Tf2O-Mediated P(O)-N Bond Formation of Either P(O)-OH or P(O)-H Reagents with Multitype Amines.

We have developed a Tf2O-mediated approach for the direct amination of either P(O)-OH or P(O)-H reagents with a variety of aliphatic or aromatic amines. Without the requirement of precious metals and toxic reagents, this protocol provides an alternative route to various phosphinamides and phosphoramides. The reaction proceeds under simple and mild conditions and can be effectively scaled up with similar efficiency.

Unsymmetrical Benzothieno-Fused BODIPYs as Efficient NIR Heavy-Atom-Free Photosensitizers.

Heavy-atom-free photosensitizers are potentially suitable for use in photodynamic therapy (PDT). In this contribution, a new family of unsymmetrical benzothieno-fused BODIPYs with reactive oxygen efficiency up to 50% in air-saturated toluene was reported. Their efficient intersystem crossing (ISC) resulted in the generation of both 1O2 and O2-• under irradiation. More importantly, the PDT efficacy of a respective 4-methoxystyryl-modified benzothieno-fused BODIPY in living cells exhibited an extremely high phototoxicity with an ultralow IC50 value of 2.78 nM. The results revealed that the incorporation of an electron-donating group at the α-position of the unsymmetrical benzothieno-fused BODIPY platform might be an effective approach for developing long-wavelength absorbing heavy-atom-free photosensitizers for precision cancer therapy.

Confinement of Oligopeptides by Terminally Functionalized Polyisoprene to Improve Their Mechanical Strength, Creep Resistance, and Antifatigue Properties.

A small amount of terminal polar phase endows natural rubber (NR) with excellent comprehensive properties superior to those of synthetic isoprene rubber. In this work, the comprehensive properties of synthetic rubber were remarkably improved by introducing a stable terminal nanoconfinement structure by combining terminal hydroxyl groups and pentapeptide molecules noncovalently into the same phases. The results show that the stable terminal phases hardly affect the free chain motion but enhance the entanglement. Under cyclic loading, the terminal polar phases undergo hierarchically structural changes such as reversible dissociation of the weak bonds, phase deformation, and crystalline reorganization, all of which dissipate the stress and are beneficial for high strength and extensibility. At the same time, synthetic rubbers demonstrate much superior fatigue resistance and lower hysteresis relative to NR and maintain comparable dimensional stability. This strategy suggests that the comprehensive properties of elastomers can be regulated and upgraded by facile terminal noncovalent interactions.

Influence of Oligopeptide Length and Distribution on Polyisoprene Properties.

The tuning of binding modes of polar groups is the key step to mimicking the structure and properties of natural rubber through the molecular design of synthetic polyisoprenes. Herein, the ordering and binding distances of oligopeptides could be altered systematically by changing their lengths and distribution along the polyisoprene chain, which impose huge impacts on the mechanical properties and chain dynamics of green rubber. In detail, a series of peptide-functionalized polyisoprenes with terminal blocks (B-2A-PIP, B-3A-PIP) or random sequences (R-2A-PIP, R-3A-PIP) are fabricated by using dipeptides (2A) or tripeptides (3A) as crosslinkers to explore the mechanism of terminal interaction on mechanism properties and chain dynamics. B-4A-PIP and R-4A-PIP served as control samples. It is found that the increased oligopeptide length and the block distribution improves the mechanical properties and confine the chain movement by elevate the contents of ordered and compact microstructures, which is indicated by XRD, broadband dielectric spectroscopy (BDS) and consistent with the result of molecular dynamics simulation. New relaxation signals belonging to oligopeptide aggregates are found which showed elevated dielectric strengths upon temperatures increase. Additionally, it also reveals that the binding modes of oligopeptide do not significantly influence the entanglements of polyisoprene.

Landscape of distant metastasis mode and current chemotherapy efficacy of the advanced biliary tract cancer in the United States, 2010-2016.

BACKGROUND: The distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed. METHOD: A total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias. RESULT: The proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P < .05 in all the subtypes) where the multi-metastasis and distant lymph node (dLN) only always indicated the worst and best prognosis, respectively. Chemotherapy presented the most significant survival impact with the lowest hazard ratio by multivariate cox model and still provided a survival improvement after PSM (all P < .001) in all subtypes. However, the median months manifested different between patients with and without chemotherapy among the subtypes (ICC, from 5 to 9; PHCC, from 6 to 10; AVC, from 4 to 9; GBC, from 6 to 7; DCC from 6 to 8). CONCLUSION: We provided a landscape about the detailed DM mode of the advanced BTC in a large population, found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes.

Suppression of SMOC2 reduces bleomycin (BLM)-induced pulmonary fibrosis by inhibition of TGF-ß1/SMADs pathway.

Although the initiation and modulation of lung fibrosis has been widely investigated, the pathogenesis was not well understood. Secreted modular calcium-binding protein 2 (SMOC2) as the secreted protein acidic is enriched in cysteine (SPARC) family of matricellular proteins, which are important in regulating cell-matrix interactions. Here we aimed to calculate the effects and molecular mechanism of SMOC2 on the progression and severity of lung fibrosis in murine bleomycin (BLM)-induced mice. The pulmonary fibrosis was significantly induced by BLM in wild type (WT) C57BL6 mice, as evidenced by the lung sections histology and collagen accumulation using H&E and Masson Trichrome staining. Notably, SMOC2 knockout (SMOC2-/-) mice treated with BLM exhibited the decrease in inflammation accompanied by the reduction of neutrophils, macrophages and lymphocytes in bronchoalveolar lavage fluids (BALF). In addition, the levels of inflammation-associated cytokines and chemokines induced by BLM were also decreased in BALF obtained from SMOC2-/- mice. Meanwhile, SMOC2-/- suppressed the progression of pulmonary fibrosis, as evidenced by the reduction in levels of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), p-SMAD2 and p-SMAD3 in lung tissue samples. Increasing expression of SMOC2 in TGF-ß1 treated cells were further observed in vitro. Of note, up regulation of SMOC2 activated-fibrosis development in MRC-5 cells, along with increase of α-SMA, p-SMAD2 and p-SMAD3 were determined. In contrast, SMOC2 knockdown reduced TGF-ß1-stimulated expressions of α-SMA, p-SMAD2 and p-SMAD3 in cells. The findings above suggested that SMOC2 knockout contributes to inhibit BLM-induced pulmonary fibrosis.

Four differentially methylated gene pairs to predict the prognosis for early stage hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) was the second most common malignant tumor with a poor prognostic condition. We aimed to identify novel methylation signatures to predict HCC patients at their early stages. Differentially expressed methylated genes between HCC patients and normal liver tissues retrieved from TCGA were screened out by SAM. Genes highly related to patients' survival were figured out by COX. The signatures that could identify relapse HCC patients were identified by the forwarding search algorithm. Besides, functional enrichment analysis was performed on the methylation genes in the signature. A total of 5,392 CPG sites that differentially methylated expressed were found out and 4,294 differentially expressed genes were obtained. A total of 197 genes among were associated with RFS of HCC patients at both stage I and stage II. Signature composed of 21 pairs was obtained to predict the prognostic situation by C-index forward search method. The function of these genes was figured out by functional enrichment analysis. To summary, the signature composed of 21 gene pairs that can predict the prognostic situation of HCC patients at both stage I and stage II, provided a reference standard for the adjuvant therapy of HCC patients after surgery.

[Application of X-Ray Fluorescence Spectrometry in Xujiahe Formation of Sichuan Basin for the Study of Sedimentary Facies].

Currently, X-ray fluorescence spectrometer (XRF) is not widely used in the determination of geological samples, and it's much less used in the study of sedimentary facies. XRF was firstly used to identify sedimentary environment of the T3x2 formation in central Sichuan region. In order to investigate the controversy of sedimentary facies and sedimentary environment of T3x2 formation of the Upper Triassic in the Central Part of Sichuan Basin, particularly whether the T3x2 formation is continental deposit or marine deposit, samples were collected in four representative zones from Xujiahe formation in Sichuan Basin. The method of X-ray fluorescence spectrometry were used to analyze the element contents and its' changing characteristics of the deposition from target formation. The sedimentary facies and sedimentary environment of target formation could be quantificationally analyzed by the symbol of corresponding element content. The results of the study show that the ratio of Sr/Ba, Mn/Fe and Sr/Ca of T3x2 formation belong to continental deposits, and it has no significant difference with characteristics of element contents from T3x3 or T3x4. The analysis results about the ratio of Sr/Cu show that the climatic environment of target formation was warm and humid, and T3x2 formation was belong to continental deposits in warm and humid environment, which is similar to the sedimentary environment of T3x3 or T3x4 formation. The relative errors between this method and conventional chemical analysis are less than 3%. The method of X ray fluorescence spectrometry is simple and feasible, which provides a quantitative analysis method for identification of sedimentary facies and sedimentary environment. The paper provides a new feasible method to solve the controversial sedimentary facies, which will promote the using of X-ray fluorescence spectrometric analysis method in geology.

Biopsy from the base and edge of gastric ulcer healing or complete healing may lead to detection of gastric cancer earlier: an 8 years endoscopic follow-up study.

BACKGROUND/AIMS: To assess the incidence of gastric cancer development in gastric benign ulcer patients and to evaluate the value of biopsy by taking specimens from both the base and edges of ulcers in contrast to the traditional biopsy which takes specimens from the edges of ulcers only. METHODOLOGY: An endoscopic followup of more than 1 year was conducted on 456 gastric ulcer patients in our hospital for a duration over 8 years. We collected clinical, endoscopic and pathological data and obtained at least 6 biopsies from both the edges and the bases of ulcers healing or complete healing, respectively and assessed H. pylori infection. RESULTS: Gastric cancers developed in 11 (2.41%) of 456 GU patients. In the experimental group, 3 cases that were diagnosed by histology showed adenocarcinoma with specimens taken from the ulcer bases and in the other 5 cases the specimens were taken from the ulcer edges. The detection rate of gastric cancer from gastric ulcer between experimental group and control group was statistically significant (4.57% vs. 1.07%, p<0.05). CONCLUSIONS: Gastric ulcer may develop into gastric cancer over a certain period of time in patients infected with H. pylori. Biopsies from ulcer bases and edges at the second or subsequent endoscopies may lead to defection of gastric cancer earlier and more effectively than the biopsies which take specimens from the edges of ulcers only.

Biopsy from the base of gastric ulcer may find gastric cancer earlier.

Gastric cancer is one of the most common malignancies in the world; however, its exact mechanism of development which may be relevant to many factors is still unclear, such as age, diet, Helicobacter pylori infection, smoking, polyps, chronic gastric ulcer and so on. Chronic gastric ulcer is considered as precancerous lesion of gastric cancer. The above-mentioned diseases are usually diagnosed by endoscopy and biopsy. In general, biopsy specimens are usually taken from the edges of lesions, seldom from the base. In patients with chronic gastric ulcer, especially healing or healed benign ulcer, we took the biopsy specimens from both the edges and the base of ulcers in the follow-up. Malignant lesions were found in several cases of chronic gastric ulcer, in which specimens were taken from the base of lesions. Therefore, we hypothesize that biopsy from the base of healing or healed chronic gastric ulcer in the second or third endoscopy may find gastric cancer earlier than traditional biopsy.