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Terpenoids are the main components of stingless bee propolis, their biological activities have not been fully quantified and investigated. In this study, the single-factor design and response surface methodology were applied to optimize the terpenoids extraction process in Heterotrigona itama (also called H. itama) propolis. Furthermore, the in vitro antioxidant and anti-inflammatory activities of terpenoid-rich extract were evaluated. The results showed with 95% ethanol/5% water, a material-liquid extraction yield of 1:30 g/ml, and extraction 72 hr for three extractions, the highest terpenoids content in H. itama propolis of 46.44 ± 0.07%. The H. itama propolis terpenoid-rich extract showed relative low antioxidant effect but inhibited inflammatory response by decreasing the inflammatory mediators iNOS, IL-1β, IL-10, and increasing the antioxidant mediators HO-1. This study provided experimental parameters for the terpenoids optimal extraction from H. itama propolis and revealed their strong anti-inflammatory activity. PRACTICAL APPLICATIONS: H. itama stingless propolis is a newly founded stingless bee propolis type recently. H. itama stingless propolis has abundant terpenoids, however, scant information were provided regarding its extraction optimization. In this study, we investigated and obtained the optimal extract parameters of terpenoids in H. itama propolis，and demonstrated their strong anti-inflammatory activities; however, their antioxidant activities are relatively low. This study provided theoretical basis for the usage of H. itama stingless propolis in industry.

Alismatis Rhizoma(Zexie) is a commonly used traditional Chinese medicine, and it is separated into "Chuan Zexie"(Sichuan and Hubei provinces), "Jian Zexie"(Fujian and Jiangxi provinces) and "Guang Zexie"(Guangxi province) according to different producing areas. Alisma plantago-aquatica and A. orientale were listed as the original plants of Alismatis Rhizoma in different editions of Chinese Pharmacopoeia(Ch.P), respectively. The botanical origins of Alismatis Rhizoma caused much controversy during a period of time. This study aimed to define the botanical origins of Alismatis Rhizoma from different producing areas, and supply scientific evidence for Ch. P 2020 edition. In this paper, we summarized the descriptions of original plants and producing areas of Alismatis Rhizoma in ancient literatures. Flowers and fruits of original plants of Alismatis Rhizoma were collected from different typical areas, and compared with the morphological description of two species from Alisma genus in the Flora of China. Thirty-nine batches of leaves from 8 different areas were identified using DNA barcoding technology. The results showed that original plants of Alismatis Rhizoma from different areas could be distinguished from each other based on morphological characteristics and molecular characteristics. Then, "Jian Zexie" was identified as A. orientale, while "Chuan Zexie" and "Guang Zexie" were identified as A. plantago-aquatica. In conclusion, combining with herbal textural research, morphologic characteristics, DNA barcoding technology and market situation, this paper recommended that the botanical sources of Alismatis Rhizoma could be revised as Alisma orientale(Sam.) Juzep. and Alisma plantago-aquatica Linn. in the Ch. P 2020 edition.

Acupuncture reduces pain by activating specific areas called acupoints on the patient’s body. When these acupoints are fully activated, sensations of soreness, numbness, fullness, or heaviness called De qi or Te qi are felt by clinicians and patients. There are two kinds of acupuncture, manual acupuncture and electroacupuncture (EA). Compared with non-acupoints, acupoints are easily activated on the basis of their special composition of blood vessels, mast cells, and nerve fibers that mediate the acupuncture signals. In the spinal cord, EA can inhibit glial cell activation by down-regulating the chemokine CX3CL1 and increasing the anti-inflammatory cytokine interleukin-10. This inhibits P38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways, which are associated with microglial activation of the C-Jun N-terminal kinase signaling pathway and subsequent astrocyte activation. The inactivation of spinal microglia and astrocytes mediates the immediate and long-term analgesic effects of EA, respectively. A variety of pain-related substances released by glial cells such as the proinflammatory cytokines tumor necrosis factor [Formula: see text], interleukin-1[Formula: see text], interleukin-6, and prostaglandins such as prostaglandins E2 can also be reduced. The descending pain modulation system in the brain, including the anterior cingulated cortex, the periaqueductal gray, and the rostral ventromedial medulla, plays an important role in EA analgesia. Multiple transmitters and modulators, including endogenous opioids, cholecystokinin octapeptide, 5-hydroxytryptamine, glutamate, noradrenalin, dopamine, [Formula: see text]-aminobutyric acid, acetylcholine, and orexin A, are involved in acupuncture analgesia. Finally, the “Acupuncture [Formula: see text]” strategy is introduced to help clinicians achieve better analgesic effects, and a newly reported acupuncture method called acupoint catgut embedding, which injects sutures made of absorbable materials at acupoints to achieve long-term effects, is discussed.

Purpose: It was reported that the novel preoperative systemic immune-inflammation index (SII) can predict survival in cases of many malignant tumors. However, the prognostic significance of preoperative SII in breast cancer remains unclear. The purpose of this study was to investigate the relationship between SII and survival in breast cancer patients.Methods: Breast cancer patients (1,026) who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. The SII was determined using the following formula: neutrophil count × platelet count/lymphocyte count. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for SII. Propensity score matching (PSM) was applied to develop comparable cohorts of high SII group and low SII group.Results: A total of 1,026 patients were included as the primary cohort, and 894 patients were matched and regarded as the matched cohort. Patients were divided into two groups based on SII value: SII 601.7. In the primary cohort, the 5-years overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) rates for high SII group and low SII group were (85.6% vs. 91.3%, P = 0.016), (95.8% vs. 96.4%, P = 0.684), and (83.5% vs. 90.6%, P = 0.007), respectively. Univariate analysis showed that histological type, T stage, N stage, PR, HER2, Ki67, and SII all showed significant associations with OS; and histological type, T stage, N stage, and SII all showed significant associations with DMFS. Multivariate survival analysis revealed that SII can independently predict OS (P = 0.017) and DMFS (P = 0.007). Similar results were found in PSM cohort.Conclusions: Preoperative SII may be a reliable predictor of OS and DMFS in patients with operable breast cancer to provide personalized prognostication and assist in formulation of the clinical treatment strategy.

Trigeminal neuralgia (TN) is debilitating and is usually accompanied by mood disorders. The lateral habenula (LHb) is considered to be involved in the modulation of pain and mood disorders, and the present study aimed to determine if and how the LHb participates in the development of pain and anxiety in TN. To address this issue, a mouse model of partial transection of the infraorbital nerve (pT-ION) was established. pT-ION induced stable and long-lasting primary and secondary orofacial allodynia and anxiety-like behaviors that correlated with the increased excitability of LHb neurons. Adeno-associated virus (AAV)-mediated expression of hM4D(Gi) in glutamatergic neurons of the unilateral LHb followed by clozapine-N-oxide application relieved pT-ION-induced anxiety-like behaviors but not allodynia. Immunofluorescence validated the successful infection of AAV in the LHb, and microarray analysis showed changes in gene expression in the LHb of mice showing allodynia and anxiety-like behaviors after pT-ION. Among these differentially expressed genes was Tacr3, the downregulation of which was validated by RT-qPCR. Rescuing the downregulation of Tacr3 by AAV-mediated Tacr3 overexpression in the unilateral LHb significantly reversed pT-ION-induced anxiety-like behaviors but not allodynia. Whole-cell patch clamp recording showed that Tacr3 overexpression suppressed nerve injury-induced hyperexcitation of LHb neurons, and western blotting showed that the pT-ION-induced upregulation of p-CaMKII was reversed by AAV-mediated Tacr3 overexpression or chemicogenetic inhibition of glutamatergic neurons in the LHb. Moreover, not only anxiety-like behaviors, but also allodynia after pT-ION were significantly alleviated by chemicogenetic inhibition of bilateral LHb neurons or by bilateral Tacr3 overexpression in the LHb. In conclusion, Tacr3 in the LHb plays a protective role in treating trigeminal nerve injury-induced allodynia and anxiety-like behaviors by suppressing the hyperexcitability of LHb neurons. These findings provide a rationale for suppressing unilateral or bilateral LHb activity by targeting Tacr3 in treating the anxiety and pain associated with TN.

The mechanism of flavor retention in chicken broth from the perspective of gelatin affecting the flavor-binding ability of emulsions was investigated. Results showed that fat was the important reservoir for aroma compounds in the emulsion. The particle sizes of emulsions significantly decreased with prolonged stewing time of gelatin, which was consistent with the results from confocal laser scanning microscopy and interfacial tension. The ability of pre-heated gelatin emulsions to bind volatile compounds with higher hydrophobicity was enhanced. When 0.1% gelatin was added into chicken broth, the total amount of the main volatile compounds (OAV > 1) increased from 458.83 ng/g to 1218.42 ng/g. In summary, the pre-heated gelatin increased the interfacial pressure of water/oil interface, resulting in a smaller particle size of oil droplets, and these further increased the binding area between oil droplets and flavor compounds. This appears to be the mechanism that gelatin enhances the flavor intensity of chicken broth.

We first design and synthesize a dendritic aromatic 6-carboxyl linker (H6TDCPB), which is successfully assembled with Cd(II) ion to construct a porous metal–organic framework with a raw Cd6 cluster...

A 3D coordination polymer [CdK6(μ2-H2O)2(BODSDC)2(H2O)]n (1) based on the novel benzophenone-3,3′-disulfonyl-4,4′-dicarboxylate (BODSDC4−) ligand was synthesized and structurally characterized. The carboxylate and sulfonate groups of the organic ligands as well as the bridging water molecules connect the Cd2+ and K+ ions to produce a 2D layer, which is linked by the benzophenone moieties to give a 3D pillared framework. Compound 1 crystallizes in an acentric space group of Cc and has a large second-harmonic-generation (SHG) response of 1.3 times that of potassium dihydrogen phosphate (KDP) in the particle size of 25–210 μm. Further SHG measurements revealed that the material is type-I phase-matchable. The observed SHG efficiency is associated with the unsymmetrical geometry of the organic ligand and the distorted coordination polyhedrons of metal centers.

The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p

The present study investigated the role of cytochrome P450 family 2 subfamily E polypeptide 1 (CYP2E1) in the development and progression of gastric cancer (GC). The expression levels of CYP2E1 in MGC-803 GC cells and normal GES-1 cells were investigated via western blotting, and it was identified that the expression of CYP2E1 was different between GES-1 and MGC-803 cells. CYP2E1 was overexpressed in MGC-803 cells using a lentiviral vector GV358. Cell Counting Kit-8, flow cytometry, cell migration and Matrigel invasion assays suggested that overexpression of CYP2E1 promoted the proliferation and invasion, and inhibited the apoptosis of GC cells. The relationship between CYP2E1 expression and key signaling molecules in the PI3K/Akt/mTOR signaling pathway was assessed. Reverse transcription-quantitative PCR analysis showed that mTOR mRNA expression was significantly increased after overexpression of CYP2E1 (P

Chiral propargyl amines are valuable synthetic intermediates for the preparation of biologically active compounds and functionalized amines. Catalytic methods to access propargyl amines containing vicinal stereocenters with high diastereoselectivity are particularly rare. We report an unprecedented strategy for the synthesis of enantioenriched propargyl amines with two stereogenic centres. An iridium complex, ligated by a phosphoramidite ligand, catalyzes the hydroalkynylation of β,β-disubstituted enamides to afford propargyl amides in a highly regio-, diastereo-, and enantioselective fashion. Stereodivergent synthesis of all four possible stereoisomers was achieved using this strategy.

BACKGROUND: To assess the impact of the 21-gene recurrence score (RS) on chemotherapy decision making and survival outcomes for breast cancer patients with >4 positive lymph nodes. METHODS: Patients with non-metastatic estrogen receptor-positive breast cancer with >4 positive lymph nodes diagnosed between 2004 and 2013 were identified using the Surveillance, Epidemiology, and End Results database. The relationships between the 21-gene RS value and survival outcomes, chemotherapy decision-making, and chemotherapy benefit were analyzed. RESULTS: A total of 410 patients were identified, including 191 (46.6%), 164 (40.0%), and 55 (13.4%) in the low-, intermediate-, and high-risk RS groups, respectively. The 21-gene RS assay results were independently related to chemotherapy receipt. A total of 59.0%, 68.0%, and 78.0% of patients received chemotherapy in the low-, intermediate-, and high-risk RS groups, respectively. The 21-gene RS was an independent indicator of breast cancer specific survival (BCSS) and overall survival (OS). Intermediate-risk [BCSS: hazards ratio (HR), 2.832, 95% confidence interval (CI): 1.160–6.910, P=0.022; OS: HR, 3.704, 95% CI: 1.750–7.836, P=0.001] and high-risk RS (BCSS: HR, 6.440, 95% CI: 2.597–15.974, P 4 positive lymph nodes.

A double-walled MOF [Zn

The effects of thinning on soil active organic carbon and related soil enzyme activities were investigated in a Larix principis-rupprechtii plantation in Taiyue Mountain. With the increases of soil depth, the content of soil labile organic carbon, soil nitrogen content and enzyme activities all reduced. For each soil layer, moderate thinning increased soil carbon and nitrogen contents dramati-cally. The activities of sucrase (SC) and peroxidase (PEO) and the activities of polyphenol oxidase (PHO) and urease (UE) in the layer of 0-10 cm could be significantly improved by low thinning and moderate thinning, respectively. For the 10-50 cm layer, the activities of SC and UE were reduced by low thinning, while moderate thinning markedly reduced the activities of cellulase. Results from redundancy analysis showed that dissolved organic carbon (DOC) was the main factor affecting soil enzyme activity in both 0-10 cm and 20-30 cm soil layers and that soil organic carbon (SOC) contents affected the activities of PHO and SC in 10-20 cm soil layer. The microbial biomass nitrogen (MBN) mainly affected the activities of PHO, PEO and UE in 30-40 cm soil layer. The contents of total P (TP) and readily oxidized carbon (ROC) played an important role in affecting soil enzyme activities in 40-50 cm soil layer. The results indicated that thinning could dramati-cally affect soil active organic carbon content and soil enzyme activity in L. principis-rupprechtii plantation. Moderate thinning treatment could obtain the highest soil nutrients and achieve better soil chemical properties such as soil pH, water content and organic matter content than other treatments, which could improve vegetation structure, litter and nutrient cycling process. Therefore, we recommended moderate density adjustment (1404-1422 trees·hm本研究以太岳山华北落叶松人工林为对象,研究间伐对土壤活性有机碳及相关土壤酶活性的影响.结果表明: 随着土壤深度的增加,土壤活性有机碳含量、土壤氮含量和酶活性降低;同一土层中,中度间伐下土壤碳、氮养分含量显著增加.在0～10 cm土层,轻度间伐处理下蔗糖酶和过氧化物酶活性显著增加,中度间伐处理下多酚氧化酶和脲酶活性显著增加;在10～50 cm土层,轻度间伐处理下蔗糖酶和脲酶活性降低,中度间伐处理下纤维素酶活性显著降低;冗余分析显示,溶解性有机碳在0～10和20～30 cm土层是影响土壤酶活性的主要因素;在10～20 cm土层中,土壤有机碳是影响多酚氧化酶和蔗糖酶的主要因素;在30～40 cm土层,微生物生物量氮主要影响多酚氧化酶、过氧化物酶和脲酶活性,土壤全磷和易氧化有机碳对40～50 cm土层土壤酶活性起着重要的作用.间伐对华北落叶松人工林土壤活性有机碳含量和土壤酶活性有显著影响,中度间伐处理下土壤养分含量总体最高,土壤pH、含水率、有机质含量等化学性质优于其他几种处理,能较好地改善林下植被、枯落物及养分循环过程.因此,建议对落叶松人工林进行适度密度调整(1404～1422 trees·hm

The management of overwintering honeybee colonies is pivotal for the apiculture industry in China. To investigate the molecular mechanisms involved in the seasonal regulation of the development of Apis mellifera carnicas hypopharyngeal gland (HG), transmission electron microscopy (TEM), and large-scale proteomics (isobaric tag for relative and absolute quantification; iTRAQ) were employed. In total, 3,025 proteins were identified at two-time points: winter (constituting group A) and early spring (constituting group B). Among them, 24 proteins were quantified and compared to identify their differential expression patterns. The TEM profiles and iTRAQ analysis results might aid in understanding the molecular mechanisms associated with the seasonal changes in honeybee HG. For example, the acinar cells of spring worker honeybees had more mature organelles. Furthermore, the ribosomal structures and protein biosynthesis were strengthened. However, the amount of exocrine royal jelly produced could not have satisfied the demand of the feeding larvae and queen. Honeybees might suffer reduced immune function during their feeding stage. The present study elucidates the regulatory mechanisms of HG on overwintering and spring arousal in honeybees. The results might provide a practical and theoretical guideline for the overwintering management program of the apicultural industry.

Background We investigated the effect of lymphadenectomy on the survival outcomes of patients with advanced epithelial ovarian cancer in the Surveillance, Epidemiology, and End Results database according to residual disease status. Methods We evaluated 3048 patients with International Federation of Gynecology and Obstetrics stage-IIIC–IV epithelial ovarian cancer. We assessed the effect of lymphadenectomy stratified by residual disease size on cause-specific survival (CSS). Results A total of 1904 (62.5%) patients received lymphadenectomy, and 1355 (71.2%) patients had nodal metastases. Lymph-node status had no significant association with residual tumor size in the lymphadenectomy group. In multivariate analysis, lymphadenectomy was associated with a significantly better CSS and was an independent prognostic factor for CSS. Patients with >10 lymph nodes removed had better CSS compared with non-lymphadenectomy and 1–10 lymph nodes removed groups. Lymphadenectomy was associated with a significantly better CSS in patients with no gross residual tumor, but not in patients with residual tumor ≤1 cm or >1 cm. Conclusions Lymphadenectomy is significantly associated with a better survival outcome in patients advanced ovarian cancer, but its positive effect diminishes as residual tumor size increases.

WC-Fe-Ni-Co cemented carbides with a constant Co content were successfully prepared through low pressure sintering, and the effects of Fe/Ni ratio on the microstructure and properties of the cemented carbides were studied in detail. The X-ray diffractometer and transmission electron microscopy results show that the Fe/Ni ratio is a critical factor that affects the structure of the Fe-Ni-Co binder in the alloys, as it gradually changes from fcc γ-(Fe,Ni) to bcc α-(Fe,Ni) with an increase in the Fe/Ni ratio. Furthermore, the WC grains have a finer and more rounded shape and are more uniformly distributed in the matrix as the Fe/Ni ratio increases. Additionally, both the magnetic saturation (CoM) and coercive force (Hc) increase as the Fe/Ni ratio increases. The relative density of all alloys is greater than 99.93% except for the alloy with the Fe/Ni ratio of 1.67 (99.01%). Ignoring the effect of the lower relative density (Fe/Ni = 1.67), increasing the Fe/Ni ratio can enhance the hardness, transverse rupture strength and wear resistance of the alloys but can reduce the fracture toughness and corrosion resistance at the same time.

The roles of the γ-aminobutyric acid (GABA) shunt and polyamine (PA) degradation pathway on GABA accumulation were investigated in fresh tea leaves under anaerobic and aerobic sequential incubations. The GABA accumulation was mainly completed in the first anaerobic incubation through the interaction of the GABA shunt with the PA degradation pathway. When treated with aminoguanidine, the diamine oxidase and polyamine oxidase activities were almost completely inhibited, and the GABA contents decreased by 40.7%, 46.4%, 41.0% and 37.5% in the tea leaves of the four cultivars 'Fuyun No. 6', 'Fudingdabai', 'Longjing No. 43' and 'Pingyangtezao', respectively. The glutamate decarboxylase activity decreased significantly, and the accumulation of GABA may increase or decrease because of varietal differences, which occurred mainly relying on the PA degradation pathway during the second anaerobic incubation. Thus, approximately 37%-47% of the GABA formed in fresh tea leaves under hypoxia was supplied by the PA pathway.

Purpose: Investigating surrogate endpoints shortening the time of therapeutic evaluation in nasopharyngeal carcinoma (NPC) after radical treatment. Patients and Methods: We retrospectively analyzed 830 patients receiving intensity-modulated radiotherapy (IMRT) from 2008 to 2010 and being stratified by the 8th edition of UICC/AJCC staging system and the plasma Epstein-Barr virus DNA (EBV DNA). The annual rates of overall survival (OS), progression-free survival (PFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were sequentially calculated using the life table and compared by the McNemar method. Results: The time of shortening therapeutic evaluation by surrogate endpoints: OS, PFS, LRFS and DMFS could be shortened to 1-year (100% vs 100%, P=1) in patients with stage I; OS, PFS, LRFS and DMFS could be shortened to 3-year (96.9% vs 96.1%, P = 1; 94.6% vs 92.2%, P = 0.125; 96.9% vs 95.3%, P = 0.5) and 4-year (92.2% vs 91.2%, P = 0.125) in stage II; In the high EBV DNA group , OS and DMFS could be shortened to 1-year (100% vs 100%, P = 1;100% vs 100%, P = 0.25) in stage II; OS and PFS could be shortened to 3-year (94.3% vs 91.4%, P = 1;82.9% vs 74.3%, P = 0.25) in stage III; OS could be shortened to 4-year (75% vs 72.7%, P = 1) in stage IVA. Conclusions: The time of therapeutic evaluation could be shortened to

Purpose: This study examined the role of marital status on survival outcome of nasopharyngeal carcinoma (NPC) patients using a population-based cancer registry. Methods: Patients with primary NPC diagnosed between 2004 and 2013 were included using the Surveillance, Epidemiology and End Results program. Patient demographic, clinicopathologic features, management, and survival outcomes were compared according to marital status. Cause-specific survival (CSS, NPC-related death) for marital status was analyzed. Results: The data of 3018 patients were included, with 61.4%, 11.1%, 21.8, and 5.6% of patients married, divorced (or separated), single, and widowed, respectively. Widowed patients had the highest proportion of elderly age (p < 0.001), were more likely to be female (p < 0.001), and had more well-to-moderately differentiated (p < 0.001) and node-negative disease (p = 0.038). Widowed patients were also less likely to have received radiotherapy and chemotherapy compared with patients of other marital status (p < 0.001). The 5-year CSS was 76.1%, 70.8%, 73.4%, and 59.8% in the married, divorced, single, and widowed groups, respectively (p = 0.001). Marital status was the independent prognostic factor for CSS. Widowed patients had a significantly increased risk of NPC-related death compared with married (hazard ratio [HR] 2.014, 95% confidence interval [CI] 1.477-2.747, p < 0.001), divorced (HR 1.580, 95% CI 1.087-2.295, p = 0.017), and single (HR 2.000, 95% CI 1.402-2.854, p < 0.001) patients. The divorced (p = 0.067) and single (p = 0.949) groups had similar CSS to the married group. Conclusions: Being widowed was associated with an increased the risk of cancer mortality in NPC compared with being married, divorced, or single.

Septic tank effluent from rural areas was an ideal medium for cultivating oleaginous microalgae. However, the characteristics of septic tank effluents varied greatly due to the different incoming wastewater, and bring uncertain risks for algal growth. In this study, an oleaginous microalgae was cultivated in septic effluents from different mixed wastewater. The results showed that the effluent from pure toilet wastewater was the best medium to achieve the highest biomass yield (1.68 g·L-1) and productivity (154.6 mg·L-1·d-1). In contrast, the discharge of kitchen or laundry wastewater reduced the biomass production by 50.5–79.1%. That caused much lower lipids production in effluents from mixed wastewater regardless of its high lipids content and saturation degree. The results suggest that the discharge of kitchen or laundry wastewater bring risks for biomass and lipids production, and should be separated from the toilet wastewater before entering into septic tank.

Chiral propargyl amides are particularly useful structural units in organic synthesis. The enantioselective synthesis of propargyl amide is highly desirable. Conventional approach involves the use of a stoichiometric amount of metal reagent or chiral auxiliary. In comparison, direct alkynylation with terminal alkyne is attractive because it avoids the use of stoichiometric organometallic reagent. The asymmetric coupling of aldehyde, amine, and alkyne (A3-coupling) provides an efficient method for the synthesis of N-alkyl and N-aryl-substituted propargyl amines, but this strategy is not amenable for the direct enantioselective synthesis of propargyl amide. We have developed a new strategy and report here a Rh-catalyzed asymmetric hydroalkynylation of enamides. Alkynylations occur regioselectively at the α position of an enamide to produce chiral propargyl amides. High yield and enantioselectivity were observed. Previous alkynylation methods to prepare chiral propargyl amine involve the nucleophilic additio...

The aim of this study was to investigate the survival of patients with signet ring cell carcinoma (SRCC) based on primary tumor location.Patient data were obtained from the Surveillance, Epidemiology, and End Results database (1988-2012) with ≥200 cases per tumor location. Cox regression analysis was used to investigate prognostic factors of cause-specific survival (CSS).We identified 24,171 patients. Of the patients, 63.4% had gastric SRCC, followed by colon (18.2%), esophageal (5.0%), rectal (3.5%), lung (3.1%), pancreatic (1.8%), breast (1.5%), bladder (1.3%), small intestine (1.1%), and gallbladder SRCC (1.0%). The 5-year CSS was 22.1%, 69.0%, 33.2%, 28.1%, 24.8%, 16.1%, 13.6%, 12.6%, 11.0%, 6.4% in patients with gastric, breast, colon, rectum, bladder, small intestine, esophageal, gallbladder, lung, and pancreatic SRCC, respectively (P 0.001). Multivariate analyses showed that the primary tumor location was an independent prognostic factor of survival. Patients with lung, small intestine, and bladder SRCC had a comparable CSS to gastric SRCC, while breast and colorectal SRCC had better survival than gastric SRCC. Esophageal, gallbladder, and pancreatic SRCC were significantly associated with poor CSS compared with gastric SRCC.Our study suggests a major difference in survival of SRCC based on the primary tumor locations.

San-Gang Wu,1,* Wen-Wen Zhang,2,* Zhen-Yu He,2 Jia-Yuan Sun,2 Yan Wang,3 Juan Zhou3 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China *These authors contributed equally to this work Introduction: There is an ongoing debate regarding the optimal local treatment modalities for stage IB1 and IIA1 cervical cancer. The aim of this study was to determine whether radical hysterectomy or definitive radiochemotherapy is superior in stage IB1 and IIA1 cervical squamous cell carcinoma (SCC).Methods: From 1990 to 2010, a total of 3,769 patients with stage IB1 and IIA1 cervical SCC were included from the Surveillance, Epidemiology, and End Results database and were stratified according to whether they received radical hysterectomy or primary radiochemotherapy.Propensity score-matching (PSM) methods were used to balance patient baseline characteristics. Cancer-specific survival (CSS) and overall survival (OS) were compared between the two groups.Results: Of the 3,769 patients, 3,653 (96.9%) and 116 (3.1%) patients received radical hysterectomy and definitive radiochemotherapy, respectively. Radiochemotherapy was rarely used for definitive treatment prior to 2000. Before PSM, patients who were older, of black ethnicity, and with larger tumor size and stage IIA1 disease were more likely to receive definitive radiochemotherapy. A total of 116 pairs were completely matched using PSM. The local treatment modalities had no effect on CSS or OS in either unmatched or matched populations. In the matched population, the 8-year CSS rates were 82.1% and 76.5% in surgery and radiochemotherapy groups, respectively (p=0.382). The 8-year OS rates were 74.6% and 67.8% in surgery and radiochemotherapy groups, respectively (p=0.205).Conclusion: Our population-based study suggests that there is no clear local treatment of choice on survival outcomes between radical hysterectomy and definitive radiochemotherapy in patients with stage IB1 and IIA1 cervical SCC. Keywords: cervical cancer, early stage, hysterectomy, radiotherapy, propensity score matching

Background To evaluate the therapeutic value of multimodal treatment including hysterectomy in locally advanced cervical squamous cell carcinoma (SCC). Methods We retrospectively reviewed patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB–III cervical SCC and received chemotherapy and radiotherapy with or without hysterectomy between 2000 and 2013 using the Surveillance, Epidemiology, and End Results program. Propensity score-matching was used to balance baseline characteristics of included patients. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors for cervical cancer specific-survival (CCSS) and overall survival (OS). Results We identified 2473 patients and 522 pairs of patients were completely matched with each other. In the unmatched population, patients with younger age, non-black race, poorly/undifferentiated disease, FIGO stage IIB disease, and node-positive disease were more likely to receive additional hysterectomy. Additional hysterectomy was associated with better CCSS and OS in unmatched and matched populations. Moreover, when evaluating the survival difference by FIGO stage, only stage IIB disease retained statistical significance but not for stage III disease in unmatched and matched populations. Conclusions Our results suggest that multimodal treatment including hysterectomy might improve survival outcomes in patients with locally advanced cervical SCC, especially for stage IIB disease.

San-Gang Wu,1,* Wen-Wen Zhang,2,* Jia-Yuan Sun,2 Feng-Yan Li,2 Yong-Xiong Chen,3 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, People’s Republic of China *These authors contributed equally to this work Introduction: Invasive micropapillary carcinoma (IMPC) of the breast poses a high risk of locoregional recurrence, and postoperative radiotherapy (PORT) may be beneficial in IMPC. Hence, we determined the clinical value of PORT in IMPC patients. Patients and methods: We assessed clinicopathological factors extracted from the Surveillance, Epidemiology, and End Results database (2004–2013). Univariate and multivariate Cox proportional hazards regressions were performed to assess the independent prognostic factors on breast cancer-specific survival (BCSS) and overall survival (OS). Results: Of the 881 study patients, 444 (50.4%) and 437 (49.6%) underwent breast-conserving surgery (BCS) and mastectomy (MAST), respectively, of whom 357 (80.4%) and 153 (35.0%) underwent PORT, respectively. Patients with young age, large tumor size, or advanced nodal stage were more likely to undergo MAST and PORT compared with MAST alone. Patients with progesterone receptor-positive disease were more likely to receive BCS and PORT compared with BCS alone. The 5-year BCSS and OS were 95.7% and 90.9%, respectively. On multivariate analyses, tumor size, histological grade, and estrogen receptor status were independent predictors of BCSS and OS. The types of surgical procedures (MAST vs. BCS) were not an independent predictor of survival outcomes. Patients who underwent MAST with or without PORT had similar BCSS and OS in the multivariate analyses. Those who underwent BCS plus PORT did not have better BCSS and OS than those who underwent BCS alone. In the low-, intermediate-, and high-risk groups, PORT was not associated with better BCSS and OS than non-PORT groups in patients who received BCS or MAST. Conclusion: IMPC has favorable BCSS and OS. Regardless of the types of surgical procedures (MAST or BCS), PORT groups were not inferior to non-PORT groups on BCSS and OS. Keywords: invasive micropapillary carcinoma, SEER, radiotherapy, survival

Purpose: To investigate the clinical value of additional local treatment strategies in occult breast cancer (OBC) after axillary lymph node dissection (ALND). Methods: Patients diagnosed with OBC between 1990 and 2013 were included from the Surveillance, Epidemiology, and End Results registry database. The significant risk factors of cause-specific survival (CSS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses. Results: We identified 980 patients, including 219 (22.3%), 252 (25.7%), 263 (26.8%), and 246 (25.1%) of patients underwent ALND, ALND + radiotherapy (RT), ALND + surgery (S) (mastectomy or breast-conserving surgery), and ALND + S + RT, respectively. Patients with younger age, diagnosed before 2000, advanced nodal stage, ER-negative disease, and PR-negative disease were more likely to undergo additional local treatment compared with ALND only. The 10-year rate CSS of the ALND only group was 57.2%, while that of the ALND + RT, ALND + S, and ALND + S + RT groups was 78.0%, 81.0%, and 71.5%, respectively (p < 0.001). The 10-year OS rate in the ALND only, ALND + RT, ALND + S, and ALND + S + RT groups was 46.0%, 69.5%, 66.1%, and 67.0%, respectively (p < 0.001). Multivariate analysis indicated that older age, advanced nodal stage, and ALND only were independent risk factors for decreased CSS and OS. CSS and OS among the groups including ALND + RT, ALND + S, and ALND + S + RT were not significantly different. Conclusions: Additional local treatment (local surgery or RT) improves survival outcomes compared with ALND only in OBC after ALND. ALND + RT may be the optimal local treatment for OBC due to no different in survival outcomes and cosmesis is better.

Purpose: To evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (CCRT) with docetaxel plus cisplatin (DP regimen) versus 5-fluorouracil plus cisplatin (PF regimen) in patients with oesophageal squamous cell carcinoma (ESCC). Patients and Methods: In this phase II randomized controlled trial, eighty-six patients with clinical stage II - IVa ESCC were randomized to receive radiotherapy concurrently with two cycles of the PF or DP regimen at 3-week intervals. The primary endpoint was overall survival (OS). The secondary end points included the overall response rate (ORR), progression-free survival (PFS) and treatment-related toxicities. Results: The ORRs were 84.4% in the DP group and 87.3% in the PF group (P = 0.653). After a median follow-up time of 25.1 months, the 1- and 2-year OS rates were 93.7% and 86.2% for the PF group and 87.3% and 69.1% for the DP group, respectively (P = 0.364). The 1- and 2-year PFS rates were 77.4% and 55.0% for the PF group and 78.8% and 69.4% for the DP group, respectively (P = 0.845). Grade 3/4 leukocytopenia/neutropenia (68.9% vs. 19.5%, P < 0.001) was significantly more common in the DP group. Conclusion: The treatment response, OS and PFS associated with using CCRT with the DP regimen were not superior to those associated with using CCRT with the PF regimen as a first-line treatment in patients with ESCC. Additionally, the DP regimen was associated with more severe haematological toxicities. This trial has been registered with the US National Institute of Health (clinicaltrials.gov, Identifier NCT 02969473).

Ethnopharmacological relevance The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. To identify the potential pharmacodynamic ingredients (PPIs) of TCM will help to achieve suitable process control procedures for industrial production and large-scale manufacturing. Aim of the study In the present study, we propose a multi-dimensional qualitative analysis method combining water-decoction spectra, in-vitro intestinal absorption spectra, in-vivo plasma spectra, and molecular docking of components to quickly identify the PPIs for the DGSN decoction of TCM. Materials and methods Water-based decoctions of DGSN were prepared in accordance with the clinical use registered in ancient books. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS) coupled with computerized modelling activity screening was used to quickly identify the PPIs of the DGSN decoction. Bioactive compounds absorbed in vitro were identified using the everted intestinal sac model from rats and compounds absorbed in vivo were confirmed in portal vein blood samples obtained following oral administration in rats. Molecular docking validation experiments were adopted to predict the binding activity to coagulation factors I, II, VII, X, and IX. The active components were further confirmed by pharmacodynamics analysis. The anticoagulant activity of the DGSN decoction was verified using rat models. Results Thirty-one compounds were identified in the DGSN decoction. According to the in vivo experiments, 22 compounds that could be absorbed in vivo were detected by the everted intestinal sac model in rats. This model greatly reduces the scope of PPIs and is easy to perform. Ten compounds were detected in the portal vein blood in rats. The compounds detected in plasma provide stronger evidence supporting the PPIs. Molecular docking in vitro experiments indicated that 7 compounds exhibited better binding activity with coagulation factors I, II, VII, X, and IX. The animal experiments confirmed that the DGSN decoction could improve the microcirculation, providing indirect proof of anticoagulant activity suggested by the molecular docking studies. Finally, based on the multi-dimensional methods, 9 potential compounds present in the DGSN decoction were identified as PPIs (i.e., ferulic acid, paeoniflorin, albiflorin, chlorogenic acid, cryptochlorogenic acid, liquiritin, liquiritin apioside, cinnamaldehyde and glycyrrhizic acid). Conclusion Overall, this study combined the water-decoction spectra, intestinal absorption spectra in vitro, plasma spectra in vivo, and molecular docking studies to establish a multi-dimensional qualitative analysis method of the DGSN decoction. Meanwhile, 9 compounds in DGSN decoction were identified as PPIs using this method, and are proposed for application as quality standards for complex TCM prescriptions.

An iridium-catalyzed enantioselective alkynylation of methylene C H bonds γ to the amide group is developed. The reaction proceeds through alkene isomerization followed by regioselective hydroalkynylation. This method provides rapid access to a wide range of stereodefined alkynylated compounds in good yields and good enantioselectivities.

The effect of frozen storage periods (0, 2, 4, 6, or 8 wk) of raw chicken meat on its flavor upon stewing was investigated by analyzing the changes of free amino acids (FAAs), 5′-nucleotides, minerals and volatile compounds and by evaluating the taste and aroma profiles using an E-nose and a human panel. Results showed that the storage time of raw material improved its taste and aroma profiles upon stewing. The total free amino acid contents and the equivalent umami concentration (EUC) increased from 159.90 mg/100 g and 3156.58 mg/100 g to 292.81 mg/100 g and 4360.72 mg/100 g, respectively, although the 5′-nucleotide concentrations decreased upon stewing. With increased frozen storage durations of raw material, the contents of the mineral elements and total volatile compound increased firstly, then deceased. Results from the electronic nose and sensory evaluation indicated a progressive difference in the overall flavor profiles among samples. The meaty, umami and salty traits of stewed meat reached the maximum scores as frozen chicken meat was stored for 6 wk, which should be related to the enhanced migration of taste-active substances and retention of aldehydes. Overall, a limited frozen storage duration of raw meat can enhance its flavor upon stewing.

A new DTBP/Mg(NO3)2-mediated bicyclization cascade of o-arylalkynylanilines with secondary arylphosphine oxides has been developed, enabling dual C(sp2)–H functionalization along with the cleavage of the C–N bond. The combination between regioselective P-centered radical-triggered [3 + 2] cyclization and C-centered radical-induced cross-coupling in a one-pot manner delivered 27 examples of tribenzo[b,e,g]phosphindole oxides with generally high regioselectivity. A reasonable mechanism for forming such products involving radical addition–cyclization cascade is proposed.

Background To assess the survival outcomes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–IIA adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the uterine cervix after hysterectomy and adjuvant radiotherapy (RT). Methods Patients with a primary diagnosis of FIGO stage I–IIA AC or SCC of the uterine cervix after hysterectomy and adjuvant RT between 1988 and 2012 were included using data from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were used to analyze the effect of histologic subtype on cause-specific survival (CSS) and overall survival (OS). Results We included 1171 patients: 919 with cervical SCC and 252 with cervical AC. In multivariate analysis, cervical AC was an independent adverse prognostic factor for survival. Patients with cervical AC had worse CSS ( p = 0.001) and OS ( p = 0.001) compared to patients with cervical SCC. In the subgroup analysis, patients with cervical SCC in the era of concurrent chemoradiotherapy (CCRT) (2000–2012) had better CSS ( p = 0.006) and OS ( p = 0.004) compared with the era of RT. However, there was no significant difference in CSS ( p = 0.079) and OS ( p = 0.053) between the eras of RT (1988–1999) and CCRT for patients with cervical AC. Conclusions Survival of cervical AC is significantly worse than that of cervical SCC. As CCRT usage increases, the survival benefit is derived only in cervical SCC, but not in cervical AC.

The aim of the present study was to examine whether single-nucleotide polymorphisms (SNPs) of β1 subunit of large-conductance Ca2+-activated K+ channel (KCNMB1) and inwardly rectifying K+ channel, subfamily J, member-11 (KCNJ11) are associated with essential hypertension (EH) in Xinjiang Kazak Chinese patients. A polymerase chain reaction-restriction fragment length polymorphism technique was applied to detect the distribution of selected alleles and genotype frequencies in a cohort of Xinjiang Kazak Chinese patients. Samples from 267 patients with EH and 259 normotensive (NT) controls were analyzed. An unconditional logistic regression analysis was used to estimate the odds ratio and 95% confidence interval of the risk factors that are associated with the development of EH. Genotype and allele frequency analyses revealed that the frequency of genotypes KCNJ11-rs2285676 and KCNMB1-rs11739136 was not significantly different between the EH and NT groups. Individuals carrying the GG genotype of KCNJ11-rs5219 had a 2.08 times higher risk of having EH than individuals carrying the GA+AA genotype of KCNJ11-rs5219. Furthermore, the G allele frequency of KCNJ11-rs5219 in the EH group was significantly higher than that of the NT group (P=0.048). Additionally, logistic regression analysis revealed that the body weight and GG genotype of KCNJ11-rs5219 were positively associated with EH in Xinjiang Kazak Chinese patients (P

A new C-center radical-triggered bicyclization cascade of N-tethered 1,7-enynes for forming 28 examples of biologically interesting spirocyclohexadienone-containing cyclopenta[c]quinolin-4-ones with two all-carbon quaternary stereocenters has been established under mild conditions. The in situ generated diazonium salts from 4-methoxyanilines and t-BuONO are served as 4-methoxyphenyl precursors without additional oxidant, enabling 6-exo-dig cyclization/5-exo-trig ipso-cyclization to construct three new C-C bonds through metal-free dearomatization. The reaction also features broad substrate scope, annulation efficiency, and high functional group tolerance.

This study decomposed the indicator of decoupling of carbon emissions due to fossil energy consumption from economic growth in China via the logarithmic mean Divisia index (LMDI) method to explore key factors influencing decoupling status in different periods. The decoupling indicator was decomposed into energy structure, energy intensity, economic structure, and economic output effects over each period. Decoupling varied due to changes in economic growth and energy intensity during different periods. The economic output effect significantly enhanced decoupling, while the energy intensity effect greatly decreased decoupling. The energy structure and economic structure effects had slight impacts on decoupling. A comparative analysis across different sectors and industrial subsectors revealed that industrial growth determined the status of decoupling of carbon emissions from economic growth in China. In terms of industrial subsectors, the major sources of carbon emissions were electricity, steam, and water production and other energy-intensive subsectors. The energy-intensive subsectors, such as coal mining and washing, petroleum and natural gas exploitation, and chemical manufacture, had great effects on the decoupling of carbon emissions, whereas non-energy-intensive subsectors, such as instruments, meters, cultural and office machinery, and ordinary equipment manufacture, had relatively slight impacts on the decoupling. Policy implications in terms of economic growth, economic structure, and energy consumption were discussed.

Using the logarithmic mean Divisia index (LMDI) method, we decomposed factors affecting the national carbon intensity (NCI) in China at a multi-regional level. A comparative analysis of regional contributions in different Five-Year Plan (5YP) periods revealed that the energy structure had inhibitory effects on NCI during the 9th and 10th 5YP periods, but had promoting effects during the 11th and start of the 12th 5YP periods. The energy structure had a strong inhibitory impact in eastern, north-eastern, and northern regions of China, but only a slight impact in central, northern, south-western, and north-western regions. Energy intensity is a major factor and had a strong inhibitory effect on NCI except during the 10th 5YP period. Energy intensity had a strong inhibitory effect in eastern and northern regions, but only a slight impact in north-western and southern regions, especially in Hainan, Ningxia, Xinjiang, and Qinghai provinces. Overall, proportional output in China had a promoting effect on NCI, which indicates regional economic development was not coordinated. The combined effects of regional carbon intensity (RCI) and proportional output determined changes in NCI, and RCI had a strong effect on NCI. Regions with high proportional output and large carbon emissions had a great impact on NCI. The total effect in developed areas such as eastern, northern, and north-eastern regions was strongly inhibitory, while the impact was slight in relatively less developed areas such as northwestern and southern regions. Some policy implications arising from our study results are discussed.

BACKGROUND: Dual source computed tomography (DSCT) plays an important role in the diagnosis of congenital heart diseases (CHD). However, the issue of radiation-related side effects constitutes a wide public concern. The aim of the study was to explore the differences in diagnostic accuracy, radiation dose and image quality between a prospectively ECG - triggered high - pitch spiral acquisition (flash model) and a retrospective ECG-gated protocol of DSCT used for the detection of CHD. MATERIAL AND METHODS: The study included 58 patients with CHD who underwent a DSCT examination, including two groups of 29 patients in each protocol. Then, both subjective and objective image quality, diagnostic accuracy and radiation dose were compared between the two protocols. RESULTS: The image quality and the total as well as partial diagnostic accuracy did not differ significantly between the protocols. The radiation dose in the flash model was obviously lower than that in the retrospective model (P

Objective: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CRT) in multiple primary cancers (MPC) of the upper digestive tract in esophageal squamous cell carcinoma (ESCC). Methods: In a screening of 1193 consecutive patients diagnosed with ESCC and received radiotherapy, 53 patients presenting synchronous MPC in the upper digestive tract were retrospectively investigated. 53 consecutive patients with esophageal non-multiple primary cancer (NPC), matched by stage, age and sex, served as control. All of the patients received concurrent CRT. The median radiation dose was 60 Gy. Chemotherapy regimens were based on platinum and/or 5-fluorouracil. Clinical outcomes and treatment toxicities were compared. Results: Clinic-pathologic characteristics were well balanced between groups. MPC mostly located in esophagus (43, 81.8%), followed by hypopharynx (8, 15.1%) and stomach (2, 3.8%). In MPC and NPC patients, 94.3% and 96.2% completed the intended treatment. The immediate response rate was 73.6% vs 75.5%, with complete response rate of 11.3% vs 24.5% and partial response rate of 62.3% vs 51.0%. Two-year overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were 52.2% vs 68.9% (p=0.026), 32.9% vs 54.0% (p=0.032), 60.8% vs 87.8% (p=0.002) and 64.0% vs 70.8% (p=0.22), respectively. Acute grade 3-4 toxicities were observed in 64.2% vs 54.7%, significantly higher in radiation esophagitis (49.1% vs 28.3%, p

In this work, the effects of NbC additions on microstructure and properties of non-uniform structure WC-7Co cemented carbides were investigated X-ray diffractometer, scanning electron microscopy (SEM), electron probe microanalysis (EPMA), mechanical properties tester and electrochemical workstation, respectively. The results show that WC phase can be partially dissolved into the NbC to form a (Nb,W)C solid solution. According to EPMA analysis, the amount of W atoms, dissolving into the NbC grains, increases with the NbC addition. Moreover, when the content of NbC is beyond 1%, the WC-Co cemented carbides with non-uniform structure are formed with significant reduction of average grain size of WC. With NbC addition increasing from 0 wt% to 2 wt%, the hardness is increased from 1475 MPa to 1570 MPa while the fracture toughness decreased from 12.1 MPa m1/2 to 10.3 MPa m1/2. However, with the further addition of NbC, the hardness slightly decreased. With NbC addition between 0 and 1 wt%, the TRS is gradually decreased from 2982 MPa to 2745 MPa, while, as the NbC content exceeds 1 wt%, the TRS leveled off. Because of the decrease of grain size and the (Nb,W)C phase formation, caused by NbC addition, the crack defection was weakened, which led to the decrease of fracture toughness. Meanwhile, the corrosion resistance of non-uniform structure WC-Co cemented carbides can be significantly improved by adding NbC to the material due to increased α-Co in binder phase.

Using the structural decomposition analysis (SDA) method, we decomposed the factors affecting the increments in CO2 emissions in China's Jiangsu Province. A comparative analysis of these factors at the holistic, sectoral, and sub-sectoral levels revealed that the effects related to the province's economic growth; in particular, the transfers-out and investment effects greatly increased Jiangsu's CO2 emissions. Overall, the import and export effects increased the emissions, reflecting the deteriorating foreign trade structure from the perspective of the emissions reduction. The energy intensity reduced Jiangsu's CO2 emissions greatly, whereas the energy structure had only a slight effect, which shows the high energy efficiency and inappropriate energy structure. The technology effect had a relatively slight reducing impact on the CO2 emissions compared with the other effects, so the input and output efficiency in Jiangsu had not yet been significantly improved. On the whole, the transfers-out, investment, and export effects increased the CO2 emissions in all sectors and subsectors, whereas the other effects on the increments in Jiangsu's CO2 emissions in the sectors and industrial subsectors differed greatly. Some policy implications arising from our study results are discussed.

DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increasedCxcr3mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5′-cytosine-phosphate-guanine-3′) island in theCxcr3gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased. SNL also increased the binding of CCAAT (cytidine–cytidine–adenosine–adenosine–thymidine)/enhancer binding protein α (C/EBPα) withCxcr3promoter and decreased the binding of DNMT3b withCxcr3promoter in the spinal cord. C/EBPα expression was increased in spinal neurons after SNL, and inhibition of C/EBPα by intrathecal small interfering RNA attenuated SNL-induced pain hypersensitivity and reducedCxcr3expression. Furthermore, SNL-induced mechanical allodynia and heat hyperalgesia were markedly reduced inCxcr3−/−mice. Spinal inhibition ofCxcr3by shRNA or CXCR3 antagonist also attenuated established neuropathic pain. Moreover, CXCL10, the ligand of CXCR3, was increased in spinal neurons and astrocytes after SNL. Superfusing spinal cord slices with CXCL10 enhanced spontaneous EPSCs and potentiated NMDA-induced and AMPA-induced currents of lamina II neurons. Finally, intrathecal injection of CXCL10 induced CXCR3-dependent pain hypersensitivity in naive mice. Collectively, our results demonstrated that CXCR3, increased by DNA demethylation and the enhanced interaction with C/EBPα, can be activated by CXCL10 to facilitate excitatory synaptic transmission and contribute to the maintenance of neuropathic pain.SIGNIFICANCE STATEMENTPeripheral nerve injury induces changes of gene expression in the spinal cord that may contribute to the pathogenesis of neuropathic pain. CXCR3 is a chemokine receptor. Whether it is involved in neuropathic pain and how it is regulated after nerve injury remain largely unknown. Our study demonstrates that spinal nerve ligation downregulates the expression of DNMT3b, which may cause demethylation ofCxcr3gene promoter and facilitate the binding of CCAAT/enhancer binding protein α withCxcr3promoter and further increase CXCR3 expression in spinal neurons. The upregulated CXCR3 may contribute to neuropathic pain by facilitating central sensitization. Our study reveals an epigenetic mechanism underlying CXCR3 expression and also suggests that targeting the expression or activation of CXCR3 signaling may offer new therapeutics for neuropathic pain.

Chronic inflammation plays an important role in tumor progression. The aim of this analysis was to evaluate whether inflammatory biomarkers such as the Glasgow prognostic score (GPS), the neutrophil‐lymphocyte ratio (NLR), the platelet‐lymphocyte ratio (PLR), and the lymphocyte‐monocyte ratio (LMR) could predict the prognosis of nasopharyngeal carcinoma (NPC). In this analysis, pretreatment GPS, NLR, PLR, LMR of 388 patients who were diagnosed as nonmetastatic NPC and recruited prospectively in the 863 Program No. 2006AA02Z4B4 were assessed. Of those, the 249 cases enrolled between December 27th 2006 and July 31st 2011 were defined as the development set. The rest 139 cases enrolled between August 1st 2011 and July 31st 2013 were defined as the validation set. The variables above were analyzed in the development set, together with age, gender, Karnofsky performance score, T stage, and N stage, with respect to their impact on the disease‐specific survival (DSS) through a univariate analysis. The candidate prognostic factors then underwent a multivariate analysis. A nomogram was established to predict the DSS, by involving the independent prognostic factors. Its predction capacity was evaluated through calculating Harrell's concordance index (C‐index) in the validation set. After multivariate analysis for the development set, age (≤50 vs. >50 years old), T stage (T1–2 vs. T3–4), N stage (N0–1 vs. N2–3) and pretreatment GPS (0 vs. 1–2), NLR (≤2.5 vs. >2.5), LMR (≤2.35 vs. >2.35) were independent prognostic factors of DSS (P values were 0.002, 0.008

A recursive multisector dynamic computable general equilibrium (DCGE) model simulates the economic impacts of carbon tariffs, as proposed by the USA, ranging from $40/t to $60/t CO2. We examine a carbon tax and export subsidy as response policies to the U.S. carbon tariff, respectively. The dynamic model shows the possible impacts of these policies on China&rsquo, s economic structure, carbon emissions, and social welfare from 2020 to 2030. Simulations show that a carbon tariff changes the structure of China&rsquo, s exports and promotes trade diversion from the USA to other countries and regions. A domestic carbon tax and subsidy policy can dampen the adverse impacts of carbon tariffs on trade. A carbon tax shows an effective impact on increasing clean energy use, decreasing the carbon intensity of output, and reducing carbon emissions. A subsidy on exports to the USA reduces the adverse impact of a carbon tariff on China&rsquo, s social welfare in the short term.

Background: Given the growing evidence that sarcopenia and inflammation influence the survival of patients with cancer, we evaluated the prognostic significance of the skeletal muscle index (SMI) combined with an inflammation marker in patients with breast cancer who underwent postoperative adjuvant radiotherapy. Methods: We conducted a retrospective analysis of 301 patients with breast cancer who received postoperative adjuvant radiotherapy between 2010 and 2012. The SMI was measured using preradiotherapy computed tomography (CT) simulation images at the level of the fourth thoracic vertebra (T4). Receiver operating characteristic curve analyses were used to determine the optimal cutoff values for the SMI and inflammatory marker. Patients were divided into 2 groups (high SMI and low SMI), based on the SMI cutoff of 10.57 cm2/m2. Results: Patients in the high-SMI group had a median overall survival (OS) of 62.4 months, which was significantly shorter than those in the low-SMI group, with a median OS of 68.5 months (P = 0.025). Patients in the high-SMI group had a median recurrence-free survival (RFS) of 62.3 months, which was shorter but not significantly than the median RFS of 65.2 months of the low-SMI group (P = 0.159). Univariate and multivariate survival analyses revealed SMI was an independent predictor of OS (P = 0.044). The SMI-MLR combination was found to be an independent predictor of OS (P = 0.006) and RFS (P = 0.009). Conclusions: The current findings support the SMI as a promising indicator for predicting clinical outcomes in patients with breast cancer receiving postoperative adjuvant radiotherapy. A high SMI accompanied by systemic inflammation was significantly associated with reduced OS and RFS.

Insufficient organics in anaerobic digestate of sludge limited algal mixotrophic culture and caused low lipids production. In this study, enhancing lipids production and pollutants removal by adding acidified starch wastewater was tested for Chlorella pyrenoidosa mixotrophic culture. The results showed that an optimal addition of acidified starch wastewater into anaerobic digestate of sludge (1:1, v/v) improved biomass and lipids production by 0.5-fold (to 2.59 g·L−1) and 3.2-fold (87.3 mg·L−1·d−1), respectively. The acidified starch wastewater addition also improved the quality of algal biodiesel with higher saturation (typically in C16:0 and C18:0). In addition, 62% of total organic carbon, 99% of ammonium and 95% of orthophosphate in mixed wastewater were effectively removed by microalgae. This study provides a promising way to improve biodiesel production and nutrients recovery from anaerobic digestate of sludge using waste carbon source.

We aimed to investigate the clinical effect of histological subtypes on survival in nasopharyngeal carcinoma (NPC), and assess the effect of nodal stage on outcome according to histological subtypes. Patients with non-metastatic NPC were identified from the Surveillance, Epidemiology and End-Results (SEER) database between 2004 and 2014. Statistical analysis was performed using the chi-squared test, Kaplan–Meier methods, and multivariate Cox regression models. We identified 2845 patients in this study including 1218 (42.8%), 849 (29.8%), and 778 (27.3%) patients with keratinizing squamous cell carcinoma (KSCC), differentiated non-keratinizing squamous cell carcinoma (DNKSCC), and undifferentiated non-keratinizing squamous cell carcinoma (UNKSCC), respectively. The multivariate analysis indicated that patients with UNKSCC subtype had better NPC-specific survival (NPC-SS) (P