Expanding the Scope of Polymerization-Induced Self-Assembly: Recent Advances and New Horizons.

Over the past decade or so, polymerization-induced self-assembly (PISA) has become a versatile method for rational preparation of concentrated block copolymer nanoparticles with a diverse set of morphologies. Much of the PISA literature has focused on the preparation of well-defined linear block copolymers by using linear macromolecular chain transfer agents (macro-CTAs) with high chain transfer constants. In this review, a recent process is highlighted from an unusual angle that has expanded the scope of PISA including i) synthesis of block copolymers with nonlinear architectures (e.g., star block copolymer, branched block copolymer) by PISA, ii) in situ synthesis of blends of polymers by PISA, and iii) utilization of macro-CTAs with low chain transfer constants in PISA. By highlighting these important examples, new insights into the research of PISA and future impact these methods will have on polymer and colloid synthesis are provided.

How the Reactive End Group of Macro-RAFT Agent Affects RAFT-Mediated Emulsion Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly via reversible addition-fragmentation chain transfer (RAFT)-mediated emulsion polymerization is an emerging method in which macro-RAFT agents are chain extended with hydrophobic monomers in water to form block copolymer nano-objects. However, almost all RAFT-mediated emulsion polymerizations are limited to AB diblock copolymers by using monofunctional macro-RAFT agents with non-reactive end groups. In this study, the first investigation on how the reactive end group of macro-RAFT agent affects RAFT-mediated emulsion polymerization is reported. Three macro-RAFT agents with different end groups are synthesized and employed in RAFT-mediated emulsion polymerization. Effects of end groups on morphologies of block copolymer nano-objects and polymerization process are studied. Block copolymer nano-objects prepared by using an asymmetric difunctional macro-RAFT agent can be functionalized by further chain extension on the surface. It is expected that the current study will not only expand the scope of RAFT-mediated emulsion polymerization, but also provide a novel strategy to prepare functional polymer nanoparticles.

Clinical outcomes of curative treatment for colorectal liver metastases combined with cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastases: a systematic review and meta-analysis of current evidence.

BACKGROUND: The optimal treatment for colorectal cancer (CRC) with synchronous peritoneal carcinomatosis (PC) and liver metastases (LM) remains controversial. We aimed to investigate clinical outcomes in patients with CRC and concomitant PC and LM who had undergone curative surgery, including resections at both metastatic sites and synchronous intraabdominal chemotherapy. METHODS: We searched PubMed, EMBASE, and Web of Science databases for eligible studies. Studies focusing on the clinical effects of curative surgery and synchronous intraabdominal chemotherapy for patients with CRC and concomitant PC and LM were included. Meta-analysis results were recorded as hazard ratios (HRs), risk ratios (RRs) and mean differences. RESULTS: We included 9 of 998 identified studies in the meta-analysis, involving 746 patients (221 patients with PC + LM, 525 patients with PC). Overall survival (pooled HR 1.68, 95% confidence interval [CI] 1.33-2.13, p < 0.01) and disease-free survival (pooled HR 1.82, 95% CI 1.51-2.20, p < 0.01) were both lower in patients with PC + LM. A higher recurrence rate (RR 1.22, 95% CI 1.04-1.44, p = 0.02) and major postoperative morbidity (RR 1.47, 95% CI 1.19-1.82, p < 0.01) were also observed in patients with PC + LM. CONCLUSION: Liver resection in combination with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with CRC and synchronous hepatic and peritoneal metastases may be associated with worse survival and higher morbidity compared with patients with isolated PC. More restricted patient inclusion criteria should be established to facilitate an optimal prognosis for this patient group.

A signature of hypoxia-related factors reveals functional dysregulation and robustly predicts clinical outcomes in stage I/II colorectal cancer patients.

BACKGROUND: The hypoxic tumor microenvironment accelerates the invasion and migration of colorectal cancer (CRC) cells. The aim of this study was to develop and validate a hypoxia gene signature for predicting the outcome in stage I/II CRC patients that have limited therapeutic options. METHODS: The hypoxic gene signature (HGS) was constructed using transcriptomic data of 309 CRC patients with complete clinical information from the CIT microarray dataset. A total of 1877 CRC patients with complete prognostic information in six independent datasets were divided into a training cohort and two validation cohorts. Univariate and multivariate analyses were conducted to evaluate the prognostic value of HGS. RESULTS: The HGS consisted of 14 genes, and demarcated the CRC patients into the high- and low-risk groups. In all three cohorts, patients in the high-risk group had significantly worse disease free survival (DFS) compared with those in the low risk group (training cohort-HR = 4.35, 95% CI 2.30-8.23, P < 0.001; TCGA cohort-HR = 2.14, 95% CI 1.09-4.21, P = 0.024; meta-validation cohort-HR = 1.91, 95% CI 1.08-3.39, P = 0.024). Compared to Oncotype DX, HGS showed superior predictive outcome in the training cohort (C-index, 0.80 vs 0.65) and the validation cohort (C-index, 0.70 vs 0.61). Pathway analysis of the high- and low-HGS groups showed significant differences in the expression of genes involved in mTROC1, G2-M, mitosis, oxidative phosphorylation, MYC and PI3K-AKT-mTOR pathways (P < 0.005). CONCLUSION: Hypoxic gene signature is a satisfactory prognostic model for early stage CRC patients, and the exact biological mechanism needs to be validated further.

Self-Assembled Borneol-Guanidine-Based Amphiphilic Polymers as an Efficient Antibiofilm Agent.

Biofilm-associated infections remain a tremendous obstacle to the treatment of microbial infections globally. However, the poor penetrability to a dense extracellular polymeric substance matrix of traditional antibacterial agents limits their antibiofilm activity. Here, we show that nanoaggregates formed by self-assembly of amphiphilic borneol-guanidine-based cationic polymers (BGNx-n) possess strong antibacterial activity and can eliminate mature Staphylococcus aureus (S. aureus) biofilms. The introduction of the guanidine moiety improves the hydrophilicity and membrane penetrability of BGNx-n. The self-assembled nanoaggregates with highly localized positive charges are expected to enhance their interaction with negatively charged bacteria and biofilms. Furthermore, nanoaggregates dissociate on the surface of biofilms into smaller BGNx-n polymers, which enhances their ability to penetrate biofilms. BGNx-n nanoaggregates that exhibit superior antibacterial activity have the minimum inhibitory concentration (MIC) of 62.5 µg·mL-1 against S. aureus and eradicate mature biofilms at 4 × MIC with negligible hemolysis. Taken together, this size-variable self-assembly system offers a promising strategy for the development of effective antibiofilm agents.

The Consistency between Registered Acupuncture-Moxibustion Clinical Studies and Their Published Studies and Update Status of Registered Information.

BACKGROUND: Few studies have analyzed the consistency between registered acupuncture-moxibustion clinical studies and their published research results as well as their update status of registered information. METHODS: We searched for acupuncture-moxibustion clinical studies that were registered at the World Health Organization International Clinical Trials Registry Platform between 2013 and 2015 and collected data regarding their characteristics and update status. Published results of these registered studies were identified and compared with registered information. RESULTS: A total of 425 registered acupuncture-moxibustion clinical studies were included; 379 (89.2%) of them were interventional studies, and the remaining 46 (10.8%) were observational studies. Forty-six studies (10.8%) were found to have published results, and 51 published articles were identified. Overall, 73.2% (311) of registered studies did not update the research status in time; 46.6% (198) stopped updating before recruiting; 21.6% (92) stopped updating after recruiting; and 4.9% (21) stopped updating after completion. Regarding the 46 studies with published results, 29 (63.0%) were considered to be affected by reporting bias. These reporting biases predominantly involved the omission of some predefined outcomes or endpoints (16 studies), contradictions regarding descriptions of sample sizes (9 studies), discrepancies in treatment measurements or group distribution (7 studies), and inconsistent treatment durations (4 studies). When compared with other studies, significant and various reporting biases could also be commonly found in fields other than acupuncture-moxibustion. CONCLUSIONS: There were many discrepancies between registered information and published reports on acupuncture-moxibustion, which could also be commonly observed in other fields. Moreover, a large proportion of registered studies did not update their research status in time. Efforts should be made to improve the reporting quality and timely updates.Es gibt nur wenige Studien, in denen die Übereinstimmung zwischen den registrierten klinischen Studien zur Akupunktur und Moxibustion mit den veröffentlichten Studienergebnissen und dem Aktualisierungsstand der Informationen im Register untersucht wurde.Wir suchten nach klinischen Studien zur Akupunktur und Moxibustion, die zwischen 2013 und 2015 auf der International Clinical Trials Registry Platform der Weltgesundheitsorganisation registriert wurden, und erhoben Daten zu ihren Merkmalen und ihrem Aktualisierungsstand. Die veröffentlichten Ergebnisse der registrierten Studien wurden identifiziert und mit den Informationen im Register verglichen.Insgesamt wurden 425 registrierte klinische Studien zur Akupunktur und Moxibustion eingeschlossen, davon waren 379 (89,2 %) Interventionsstudien und die restlichen 46 (10,8 %) waren Beobachtungsstudien. Es wurden 46 Studien (10,8 %) mit veröffentlichten Ergebnissen gefunden und 51 veröffentlichte Artikel identifiziert. Insgesamt wurde bei 73,2 % (311) der registrierten Studien der Forschungsstand nicht zeitnah aktualisiert; bei 46,6 % (198) wurde die Aktualisierung vor der Rekrutierung eingestellt; bei 21,6 % (92) wurde die Aktualisierung nach der Rekrutierung eingestellt und bei 4,9 % (21) wurde die Aktualisierung nach Abschluss der Studie eingestellt. Von den 46 Studien mit veröffentlichten Ergebnissen wurden 29 (63,0 %) als von Publikationsverzerrung betroffen angesehen. Diese Publikationsverzerrung betraf vor allem die Auslassung einiger vordefinierter Zielkriterien oder Endpunkte (16 Studien), Widersprüche bei der Beschreibung des Stichprobenumfangs (9 Studien), Diskrepanzen bei den Behandlungsmessungen oder der Gruppenverteilung (7 Studien) und Inkonsistenzen bei der Behandlungsdauer (4 Studien). Beim Vergleich mit anderen Studien wurden auch in anderen Bereichen als Akupunktur und Moxibustion häufig signifikante und unterschiedliche Publikationsverzerrungen festgestellt.Es bestanden zahlreiche Diskrepanzen zwischen den Informationen im Register und den veröffentlichten Berichten über Akupunktur und Moxibustion, die auch in anderen Bereichen häufig zu beobachten waren. Darüber hinaus wurde bei einem Großteil der registrierten Studien der Forschungsstand nicht zeitnah aktualisiert. Es sollten Anstrengungen unternommen werden, um die Qualität der Berichterstattung und die zeitnahe Aktualisierung zu verbessern.

IGSF6 is a novel biomarker to evaluate immune infiltration in mismatch repair-proficient colorectal cancer.

Immunotherapy has dramatically changed the landscape of treatment for colorectal cancer (CRC), but currently lack of effective predictive biomarker, especially for tumors with mismatch repair (MMR) proficiency. The response of immunotherapy is associated with the cell-cell interactions in tumor microenvironment, encompassing processes such as cell-cell recognition, binding, and adhesion. However, the function of immunoglobulin superfamily (IGSF) genes in tumor immune microenvironment remains uncharacterized. This study quantified the immune landscape by leveraging a gene expression matrix from publicly accessible databases. The associations between IGSF6 gene expression and immune cell infiltration were assessed. The expression levels of IGSF6, CD8+ T cells, CD4+ T cells and CD68+ macrophage cells in cancer tissues from CRC patients and CRC cell lines were evaluated. IGSF6 was more highly expressed in CRC tumor tissues than adjacent normal tissues. And IGSF6 was significantly correlated with immune cell infiltration in MMR-proficient patients. Remarkably, MMR-proficient patients with high IGSF6 expression showed more sensitive to immunotherapy and chemotherapy than those with low IGSF6 expression. In summary, IGSF6 could be a novel biomarker to evaluate immune infiltration and predict therapeutic effect for MMR-proficient CRC.

Effects of Initial Turbulence on the Explosion Limit and Flame Propagation Behaviors of Premixed Syngas-Air Mixtures.

Syngas with important industrial applications has explosive hazards because of its flammability. It is necessary and valuable to study the combustion and explosion characteristics of syngas under actual working conditions. To explore the effects of initial turbulence on the explosion limits and the flame propagation behavior of the syngas-air mixtures, the explosion limits were tested by the explosive limit instrument, and the flame propagation process in the spherical pressure vessel was recorded by a high-speed camera. By adjusting the rotating speed of the stirrer to obtain turbulence of different intensities, the explosion limit and flame propagation behavior of syngas under different turbulent conditions were analyzed. The explosion limit of syngas in the macro-static state was 9.5-76.1%, and its flame front was relatively smooth. However, with the increase in turbulence intensity, both the upper and lower explosion limits of syngas decreased. The disturbance of turbulence made the flame shape change. The flame front was wrinkled, and the flame boundary was blurred, which became more and more obvious with the increase in turbulence intensity. The maximum velocity and duration of flame propagation increased with the increase in turbulence intensity. Under the same turbulence intensity, the flame propagation velocity generally augmented first and then lessened.

Genome-Wide Analysis Reveals Hypoxic Microenvironment Is Associated With Immunosuppression in Poor Survival of Stage II/III Colorectal Cancer Patients.

Background: Hypoxia is associated with a poorer clinical outcome and resistance to chemotherapy in solid tumors; identifying hypoxic-related colorectal cancer (CRC) and revealing its mechanism are important. The aim of this study was to assess hypoxia signature for predicting prognosis and analyze relevant mechanism. Methods: Patients without chemotherapy were selected for the identification of hypoxia-related genes (HRGs). A total of six independent datasets that included 1,877 CRC patients were divided into a training cohort and two validation cohorts. Functional annotation and analysis were performed to reveal relevant mechanism. Results: A 12-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohorts [TCGA, n = 509, hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.18 - 3.89, P = 0.01; metavalidation, n = 590, HR = 2.46, 95% CI = 1.59 - 3.81, P < 0.001]. High hypoxic risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 5.1, 95% CI = 2.51 - 10.35, P < 0.001). After integration with clinical characteristics, hypoxia-related gene signature (HRGS) remained as an independent prognostic factor in multivariate analysis. Furthermore, enrichment analysis found that antitumor immune response was suppressed in the high hypoxic group. Conclusions: HRGS is a promising system for estimating disease-free survival of stage II/III CRC patients. Hypoxia tumor microenvironment may be via inhibiting immune response to promote chemoresistance in stage II/III CRC patients.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

Effective Insensitiveness of Melamine Urea-Formaldehyde Resin via Interfacial Polymerization on Nitramine Explosives.

To improve the safety of ammonium nitrate explosives, the melamine urea-formaldehyde resin (MUF resin) was selected for the preparation of three typical nitramine explosives (cyclotetramethylenetetranitramine, HMX; cryclo-trimethylenetrinitramine, RDX; and hexanitrohexaazaisowurtzitane, CL-20) based green polymer-bonded explosives (GPBXs) via interfacial polymerization. Meanwhile, the corresponding composite particles prepared by physical mixing and drying bath methods were studied and compared. The particle morphology, crystal structure, thermal stability, and safety performance of the resultant composite particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectra, differential scanning calorimeter (DSC), and impact sensitivity test, respectively. SEM results showed that MUF was successfully coated on the surface of the three explosives, and different composite particles prepared by the same method have their own unique characteristics. Such effect is attributed to the resin's ability to isolate and buffer external stimuli. It is obvious that the interfacial polymerization is an effective desensitization technique to prepare core-shell composite particles for explosives.

Analysis of the Registration Information on Interventions of Acupuncture and Moxibustion Trials in the International Clinical Trials Registry Platform.

PURPOSE: To analyze and compare the clinical registration information about acupuncture and moxibustion for intervention characteristics. METHODS: Clinical trials from the International Clinical Trials Registry Platform of the World Health Organization in acupuncture and moxibustion were comprehensively collected from 2013 to 2015; data were independently screened and extracted by two retrievers, and relevant data involving either basic descriptions or intervention characteristics were analyzed. RESULTS: 425 acupuncture and moxibustion registered clinical trials were included; 88.00% (374/425) were designed as controlled studies, among which 38.59% (164/425) had sham acupuncture as the control group. The most common diseases were pain-related at approximately 19.29% (82/425) of trials. Reports on the intervention information in these acupuncture and moxibustion clinical studies were not sufficiently presented; these reports included the reporting of names of points (39.8%), the method of needle stimulation (32.5%), needle type (29.6%), needle retention time (34.1%), the number of treatment sessions (22.4%), and the frequency and duration of treatment sessions (38.1%). CONCLUSION: The registration information for the clinical trials of acupuncture and moxibustion was quite low according to this investigational study. Steps should be taken to improve the quality of acupuncture and moxibustion registration information.

Overexpression of G protein-coupled receptor 31 as a poor prognosticator in human colorectal cancer.

AIM: To investigate the expression of G protein-coupled receptor 31 (GPR31) and its clinical significance in human colorectal cancer (CRC). METHODS: To determine the association between the GPR31 expression and the prognosis of patients, we obtained paraffin-embedded pathological specimens from 466 CRC patients who underwent initial resection. A total of 321 patients from the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were included as a training cohort, whereas 145 patients from the Sixth Affiliated Hospital of Sun Yat-sen University from January 2007 to November 2008 were included as a validation cohort. We examined GPR31 expression levels in CRC tissues from two independent cohorts via immunohistochemical staining. All patients were categorized into either a GPR31 low expression group or a GPR31 high expression group. The clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group were compared. RESULTS: We compared the clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group. Significant differences were observed in the number of patients in pM classification between patients in the GPR31 low expression group and GPR31 high expression group (P = 0.007). The five-year survival and tumor-free survival rates of patients were 84.3% and 82.2% in the GPR31 low expression group, respectively, and both rates were 59.7% in the GPR31 high expression group (P < 0.05). Results of the Cox proportional hazard regression model revealed that GPR31 upregulation was associated with shorter overall survival and tumor-free survival of patients with CRC (P < 0.05). Multivariate analysis identified GPR31 expression in colorectal cancer as an independent predictive factor of CRC patient survival (P < 0.05). CONCLUSION: High GPR31 expression levels were found to be correlated with pM classification of CRC and to serve as an independent predictive factor of poor survival of CRC patients.