Organic Photoredox-Catalyzed Hydrosilylation of Vinylboronic Esters for the Synthesis of Geminal and Vicinal Borosilanes.

Geminal and vicinal borosilanes have unique applications in functional materials and synthetic transformations. Herein, a convenient method for the synthesis of geminal and vicinal borosilanes is developed via photoredox metal-free hydrosilylation of vinylboronic esters. This strategy features the advantages of high atom economy, environmental friendliness, and excellent functional group compatibility. The mechanism studies reveal that the catalytic reaction goes through photoredox HAT catalysis and a radical addition pathway.

Photoredox Catalyzed Tandem Denitrogenative [4 + 2] Annulation of 1,2,3-Benzotriazin-4(3H)-ones with Terminal Olefins.

The dihydroisoquinolones skeleton is ubiquitous in natural products and biological molecules. Reported strategies for constructing dihydroisoquinolones usually require noble metal catalysts or stoichiometric oxidants, which limit their wide applications. Herein, we developed a photoredox catalyzed tandem denitrogenative [4 + 2] annulation reaction of 1,2,3-benzotriazin-4(3H)-ones with terminal olefins. A variety of dihydroisoquinolones can be accessed in moderate to excellent yield. This protocol features high atom-economy, mild reaction conditions, and is external oxidant-free, enabling the synthesis of various substituted dihydroisoquinolones.

Identification of antibacterial constituents from Rhododendron simsii Planch with an activity-guided method.

Bacterial infections and antibiotic resistance pose significant public health challenges globally. Natural products serve as valuable sources for discovering antimicrobial agents. Rhododendron simsii Planch, a folk medicine, is traditionally used to treat various inflammatory diseases. In this study, we investigated the antibacterial metabolites derived from R. simsii Planch. Rhodosimsiin A (1), bearing a 1,5-seco-1,6 and 3,6-epoxy grayanane diterpene skeleton, representing a novel 5/6/7/6/5 pentacyclic ring system, and 3ß,16α-dihydroxy-6ß-ethoxy-14ß-acetoxy-grayan-1(5)-ene-10-one (4), which represents the first example of the degradation of C-20 and carbonylation in C-10 diterpenoid, together with two new grayanane diterpenes (2-3), three new triterpenes (13-15), and known analogs (5-12, 16-30), were isolated from the leaves of R. simsii Planch by using the bioassay-guided method. Their structures were elucidated by comprehensive spectroscopic analyses, and absolute configurations were established by single-crystal X-ray diffraction and calculated ECD spectra. Compounds 14, 15, 18, 20, 27, 28, and 30 exhibited potent antibacterial activity with an MIC50 of 1.4-24.3 µg/mL against Staphylococcus aureus. The findings of this research indicate that secondary metabolites derived from R. simsii Planch are promising natural antimicrobial candidates.

Photoredox-catalyzed C(sp2)-H trifluoromethylation of 3-methylene-isoindolin-1-ones under metal-free conditions.

A facile synthetic method for direct C(sp2)-H bond trifluoromethylation of 3-methylene-isoindolin-1-ones under visible-light-induced metal-free conditions is presented. This protocol features mild reaction conditions, broad substrate scope and excellent functional group tolerance, resulting in a range of structurally diverse trifluoromethylated products in good to excellent yields.

Electroreductive Cross-Coupling between Aromatic Aldehydes and Chlorosilanes Enabling the Synthesis of α-Silyl Alcohols.

α-Silyl alcohols are powerful structural motifs for pharmaceutical chemistry, materials chemistry, and organic synthesis. The limitations of current synthetic techniques encompass a requirement for difficult-to-obtain silyl precursors, noble-metal catalysts, and narrow substrate scopes. Here, we developed a general synthetic method for α-silyl alcohols through electroreductive cross-coupling of aldehydes and chlorosilane. This method features easily available reagents, mild conditions, and a wide substrate scope. The establishment of this protocol will provide an alternative for access to α-silyl alcohols.

Electroreductive carboxylation of benzylphosphonium salts with CO2 through the cleavage of the C(sp3)-P bond.

Herein, a electroreductive carboxylation of benzylphosphonium salts was achieved by the cleavage of the C(sp3)-P bond, and various valuable arylacetic acids could be synthesized by this strategy. Also, based on control experiments and previous studies, a plausible reaction mechanism was proposed to explain the reaction process. The establishment of this procedure will provide a new paradigm for the functionalization of alkyl phosphonium salts.

Safety and efficacy of peripheral metaraminol infusion in patients with neurological conditions: a single-center retrospective observational study.

Introduction: Metaraminol is a sympathomimetic amine vasopressor that can be administrated through a peripheral venous access. However, limited evidence restricts its application in critically ill patients. This study aimed to investigate the safety and efficacy of peripheral metaraminol infusion in patients with neurological conditions. Methods: Patients who received peripheral metaraminol infusion between May 2019 and April 2022 were recruited. Data on baseline characteristics, clinical parameters, and infusion-related complications were retrospectively collected and analyzed. Results: 273 patients who received metaraminol were enrolled. Of these, 35 (12.8%) patients required central venous catheter insertion due to inability in achieving hemodynamic stability following peripheral metaraminol monotherapy. In 29,574.2 hours of vasopressor infusion, metaraminol infusion resulted achievement of the target blood pressure 73.4% of the time. Meanwhile, adverse events occurred in 5 patients and resolved after local tissue treatment. Discussion: Metaraminol could provide hemodynamic support and avoid complications associated with a central venous catheter and delay in vasopressor administration. Through careful and close monitoring, peripheral metaraminol infusion is safe and feasible for patients with neurological conditions. Future large-scale, prospective, multicenter studies are needed to evaluate the safety and efficacy of metaraminol infusion through a peripheral intravenous catheter.

Electrochemical benzylic deuteration of p-QMs enabling the synthesis of benzylic deuterated diarylmethanes.

Herein, electroreductive umpolung benzylic deuteration of p-QMs using cheap and easily accessible D2O as a deuterium source is reported. Various value-added benzylic deuterated diarylmethanes can be synthesized without the requirement of noble metal catalysts, redox reagents, and strong bases. The establishment of this protocol will provide an alternative strategy for acquiring benzylic deuterated diarylmethanes.

Electroreductive Arylcarboxylation of Styrenes with CO2 and Aryl Halides via a Radical-Polar Crossover Mechanism.

2,3-Diaryl propanoic acids are important structures as a result of their widespread presence in numerous bioactive compounds. However, the limitations of existing synthetic techniques include the requirement for costly catalysts and limited substrates. Here, we developed a novel electroreductive arylcarboxylation of alkenes with CO2 based on a radical-polar crossover pathway assisted by easily accessible dimethyl terephthalate as a reductive mediator. This method will provide an efficient strategy for the synthesis of 2,3-diarylpropanoic acids.

Silylation and (Hetero)aryl/alkenylation of Unactivated Alkenes via Radical-Mediated Distal 1,4-Migration with Hydrosilanes under Organophotocatalysis.

We report a novel organic photoredox catalysis to achieve unprecedented γ-(hetero)aryl/alkenyl-δ-silyl aliphatic amines via silyl-mediated distal (hetero)aryl/alkenyl migration of aromatic/alkenyl amines bearing unactivated alkenes with hydrosilanes. This protocol features mild and metal-free reaction conditions, high atom economy, excellent selectivity, and functional group compatibility. Mechanistic studies suggest that silylation and (hetero)aryl/alkenylation involve photoredox hydrogen atom transfer catalysis and subsequent 1,4-migration of a remote (hetero)aryl/alkenyl group from nitrogen to carbon.

Photoredox Synthesis of Silicon-Containing Isoindolin-1-ones and Deuterated Analogues Through Hydrosilylation and Deuterium-silylation.

An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.

Difluoromethylation-Carboxylation and -Deuteration of Alkenes Triggered by Electroreduction of Difluoromethyltriphenylphosphonium Bromide.

It is significant to develop novel difluoromethylation methods because of the important roles of difluoromethyl groups in the medicinal chemistry and material industries. Here, we developed a novel difluoromethylation-carboxylation and difluoromethylation-deuteration method triggered by a difluoromethyl radical generated by electroreduction of stable and easily available difluoromethyltriphenylphosphonium bromide. Various molecules containing difluoromethyl and carboxyl or deuterium groups can be synthesized through this method. The establishment of this method will provide an alternative to radical difluoromethylation reactions.

Photoredox Metal-Free Synthesis of Unnatural ß-Silyl-α-Amino Acids via Hydrosilylation.

An efficient, practical and metal-free methodology for the synthesis of ß-silyl-α-amino acid motifs via photoredox and hydrogen atom transfer (HAT) process is described. This protocol enables the direct hydrosilylation of dehydroalanine derivatives and tolerates a wide array of functional groups and synthetic handles, leading to valuable ß-silyl-α-amino acids with moderate to good yields.

Magnesium-Mediated Umpolung Carboxylation of p-Quinone Methides with CO2.

Magnesium-mediated reductive carboxylation of p-QMs with CO2 via an Umpolung strategy has been developed, which can be used for the preparation of various aryl acetic acids. This protocol featured high atom economy, mild conditions, and operational simplicity. The creation of this Umpolung carboxylation of p-QMs will unprecedentedly extend the application of p-QMs to nucleophilic reagents.

Thrust generation and propulsive efficiency in dolphin-like swimming propulsion.

Given growing interest in emulating dolphin morphology and kinematics to design high-performance underwater vehicles, the current research effort is dedicated to studying the hydrodynamics of dolphin-like oscillatory kinematics in forward propulsion. A computational fluid dynamics method is used. A realistic three-dimentional surface model of a dolphin is made with swimming kinematics reconstructed from video recording. The oscillation of the dolphin is found to enhance the attachment of the boundary layer to the posterior body, which then leads to body drag reduction. The flapping motion of the flukes is found to generate high thrust forces in both the downstroke and the upstroke, during which vortex rings are shed to produce strong thrust jets. The downstroke jets are found to be on average stronger than the upstroke jet, which then leads to net positive lift production. The flexion of the peduncle and flukes is found to be a crucial feature of dolphin-like swimming kinematics. Dolphin-inspired swimming kinematics were created by varying the flexion angle of the peduncle and flukes, which then resulted in significant performance variation. The thrust benefits and propulsive efficiency benefits are associated with a slight decrease and slight increase of the flexion of the peduncle and flukes, respectively.

m6A modification-tuned sphingolipid metabolism regulates postnatal liver development in male mice.

Different organs undergo distinct transcriptional, epigenetic and physiological alterations that guarantee their functional maturation after birth. However, the roles of epitranscriptomic machineries in these processes have remained elusive. Here we demonstrate that expression of RNA methyltransferase enzymes Mettl3 and Mettl14 gradually declines during postnatal liver development in male mice. Liver-specific Mettl3 deficiency causes hepatocyte hypertrophy, liver injury and growth retardation. Transcriptomic and N6-methyl-adenosine (m6A) profiling identify the neutral sphingomyelinase, Smpd3, as a target of Mettl3. Decreased decay of Smpd3 transcripts due to Mettl3 deficiency results in sphingolipid metabolism rewiring, characterized by toxic ceramide accumulation and leading to mitochondrial damage and elevated endoplasmic reticulum stress. Pharmacological Smpd3 inhibition, Smpd3 knockdown or Sgms1 overexpression that counteracts Smpd3 can ameliorate the abnormality of Mettl3-deficent liver. Our findings demonstrate that Mettl3-N6-methyl-adenosine fine-tunes sphingolipid metabolism, highlighting the pivotal role of an epitranscriptomic machinery in coordination of organ growth and the timing of functional maturation during postnatal liver development.

The Interactive Effects of Deficit Irrigation and Bacillus pumilus Inoculation on Growth and Physiology of Tomato Plant.

The effects of inoculating plant growth promoting rhizobacteria (PGPR) and soil water deficits on crop growth and physiology remain largely unknown. Here, the responses of leaf gas exchange, growth, and water use efficiency (WUE) of tomato plants to Bacillus pumilus (B.p.) inoculation under four irrigation strategies (I1-I4) were investigated in a greenhouse. Results showed that soil water deficits, especially at I4 (20%, v/v), significantly decreased leaf stomatal conductance (gs), transpiration rate (Tr), and photosynthetic rate (An), and the decrease of gs and Tr were more pronounced than An. Reduced irrigation regimes significantly lowered dry matter and plant water use both in the non-B.p. control and the B.p. plants, while reduced irrigation significantly increased plant WUE, and B.p. inoculation had little effect on this parameter. Synergistic effects of PGPR and deficit irrigation on leaf gas exchange, leaf abscisic acid content, and stomatal density were found in this study, and specifically, B.p. treated plants at I4 possessed the highest WUE at stomatal and leaf scales, suggesting that B.p. inoculation could optimize water use and partly alleviate the negative effects of soil water deficit. These findings provide useful information for effective irrigation management and the application of PGPR in agriculture in the future.

Efficacy and cost of double filtration plasmapheresis in severe hypertriglyceridemia-induced pancreatitis: A retrospective observational study.

BACKGROUND: The value of double filtration plasmapheresis (DFPP) in severe hypertriglyceridemia-induced pancreatitis (sHTGP) is controversial. This study aimed to investigate the efficacy of DFPP on clinical outcomes in patients with sHTGP and the costs associated with the procedure. METHODS: Patients who underwent DFPP after admission between January 2016 and December 2021 were recruited. Data on lipid profile, clinical parameters, and costs were retrospectively collected and analyzed. RESULTS: Fifty sHTGP patients who received DFPP were enrolled. All of the lipid profile were significantly reduced and maintained a downward trend. The APACHE II score on admission was higher and the reduction after DFPP was more obvious (P < 0.05) in patients with higher triglyceride (TG) levels (≥33.9 mmol/L) than in patients with lower TG levels. More material fees were expended in the higher TG group due to more DFPP sessions (P < 0.05), but no significant differences existed in total hospital costs between the two groups. CONCLUSION: DFPP could rapidly and effectively reduce TGs to a safe level. APACHE II score reduction was obvious in patients with TGs ≥33.9 mmol/L and was associated with lipid profile changes. DFPP may benefit sHTGP patients with a TG level higher than the current initiation threshold.

LRP1-Mediated Endocytosis May Be the Main Reason for the Difference in Cytotoxicity of Curcin and Curcin C on U2OS Osteosarcoma Cells.

Curcin and Curcin C, both of the ribosome-inactivating proteins of Jatropha curcas, have apparent inhibitory effects on the proliferation of osteosarcoma cell line U20S. However, the inhibitory effect of the latter is 13-fold higher than that of Curcin. The mechanism responsible for the difference has not been studied. This work aimed to understand and verify whether there are differences in entry efficiency and pathway between them using specific endocytosis inhibitors, gene silencing, and labeling techniques such as fluorescein isothiocyanate (FITC) labeling. The study found that the internalization efficiency of Curcin C was twice that of Curcin for U2OS cells. More than one entering pathway was adopted by both of them. Curcin C can enter U2OS cells through clathrin-dependent endocytosis and macropinocytosis, but clathrin-dependent endocytosis was not an option for Curcin. The low-density lipoprotein receptor-related protein 1 (LRP1) was found to mediate clathrin-dependent endocytosis of Curcin C. After LRP1 silencing, there was no significant difference in the 50% inhibitory concentration (IC50) and endocytosis efficiency between Curcin and Curcin C on U2OS cells. These results indicate that LRP1-mediated endocytosis is specific to Curcin C, thus leading to higher U2OS endocytosis efficiency and cytotoxicity than Curcin.