Significant evidence implicates α3β1 integrin in promoting breast cancer tumorigenesis and metastasis-associated cell behaviors in vitro and in vivo. However, the extent to which α3β1 is actually required for breast cancer metastasis remains to be determined. We used RNA interference to silence α3 integrin expression by ~70% in 4T1 murine mammary carcinoma cells, a model of aggressive, metastatic breast cancer. Loss of α3 integrin reduced adhesion, spreading, and proliferation on laminin isoforms, and modestly reduced the growth of orthotopically implanted cells. However, spontaneous metastasis to lung was strikingly curtailed. Experimental lung colonization after tail vein injection revealed a similar loss of metastatic capacity for the α3-silenced cells, suggesting that critical, α3-dependent events at the metastatic site could account for much of α3β1’s contribution to metastasis in this model. Re-expressing α3 in the α3-silenced cells reversed the loss of metastatic capacity, and silencing another target, the small GTPase RhoC, had no effect, supporting the specificity of the effect of silencing α3. Parental, α3-silenced, and α3-rescued cells all secreted abundant laminin α5, an α3β1 integrin ligand, suggesting that loss of α3 integrin might disrupt an autocrine loop that could function to sustain metastatic growth. Analysis of human breast cancer cases revealed reduced survival in cases where α3 integrin and laminin-α5 are both over-expressed. Implications: α3 integrin or downstream effectors may be potential therapeutic targets in disseminated breast cancers, especially when laminin-α5 or other α3 integrin ligands are also over-expressed.

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Full‐thickness skin injuries have always been an intricate problem in clinical treatment. The application of biomaterials provides an artificial matrix for the recruitment of cells and deposition of extracellular matrix to accelerate wound healing. For the recovery of full‐thickness skin defects, the double cross‐linking of MgO‐catechol and Schiff's base bonds are used as part of the gel‐forming mechanism, and a bio‐multifunctional hydrogel (CCOD‐MgO) is prepared by adding MgO to catechol‐modified chitosan (CHI‐C) and oxidized dextran (ODex). The CCOD‐MgO demonstrates high tissue adhesion, excellent self‐repairing, hemostasis function, and low swelling rate. With the addition of MgO and catechol chelation, the adhesion strength of CCOD‐MgO is about 35 kpa, which is much greater than fibrin glue. Moreover, the CCOD‐MgO has better antibacterial properties than CHI‐C/ODex hydrogel (CCOD) due to the synergy of chitosan and MgO in vitro. Accordingly, the CCOD‐MgO can protect the wounds from infection and accelerate the healing speed of the epidermis in full‐thickness cutaneous defect and burn model in vivo. These results demonstrate that the CCOD‐MgO would be a promising therapeutic strategy in full‐thickness skin injuries for clinical therapies.

Whole blood metabolomics is a feasible approach to identify potential biomarker candidates of paclitaxel-induced PN. The findings suggest that pretreatment concentrations of histidine, phenylalanine, and threonine may be predictive of the severity of future PN and paclitaxel-induced metabolic changes may be related to disruption of energy homeostasis.

BackgroundPreoperative diagnosis of central lymph node metastasis (CLNM) poses to be a challenge in clinical node-negative papillary thyroid microcarcinoma (PTMC). This research work aims at investigating the association existing between BRAF mutation, clinicopathological factors, ultrasound characteristics, and CLNM, in addition to establishing a predictive model for CLNM in PTMC.Materials and methodsThe study included 673 PTMC patients, already undergone total thyroidectomy or lobectomy with prophylactic central lymph node dissection. The predictor factors were identified through univariate and multivariate analyses. The support vector machine was put to use to develop statistical models, which could predict CLNM on the basis of independent predictors.ResultsTumor size (>5 mm), lower location, no well-defined margin, contact of >25% with the adjacent capsule, display of enlarged lymph nodes, and BRAF mutation were independent predictors of CLNM. Through the use of the predictive model, 79.6% of the patients were classified accurately, the sensitivity and specificity amounted to be 85.1% and 75.8%, respectively, and the positive predictive value and negative predictive value stood at 71.6% and 87.6%, respectively.ConclusionsWe established a predictive model in order to predict CLNM preoperatively in PTMC when preoperative diagnosis of CLNM was not clear.

Background.New-onset stage 4–5 chronic kidney disease (CKD) after liver transplantation (LT) is associated with high morbidity, mortality, and economic burden. In 2010, we instituted an early renal sparing immunosuppression (RSI) protocol for LT recipients with severe renal dysfunction (pre-LT dialysis/estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m2 or post-LT acute kidney injury) consisting of 2 doses of basiliximab for induction and delaying tacrolimus to post-LT day 4–7. We examined the effect of early RSI on post-LT renal outcomes.Methods.Data on all adults who had LT between January 1, 2010, and December 12, 2014 were collected. We calculated the renal risk index (RRI) score for each LT recipient (https://rri.med.umich.edu). Primary outcome was new-onset post-LT stage 4–5 CKD.Results.Of 214 LT recipients, 121 (57%) received early RSI and 93 (43%) received standard immunosuppression. Cumulative incidence of new-onset stage 4–5 CKD was higher in early RSI compared with standard immunosuppression (P = 0.03). Female sex and RRI score were the significant risk factors for development of post-LT stage CKD in the entire study cohort as well as the LT recipients with RRI ≥ sixth decile (high-risk group).Conclusions.Delaying tacrolimus initiation combined with basiliximab induction did not have a durable effect on long-term renal outcomes in high-risk LT recipients. Further studies are needed to identify the effective strategies to preserve renal function by targeting patients at high risk for CKD progression.

BackgroundSkip metastasis is defined as metastasis incident to the lateral compartment without involvement of the central compartment, and is generally unpredictable in papillary thyroid cancer (PTC). The present study aimed to investigate the frequency and predictor value of skip metastasis in PTC patients.Material/MethodsA total of 355 patients diagnosed with thyroid cancer who had received a prior complete thyroidectomy with bilateral central neck and ipsilateral lateral neck lymph node dissection were enrolled in this study. The clinicopathological and ultrasound features were analyzed. A univariate and multivariate analysis were performed to identify the risk factors of skip metastasis.ResultsThe frequency of skip metastasis was 12.4% (44/355). The PTC patients with skip metastasis exhibited fewer lymph node metastasis, which was more commonly detected in tumor size ≤1 cm (OR 9.354; p=0.001; 95% confidence interval (CI) 1.865–26.735), tumors located in upper pole (OR 3.822; p<0.001; 95% CI 1.935–7.549), without a well-defined margin (OR 2.528; p=0.016; CI 1.191–5.367), and extrathyroidal extension (OR 2.406; p=0.013; CI 1.691–4.367).ConclusionsSkip metastasis was common in PTC. The PTC patients with a tumor size ≤1.0 cm, located in the upper pole, without a well-defined margin and extrathyroidal extension should be carefully evaluated for skip metastasis.

Abstract:In the advanced research fields of solar cell and energy storing materials, graphene and graphene oxide (GO) are two of the most promising materials due to their high specific surface area, and excellent electrical and physical properties. However, they was seldom studied in the traditional materials because of their high cost. Nowadays, graphene and GO are much cheaper than before with the development of production technologies, which provides the possibility of using these extraordinary materials in the traditional construction industry. In this paper, GO was selected as a nano-material to modify two different asphalts. Then a thin film oven test and a pressure aging vessel test were applied to simulate the aging of GO-modified asphalts. After thermal aging, basic physical properties (softening point and penetration) were tested for the samples which were introduced at different mass ratios of GO (1% and 3%) to asphalt. In addition, rheological properties were tested to investigate how GO could influence the asphalts by dynamic shearing rheometer tests. Finally, some interesting findings and potential utilization (warm mixing and flame retardants) of GO in asphalt pavement construction were explained.