Shape memory polymer with programmable recovery onset.

Stimulus-responsive shape-shifting polymers1-3 have shown unique promise in emerging applications, including soft robotics4-7, medical devices8, aerospace structures9 and flexible electronics10. Their externally triggered shape-shifting behaviour offers on-demand controllability essential for many device applications. Ironically, accessing external triggers (for example, heating or light) under realistic scenarios has become the greatest bottleneck in demanding applications such as implantable medical devices8. Certain shape-shifting polymers rely on naturally present stimuli (for example, human body temperature for implantable devices)8 as triggers. Although they forgo the need for external stimulation, the ability to control recovery onset is also lost. Naturally triggered, yet actively controllable, shape-shifting behaviour is highly desirable but these two attributes are conflicting. Here we achieved this goal with a four-dimensional printable shape memory hydrogel that operates via phase separation, with its shape-shifting kinetics dominated by internal mass diffusion rather than by heat transport used for common shape memory polymers8-11. This hydrogel can undergo shape transformation at natural ambient temperature, critically with a recovery onset delay. This delay is programmable by altering the degree of phase separation during device programming, which offers a unique mechanism for shape-shifting control. Our naturally triggered shape memory polymer with a tunable recovery onset markedly lowers the barrier for device implementation.

Integrin αvß6 contributes to the development of intestinal fibrosis via the FAK/AKT signaling pathway.

Intestinal fibrosis is one of the most severe complications of inflammatory bowel disease (IBD) and frequently requires surgery due to intestinal obstruction. Integrin αvß6, which is mainly regulated by the integrin ß6 subunit gene (ITGB6), is a special integrin subtype expressed only in epithelial cells. In our previous study, we found integrin αvß6 can promote the development of IBD, but the role of integrin αvß6 in intestinal fibrosis remains unclear. In this study, we observed a gradual increase of ITGB6 mRNA expression from normal region to stenotic region of IBD patients' intestinal specimens. Next, we established a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and a heterotopic intestinal transplant model, and found intestinal fibrosis was decreased in ITGB6-deficient mice compared to wild-type (WT) mice. Furthermore, we performed RNA-sequencing and KEGG pathway analysis on intestinal tissues from ITGB6-overexpressing transgenic mice and WT mice, and found multiple pathways containing ITGB6, are related to the activation of focal adhesion kinase (FAK); finding was confirmed by Western blot. At last, we generated a heterotopic intestinal transplant model found the FAK/AKT pathway was inhibited in ITGB6-deficient mice. In conclusion, our data demonstrate that integrin αvß6 promotes the pathogenesis of intestinal fibrosis by FAK/AKT pathway, making integrin αvß6 a potential therapeutic target to prevent this condition.

HNF6 promotes tumor growth in colorectal cancer and enhances liver metastasis in mouse model.

Hepatocyte nuclear factor 6 (HNF6), as a transcription factor, has been reported to be involved in cell proliferation, carcinogenesis, and tumor metastasis. Here, we demonstrated the role of HNF6 in tumor growth and liver metastasis in colorectal cancer (CRC). Through bioinformatics and clinical samples analysis, we found HNF6 messenger RNA was upregulated both in CRC primary sites and liver metastases, and its high expression indicated poor survival in CRC patients. In vitro studies confirmed that HNF6 promoted cell proliferation and colony formation. What is more, in mouse models, the xenografts grew significantly faster and liver metastasis rate was nearly 45% higher in mice injected with HNF6-overexpressing cells. Further mechanism exploration showed that HNF6 expression affected cell adhesion and conferred resistance to anoikis in CRC cells. Taken together, HNF6 expression was upregulated in CRC and closely correlated with poor survival. HNF6 promoted CRC cell proliferation and tumor growth, and may contribute to liver metastasis via conferring cell resistance to anoikis.

Effects of humic acid-modified magnetic Fe3O4/MgAl-layered double hydroxide on the plant growth, soil enzyme activity, and metal availability.

The synthesis of a humic acid-layered double hydroxide (HA-LDH) hybrid was purposed for the remediation of contaminated soils in mining area. The hybrid was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscope and energy dispersive spectrometer. In order to investigate the effect of HA-LDH on the mine soil, greenhouse experiments of Artemisia ordosica were carried out under different concentrations of amendments (0, 1%, 3%, 5%, 7%). The plant growth, metal availability, and soil enzyme activities were studied to determine the effects of HA-LDH. The mine soil with 5% HA-LDH was the optimum proportion, and the growth of Artemisia ordosica was in good status. The HA-LDH and Artemisia ordosica could effectively decrease the bioavailability of heavy metals (such as Pb, Cr, Ni, Cd, Zn, and As) in the mine soil, and improve the enzyme activities of ß-glucosidase, urease, and phosphatase. The HA-LDH with magnetism could be easily separated. The characteristics and reusability of HA-LDH could be well maintained after five cycles of remediation. Consequently, the HA-LDH is promising for the remediation of contaminated soils in mining area.

Effects of Coking Wastewater on the Growth of Five Wetland Plant Species.

In order to investigate the effect of wetland plants in the treatment of coking wastewater, Oenanthe javanica (Blume) DC (OC), Artemisia selengensis Turcz. ex Bess. (AB), Echinochloa crusgalli (L.) Beauv. (EB), Brasenia schreberi J.F.Gmel. (BG), and Lythrum salicaria L. (LL) were used to remove ammonia-nitrogen and chemical oxygen demand (COD) from coking wastewater. Results showed high concentrations (> 30%, diluted by deionized water) of coking wastewater caused decreased photosynthetic rate, transpiration rate, and relative growth rate in all studied plants. OC, BG, and LL showed higher adaptability than AB and EB. Wastewater concentrations < 30% resulted in less affected growth of OC, BG, and LL; However, AB and EB were suppressed when coking wastewater concentrations were > 15%. High concentrations of coking wastewater generated oxidative stress which resulted in increased malondialdehyde and proline contents and inhibition of superoxide dismutase. OC, BG, and LL were considered tolerable species in purifying coking wastewater (concentrations < 30%).

Circulation immune cell landscape in canonical pathogenesis of colorectal adenocarcinoma by CyTOF analysis.

Current studies on the immune microenvironment of colorectal cancer (CRC) were mostly limited to the tissue level, lacking relevant studies in the peripheral blood, and failed to describe its alterations in the whole process of adenocarcinoma formation, especially of adenoma carcinogenesis. Here, we constructed a large-scale population cohort and used the CyTOF to explore the changes of various immune cell subsets in peripheral blood of CRC. We found monocytes and basophils cells were significantly higher in adenocarcinoma patients. Compared with early-stage CRC, effector CD4+T cells and naive B cells were higher in patients with lymph node metastasis, whereas the basophils were lower. We also performed random forest algorithm and found monocytes play the key role in carcinogenesis. Our study draws a peripheral blood immune cell landscape of the occurrence and development of CRC at the single-cell level and provides a reference for other researchers.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.

KIF15 knockdown inhibits colorectal cancer proliferation and migration through affecting the ubiquitination modification of NRAS.

As one of the most common malignancies, colorectal cancer (CRC) requires a thorough understanding of the mechanisms that promote its development and the discovery of new therapeutic targets. In this study, immunohistochemical staining confirmed significantly higher expression levels of KIF15 in CRC. qPCR and western blot results demonstrated the effective suppression of KIF15 mRNA and protein expression by shKIF15. Downregulation of KIF15 inhibited the proliferation and migration of CRC cells while promoting apoptosis. In addition, evidence from the xenograft experiments in nude mice demonstrated that KIF15 knockdown also suppressed tumor growth. Through bioinformatics analysis, the downstream molecular NRAS and Rac signaling pathway associated with KIF15 were identified. KIF15 knockdown was found to inhibit NRAS expression and disrupt Rac signaling pathway. Moreover, WB and Co-IP assays revealed that KIF15 reduced the ubiquitination modification of NRAS protein by interacting with the E3 ligase MDM2, thereby enhancing NRAS protein stability. Functionally, NRAS knockdown was shown to inhibit cell proliferation and migration. In conclusion, KIF15 promoted CRC progression by regulating NRAS expression and Rac signaling pathway.

Hepatoid adenocarcinoma-Clinicopathological features and molecular characteristics.

Hepatoid adenocarcinoma (HAC) is a rare, malignant, extrahepatic tumor with histologic features similar to those of hepatocellular carcinoma. HAC is most often associated with elevated alpha-fetoprotein (AFP). HAC can occur in multiple organs, including the stomach, esophagus, colon, pancreas, lungs, and ovaries. HAC differs greatly from typical adenocarcinoma in terms of its biological aggression, poor prognosis, and clinicopathological characteristics. However, the mechanisms underlying its development and invasive metastasis remain unclear. The purpose of this review was to summarize the clinicopathological features, molecular traits, and molecular mechanisms driving the malignant phenotype of HAC, in order to support the clinical diagnosis and treatment of HAC.

Poorly differentiated mucinous carcinoma with signet ring cells in an ovarian endometriotic cyst: a case report.

BACKGROUND: Ovarian signet ring cell carcinomas are predominantly metastatic. Cases coexisting with endometriotic cysts are extremely rare, and are supposed to be primary. However, such cases have not been well-documented to date. CASE PRESENTATION: A 46-year-old Chinese woman had an incidental small nodule in the right ovarian endometriotic cyst. She underwent a staging surgery due to an unexpected ovarian carcinoma from her frozen section. Laparotomy exploration, MRI and gastrointestinal endoscopy revealed no other abnormalities in the abdominal organs. She had a pelvic recurrence at 7 months and was alive with disease for 13 months at present. Gross examination showed a small mural nodule (l.0 × 0.5 × 0.2 cm) in the wall of the right ovarian cyst (18x15x14 cm). Microscopically, the neoplastic cells arranged in solid nests, crowded small irregular glands and scattered single cells. They had abundant cytoplasmic mucin and contained a significant component of signet ring cells. The stroma was desmoplastic and occasionally contained extracellular mucin deposits. The surrounding endometriotic cyst had several foci of atypical surface epithelium (atypical endometriotic cyst) that was continuous with the mucinous carcinoma. Immunohistochemistry demonstrated that the tumor cells were diffusely positive for CK7 and negative for CK20 and CDX2. CONCLUSIONS: Primary ovarian poorly differentiated mucinous carcinoma with signet ring cells can occur in an atypical endometriotic cyst. This rare case addresses the necessity of careful and extensive pathological examination on large ovarian endometriotic cysts.

Simultaneous disintegration of municipal sludge and generation of ethanol with magnetic layered double hydroxides.

In order to investigate the effect of magnetic ZnCaFe-layered double hydroxides (MLDH) on the disintegration of municipal sludge and generation of ethanol, the MLDH was synthesized for use in the treatment of municipal sludge. The results indicated that the disintegration performance of municipal sludge was obviously enhanced by the MLDH under visible light irradiation, and the MLDH could also improve saccharification and fermentation in the dark. The yields of 468.9 mg/g for reducing sugar and 136.3 mg/g for ethanol were achieved respectively when the MLDH was 0.3 mg/mL, pretreatment time was 80 min, simultaneous saccharification and fermentation (SSF) time was 120 h, and enzyme loading was 60 FPU/g. The conversion yields were still higher than that of control group after 6 cycles of the MLDH. Therefore, the recyclable MLDH is promising for the treatment and energy conversion of municipal sludge.

SP1-induced lncRNA TINCR overexpression contributes to colorectal cancer progression by sponging miR-7-5p.

Mounting evidences have indicated that long noncoding RNAs (lncRNAs) play pivotal roles in human diseases, especially in cancers. Recently, TINCR was proposed to be involved in tumor progression. However, its role in colorectal cancer (CRC) remains elusive. In our study, we found that SP1-induced TINCR was significantly upregulated in CRC tissues and cell lines. Moreover, cox multivariate survival analysis revealed that high TINCR was an independent predictor of poor overall survival (OS). Functionally, knockdown of TINCR obviously suppressed CRC cells proliferation, migration and invasion in vitro, and inhibited CRC cells growth and metastasis in vivo. Mechanistically, we identified TINCR could act as a miR-7-5p sponge using RNA pull down, luciferase reporter and RIP assays. Furthermore, we showed that TINCR might promote CRC progression via miR-7-5p-mediated PI3K/Akt/mTOR signaling pathway. Lastly, we revealed that plasma TINCR expression was upregulated in CRC when compared to healthy controls and could be a promising diagnostic biomarker for CRC. Based on above results, our data indicated that TINCR might serve as a potential diagnostic and prognostic biomarker for CRC.

[Associated vessel heteromorphosis in laparoscopic complete mesocolic excision and solutions to intraoperative hemorrhage].

Vessel identification and dissection are the key processes of laparoscopic complete mesocolic excision (CME). Vascular injury will lead to complications such as prolonged operative time, intraoperative hemorrhage and ischemia of anastomotic stoma. Superior mesenteric artery (SMA), superior mesenteric vein(SMV), gastrointestinal trunk, left colic artery(LCA), sigmoid artery and marginal vessels in the mesentery have been found with possibility of heteromorphosis, which requires better operative techniques. Surgeons should recognize those vessel heteromorphosis carefully during operations and adjust strategies to avoid intraoperative hemorrhage. Preoperative abdominal computed tomography angiography(CTA) with three-dimensional reconstruction can find vessel heteromorphosis within surgical area before operation. Adequate dissection of veins instead of violent separation will decrease intraoperative bleeding and be helpful for dealing with the potential hemorrhage. When intraoperative hemorrhage occurs, surgeons need to control the bleeding by simple compression or vascular clips depending on the different situations. When the bleeding can not be stopped by laparoscopic operation, surgeons should turn to open surgery without hesitation.

Neuroendocrine differentiation is predictive of poor survival in patients with stage II colorectal cancer.

The diagnosis of neuroendocrine differentiation (NED) is made primarily on the basis of ultrastructure and/or immunohistochemistry (IHC). Synaptophysin (Syn) and chromogranin A (CgA) are two important frequently used NED markers in colorectal cancer (CRC). The association between NED and the prognosis of stage II CRC remains controversial. Administration of adjuvant chemotherapy remains challenging for stage II CRC. Identification of reliable factors that improve the selection of patients with stage II CRC at high risk following surgery is of great importance. A total of 151 cases of patients with stage II CRC who received radical surgery in The Second Affiliated Hospital of Zhejiang University (Hangzhou, China) between January 2002 and March 2011 were assayed for Syn and CgA using IHC, following which patients were classified as NED(+) or NED(-). Survival curves were constructed using the Kaplan-Meier estimator, and the prognostic value was determined using a log-rank test and Cox's regression test. In the 151 cases of stage II CRC examined, the incidence of NED was 34.44%. The overall survival of the NED(+) group was significantly less favorable than that of the NED(-) group (P=0.001). The 5-year survival rate was 68% for NED(+) (n=51) and 90% for NED(-) (n=97). The independent prognostic factors of survival of patients with stage II CRC following multivariate analysis were age ≥65 years (P=0.007) and NED-positivity (P=0.014). NED was revealed to be an independent factor of poor prognosis for patients with stage II CRC, which may offer potential for improved therapy stratification.

[Integrative management of operation, perioperative rehabilitation and postoperative adjuvant chemotherapy in elderly patients with colorectal carcinoma].

With the aging of the Chinese population, it seems obvious that the number of elderly patients with the disease of colorectal carcinoma grows significantly. Meanwhile, no evidence-based practical guideline for the treatment of colorectal carcinoma are available in this particular age group. Therefore, the concept of integrative management has been brought up by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University, which combines the processes of surgery, perioperative rehabilitation and adjuvant chemotherapy together. In this way, the cooperation and complementarity between different clinical departments could cooperate and complete tasks together to integrate the treatment processes into a cohesive one. To achieve the goal of integrative management, the project is divided into horizontal and vertical aspects. The horizontal integration means the cooperation between different clinical departments, which is also known as multi-discipline treatment (MDT). The vertical integration reflects the completeness of the entire treatment under the goal of consistency, strictness and job separation, which could also be explained as the clinical pathway. Furthermore, this review stresses on the integrative strategy of both clinical and biochemical indexes rehabilitation, as well as the operation and postoperative adjuvant chemotherapy which has been put in execution several years by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University.

Neuroendocrine differentiation is a prognostic factor for stage II poorly differentiated colorectal cancer.

Neuroendocrine differentiation (NED) in colorectal cancer is an indistinct phenomenon and may define a new cancer subtype, especially in the poorly differentiated colorectal cancer (PDCRC). The clinical features of PDCRC with NED remain controversial, thus confusing the implementation of individualized treatment. This study included 171 patients who underwent surgery from 2000 to 2011 and had pathology-confirmed PDCRC. Each sample was examined by immunohistochemistry for the biological markers of NED, synaptophysin (Syn), and chromogranin (CgA). Patients with Syn(+) and/or CgA(+) cells were classified as NED(+); otherwise, they were NED(-). Data were collected for patients who were followed up for at least two years. NED(+) staining was present in 71 (41.5%) patients. The median survival time was 36.9 months. No survival differences existed between the NED(-) and NED(+) groups (P > 0.05). However, stage II NED(+) patients had a significantly worse prognosis than NED(-) patients (P = 0.018). For the NED(+) group, the median survival was 38.56 months, and the 5-year survival was 65%. For the NED(-) group, the median survival was 53.18 months, and the 5-year survival was 90%. NED is a common event in primary PDCRC. For stage II PDCRC, NED(+) indicates a poor prognosis.

Transcription-mediated chimeric RNAs in prostate cancer: time to revisit old hypothesis?

Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer-specific fusion genes were recently reported in Chinese cases. We attempted to confirm one of the fusion genes, USP9Y-TTTY15, by reverse transcription PCR, but detected the presence of the USP9Y-TTTY15 fusion transcript in cancer samples, nonmalignant prostate tissues, and normal tissues from other organs, demonstrating that it is a transcription-induced chimeric RNA, which is commonly produced in normal tissues. In 105 prostate cancer samples and case-matched adjacent nonmalignant tissues, we determined the expression level of USP9Y-TTTY15 and a previously reported transcription-induced chimeric RNA, SLC45A3-ELK4. The expression levels of both chimeric RNAs vary greatly in cancer and normal cells. USP9Y-TTTY15 expression is neither higher in cancer than adjacent normal tissues, nor correlated with features of advanced prostate cancer. Although the expression level of SLC45A3-ELK4 is higher in cancer than normal cells, and a dramatic increase in its expression from normal to cancer cells is correlated with advanced disease, its expression level in cancer samples alone is not correlated with any clinical parameters. These data show that both chimeric RNAs contribute less to prostate carcinogenesis than previously reported.