper bounds on their latitudinal and altitudinal distribution. Combined with model-determined paleoterrestrial lapse rates, this shows that a high plateau cannot have existed in the core of Tibet in the Paleogene. Instead, a deep paleovalley, whose floor was <2.3 km above mean sea level bounded by (>4 km) high mountain systems, formed a topographically highly varied landscape. This finding challenges prevailing views on tectonic processes, monsoon dynamics, and the evolution of Asian biodiversity.

EDACO, a derivative of myricetin, inhibits the differentiation of Gaoyou duck embryonic osteoclasts in vitro.

1. This study determined the effects of (E)-3-(2-(4-(3-(2,4-dimethoxyphenyl)acryloyl)phenoxy)ethoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (EDACO) on the differentiation of Gaoyou duck embryonic osteoclasts cultured in vitro. 2. Bone marrow mononuclear cells (BM-MNC) were collected from 23-d-old Gaoyou duck embryos and induced by macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand in the presence of EDACO at different concentrations (i.e. 10, 20, 40, 80 and 160 µM). Tartrate-resistant acid phosphatase (TRAP) staining and resorption ability determination were conducted. 3. Results suggested that EDACO suppressed the shaping of positive multinucleated cells and the number of TRAP-positive cells in the 20, 40, 80 and 160 µM EDACO groups was significantly decreased (P < 0.05 or P < 0.01). Besides, the absorption activity of differentiated duck embryonic osteoclasts was significantly inhibited (P < 0.05) in both 80 and 160 µM EDACO groups. 4. Overall, EDACO can inhibit the differentiation of BM-MNC into mature osteoclasts in duck embryos.1.

Low-modulus biomedical Ti-30Nb-5Ta-3Zr additively manufactured by Selective Laser Melting and its biocompatibility.

Low Young's modulus titanium alloys, such as Ti-30Nb-5Ta-3Zr (TNTZ) of this study, were promising biocompatible implant materials. In this work, TNTZ samples with relative density of 96.8%-99.2% were additively manufactured by powder-bed based Selective Laser Melting (SLM) through tuning processing parameters, i.e. varying the point distance between 50 and 75 µm, laser exposure time between 135 and 200 µs, and a fixed laser power of 200 W. The microstructure, elastic properties, fatigue properties and machining accuracy of the fabricated samples have been investigated. Lattice structure TNTZ samples with porosity of 77.23% were also fabricated to further reduce the Young's modulus of the TNTZ. According to the Relative Growth Rate (RGR) value, the as-printed TNTZ samples exhibited no cell cytotoxicity, where they showed even better biocompatibility than the comparative, as-printed Ti-6Al-4V samples. The as-printed TNTZ developed by the study demonstrates good biocompatibility, low stress shielding tendency and high mechanical properties.