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Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors mobilize and activate the anti-tumor activity of the immune system by blocking the inhibitory effects of the PD-1/PD-L1 signaling pathway in T cells. Several anti-PD-1 or -PD-L1 monoclonal antibodies have been approved for the treatment of advanced solid tumors. However, most of immune checkpoint inhibitors (ICIs) are administered via intravenous infusion, which is inconvenient and leads to unsatisfactory patient compliance in the treatment process. Therefore, subcutaneous envafolimab is a potential treatment modality for advanced solid tumors.A phase I clinical trial showed that the safety and pharmacokinetic profiles of envafolimab were similar to those of other traditional antibodies. Additionally, clinical findings from a phase II trial revealed that envafolimab monotherapy exhibited satisfactory clinical therapeutic effects and no significant adverse events in patients with microsatellite instability-high/deficient mismatch Repair (MSI-H/dMMR) solid tumors who failed at least one line of prior systemic therapy.Subcutaneous envafolimab may serve as a more convenient and acceptable treatment modality than those approved PD-1/PD-L1 inhibitors for patients with an advanced solid tumor, which may revolutionize the modes of immunotherapy in the future.

Side-chain tailoring is a promising method to optimize the performance of organic solar cells (OSCs). However, asymmetric alkyl chain-based small molecular acceptors (SMAs) are still difficult to afford. Herein, we adopted a novel asymmetric n-nonyl/undecyl substitution strategy and synthesized two A-D1A'D2-A double asymmetric isomeric SMAs with asymmetric selenophene-based central core for OSCs. Crystallographic analysis indicates that AYT9Se11-Cl forms a more compact and order intermolecular packing compared to AYT11Se9-Cl, which contributed to higher electron mobility in neat AYT9Se11-Cl film. Moreover, the PM6:AYT9Se11-Cl blend film shows a better morphology with appropriate phase separation and distinct face-on orientation than PM6:AYT11Se9-Cl. The OSCs with PM6:AYT9Se11-Cl obtain a superior PCE of 18.12% compared to PM6:AYT11Se9-Cl (17.52%), which is the best efficiency for the selenium-incorporated SMAs in binary BHJ OSCs. Our findings elucidate that the promising double asymmetric strategy with isomeric alkyl chains precisely modulates the crystal packing and enhances the photovoltaic efficiency of selenophene-incorporated SMAs.

Despite dihalogenation of terminals is an effective strategy to achieve efficient nonfullerene acceptors (NFAs)-based organic solar cells (OSCs), hetero-dihalogenated terminals are quite difficult to obtain. Here, we firstly synthesized two new hetero-dihalogenated terminals (FCl-IC and FBr-IC) with a pair of fluorine/chlorine or fluorine/bromine at one terminal and three NFAs (Y-BO-FCl, Y-BO-FBr, and Y-BO-ClBr) with three hetero-dihalogenated terminals (FCl-IC, FBr-IC, and ClBr-IC) in a general process for OSCs, respectively. Y-BO-FCl neat film presents slightly lower energy level in comparison with those of Y-BO-FBr and Y-BO-ClBr. We, for the first time, obtained the single crystals of hetero-dihalogenated NFAs. From Y-BO-ClBr single crystal to fluorinated acceptor single crystals, the crystal systems and the intermolecular packing motifs have been significantly improved. The crystallographic and theoretical analysis indicate that Y-BO-FCl exhibits the most planar molecular geometry, the smallest intermolecular packing distance and the largest π−π electronic coupling among these acceptors. Moreover, PM6:Y-BO-FCl blend films present more order face-on orientation crystallinity, more suitable fiber-like phase separation, higher and more balanced charge mobility, weaker charge recombination in comparison with those of PM6:Y-BO-FBr and PM6:Y-BO-ClBr. As a result, up to remarkable PCE of 17.52% with enhanced FF of ca. 78% was achieved in binary Y-BO-FCl:PM6 devices compared to that of PM6:Y-BO-FBr (16.47%) and PM6:Y-BO-ClBr (13.61%), which is the highest efficiency for the hetero-halogenated NFAs-based OSCs. Our investigations demonstrate that fluorine/chlorine hetero-dihalogenated terminal is a new and effective synergistic strategy to induce significant difference in single crystallography and achieve high-performance hetero-halogenated NFAs-based OSCs.

Herein, we synthesized new hetero-halogenated end groups with well-determined fluorinated and chlorinated substitutions (o-FCl-IC and FClF-IC), and synthesized regioisomer-free small molecular acceptors (SMAs) Y-Cl, Y-FCl, and Y-FClF with distinct hetero-halogenated terminals, respectively. The single-crystal structures and theoretical calculations indicate that Y-FClF exhibits more compact three-dimensional network packing and more significant π-π electronic coupling compared to Y-FCl. From Y-Cl to Y-FCl to Y-FClF, the neat films exhibit a narrower optical band gap and gradually enhanced electron mobility and crystallinity. The PM6 : Y-FClF blend film exhibits the strongest crystallinity with preferential face-on molecular packing, desirable fibrous morphology with suitable phase segregation, and the highest and balanced charge mobilities among three blend films. Overall, the PM6 : Y-FClF organic solar cells (OSCs) deliver a remarkable efficiency of 17.65 %, outperforming the PM6 : Y-FCl and PM6 : Y-Cl, which is the best PCE for reported hetero-halogens-based SMAs in binary OSCs. Our results demonstrate that difluoro-monochloro hetero-terminal is a superior regio-regular unit for enhancing the intermolecular crystal packing and photovoltaic performance of hetero-halogenated SMAs.

A two-dimensional electron-rich fused-ring moiety (ClBDSe) based on benzo[1,2-b:4,5-b']diselenophene is synthesized. Three copolymers (PBDT-Se, PBDSe-T, and PBDSe-Se) are obtained by manipulating the connection types and number of selenophene units on the conjugated main chains with two 2D fused-ring units and two different π-bridges, respectively. In comparison with PBDT-Se and PBDSe-Se, PBDSe-T with benzo[1,2-b:4,5-b']diselenophene unit and thiophene π-bridge exhibits the deepest HOMO energy level and the strongest crystallinity in neat films. The PBDSe-T:Y6 blend film exhibits the best absorption complementarity, the most distinctive face-on orientation with proper phase separation, the highest carrier mobilities, and the lowest charge recombination among three blend films. Finally, the PBDSe-T:Y6-based device delivers an impressive power conversion efficiency (PCE) of 14.50 %, which is higher than those of PBDT-Se:Y6 and PBDSe-Se:Y6. Moreover, a decent open-circuit voltage (Voc ) of 0.89 V with a remarkably small energy loss of 0.44 eV is achieved for PBDSe-T:Y6. The efficiency of 14.50 % is the highest value for selenophene-containing copolymer-based binary organic solar cells (OSCs). This study provides evidence that introduction of 2D-benzo[1,2-b:4,5-b']diselenophene as a fused electron-rich unit with π-bridging into copolymeric donors is a valid strategy for providing high Voc and excellent PCE simultaneously in selenophene-based OSCs.

Solvents, components of pesticide emulsifiable concentrates (ECs), emit quantities of volatile organic compounds (VOCs) into the atmosphere. In the air, their active involvement in oxidative chemical reactions with oxidants exposed to ultraviolet solar radiation can result in the formation of ozone. The quantitative assessment of VOC emissions from agricultural pesticide applications remains hampered by many factors, especially the volatility coefficient of solvents in pesticides. Therefore, this study identified solvents in 20 widely used pesticide products in China. The volatility coefficients of the solvents were investigated based on a spraying test to evaluate VOC emissions from agricultural pesticide applications and their ozone formation potential (OFP). The results suggest that VOC emissions from agricultural pesticide applications amount to 0.60 Mt in 2017, with insecticides, fungicides, and herbicides contributing 0.39 Mt, 0.12 Mt, and 0.09 Mt of VOCs, respectively. Since VOC emission and maximum incremental reactivity (MIR) led to an OFP value (2.1 g ozone/g product) for insecticides, a primary consideration should be to decrease use of solvents with high volatility coefficients and large MIR values in insecticide products. This work could provide valuable insights regarding response options to reduce VOC emissions and ozone formation.

Intramolecular Cl-S non-covalent interaction is introduced to modify molecular backbone of a benzodithiophene terthiophene rhodamine (BTR) benchmark structure, helping planarize and rigidify the molecular framework for improving charge transport. Theoretical simulations and temperature-variable NMR experiments clearly validate the existence of Cl-S non-covalent interaction in two designed chlorinated donors and explain its important role in enhancing planarity and rigidity of the molecules for enhancing their crystallinity. The asymmetric isomerization of side-chains further optimizes the molecular orientation and surface energy to strike a balance between its crystallinity and miscibility. This carefully manipulated molecular design helps result in increased carrier mobility and suppressed charge recombination to obtain simultaneously enhanced short-circuit current (J

How to manipulate the phase separation and molecular arrangement to meet the need of efficient charge generation and extraction remains a long-standing challenge in all-small-molecule organic solar cells (ASM-OSCs). Herein, a small molecule acceptor Y7 as a morphology modulator was incorporated into a B1:BO-4Cl matrix to fabricate ternary ASM-OSCs. Y7 possesses excellent compatibility with the acceptor BO-4Cl but poor compatibility with the donor B1. The two acceptors prefer to form an alloy-like structure in ternary blends due to their good compatibility, which is conducive to fine-tuning the molecular arrangement for facilitating charge extraction. The inferior compatibility originating from the strong intermolecular interaction between Y7 and B1 can provide a driving force to manipulate the phase separation between the donor and acceptor for gaining well-formed nanofibrous and bi-continuous interpenetrating networks, leading to efficient charge separation, transport and collection in ternary blends. The ternary ASM-OSCs with 10 wt% Y7 in acceptors achieve a top-ranked power conversion efficiency of 16.28% with a holistic improvement of short-circuit current density, open-circuit voltage and fill factor. This work opens a new avenue to optimize the morphology for further boosting the performance of OSCs.

Dissolved organic matter regulates the interaction between microplastics (MPs) and organic pollutants. Here, this paper investigated the effect and mechanism of humic acid (HA) on the adsorption behavior of thiacloprid at two microfibers (MFs)/water interface, and compared the differences in the performance of MFs and pure MPs. The results showed that 10 mg L

A novel peroxo-functionalized Ti

Remediation of hexavalent chromium [Cr(VI)] has been widely studied for its high mobility and toxicity. As Cr(VI) migrates in natural environment, both soils and groundwater are contaminated simultaneously. In the present study, a novel reactor combining adsorption and microbial fuel cell (A-MFC) using Platanus acerifolia leaves was developed for removing Cr(VI) from groundwater and soils. When initial Cr(VI) concentration was 50 mg/L, the adsorption efficiency of A-MFC achieved 98% after 16 h. Afterwards, the leaves were used for fabricating an MFC-integrated leaching reactor. The A-MFC significantly improved the overall Cr(VI) removal efficiency through leaching and 40% of Cr(VI) in the soil column was removed. The electrical voltage and current of A-MFC reactor achieved averagely 343 mV and 141 μA to maintain the system operation without extra energy supply. This novel A-MFC reactor is an environmentally friendly technology which achieved efficient Cr(VI) removal from groundwater and soils using natural materials, proving the concept that integrated self-remediation of Cr(VI) in contaminated soil and groundwater with natural material and energy.

OLIG2 is a transcription factor that activates the expression of myelin-associated genes in the oligodendrocyte-lineage cells. However, the mechanisms of myelin gene inactivation are unclear. Here, we uncover a non-canonical function of OLIG2 in transcriptional repression to modulate myelinogenesis by functionally interacting with tri-methyltransferase SETDB1. Immunoprecipitation and chromatin-immunoprecipitation assays show that OLIG2 recruits SETDB1 for H3K9me3 modification on the Sox11 gene, which leads to the inhibition of Sox11 expression during the differentiation of oligodendrocytes progenitor cells (OPCs) into immature oligodendrocytes (iOLs). Tissue-specific depletion of Setdb1 in mice results in the hypomyelination during development and remyelination defects in the injured rodents. Knockdown of Sox11 by siRNA in rat primary OPCs or depletion of Sox11 in the oligodendrocyte lineage in mice could rescue the hypomyelination phenotype caused by the loss of OLIG2. In summary, our work demonstrates that the OLIG2-SETDB1 complex can mediate transcriptional repression in OPCs, affecting myelination.

A novel peroxo-functionalized Ti3C2Tx adsorbent with abundant surface termination groups was facilely prepared in situ to remove aqueous anionic and cationic dyes. The adsorption behavior of methylene blue on peroxo-functionalized Ti3C2Tx was systematically investigated by adsorption kinetics, isotherms, and thermodynamics. Compared with Ti3C2Tx, the adsorption capacities of peroxo-functionalized Ti3C2Tx for cationic dyes methylene blue (558.0 mg g−1), rhodamine B (524.6 mg g−1) and anionic dyes methyl orange (292.6 mg g−1), congo red (258.2 mg g−1) were increased at room temperature without adjustment of pH, background ions and humic acid, etc of the contaminant solution by 7.9, 5.3, 5.9 and 4.6 times, respectively. In addition, peroxo-functionalized Ti3C2Tx could well tolerate the effects of pH, ionic strength, and humic acid. As revealed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, the adsorption mechanism of peroxo-functionalized Ti3C2Tx for anionic and cationic dyes was mainly attributed to the electrostatic interaction, hydrogen bonding interaction, and noncovalent surface-π attraction interaction. This study demonstrates a facile modification strategy for Ti3C2Tx adsorbent materials and aims to provide insights for the development of excellent Ti3C2Tx-based adsorbent materials.

Removal of hexavalent chromium [Cr(VI)] from soils and water has been widely studied for its high toxicity. Although leaching method is viewed as an effective approach to eliminate Cr(VI) and some studies attempted to enhance leaching performance via the external electric field, there is little knowledge about the influential factor in electro-leaching system on Cr(VI) removal performance. In this study, an electro-leaching technology was developed for removing Cr(VI) from groundwater aquifer to comprehensively discuss the correlation between the operational parameters and Cr(VI) removal efficiency. When the applied voltage was 20 V and the initial Cr(VI) concentration was 40 mg/kg, Cr(VI) removal efficiency achieved 99.9% in 120 min in the electro-leaching system, 15% higher than the system without the electric field. Cr(VI) removal efficiencies increased with the voltage demonstrating the significant enhancement of the electro-leaching method in removing Cr(VI). When Cr(VI) concentration climbed to 120 mg/kg, Cr(VI) removal efficiency remained above 85%. The effects of different voltages, Cr(VI) concentrations, pollutant distribution and salt content of leaching solution on the leaching effect were also investigated. Meanwhile, the relationship between the current intensity change and the amount of removed Cr(VI) during the electro-leaching process was first investigated, and the relevant model was fitted. There is a quadratic linear correlation between the amount of current change and the amount of removed Cr(VI). This novel electro-enhanced leaching method can effectively remove Cr(VI) from contaminated groundwater aquifer by enhancing the migration of charged contaminant ions during the leaching process, and it is worthy of further study of heavy metal remediation.

This study investigated the early responses of four common food crops (Italian lettuce, radish, wheat and corn) by exposing their seeds to suspensions of polystyrene nanoparticles (nano-PS) and microspheres (micro-PS). We found that the crop responses to exposure to nano-PS and micro-PS at different doses were dependent on the plant species. Among the four species, Italian lettuce was the most sensitive crop in terms of seed germination and its germination index after polystyrene exposure for 7 days was inhibited by 18.2%-36.0% compared with that of the control (p < 0.05). The root growth (root dry weight, root/shoot ratio and root length) of Italian lettuce and corn was significantly inhibited by the exposure treatment (p < 0.05), whereas that of radish and wheat was hardly affected. Analyses of antioxidant enzymatic activities, lipid peroxidation, and integrated biomarker indexes confirmed that the toxic effects of nano-PS and micro-PS on crops are likely due to oxidative stress. The observed distribution of fluorescent nano-PS in the roots or germs of the tested crops suggests that nanoplastics can be taken up by plants even at a very early growth stage (

Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal‐resolution investigation of transcriptomes with FACS‐sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron‐glia network. It is found that the peak time of GCs migration (P7‐10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7‐10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix‐Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG's transcriptomic landscapes offer an insight into the mechanism by which BG are in depth integrated in cerebellar neural network., Functional cerebellum relays on the coordinated spatiotemporal interplay between neurons and glia. The remarkable down‐regulation of components of ECM is critical for GCs migration at very narrow time window (P7–P10), and transcription factor Nfix recruits Setdb1, a tri‐methyltransferase of H3K9 to load H3K9me3 modification on ECM genes that should be repressed in BG at P7–P10.

Production of chrysanthemum (Dendranthema grandiflora) in greenhouses often requires intensive pesticide use, which raises serious concerns over food safety and human health. This study investigated uptake, translocation and residue dissipation of typical fungicides (metalaxyl-M and fludioxonil) and insecticides (cyantraniliprole and thiamethoxam) in greenhouse chrysanthemum when applied in soils. Chrysanthemum plants could absorb these pesticides from soils via roots to various degrees, and bioconcentration factors (BCFLS) were positively correlated with lipophilicity (log Kow) of pesticides. Highly lipophilic fludioxonil (log Kow = 4.12) had the greatest BCFLS (2.96 ± 0.41 g g−1), whereas hydrophilic thiamethoxam (log Kow = −0.13) had the lowest (0.09 ± 0.03 g g−1). Translocation factors (TF) from roots to shoots followed the order of TFleaf > TFstem > TFflower. Metalaxyl-M and cyantraniliprole with medium lipophilicity (log Kow of 1.71 and 2.02, respectively) and hydrophilic thiamethoxam showed relatively strong translocation potentials with TF values in the range of 0.29–0.81, 0.36–2.74 and 0.30–1.03, respectively. Dissipation kinetics in chrysanthemum flowers followed the first-order with a half-life of 21.7, 5.5, 10.0 or 8.2 days for metalaxyl-M, fludioxonil, cyantraniliprole and thiamethoxam, respectively. Final residues of these four pesticides, including clothianidin (a primary toxic metabolite of thiamethoxam), in all chrysanthemum flower samples were below the maximum residue limit (MRL) values 21 days after two soil applications each at the recommended dose (i.e., 3.2, 2.1, 4.3 and 4.3 kg ha−1, respectively). However, when doubling the recommended dose, the metabolite clothianidin remained at concentrations greater than the MRL, despite that thiamethoxam concentration was lower than the MRL value. This study provided valuable insights on the uptake and residues of metalaxyl-M, fludioxonil, cyantraniliprole and thiamethoxam (including its metabolite clothianidin) in greenhouse chrysanthemum production, and could help better assess food safety risks of chrysanthemum contamination by parent pesticides and their metabolites.

Chrysanthemum (Dendranthema grandiflora) flowers are consumed as a popular, traditional herbal tea worldwide. During tea infusion with hot water pesticide residues in chrysanthemum flowers can be transferred into tea solution, posing potential health risks to consumers. Using greenhouse chrysanthemum this study systematically investigated the transfer of metalaxyl-M, fludioxonil, cyantraniliprole, thiamethoxam, and clothianidin (a major metabolite of thiamethoxam) from dry chrysanthemum flowers to tea solution at a range of infusion repetitions, duration and water temperature. The tested pesticides were released into tea solution at varying degrees, and the maximum transfer percentage was 59.9%, 9.8%, 29.4%, 88.2% and 68.4% for metalaxyl-M, fludioxonil, cyantraniliprole, thiamethoxam, and clothianidin, respectively. The transfer of pesticides into tea solution generally increased with increasing pesticide water solubility, water temperature, infusion duration, and pesticide concentrations in dry chrysanthemum flowers, but decreased with increasing octanol-water partition coefficient and the number of infusion repetitions. Risk quotient for pesticide intake via consuming tea solution of chrysanthemum flowers (one and two times of recommended pesticide dosages) ranged from0.00003 to 0.0924, indicating a low health risk. This study provides useful information for risk assessment of pesticide residues in greenhouse chrysanthemum flowers and may help establish realistic maximum residue limit of pesticides in chrysanthemum flowers and tea solution.

Biodegradable plastics have been introduced and widely used as a promising alternative to traditional nondegradable plastics. However, the differences in sorption behavior of pesticides on nondegradable and biodegradable microplastics has been insufficiently studied. Here, four types of nondegradable [polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), polypropylene (PP)] and two types of biodegradable [polylactic acid (PLA), polybutylene succinate (PBS)] microplastics were selected to investigate the sorption mechanism of fipronil based on their sorption kinetics and isotherms. The results indicated that the sorption rates of PLA and PBS were much higher than those of PE, PP, PVC and PS and that the sorption capacities of fipronil on microplastics followed the order of PBS > PLA > PP > PE > PS > PVC. The sorption kinetics followed a pseudo-second-order kinetics model (R2 = 0.953–0.998) for all tested microplastics. External mass transport and intraparticle diffusion were the main rate controlling steps of the sorption of fipronil on microplastics. Furthermore, isotherm results indicated that a Langmuir model provided the best fit for fipronil sorption on PE, PS, PVC and PP (R2 = 0.997–0.999), while a Freundlich model was the most appropriate model for PLA and PBS (R2 = 0.998–0.999). The presence of surface O-containing functional groups and the spatial arrangement of rubbery domains are likely to affect the sorption process. The results from this work suggest that microplastics, especially biodegradable ones, may play an important role in the fate and transport of pesticides, and their effects on soil organisms (e.g., earthworms) require further investigation.