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Introduction Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. Methods Mendelian randomization (MR) study was used to analyze the genomewide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). Results After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013–1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039– 5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013–1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161–1.538; p

Summary: Background: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. Methods: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y–V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. Results: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y–V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. Conclusion: Constricted posterior fourchette seriously affects the quality of life. Y–V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.

Cr3+-activated near-infrared (NIR) phosphors are key for NIR phosphor-converted light emitting diodes (NIR pc-LED). While, the site occupancy of Cr3+ is one of the debates that have plagued researchers. Herein, Y2Mg2Al2Si2O12 (YMAS) with multiple cationic sites is chosen as host of Cr3+ to synthesize YMAS: xCr3+ phosphors. In YMAS, Cr3+ ions occupy simultaneously Al/SiO4 tetrahedral, Mg/AlO6 octahedral, and Y/MgO8 dodecahedral sites which form three luminescent centers named as Cr1, Cr2, and Cr3, respectively. Cr1 and Cr2 relate to an intermediate crystal field, with transitions of 2E→4A2 and 4T2→4A2 occurring simultaneously. As Cr3+ concentration increases, the 4T2→4A2 transition becomes more pronounced in Cr1 and Cr2, resulting in a red-shift and broadband emission. Cr3 consistently behaves a weak crystal field and exhibits the broad and long-wavelength emission. Wide-range NIR emission centering at 745 ​nm is realized in YMAS: 0.03Cr3+ phosphor. This phosphor has high internal quantum efficiency (IQE ​= ​86%) and satisfying luminescence thermal stability (I423 K ​= ​70.2%). Using this phosphor, NIR pc-LEDs with 56.6 ​mW@320 ​mA optical output power is packaged and applied. Present study not only demonstrates the Cr3+ multi-site occupancy in a certain oxide but also provides a reliable approach via choosing a host with diverse cationic sites and local environments for Cr3+ to achieve broadband NIR phosphors.

Objective: To investigate the safety and feasibility of laparoscopic resection of focal nodular hyperplasia (FNH) in the hepatic caudate lobe. Methods: The clinical data of eight patients who underwent laparoscopic hepatic caudate lobe FNH resection at the Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of Army Medical University, were retrospectively analyzed. Results: The laparoscopic procedures were successful in all eight patients, and no patients required conversion to open surgery. Five patients underwent partial caudate lobe resection, one patient underwent caudate lobe resection, and two patients underwent combined left hemihepatectomy with caudate lobe resection. Tumor resection was performed using the left approach in five cases, the right approach in one case, the middle hepatic fissure approach in one case, and the left and right combined approach in one case. The operation time ranged from 120 to 360 min, with a mean of 225 min. The intraoperative blood loss ranged from 50 to 600 ml, with a mean of 235 ml. No postoperative bleeding, bile leakage or abdominal infection occurred. Conclusions: Laparoscopic resection of hepatic caudate lobe FNH was safe and feasible in appropriate patients. Skilled laparoscopic hepatectomy techniques, adequate preoperative evaluation, appropriate choice of surgical approach and the control of intraoperative bleeding are critical to perform this surgery.

Abstract As a transcriptional factor, the Forkhead box (FOX) gene family is closely connected with apoptosis, proliferation, and other cellular processes. FOXD2, as one descendant of the FOX gene family, has been mentioned in many articles to show a high expression in several cancers. However, whether FOXD2 has a connection with gastric adenocarcinoma remains an unanswered question. Expression of FOXD2 and IQGAP3 in gastric adenocarcinoma was evaluated by bioinformatics analysis, which was further detected by real‐time quantitative PCR (qRT‐PCR) and western blot. The downstream target genes of FOXD2 were also mined by bioinformatics analysis. Pathway enrichment analysis was then performed on the target genes. Chromatin immunoprecipitation assay (ChIP) and dual‐luciferase reporter assay were conducted to validate the regulatory relationship between FOXD2 and its downstream target gene IQGAP3. Methyl thiazolyl tetrazolium assay (MTT), combined with cell colony formation assay, was employed to assess the effect of FOXD2 and IQGAP3 on the proliferation of gastric adenocarcinoma cells. Intracytoplasmic Ca2+ concentration was measured by Fluo‐3 fluorescence staining. FOXD2 showed a high expression in gastric adenocarcinoma tissues and cells, and FOXD2 silencing considerably attenuated gastric adenocarcinoma cell proliferation. IQGAP3, a downstream target gene of FOXD2, had a positive connection with the expression of FOXD2. The binding relationship between FOXD2 and the promoter region of IQGAP3 was further verified by ChIP and dual‐luciferase reporter assays. The results of cell function experiments indicated that FOXD2 could promote gastric adenocarcinoma cell proliferation by transcriptionally activating IQGAP3 to induce an increase in intracellular Ca2+ level. This study confirmed that FOXD2 increased intracellular Ca2+ level through transcriptional activation of IQGAP3, which in turn propelled the proliferation of gastric adenocarcinoma cells, revealing the considerable significance of FOXD2 in the development of gastric adenocarcinoma.

The use of thermoplastic composites (TPCs) as one of the lightweight solutions will inevitably encounter problems in connection. Resistance welding has the characteristics of high strength, simplicity, and high reliability, and is considered a very potential hot-melt connection technology. The resistance welding technology of unidirectional carbon fiber-reinforced polyphenylene sulfide composites (UCF/PPS) was systematically studied. The experimental results show that the 100-mesh brass mesh has the best resin wetting effect and heating efficiency, and the PPS/oxidized 100-mesh brass mesh composite resistance element (Ox-RE/PPS) has the highest welding strength. The welding failure mode changes from interface failure and RE failure to interlayer structure damage and fiber fracture. The single-factor experimental results show that the maximum welding strength is reached at 310 °C, 1.15 MPa, and 120 kW/m2. According to the conclusion of the single-factor experiment, the Box–Behnken method was further used to design a three-factor, three-level experiment, and a quadratic regression model was established according to the test results. The results of variance analysis, fitting curve analysis, and perturbation plot analysis proved that the model had high fitting and prediction abilities. From the 3D surface diagram analysis, the influence of power density is the largest, and the interaction between welding temperature and power density is the most significant. Combined with the analysis of Design Expert 13 software, the optimal range of process parameters was obtained as follows: welding temperature 313–314 °C, welding pressure 1.04–1.2 MPa, and power density 124–128 kW/m2. The average strength of resistance welding joints prepared in the optimal range of process parameters was 13.58 MPa.

Zhang et al. perform high-precision zinc (Zn) isotopic analysis on lavas from St. Helena Island in the Atlantic, and Cook-Austral Islands in the Pacific, and confirm that ancient superficial carbonates were transported into the deep mantle billions of years ago.

Poly(arylene sulfide sulfone)/graphene nanoplate (PASS/GNP) composites with segregated structure based on continuous polymer fiber skeletons were fabricated by coating a thin conductive layer on the PASS fibers and then performing compression molding. The formation of a unique segregated conductive network endowed the PASS/GNP composites with high electrical conductivity and excellent electromagnetic interference (EMI) shielding effectiveness (SE), reaching 17.8 ​S/m and 30.1 ​dB, respectively, when the content of the GNPs in the conductive layer was 20 ​wt%. The PASS/GNP composites also exhibited outstanding mechanical properties, which was attributed to the continuous PASS fiber skeletons that could withstand large loads and the strong interfacial interaction between the conductive layers and the PASS fibers that could provide good stress transfer. This approach is suitable for most soluble polymers.

Poly (decamethylene terephthalamide/decamethylene isophthalamide)-block-polyvinyl alcoho) (PA10T/10I-PEG) copolymer/graphene oxide (GO) composites were prepared via in-situ melt polymerization and two different nano-filler addition approaches were compared. The relationship between the micro-structure and performance of the elastomer composites prepared by one-step and two-step methods was explored. The results show that the two-step method significantly promoted the dispersion of the GO in a polymer matrix, and facilitated the grafting of more hard molecular chains. Thus, the elastic modulus and tensile strength of the nano-composite have been significantly improved by the presence of GO. This was because of the strong interaction between the functional groups on the surface of the GO and the hard molecular chains. This would be also be favorable to load transfer across the interface. Additionally, the elongation at the break of composites increased by 10% with the addition of a small amount of GO (0.2% wt). This is because hard domains tend to be enriched on the surface of GO in composites and act as a lubricating layer at the interface between the GO and matrix, leading to increased deformation ability. This work provides an effective strategy to prepare elastomer composites with high strength and toughness.

Background and AimsAbnormal expression of E3 ubiquitin ligase plays an important role in the development and progression of hepatocellular carcinoma (HCC), although the mechanism has remained elusive. This study aimed to investigate the biological function and potential mechanism of FBXO43 in HCC.MethodsFBXO43 expression in tissues and cells were detected by quantitative real-time PCR (qRT−PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method and Cox regression analysis were used to explore the correlation between the expression level of FBXO43 and the clinical survival. MTT assay, EdU incorporation, colony formation, Transwell, and wound healing assays were performed to evaluate the function of FBXO43 in cell proliferation and migration in vitro. The interaction between FBXO43 and cyclin D1 (CCND1) was assessed by co-immunoprecipitation (Co-IP) assay and in vivo ubiquitination assay.ResultsWe found that FBXO43 was upregulated in HCC patient tissues and positively associated with poor clinicopathological features. Meanwhile, HCC patients with high expression of FBXO43 had shorter overall survival (OS) and disease-free survival (DFS). Furthermore, knockdown of FBXO43 inhibited HCC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in HCC cells. Mechanistically, FBXO43 interacted with CCND1 and promoted its stability by polyubiquitination, leading to HCC cell proliferation, migration and EMT. Functional rescue experiments demonstrated that knockdown of CCND1 blocks FBXO43-mediated cell proliferation and metastasis.ConclusionsFBXO43, as an independent prognostic biomarker, promotes HCC cell proliferation, metastasis and EMT by stability of CCND1, which provides a new potential strategy for HCC treatment by targeting FBXO43-CCND1 axis.

This study improved homemade apparatus for characterizing the interfacial shear strength (IFSS) of carbon-fiber-reinforced polyphenylene sulfide (PPS/CF) composites. The upgraded generation II experimental device includes a newly developed experimental clamp for samples, as well as testing systems. Compared with the initial generation I apparatus and the commercial Toei instrument, the generation II device is easier and more efficient to operate. The average interfacial adhesion values obtained using these devices were consistently approximately 40 MPa, with relatively low data scatter, showing excellent repeatability and applicability during microbond tests. Notably, the generation II experimental device was equipped with an additional high-frequency data-capturing tool to identify the debonding peak force more precisely, which demonstrated a higher interfacial shear strength of 42.81 MPa during testing. Therefore, the new instrument was able to reflect the change in the interfacial stress state during the interface debonding process more accurately and reliably.

Cr3+-Yb3+-co-doped phosphors that emit intense short-wave infrared light in the 900–1200 nm upon blue light excitation have been developed.

The in-situ formed MgAl2O4–CaAl12O19 (MA–CA6) composites were fabricated in this study. To clarify the influence of the evolution of CA6 phase on the properties of MA–CA6 composites, the sintering temperature was carried out at 1200–1700 °C for 2 h. The results show that the growth and development of CA6 grains improves the densification and flexural strength of MA–CA6 composites. The formation of MA phase occurs at 1200 °C, while the CA6 phase is formed by the reaction of CaAl4O7 (CA2) and Al2O3 appears at 1400 °C. The plate-like CA6 grains intersect with each other, presenting regular hexagonal morphology with a high aspect ratio at 1500 °C. The CaO–Al2O3–SiO2 phase acts as an interface phase to regulate the growth and development of MA and CA6 grains. The CA6 phase was crystallized from the transient liquid phase CaO–Al2O3–SiO2 to significantly increase its thickness at 1600 °C. At the same time, as the sintering temperature rises, the apparent porosity of the sample decreases from 24% at 1400 °C to 4% at 1600 °C, and the flexural strength correspondingly increases from 96.6 MPa to 167 MPa. However, the suitable sintering temperature should not exceed 1600 °C for better properties of the composites.

Ultraviolet‐C illumination may provide a promising solution for the disinfection technology, and thus the development of novel type of ultraviolet‐C light sources is continuously expected. Herein, a conceptual design of ultraviolet‐C light source based on up‐conversion luminescence of phosphor material is introduced. Accordingly, a composite film is prepared using YBO3:Pr3+ phosphor and a transmissive remote phosphor‐converted light source is built by combing the phosphor film with a 447 nm laser. Spectral measurements show that the phosphor‐converted design emits ultraviolet‐C light peaking at 263 and 274 nm with tunable emission intensities. Moreover, ultraviolet imaging demonstration implies that the present design has a potential to serve as an ultraviolet‐C germicidal light source for surface decontamination.

Purpose The life quality of cervical cancer patients is severely compromised due to the vaginal stump contracture after surgery combined with radiotherapy. Therefore, our study focuses on ameliorating or preventing postoperative vaginal contracture. The objectives of this study were (1) to evaluate the method of ileal graft with vascular pedicle to extend the length of vagina and (2) to investigate the effect of the operation to prevent vaginal stump contracture after cervical cancer surgery combined with radiotherapy. Methods Twenty-five patients with vaginal stump contracture after cervical cancer radical resection with sequential radiotherapy were recruited for the study between 2011 and 2014. The therapy includes releasing the adhesion between vaginal stump and rectum as well as bladder, resecting the vaginal stump but reserving the exterior orifice of vagina, and extending the vaginal length using vascularized ileal graft. Results No postoperative complications such as infection and bleeding were observed in all 25 patients. The patients were satisfied with the length and width of vagina after extension; the discharge of reconstructed vagina was acceptable. All patients had sexual intercourse on the follow-up examination, and five patients complained of vaginal bleeding during or after sexual intercourse, although no abnormality was found on colposcopy. Conclusions The patients demonstrated a high level of safety, efficacy, and satisfaction with the ileal–vaginal extension for treating vaginal stump contracture after cervical cancer surgery combined with radiotherapy, suggesting that this method is valid for broad clinical application to improve the life quality of cervical cancer patients after surgery.

BackgroundThe competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA characteristics, pathways and drug candidates in SCLC.MethodWe determined the plasma messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) expression levels using whole-transcriptome sequencing technology in our SCLC plasma cohort. Significantly expressed plasma mRNAs were then overlapped with the Gene Expression Omnibus (GEO) tissue mRNA data (GSE 40275, SCLC tissue cohort). Next, we applied a multistep multi-omics (transcriptome, regulome, genome and pharmacogenome) integration analysis to first construct the network and then to identify the lncRNA/circRNA-miRNA-mRNA ceRNA characteristics, genomic alterations, pathways and drug candidates in SCLC.ResultsThe multi-omics integration-based prioritisation of SCLC ceRNA regulatory networks consisted of downregulated mRNAs (CSF3R/GAA), lncRNAs (AC005005.4-201/DLX6-AS1-201/NEAT1-203) and circRNAs (hsa_HLA-B_1/hsa_VEGFC_8) as well as upregulated miRNAs (hsa-miR-4525/hsa-miR-6747-3p). lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibited effects of hsa-miR-6747-3p for CSF3R expression in SCLC, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa-miR-4525 for GAA in SCLC. CSF3R and GAA were present in the genomic alteration, and further identified as targets of FavId and Trastuzumab deruxtecan, respectively. In the SCLC-associated pathway analysis, CSF3R was involved in the autophagy pathways, while GAA was involved in the glucose metabolism pathways.ConclusionsWe identified potential lncRNA/cirRNA-miRNA-mRNA ceRNA regulatory mechanisms, pathways and promising drug candidates in SCLC, providing novel potential diagnostics and therapeutic targets in SCLC.

Acquisition of stable nitritation and efficient anammox play a crucial role in partial nitritation (PN) combined with anammox for nitrogen removal from ammonium-rich wastewater. Due to the limitation of ammonia-oxidizing bacteria (AOB) enrichment and nitrite-oxidizing bacteria (NOB) control in traditional membrane biological reactor (MBR), it can result in a lower nitrite production rate (NPR) and unstable PN, eventually reducing the nitrogen removal rate (NRR) via PN-anammox. In this study, we developed a zeolite membrane biological reactor (ZMBR) to enhance the PN of iron oxide red wastewater (IORW), in which the biofilm derived from the zeolite surface can provide free ammonia (FA)-containing microenvironment for AOB enrichment and NOB inhibition. The results showed that ZMBR can tolerate a higher influent nitrogen loading rate (NLR) of 2.78 kg/(m3⋅day) in comparison to the traditional MBR [2.02 kg/(m3⋅day)] and the NPR in ZMBR and traditional MBR were 1.39 and 0.96 kg/(m3⋅day), respectively. The mass concentration ratio of NO2--N/NH4+-N ranged from 1.05 to 1.33 in ZMBR, suggesting a suitable condition for nitrogen removal via anammox. Subsequently, the domesticated granular sludge obtained from a paper-making wastewater treatment was used as the carrier of anammox bacteria to remove nitrogen. After 93 days of operation, the NRR was observed to be 2.33 kg/(m3⋅day) and high-throughput sequencing indicated that the relatively higher abundance (45.0%) of Candidatus Kuenenia stuttgartiensis was detected in the granular sludge of the bottom part of the reactor, which can produce more proteins and lipids, suggesting a good settleability. Overall, this study provides a high-efficient method to control PN and domesticate anammox for nitrogen removal from IORW.

The soil-water characteristic curve is the basic constitutive relation to express the water-holding characteristics of ion-absorbed rare earth. The simulated solution mining test and pressure plate apparatus tests were carried out, the relationship between matric suction and water content under different leaching actions was obtained. Using the Fredlund and Xing four-parameter model, the soil-water characteristic curves of ion-absorbed rare earth under different leaching actions were obtained, and the changing trend of each parameter was analyzed, and the influence of different leaching methods on the water-holding characteristic of soil was obtained. For different types of leaching solutions, the water-holding capacity of the soil varies from strong to weak for pure water, the 3% magnesium sulfate solution, and the 3% ammonium sulfate solution; as the concentration of the leaching solution increases, the water-holding capacity of the sample gradually decreases, and it decreases most significantly from 0% to 2%. Moreover, the saliency of the “hysteresis effect” of the soil-water characteristic curve was from high to low for pure water, the 3% magnesium sulfate solution, and the 3% ammonium sulfate solution, and the “hysteresis effect” showed a decreasing trend with the increase in the concentration.

Urban heat islands (UHIs) have become one of the most critical issues around the world, especially in the context of rapid urbanization and global climate change. Extensive research has been conducted across disciplines on the factors related to land surface temperature (LST) and how to mitigate the UHI effect. However, there remain deficiencies in the exploration of LST changes across time and their relationship with underlying surfaces in different temperature ranges. In order to fill the gap, this study compared the LST of each month by using the quantile classification method taking the Landsat 8 images of Nanjing on May 18th, July 21st, and October 9th in 2017 as the subject and then calculated the differences between July and May as well as that between July and October by an intersection tool taking the LST classes of July as the baseline. Additionally, the spatial pattern of each temperature class and intersection area was analyzed with the help of several landscape metrics, and the land contribution index (LCI) was utilized to better quantify the thermal contribution of each underlying surface to the area. The results indicated that the difference between months mainly reflected in the medium temperature area, especially between July and October, in which landscape patterns illustrated a trend of fragmentation and decentralization. The proportions of underlying surfaces in different types of intersection revealed the distinction of their warming and cooling degrees over time, in which the warming degree of other rigid pavement was higher in the warming process from May to July, and the cooling degree of buildings was greater in the cooling process from July to October. The LCI of each underlying surface in the entire study area was different from that in each temperature class, indicating that underlying surfaces had distinguished thermal contributions in different temperature ranges. This study is expected to fill the gap in previous studies and provide a new perspective on the mitigation of UHI.

As a matter of experience, people always take it for granted that ambient light should be eliminated for the research and application of storage phosphors. Such an empirical viewpoint has hindered the development of storage phosphors in a lighting environment. Herein, we introduce a glow-in-the-daylight phenomenon, which is essentially photostimulated luminescence of ultraviolet phosphor upon stimulation by polychromatic daylight. As a proof of concept, imaging and spectral experiments are carried out using an x-ray-charged LuPO_{4}:Pr^{3+} phosphor to demonstrate the glow performance. The charged phosphor exhibits solar-blind ultraviolet (200–280 nm) emission under sunlight, while its persistent luminescence is nearly absent in a dark environment, revealing the role of sunlight in releasing the stored energy of the phosphor. Moreover, inspired by the case of LuPO_{4}:Pr^{3+}, we expect to revisit other ultraviolet phosphors that do not exhibit persistent luminescence in the dark, enabling more glow-in-the-daylight materials to be developed.

Sustainable development can only be achieved with an innovative improvement from the way we currently analyze, design, build and manage our urban spaces. Current digital analysis and design methods for cities, such as visibility analysis, deeply rely on mapping and modeling techniques. However, most methods fall short of depicting the real visual landscape in the urban realm and this could bring a significant error in visibility calculations which may lead to an improper decision for urban spaces. The technical development of light detection and ranging(LiDAR) technology introduces new approaches for urban study. LiDAR utilizes point clouds including thousands or even millions of georeferenced points, and thus can support 3-D digital representation of urban landscape with detailed information and high resolution. Besides the superiority in representing urban landscape, LiDAR point clouds also has a clear advantage in quantitative analysis and provides better visibility than traditional models. In this paper, we first introduced a novel approach to map visibility in the urban built environment involving vegetation data directly using airborne LiDAR point clouds. This approach calculates neighborhood statistics for occlusion detection. Then we presented 2 case with different scenarios showing how our approach can be used to obtain a precise visibility in an urban area in the Netherlands. At last, we discussed how point clouds based visibility models can be further explored and can better assist urban design.

The appropriate resolution has been confirmed to be crucial to the extraction of urban green space and the related research on ecosystem services. However, the factors affecting the differences between various resolutions of data in certain application scenarios are lacking in attention. To fill the gap, this paper made an attempt to analyze the differences of various resolutions of data in green space extraction and to explore where the differences are reflected in the actual land unit, as well as the factors affecting the differences. Further, suggestions for reducing errors and application scenarios of different resolutions of data in related research are proposed. Taking a typical area of Nanjing as an example, data taken by DJI drone (0.1 m), GaoFen-1 (2 m) and Sentinel-2A (10 m) were selected for analysis. The results show that: (1) There were minimal differences in the green space ratio of the study area calculated by different resolutions of data on the whole, but when subdivided into each land use type and block, the differences were obvious; (2) The function, area and shape of the block, as well as the patch density and aggregation degree of the internal green space, had a certain impact on the differences. However, the specific impact varied when the block area was different; and (3) For the selection of the data source, the research purpose and application scenarios need to be comprehensively considered, including the function and attributes of the block, the distribution characteristics of green space, the allowable error limits and the budget. The present study highlighted the reasons of differences and hopefully it can provide a reference for the data selection of urban green space in the practical planning and design.

Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide. Even with the development of novel drugs, nearly one-half of the patients with ovarian cancer die within five years of diagnosis. These situations indicate the need for novel therapeutic agents for ovarian cancer. Increasing evidence has shown that hypoxia-inducible factor-1α(HIF-1α) plays an important role in promoting malignant cell chemoresistance, tumour metastasis, angiogenesis, immunosuppression and intercellular interactions. The unique microenvironment, crosstalk and/or interaction between cells and other characteristics of ovarian cancer can influence therapeutic efficiency or promote the disease progression. Inhibition of the expression or activity of HIF-1α can directly or indirectly enhance the therapeutic responsiveness of tumour cells. Therefore, it is reasonable to consider HIF-1α as a potential therapeutic target for ovarian cancer. In this paper, we summarize the latest research on the role of HIF-1α and molecules which can inhibit HIF-1α expression directly or indirectly in ovarian cancer, and drug clinical trials about the HIF-1α inhibitors in ovarian cancer or other solid malignant tumours.

Abstract. Background. The relationship of uric acid (UA) with the thyroid function among healthy individuals remains unclear. We aimed to examine the relationship between UA contents and thyroid hormone levels in healthy Chinese individuals. Methods. This was a cross-sectional study of 1186 Chinese adults (736 men and 450 women) who underwent a health check-up at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1, 2010 and July 31, 2018. Clinical and thyroid hormone levels were compared in different UA groups (in male and menopause women groups, MG1: UA < 5 mg/dL; MG2: 5 mg/dL ≤ UA< 7 mg/dL; and MG3: UA ≥ 7 mg/dL; in female groups, FG1 to FG3 represent the UA levels of

Dysregulation of microRNAs (miRNAs) is acknowledged in human cutaneous squamous cell carcinoma (cSCC). We hereby evaluated the ability of miRNA-216b (miR-216b) to impact human cSCC. cSCC tissues with corresponding adjacent normal tissues were collected from 40 patients diagnosed with cSCC where the expression pattern of miR-216b and targeting protein for Xenopus kinesin-like protein 2 (TPX2) was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot analysis. A431 cells were transfected with miR-216b mimic, miR-216b inhibitor, or short interfering RNA against TPX2 to evaluate cell proliferation, invasion, migration, and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. TPX2 was highly expressed in cSCC tissues while miR-216b was poorly expressed in association with tumor differentiation, lymph node metastasis, and tumor node metastasis staging in patients with cSCC. In response to overexpressed miR-216b or silenced TPX2, cSCC cell proliferation, invasion, and migration were suppressed and apoptosis was stimulated, along with activated p53 signaling. Thus, upregulated miR-216b was capable of promoting apoptosis and inhibiting proliferation, invasion, and migration of cSCC cells by downregulating TPX2 through activation of the p53 signaling, highlighting a novel biomarker for novel treatment modalities against cSCC.

Abstract The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.

Objective: A robust, quick, and reliable ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for the quantification of erdafitinib in beagle dog plasma was developed and validated to evaluate the changes of posaconazole and isavuconazole on the pharmacokinetics of erdafitinib in beagle dogs, respectively.Methods: This experiment adopted a three-period self-control experimental design. In the first period (group A), erdafitinib was orally administered to six beagle dogs at a dose of 4 mg/kg. In the second period (group B), the same six beagle dogs were orally given posaconazole at a dose of 7 mg/kg, and after 30 min, erdafitinib was orally given. In the third period (group C), isavuconazole at a dose of 7 mg/kg was given orally, and then, erdafitinib was orally given. At the different time points after erdafitinib was given in the three periods, the blood samples were collected. The concentration of erdafitinib was detected by the developed UPLC-MS/MS method. DAS 2.0 was used to calculate the pharmacokinetic parameters of erdafitinib.Results: Erdafitinib had a good linear relationship in the range of 1–500 ng/ml, and the lower limit of quantification was 1 ng/ml. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. After erdafitinib was combined with posaconazole, the Cmax and AUC0→t of erdafitinib increased by 27.19% and 47.62%, respectively, and the t1/2 was prolonged to 6.33 h. After erdafitinib was combined with isavuconazole, the Cmax and AUC0→t of erdafitinib increased by 23.13% and 54.46%, respectively, and the t1/2 was prolonged to 6.31 h.Conclusion: A robust and reliable UPLC-MS/MS method was fully optimized and developed to detect the plasma concentration of erdafitinib in beagle dogs. Posaconazole and isaconazole could inhibit the metabolism of erdafitinib in beagle dogs and increase the plasma exposure of erdafitinib.

Background: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hypothesis was proposed that the multi-target solution of GGQLD produced anti-inflammatory effects on ameliorating hyperuricemia (HUA).Methods: A total of 30 primary HUA patients receiving GGQLD treatment (two doses daily) for 4 weeks were selected. Then, differences in uric acid (UA) levels and expression of peripheral blood mononuclear cells (PBMCs) and urinary exosomes before and after treatment were analyzed. The therapeutic indexes for the active ingredients in GGQLD against HUA were confirmed through pharmacological subnetwork analysis. Besides, the HUA rat model was established through oral gavage of potassium oxonate and treated with oral GGQLD. In addition, proximal tubular epithelial cells (PTECs) were stimulated by UA and intervened with GGQLD for 48 h. Subsequently, RNA-seq, flow cytometry, and confocal immunofluorescence microscopy were further conducted to characterize the differences in UA-mediated inflammation and apoptosis of human renal tubular epithelial cells pre- and post-administration of GGQLD. In the meanwhile, quantitative real-time PCR (qPCR) was carried out to determine gene expression, whereas a western blotting (WB) assay was conducted to measure protein expression.Results: Our network analysis revealed that GGQLD treated HUA via the anti-inflammatory and antiapoptotic pathways. Additionally, NLPR3 expression significantly decreased in PBMCs and urinary exosomes of HUA patients after GGQLD treatment. In vivo, GGQLD treatment alleviated HUA-induced renal inflammation, which was associated with decreased expression of NLRP3 inflammasomes and apoptosis-related mRNAs. Moreover, GGQLD promoted renal UA excretion by inhibiting the activation of GSDMD-dependent pyroptosis induced by NLRP3 inflammasomes and by reducing apoptosis via the mitochondrial apoptosis signaling pathway in vitro.Conclusion: This study indicates that GGQLD efficiently reduces inflammatory responses while promoting UA excretion in HUA. Our findings also provide compelling evidence supporting the idea that GGQLD protects against the UA-mediated renal tubular epithelial cell inflammation through the mitochondrial apoptosis signaling pathways. Taken together, these findings have demonstrated a novel therapeutic method for the treatment of HUA.

Extracting valuable information to enhance the performance of forecasting models from the imbalanced and big data requires the scalable implementation of advanced statistical learning methods. This paper proposes the online mixture model (OMM) and applies it to the Mach number forecasting. Treating the key variable (e.g., Mach number) forecasting under all working conditions as an entire task, and viewing that of each individual working condition as a subtask, the OMM separates the dense samples from the sparse ones on the basis of subtasks. The subtask models are independently learnt on the samples with reduced volume, and updated for the new working conditions without retaining samples from the old working conditions. Moreover, the tree-structure ensemble (TSE)-feature subsets ensembles (FSEs) algorithm is presented to fit the nonlinear function of a subtask model, where the FSE local models with low-dimensional input features are established on the non-overlapping sample subsets constructed by the TSE method. The TSE-FSEs not only reduce the volume of data but also perform distributed computing with parallel structure, and thus has the advantage of the learning of big data. Experiments carried out on the measurement data of wind tunnel indicate that the OMM with the TSE-FSEs outperforms other learning algorithms for the Mach number forecasting, and meets the precision and forecasting speed requirements in engineering.

Many classification tasks suffer from the class imbalance problem that seriously hinders the precision of classifiers. The existing algorithms frequently incorrectly categorize new instances into the majority class. The ensemble learning is an effective method to address the imbalance problem, as is the Splitting Balancing Ensemble (SBE) method that learns the unbalanced dataset by converting it into multiple balanced subsets on which sub-classifiers are built. However, the SBE generates balanced subsets that are too small when learning a highly unbalanced dataset and lead to under-fitting. We propose the Distance-based Balancing Ensemble (DBE) method to deal with this issue and improve the generalization performance of the classification algorithm. The DBE divides highly unbalanced learning set into multiple unbalanced subsets with a much lower imbalance ratio and then applies a modified adaptive semi-unsupervised weighted oversampling method to each subset to obtain balanced subsets for the sub-classifiers. We further propose our Distance-based Combination Rule (DCR) as a more effective method for combining the ensemble results. Tests with 48 public unbalanced datasets from public repositories are performed to demonstrate the effectiveness of the DBE model with the DCR. The results show that the DBE-DCR model outperforms other ensemble models.

A multicast scheme based on fidelity metrics in quantum networks is proposed in this paper. First of all, according to the fidelity of copies in an asymmetric mechanism of 1→ 1+ 1+ 1+1 which is derived, the way of information transmission in the quantum networks is defined: one is one-to-one transmission based on the teleportation and the other is one-to-many lossy transmission based on quantum cloning mechanism. Second, in a specified quantum network which is a connected graph, a source node can randomly assign multicast group members. Then, with constraints of the number of replicas and the maximum number of hops of the shortest path, an optimal multicast tree is constructed to obtain maximum fidelity. Finally, the simulation results show that the proposed scheme can select the optimal path from the source node to the multicast members for the specified quantum network. With the increase of multicast group members, the average value of information fidelity obtained by all members decreases. Compared with the multicast tree constructed by the KMB algorithm, which is used to construct the Steiner tree in classical communication, the proposed schemes make the information fidelity obtained by multicast group members improve significantly.

BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.

Background:. Beauty standards vary by race and region, which must be accounted for in creating beauty. Chinese have unique features, including a depressed nose, flat midface, and small chin, and have different cosmetic concerns. We performed a consensus study on filler injections based on the Chinese standard of beauty due to a lack of such study. Methods:. We organized the YVOIRE Consensus Group, including 5 plastic surgeons. We discussed common problematic areas seen in Chinese and described techniques based on our experience with hyaluronic acid fillers, while considering peer-reviewed articles, followed by multiple consensus-developing sessions. Results:. Chinese faces are characterized by retruded forehead, chin, and low nasal bridge, with certain features believed to bring good fortune. Therefore, profiles of the forehead, nose, lip, and chin have substantial effects on attractiveness. The demand for cosmetic procedures is high among the young generation who particularly desire nose and chin augmentation. Attractive Chinese facial shapes are characterized by a long, slender facial shape and pointed chin. Lips are narrow and thick. When injecting fillers for Chinese, it is necessary to apply special methods that produce results consistent with these characteristics. Conclusions:. Understanding the concept and demand of beauty depending on race and region is important. Patients should be evaluated before aesthetic procedures. Maintaining hygiene during the procedure is crucial. Moreover, methods for preventing pain are essential. Fillers should be injected into the correct anatomical site and layer to minimize side effects and maximize effectiveness.

Purpose – The purpose of this paper is to develop a statistical-based model to forecast future domestic water demand in the context of climate change, population growth and technological development in Yellow River. Design/methodology/approach – The model is developed through the analysis of the effects of climate variables and population on domestic water use in eight sub-basins of the Yellow River. The model is then used to forecast water demand under different environment change scenarios. Findings – The model projected an increase in domestic water demand in the Yellow River basin in the range of 67.85 × 10 8 to 62.20 × 10 8 m 3 in year 2020 and between 73.32 × 10 8 and 89.27 × 10 8 m 3 in year 2030. The general circulation model Beijing Normal University-Earth System Model (BNU-ESM) predicted the highest increase in water demand in both 2020 and 2030, while Centre National de Recherches Meteorologiques Climate Model v.5 (CNRM-CM5) and Model for Interdisciplinary Research on Climate- Earth System (MIROC-ESM) projected the lowest increase in demand in 2020 and 2030, respectively. The fastest growth in water demand is found in the region where water demand is already very high, which may cause serious water shortage and conflicts among water users. Originality/value – The simple regression-based domestic water demand model proposed in the study can be used for rapid evaluation of possible changes in domestic water demand due to environmental changes to aid in adaptation and mitigation planning.

A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites. This method was called liquid state settling technique in which TC4 particles would settle down under the force of gravity. High volume fraction (50%) particle reinforced AZ91 composites could be easily obtained via this novel method. This is difficult to achieve for other traditional liquid fabrication methods. In addition, there was a good dispersion of TC4 particles in the AZ91 matrix and no clusters were found, which indicate that this method was feasible. Interfacial reaction occurred and the reaction product was confirmed to be Al2Ti. Three kinds of pre-dispersion technologies were used before the settling process and different interfacial microstructures were found. Theoretical calculation and experimental results both indicated that the interfacial product which was embedded in the matrix strengthened the composites and improved the tensile strength.

Objective: This study aims to investigate the effects of CDKN2A (p16INK4A/p14ARF) over-expression on the proliferation and migration of human melanoma A375 cells. Methods: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16INK4A) and CDKN2A (p14ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16INK4A and p14ARF groups. The expression of CDKN2A (p16INK4A) and CDKN2A (p14ARF) mRNA and protein was detected by qRT-PCR and Western blotting. CCK-8, flow cytometry and Transwell assays were applied to observe cell proliferation, the cell cycle and apoptosis, and migration and invasion, respectively. The model of subcutaneous xenografts in nude mice was established to measure cell growth in vivo. Results: Compared with pigmented nevi tissues, CDKN2A (p16INK4A) and CDKN2A (p14ARF) mRNA and protein expression were significantly decreased in melanoma tissues. CDKN2A (p16INK4A) and CDKN2A (p14ARF) over-expression inhibited proliferation, migration, invasion and progression from G0/G1 to S phase of A375 cells and xenograft tumor growth, but promoted apoptosis. Conclusion: Our study demonstrated that over-expression of CDKN2A (p16INK4A) and CDKN2A (p14ARF) suppressed proliferation and migration of human melanoma A375 cells.

Obesity is a metabolic condition associated with multiple health problems such as endocrine and metabolic dysfunction and chronic inflammation in adipose tissues. In this study, the ADSCs could be stimulated to differentiate into brown adipocyte with rosiglitazone treatment based on the Oil-Red-O staining trial. Furthermore, the multilocular lipid droplets located in the center was increased in differentiated brown adipocytes, and brown fat-associated proteins, UCP1, PPAR-γ, and LPL were highly expressed in brown adipocytes differentiated from ADSCs. Additionally, the results of animal experiments showed that both weight and amount of VLDL and LDL were decreased in the serum of obese mice after transplantation of rosiglitazone-induced brown adipocytes, while the level of HDL increased. Moreover, the proteins associated with lipid metabolism, LPA and UCP1, were downregulated, and the inflammatory response was suppressed through inhibition of the ITGAM/NF-κB-mediated proinflammatory responses and polarization of M2 macrophages. Similarly, the amounts of proinflammatory cytokines, TNF-α, IL-6, and IL-1β were decreased after rosiglitazone-induced brown adipocyte transplantation. On the contrary, anti-inflammatory cytokine IL-10 was significantly increased in both groups of obese mice, with or without brown adipocyte transplantation. Therefore, the adipose-derived stromal cells with induced browning could promote lipid consumption and alternative polarization of M2 macrophages to attenuate adipose inflammation in obesity mouse models, which thus provides a potential therapy for obesity.

A series of novel thermoplastic elastomers based on (poly(decamethylene terephthalamide/decamethylene isophthalamide), PA10T/10I) and poly(ethylene glycol) (PEG) were synthesized via a facile one-pot, efficient and pollution-free method. The thermal analysis demonstrates that the melting points of the resultant elastomers were in the range of 217.1–233.9 °C, and their initial decomposition temperatures were in the range of 385.3–387.5 °C. That is higher than most commercial polyamide-based thermoplastic elastomers. The tensile strength of the resultant elastomers ranges from 21.9 to 41.1 MPa. According to the high-temperature bending test results, the resultant samples still maintain considerably better mechanical properties than commercial products such as Pebax® 5533 (Arkema, Paris, France), and these novel thermoplastic elastomers could potentially be applied in high-temperature scenes. The non-isothermal crystallization kinetics of the resultant elastomers and PA10T/10I was investigated by means of Jeziorny and Mo’s methods. Both of them could successfully describe the crystallization behavior of the resultant elastomers. Additionally, the activation energy of non-isothermal crystallization was calculated by the Kissinger method and the Friedman equation. The results indicate that the crystallization rates follow the order of TPAE-2000 > TPAE-1500 > PA10T/10I > TPAE-1000. From the crystallization analysis, the crystallization kinetics and activation energies are deeply affected by the molecular weight of hard segment.

Dengue virus (DENV) has become a global health threat with about half of the world’s population at risk of infection. Although the disease caused by DENV is self-limiting in the first infection, the antibody-dependent enhancement (ADE) effect increases the mortality in the second infection with a heterotypic virus. Since there is no specific efficient medicine in treatment, it is urgent to develop vaccines to prevent infection and disease progression. Currently, only a live attenuated vaccine, chimeric yellow fever 17D—tetravalent dengue vaccine (CYD-TDV), has been licensed for clinical use in some countries, and many candidate vaccines are still under research and development. This review discusses the progress, strengths, and weaknesses of the five types of vaccines including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral vectored vaccine, and DNA vaccine.

Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors.

Objective: Clinical application of autologous fat grafting (AFG) is quickly expanding. Despite the widely acceptance, long-term survival rate (SR) of AFG remains a question not yet solved. Meanwhile, although rare, severe complications related to AFG including vision loss, stroke even death could be seen in the literature. Data Sources: A comprehensive research of PubMed database to June 2013 was performed according to guidelines of the American Society of Plastic Surgeons Fat Graft Task Force Assessment Methodology. Articles were screened using predetermined inclusion and exclusion criteria. Study Selection: Data collected included patient characteristics, surgical technique, donor site, recipient site, graft amount, and quantified measurement methods. Patient cohorts were pooled, and SR was calculated. All the severe complications were also summarized according to the different clinical characteristics. Results: Of 550 articles, 16 clinical articles and 10 animal studies met the inclusion criteria and provided quantified measurement methods. Totally, 596 patients were included. SR varied from 34% to 82% in breast and 30-83% in the facial area. Nude mice were applied to investigate human fat grafting SR (38.3-52.5% after 15 weeks). Rabbits were commonly used to study animal AFG SR (14.00-14.56% after 1-year). Totally, 21 severe complications were reported, including death (2), stroke (10), vision loss (11, 8 of which accompanied with stroke), sepsis (3), multiple abscess (1) and giant fat necrotic cyst (2). Ten of these complications happened within 10 years. Conclusions: There is no unified measurement method to evaluate fat graft SR until now and no clinical evidence to show better SR according to different donor and recipient cite. Body mass index change between pre- and postoperation may be the bias factor in evaluating fat SR. Fat embolisms of the ophthalmic artery and the middle cerebral artery are the most severe complication of AFG and still lack of effective treatment.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell–associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR) gene in an effort to provide an improved large animal model of familial hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models because of similarities to humans in physiology, anatomy, genetics, and size. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, male and female LDLR+/- pigs were generated. Subsequent breeding of heterozygotes produced LDLR-/- pigs. When fed a standard swine diet (low fat, no cholesterol), LDLR+/- pigs exhibited a moderate, but consistent increase in total and LDL cholesterol, while LDLR-/- pigs had considerably elevated levels. This severe hypercholesterolemia in homozygote animals resulted in atherosclerotic lesions in the coronary arteries and abdominal aorta that resemble human atherosclerosis. These phenotypes were more severe and developed over a shorter time when fed a diet containing natural sources of fat and cholesterol. LDLR-targeted Yucatan miniature pigs offer several advantages over existing large animal models including size, consistency, availability, and versatility. This new model of cardiovascular disease could be an important resource for developing and testing novel detection and treatment strategies for coronary and aortic atherosclerosis and its complications.

Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes.In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass.Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery.These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.

BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.