Thiosuccinimide enabled S-N bond formation to access N-sulfenylated sulfonamide derivatives with synthetic diversity.

A thiosuccinimide enabled S-N cross-coupling strategy has been established for the intermolecular N-sulfenylation of clinically approved sulfa drugs under additive-free conditions. This approach features simple operation, high chemoselectivity for sulfenylating the phenylamino group of sulfonamides, wide substrate scope, and easy scale production, affording N-sulfenylated products in moderate to excellent yields (up to 90%). In addition, we also found that this transformation can be realized in a one-pot manner by employing readily available thiols as starting materials, and the obtained sulfonamide derivatives are capable of various late-stage functionalizations, including oxidation, arylation, benzylation, and methylation.

Adapting Crystal Structure and Grain Boundaries through Sm3+ Doping in Na3Zr2Si2PO4 for Boosting Applicability in Sodium Solid-State Batteries.

Solid-state sodium batteries represent a highly promising option for future electrochemical energy storage applications. The ionic conductivity of solid-state electrolytes is one of the significant factors limiting the development of solid-state batteries. In this study, we establish that Sm3+ doping effectively boosts the ionic conductivity of Na3Zr2Si2PO12 (NZSP). The optimal composition, Na3.2Zr1.8Sm0.2Si2-PO12 (NZSP-S20), exhibits a total conductivity of 1.87 mS cm-1 at 23 °C. Structural and microscopic morphology analyses reveal that Sm3+ doping enhances the ionic conductivity of NZSP through structural modulation, phase fraction adjustment, and grain size reduction. High-frequency impedance spectroscopy (40 Hz to 110 MHz) demonstrates that bulk and grain boundaries contribute 49.4 and 50.6%, respectively, to the total conductivity. The structural and microscopic morphology analyses reveal that Sm3+ doping enhances the ionic conductivity of NZSP. Furthermore, the critical current density (CCD) attained in the symmetric cell, assembled by using NZSP-S20 as the solid-state electrolyte and NaSn alloy as the electrode, reaches 2.2 mA cm-1. These results furnish a theoretical foundation for comprehending the modification of solid-state electrolytes.

A Hepatocellular Carcinoma Targeting Nanostrategy with Hypoxia-Ameliorating and Photothermal Abilities that, Combined with Immunotherapy, Inhibits Metastasis and Recurrence.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prone to recurrence and metastasis and has no effective treatment. Unsurprisingly, its prognosis is quite poor; early detection methods and effective low-toxicity treatments are urgently needed. To achieve these goals, we designed a multifunctional, U.S. Food and Drug Administration-approved Prussian blue (PB) nanoparticle (NP) with a porous metal organic frame loaded with sorafenib (SF), conjugated with HCC-specific targeting peptide SP94 and the near-infrared dye cyanine (Cy)5.5. These NPs are amenable to multimodal imaging for dynamic monitoring of their biodistribution and tumor-targeting effects. The SP94-PB-SF-Cy5.5 NPs achieved targeted delivery and controlled SF release and exhibited good photothermal effects. In this strategy, photothermal therapy and SF treatment complement each other, reducing the side effects of SF and achieving a therapeutic effect without local tumor recurrence. In addition, the catalase-like ability of the NPs alleviates tumor hypoxia, and their photothermal effects induce immunogenic cell death, leading to the release of tumor-associated antigens. These effects combine to trigger an antitumor immune response; the NPs also displayed promising inhibitory effects on tumor metastasis and recurrence and produced an abscopal effect and long-term immunological memory when combined with antiprogrammed death-ligand 1 (PD-L1) immunotherapy. These safe, multifunctional NPs represent a valuable treatment option for HCC. In addition, this next-generation treatment model may provide some ideas for the management of HCC and other cancers.

Susceptibility of Aedes albopictus and Aedes aegypti to three imported Chikungunya virus strains, including the E1/226V variant in Taiwan.

BACKGROUND/PURPOSE: An E1/226V variant Chikungunya virus (CHIKV) efficiently transmitted by Aedes albopictus to humans poses a significant threat to public health for those areas with the presence of Aedes albopictus, including Taiwan. METHODS: We infected three imported CHIKV isolates including the E1/226V variant with Ae. albopictus and Aedes aegypti in the laboratory to understand the disease risk. Viral RNA was measured by real time reverse transcription polymerase chain reaction. RESULTS: The viral susceptibility varied by virus strain and mosquito species and strain. The Asian virus strain started to replicate at 5-6 days post infection (dpi) with the maximum virus yield, ranging from 10(3.63) to 10(3.87) at 5-10 dpi in both species. The variant CHIKV Central/East/South African (CESA) virus genotype replicated earlier at 1 dpi with the maximum virus yield ranging from 10(5.63) to 10(6.52) at 3-6 dpi in Ae. albopictus females while the nonvariant virus strain replicated at 1-2 dpi with the maximum virus yield ranging from 10(5.51) to 10(6.27) at 6-12 dpi. In Ae. aegypti, these viruses replicated at 1-2 dpi, with maximum yields at 4-5 dpi (range from 10(5.38) to 10(5.62)). CONCLUSION: We concluded that the risk of CHIKV in Taiwan is high in all distribution areas of Ae. aegypti and Ae. albopictus for the CESA genotype and that the E1/226V variant virus strain presents an even higher risk.

[Clinical observation of tramadol on postoperative painment from LASEK].

PURPOSE: To evaluate the efficacy and safety of tramadol for controlling post-operative ocular pain from laser assisted subepithelial keratomileusis (LASEK). METHODS: A randomized and controlled study was used. Tramadol tablet is taken orally two times a day plus Tobradex and Diclofenac sodium eyedrops were administered four times a day to the study group and Tobradex and Diclofenac sodium eyedrops only were administered four times a day to the control group. Slitlamp biomicroscopy and clinical scoring (0 to 4) were used to assess pain, photophobia, tearing, stinging-burning (0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severes pain; 4 = very severe pain). The assessments were made at anterioroperation, 1 day, 4 days,7 days postoperatively. RESULTS: Post-operative pain cores for the study group and the control group were 0.48 +/- 0.67 and 1.70 +/- 0.69 (P < 0.001) at 1 day, 0.18 +/- 0.39 and 0.65 +/- 0.55 (P < 0.05) at 4 days, respectively. No severe complications were found in either group. CONCLUSION: tramadol plays an important role in efficacy and safety for controlling ocular pain and inflammation after LASEK.

Safrole-DNA adducts in human peripheral blood--an association with areca quid chewing and CYP2E1 polymorphisms.

It has been recently demonstrated that safrole (4-allyl-1,2-methylenedioxybenzene)-DNA adducts are present in oral cancer tissue from patients who have chewed areca quid (AQ) containing high concentration of safrole. In this study, the presence of safrole-DNA adducts in peripheral white blood cells from 88 subjects with a known AQ chewing history and 161 matched controls were studied with the aim of identifying the adducts as a biomarker for safrole exposure. This study also analyzed the correlation between the level of safrole-DNA adducts and polymorphism of the CYP2E1 gene, alone and in combination with the GST M1 and GST T1-deletion polymorphisms. The results demonstrated the presence of safrole-DNA adducts in 83 (94.32%) of the DNA samples from subjects with current AQ chewing history and 21 (13.04%) of the control samples without known AQ chewing habit ( [Formula: see text] ). Individuals with at least one CYP2E1 c2 allele had a significant higher frequency of safrole-DNA adducts (odds ratio (OR), 4.00; 95% confidence interval (CI), 1.03-15.53) than those with the CYP2E1 c1c1 genotype while chewing less than 20 areca quids per day. In conclusion, this study demonstrates the presence of safrole-DNA adducts in peripheral blood lymphocytes (PBL), and the presence of these safrole-DNA adducts is correlated with AQ chewing. In addition, the CYP2E1 would seem to play an important role in the modulation of safrole-DNA adduct formation.

The XRCC1 399Gln polymorphism and the frequency of p53 mutations in Taiwanese oral squamous cell carcinomas.

DNA repair gene polymorphisms have been implicated as susceptibility factors in cancer development. It is possible that DNA repair polymorphisms may also influence the risk of gene mutation. The 399Gln polymorphism in the DNA repair gene XRCC1 has been indicated to have a contributive role in DNA adduct formation, sister chromatid exchange, and an increased risk of cancer development. Two hundred thirty-seven male oral squamous cell carcinomas (OSCCs) were included in a study to investigate the role of the XRCC1 194Trp, 280His, and 399Gln polymorphisms on p53 gene mutation. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the conserved regions of the p53 gene (exons 5-9). The XRCC1 genotype was determined by PCR-RFLP. Nineteen (8.02%) of the 237 OSCCs had a Gln/Gln genotype. One hundred six (43.88%) of the 237 OSCCs showed p53 gene mutations at exons 5-9. The OSCC patients with a Gln/Gln genotype exhibited a significantly higher frequency of p53 mutation than those with an Arg/Gln and an Arg/Arg genotype. After adjustment for age, cigarette smoking, areca quid chewing, and alcohol drinking, the Gln/Gln genotype still showed an independent association with the frequency of p53 mutation (odd ratio, 4.50; 95% confidence interval, 1.52-13.36). The findings support the hypothesis that XRCC1 Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in a DNA repair deficiency. This study also suggests an important role for the XRCC1 399Gln polymorphism in p53 gene mutation in Taiwanese OSCCs.