Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned ...co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.
We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 95% CI 0.34 to 0.78; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.
Seed bank is an important source of regenerative material in wetlands, and can be of value in the restoration of farmed wetlands if the seeds can survive periods of cultivation. A seed bank assay of ...soils from sedge meadows was conducted to determine the extent to which seeds are maintained during farming for various lengths of time. Soils from natural sedge meadows, soybean fields and paddy fields farmed for 1–30 years were collected in Sanjiang Plain, northeastern China. Soils were placed in a glasshouse setting in freely drained condition. We found that species richness and seed density in sedge meadows were higher than in soybean and paddy fields. There were significantly negative effects of the length of time of farming on the seed bank in soybean fields. Important wetland species survived cultivation as seeds within 10 years (e.g., Calamagrostis angustifolia and Polygonum amphibium), but most sedge meadow species disappeared when farmed for more than 10 years in soybean fields. Species richness and seed densities of species kept in a very low level in paddy fields farmed for various periods. Key structural dominants Carex species maintained with low seeds in natural wetlands and soybean fields farmed for 1–5 years, and tussock-forming Carex (e.g., Carex appendiculata and Carex meyeriana) were all absent in farmed fields. The structure of the seed bank was related to environmental factors including latitude, number of years farmed and field water depth as based on Non-metric Multidimensional Scaling analysis. Critical components of the vegetation are not maintained in seed banks, which may make these floodplain wetlands difficult to restore via natural recolonization. To re-establish the structure imposed by tussock sedges, specific technologies (e.g., planting, hydrochory) might be developed to encourage the development of tussocks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Oxidative stress and inflammation are implicated in the development of sepsis-related acute lung injury (ALI). MicroRNA-1224-5p (miR-1224-5p) plays critical roles in regulating inflammatory response ...and reactive oxygen species (ROS) production. The present study is aimed at investigating the role and underlying mechanisms of miR-1224-5p in sepsis-related ALI. Mice were intratracheally injected with lipopolysaccharide (LPS, 5 mg/kg) for 12 h to induce sepsis-related ALI. To manipulate miR-1224-5p level, mice were intravenously injected with the agomir, antagomir, or matched controls for 3 consecutive days. Murine peritoneal macrophages were stimulated with LPS (100 ng/mL) for 6 h to further validate the role of miR-1224-5p in vitro. To inhibit adenosine 5′-monophosphate-activated protein kinase alpha (AMPKα) or peroxisome proliferator activated receptor-gamma (PPAR-γ), compound C or GW9662 was used in vivo and in vitro. We found that miR-1224-5p levels in lungs were elevated by LPS injection, and that the miR-1224-5p antagomir significantly alleviated LPS-induced inflammation, oxidative stress, and ALI in mice. Conversely, the miR-1224-5p agomir aggravated inflammatory response, ROS generation, and pulmonary dysfunction in LPS-treated mice. In addition, the miR-1224-5p antagomir reduced, while the miR-1224-5p agomir aggravated LPS-induced inflammation and oxidative stress in murine peritoneal macrophages. Further findings revealed that miR-1224-5p is directly bound to the 3′-untranslated regions of PPAR-γ and subsequently suppressed PPAR-γ/AMPKα axis, thereby aggravating LPS-induced ALI in vivo and in vitro. We demonstrate for the first time that endogenous miR-1224-5p is a critical pathogenic factor for inflammation and oxidative damage during LPS-induced ALI through inactivating PPAR-γ/AMPKα axis. Targeting miR-1224-5p may help to develop novel approaches to treat sepsis-related ALI.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Emulsion is inevitable during the aqueous extraction of oil from oilseeds. In this study, a new aqueous extraction method for camellia oil is investigated. During the extraction, the emulsified oil ...is collected, frozen, and thawed, and the free oil is obtained (AEEF). The optimal processing conditions are as follows: three times as much water as camellia seed powder (w/w), grinding at 70 °C for 6 min, repeating 2 cycles to collect the emulsified oil; then the emulsified oil is frozen (−20 °C) /thawed (50 °C) for 2 cycles. The yield of camellia oil is 89.37 ± 0.51%, which is significantly higher (p < 0.05) than that of microwave‐assisted aqueous enzymatic extraction (MAAEE, 83.05 ± 1.14%), and is similar to that of cold press extraction (CPE, 90.85 ± 2.05%), as well as solvent extraction (SE) coupled with refining. Additionally, the total oxidation value (TOTOX) of the free oil extracted by using AEEF (AEEF‐Oil, 6.82 ± 0.12%) is significantly lower (p < 0.05) than those of MAAEE, CEP, or SE. In comparison to SE‐Oil and CEP‐Oil, AEEF‐Oil has higher (p < 0.05) contents of α‐tocopherol and squalene, and lower (p < 0.05) benzo(a)pyrene contents, and contains more favorable natural volatile compounds. The results indicate that the novel AEEF may be a promising aqueous extraction method.
Practical Application: The novel aqueous extraction method for camellia oil by emulsified oil – frozen/thawed has acceptable oil yields. The obtained camellia oil has high levels of bioactive components, low contents of hazardous substances, and more characteristic volatile flavor compounds. AEEF is an improved aqueous extraction technology for edible oil without refining and using n‐hexane, which could be potentially applied in industrial production of camellia oil due to its safety, nutrition, and environment‐friendly treatments.
Aqueous extraction is a promising technique for edible oil extraction from oilseeds. The novel technology of aqueous extraction for camellia oil through emulsified oil – frozen/thawed (AEEF) is investigated. In comparison to solvent extraction, cold press extraction, and microwave‐assisted aqueous enzymatic extraction of camellia oil, the obtained camellia oil by AEEF has an acceptable oil yield, high quality, and nutritional value. AEEF is a safe, simple and environmental‐friendly aqueous extraction technology.
Aqueous extraction is a promising technique for edible oil extraction from oilseeds. The novel technology of aqueous extraction for camellia oil through emulsified oil – frozen/thawed (AEEF) is investigated. In comparison to solvent extraction, cold press extraction, and microwave‐assisted aqueous enzymatic extraction of camellia oil, the obtained camellia oil by AEEF has an acceptable oil yield, high quality, and nutritional value. AEEF is a safe, simple and environmental‐friendly aqueous extraction technology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of ...meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression.
We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA-gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA.
Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)-receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA-gene network.
These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Fiber-shaped solid-state zinc-ion battery (FZIB) is a promising candidate for wearable electronic devices, but challenges remain in terms of mechanical stability and low temperature tolerance. ...Herein, we design and fabricate a FZIB with an integrated device structure through effective incorporation of the active electrode materials with a carbon fiber rope (CFR) and a gel polymer electrolyte. The gel polymer electrolyte incorporated with ethylene glycol (EG) and graphene oxide (GO) endows the FZIB with a high Zn stripping/plating efficiency under extreme low temperature conditions. A high power density of 1.25 mW cm–1 and large energy density of 0.1752 mWh cm–1 are obtained. In addition, a high capacity retention of 91% after 2000 continuous bending cycles is achieved. Furthermore, the discharge capacity is fairly retained at more than 22% even at the low temperature of −20 °C. Toward practical applications, the FZIB integrated into textiles to power electronic products is demonstrated.
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IJS, KILJ, NUK, PNG, UL, UM
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. ...Interleukin‐17 (IL‐17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL‐17 in CP/CPPS are not clear. We confirmed that IL‐17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL‐17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL‐17‐neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti‐Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL‐17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Recently pyrolysis has become the sustainable and huge environmental-friendly method for agricultural straw waste (ASW) to evaluate the bioenergy potential. Whereas, the thermal decomposition ...behavior of chili straw waste (CSW) has not never been explored. This present research systematically studied the bioenergy potential of CSW using three multiple direct characterization tools, including thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectrometer, and Curie-point pyrolyzer-gas chromatograph/mass spectrometer (CPP-GC/MS). Thermal decomposition of CSW has been investigated by TGA under the non-isothermal pyrolysis temperature at four heating rates of 5, 10, 20, and 30 °C min−1, respectively, which can be separated into three processes. Four isoconversional model-free methods such as Kissinger-Akahira-Sunose (KAS), Friedman, Flynn-Wall-Ozawa (FWO), and Starink, were determined the kinetic, ΔH, ΔG, and ΔS of CSW pyrolysis. The average activation energy (Ea) for CSW pyrolysis obtained by Starink, KAS, and FWO methods (195.48, 199.70, and 196.37 kJ mol−1) were lower than that Friedman model (227.15 kJ mol−1). FTIR analysis result showed that CSW was rich in oxygen-containing species and had the great potential for its valuable conversion into renewable bio-fuel. Besides, based on the CPP-GC/MS analysis, oxygenated components including phenols, esters, and acids were major volatile products (VPs) of CSW.
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•Pyrolysis behavior of CSW was investigated by TGA and CPP-GC/MS.•Four model-free methods were applied to estimate the pyrolysis kinetic of CSW.•Kinetic and thermodynamics analysis suggested that CSW was suitable for pyrolysis.•The reaction mechanism of CSW pyrolysis followed D3 and F2, respectively.•The flash pyrolysis VPs of 400 °C contained less phenols than that of 500 °C.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mitochondrial genome has aseries of characteristics such as simple structure, no recombination, maternalinheritance, stable structure, fast evolution rate, and high copy number. Moreover, it is easy ...to be sequenced,contains high-resolution phylogenetic information, and exists in a wide rangeof taxa. Therefore, it is widely used in the study of biological phylogeny. Atpresent, phylogenetic studies focus mainly on D-loop region, cytochrome b gene,and protein-coding sequence. Phylogenetic studies using the mitochondrialcomplete sequence are rarely reported in yak. Therefore, the present studyaimed to construct phylogenetic tree using yak mitochondrial complete sequenceand compare the subsequent results with previous findings obtained usingpartial sequences.
Complete mitochondrial sequences of five yakpopulations from Qinghai and Xinjiang were obtained. The mitotype diversity ofthe five populations was Xueduo yak (0.992 ± 0.015), Pamir yak (0.990 ± 0.014),Yushu yak (0.963 ± 0.033), Qilian yak (0.948 ± 0.036), and Huanhu yak (0.905 ±0.048), which showed a higher mitotype diversity compared with other breeds fromthe previous reports, including Jiulong yak, Maiwa yak, Zhongdian yak, andTianzhu yak. A total of 78 mitotypes were obtained from 111 individuals. Amongthese, Yushu yak, Huanhu yak, Xueduo yak, and Qilian yak all shared mitotypes,but the Pamir yak did not share mitotypes with these four populations.Phylogenetic analysis showed that yak populations were separable into threedistinct branches. The analysis identified a new phylogenetic branch containingboth wild and domestic yaks. The 155 mitotypes found in 206 individuals weredivided into 3 haplogroups by mitotype clustering. Thehaplogroup was not associated with the geographical distribution of yaks. Theyaks in the same population or the same ecological environment were distributedin different haplogroups. Among the threehaplogroups, haplogroup A and haplogroup B showed a star-shaped distribution ofmitotypes. The central mitotypes were widely distributed and had a highfrequency.
Thegenetic diversity of yaks in Qinghai was high. Both domestic and wild yaks clusteredinto three branches.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flexible pressure sensors have broad applications in the fields of electronic skin, human–computer interaction, and health monitoring. It remains a great challenge to develop advanced sensors with ...mechanical flexibility while gaining high sensitivity, fast response time, and wide detection range. Herein, the design and fabrication of a new type of flexible supercapacitive pressure sensor with a device configuration of planar electrodes incorporated with porous ionic gel is reported. Taking advantage of both the electric double layer capacitance and the micro‐structured organogel electrolyte, the developed sensor exhibits ultra‐high sensitivity (1126.96 kPa−1), wide detection range (300 kPa), fast response time (25 ms), and excellent stability over 6000 compression‐release cycles. With consistent and stable performance, the proposed pressure sensor can be used in many applications such as finger pressing, carotid pulse measurement, and finger bending. This work provides a facile and economical approach for fabricating flexible and ultra‐sensitive pressure sensors that are promising in wearable electronics.
Flexible supercapacitive pressure sensors with planar electrodes and porous ionic gel are designed. Taking advantages of electric double‐layer capacitance and microstructured organogel electrolyte, the developed sensor exhibits ultrahigh sensitivity (1126.96 kPa−1) and a wide detection range (300 kPa). Herein, a facile way to fabricate flexible and ultrasensitive pressure sensors that are promising in wearable electronics is provided.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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