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The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as a powerful strategy in drug design. To date, the most established method for accessing enantioenriched difluoromethyl compounds involves the enantioselective functionalization of nucleophilic and electrophilic CF₂H synthons. However, this approach is limited by lower reactivity and reduced enantioselectivity. Leveraging the unique fluorine effect, we design and synthesize a radical CF₂H synthon by incorporating isoindolinone into alkyl halides for asymmetric radical transformation. Here, we report an efficient strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling. This approach demonstrates mild reaction conditions and excellent enantioselectivity. Given that optically pure difluoromethylated amines and isoindolinones are key structural motifs in bioactive compounds, this strategy offers a practical solution for the efficient synthesis of CF₂H-containing chiral drug-like molecules. The difluoromethyl group is a crucial fluorinated moiety, and the synthesis of chiral CF₂H-containing analogs is a powerful strategy in drug design and screening. Here, the authors report a strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling.

Sulfur hexafluoride (SF6), a chemically inert and stable gas essential to the electric power industry, poses severe environmental risks due to its persistence and high global warming potential. While traditional degradation methods are inefficient, photocatalytic single electron reduction (SER) enables SF6 activation into SF5 radicals, creating opportunities for both degradation and reutilization. The SF5 group, renowned for its strong electron-withdrawing, lipophilic, and bioisosteric features, has great potential in drug discovery, while efficient methods for synthesizing alkyl- or BCP-SF5 motifs remain scarce. As a safe, inexpensive, and atom-economical alternative to conventional SF5 reagents, SF6 serves as an ideal yet underexplored SF5 source. Herein, we present a photocatalytic strategy for the direct synthesis of diverse SF5-containing scaffolds, including ketones, acetals, and bicyclo[1.1.1]pentane derivatives. Derivatization studies demonstrate its synthetic versatility, particularly in accessing α-SF5-substituted acetaldehydes. Mechanistic and density functional theory (DFT) studies confirm the single electron reduction of SF6, highlighting a mild, efficient, and broadly applicable route for constructing SF5-functionalized architectures in fluorinated drug development.Sulfur hexafluoride (SF6), a chemically inert and stable gas essential to the electric power industry, poses severe environmental risks due to its persistence and high global warming potential. While traditional degradation methods are inefficient, photocatalytic single electron reduction (SER) enables SF6 activation into SF5 radicals, creating opportunities for both degradation and reutilization. The SF5 group, renowned for its strong electron-withdrawing, lipophilic, and bioisosteric features, has great potential in drug discovery, while efficient methods for synthesizing alkyl- or BCP-SF5 motifs remain scarce. As a safe, inexpensive, and atom-economical alternative to conventional SF5 reagents, SF6 serves as an ideal yet underexplored SF5 source. Herein, we present a photocatalytic strategy for the direct synthesis of diverse SF5-containing scaffolds, including ketones, acetals, and bicyclo[1.1.1]pentane derivatives. Derivatization studies demonstrate its synthetic versatility, particularly in accessing α-SF5-substituted acetaldehydes. Mechanistic and density functional theory (DFT) studies confirm the single electron reduction of SF6, highlighting a mild, efficient, and broadly applicable route for constructing SF5-functionalized architectures in fluorinated drug development.

Sulfur hexafluoride (SF 6 ), a chemically inert and stable gas essential to the electric power industry, poses severe environmental risks due to its persistence and high global warming potential. While traditional degradation methods are inefficient, photocatalytic single electron reduction (SER) enables SF 6 activation into SF 5 radicals, creating opportunities for both degradation and reutilization. The SF 5 group, renowned for its strong electron‐withdrawing, lipophilic, and bioisosteric features, has great potential in drug discovery, while efficient methods for synthesizing alkyl‐ or BCP‐SF 5 motifs remain scarce. As a safe, inexpensive, and atom‐economical alternative to conventional SF 5 reagents, SF 6 serves as an ideal yet underexplored SF 5 source. Herein, we present a photocatalytic strategy for the direct synthesis of diverse SF 5 ‐containing scaffolds, including ketones, acetals, and bicyclo[1.1.1]pentane derivatives. Derivatization studies demonstrate its synthetic versatility, particularly in accessing α‐SF 5 ‐substituted acetaldehydes. Mechanistic and density functional theory (DFT) studies confirm the single electron reduction of SF 6 , highlighting a mild, efficient, and broadly applicable route for constructing SF 5 ‐functionalized architectures in fluorinated drug development.

The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as a powerful strategy in drug design. To date, the most established method for accessing enantioenriched difluoromethyl compounds involves the enantioselective functionalization of nucleophilic and electrophilic CF₂H synthons. However, this approach is limited by lower reactivity and reduced enantioselectivity. Leveraging the unique fluorine effect, we design and synthesize a radical CF₂H synthon by incorporating isoindolinone into alkyl halides for asymmetric radical transformation. Here, we report an efficient strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling. This approach demonstrates mild reaction conditions and excellent enantioselectivity. Given that optically pure difluoromethylated amines and isoindolinones are key structural motifs in bioactive compounds, this strategy offers a practical solution for the efficient synthesis of CF₂H-containing chiral drug-like molecules.

In order to improve the precision of the short-term load prediction, a new method based on radial basis function (RBF) neural network is proposed. The weather data of samples includes the temperature, humidity, date, type, etc., and is quantified according the relevance to load, and then forecasting the power load using RBF neural network model in a region, Actual example shows that this method improves the convergence speed and prediction accuracy of load forecasting.

Background The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk. Methods Databases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach. Results Eighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12–1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10–1.28) and sisters only (RR 1.71, 95% CI 1.43–2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74–4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04–1.34) with low-quality evidence. Conclusions This review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.

Root exudates have a key role in communication between plants and microbes in the rhizosphere. Fusarium wilt of watermelon, caused by Fusarium oxysporum f. sp. niveum (Fusarium oxysporum), drastically reduces watermelon yields in continuous cultivation systems, but it can be significantly alleviated using watermelon/aerobic rice intercropping system as shown by the research carried out in this laboratory. It is important to evaluate the interaction between root exudates from the two crops and the pathogen and thus to clarify the mechanism of disease suppressiveness in the intercropping system. The effects of phenolic acids, sugars and free amino acids in root exudates from watermelon (REW) and rice (RER) on the growth of Fusarium oxysporum were studied. The results obtained are listed as follows: (1) REW significantly increased spore germination and sporulation, whereas RER had inhibitory effects on those two parameters. (2) HPLC analysis showed that salicylic acid, p-hydroxybenzoic acid and phthalic acid were identified in exudates from both plants, but p-coumaric acid was only detected in rice and ferulic acid only in watermelon. Moreover, of the total rice exudates a high proportion (37.9 %) of p-coumaric acid was detected and the total amount of phenolic acids was 1.4-fold as high as that in watermelon. (3) Considerable differences in the components and contents of both sugars and amino acids were found between REW and RER exudates. (4) Exogenously applied alanine (Ala) increased spore germination and sporulation. In contrast, addition of exogenous p-coumaric acid reduced spore germination and sporulation, relative to controls. It was concluded that the rice root exudates had anti-fungal properties while that from watermelon promoted pathogen growth. This discovery provided a scientific basis for practicing watermelon/aerobic rice intercropping to control Fusarium wilt in watermelon.

Osteosarcoma (OS) is the most common primary bone malignancy, characterized by aggressive local invasion and a high propensity for metastasis. We previously reported that cyclin E1 is upregulated in osteosarcoma. In this study, we identified a cytoplasmic, low molecular weight cyclin E1 isoform (LMW-cyclin E1) in osteosarcoma that is significantly associated with poor patient outcomes. We collected RNA sequencing data to analyze the cyclin E1 ( ) expression and performed Western blot assay, immunofluorescence, and immunohistochemistry staining to validate cyclin E1 expression in OS. We also analyzed the correlation between its expression levels and the overall and progression-free survival rates of patients with OS. Small interfering RNA and plasmids were constructed to regulate neutrophil elastase (ELA2) expression to explore the mechanism of low molecular weight cyclin E1 formation in OS. Neutrophils isolated from healthy donors were cocultured with OS cells to test the function of ELA2, and its effect was further validated in BALB/c mice. The relationship between neutrophil infiltration and OS progression was analyzed in 34 primary OS tissues and 33 OS lung metastasis tissues. Mechanistically, we found that ELA2, primarily derived from tumor-associated neutrophils, cleaves full-length cyclin E1 to generate LMW-cyclin E1, which accelerates OS proliferation. Moreover, neutrophil infiltration was associated with OS lung metastasis. OS cells also induced neutrophil extracellular trap formation, which further amplified ELA2 release. Depleting neutrophils or inhibiting ELA2 significantly suppressed OS malignancy. Hence, targeting neutrophil-osteosarcoma crosstalk may be a potential novel therapeutic strategy.

Surgical resection of primary solid tumor under anesthesia remains a common practice. It has been concerned whether general anesthetics, especially volatile anesthetics, may promote the growth, migration, and invasion of cancer cells. In this study, we examined the effects of sevoflurane on human glioblastoma cells and determined the role of cluster of differentiation (CD) 44, a cell surface protein involved in cell growth, migration, and invasion, in sevoflurane’s effects. We showed that exposure to 1%–4% sevoflurane did not change the cell proliferation, but concentration-dependently increased the invasion of human glioblastoma U251 cells. Furthermore, 4% sevoflurane significantly increased the migration and colony-forming ability of U251 cells. Similar results were observed in human glioblastoma A172 cells. Exposure to sevoflurane concentration-dependently increased the activity of calpains, a group of cysteine proteinases, and CD44 protein in U251 and A172 cells. Knockdown of CD44 with siRNA abolished sevoflurane-induced increases in calpain activity, migration, invasion, and colony-forming ability of U251 cells. Inhalation of 4% sevoflurane significantly increased the tumor volume and invasion/migration distance of U87 cells from the tumor mass in the nude mice bearing human glioblastoma U87 xenograft in the brain. The aggravation by sevoflurane was attenuated by CD44 silencing. In conclusion, sevoflurane increases the migration, invasion, and colony-forming ability of human glioblastoma cells in vitro, and their tumor volume and invasion/migration in vivo. Sevoflurane enhances these cancer cell biology features via increasing the expression of CD44.

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.