Palladium-Catalyzed Synthesis of Functionalized Indoles by Acylation/Allylation of 2‑Alkynylanilines with Three-Membered Rings

Palladium-catalyzed synthesis of 3-acyl and -allyl indoles has been realized by merging nucleophilic cyclization of ortho-alkynylanilines with ring opening of three-membered rings such as cyclopropenones and gem-difluorinated cyclopropanes. These functionalized indoles were obtained in moderate to high yields with high stereoselectivity in both cases. This protocol provides an alternative method toward functionalized indoles under mild and redox-neutral conditions

Palladium-Catalyzed [3 + 2] Annulation of Aryl Halides with 7‑Oxa- and 7‑Azabenzonorbornadienes via C(sp² or sp³)–H Activation

A series of epoxybenzo[k]fluoranthenes, epoxy-5H-benzo[b]fluorenes, and their aza analogues have been accessed via palladium-catalyzed exo-selective [3 + 2] annulation between aryl halides and 7-oxa- and 7-azabenzonorbornadienes. The reaction is initiated by the oxidative addition of a carbon–halogen bond, with intramolecular C(sp2 or sp3)–H activation being a key step. The enantioselective version of the reaction was also briefly explored

Spontaneous Oxidation of Thiols and Thioether at the Air–Water Interface of a Sea Spray Microdroplet

The transport of dissolved organic sulfur, including thiols and thioethers, from the ocean surface to the atmosphere through sea spray aerosol (SSA) is of great importance for the global sulfur cycle. Thiol/thioether in SSA undergoes rapid oxidation that is historically linked to photochemical processes. Here, we report the discovery of a non-photochemical, spontaneous path of thiol/thioether oxidation in SSA. Among 10 investigated naturally abundant thiol/thioether, seven species displayed rapid oxidation in SSA, with disulfide, sulfoxide, and sulfone comprising the major products. We suggest that such spontaneous oxidation of thiol/thioether was mainly fueled by thiol/thioether enrichment at the air–water interface and generation of highly reactive radicals by the loss of an electron from ions (e.g., glutathionyl radical produced from ionization of deprotonated glutathione) at or near the surface of the water microdroplet. Our work sheds light on a ubiquitous but previously overlooked pathway of thiol/thioether oxidation, which could contribute to an accelerated sulfur cycle as well as related metal transformation (e.g., mercury) at ocean–atmosphere interfaces

The results of qRT-PCR for validated genes

The results of qRT-PCR for validated gene

Additional file 1 of Global incidence and death estimates of chronic kidney disease due to hypertension from 1990 to 2019, an ecological analysis of the global burden of diseases 2019 study

Supplementary Material

Table_1_Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients.docx

Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of albumin-bound paclitaxel (QL, HR, ZDTQ) among Chinese breast cancer patients.Methods: Three randomized, open-label, two-period crossover bioequivalence studies were conducted with albumin-bound paclitaxel. Each subject received a single dose of 260 mg/m2 albumin-bound paclitaxel [sponsor 1 (QL, light food), sponsor 2 (HR, fasting), sponsor 3 (ZDTQ, light food); test] or Abraxane® (reference) and was monitored for 72 h. Serum concentrations of total paclitaxel and unbound paclitaxel were measured using liquid chromatography/mass spectrometry (LC/MS), and appropriate pharmacokinetic parameters were determined by non-compartmental methods. Safety assessments included adverse events, hematology and biochemistry tests.Results: The bioequivalence analyses of the QL, HR, and ZDTQ products included 24, 23, and 24 patients, respectively. The mean t1/2 was 20.61–27.31 h for total paclitaxel. Food intake did not affect the pharmacokinetics of paclitaxel. From the comparison of total paclitaxel and unbound paclitaxel, the 90% confidence intervals (CIs) for the ratios of Cmax, AUC0−t, and AUC0−∞ were within 80.00–125.00%. The intra-subject variability ranged from 6.4–11% to 9.85–15.87% for total paclitaxel and unbound paclitaxel, respectively. Almost all subjects in the test and Abraxane® (reference) groups experienced mild or moderate adverse events. No fatal AEs or study drug injection site reactions related to these drugs were observed.Conclusion: Albumin-bound paclitaxel (QL, HR or ZDTQ; test products) showed bioequivalence to Abraxane® (reference) with lower intra-subject variability, which was less than 16% in all cases, and was well-tolerated in Chinese breast cancer patients. Twenty-two patients are enough for an albumin-bound paclitaxel bioequivalence study.</p

Histogram representation of Clusters of Orthologous Groups (COG) classification.

Histogram representation of Clusters of Orthologous Groups (COG) classification.</p

qRT-PCR–based verification and analysis of the differential expression of the identified genes.

Data are shown as means of three replicates ± standard deviation (SD). Asterisks above bars indicate significance differences between the treatment and control groups (t-test, PD.citri infected by L. attenuatum.</p

Spontaneous Oxidation of Thiols and Thioether at the Air–Water Interface of a Sea Spray Microdroplet

The transport of dissolved organic sulfur, including thiols and thioethers, from the ocean surface to the atmosphere through sea spray aerosol (SSA) is of great importance for the global sulfur cycle. Thiol/thioether in SSA undergoes rapid oxidation that is historically linked to photochemical processes. Here, we report the discovery of a non-photochemical, spontaneous path of thiol/thioether oxidation in SSA. Among 10 investigated naturally abundant thiol/thioether, seven species displayed rapid oxidation in SSA, with disulfide, sulfoxide, and sulfone comprising the major products. We suggest that such spontaneous oxidation of thiol/thioether was mainly fueled by thiol/thioether enrichment at the air–water interface and generation of highly reactive radicals by the loss of an electron from ions (e.g., glutathionyl radical produced from ionization of deprotonated glutathione) at or near the surface of the water microdroplet. Our work sheds light on a ubiquitous but previously overlooked pathway of thiol/thioether oxidation, which could contribute to an accelerated sulfur cycle as well as related metal transformation (e.g., mercury) at ocean–atmosphere interfaces