Towards Effective Management: Toxicity, Causal Mechanism and Controlling Strategy of Toxic Rangeland Weeds in Western China

Toxic rangeland weeds (TRWs) pose a great threat to animal husbandry. Currently, an estimated 33 million hectares of pasture (10%) in western China is infested by a variety of toxic weeds, including Stellera chamaejasme, Oxytropis spp., Astragalus spp., Achnatherum inebrians. The spread of these toxic weeds results in huge annual economic losses of more than $2.4 billion USD (direct and indirect). A combination of ecology, molecular biology, biochemistry and field practise methods will be used to identify and evaluate TRWs, explore the mechanism of toxicity, and more importantly, understand the causal mechanism by which TRWs flourish. The knowledge will underpin the development of effective management strategies

Study of peripheral dose from low-dose CT to adaptive radiotherapy of postoperative prostate cancer

ObjectivesThe increasing use of computed tomography (CT) for adaptive radiotherapy (ART) has raised concerns about the peripheral radiation dose. This study investigates the feasibility of low-dose CT (LDCT) for postoperative prostate cancer ART to reduce the peripheral radiation dose, and evaluates the peripheral radiation dose of different imaging techniques and propose an image enhancement method based on deep learning for LDCT.Materials and methodsA linear accelerator integrated with a 16-slice fan-beam CT from UIH (United Imaging Healthcare, China) was utilized for prostate cancer ART. To reduce the tube current of CT for ART, LDCT was acquired. Peripheral doses of normal-dose CT (NDCT), LDCT, and mega-voltage computed tomography (MV-CT) were measured using a cylindrical Virtual Water™ phantom and an ion chamber. A deep learning model of LDCT for abdominal and pelvic-based cycle-consistent generative adversarial network was employed to enhance the image quality of LDCT. Six postoperative prostate cancer patients were selected to evaluate the feasibility of low-dose CT network restoration images (RCT) by the deep learning model for ART. The three aspects among NDCT, LDCT, and RCT were compared: the Hounsfield Unit (HU) of the tissue, the Dice Similarity Coefficient (DSC) criterion of target and organ, and dose calculation differences.ResultsIn terms of peripheral dose, the LDCT had a surface measurement point dose of approximately 1.85 mGy at the scanning field, while the doses of NDCT and MV-CT were higher at 22.85 mGy and 29.97 mGy, respectively. However, the image quality of LDCT was worse than NDCT. When compared to LDCT, the tissue HU value of RCT showed a significant improvement and was closer to that of NDCT. The DSC results for target CTV between RCT and NDCT were also impressive, reaching up to 94% for bladder and femoral heads, 98% for rectum, and 94% for the target organ. Additionally, the dose calculation differences for the ART plan based on LDCT and NDCT were all within 1%. Overall, these findings suggest that RCT can provide an effective alternative to NDCT and MV-CT with similar or better outcomes in HU values of tissue and organ damage. More testing is required before clinical application

A hybrid energy-based and AI-based screening approach for the discovery of novel inhibitors of JAK3

The JAKs protein family is composed of four isoforms, and JAK3 has been regarded as a druggable target for the development of drugs to treat various diseases, including hematologic tumors, cancer, and neuronal death. Therefore, the discovery of JAK3 inhibitors with novel scaffolds possesses the potential to provide additional options for drug development. This article presents a structure-based hybrid high-throughput virtual screening (HTVS) protocol as well as the DeepDock algorithm, which is based on geometric deep learning. These techniques were used to identify inhibitors of JAK3 with a novel sketch from a specific “In-house” database. Using molecular docking with varying precision, MM/GBSA, geometric deep learning scoring, and manual selection, 10 compounds were obtained for subsequent biological evaluation. One of these 10 compounds, compound 8, was found to have inhibitory potency against JAK3 and the MOLM-16 cell line, providing a valuable lead compound for further development of JAK3 inhibitors. To gain a better understanding of the interaction between compound 8 and JAK3, molecular dynamics (MD) simulations were conducted to provide more details on the binding conformation of compound 8 with JAK3 to guide the subsequent structure optimization. In this article, we achieved compound 8 with a novel sketch possessing inhibitory bioactivity against JAK3, and it would provide an acceptable “hit” for further structure optimization and modification to develop JAK3 inhibitors

High Density Lipoprotein Protects Mesenchymal Stem Cells from Oxidative Stress-Induced Apoptosis via Activation of the PI3K/Akt Pathway and Suppression of Reactive Oxygen Species

The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS

Dyslipidemia in diffuse large B-cell lymphoma based on the genetic subtypes: a single-center study of 259 Chinese patients

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes.ResultsThis study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p <0.001) is higher in the EZB subtype than in others, especially hypertriglyceridemia (78.3%, p = 0.001) in the EZB subtype. Based on the pathological gene-sequencing, patients with BCL2 gene fusion mutation are significantly correlative with hyperlipidemia (76.5%, p = 0.006) and hypertriglyceridemia (88.2%, p = 0.002). Nevertheless, the occurrence of dyslipidemia has no remarkable influence on prognosis.ConclusionIn summary, dyslipidemia correlates with genetic heterogeneity in DLBCL without having a significant influence on survival. This research first connects lipids and genetic subtypes in DLBCL

A Nomogram to Predict the Overall Survival of Patients With Resected T1-2N0-1M0 Non-Small Cell Lung Cancer and to Identify the Optimal Candidates for Adjuvant Chemotherapy in Stage IB or IIA Non-Small Cell Lung Cancer Patients

Background The benefit of adjuvant chemotherapy for IB/IIA non-small cell lung cancer (NSCLC) patients remains uncertain. This study aimed to develop a prognostic model to predict overall survival in resected NSCLC patients with T1-2N0-1M0 stage and identify optimal candidates for postoperative chemotherapy among those with stage IB or IIA disease. Methods We conducted a retrospective study using the SEER 18 database (2000–2018, November 2020 submission) of patients who underwent radical surgery for T1-2N0-1M0 NSCLC. The patients not receiving adjuvant chemotherapy were randomly divided into training and validation cohorts. A prognostic nomogram was established and evaluated using calibration and receiver operating characteristic curves. Based on the nomogram, stage IB and IIA patients were categorized into two prognostic groups, each further divided into cohorts based on adjuvant chemotherapy status. Kaplan-Meier analysis and log-rank tests were used to compare overall survival between these groups. Results A total of 14 789 patients were enrolled and randomly assigned to the training cohort (n = 10 352) and validation cohort (n = 4437). Ten independent prognostic factors were identified and integrated into the prognostic model. The area under the receiver operating characteristic curve was .706, .699, and .705 in the training cohort, and .700, .698, and .695 in the validation cohort at 1, 3, and 5 years, respectively. Among stage IB and IIA patients, only those in the high-risk group showed a significant benefit from adjuvant chemotherapy, with a 16.4% absolute increase in 5-year overall survival. Conclusions The nomogram developed in the study may help physicians choose the most appropriate management strategy for each patient

Spatiotemporal Variation in the Land Use/Cover of Alluvial Fans in Lhasa River Basin, Qinghai–Tibet Plateau

Alluvial fans are an important land resource with agricultural potential in Qinghai–Tibet Plateau. The spatiotemporal variation in land use/cover is an important indicator to understand the value of alluvial fans and protect and make scientific use of such fans. In this study, the spatiotemporal characteristics of land use/cover are determined by analysing the land use/cover changes of alluvial fans in the Lhasa River Basin (LRB) at different times, counties/districts, altitudes, and gradients. Results show that the area of cultivated land and the artificial land provided by alluvial fans for LRB has continuously increased. In 2000, 2010, and 2020, 17.72%, 21.84%, and 24.17% of cultivated land and 7.89%, 7.51%, and 25.24% of artificial land in LRB were provided by alluvial fans, respectively. At all altitudes and slopes, cultivated land and artificial land are increasing but the increasing part is basically due to the massive loss of grassland. The spatiotemporal changes in all land use/cover types of alluvial fans were dominated by human activities, although they were also influenced by natural factors to some degree