Palladium-Catalyzed Four-Component Radical Cascade Carbonylation Access to 2,3-Disubstituted Benzofuran Derivatives.

Multicomponent radical tandem reactions have emerged as a crucial technique for synthesizing complex molecules in organic chemistry. In this study, we report a palladium-catalyzed four-component difluoroalkylative carbonylation of enynes and ethyl difluoroiodoacetate. This transformation proceeds through a multistep sequential reaction that introduces reactive difluoro and carbonyl groups while constructing the benzofuran skeleton. Moreover, a variety of valuable 2,3-disubstituted benzofuran derivatives were obtained in respectable yields with excellent functional group compatibility.

Nickel-Catalyzed Narasaka-Heck Cyclization Carbonylation of Unsaturated Oxime Esters with Arylboronic Acids.

The Narasaka-Heck reaction is one of the most straightforward methods for constructing pyrroline derivatives. Herein, we report a novel nickel-catalyzed three-component carbonylation reaction, which cleverly realizes the continuous construction of C(sp3)-N bonds and C(sp3)-C(sp2) bonds and effectively promotes the synthesis of acyl-substituted pyrroline derivatives. Furthermore, this strategy not only expands the conversion pathway of γ,δ-unsaturated oxime esters but also provides a new method for the synthesis of nitrogen-containing heterocyclic compounds.

Erratum: Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming: Erratum.

[This corrects the article DOI: 10.7150/thno.28219.].

Interfacial double-coordination effect reconstructing anode/electrolyte interface for long-term and highly reversible Zn metal anodes.

The highly reversible electrochemical deposition and dissolution of zinc metal anode is a critical feature for the practical application of aqueous zinc-ion batteries (ZIBs). Nevertheless, this process is seriously hindered by the uncontrollable electrodeposition and interfacial side reactions caused by thermodynamically unstable anode/electrolyte interface (AEI). Guided by the electrode/electrolyte interface chemistry, thiamine hydrochloride (TH) as a novel additive is added into traditional ZnSO4 (ZS) electrolyte to induce sustained reversible Zn deposition/stripping. Spectroscopic characterizations and electrochemical tests reveal that TH can adsorbed on the anode surface owning to the strong double-coordination effect between N, S atoms and Zn atoms via Zn-N and Zn-S chemical bonds. In addition, there are polar hydroxyl groups in the TH molecular structure which can form hydrogen bonds with water molecules. Thus, the adsorbed TH layer can not only guide the diffusion of Zn2+ ions and achieve dendrite-free electrodeposition process, but also prevent intimate contact between water and anode to suppress the occurrence of interface side reactions. Based on these benefits, the TH additive achieves an ultra-long stable cycle lifespan to 2045 h at 1 mA cm-2 and 1 mAh cm-2. Even at a higher current density of 5 mA cm-2, prolonged cycling performance about 773 h is demonstrated. Besides, the assembled Zn//NVO full cells reveal excellent capacity retention and rate performance under practical conditions, highlighting the efficient and reliable coordination effect of TH additive at the AEI.

Effect analysis of 847 nasopharyngeal carcinoma cases treated with intensity modulated radiation: Experience and suggestions.

OBJECTIVES: To identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. METHODS: Data on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. RESULTS: The 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. CONCLUSION: NPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local-regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.

Synthesis of C-Alkyl Glycosides from Alkyl Bromides and Glycosyl Carboxylic Acids via Ni/Photoredox Dual Catalysis.

C-Alkyl glycosides, an important class of C-glycosides, are widely found in various drugs and natural products. The synthesis of C-alkyl glycosides has attracted considerable attention. Herein, we developed a Ni/photoredox catalyzed decarboxylative C(sp3)-C(sp3) coupling reaction of stable glycosylcarboxylic acids with simple aliphatic bromides to generate C-alkyl glycosides. The method successfully linked several functional molecular fragments (natural products or drugs) to a sugar moiety, showing the extensive application prospects of this transformation. Controlled experiments and DFT calculations demonstrated that the reaction pathway contains a free radical process, and a possible mechanism is proposed.

External validation of a novel nomogram for diagnosis of Protein Energy Wasting in adult hemodialysis patients.

Background: Protein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients. Methods: The novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility. Results: From September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741-0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p > 0.05). Conclusion: Our results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.

Pnictogen-Bonding Enzymes.

The objective of this study was to create artificial enzymes that capitalize on pnictogen bonding, a s-hole interaction that is essentially absent in biocatalysis.  For this purpose, stibine catalysts were equipped with a biotin derivative and combined with streptavidin mutants to identify an efficient transfer hydrogenation catalyst for the reduction of a fluorogenic quinoline substrate.  Increased catalytic activity from wild-type streptavidin to the best mutants coincides with the depth of the s hole on the Sb(V) center, and the emergence of saturation kinetic behavior.  Michaelis-Menten analysis reveals transition-state recognition in the low micromolar range, more than three orders of magnitude stronger than the millimolar substrate recognition.  Carboxylates preferred by the best mutants contribute to transition-state recognition by hydrogen-bonded ion pairing and anion-π interactions with the emerging pyridinium product.  The emergence of challenging stereoselectivity in aqueous systems further emphasizes compatibility of pnictogen bonding with higher order systems catalysis.

[Modified Fangji Huangqi Decoction alleviates renal interstitial fibrosis by inhibiting TGF-ß1/Smad/Snail signaling pathway during epithelial-mesenchymal transition].

This study investigated the effects of modified Fangji Huangqi Decoction on the expression of proteins related to epithelial-mesenchymal transition(EMT) in a mouse model of unilateral ureteral obstruction( UUO) and in a rat renal tubular epithelial cell(NRK-52E) model of fibrosis induced by transforming growth factor ß1(TGF-ß1). It aims to decipher the molecular mechanism by which modified Fangji Huangqi Decoction alleviates renal interstitial fibrosis. C57/BL mice were subjected to UUO.After the surgery, the mice were treated with 0. 5-fold and 2-fold concentrations of modified Fangji Huangqi Decoction and fosinopril sodium(positive control) for 7 days. The interstitial collagen deposition in the kidney was assessed by Masson staining. Western blot and RT-qPCR were employed to determine the expression levels of TGF-ß1, phosphorylated Smad2/3(p-Smad2/3), Smad2/3, Snail,epithelial cadherin(E-cadherin), alpha smooth muscle actin(α-SMA), and vimentin. The NRK-52E cell model induced by TGF-ß1was treated with the serum samples collected from SD rats treated with different concentrations of modified Fangji Huangqi Decoction.The CCK-8 assay was employed to examine the effects of the serum samples on NRK-52E cell proliferation. The cell morphology in different groups was observed under a microscope. Furthermore, the modeled cells were treated with the serum containing 1-fold decoction. Western blot and RT-qPCR were then employed to measure the expression levels of p-Smad2/3, Smad2/3, Snail,E-cadherin, α-SMA, and vimentin in the cells. Under the same conditions, sh RNA was used to silence the Snail gene, and measurements were repeated before and after treatment with the serum containing 1-fold decoction. The results indicated that modified Fangji Huangqi Decoction alleviated the fibrotic injury in the mouse model of UUO and the fibrosis in the NRK-52E cell model. The treatment with the decoction down-regulated the protein and m RNA levels of EMT-related indicators including p-Smad2/3, α-SMA,Snail, and vimentin, while it up-regulated the expression of E-cadherin. After sh RNA silencing of the Snail gene, the protein and m RNA levels of E-cadherin, α-SMA, and vimentin showed no significant differences before and after treatment with the serum containing the decoction. The results suggest that modified Fangji Huangqi Decoction may alleviate renal interstitial fibrosis by inhibiting the TGF-ß1/Smad/Snail signaling pathway and regulating the EMT process.

Fluoride-Mediated Aryne 1,2-Difunctionalization Involving C═S Bond Heterolysis.

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

[3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles.

An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.

An evolved artificial radical cyclase enables the construction of bicyclic terpenoid scaffolds via an H-atom transfer pathway.

While natural terpenoid cyclases generate complex terpenoid structures via cationic mechanisms, alternative radical cyclization pathways are underexplored. The metal-catalysed H-atom transfer reaction (M-HAT) offers an attractive means for hydrofunctionalizing olefins, providing access to terpenoid-like structures. Artificial metalloenzymes offer a promising strategy for introducing M-HAT reactivity into a protein scaffold. Here we report our efforts towards engineering an artificial radical cyclase (ARCase), resulting from anchoring a biotinylated [Co(Schiff-base)] cofactor within an engineered chimeric streptavidin. After two rounds of directed evolution, a double mutant catalyses a radical cyclization to afford bicyclic products with a cis-5-6-fused ring structure and up to 97% enantiomeric excess. The involvement of a histidine ligation to the Co cofactor is confirmed by crystallography. A time course experiment reveals a cascade reaction catalysed by the ARCase, combining a radical cyclization with a conjugate reduction. The ARCase exhibits tolerance towards variations in the dienone substrate, highlighting its potential to access terpenoid scaffolds.

Identification of Attractants from Three Host Plants and How to Improve Attractiveness of Plant Volatiles for Monochamus saltuarius.

As a new vector insect of pine wood nematodes in China, the Monochamus saltuarius (Coleoptera: Cerambycidae) vectors pine wilt nematodes into healthy pine trees through feeding and oviposition, resulting in huge economic losses to forestry. A promising control strategy is to develop safe and efficient attractants. This study aims to screen for the key active volatiles of Pinus koraiensis (Pinales: Pinaceae), Pinus tabuliformis (Pinales: Pinaceae), and Picea asperata (Pinales: Pinaceae) that can attract M. saltuarius, and to study the synergistic attraction of the main attractant plant volatiles with ethanol and insect aggregation pheromones. The preference of M. saltuarius for three hosts is P. koraiensis > P. tabuliformis > Picea asperata. We detected 18 organic volatiles from three host plants. Through EAG assays and indoor Y-tube behavioral experiments, 3-carene, (-)-camphor, ß-pinene, α-phellandrene, terpinolene, α-pinene, D-limonene, and myrcene were screened to have attractive effects on M. saltuarius. We found that 3-carene, ß-pinene, and α-pinene are the most attractive kairomones in field experiments, which may play a crucial role in the host localization of M. saltuarius. Ethanol has a synergistic effect on the attractant activity of 3-carene and ß-pinene, and the synergistic effect on ß-pinene is the best. The mixture of ethanol, 2-undecyloxy-1-ethanol, and ipsdienol can significantly enhance the attraction effect of ß-pinene on M. saltuarius. These new findings provide a theoretical basis for the development of attractants for adult M. saltuarius and contribute to the green control of M. saltuarius.

Minimizing Redundancy and Data Requirements of Machine Learning Potential: A Case Study in Interface Combustion.

The machine learning potential has emerged as a promising approach for addressing the accuracy-versus-efficiency dilemma in molecular modeling. Efficiently exploring chemical spaces with high accuracy presents a significant challenge, particularly for the interface reaction system. This study introduces a workflow aimed at achieving this goal by incorporating the classical SOAP descriptor and practical PCA strategy to minimize redundancy and data requirements, while successfully capturing the features of complex potential energy surfaces. Specifically, the study focuses on interface combustion behaviors within promising alloy-based solid propellants. A neural network potential model tailored for modeling AlLi-AP interface reactions under varying conditions is constructed, showcasing excellent predictive capabilities in energy prediction, force estimation, and bond energies. A series of large-scale MD simulations reveal that Li doping significantly influences the initial combustion stage, enhancing reactivity and reducing thermal conductivity. Mass transfer analysis also highlights the considerably higher diffusion coefficient of Li compared to Al, with the former being three times greater. Consequently, the overall combustion process is accelerated by approximately 10%. These breakthroughs pave the way for virtual screening and the rational design of advanced propellant formulations and microstructures incorporating alloy-formula propellants.

The fate of plastic wraps in constructed wetland: Surface structure and microbial community.

The high use of plastic wraps leads to significant environmental pollution. In this study, the surface structure and microbial community evolution of commercially available plastic wraps [polyethylene (PE), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), and polylactic acid (PLA)] in constructed wetlands (CWs) were investigated. The results indicated that all plastic wraps gradually decreased in molecular weight, crystallinity, melting, and crystallization temperatures, whereas a gradual increase was observed in the surface roughness, polymer dispersity index (PDI), carbonyl index (CI) and Shannon index of microorganisms colonizing the CWs. The aging rate of the plastic wrap was in the order: PLA > PVC > PE > PVDC, at the same site in the CWs, and it was in the order: soil surface > plant roots > subsoil, for the same plastic wrap. The diversity of microorganisms colonizing the same plastic wrap was in the order: plant roots > subsoil > soil surface. The Shannon indices of microorganisms on plastic wraps were lower than those in the soil, indicating that the diversity of microorganisms colonizing plastic wraps is limited. Additionally, the microbial community structure on the plastic surface was co-differentiated by the plastic type, placement position in the CWs, and aging time. Significantly different microbial community structures were found on the PVC and PVDC wrap surfaces, revealing that the chlorine in plastics limits microbial diversity. Unclassified members of Rhizobiaceae and Pseudomonadaceae were the dominant genera on the surface of the plastic wraps, suggesting that they may be the microorganisms involved in plastic degradation processes. The study provides valuable perspectives to facilitate a comprehensive understanding of the migration, fate, and environmental risks associated with microplastics (MPs) in wetlands.

Palladium-Catalyzed Three-Component Cascade Carbonylation Reaction to Construct Benzofuran Derivatives.

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

Hydrazone Phosphaketene as a Synthetic Platform To Obtain Three Classes of 1,2,4-Diazaphosphol Derivatives by Switchable Chemoselectivity Strategies.

We introduce switchable chemoselectivity strategies based on the hydrazone phosphaketene intermediate to synthesize three classes of 1,2,4-diazaphosphol derivatives. First, the five-membered heterocyclic P and O anion intermediates acted as nucleophilic agents in the selective construction of C-P and C-O bonds. Second, the phosphinidene served as a phosphorus synthon, allowing for the formation of C-P and C-N bonds. Finally, a stepwise mechanism, supported by DFT calculations, was invoked to explain the reaction selectivity.

Pd(II)-Catalyzed 1,2-Oxyarylation of Alkenes with O-Acylhydroxylamines as the Oxygen Source.

O-Acylhydroxylamine has been widely employed as an electrophilic amination reagent in transition-metal-catalyzed C-N coupling reactions, but its use as an electrophilic oxygen source has not been disclosed. Here, we report a Pd-catalyzed 1,2-oxyarylation of alkenes with O-acylhydroxylamines as an oxidant and an oxygen source for the first time. With simple amide as the monodentate directing group, this method features a broad substrate scope, good functional group tolerance, and mild conditions.

Interaction between hydroxymethanesulfonic acid and several organic compounds and its atmospheric significance.

The interactions of the micro-mechanism of hydroxymethanesulfonic acid (HMSA) with the typical small organic molecule in atmospheric (X = methanol, formaldehyde, formic acid, methyl formate, dimethyl ether, acetone) has been investigated by density functional theory (DFT), quantum theory of atoms in molecules (QTAIM), Generalized Kohn-Sham Enery Decomposition Analysis (GKS-EDA) and the atmospheric clusters dynamic code (ACDC). The results of DFT show that the stable six- to eight-membered ring structures are easily formed in HMSA-X clusters. According to the topological analysis results of the AIM theory and the IRI method, a strong hydrogen bonding interaction is present in the complex. GKS-EDA results show that electrostatic energy is the main contributor to the interaction energy as it accounts for 51 %-55 % of the total attraction energy. The evaporation rates of HMSA-HMSA and HMSA-HCOOH clusters were much lower than those of the other HMSA complexes. In addition, the Gibbs energy of formation (ΔG) of HMSA-X dimers is investigated under atmosphere temperature T = 217-298 K and p = 0.19-1.0 atm, the ΔG decreased with decreasing of the atmosphere temperature and increased with the decrease of atmospheric pressure, indicating that the low temperature and high pressure may significantly facilitate to the formation of dimers.

Achieving Dendrite-Free Zinc Metal Anodes via Molecule Anchoring and lon-Transport Pumping.

The potential for scale-up application has been acknowledged by researchers for rechargeable aqueous zinc-ion batteries (ZIBs). Nonetheless, the progress of the development is significantly impeded due to the instability of the interface between the zinc anode and electrolyte. Herein, efficient and environmentally benign valine (Val) were introduced as aqueous electrolyte additive to stabilize the electrode/electrolyte interface (EEI) via functional groups in additive molecules, thus achieving reversible dendrite-free zinc anode. The amino groups present in Val molecules have a strong ability to adsorb on the surface of zinc metal, enabling the construction of anchored molecular layer on the surface of zinc anodes. The strongly polar carboxyl groups in Val molecules can act as ion-transport pumps to capture zinc ions in the electric double layer (EDL) through coordination chemistry. Therefore, this reconstructed EEI could modulate the zinc ion flux and simultaneously suppress side reactions and dendritic growth of Zn. Consequently, a long stable cycling up to 1400 h at a high current density of 20 mA cm-2 is achieved. Additionally, Zn//V2O5 full cell with Val additive exhibit enhanced cyclability, retaining 77 % capacity after 3000 cycles, displaying significant potential in promoting the commercialization of ZIBs.