A new gold(I) phosphine complex induces apoptosis in prostate cancer cells by increasing reactive oxygen species.

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis. It is frequently overexpressed in various cancer cells, including prostate cancer, making it a promising target for the development of anti-cancer drugs. In this study, we screened a series of newly designed complexes of gold(I) phosphine. Specifically, Compound 5 exhibited the highest cytotoxicity against prostate cancer cells and demonstrated stronger antitumor effects than commonly used drugs, such as cisplatin and auranofin. Importantly, our mechanistic study revealed that Compound 5 effectively inhibits the TrxR system in vitro. Additionally, Compound 5 promoted intracellular accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and irreversible apoptosis in prostate cancer cells. Our in vivo xenograft study further demonstrated that Compound 5 has excellent antitumor activity against prostate cancer cells, but does not cause severe side effects. These findings provide a promising lead Compound for the development of novel antitumor agents targeting prostate cancer and offer a valuable tool for investigating biological pathways involving TrxR and ROS modulation.

Clinical profiles and related factors in tuberculosis patients with positive sputum smear mycobacterium tuberculosis tests.

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75-89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.

Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to α,ß,γ,δ-unsaturated sulfonic esters: controlling regioselectivity by rational selection of electron-withdrawing groups.

Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to electron-deficient dienes was developed through rational selection of electron-withdrawing groups on the dienes. Various chiral allylic phosphine derivatives were synthesized in good yields with high enantioselectivity (up to 96% ee).

Palladium-catalyzed asymmetric addition of diarylphosphines to α,ß-unsaturated sulfonic esters for the synthesis of chiral phosphine sulfonate compounds.

Highly stereoselective addition of diarylphosphines to α,ß-unsaturated sulfonic esters catalyzed through a PCP pincer-Pd complex is developed to synthesize chiral phosphine sulfonic esters with excellent enantioselectivity (up to 99.5% ee). The transformation of the chiral adduct into a useful palladium phosphine sulfonate complex is also demonstrated.

Catalytic asymmetric construction of chiral hydropyridazines via conjugate addition of N-monosubstituted hydrazones to enones.

The first example of a highly enantioselective and scalable formal diaza-ene reaction between N-monosubstituted hydrazones and enones catalyzed by a simple chiral primary-second diamine salt has been developed. The catalytic process provides a highly practical and stereoselective synthetic method for chiral hydropyridazines.