Characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire in patients with advanced lung cancer.

Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor-reactive T cells. The aim of this study was to determine the basic characteristics and clinical significance of the peripheral blood T-cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high-throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR ß chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre- and post-treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy.

Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

Iodine(III)-Mediated Trifluoroacetylation of a C(sp2)-H or C(sp)-H Bond with Masked Trifluoroacyl Reagents.

A novel strategy for incorporating a trifluoroacetyl functionality into a range of structurally varied unsaturated bonds was developed by using PhI(OCOMe)2 as an oxidant with a masked trifluoroacyl reagent as a trifluoroacetyl radical precursor. The oxidative decarboxylation of the masked trifluoroacyl precursor followed by a tandem radical process provides versatile access to 5-exo-trig cyclization of N-arylacrylamides, direct C(sp2)-H trifluoroacetylation of quinolines, isoquinoline, 2H-indazole, and quinoxalin-2(1H)-ones, and C(sp)-H trifluoroacetylation of alkynes. This protocol is characterized by mild reaction conditions, operational simplicity, and broad functional group compatibility.

Visible-Light-Induced, Catalyst-Free Monofluoromethyl Sulfonylation of Alkenes with Iodine(III) Reagent and DABSO.

A visible-light-induced radical relay strategy to access heterocycles bearing a monofluoromethylsufonyl moiety is reported, with PhI(OCOCH2F)2 as the CH2F radical precursor and DABSO as the SO2 source. A range of oxindoles, containing a CH2FSO2CH2- group at the C3 position, were synthesized from N-arylacrylamides in up to 97% yields. The protocol features catalyst-free photochemical tandem, mild reaction conditions, broad functional group compatibility, and good to excellent yields.

Biochar Addition Inhibits Nitrification by Shifting Community Structure of Ammonia-Oxidizing Microorganisms in Salt-Affected Irrigation-Silting Soil.

Biochar has been widely recognized as an effective and eco-friendly ameliorant for saline soils, but information about the mechanism of how biochar influences nitrification in salt-affected agroecosystem remains fragmented. An incubation experiment was performed on the salt-affected soil collected from a three-consecutive-year experiment at biochar application gradients of 7.5 t⋅ha-1, 15 t⋅ha-1 and 30⋅t ha-1 and under nitrogen (N) fertilization. Responses of the nitrification rate (NR), numbers of ammonia monooxygenase (amoA) gene copies, and community structures of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to biochar application were investigated. The results indicated that, under N fertilization, the NR and numbers of amoA-AOB and amoA-AOA gene copies negatively responded to biochar addition. Biochar application increased the community diversity of AOB but decreased that of AOA. Biochar addition and N fertilization shifted the AOB community from Nitrosospira-dominated to Nitrosospira and Nitrosomonas-dominated, and altered the AOA community from Nitrososphaera-dominated to Nitrososphaera and Nitrosopumilus-dominated. The relative abundance of Nitrosospira, Nitrosomonas and Nitrosopumilus decreased, and that of Nitrosovibrio and Nitrososphaera increased with biochar application rate. Soil SOC, pH and NO3--N explained 87.1% of the variation in the AOB community, and 78.1% of the variation in the AOA community was explanatory by soil pH and SOC. The SOC and NO3--N influenced NR through Nitrosovibrio, Nitrosomonas, Norank_c_environmental_samples_p_Crenarchaeota and amoA-AOB and amoA-AOA gene abundance. Therefore, biochar addition inhibited nitrification in salt-affected irrigation-silting soil by shifting the community structures of AOB and AOA and reducing the relative abundance of dominant functional ammonia-oxidizers, such as Nitrosospira, Nitrosomonas and Nitrosopumilus.

[Characteristics and influencing factors of soil nitrification potential in coastal salinized farmland]. / æ»¨æµ·ç›æ¸å†œç”°åœŸå£¤ç¡åŒ–åŠ¿ç‰¹å¾åŠå ¶å½±å“å› ç´ .

Understanding the nitrification capacity of coastal saline farmland soils and its main drivers is of great significance to regulate soil nitrification and improve the utilization efficiency of nitrogen fertilization in farmland. Using a combination of field investigations and laboratory analyses, we examined farmland soil nitrification potential and soil physical, chemical, and biological properties in the coastal muddy tidal flat saline soil area (Dongying and Dongtai). We established the correlation between soil properties and soil nitrification potential with multiple stepwise regression analyses and structural equation modeling (SEM). The results showed that soil pH value was relatively stable and other soil properties and soil nitrification potential varied in coastal saline farmland. The soil nitrification potential ranged from 0.04 to 10.42 mg·kg-1·d-1 and decreased with the increases of soil salinization level. Soil nitrification potential had the strongest correlation with soil organic matter, cation exchange capacity, and Cl-, with the correlation coefficient being 0.409, 0.397 and -0.337, respectively. The results of multiple stepwise regression analysis showed that Na+, silt, cation exchange capacity, and CO32-+HCO3- were the main influencing factors of soil nitrification potential. The results from the SEM analysis suggested that Na+, silt, cation exchange capacity, and CO32-+HCO3- directly affected soil nitrification potential, and soil organic matter, clay, Cl- and SO42- had indirect effects. In all, soil Na+ and cation exchange capacity were the two main factors affecting nitrification. Adjusting soil NaCl content and cation exchange capacity was an effective means of regulating soil nitrification.

Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature.

BACKGROUND: Gefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib. CASE PRESENTATION: Two patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT), and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously. CONCLUSION: We speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.

Biochar and fulvic acid amendments mitigate negative effects of coastal saline soil and improve crop yields in a three year field trial.

China with large area of land planted with crops are suffering secondary salinization in coastal area for the lack of fresh water and saltwater intrusion to the groundwater. The purpose of this study was to investigate the effects of biochar (BC) and fulvic acid (FA) on the amelioration of coastal saline soil and their impact on crop yields under maize-barley rotation system. A three year field experiment was conducted in a saline soil on a farm in coastal area of east Jiangsu Province, China. A maize-barley rotation system had been carried out for ten years with local conventional management before the experiment. The saline soil was amended with BC at rates of 0, 7.5 t ha-1 (BC1), 15 t ha-1 (BC2) and 30 t ha-1 (BC3) alone or combined with fulvic acid (1.5 t ha-1) compared with control. Fertilizers were applied under normal planting strategies. The BC was added only once during the four growing seasons, and the FA was applied before each sowing. Soil salinity changed significantly during the three year field experiment. This was mainly due to the great quantity of rain during the period of maize cultivation. Although Na+, Cl- and SO42- in BC and /or FA treatments significantly decreased, the pH value increased up to 9.0 as the CO32- + HCO3-content increased. Total organic carbon (TOC) and phosphorus (TP) responded positively to biochar addition rate. BC applied with appropriate rate at 15 t ha-1 (BC2) in combination with FA showed optimal effects on soil salinity amelioration, soil physics properties regulation, soil nutrition improvement and crop yields increase. The TOC and TP was 5.2 g kg-1 and 507 mg kg-1 in BC2 + FA treatment, which were lower than BC3 and BC3 + FA treatments. However, the highest total grain yield was obtained in the BC2 + FA treatment, and the total yield was increased by 62.9% over the CK. This study emphasizes that using combined organic amendment of BC with FA for profitable and sustainable use of salt-affected soils would be practicable.

[Influencing mechanism of soil salinization on nitrogen transformation processes and efficiency improving methods for high efficient utilization of nitrogen in salinized farmland]. / ç›æ¸åŒ–å¯¹å†œç”°æ°®ç´ è½¬åŒ–è¿‡ç¨‹çš„å½±å“æœºåˆ¶å’Œå¢žæ•ˆè°ƒæŽ§é€”å¾„.

Based upon the review of the status of nitrogen use efficiency in salinized farmland in China, we summarized the effect of salinization on key processes of nitrogen transformation in farmland soil, analyzed the microbial mechanism underlying nitrogen transformation, and summed up the main ways for high efficient utilization of nitrogen in salinized farmland. Salinization had thre-shold effects on mineralization, nitrification, and denitrification of nitrogen from farmland soil, with the influence varying greatly in different scopes. Salinity and secondary barriers had different effects on microorganisms, with threshold in their effects. The most widely used methods for nitrogen synergism regulation in salinized farmland include soil conditioner, biomass material, growing salt-tole-rant plants, optimizing the ratio of different nitrogen forms, and biological inhibitor. We proposed current research shortcomings and future research directions of nitrogen cycle processes in salinized farmland. This study was of great significance for reducing nitrogen loss, enhancing utilization of nutrient from fertilizers, and controlling agricultural non-point source pollution in salinized farmland.

Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy.

Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK). However, the concomitant oncogenic drivers may affect the sensitivity of crizotinib. Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. Although the patient received timely and comprehensive treatment, the overall survival was only 8 months. Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis. In addition, the novel SPTBN1-ALK fusion gene may become a potential target for anti-tumor therapy.

[Development of a prototype of space vegetable-cultivating facility for ground-based experiments].

OBJECTIVE: To develop a ground-based experimental prototype of space vegetable-cultivating facility (GEPSVF), so as to solve the main key techniques related to higher plant cultivation in space environmental conditions, and to further lay a foundation for future development and application of the prototype of space vegetable-growing facility. METHOD: Based on detailed demonstration and design of technique plan, the blueprint design and machining of components, whole facility installment, debugging, trial operations and verification experiments were done. RESULT: The parameters in the growing chamber such as temperature, relative humidity, wind velocity, total pressure, O2 partial pressure, CO2 partial pressure and water content of the growing media were totally and effectively controlled; the light source was electronic fluorescent lamp; the average vegetable-producing output reached 60 g (fresh weight) d-1. CONCLUSION: The prototype could operate stably; its actual performance indexes achieved the expected ones basically; some of its operating principles can adapt to space microgravity condition. Therefore, the prototype is a good beginning for future development of space vegetable-producing facilities.

Predictive factors of brain metastasis in patients with breast cancer.

The aim of this study is to determine the risk factors associated with metastasis to the brain of primary breast cancer patients and evaluate a predictive model. The clinicopathological characteristics of 206 patients with primary breast cancer were analyzed retrospectively with a univariate and multivariate logistic regression model. A predictive model was generated, and its validity evaluated with a receiver operating characteristic (ROC) curve. Independent risk factors for brain metastasis in patients with primary breast cancer were: being younger than 35 years old at the time of diagnosis, having four or more metastatic axillary nodes, being estrogen receptor-negative, and with 24 months of metastasis-free survival. The predictive value of the brain metastasis risk model, measured as the area under the ROC curve, was 0.765 ± 0.040 (95 % CI 0.688-0.842). When 0.8 was considered the cutoff point of probability calculated by the model, the sensitivity and specificity for predicting the occurrence of brain metastases in these patients were 0.769 and 0.713, respectively. The predictive model constructed in this study can be used to forecast brain metastasis in breast cancer. Patients with a predictive level ≥0.8 could be treated preventively for brain metastases.

[Scale-dependency of spatial variability of soil available nutrients].

With the support of GIS and by using classical statistics and geostatistics methods, the spatial variability of soil available P (AP) and available K (AK) in cultivated lands in Yucheng City of Shandong Province was approached at county and township scales. The results showed that both the soil AP and AK followed the logarithmic normal distribution, with the coefficient of variation (CV) at the two scales being 26.5% - 36.6% and presenting a moderate variation. With the decrease of the scale, the CV of the soil AP and AK increased. Both the soil AP and AK were spatially correlated with scale. At county scale, the soil AP and AK had a larger spatial correlation distance, being 9.0 km and 26.5 km, respectively; while at township scale, the soil AP and AK had a smaller spatial correlation distance, being 1.7 km and 2.8 km, respectively. The spatial distribution of the soil AP and AK at the two scales was obviously different, which was mainly affected by structural factors and random factors.

Adenovirus-mediated suicide gene therapy under the control of Cox-2 promoter for colorectal cancer.

Colorectal cancer is a most frequent type of gastrointestinal tract cancers. The prognosis of patients with colorectal cancer remains poor despite intensive interventions. Tumor specific promoter-directed gene therapy and adenoviral technology can be promising strategies for such advanced disease. This study was conducted to explore the possible therapeutic approach of Cox-2 promoter-directed suicide gene therapy with herpes simplex virus thymidine kinase (HSV-tk) in combination with adenoviral technology for advanced colorectal cancer. Firstly, the activity of Cox-2 promoter was assessed by dual luciferase and enhanced green fluorescent protein reporter gene assays in colorectal cancer cell lines and normal human intestinal epithelial cell line. Then, the expression of coxsackievirus and adenovirus receptor (CAR) was detected in colorectal cancer cell lines. The Cox-2 promoter-directed HSV-tk/ganciclovir (GCV) system mediated by adenovirus (Ad-Cp-TK) was developed (Ad-CMVp-TK, Ad-null and no Ad as controls). In vitro cytoxicity, colony formation and apoptosis assays were performed using Ad-Cp-TK. An animal study was carried out in which BALB/C nude mice bearing tumors were treated with Ad-Cp-TK and GCV treatments. Results showed that Cox-2 promoter possessed high transcriptional activity in a tumor-specific manner. All colorectal cancer cells were detected CAR-positive. In vitro cytotoxic and colony formation assays showed that colorectal cancer cells infected with Ad-Cp-TK became more sensitive to GCV but the sensitivity of normal cells infected with Ad-Cp-TK to GCV were not altered. Moreover, the Ad-Cp-TK system combined with GCV treatment could significantly induce apoptosis of colorectal cancer cells but not normal intestinal epithelial cells. Furthermore, this system also significantly inhibited the growth of subcutaneous tumors and prolonged survival of mice. Thus, adenovirus primary receptor was positive in colorectal cancer cells and adenovirus-mediated suicide gene therapy under the control of Cox-2 promoter could provide a promising treatment modality for advanced colorectal cancer with tumor specificity.

[Characteristics of soil salinity profiles and their electromagnetic response under various vegetation types in coastal saline area].

Aiming at the intrinsic relationships between vegetation type and soil salinity in coastal saline area, and by using electromagnetic induction EM38 and field sampling method, the characteristics of soil salinity profiles under various vegetation types in typical coastal saline region of the Yellow River Delta were analyzed, and the electromagnetic response characters of the salinity profiles were compared. The results showed that across the study area, soil salinity exhibited the characteristics of top enrichment and strong spatial variation. The horizontal electromagnetic conductivity EM(h) responded well to soil salinity at upper layers, and the response of vertical electromagnetic conductivity EM(v) to soil salinity at deeper layers was superior to that of EM(h). Soil salinity profiles were classified into inverted, normal, and uniform types. The vegetation types of inverted salinity profiles were mainly bare land and Suaeda salsa, while those of normal and uniform salinity profiles were cotton and weed, respectively. The sequence of top enrichment intensity was bare land > S. salsa land > weed land > cotton land. With the change of vegetation type of cotton-weed-S. salsa-bare land, the EM(v)/EM(h) value of salinity profiles decreased gradually. Nonparametric test results showed that there was a significant correlation between vegetation type and electromagnetic response characters, and the distribution characters of EM(v)/EM(h) under various vegetation types varied significantly.