IMPORTANCE: Hepatitis B virus (HBV) reactivation is a serious complication for patients with lymphoma treated with rituximab-containing chemotherapies, despite lamivudine prophylaxis treatment. An ...optimal prophylactic antiviral protocol has not been determined. OBJECTIVE: To compare the efficacy of entecavir and lamivudine in preventing HBV reactivation in patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). DESIGN, SETTING, AND PATIENTS: Randomized, open-label, phase 3 study conducted from February 2008 through December 2012 at 10 medical centers in China. This study was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma. Patients enrolled in the parent study who were seropositive for the hepatitis B surface antigen and had normal liver function, serum HBV DNA levels of less than 103 copies/mL, and no prior antiviral therapy were randomized to entecavir (n = 61) or lamivudine (n = 60). INTERVENTIONS: Daily entecavir (0.5 mg) or lamivudine (100 mg) beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end points included rates of HBV reactivation, chemotherapy disruption due to hepatitis, and treatment-related adverse events. RESULTS: There were 121 patients randomly assigned to receive entecavir (n = 61) or lamivudine (n = 60). The date of last patient follow-up was May 25, 2013. The rates were significantly lower for the entecavir group vs the lamivudine group for HBV-related hepatitis (0% vs 13.3%, respectively; difference between groups, 13.3% 95% CI, 4.7% to 21.9%; P = .003), HBV reactivation (6.6% vs 30%; difference, 23.4% 95% CI, 10.2% to 36.6%; P = .001), and chemotherapy disruption (1.6% vs 18.3%; difference, 16.7% 95% CI, 6.4% to 27.0%; P = .002). Of the 61 patients in the entecavir group, 15 (24.6%) experienced treatment-related adverse events. Of 60 patients in the lamivudine group, 18 (30%) experienced treatment-related adverse events (difference between entecavir and lamivudine groups, 5.4% 95% CI, −10.5% to 21.3%; P = .50). CONCLUSIONS AND RELEVANCE: Among patients seropositive for the hepatitis B surface antigen with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy, the addition of entecavir compared with lamivudine resulted in a lower incidence of HBV-related hepatitis and HBV reactivation. If replicated, these findings support the use of entecavir in these patients. TRIAL REGISTRATIONS: clinicaltrials.gov Identifier: NCT01793844; Chinese Clinical Trial Registry Identifier: CTR-TRC-11001687
The KNOX (KNOTTED1-like homeobox) transcription factors play an important role in leaf, shoot apical meristem and seed development and respond to biotic and abiotic stresses. In this study, we ...analyzed the diversity and evolutionary history of the
gene family in the genome of tetraploid cotton (
). Forty-four putative
genes were identified. All
genes from seven higher plant species were classified into KNOXI, KNOXII, and KNATM clades based on a phylogenetic analysis. Chromosomal localization and collinearity analysis suggested that whole-genome duplication and a polyploidization event contributed to the expansion of the cotton
gene family. Analyses of expression profiles revealed that the
genes likely responded to diverse stresses and were involved in cotton growth developmental processes. Silencing of
enhanced the salt tolerance of cotton seedlings, whereas silencing of
and
reduced seedling tolerance to salt stress. Silencing of
influenced the cotton flowering time and plant development. These findings clarify the evolution of the cotton
gene family and provide a foundation for future functional studies of KNOX proteins in cotton growth and development and response to abiotic stresses.
The flat terrain in the plain areas of Beijing, China makes the land easily accessible for cultivation and farming, providing vast opportunities for agricultural development. Meanwhile, these areas ...are also crucial for urban construction and economic growth. Soil type mapping plays a key role in understanding soil characteristics and guiding land management practices. However, accurately mapping soil types in plain regions can be challenging due to their low spatial variability and diverse land use types. Although land cover changes due to phenomena such as urbanization, agricultural expansion, and conversion of natural vegetation can significantly affect soil properties and distribution patterns, their impacts on soil type mapping remain unclear. This study investigated the impacts of land cover changes in plain areas on the accuracy of soil type mapping, hoping to provide effective assistance for soil type mapping in plain areas by analyzing their coupling relationship. Focusing on the 20 year land cover changes in Tongzhou District, this study utilizes a unified approach that combines expert knowledge, mixed sampling methods, and RF mapping techniques, while incorporating environmental covariates that have minimal period influence and synergistically using NDVI and land cover data from the same year. Transition matrices are used to reveal land cover changes, confusion matrices, and their derived indicators to analyze changes in soil type mapping accuracy, and coupling analysis is conducted between soil type change areas and land cover change areas. The results show that Tongzhou District has experienced rapid development over the past 20 years, with the area of construction land nearly doubling. Additionally, 29% of arable land has been converted into construction land, resulting in an increase in the accuracy of the soil map from 58.99% to 66.91% over the 20 year period. The soil type change area during this period accounts for 16.5% of the total area, with 51.9% of the changed areas overlapping with land cover change areas. These overlapping regions are predominantly influenced by human activities. In terms of cultivated land types in the study area, the quantity of arable land has decreased by approximately 29% over 20 years, while the proportion of Sandy loam calcareous fluvo-aquic soil and Light loam calcareous fluvo-aquic soil, which constitute nearly half of the soil type, has increased. These data demonstrate the coupling relationship between land cover changes and soil type variations. It is evident that improving the extent of land use in plain areas enhances the credibility of soil type mapping. Meanwhile, human activities impact land cover, which, in turn, affects and reflects changes in the soil type.
Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This ...prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings.
Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method.
Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1).
The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment.
This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As global industrialization and its associated anthropogenic activities rapidly increase, so too does the areal extent of human-altered soils. The soil classification framework must incorporate the ...classification schemes of these disturbed soils in order to remediate land. Soil Taxonomy (ST) and the World Reference Base for Soil Resources (WRB) are the most widely used soil classification systems in the world. In this study, 15 typical anthropogenic soil profiles with engineering and technical characteristics from China were selected for a classification study. The aim of this study was to clarify the classifications of these soil profiles in the ST, WRB, Chinese Soil Taxonomy (CST), and Geogenetic Soil Classification of China (GSCC), and make references accordingly. The results showed that the WRB can classify these soils as Technosols in the first level. ST can classify most of these soils as subgroups within the different great groups under Entisols, as well as the Human-Altered and Human-Transported Material classes within the soil family differentiae. For Chinese soil classification schemes, there is a large loophole in the CST regarding the classification of anthropogenic soils. Many anthropogenic soils cannot reflect these soils’ artificial and technical naming characteristics. For the CST, revised proposals based on the WRB and ST were proposed. Based on the artificial disturbance of soil layers, a manufactured layer was added to the diagnostic basis. The Artificalic Anthrosols suborder was added, and it can be divided into the Transporti-Artificalic Anthrosols and Alteri-Artificalic Anthrosols groups. The subgroups were defined by their levels of contamination, imperviousness, and artifact content. The “T” layer symbol was added to soil profile descriptions to reflect a specific layer about technology, such as A, E, B, and C, to reflect the main genetic horizons. This revised classification system is proposed for inclusion in the revised CST to account for the very large and expanding extent of disturbed soils in China and to remain current with other global soil taxonomy systems.
Although androgen deprivation therapy remains the standard treatment for the initial therapy of advanced prostate cancer (PC), castration does not eliminate persistent intratumoral androgens within ...the prostate tumor microenvironment, which is capable of activating androgen receptor. Abiraterone effectively target adrenal and tumor androgen production in castration-resistant PC (CRPC). However, abiraterone-resistant CRPC is now common challenge in clinic via multiple mechanisms.
In this study, human CRPC cell line PC3 and androgen-sensitive cells LNCaP were used. The authors investigated the role of autophagy during the therapy of abiraterone in CRPC by analysis of transmission electron microscopy (TEM), Western blot and immunofluorescence assay. Cell cycle and apoptosis using flow cytometry analysis.
The analysis of TEM showed more autophagic vesicles (AVs) in PC3 cell line than that in LNCaP cell line and indicated the high basic cellular autophagy in CRPC cell line PC3, which was confirmed by the upregulation of autophagy-related protein LC3, Atg5, and Beclin1. Interestingly, the treatment of abiraterone reduced the level of autophagic vesicles in two cell lines and inhibited the expressions of autophagic markers LC3, Atg5 and Beclin1 in parallel with decreased cell vitality and induced G2/M arrest in PC3 cell line and LNCaP cell line. Moreover, the addition of the autophagy inhibitor 3-methyladenine to the treatment of abiraterone inhibited the formation of AVs with downregulated autophagic markers, and inhibition of autophagy promoted the efficiency of cytotoxicity of abiraterone with further impaired cell vitality and G2/M arrest.
These data suggested that inhibition of autophagy by its inhibitor benefits the treatment of abiraterone for CRPC patients.
Background
There were significant differences in the change of moisture content and grain composition at the late stage of grain development among different maize varieties, but the regulation ...mechanism is not clear.
Objective
To explore the key genes causing the variation in physiological traits of two typical maize inbred lines in late grain development.
Methods
The grains at different development stages were selected as materials to determine the content of water, sucrose, starch and ABA. Transcriptomic and proteomic analysis of the materials were performed to screen relevant genes.
Results
The grain dehydration rate and the content of sucrose, starch and ABA were showed significant differences between two varieties in the late stage of grain development. The enrichment analysis of common differentially expressed genes (proteins) showed that most of the genes (proteins) were enriched in the extracellular region. The downregulated genes were mainly concentrated in carbohydrate metabolism and lipid metabolism, while the upregulated genes were mainly in response to stress. Furthermore, this study also identified many key candidate genes (dehydrin genes, pathogenesis-related genes, sucrose synthase and secondary metabolites related genes) related to late grain development of maize.
Conclusions
The suggested genes related to late grain development of maize can be candidates for further functional study.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Existing treatments for cholangiocarcinoma have poor efficacy. However, chimeric antigen receptor‐T (CAR‐T) cells are emerging as a potential therapeutic strategy. Solid tumors possess ...multiple adverse factors in an immunosuppressive microenvironment that impair CAR‐T cell infiltration and function. This study aimed to improve the function of CAR‐T cells through knock down immune checkpoints and immunosuppressive molecular receptors.
Methods
We evaluated the expression of epidermal growth factor receptor (EGFR) and B7 homolog 3 protein (B7H3) antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry. Subsequently, we engineered CAR‐T cells targeting EGFR and B7H3 antigens. We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR‐T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR‐T cells for antitumor activity both in vitro, using tumor cell lines and cholangiocarcinoma organoid models, and in vivo, using humanized mouse models.
Results
We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues. EGFR‐CAR‐T and B7H3‐CAR‐T cells demonstrated specific anti‐tumor activity. We found an abundance of programmed cell death protein 1 (PD‐1), T cell immunoglobulin and mucin domain‐containing protein 3 (Tim‐3), and T cell immunoglobulin and ITIM domain (Tigit) on infiltrated CD8+ T cells in the cholangiocarcinoma microenvironment. We then decreased the expression of these 3 proteins on the surface of CAR‐T cells, named PTG‐scFV‐CAR‐T cells. Furthermore, we knocked‐down the expression of transforming growth factor beta receptor (TGFβR), interleukin‐10 receptor (IL‐10R), and interleukin‐6 receptor (IL‐6R) of PTG‐scFV‐CAR‐T cells. Those cells, named PTG‐T16R‐scFV‐CAR‐T cells, potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoid model. Finally, the PTG‐T16R‐scFv‐CAR‐T cells showed greater inhibitory effect on tumor growth in vivo, and were superior in prolonging the survival of mice.
Conclusions
Our results revealed that PTG‐T16R‐scFV‐CAR‐T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long‐term efficacy both in vitro and in vivo. This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Maize breeding is greatly affected by hybrid vigor, a phenomenon that hybrids exhibit superior performance than parental lines. The immortalized F2 population (IMF2) is ideal for the genetic ...dissection and prediction of hybrid performance. Here, in this study, we conducted the QTL mapping and genomic prediction of six traits related to plant architecture using an IMF2 population. Broad-sense heritability of these traits ranged from 0.85 to 0.94. Analysis of genetic effects showed that additive variance was the main contributor to phenotypic variations. The mapping of quantitative trait loci (QTLs) revealed 10 to 16 QTLs (including pleiotropic loci and epistatic QTLs) for the six traits. Additionally, we identified 15 fine-tuning QTLs for plant height (PH). For genomic prediction (GP), the model of additive and dominance (AD) exhibited higher prediction accuracy than those fitting general combining ability (GCA) and its combination with special combining ability (SCA) effects for all tested traits. And adding the epistasis (E) effect into the AD model did not significantly increase its prediction accuracy. Moreover, the identified 15 fine-tuning QTLs of PH, which exerted large genomic prediction effects, were verified by the marker effect of GP. Our results not only provide an approach for the fine-mapping of fine-tuning QTLs but also serve as references for GP breeding in crops.
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