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Aggression among adolescents is a significant public health concern worldwide. To safeguard adolescents' physical and mental health, controlling the incidence of aggressive behavior and its triggers and drivers is necessary. Different risk factors in each environment drive adolescent aggression. These factors are interconnected, making the environment an ecosystem of aggression. This study aims to analyze the factors that influence adolescents' aggressive behavior and provide a basis for formulating measures to reduce such behavior in the future. This multicenter cross-sectional study was conducted in five middle schools in Lingbao City. The participants were junior high school students aged 11-15 years. Data were analyzed from January to March 2020 using the decision tree analysis method. The aggressive behavior scale, adolescent emotion regulation scale, family intimacy and adaptation scale, parental education participation scale, and a simple parenting style questionnaire were used for the investigation. Of the 581 participants, 25.5% demonstrated a tendency for aggressive behavior, while the remaining did not. The decision tree analysis showed that the incidence of adolescent aggression was the highest (54.8%) when the maternal overprotective score was greater than or equal to 17, the adolescent had low emotional control, and the mother's intelligence score was higher than 30. The decision tree model reflects the influencing factors of adolescent aggressive behavior from multiple levels and provides a reference for formulating effective intervention measures to control such behavior and its influencing factors.

Elevating stiffness without compromising compliance and agility is a key problem for soft finger applications, especially for articulate ones. Inspired by human finger, a multijoint soft finger with dual morphing through active/passive variable rigidity is proposed. The fabricated soft finger weighs 27.4 g. Conductive thermoplastic starch polymers (CTPSs) are embedded in a U-shape-joint pneumatic soft actuator segmentally like biological phalanges. Their stiffness can be independently adjusted utilizing customized thermomechanical property. Yoshimura origami imitating ligaments can passively match deformation and stiffness of the joints. Through electrothemal activation of CTPSs, the finger can realize dual independent articulate morphing: stiffened phalanges (mode 1) for dexterous manipulation and heavy load, softened phalanges (mode 2) for large deformation contact and light load. Comparative experiments of bending angle, output force, and stiffness are carried out between the active and passive stiffness adjustment of mode 1 and mode 2. The results show that the output force and stiffness of the finger adopting mode 1 can be improved more than two times and five times, and its compliance using mode 2 is almost similar, compared with the pure soft one. To further demonstrate performances of dual-mode morphing, a three-fingered gripper is assembled for grasping and manipulating targets with different shapes, sizes, rigidity, and weight, including playing card, unshelled raw egg, grapes, and unscrewing the bottle cap. It can successfully lift a dumbbell weighing 1460 g with a 7.6 load/weight ratio through a two-mode switch.

Table S1:Summary of baseline pathological diagnosis; Table S2:Noncompartmental Pharmacokinetic Summary Following Oral Administration of ralimetinib on Day 1 and on Day 14 (Cycle 1) - Capsule Formulation; Table S3: Noncompartmental Pharmacokinetic Summary Following Oral Administration of ralimetinib on Day 1 and on Day 14 (Cycle 1) - Tablet Formulation

Trial Profile

Purpose: p38 MAPK regulates the production of cytokines in the tumor microenvironment and enables cancer cells to survive despite oncogenic stress, radiotherapy, chemotherapy, and targeted therapies. Ralimetinib (LY2228820 dimesylate) is a selective small-molecule inhibitor of p38 MAPK. This phase I study aimed to evaluate the safety and tolerability of ralimetinib, as a single agent and in combination with tamoxifen, when administered orally to patients with advanced cancer.Experimental Design: The study design consisted of a dose-escalation phase performed in a 3+3 design (Part A; n = 54), two dose-confirmation phases [Part B at 420 mg (n = 18) and Part C at 300 mg (n = 8)], and a tumor-specific expansion phase in combination with tamoxifen for women with hormone receptor–positive metastatic breast cancer refractory to aromatase inhibitors (Part D; n = 9). Ralimetinib was administered orally every 12 hours on days 1 to 14 of a 28-day cycle.Results: Eighty-nine patients received ralimetinib at 11 dose levels (10, 20, 40, 65, 90, 120, 160, 200, 300, 420, and 560 mg). Plasma exposure of ralimetinib (Cmax and AUC) increased in a dose-dependent manner. After a single dose, ralimetinib inhibited p38 MAPK–induced phosphorylation of MAPKAP-K2 in peripheral blood mononuclear cells. The most common adverse events, possibly drug-related, included rash, fatigue, nausea, constipation, pruritus, and vomiting. The recommended phase II dose was 300 mg every 12 hours as monotherapy or in combination with tamoxifen. Although no patients achieved a complete response or partial response,19 patients (21.3%) achieved stable disease with a median duration of 3.7 months, with 9 of these patients on study for ≥6 cycles.Conclusions: Ralimetinib demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. Clin Cancer Res; 22(5); 1095–102. ©2015 AACR.

The impacts of body mass index (BMI) on the prognosis of primary IgA nephropathy (IgAN) remain controversial. This systematic review and meta-analysis aimed to solve these issues. We searched the PubMed, EMBASE, and Cochrane Library to screen articles investigating the BMI and primary IgAN. BMI was classified according to the World Health Organization as high (≥ 25.0 kg/m2) and low (

Sheng Yin,1,* Wen Gao,2,* Peipei Shi,1 Meili Xi,1 Wenbin Tang,1 Jiarong Zhang1 1Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Gynaecologic Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiarong ZhangDepartment of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Fenglin Road, 180#, Xuhui District, Shanghai, 200032, People’s Republic of ChinaTel +86 21-64041990Email zhang.jiarong@zs-hospital.sh.cnPurpose: Minimally invasive surgery (MIS) is performed frequently in early-stage ovarian cancer patients, especially in ovarian clear cell carcinoma (OCCC). The aim of this study was to investigate whether primary laparoscopic surgery influences prognosis in patients with early-stage OCCC.Patients and Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I OCCC were retrospectively reviewed in two hospitals between April 2010 and August 2020. Clinical data were abstracted, and patients were followed up until February 2021. Patients were divided into open surgery (laparotomy) and laparoscopy groups, and the Kaplan–Meier method was applied to compare progression-free survival (PFS) and overall survival (OS) between the groups. Statistical differences were determined by the Log rank test.Results: Eighty-nine patients were included in the study; 20 (22.5%) and 69 (77.5%) patients underwent laparoscopic and open surgery, respectively. The patients’ characteristics were well-balanced except that patients in the laparoscopy group tended to have smaller tumors and lower frequency of omentectomy and lymphadenectomy compared with the open surgery group. The median follow-up duration was 42.6 and 36.5 months in the laparoscopy and open surgery groups, respectively. Nine (10.1%) patients developed recurrence, and 4 (4.5%) died of the disease; all in the open surgery group. The estimated 2-year PFS rates were 100.0% and 90.1%, and the estimated 5-year OS rates were 100.0% and 91.9% in the laparoscopy and open surgery groups, respectively. No significant survival differences were found between the groups.Conclusion: Survival was not compromised when primary laparoscopic surgery was performed in early-stage OCCC patients. A well-designed randomized controlled trial is warranted.Keywords: laparoscopic surgery, early-stage ovarian clear cell cancer, prognosis

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

Background Renal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear. Materials and methods HK-2 cells were treated with TGF-β1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo. Results PVT1 was upregulated in TGF-β1-treated HK-2 cells. In addition, TGF-β1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-βR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo. Conclusion Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.

Advanced technologies and big data have brought new visions and methods to urban planning research. Based on the Baidu heat map and POI data of two typical days (a weekend day and a workday) in 2018, this paper analyses the spatial and temporal aggregation patterns of crowds in the urban centre of Wuhan using ArcGIS. Aggregation patterns are defined by the intensity of population activities and the places where crowds gather. In terms of time, the daily change of population aggregation intensity is studied by counting the heat value of 24 moments captured throughout the day. The results show that on rest days, people prefer to travel around noon and in the afternoon, reaching the highest peak of the day around 15:00, while on workdays, residents' activities are affected by commuting, with obvious 'morning rush hours' and 'evening rush hours'. Firstly, the spatial correlation between the density of POI distribution and the degree of population aggregation has been studied by the spatial coupling relationship between the Baidu heat map and POI data. Secondly, the index of correlation between the aggregation of different POIs and population (ICPP) are mentioned to analyse the purposes and the degrees of aggregation during weekend and workday rush hours. Based on the ICPP, we analyse activities from three aspects: the different ICPPs between the workday and the weekend; the different ICPPs between the morning, afternoon and evening; and the different ICPPs among different POIs.

Large convolutional neural network models have recently demonstrated impressive performance on video attention prediction. Conventionally, these models are with intensive computation and large memory. To address these issues, we design an extremely light-weight network with ultrafast speed, named UVA-Net. The network is constructed based on depth-wise convolutions and takes low-resolution images as input. However, this straight-forward acceleration method will decrease performance dramatically. To this end, we propose a coupled knowledge distillation strategy to augment and train the network effectively. With this strategy, the model can further automatically discover and emphasize implicit useful cues contained in the data. Both spatial and temporal knowledge learned by the high-resolution complex teacher networks also can be distilled and transferred into the proposed low-resolution light-weight spatiotemporal network. Experimental results show that the performance of our model is comparable to 11 state-of-the-art models in video attention prediction, while it costs only 0.68 MB memory footprint, runs about 10,106 FPS on GPU and 404 FPS on CPU, which is 206 times faster than previous models.

Phytomining is suggested as a technology to obtain platinum group metals (PGMs) nanoparticles from plants grown on the mineralized soils or tailings. Samples from North American Palladium (Canada) and gossans from Broken Hill (BH) (Australia) were studied to assess the possibility of using these PGM-rich samples as substrates for phytomining. The bioavailability of PGMs was indirectly assessed using geochemical procedures. The selective extractions showed that the highest available concentration of Pd is 5.38 ppm in BH gossan 1. The extraction of PGMs by ammonium acetate, fulvic acid or citrate-dithionite indicates natural availability to plants. The BH gossan 1 was the best of the five studied samples for phytomining of Pd due to available Pd concentration (> 2 mg/kg), low Electric Conductivity (< 2dS/m), high CEC (Cation Exchange Capacity) (38.8 meq/100g), and proper pH (6.5). Cu-tolerant plant species should be chosen to grow on BH gossan 1. A criterium for choosing substrates for phytomining of Pd was developed comprising various classical soil parameters plus selective extraction procedures.

Objective To investigate the renal pathology and transitions of children who received a renal biopsy at the First Affiliated Hospital of Zhengzhou University between 2012 and 2020. Methods The clinical and pathological data of children with a renal biopsy were analyzed retrospectively. The changes in the distribution of pathological types were examined in age groups of 3 years (-1, -3, -6, -12, -16 years) and gender. Results 1928 children with renal biopsies were included in the analysis. The mean age of the children was 8.18±SD 3.40 years and the ratio of males to females was 1.71. The main pathological types of primary glomerular disease were minimal change disease (MCD) and IgA nephropathy, while the main pathological types of secondary glomerulonephritis were lupus nephritis and Henoch-Schonlein purpura (HSPN). The male to female ratio and age distribution between lupus nephritis and HSP were significantly different.

The pathophysiology of septic acute kidney injury (AKI) is very complex and the fatality is high. Nrf2 is crucial for septic AKI, and dihydromyricetin (DMY) has a protective effect on LPS-induced AKI. We aimed to explore whether DMY could affect Nrf2 pathway by regulating miR-199b-3p and played a protective role in septic AKI. The mouse model was induced by cecal ligation and puncture (CLP) and the cell model was stimulated by LPS. Enzyme-linked immunosorbent assay was conducted to examine MDA, SOD, LDH, GSH, TNF-α, kidney injury molecule 1 (KIM-1), and IL-6 levels. The pathological changes were observed by hematoxylin–eosin staining. The targeted relationship between miR-199b-3p and Nrf2 was verified by a dual-luciferase reporter assay. Levels of SOD, GSH, NQO-1, Nrf2, and HO-1 were decreased, MDA, LDH, TNF-α, IL-6, and KIM-1, and miR-199b-3p were increased in the CLP group and LPS-induced HK-2 cells, while the effect was reversed after DMY treatment. There existed renal tubule cell edema and necrosis, inflammatory cell infiltration in the CLP group, the situation was partially improved by DMY. MiR-199b-3p bound to Nrf2. Nrf2 levels were increased, TNF-α, IL-6, and KIM-1 were decreased after transfected with miR-199b-3p inhibitor, these effects were reversed when co-transfected with si-Nrf2. TNF-α, IL-6, KIM-1, and miR-199b-3p levels were increased; Nrf2, NQO-1, and HO-1 levels were decreased in the LPS + DMY + mimics-miR group. MiR-199b-3p was increased in septic AKI models, DMY might alleviate septic AKI by regulating miR-199b-3p to affect the Nrf2 pathway.

Achieving both high compliance and stiffness is a key issue in stiffness-tunable soft robots. A wide-range variable-stiffness method keeping pure soft characteristic is proposed by bioinspired design of deep-sea glass sponges adopting thermoplastic starch. The stiffness-tunable mechanism is designed through force analysis and optimization of its bionic cellular structure. It is fabricated with load-weight ratio exceeding 470. Then, a wide-range stiffness-tunable omnidirectional-bending soft actuator (WOSA) is realized, and the bending stiffness model is established. Comparative experiments of stiffness and deformation are conducted on WOSA and a pure soft actuator (PSA) with the same size. Results show that the WOSA can get 92.3 times initial bending and 70.8 times torsional stiffness variation range, of which the flexibility is even better than PSA. A gripper assembled by three WOSAs is verified through stiffness adjustment that it can grasp different weight fragile, soft items from the unshelled fresh egg, boiled egg yolk to grapes. It can even lift a dumbbell weighting 3.32 kg. Finally, a manipulator demonstrated its potential in future minimally invasive surgical applications due to its wide stiffness range and large deformation capacity.

Mesoporous silica nanoparticles have been extensively explored in anticancer nanomedicine due to their excellent biodegradability, which is one important focus in their further clinical translations. However, the traditional design concepts based on the functional modification with active groups cannot significantly improve the controlled drug release efficiency and anticancer effect. Herein, a molecularly organic–inorganic hybrid mesoporous silica nanoparticle (HMSN) nanocarrier coated with hyaluronic acid (HA) and polyethyleneimine (PEI) was constructed for the gene/chemo-synergetic therapy of breast cancer. Notably, HMSN with tumor-sensitive disulfide bond and targeting ligand HA can be decomposed when it encounters high concentration of glutathione (GSH) and hyaluronidase (HAase). The biodegradability of host molecules and the fast disintegration of the framework in tumor microenvironment can also accelerate the stimuli responsive release of cargos inside the pore space. Furthermore, the grafting of polyethyleneimine (PEI) could increase gene loading efficiency. From the above, the smart approach involves a combination of biodegradability and biological effect and results in synergetic antitumor effect of gene and chemical drug on breast cancer. All these findings demonstrated that HMSN/HA/PEI nanocarriers can be suitable for biomedical application, paving the way to fast development of multi-functional nano-biomedicine.

Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of some cancer types, but little is known whether it is a bystander or an actual player on driving immune infiltration in ovarian cancer.Methods: In this study, the expression of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and SPP1 immumohistochemical staining analysis was assessed by The HPA database. The clinical outcomes between SPP1 expression and ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were explored using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database.Results: SPP1 was found overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter OS and PFS survivals. Particularly, elevated SPP1 expression was significantly associated with stage III ovarian cancer. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in ovarian cancer. Of particular importance, functional enrichment analysis suggested that SPP1 strong related with immune response.Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer.Trial registration: Not applicable.

Continuous subcutaneous insulin infusion (CSII) is an intensive insulin therapy for patients with type 2 diabetes mellitus (T2DM) who have poor glycemic control, but its effect on T2DM-related bone disorder is unclear. This study described the possible mechanisms by which CSII affects bone remodeling, structures, and mechanical properties in T2DM rats. Herein, male rats (6-week-old) were assigned randomly to 4-week and 8-week administration groups, each of which included healthy control, T2DM, CSII, and Placebo groups. Then, metabolic markers, bone formation and resorption markers in serum and protein expressions of osteoclastogenesis regulators in tibias were detected. Meanwhile, microstructures, nanostructures, macro-mechanical properties, nano-mechanical properties, and mineral compositions in femurs were evaluated. 4-week later, CSII treatment restored circulatory metabolites, bone formation and resorption markers, and osteoclastogenesis regulators, improved certain bone microstructures, decreased matrix mineralization, and increased fracture toughness in T2DM rats. For 8-week group, CSII treatment restored bone formation and resorption markers, osteoclastogenesis regulators, and bone microstructures, besides improved bone mineral compositions and nanostructures, enhanced bone mechanical properties such as fracture toughness, maximum load, elastic modulus, indentation modulus and hardness. Collectively, 8-week CSII treatment is more conducive to ameliorating bone structures and mechanical properties in T2DM rats by regulating bone remodeling compared with 4-week CSII treatment, thus improving whole bone quality and providing valuable information for clinical prevention and treatment of T2DM-related bone disorders.

BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare, difficult-to-treat type of smooth muscle tumor that originates from the uterine myoma. However, its clinical characteristics, management, and prognosis are not clearly understood. Moreover, the 2 different methods used to diagnose IVL—incidental and nonincidental—result in completely different treatments. METHODS: We conducted a single-center, retrospective study. Our real-life case series included patients pathologically diagnosed with IVL between July 2011 and December 2020. All patients with IVL were divided into 2 groups: an incidental group and a nonincidental group. Medical records of patients, including clinical characteristics, primary treatment, treatment after recurrence, and prognosis, were reviewed. RESULTS: A total of 39 patients were included in the study, with a median patient age of 47 years. Of the 39 cases, 15 (38.5%) were incidentally diagnosed with only intrapelvic tumors. Among the 24 patients with IVL in the nonincidental group, tumor spread in the inferior vena cava, right heart, and pulmonary artery was identified in 4, 17, and 3 patients, respectively. The most common symptoms were abnormal uterine bleeding in the incidental group and chest distress and dyspnea in the nonincidental group. Among the 15 patients in the incidental group, ovary-preserving surgery was performed in 6 young women (≤40 years old), of whom 3 underwent myomectomy. All 24 patients with IVL in the nonincidental group underwent thrombectomy without uterine or ovary preservation by multidisciplinary surgical treatment. Only 1 patient in each group underwent postoperative adjuvant therapy. During the median follow-up of 36.0 months, recurrence was recorded in 5 (12.8%) cases in the incidental group, with no deaths recorded. Only 1 patient was lost to follow-up. No recurrence was noted in the cases in the nonincidental group. Among the 5 patients who experienced recurrence, 4 received secondary surgical treatment and 1 received hormone therapy. All patients were alive as of this report. CONCLUSIONS: Patients with IVL who are diagnosed incidentally have a higher recurrence risk than those who are diagnosed nonincidentally and undergo complete tumor resection. However, patients incidentally diagnosed with IVL can still experience long disease-free survival rates following secondary surgical treatment after recurrence.

Poor bone quality induced by non-enzymatic glycation (NEG) of bone tissue in patients with type 2 diabetes mellitus (T2DM) is regarded as the major factor of bone fragility and affecting bone mechanical properties. A comprehensive and systemic mechanical investigation for evaluating the effect of NEG on bone was still lacking. In order to provide additional information for the bone quality of T2DM, the effects of NEG on mechanical properties of cortical bone were investigated in terms of elastoplasticity, fracture toughness and viscoelasticity. All samples of cortical bone, including the samples of strength test (n = 20), fracture toughness test (n = 40, quasi-static and fall-like conditions with displacement rates of 10−3 mm/s and 10 mm/s, respectively) and stress relaxation test (n = 20), were harvested from bovine tibiae. The samples of each test were equally divided into incubated-control group and ribose-incubated group. All mechanical tests were performed after incubating all samples for 15 days. Post-yield strain (p = 0.014), post-yield energy (p

Background Renal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear. Materials and Methods HK-2 cells were treated with TGF-β1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo. Results PVT1 was upregulated in TGF-β1-treated HK-2 cells. In addition, TGF-β1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-βR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo. Conclusion Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.

NLRP3 is associated with multiple risks in graft-versus-host disease, though unifying principles for these findings remain largely unknown. To explore the effects and mechanisms of the absence of NLRP3 function on hepatic graft-versus-host-disease, we established an allogeneic hematopoietic cell transplantation mice model by infusing bone marrow mononuclear cells and spleno-T cells of the BALB/c mouse into either NLRP3 knockout (NLRP3-/- ) or wild-type C57BL/6 mice. Elevated inflammatory cell infiltration, liver fibrosis, and secretions of alanine aminotransferase (ALT) and aspartate transaminase (AST), together with weight loss, were observed in C57BL/6 recipients after transplantation. However, moderate injury pathology was detected in the liver of NLRP3-/- recipients at day 14, which gradually improved over time. Likewise, proinflammatory cytokine IL-1β, a downstream effecter of NLRP3 inflammasome activation, showed significantly lower expression (P < .05) in the liver of NLRP3-/- recipients relative to C57BL/6 recipients at day 7 and day 21. Moreover, compared with C57BL/6 recipients, the expression of both TNF-α and IL-1β were decreased 3-fold and 4.7-fold, respectively, at day 21 in NLRP3-/- recipients. Interestingly, NLRP1a was expressed at a significantly reduced level in the liver of NLRP3-/- recipients (P < .001). Furthermore, systemic inflammation was analyzed by measuring the concentration of IL-1β and adenosine triphosphate (ATP) in serum. The concentration of IL-1β achieved a maximum at day 14, then decreased at day 21 and day 28 in NLRP3-/- recipients. In contrast, the concentration of IL-1β in C57BL/6 recipients gradually increased from day 7 to day 28. ATP levels reduced from day 7 to day 28 in NLRP3-/- recipients, but were extremely high in C57BL/6 recipients from day 14 to day 28 (P < .01). The decreased levels of P2X7R were connected to less ATP in NLRP3-/- recipients at day 21 and day 28. In conclusion, NLRP3 knockout in recipients could significantly relieve liver injury after transplantation and block the NLRP3 inflammasome pathway, thus providing a promising strategy for the treatment of graft-versus-host disease prophylaxis.

The rising of flexible and potable electronics urgently calls for matchable and miniaturized energy storage system as power supply. Herein, we develop a solution-processable method to fabricate Ni@Ni(OH)(2) fiber to design an all-solid-state fiber-shaped Zn//Ni(OH)(2) battery. This battery exhibits a high open circuit voltage of 1.75 V which is close to the theoretical value, considerable discharge capacity of 704 mu Ah cm(-3) at current density of 0.5 A g(-1), good rate capability with 75 % capacity retention when the discharge current increases from 0.5 A g(-1) to 5 A g(-1) and good cycling stability (92 % capacity retention after 2000 charge-discharge cycles). Furthermore, the device performance remains unchanged under bending conditions, showing good flexibility and stability. It is believed that our design provides a promising strategy to fabricate long fiber-shaped Zn//Ni(OH)(2) battery as power supply for wearable electronics in future practical applications.

A sensitive fiber microelectrode for nonenzymatic glucose determination was fabricated by incorporating nickel hydroxide nanosheets into highly-aligned carbon nanotube scaffold. The as-prepared microelectrode featured a detection limit of 0.645 μM, high sensitivity of 12.2 mA cm−2 mM−1, wide linear-detection range from 20 μM to 10.5 mM, as well as an excellent anti-interference ability and repeatability.

The reactions of Ge, Sn, Pb, Sb, Bi, and Te atoms with silane molecules were studied using matrix-isolation Fourier transform infrared spectroscopy and density functional theoretical (DFT) calculations. All metals generate the inserted complexes HM-SiH3, which were stabilized in an argon matrix, while H2M═SiH2 and H3M≡SiH were not observed. DFT and CCSD(T) calculations show the insertion complex HM-SiH3 is the most stable isomer with a near right angle H–M–Si moiety. However, silydene complexes H2M═SiH2 (M = C, Si) were calculated and identified as the most stable complexes with the lighter elements. The bonding difference is mainly due to relativistic effects, which is that for heavier metal atoms valence s and p orbitals have a lower tendency to form hybrid orbitals.

Summary Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached. In part B (dose confirmation), patients received MTD. Safety, pharmacokinetics, pharmacodynamics, and tumor response data were evaluated. Results MTD was 30 mg Q12H. The most frequent treatment-related adverse events (>10%) were tremor, rash, stomatitis, increased blood creatine phosphokinase, and fatigue. Grade ≥ 3 treatment-related adverse events included upper gastrointestinal haemorrhage and increased hepatic enzyme, both occurring at 40 mg Q12H and considered dose-limiting toxicities. LY3007113 exhibited an approximately dose-proportional increase in exposure and time-independent pharmacokinetics after repeated dosing. Maximal inhibition (80%) of primary biomarker MAPK-activated protein kinase 2 in peripheral blood mononuclear cells was not reached, and sustained minimal inhibition (60%) was not maintained for 6 h after dosing to achieve a biologically effective dose (BED). The best overall response in part B was stable disease in 3 of 27 patients. Conclusions The recommended phase 2 dosage of LY3007113 was 30 mg Q12H. Three patients continued treatment after the first radiographic assessment, and the BED was not achieved. Further clinical development of this compound is not planned as toxicity precluded achieving a biologically effective dose.

Reactions of laser-ablated cerium atoms with silane were investigated by matrix isolation infrared spectroscopy and theoretical calculations. The reaction products, Si( μ -H) 3 CeH, H 3 SiCeH, H 2 Si( μ -H)CeH and HSi( μ -H) 2 CeH were identified on the basis of the SiD 4 isotopic substitutions and DFT frequency calculations. In the solid argon or krypton matrix, the inserted H 3 SiCeH molecule was observed as initial product on deposition, which rearranged to hydrogen bridge species Si( μ -H) 3 CeH on follow-up annealing through H 2 Si( μ -H)CeH and HSi( μ -H) 2 CeH species. The Si H Ce hydrogen bridge was investigated by NBO and ELF analysis. Calculation suggested that in Si( μ -H) 3 CeH molecule Ce atom donated one electron to Si atom, resulting in electron-rich SiH 3 subunit, which was confirmed by ESP and AIM analysis. The increased basicity of Si H bond facilitates the formation of hydrogen bridge bond between Si and Ce. For comparison only insertion H 3 CCeH structure was obtained from the reaction of Ce atoms with CH 4 .

Ultrathin vanadium oxide (V2O5) nanosheets with lateral sizes of up to tens of micrometers were synthesized, and then incorporated into multi-walled carbon nanotube (MWCNT) fibers. The solid-state supercapacitor based on such hybrid fibers exhibited an improved volumetric capacitance of 31 F cm−3 at 1.0 A cm−3, and a volumetric energy density of 2.1 mW h cm−3 at 1.5 W cm−3.

Soft robot has become a hot point because it has excellent adaptability and safety with environment However, poor motion accuracy and low stiffness have limit its applications. This paper proposes a cable-driven soft module coupled with spring. It has compact structure, large range of motion, standard plug-and-connect connector, and can be easily assembled into a soft manipulator or a gripper. The kinematics of the module and modular manipulator are established based on the piece-wise constant curvature (PCC) method. The nonlinear friction of cables and the gravity of the modules have been analyzed to obtain an accurate model. Experiments on modules and manipulators with different sizes and stiffness have demonstrated its accuracy. The modules can reach a maximum bending angle of 180°, and the error is within 2.5°. The manipulators can reach a total bending angle more than 270°, and the error does not exceed 5°. Finally a gripper equipped with three modules is developed. It can grasp objects with different shapes, fragility and weights range from 1g to 0.43kg. It also demonstrates the good flexibility and load capacity of the module.