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Figure S1-9, Table S1

Irreversible hypofunction of salivary glands is a common side effect of radiotherapy for head and neck cancer and is difficult to remedy. Recent studies indicate that transient activation of Hedgehog signaling rescues irradiation-impaired salivary function in animal models, but the underlying mechanisms are largely unclear. Here, we show in mice that activation of canonical Gli-dependent Hedgehog signaling by Gli1 gene transfer is sufficient to recover salivary function impaired by irradiation. Salivary gland cells responsive to Hedgehog/Gli signaling comprised small subsets of macrophages, epithelial cells, and endothelial cells, and their progeny remained relatively rare long after irradiation and transient Hedgehog activation. Quantities and activities of salivary gland resident macrophages were substantially and rapidly impaired by irradiation and restored by Hedgehog activation. Conversely, depletion of salivary gland macrophages by clodronate liposomes compromised the restoration of irradiation-impaired salivary function by transient Hedgehog activation. Single-cell RNA sequencing and qRT-PCR of sorted cells indicated that Hedgehog activation greatly enhances paracrine interactions between salivary gland resident macrophages, epithelial progenitors, and endothelial cells through Csf1, Hgf, and C1q signaling pathways. Consistently, expression of these paracrine factors and their receptors in salivary glands decreased following irradiation but were restored by transient Hedgehog activation. These findings reveal that resident macrophages and their prorepair paracrine factors are essential for the rescue of irradiation-impaired salivary function by transient Hedgehog activation and are promising therapeutic targets of radiotherapy-induced irreversible dry mouth.Significance:These findings illuminate a novel direction for developing effective treatment of irreversible dry mouth, which is common after radiotherapy for head and neck cancer and for which no effective treatments are available.

BACKGROUND: To assess the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP) for patients with prostate volume less than 100 mL or 100 g. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to July 2021 to collect randomized controlled trials. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for meta-analysis. We synthesised effect estimates using risk ratios (RR), mean difference (MD), and standardized mean differences (SMD). RESULTS: A total of eight studies were included, involving 764 patients, 384 patients in the HoLEP group and 380 patients in the TURP group. The meta-analysis showed that the catheterization time (SMD =−1.44; 95% CI: −2.17 to −0.70; P=0.0001), hospital stay (SMD =−1.01; 95% CI: −1.58 to −0.44; P=0.0005), haemoglobin loss (MD =−0.29; 95% CI: −0.52 to −0.07; P=0.01), and transfusion rate (RR =0.16; 95% CI: 0.05–0.49; P=0.001) in the HoLEP group were lower than those in the TURP group. In addition, the 12-month postvoid residual volume (PVR) of the HoLEP group (MD =−9.93 95% CI: −18.59 to −1.27; P=0.02) were superior to the TURP group. Although the operation time of the HoLEP group was longer (MD =17.89; 95% CI: 9.18–26.60; P

Xuegang Wang,1,&ast; Weiquan Li,2,&ast; Ning Lou,3,&ast; Weiwei Han,3 Bo Hai,2 Wen Xiao,2 Xiaoping Zhang2 1Department of Urology, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xiao; Bo, Hai, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Tel +86-17088353610, Fax +86 85776343, Email xiaowenx11@163.com; Haibo2022@hust.edu.cnBackground: Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC.Methods: Kaplan–Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC.Results: DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC.Conclusion: This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.Keywords: DNTTIP1, ccRCC, gene therapy, prognostic indicator

Recent research indicated that extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) are a promising alternative to MSCs for immunomodulatory therapy. However, the contents of MSC-EVs would change as their parent MSCs change, hence the therapeutic efficacy of MSC-derived EVs (MSC-EVs) would largely depend on donors, tissue sources and culture conditions of MSCs. To overcome limitations of tissue-derived MSCs, we previously used MSCs derived from human induced pluripotent stem cells (iMSCs) to produce EVs and demonstrated their therapeutic potential in a mouse model of secondary Sjo¨gren's Syndrome. Here, we further found that EVs from early-passage iMSCs had better immunomodulatory potency than EVs from late-passage iMSCs in TLR4-stimulated splenocytes and in a mouse model of primary Sjogren's syndrome. Comparative molecular profiling using proteomics and microRNA sequencing revealed distinctive molecular profiles of iMSC-EVs with or without immunomodulation capacity. Amongst them, manipulation of TGF-β1, miR-21 and miR-125b levels in iMSC-EVs significantly affected their immunosuppressive effects. These findings would help improve our understanding of the molecular mechanism underlying iMSC-EV-mediated immunomodulation and further provide strategies to improve regulatory function of EVs for the treatment of immune-mediated diseases.

In this study, biodiesel has been successfully prepared from Xanthoceras sorbifolia seed kernel by SO42-/SnO2-Hangjin2#clay as catalyst. Based on the Central Composite Design method, the effect of ...

Process uncertainty makes remanufacturing operations management sophisticated. To reduce the uncertainty of the timing, quality and quantity of product returns in remanufacturing, motivated by the selling and leasing of electric vehicle batteries, we consider a monopolist vendor who markets her products by adopting two models: (1) a single leasing model, and (2) a single selling model. We first investigate the firm's marketing model with remanufacturing and analyze the impact of the quality level of the returned products on the firm's marketing and remarketing models. Then we compare selling and leasing models. We first find that only when the quality level of returned sold products is relatively high will the vendor choose to remanufacture under the single selling model. Conversely, only when the quality level of returned leased products is relatively low will the vendor decide to remanufacture under the single leasing model. Secondly, we show that the space of remanufacturable quality level under the single selling model is bigger than the space under the single leasing model. Thirdly, selling is more profitable than leasing when the quality level of returned sold products is sufficiently high. These results are further demonstrated by a numerical study. Our study provides firms with guidance on how to optimally adopt remanufacturing and marketing strategies that take into account the quality level of the returned products.

Management of a long proximal ureteral stricture is challenging. Lingual mucosal graft ureteroplasty (LMGU) is a novel minimally invasive technique for ureteral reconstruction that avoids the morbidity of bowel interposition or autotransplantation.To evaluate the long-term effectiveness of LMGU for managing long, complex proximal ureteral strictures in a multi-institutional cohort of patients.This retrospective study involved data for 41 patients treated with LMGU at three centers between June 2015 and January 2021.LMGU was performed using either an onlay ureteroplasty in which the diseased ureter was incised ventrally and repaired with a lingual mucosal graft (LMG) to widen the ureteral lumen, or an augmented anastomotic technique in which the obliterated segment of the ureter was excised and reanastomosed primarily on dorsal side, and an LMG was placed on the ventral side.Pre-, intra-, and postoperative variables and outcomes were assessed. A descriptive statistical analysis was performed.Of 41patients, 40 were operated with laparoscopic procedures and one with a robot. Twenty-four (59%) patients underwent an onlay ureteroplasty, and 17 (41%) underwent an augmented anastomotic ureteroplasty. The reconstructed ureter was wrapped with omentum in 90% of cases. The median (range) stricture length was 4.8 cm (2.0-8.0), operative time was 166 min (98-306), and estimated blood loss was 65 ml (15-220). No open conversions and intraoperative complications occurred. At a median follow-up of 35 mo (range 13-80), the overall success rate was 97.6% (40/41).LMGU is a safe, feasible, and effective long-term technique for managing long, complex proximal ureteral strictures.We reported a novel technique for long proximal complex ureteral strictures using an onlay lingual mucosal graft (LMG). Our 6-yr outcomes demonstrate that onlay LMG ureteroplasty is a safe, feasible, and effective long-term procedure for ureteral reconstruction.

Delta-like ligands (DLLs) control Notch signaling. DLL1, DLL3 and DLL4 are frequently deregulated in cancer and influence tumor growth, the tumor vasculature and tumor immunity, which play different roles in cancer progression. DLLs have attracted intense research interest as anti-cancer therapeutics. In this review, we discuss the role of DLLs in cancer and summarize the emerging DLL-relevant targeting methods to aid future studies.

Delta-like ligands (DLLs) control Notch signaling. DLL1, DLL3 and DLL4 are frequently deregulated in cancer and influence tumor growth, the tumor vasculature and tumor immunity, which play different roles in cancer progression. DLLs have attracted intense research interest as anti-cancer therapeutics. In this review, we discuss the role of DLLs in cancer and summarize the emerging DLL-relevant targeting methods to aid future studies.

In recent years, the nations of the world have presented the development strategy of manufacturing. Manufacturing is the foundation of a country. However, with the increasing global resource constraints and market heterogeneity, the variety of individual demands, and the long-term goals of sustainable development, with the support of emerging information and communication technologies such as Internet, cyber-physical system, Internet of Things, cloud computing, and big data, industrial value creation is causing a paradigm shift in manufacturing. This paper studies a range of new manufacturing paradigms and presents a state-of-the-art survey of published works. It explores the corresponding current manufacturing concepts, technologies, framework features, application effects, resource optimization, and future challenges in these new paradigms. The integration of various manufacturing paradigms is also analyzed. Through this survey, the developments of these new manufacturing paradigms are explained and the future prospects are also discussed.

The yellow-feather broiler is a popular poultry breed in Asia, particularly in China. In this study, we performed RNA-seq analysis to identify differentially expressed genes (deGs) in the liver of yellow-feather broilers that had been subjected to acute heat stress treatment (38±1°C for 4 h, recovery 2 h) and determine the response of the liver to high temperature and its effects on yellow-feather broiler physiology. We found that the cloacal temperature and respiratory rate of yellow-feather chickens were significantly increased immediately after the initiation of acute heat stress (38°c) treatment. And after recovery for 2 h, there was no difference in the cloacal temperature and respiratory rate between the acute heat stress and control groups. A total of 834 DEGs were observed in response to heat stress by RNA-seq. Almost half of the DEGs were involved in the lipid and energy metabolism, including fatty acid metabolism (ACOX1, ACACA, ACSL1, ACSL6, ACAA1, ACAA2, HADHB, and FASN) and propanoate metabolism (ACSS2, ALDH2, ACACA, DLAT, ALDH7A1, MDH1, ME1, ABAT, SUCLG2, and ACSS3). Our findings provide the context for RNA-seq studies in the liver of yellow-feather chickens and suggest that the liver of yellow-feather broilers has the lipid and energy metabolism physiological mechanisms activated in response to heat stress.

The blocks of polymer flooding have gradually entered into the stage of chase water flooding after polymer flooding in Daqing Oilfield and the comprehensive water cut is close to the exploitation limit of 98%. So it is urgent to develop some new technologies to further enhance oil recovery after polymer flooding. On the basis of laboratory research, a field test of alkali/surfactant/polymer flooding was carried out after polymer flooding in Daqing Oilfield in 2015, which achieved good development effect, but the polymer concentration was relatively large. Based on the field test of alkali/surfactant/polymer flooding, a new technology of the lower initial viscosity gel/alkali/surfactant/polymer flooding has further been studied according to the technical route combining plugging, adjusting and displacing, which can reduce the polymer dosage greatly under the premise of ensuring good oil displacing effect. In this paper, some laboratory studies are carried out, which realize significant technology breakthrough. Firstly, the adjusting and plugging agent of lower initial viscosity gel is screened out, which can be injected into the high permeability layers of low flow resistance like the water and migrate to the deep location of the high permeability layers and then gelatinize on spot. Therefore it can plug high permeability layers effectively and does not pollute the middle and low permeability layers at the same time. Secondly, the injection parameters of lower initial viscosity gel/alkali/surfactant/polymer system are optimized. The results of laboratory experiments show that the lower initial viscosity gel/alkali/surfactant/polymer system can enhance oil recovery by 13.5% OOIP under the optimal injection parameters, which is 1.2% OOIP more than that of the alkali/surfactant/polymer flooding and can save polymer dosage by 17.8%. In view of the good results obtained in laboratory experiments, the scenario design of field test is carried out and the incremental oil recovery is 10.1% OOIP predicted by numerical simulation. The field test is expected to start chemical flooding in 2021.

Maize and soybean intercropping is a cereal-legume intercropping pattern that not only increases grain yield but also improves the nutritional value of silage. Experiments were conducted in the summer season to compare the yield and nutritional composition of the forage and silage quality of mono-cropped maize and intercropped maize-soybean harvested at two stages of maturity. The main treatments were one sole crop maize (SM) and four maize-soybean intercropping patterns (one-row maize to one-row soybean (1M1S), one-row maize to two-row soybean (1M2S), one-row maize to three-row soybean (1M3S), and two-row maize to one-row soybean (2M1S). The crops were harvested when the maize reached the milk (R3) and maturity (R6) stages. Results indicated a significant increase in the fresh biomass and dry-matter production of maize fodder alone compared with those of maize intercropped with soybean fodder. After 60 days of ensiling period, silage samples were analyzed for pH, organic acids, dry matter, crude protein (CP), ether extract, neutral detergent fiber (NDF), acid detergent fiber (ADF), and other mineral compositions. All intercropped silages showed higher CP values (1M1S, 12.1%, 1M2S, 12.2%, 1M3S, 12.4%, and 2M1S, 12.1%) than the SM silage (8.7%). Higher organic acids were produced in 1M3S than in the other silages. Correlation data showed that CP was highly correlated with lactic acid but negatively associated with crude fiber, nitrogen-free extract, and NDF. Thus, the intercropping of maize and soybean silage is recommended due its enhanced crop production, nutritional values in dairy animals, and prolific animal feedings and because it was scientifically evaluated as a feed stuff. This study indicated that 1M3S was the most preferable among intercropped silages in terms of nutrient composition.