Precise coordination of high-loading Fe single atoms with sulfur boosts selective generation of nonradicals.

Nonradicals are effective in selectively degrading electron-rich organic contaminants, which unfortunately suffer from unsatisfactory yield and uncontrollable composition due to the competitive generation of radicals. Herein, we precisely construct a local microenvironment of the carbon nitride-supported high-loading (~9 wt.%) Fe single-atom catalyst (Fe SAC) with sulfur via a facile supermolecular self-assembly strategy. Short-distance S coordination boosts the peroxymonosulfate (PMS) activation and selectively generates high-valent iron-oxo species (FeIV=O) along with singlet oxygen (1O2), significantly increasing the 1O2 yield, PMS utilization, and p-chlorophenol reactivity by 6.0, 3.0, and 8.4 times, respectively. The composition of nonradicals is controllable by simply changing the S content. In contrast, long-distance S coordination generates both radicals and nonradicals, and could not promote reactivity. Experimental and theoretical analyses suggest that the short-distance S upshifts the d-band center of the Fe atom, i.e., being close to the Fermi level, which changes the binding mode between the Fe atom and O site of PMS to selectively generate 1O2 and FeIV=O with a high yield. The short-distance S-coordinated Fe SAC exhibits excellent application potential in various water matrices. These findings can guide the rational design of robust SACs toward a selective and controllable generation of nonradicals with high yield and PMS utilization.

Visible-Light-Induced Photoredox 1,2-Dialkylation of Styrenes with α-Carbonyl Alkyl Bromides and Pyridin-1-ium Salts.

A visible-light-driven photoredox dialkylation of styrenes with α-carbonyl alkyl bromides and pyridin-1-ium salts for the synthesis of polysubstituted 1,4-dihydropyridines is reported. This reaction enables the formation of two new C(sp3)-C(sp3) bonds in a single reaction step and provides a strategy that employs pyridin-1-ium salts as the functionalized alkylating reagents via dearomatization to directly trap the resulting alkyl radicals from radical addition of alkenes and then terminate the alkene dialkylation.

Nickel-Catalyzed Reductive Cross-Coupling of Propargylic Acetates with Chloro(vinyl)silanes: Access to Silylallenes.

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve. Herein, nickel-catalyzed reductive cross-coupling reactions between propargyl acetates and substituted vinyl chlorosilanes for the synthesis of tetrasubstituted silylallenes are described. Therein, metallic zinc is a crucial reductant that effectively enables two electrophilic reagents to selectively construct C(sp2)-Si bonds. Additionally, a Ni-catalyzed reductive mechanism involving a radical process is proposed on the basis of deuteration-labeled experiments.

Impacts of Perfluoroalkyl Substances on Aqueous and Nonaqueous Phase Liquid Dechlorination by Sulfidized Nanoscale Zerovalent Iron.

Per- and poly fluoroalkyl substances (PFASs) are often encountered with nonaqueous phase liquid (NAPL) in the groundwater at fire-fighting and military training sites. However, it is unclear how PFASs affect the dechlorination performance of sulfidized nanoscale zerovalent iron (S-nFe0), which is an emerging promising NAPL remediation agent. Here, S-nFe0 synthesized with controllable S speciation (FeS or FeS2) were characterized to assess their interactions with PFASs and their dechlorination performance for trichloroethylene NAPL (TCE-NAPL). Surface-adsorbed PFASs blocked materials' reactive sites and inhibited aqueous TCE dechlorination. In contrast, PFASs-adsorbed particles with improved hydrophobicity tended to enrich at the NAPL-water interface, and the reactive sites were re-exposed after the PFASs accumulation into the NAPL phase to accelerate dechlorination. This PFASs-induced phenomenon allowed the materials to present a higher reactivity (up to 1.8-fold) with a high electron efficiency (up to 99%) for TCE-NAPL dechlorination. Moreover, nFe0-FeS2 with a higher hydrophobicity was more readily enriched at the NAPL-water interface and more reactive and selective than nFe0-FeS, regardless of coexisting PFASs. These results unveil that a small amount of yet previously overlooked coexisting PFASs can favor selective reductions of TCE-NAPL by S-nFe0, highlighting the importance of materials hydrophobicity and transportation induced by S and PFASs for NAPL remediation.

Thioalkynes in Ring Forming Reactions.

Organic cycles play an important role in chemistry, pharmacology and material science for their unique properties. Construction of organic cycles from thioalkynes attracted increasing attention due to the facile access of thioalkynes. 2H-Azirines were synthesized successfully from thioalkynyl oxime ethers. Cyclobutanes were formed through chiral titanium catalyzed cycloaddition of thioalkynes. Cyclopentenes were afforded by annulation of thioalkynes. Thioalkynes could be also applied to synthesize thiophenes, oxazoles, benzo[b]thiophenes, 2H-chromenes, 2-phenylbenzothiazoles, diazacyclobutene, etc. In this review, construction of organic cycles from thioalkynes were highlighted. Firstly, the property and application of organic cyclic compounds were simply introduced. After presenting the general methods to access organic cycles, applications of thioalkynes as synthons to prepare organic cycles were classified and presented in detail. Based on different kinds of organic cycles obtained from thioalkynes, organic reactions for synthesis of three-, four-, five-, six-membered as well as fused cycles would be summarized and the plausible reaction mechanisms could be presented if available.

Experimental study on the microwave radiation disinfection of E. coli on SiC composite filter.

Filter is an important component in the air-conditioning system. The airborne microorganisms can be intercepted and further multiply on the filter, which might cause a secondary pollution. The present work proposed a SiC composite filter (SCF), namely combining the filter with the absorbing material SiC. The disinfection efficiency (η) and mechanism of the microwave radiation method (MRM) on E. coli and S. aureus attached to the SCF were experimentally explored. The impacts of the microwave power (P) and disinfection time (t) on η were investigated. The results show that the SCF can be heated well by the microwave, but the normal filter (NF) cannot. The MRM can effectively and rapidly disinfect bacteria on the SCF at a sufficiently high P and an appropriate t. Generally, η increases with P and t. Under a specific P, η can be only increased with t at a certain range and a peak η might be reached. When this peak is achieved, η will not be further increased with t. The disinfection by the MRM is attributed to the thermal and non-thermal effects. Specially, at P = 600 W and t = 10 min, the non-thermal effect contributes about 89.6% to the disinfection of the E. coli and about 43.1% to the S. aureus. A universal relationship between η and temperature is given for E. coli and S. aureus to predict η at various P and t. Finally, the effective temperatures required by the MRM to satisfactorily disinfect bacteria on the SCF are identified, i.e., about 41 °C for E. coli and 71 °C for S. aureus.

Can the apparent transverse relaxation rate (R2*) evaluate the efficacy of concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma? a preliminary experience.

BACKGROUND: The use of the apparent transverse relaxation rate (R2*) in nasopharyngeal carcinoma (NPC) has not been previously reported in the literature. The aim of this study was to investigate the role of the R2* value in evaluating response to concurrent chemoradiotherapy (CCRT) in patients with NPC. METHODS: Forty-one patients with locoregionally advanced NPC confirmed by pathology were examined by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) before and after CCRT, and conventional MRI was performed 3 months after the completion of CCRT. All patients were divided into a responding group (RG) and a nonresponding group (NRG), according to MRI findings 3 months after the end of treatment. The R2* values before (R2*preT) and after (R2*postT) CCRT and the ΔR2* (ΔR2*=R2*postT - R2*preT) were calculated in the tumor. RESULTS: Among the 41 patients, 26 were in the RG and 15 were in the NRG. There was no statistical difference in the R2*preT between RG and NRG (P = 0.307); however, there were significant differences in R2*postT and ΔR2* (P < 0.001). The area under the curve of R2*postT and ΔR2* for predicting the therapeutic response of NPC was 0.897 and 0.954, respectively, with cutoff values of 40.95 and 5.50 Hz, respectively. CONCLUSION: The R2* value can be used as a potential imaging indicator to evaluate the therapeutic response of locoregionally advanced NPC.

Zero-valent iron-peroxydisulfate as synergistic co-milling agents for enhanced mechanochemical destruction of 2,4-dichlorophenol: Coupling reduction with oxidation.

Mechanochemical (MC) remediation with zero-valent iron (ZVI) as co-milling agent enables the non-combustion and solvent-free disposal of solid halogenated organic pollutants (HOPs) via solid-phase reaction, but suffers from incomplete dechlorination (especially for less chlorinated chemicals). Herein, a reduction-oxidation coupling strategy using ZVI and peroxydisulfate as synergistic (ZVI-PDS) co-milling agents was investigated, with 2,4-dichlorophenol (2,4-DCP) as probe contaminant. By revisiting the MC destruction process of 2,4-DCP by ZVI, the contribution of both reductive and oxidative routes is confirmed, and the inefficient •OH generation is addressed. With ball-to-material and reagent-to-pollutant mass ratios of 30:1 and 13:1, respectively, ZVI-PDS achieves higher dechlorination ratio (86.8%) for 2,4-DCP within 5 h, outcompeting sole ZVI (40.3%) or PDS (33.9%), due to the accumulation of numerous SO4•-. As suggested by a two-compartment kinetic model, the optimal ZVI/PDS molar ratio of 4:1 is determined, which balances the relative contribution of reductive/oxidative routes and leads to a maximum mineralization efficiency of 77.4%. The analysis on product distribution verifies the generation of dechlorinated, ring-opening and minor coupling products (with low acute toxicity). This work validates the necessity to couple reduction with oxidation in MC destruction for solid HOPs, and may provide information on reagent formulation.

Paired Electrolysis Enabled Cyanation of Diaryl Diselenides with KSCN Leading to Aryl Selenocyanates.

The first example of paired electrolysis-enabled cyanation of diaryl diselenides, with KSCN as the green cyanating agent, has been developed. A broad range of aryl selenocyanates can be efficiently synthesized under chemical-oxidant- and additive-free, energy-saving and mild conditions.

Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial.

BACKGROUND: A substantial proportion of patients with unresectable stage III non-small-cell lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so sequential chemoradiotherapy is commonly used. We assessed the efficacy and safety of sugemalimab, an anti-PD-L1 antibody, in patients with stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy. METHODS: GEMSTONE-301 is a randomised, double-blind, placebo-controlled, phase 3 trial in patients with locally advanced, unresectable, stage III NSCLC, done at 50 hospitals or academic research centres in China. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had not progressed after concurrent or sequential chemoradiotherapy. We randomly assigned patients (2:1, using an interactive voice-web response system) to receive sugemalimab 1200 mg or matching placebo, intravenously every 3 weeks for up to 24 months. Stratification factors were ECOG performance status, previous chemoradiotherapy, and total radiotherapy dose. The investigators, trial coordination staff, patients, and study sponsor were masked to treatment allocation. The primary endpoint was progression-free survival as assessed by blinded independent central review (BICR) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of assigned study treatment. The study has completed enrolment and the results of a preplanned analysis of the primary endpoint are reported here. The trial is registered with ClinicalTrials.gov, NCT03728556. FINDINGS: Between Aug 30, 2018 and Dec 30, 2020, we screened 564 patients of whom 381 were eligible. Study treatment was received by all patients randomly assigned to sugemalimab (n=255) and to placebo (n=126). At data cutoff (March 8, 2021), median follow-up was 14·3 months (IQR 6·4-19·4) for patients in the sugemalimab group and 13·7 months (7·1-18·4) for patients in the placebo group. Progression-free survival assessed by BICR was significantly longer with sugemalimab than with placebo (median 9·0 months [95% CI 8·1-14·1] vs 5·8 months [95% CI 4·2-6·6]; stratified hazard ratio 0·64 [95% CI 0·48-0·85], p=0·0026). Grade 3 or 4 treatment-related adverse events occurred in 22 (9%) of 255 patients in the sugemalimab group versus seven (6%) of 126 patients in the placebo group, the most common being pneumonitis or immune-mediated pneumonitis (seven [3%] of 255 patients in the sugemalimab group vs one [<1%] of 126 in the placebo group). Treatment-related serious adverse events occurred in 38 (15%) patients in the sugemalimab group and 12 (10%) in the placebo group. Treatment-related deaths were reported in four (2%) of 255 patients (pneumonia in two patients, pneumonia with immune-mediated pneumonitis in one patient, and acute hepatic failure in one patient) in the sugemalimab group and none in the placebo group. INTERPRETATION: Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion. FUNDING: CStone Pharmaceuticals and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

CDC Like Kinase 2 plays an oncogenic role in colorectal cancer via modulating the Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality, and significant heterogeneity among patients. In this study, we aimed to explore the role and mechanism of CLK2 in CRC, a kinase that phosphorylates SR proteins involved in splicing. Based on the analysis from The Cancer Genome Atlas (TCGA) dataset and tissue microarray, we found that CLK2 was upregulated in CRC tissues and associated with a higher tumor stage and poorer overall survival. Consistent with the bioinformatics analysis, the functional experiments validated that CLK2 acted as a tumor-promoting factor in CRC progression. CLK2 knockdown suppressed aggressive cell proliferation, migration, and invasion in vitro, as well as restrained tumor growth in vivo. In terms of mechanism, we found that the Wnt/ß-catenin signaling pathway was responsible for the CLK2-induced CRC progression, based on the results of pathway enrichment analysis and subsequent experimental validation. Thus, our study, for the first time, identified the role of CLK2 in CRC development and provided a compelling biomarker for targeted therapy in CRC treatment.

Effects of oral health intervention strategies on cognition and microbiota alterations in patients with mild Alzheimer's disease: A randomized controlled trial.

We explored the effects of an oral health intervention on the oral microbiome and cognitive function of patients with mild Alzheimer's disease (AD) and determined the influence on disease progression. Sixty-six patients with mild AD were randomly assigned to intervention or control groups and received a 24-week oral health intervention and routine care, respectively. Data were collected at baseline and week 24. 16 S rRNA sequencing was used to analyze oral microbiota. After 24 weeks of oral health intervention, Kayser-Jones Brief Oral Health Status Examination (BOHSE), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Nursing Home Adjustment Scale (NHAS), and Alzheimer's Disease Cooperative Study-ADL (ADCS-ADL) scores were different between groups (p < 0.05). Subgingival plaque in patients with AD showed significant differences in the diversity and abundance of oral microbiomes, with a higher abundance of normal oral flora in the intervention group. We found oral health intervention strategies are effective in modifying subgingival microbiota differences and slowing cognitive decline in mild AD patients.

Unveiling the Role of Sulfur in Rapid Defluorination of Florfenicol by Sulfidized Nanoscale Zero-Valent Iron in Water under Ambient Conditions.

Groundwater contamination by halogenated organic compounds, especially fluorinated ones, threatens freshwater sources globally. Sulfidized nanoscale zero-valent iron (SNZVI), which is demonstrably effective for dechlorination of groundwater contaminants, has not been well explored for defluorination. Here, we show that SNZVI nanoparticles synthesized via a modified post-sulfidation method provide rapid dechlorination (∼1100 µmol m-2 day-1) and relatively fast defluorination (∼6 µmol m-2 day-1) of a halogenated emerging contaminant (florfenicol) under ambient conditions, the fastest rates that have ever been reported for Fe0-based technologies. Batch reactivity experiments, material characterizations, and theoretical calculations indicate that coating S onto the metallic Fe surface provides a highly chemically reactive surface and changes the primary dechlorination pathway from atomic H for nanoscale zero-valent iron (NZVI) to electron transfer for SNZVI. S and Fe sites are responsible for the direct electron transfer and atomic H-mediated reaction, respectively, and ß-elimination is the primary defluorination pathway. Notably, the Cl atoms in florfenicol make the surface more chemically reactive for defluorination, either by increasing florfenicol adsorption or by electronic effects. The defluorination rate by SNZVI is ∼132-222 times higher with chlorine attached compared to the absence of chlorine in the molecule. These mechanistic insights could lead to new SNZVI materials for in situ groundwater remediation of fluorinated contaminants.

Numerical investigation on the transmission and dispersion of aerosols in a 7-stories building drainage system.

In previous reports, the positive SARS-CoV-2 nucleic acid was detected in the fecal samples from confirmed pneumonia patients, suggesting a high probability of the fecal-oral transmission. To date, however, the role played by the drainage system of a high-rise building in the virus transmission is not clear and especially studies on the dynamics mechanism behind is scarce. From this point of view, the present work carries out a computational fluid dynamics (CFD) modeling to investigate the effects of the water seal effectiveness of the floor drain, the negative/positive pressures (P 1 , P 2 ) in the bathroom, temperature differential (ΔT), outside wind velocity (v), the piping fittings and the negative pressure at the cowl (P 3 ) on the transmission of the virus-laden aerosol particles in a drainage system of a typical 7-storeys residential building. The CFD models are first validated by the previous experiments in literature. Numerical results imply that the drainage system might play an essential role to the virus transmission. Then, results indicate that, the leakage risk of the aerosol particles via the floor drain with inefficient water-seal (UFD) mainly exists at the upper floors above the neutral pressure level (NPL). Besides, the negative and positive pressures at the bathroom can enhance and reduce the exposure risk of aerosol particles from the corresponding UFD, respectively. The ΔT increasing does not modify the location of the NPL. Moreover, the exposure risk of aerosol particles can be effectively avoided by the well water-sealed floor drains and/or the presence of a proper negative pressure at the cowl on the top floor. Finally, based on the CFD results, several protection suggestions on the drainage system and human activities are provided.

Near-Infrared Light-Driven Shape-Morphing of Programmable Anisotropic Hydrogels Enabled by MXene Nanosheets.

Herein, we report near-infrared (NIR) light-driven shape-morphing of programmable MXene-containing anisotropic hydrogel actuators that are fabricated through in situ free-radical copolymerization of a judiciously designed MXene nanomonomer with thermosensitive hydrogel network. A low electric field (few V mm-1 ) was found to enable a spatial distribution of MXene nanosheets and hence introduce anisotropy into the hydrogel network. Programmable anisotropic hydrogel actuators were developed by controlling ITO electrode pattern, direct-current (DC) electric field direction and mask-assisted photopolymerization. As a proof-of-concept, we demonstrate NIR light-driven shape morphing of the MXene-containing anisotropic hydrogel into various shapes and devise a four-arm soft gripper that can perform distinct photomechanical functions such as grasping, lifting/lowering down and releasing an object upon sequential NIR light exposure.

Effects of environmental factors on the removal of heavy metals by sulfide-modified nanoscale zerovalent iron.

Sulfide-modified nanoscale zerovalent iron (S-nZVI) has excellent reducing performance for heavy metals in water. The influence of environmental factors on the reactivity can be used to explore the practical feasibility of S-nZVI and analyze the reaction mechanism in depth. This study compared the removal effect and mechanism of Cu2+ and Ni2+ by nanoscale zerovalent iron (nZVI), S-nZVI, and carboxymethyl cellulose-modified nanoscale zerovalent iron (CMC-nZVI). The results show that the pseudo-first-order kinetic constant of Cu2+ removal by nZVI, S-nZVI, and CMC-nZVI was 1.384, 1.919, and 2.890 min-1, respectively, and the rate of Ni2+ removal was 0.304, 0.931, and 0.360 min-1, respectively. The removal mechanism of S-nZVI was similar to that of nZVI and CMC-nZVI. Specifically, Cu2+ was predominantly removed by reduction, while Ni2+ removal included adsorption and reduction. Environmental factors had a specific inhibitory effect on the removal of Cu2+ but had a negligible impact on Ni2+. The condition of low pH, the presence of Cl- and humic acid (HA) promoted the corrosion consumption of Fe0, in which H+ directly corroded Fe0 at low pH. At the same time, Cl- and HA inhibited the adsorption or binding of heavy metal ions on the particle surface, thereby reducing the electron transfer and utilization efficiency. The passivation of NO3- reduced the anaerobic corrosion of the material in water but suppressed the release of electrons, thereby reducing the reduction efficiency of the three types of materials. The anaerobic corrosion of S-nZVI was less affected by environmental factors, and it can still maintain more than 80% of the electronic utilization efficiency under different environmental factors, which illustrates that S-nZVI has broad prospects for practical applications in heavy metal polluted water.

Sulfur Dose and Sulfidation Time Affect Reactivity and Selectivity of Post-Sulfidized Nanoscale Zerovalent Iron.

Exposing nanoscale zerovalent iron (NZVI) to dissolved sulfide species improves its performance as a remediation agent. However, the impacts of sulfur dose and sulfidation time on morphology, sulfur content, reactivity, and selectivity of the resulting sulfidized NZVI (SNZVI) have not been systematically evaluated. We synthesized SNZVI using different sulfur doses and sulfidation times and measured their properties. The measured S/Fe molar ratio in the particles ([S/Fe]particle) was 10-500 times lower than [S/Fe]dosed but was predictable based on [S/Fe]dosed × tsulfidation. The low sulfur content (0.02-0.65 mol % S/Fe) inhibited the reaction of SNZVI with water (up to 13-fold) and increased its reactivity with trichloroethene (TCE) (up to 14-fold) and its electron efficiency (up to 20-fold). A higher [S/Fe]particle (0.86-1.13 mol % S/Fe) led to complex particle structures and lowered the resistance to electron transfer but did not improve the benefits realized at the lower S/Fe ratios. Adding small amounts of sulfur into NZVI led to more accumulation of acetylene, especially for low Fe/TCE conditions, suggesting that sulfur lowers the rate of hydrogenation of acetylene to ethene. These results show that [S/Fe]dosed × tsulfidation can be used to predict the measured S content in the particles and that affects reactivity, longevity, and electron selectivity, for post-SNZVI.

Metal-free difunctionalization of alkynes leading to alkenyl dithiocyanates and alkenyl diselenocyanates at room temperature.

A simple and practical method for the synthesis of alkenyl dithiocyanates and alkenyl diselenocyanates has been developed via stereoselective difunctionalization of alkynes with NaSCN or KSeCN at room temperature. Through this methodology, a series of alkenyl dithiocyanates and alkenyl diselenocyanates could be efficiently and conveniently obtained in moderate to good yields under mild and metal-free conditions by the simple use of oxone and PhI(OAc)2 as the oxidants.

Molecular iodine-mediated synthesis of thiocarbamates from thiols, isocyanides and water under metal-free conditions.

A simple and practical molecular iodine-mediated method for the efficient construction of thiocarbamates from isocyanides, thiols and water under metal-free and mild conditions has been developed. A variety of thiocarbamates were easily synthesized through this methodology, which has the advantages of simple operation, eco-friendly conditions, good functional group tolerance, and readily accessible raw materials.

Palladium-catalyzed selective synthesis of 3,4-dihydroquinazolines from electron-rich arylamines, electron-poor arylamines and glyoxalates.

A simple palladium-catalyzed selective synthesis of structurally diverse 3,4-dihydroquinazolines from electron-rich arylamines, electron-poor arylamines and glyoxalates has been developed under mild conditions. This reaction is carried out in a tandem manner constituted by the condensation of arylamines and glyoxalates, the selective Diels-Alder cycloaddition and oxidation processes, in which 4-nitrothiophenol was used as the key ligand.