Design, synthesis, and biological evaluation of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives as TRPM4 inhibitors for the treatment of prostate cancer.

Transient receptor potential melastatin 4 (TRPM4) is considered to be a potential target for cancer and other human diseases. Herein, a series of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives were designed and synthesized as new TRPM4 inhibitors, aiming to improve cellular potency. One of the most promising compounds, 7d (ZX08903), displayed promising antiproliferative activity against prostate cancer cell lines. 7d also suppressed colony formation and the expression of androgen receptor (AR) protein in prostate cancer cells. Furthermore, 7d can concentration-dependently induce cell apoptosis in prostate cancer cells. Collectively, these findings indicated that compound 7d may serve as a promising lead compound for further anticancer drug development.

Design, Synthesis, and Biological Evaluation of Hydrophobic-Tagged Glutathione Peroxidase 4 (GPX4) Degraders.

Ferroptosis is an iron-dependent form of oxidative cell death induced by lipid peroxidation accumulation. Glutathione peroxidase 4 (GPX4) plays a key role in the regulation of ferroptosis and is considered to be a promising therapeutic target for cancer and other human diseases. Herein, we describe our design, synthesis, and biological evaluation of a series of HyT-based degraders of the GPX4. One of the most promising compounds, 7b (ZX782), effectively induces dose- and time-dependent degradation of GPX4 protein and potently suppresses the growth of human fibrosarcoma HT1080 cells, which are highly sensitive to ferroptosis and widely used for evaluating compound specificity in ferroptosis. Mechanism investigation indicated that 7b depletes GPX4 through both the ubiquitin-proteasome and the autophagy-lysosome. Furthermore, the degradation of GPX4 induced by 7b could significantly increase the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, ultimately leading to ferroptosis. Overall, compound 7b exhibits robust potency in depleting endogenous GPX4, thereby modulating ferroptosis in cancer cells.

Text information security protection method based on computer-generated holograms.

Currently, computer-generated holograms (CGHs) based on ray tracing technology are generated faster and faster, and the reconstructed scenes are getting bigger and bigger and contain more and more information. Based on this situation, there are also more applications of using CGHs to hide information, but there is a lack of research on the ability to hide information. To address this issue, this paper proposes a point-sampling CGH method based on ray tracing. Our method utilizes ray tracing techniques to rapidly sample text information at different depths in the scene and hides the depth-encoded text information in the carrier image using discrete cosine transform. The reconstructed image after embedding shows good results, with a peak signal-to-noise ratio (PSNR) of 29.56 dB between the hidden images before and after embedding. The PSNR value between the embedded carrier image and the original carrier image is 51.66 dB, making it difficult for the human eye to distinguish, thereby effectively protecting the generated CGH. We also analyzed the maximum information density and observed that computational holograms obtain the maximum information density at 200×200 resolution.

Meta-analysis of the accuracy of the serum procalcitonin diagnostic test for osteomyelitis in children.

OBJECTIVE: This study sought to assess the sensitivity, specificity, and predictive utility of serum procalcitonin (PCT) in the diagnosis of pediatric osteomyelitis. METHODS: A systematic computer-based search was conducted for eligible literature focusing on PCT for the diagnosis of osteomyelitis in children. Records were manually screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Statistical analysis was performed using Review Manager software 5.3, Meta-disc software1.4, STATA 12.0, and R 3.4 software. RESULT: A total of 5 investigations were included. Of these, 148 children with osteomyelitis were tested for bacterial cultures in PCT. For PCT in the diagnosis of pediatric osteomyelitis, diagnostic meta-analysis revealed a pooled sensitivity and specificity of 0.58 (95% confidence interval (CI): 0.49 to 0.68) and 0.92 (95% CI: 0.90 to 0.93) respectively. The PCT had the greatest area under the curve (AUC) at 0.80 for the diagnosis of osteomyelitis in children. The Deeks' regression test for asymmetry results indicated that there was no publication bias when evaluating publication bias (P = 0.90). CONCUSION: This study provided a comprehensive review of the literature on the use of PCT in pediatric osteomyelitis diagnosis. PCT may be used as a biomarker for osteomyelitis diagnosis; however, its sensitivity was low. It still needs to be validated by a large sample study.

Improving the productivity of Xinjiang cotton in heat-limited regions under two life history strategies.

Cotton is a major cash crop globally, playing a pivotal role in the textile sector. However, cotton growers in Xinjiang region are experiencing cotton yield penalty caused by limited heat environment. In this region, limited heat conditions strongly arrest cotton plant growth and development resulting in recued productivity. To counteract this problem, there is an urgent need to robustly identify efficient management strategies to improve plant performance and increase cotton yield under heat-limited situations. This will hold crucial implications for agricultural sustainability and global cotton supply. This review article identified challenges faced by cotton producers under heat limited environments with potential solutions to enhance cotton productivity. Specifically, we focused on the implementation of two life history strategies including planting early maturing and cold tolerant cultivars, and adjusting sowing date that can promote early maturity and increase cold stress tolerance. These strategies have shown promising results in protecting cotton plants from limited heat injury and consequently improved cotton productivity. By focusing on Xinjiang province unique climate and associated agronomic practices, valuable insights can be gained, which may have broader applications in other heat-limited cotton-growing regions globally. This comprehensive review endeavors to provide a foundation for future research and practical interventions aimed at boosting cotton yields under limited heat areas.

Clinical characteristics and prognostic factors for primary pediatric and adolescent Non-Hodgkin Lymphomas of the gastrointestinal tract: a population-based study.

PURPOSE: To investigate the clinical features and survival outcomes of primary gastrointestinal non-Hodgkin lymphomas (PGINHL) in pediatric and adolescent population, we conducted a population-based cohort study. METHODS: All pediatric and adolescent patients with PGINHL diagnosed between 2000 and 2019 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplane-Meier estimations were used to generate survival curves based on various criteria. To compare survival curves, the log-rank test was applied. A multivariate Cox proportional hazards model was developed to investigate the effect of each component on overall survival. RESULTS: A total of 334 pediatric and adolescent with PGINHL patients were identified. The median age at diagnosis was 12 years (range 1.0-19 years). Tumors were most commonly found in the small bowel (47.3%), followed by the large bowel (42.8%) and the stomach (9.9%). Overall, the most common histological subtype was Burkitt lymphoma (56.9%), followed by diffuse large B-cell lymphoma (DLBCL) (27.8%). Overall survival rates for all patients were 92.2% at 5- year and 91.6% at 10- year, respectively. The Cox proportional hazard regression revealed that only chemotherapy was an important independent predictor in this model. Patients with chemotherapy have a higher survival rate than those without. CONCLUSIONS: Our study revealed that only chemotherapy was found to be the most important predictor of the OS in pediatric and adolescent PGINHL, providing critical information for therapeutic care.

Molecular Interrogation to Crack the Case of O-GlcNAc.

The O-linked ß-N-acetylglucosamine (O-GlcNAc) modification, termed O-GlcNAcylation, is an essential and dynamic post-translational modification in cells. O-GlcNAc transferase (OGT) installs this modification on serine and threonine residues, whereas O-GlcNAcase (OGA) hydrolyzes it. O-GlcNAc modifications are found on thousands of intracellular proteins involved in diverse biological processes. Dysregulation of O-GlcNAcylation and O-GlcNAc cycling enzymes has been detected in many diseases, including cancer, diabetes, cardiovascular and neurodegenerative diseases. Here, recent advances in the development of molecular tools to investigate OGT and OGA functions and substrate recognition are discussed. New chemical approaches to study O-GlcNAc dynamics and its potential roles in the immune system are also highlighted. It is hoped that this minireview will encourage more research in these areas to advance the understanding of O-GlcNAc in biology and diseases.

Copper-Catalyzed Ring-Opening Defluorinative Alkylation of Siloxydifluorocyclopropanes: Synthesis of γ-Fluoro-δ-Ketoesters and γ,δ-Diketonitriles.

In view of the importance of both fluorinated synthons and homoenolate equivalents, synthetic application of difluorocyclopropanols is desired but remains challenging due to their thermodynamic instability. Herein, we use siloxydifluorocyclopropanes as difluorocyclopropanol precursors to carry out new Cu-catalyzed ring-opening defluorinative alkylation. With α-bromo carboxylic esters as coupling partners, the reaction affords γ-fluoro-δ-ketoesters via a CuI/CuII catalytic cycle. Interestingly, by the use of α-bromoamides, the ring-opening defluorinative alkylation is followed by an additional intramolecular C-N oxidative coupling to deliver a lactam intermediate, which further undergoes defluorination, hydrolysis, ring opening, and dehydration cascade via a CuI/CuII/CuIII catalytic pathway, leading to γ,δ-diketonitriles as the final products.

The Effects of Online Homeschooling on Children, Parents, and Teachers of Grades 1-9 During the COVID-19 Pandemic.

BACKGROUND Beginning in the 2020 spring semester, due to the COVID-19 pandemic, all school-age children in China were homeschooled via live/recorded broadcasts, online group communication, and software-based homework submission. This study assessed the effects of and proper preparation for this educational approach. MATERIAL AND METHODS The homeschooling behaviors and feelings of school-age children were assessed with 2010 online surveys obtained separately from students, parents, and teachers of grades 1-9 in 15 Chinese provinces. Answers were compared among low- (grades 1-3), middle- (grades 4-6), and high- (grades 7-9) grade groups. The chi-square test was used to identify significant differences between groups. RESULTS We found that 76% of the respondents thought the homeschooling style was acceptable. However, teachers were concerned that students' interest, focus, and academic performance would decline. Sixty-nine percent of the parents reported their children had more than 3 hours of daily screen time, and 82% of students had less than 2 hours of daily outdoor activity. Ninety-five percent of the parents were concerned about their children's eyesight. Additionally, 17.6% of the students were suspected to have emotional or behavioral problems according to the parent-rated Strengths and Difficulties Questionnaire (SDQ) results. The Self-Rating Anxiety Scale (SAS) results of parents and teachers showed higher levels of anxiety than usual. CONCLUSIONS Students should continue the going-to-school rhythm at home to cope with changes caused by the COVID-19 pandemic. Integrated grade-specific approaches are needed. Because long screen time and insufficient outdoor activities can severely affect children's eyesight, appropriate eye-protection measures should be implemented.

KIF20B promotes the progression of clear cell renal cell carcinoma by stimulating cell proliferation.

Renal cell carcinoma (RCC) is a common urinary system cancer with high morbidity and mortality rate. Clear cell renal cell carcinoma (ccRCC) is a highly aggressive and common type of RCC. More and effective therapeutic targets are badly needed for the treatment of ccRCC. Kinesin family protein (KIF)20B, also named M-phase phosphoprotein 1, was reported as a microtubule-associated, plus-end-directed kinesin. KIF20B was involved in multiple cellular processes such as cytokinesis. Multiple studies indicated the oncogenic role for KIF20B in several types of tumors, including breast cancer and bladder cancer. However, the possible role of KIF20B in the progression of renal carcinoma is still unknown. Herein, our study demonstrated that KIF20B was relatively highly expressed in ccRCC tissues. In addition, KIF20B was inversely related to the clinical features including tumor size and T stage. We further found that inhibition of the KIF20B expression by a specific short hairpin RNA obviously reduces proliferation of ccRCC cells both in vitro and in vivo. Our study reveals the involvement of KIF20B in ccRCC progression. Generally, KIF20B is a promising novel therapeutic for the treatment of clear cell RCC.