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Ai-Ling Liang,1–3,* Hai-Li Qian,4,* Ting-Ting Zhang,1–3 Ning Zhou,1–3 Hai-Juan Wang,4 Xi-Ting Men,4 Wei Qi,5 Ping-Ping Zhang,6 Ming Fu,4 Xiao Liang,4 Chen Lin,4 Yong-Jun Liu1–3 1Medical Molecular Diagnostics Key Laboratory of Guangdong, 2Department of Biochemistry and Molecular Biology, 3Department of Clinical Biochemistry, Guangdong Medical University, Dongguan, Guangdong, 4State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, 5Electroencephalogram Room, 6Department of Orthopedics, Guangdong Medical University Affiliated Hospital, Zhanjiang, Guangdong, People’s Republic of China *These authors contributed equally to this study Abstract: Breast cancer is the most common cancer and the leading cause of cancer-related death among women worldwide, with urgent need to develop new therapeutics. Targeted therapy is a promising strategy for breast cancer therapy. Stromal-derived factor-1/CXC chemokine receptor 4 (CXCR4) has been implicated in the metastasis of breast cancer, which renders it to be therapeutic target. This study aimed to evaluate the anticancer effect of fused TAT–DV1–BH3 polypeptide, an antagonist of CXCR4, and investigate the underlying mechanism for the cancer cell-killing effect in the treatment of breast cancer in vitro and in vivo. This results in a potent inhibitory effect of fused TAT–DV1–BH3 polypeptide on tumor growth and metastasis in nude mice bearing established MDA-MB-231 tumors. Fused TAT–DV1–BH3 polypeptide inhibited the proliferation of MDA-MB-231 and MCF-7 cells but did not affect that of HEK-293 cells. The fused TAT–DV1–BH3 polypeptide colocalized with mitochondria and exhibited a proapoptotic effect through the regulation of caspase-9 and -3. Furthermore, the fused TAT–DV1–BH3 polypeptide suppressed the migration and invasion of the highly metastatic breast cancer cell line MDA-MB-231 in a concentration-dependent manner. Notably, the DV1-mediated inhibition of the stromal-derived factor-1/CXCR4 pathway contributed to the antimetastasis effect, evident from the reduction in the level of phosphoinositide 3 kinase and matrix metalloproteinase 9 in MDA-MB-231 cells. Collectively, these results indicate that the apoptosis-inducing effect and migration- and invasion-suppressing effect explain the tumor regression and metastasis inhibition in vivo, with the involvement of caspase- and CXCR4-mediated signaling pathway. The data suggest that the fused TAT–DV1–BH3 polypeptide is a promising agent for the treatment of breast cancer, and more studies are warranted to fully elucidate the therapeutic targets and molecular mechanism. Keywords: bifunctional, fused polypeptide, CXCR4, breast cancer, apoptosis, transfer

Nanochannel membranes are promising materials for enantioselective sensing. However, it is difficult to make a compromise between the selectivity and permeability in traditional nanochannel membranes. Therefore, new types of nanochannel membranes with high enantioselectivity and excellent permeability should be explored for chiral analysis. Here, asymmetric catalysis strategy is reported for interfacial polymerization synthesis of chiral covalent-organic framework (cCOF) nanochannel membrane for enantioselective sensing. Chiral phenylethylamine (S/R-PEA) and 2,4,6-triformylphloroglucinol (TP) are used to prepare chiral TP monomer. 4,4',4″-triaminotriphenylamine (TAPA) is then condensed with chiral TP to obtain cCOF nanochannel membrane via a C═N Schiff-base reaction. The molar ratio of TP to S/R-PEA is adjusted so that S/R-PEA is bound to the aldehyde only or both the aldehyde and hydroxyl groups on TP to obtain chiral-induced COF (cCOF-1) or both chiral-induced and modified COF (cCOF-2) nanochannel membrane, respectively. The prepared cCOF-2 nanochannel membrane showed two times more selectivity for limonene enantiomers than cCOF-1 nanochannel membrane. Furthermore, cCOF-2 nanochannel platform exhibited excellent sensing performance for other chiral molecules such as limonene, propanediol, methylbutyric acid, ibuprofen, and naproxen (limits of detection of 19-42 ng L -1 , enantiomer excess of 63.6-86.3%). This work provides a promising way to develop cCOF-based nanochannel enantioselective sensor., (© 2024 Wiley‐VCH GmbH.)

Sensitive and selective detection of trace aflatoxin B1 (AFB1) in foods is of great importance to guarantee food safety and quality but still challenging because of its trace amount and the interference from the complex food matrix. Here, we report the integration of aptamer (Apt) and an ordered 2D covalent organic framework (COF) to solid-state anodic aluminum oxide (AAO) nanochannels (Apt/COF/AAO) for selective and sensitive detection of trace AFB1. The high specificity of Apt for AFB1 led to a selective change in the surface charge of Apt/COF/AAO and in turn the current change of the nanochannel, permitting the selective and sensitive determination of trace AFB1 in complex food samples. The developed nanofluidic sensor gave a wide linear range (1-500 pg mL -1 ), low detection limit (0.11 pg mL -1 ), and good precision (relative standard deviation of 1.5% for 11 replicate determinations of 100 pg mL -1 ). In addition, the developed sensor was successfully used for the detection of AFB1 in food samples with the recovery of 86.9%-102.5%. The coupling of Apt-conjugated 2D COF with an AAO nanochannel provides a promising way for sensitive and selective determination of food contaminants in complex samples.

Specific recognition and selective extraction of mycotoxin in environmental and food matrixes is significant to guarantee public health. Covalent organic frameworks (COFs) are promising adsorbents with tailorable functionality, but their low binding affinity and poor selectivity hamper their wide application for selective extraction of trace mycotoxin from complex matrix. Herein, we report calixarene incorporated molecular imprinting on COF to prepare molecularly imprinted calix[4]arene-containing COF (MICOF-CX4) for supramolecular recognition and specific adsorption of citrinin. Calixarene with host-guest chemistry was used as a functional monomer, while amine units with different topologies and function groups were selected to regulate MICOF-CX4 to match with citrinin. The complementary shape and supramolecular interactions of MICOF-CX4 gave highly selective recognition for citrinin. Moreover, MICOF-CX4 with vast accessible surface and plentiful imprinting sites exhibited faster adsorption kinetics and 4-fold higher adsorption capacity for citrinin adsorption than no-imprinted COF-CX4. Combination of MICOF-CX4 based solid-phase extraction with high-performance liquid chromatography-mass spectrometry allowed interference free determination of trace citrinin in real samples with a low detection limit of 0.03 ng mL -1 , good precision of 4.5 % and quantitative recovery of 88.2 %-101.4 %. The cooperative functions of calixarene and molecular imprinting make COF promising adsorbent for specific adsorption of trace targets in complex matrixes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Covalent organic frameworks (COFs) are attractive materials for sample pretreatment due to their tunable structures and functions. However, the precise recognition of contaminant in complex environmental matrices by COFs remains challenging owing to their insufficient specific active sites. Herein, we report Co 2+ coordination-assisted molecularly imprinted flexible COF (MI-COF@Co 2+ ) for selective recognition of ochratoxin A (OTA). The MI-COF@Co 2+ was prepared via one-step polymerization of 3,3-dihydroxybenzidine, 2,4,6-tris(4-formylphenoxy)- 1,3,5-triazine, Co 2+ and template. The flexible units endowed COFs with the self-adaptable ability to regulate the molecular conformation and coordinate with Co 2+ to locate the imprinted cavities. The coordination interaction greatly improved the adsorption capacity and selectivity of MI-COF@Co 2+ for OTA. The prepared MI-COF@Co 2+ was used as solid phase extraction adsorbent for high-performance liquid chromatography determination of OTA with the detection limit of 0.03 ng mL -1 and the relative standard deviation of < 2.5 %. In addition, this method permitted interference-free determination of OTA in real samples with recovery from 89.5 % to 102.8 %. This work provides a simple way to improve the selectivity of COFs for the determination of hazardous compounds in complex environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Here, we report a monomer planarity modulation strategy for room-temperature constructing molecularly imprinted-covalent organic frameworks (MI-COFs) for selective extraction of ochratoxin A (OTA). 2,4,6-triformylphloroglucinol (Tp) was used as basic building block, while three amino monomers with different planarity were employed as modulators to explore the effect of planarity on the selectivity of MI-COFs. The MI-TpTapa constructed from Tp and the lowest planarity of monomer Tapa gave the highest selectivity for OTA, and was further used as the adsorbent for dispersed-solid phase extraction (DSPE) of OTA in alcohol samples. Coupling MI-TpTapa based DSPE with high-performance liquid chromatography allowed the matrix-effect free determination of OTA in alcohol samples with the limit of detection of 0.023 μg kg -1 and the recoveries of 91.4-97.6%. The relative standard deviation (RSD, n = 6) of intra and inter day was <3.2%. This work provides a new way to construct MI-COFs for selective extraction of hazardous targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Covalent organic frameworks (COFs) has shown great potential as stationary phase in gas chromatography separation. However, designing COF stationary phases with high separation performance remains challenging. Here, we report a novel strategy to enhance the separation ability of COF stationary phases through tuning the interlayer stacking of COF. A rare interlayer modulation of 2D COFs from eclipsed-AA to slipped-AA was achieved through a two-step synthesis method. Simply changing the solvent used in step 1 allowed an interlayer modulation from slipped-AA to eclipsed-AA. As the proof-of-concept, 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphyrin (Tph) and 2,5-dihydroxyterephthalaldehyde (DHTA) were condensed to prepare 2D COF Tph-DHTA. The interlayer stacking of the 2D COF Tph-DHTA was tuned from eclipsed-AA model to slipped-AA by changing the solvent from o-dichlorobenzene + n-butanol (3:1, v/v) to tetrahydrofuran + n-butanol (1:7, v/v) in step 1. The as-prepared Tph-DHTA with slipped-AA stacking (s-Tph-DHTA) showed higher resolution and faster separation of C8 aromatic isomers than that with eclipsed-AA stacking (e-Tph-DHTA). The formation of slipping stacking of s-Tph-DHTA facilitated the thermodynamics, but did not affect the mass transfer resistance for the separation of C8 aromatic isomers. This work not only provides a promising way to modulate the stacking structure of COFs, but also opens a new strategy to design COF stationary phases for the separation of intractable isomers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The scarcity of selective adsorbents for efficient extraction and removal of microcystins (MCs) from complex samples greatly limits the precise detection and effective control of MCs. Three-dimensional covalent organic frameworks (3D COFs), characterized by their large specific surface areas and highly ordered rigid structure, are promising candidates, but suffer from lack of specific recognition. Herein, we design to engineer molecularly imprinted cavities within 3D COFs via molecularly imprinted technology, creating a novel adsorbent with exceptional selectivity, kinetics and capacity for the efficient extraction and removal of MCs. As proof-of-concept, a new CC bond-containing 3D COF, designated JNU-7, is designed and prepared for copolymerization with methacrylic acid, the pseudo template L-arginine and ethylene dimethacrylate to yield the JNU-7 based molecularly imprinted polymer (JNU-7-MIP). The JNU-7-MIP exhibits a great adsorption capacity (156 mg g -1 ) for L-arginine. Subsequently, the JNU-7-MIP based solid-phase extraction coupled with high performance liquid chromatography-mass spectrometry achieves low detection limit of 0.008 ng mL -1 , wide linear range of 0.025-100 ng mL -1 , high enrichment factor of 186, rapid extraction of 10 min, and good recoveries of 92.4%-106.5% for MC-LR. Moreover, the JNU-7-MIP can rapidly remove the MC-LR from 1 mg L -1 to levels (0.26-0.35 μg L -1 ) lower than the WHO recommended limit for drinking water (1 μg L -1 ). This work reveals the considerable potential of 3D COF based MIPs as promising adsorbents for the extraction and removal of contaminants in complex real samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Understanding the individual fluorescence response mechanism of covalent organic frameworks (COFs) at a single-crystal level is of great significance for the rational design of COF-based microsensors but unreachable because all previous COF-based sensors are performed with average fluorescence response behavior of various sized polycrystalline COFs. Herein, we design to explore the fluorescence response of a monodisperse single-crystal COF and further reveal the individual heterogeneity of the response mechanism. Three-dimensional single-crystal COF-301 (SCOF-301) with an intramolecular H-bond-induced excited-state intramolecular proton-transfer effect is selected as a proof-of-concept SCOF. With ethanol, benzene, and ammonia as model analytes, three different deformation and competition H-bond site-induced fluorescence response mechanisms related to crystal size are revealed. Small single particles of SCOF-301 (SSCOF-301) exhibit a more flexible structure, leading to the dominant role of deformation in the fluorescence response of small-sized SSCOF-301. The decreasing flexibility of SSCOF-301 with the increase of crystal size results in involvement of competition of the H-bond site to the fluorescence response besides deformation. Further increase of the crystal size makes the large-sized SSCOF-301 difficult to deform; thus, the competition of the H-bond site dominates the fluorescence response. This work provides a deep understanding of the individual fluorescence response mechanism of COFs to guide the design of a functional COF sensor with suitable size and mechanism for different structural analytes.

Covalent organic frameworks (COFs) are promising adsorbents for extraction, but their selectivity for molecular recognition remains a challenging issue due to the very limited structural design with rigid structure. Herein, we report an elegant strategy for the design and synthesis of molecularly imprinted flexible COFs (MI-FCOFs) via one-pot reaction between the flexible building block of 2,4,6-tris(4-formylphenoxy)- 1,3,5-triazine and linear 4-phenylenediamine for selective extraction of aflatoxins. The flexible chain structure enabled the developed MI-FCOF to adjust the shape and conformation of frameworks to suit the template molecule, giving high selectivity for aflatoxins recognition. Moreover, MI-FCOF with abundant imprinted sites and function groups exhibited an exceptional adsorption capacity of 258.4 mg g -1 for dummy template which is 3 times that of no-imprinted FCOF (NI-FCOF). Coupling MI-FCOF based solid-phase extraction with high-performance liquid chromatography gave low detection limits of 0.003-0.09 ng mL -1 and good precision with relative standard deviations ≤ 6.7% for the determination of aflatoxins. Recoveries for the spiked rice, corn, wheat and peanut samples were in the range of 85.4%- 105.4%. The high selectivity of the developed MI-FCOF allows matrix-free determination of AFTs in food samples. This work offers a new way to the design of MI-FCOF for selective molecular recognition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m -2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications., (© 2024 Wiley‐VCH GmbH.)

The first direct catalytic asymmetric Mannich reaction of 2-alkylazaarenes and ketimines was realized with a chiral Cu-bis(oxazoline) complex as the catalyst. The asymmetric addition of 2-alkylpyridines to isatin-derived ketimines proceeded smoothly to afford α,β-functionalized 2-substituted pyridines bearing 3-amino-3,3-disubstituted oxindole motifs with excellent results (≤99% yield, 99:1 dr, and 98% ee). The catalytic system was also extended to 2-alkylbenzothiazoles as nucleophiles for the asymmetric Mannich reaction of ketimines.

Covalent organic frameworks (COFs) are attractive adsorbents for sample pretreatment due to their unique structure and properties. However, the selectivity of COFs for the extraction of hazardous compounds is still limited due to the lack of specific interactions between COFs and targets. Herein, we report a pore size adjustment strategy for room-temperature synthesis of molecularly imprinted COF (MICOF) for selective extraction of zearalenone (ZEN) in complex food samples. The three-dimensional building block tetra(4-aminophenyl) methane was used as a functional monomer, while dialdehyde monomers with different numbers of benzene ring were used to adjust the pore size of MICOF to match with the size of ZEN molecules. The prepared MICOF gave the largest adsorption capacity of 177.2 mg g -1 and the highest imprinting factor of 10.1 for ZEN so far. MICOF was used as the adsorbent for dispersed solid-phase extraction in combination with high-performance liquid chromatography for the determination of trace ZEN in cereals. The high selectivity of the developed method allows simple aqueous standard calibration for the matrix effect-free determination of ZEN in food samples. The limit of detection and the recoveries of the developed method were 0.21 μg kg -1 and 93.7-101.4%, respectively. The precision for the determination of ZEN was less than 3.8% (RSD, n = 6). The developed method is promising for the selective determination of ZEN in complex matrices.

Chiral flavor substances play an important role in the human perception of different tastes. Here, we report a pure covalent-organic framework (COF) membrane nanochannel in combination with a chiral gold nanoparticles (AuNPs) selector for sensing chiral flavor substances. The pure COF membrane with a proper pore size is selected as the nanochannel, while l-cysteine-modified AuNPs (l-Cys-AuNPs) are used as the chiral selector. l-Cys-AuNPs show stronger binding to the S -enantiomer than the R -enantiomer, causing current reduction to different degrees for the R - and S -enantiomer to achieve chiral sensing due to the synergistic effect of the size exclusion of the COF nanochannel and the chiral selectivity of l-Cys-AuNPs. The developed COF membrane nanochannel sensing platform not only allows an easy balance of the permeability and selectivity, which is difficult to achieve in traditional polymer membrane nanochannel sensors, but also exhibits better chiral performance than commercial artificial anodic aluminum oxide (AAO) nanochannel sensors. The developed nanochannel sensor is successfully applied for sensing flavor enantiomers such as limonene, propanediol, methylbutyric acid, and butanol with the enantiomer excess values of 55.2% (propanediol) and 72.4% (limonene) and the low detection limits of 36 (limonene) and 71 (propanediol) ng L -1 . This study provides a new idea for the construction of nanochannel platforms based on the COF for sensitive and selective chiral sensing.

Covalent organic frameworks (COFs) are promising as stationary phases for gas chromatography (GC). The successful anchoring of COFs to the inner walls of the capillary with good uniformity is an important prerequisite to ensure the excellent separation performance of columns. However, current methods for the fabrication of COF-based capillary columns cannot always meet this requirement when faced with different COFs, which hampers the further development of COF-based GC stationary phases. Here, we show a general two-step method for the fabrication of COF-bound capillary column. The first step enables the formation of uniform amorphous polymer layer on the inner walls of capillary, while the second step allows the facile transformation of the amorphous polymer layer into a highly crystalline COF layer. COF-bound capillary columns with different framework structures were fabricated successfully by the developed two-step method. Impressively, the COF layers bound on the inner walls of these capillary columns showed good uniformity and high crystallinity. More importantly, as an example, the fabricated Tab-DHTA-bound capillary column showed good resolution ( R > 1.5) and high column efficiency (700-39,663 plates m -1 ) for the tested isomers of ethylbenzene, xylene, dichlorobenzene, chlorotoluene, pinene, 1,3-dichloropropene, and propylbenzene with good precision (RSD, run-to-run, n = 5) (retention time, 0.2-0.6%; peak area, 0.5-1.1%; and peak height, 0.5-1.4%). In general, the fabricated Tab-DHTA-bound capillary column exhibited better performance for the separation isomers than commercial columns DB-5 and HP-FFAP. These results indicate that the two-step method is an efficient way to fabricate the COF-bound capillary column with excellent separation performance.

Carbon dots (CDs)-enabled agriculture has been developing rapidly, but small-scale synthesis and high costs hinder the agricultural application of CDs. Herein, biomass-derived carbon dots (B-CDs) were prepared on a gram-level with low cost, and these B-CDs significantly improved crop photosynthesis. The B-CDs, exhibiting small size and blue fluorescence, were absorbed by crops and enhanced photosynthesis via light-harvesting. Foliar application of B-CDs (10 mg·kg -1 ) could promote chlorophyll synthesis (30-100 %), Ferredoxin (Fd, 40-80 %), Rubisco enzyme (20-110 %) and upregulated gene expression (20-70 %), resulting in higher net photosynthetic rates (130-300 %), dry biomass (160-300 %) and fresh biomass (80-150 %). Further, the B-CDs could increase crop photosynthesis under nutrient deficient conditions, which was attributed to the release of nutrients from B-CDs. Therefore, the B-CDs enhanced the photosynthesis via enhancing light conversion and nutrient supply. This study provides a promising material capable of enhancing photosynthesis for sustainable agriculture production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Molecularly imprinting on covalent organic frameworks (MI-COF) is a promising way to prepare selective adsorbents for effective extraction of fluoroquinolones (FQs). However, the unstable framework structure and complex imprinting process are challenging for the construction of MI-COF. Here, we report a facile surface imprinting approach with dopamine to generate imprinted cavities on the surface of irreversible COF for highly efficient extraction of FQs in food samples. The irreversible-linked COF was fabricated from hexahydroxytriphenylene and tetrafluorophthalonitrile to ensure COF stability. Moreover, the introduction of dopamine surface imprinted polymer into COF provides abundant imprinted sites and endows excellent selectivity for FQs recognition against other antibiotics. Taking enrofloxacin as a template molecule, the prepared MI-COF gave an exceptional adsorption capacity of 581 mg g -1 , a 2.2-fold enhancement of adsorption capacity compared with nonimprinted COF. The MI-COF was further explored as adsorbent to develop a novel solid-phase extraction method coupled with high-performance liquid chromatography for the simultaneous determination of enrofloxacin, norfloxacin and ciprofloxacin. The developed method gave the low limits of detection at 0.003-0.05 ng mL -1 , high precision with relative standard deviations less than 3.5%. The recoveries of spiked FQs in food samples ranged from 80.4% to 110.7%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Probe nanoelectrospray ionization mass spectrometry (PESI-MS) is practically desirable for rapid and ultra-sensitive analysis of trace contaminants in environment, but limited with the stable and selective probe coating. Herein, we show the design and preparation of irreversible fluorine-based covalent organic framework (TFPPA-F 4 ) covalently bonded probe to couple with ESI-MS (TFPPA-F 4 -PESI-MS) for direct and rapid determination of perfluoroalkyl carboxylic acids (PFCAs) in environmental water. Chemical bonding coating of irreversible crystalline TFPPA-F 4 not only improved stability of the probe, but also offered accessible multiple interactions including hydrophobic, hydrogen bonding and F-F interactions to promote the kinetics and selectivity for PFCAs. The proposed TFPPA-F 4 -PESI-MS realized rapid determination of PFCAs (about 4 min) with low limits of detection of 0.06-0.88 ng L -1 and wide linear range of 1-5000 ng L -1 (R 2 of 0.9982-0.9998). Recoveries for the spiked lake and pond water were 85.9-111.1 %. TFPPA-F 4 based probe can maintain the extraction performance after 100 times of extraction. This work shows the great potential of the irreversible covalent organic framework based PESI-MS in rapid and ultra-sensitive determination of contaminants in environmental samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastasis (BrM) and a poor prognosis. As the most lethal form of breast cancer, BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis (BCBrM), but the underlying mechanisms are far from being fully elucidated., Methods: Through analysis of BCBrM transcriptome data from mice and patients, and immunohistochemical validation on patient tissues, we identified and verified the specific down-regulation of retinoic acid receptor responder 2 (RARRES2), a multifunctional adipokine and chemokine, in BrM of TNBC. We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies. Key signaling pathway components were evaluated using multi-omics approaches. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2., Results: We found that down-regulation of RARRES2 is specifically associated with BCBrM, and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue (PTEN)-mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment., Conclusions: Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM. RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM., (© 2023. The Author(s).)

Development of novel functional materials for effective isomer separation is of great significance in environmental science, chemical industry, and life science due to the different functions of isomers. However, the similar physicochemical properties of isomers make their separation greatly challenging. Here, we report the fabrication of trifluoromethyl-functionalized 2D covalent organic framework (COF) TpTFMB with 2,2'-bis(trifluoromethyl)benzidine (TFMB) and 1,3,5-triformylphloroglucinol (Tp) for the separation of isomers. TpTFMB was in situ-grown on the inner surface of a capillary for the high-resolution separation of isomers. The introduction of hydroxyl and trifluoromethyl functional groups with uniform distribution in 2D COFs is a powerful tactic to endow TpTFMB with various functions such as hydrogen bonding, dipole interaction, and steric effect. The prepared TpTFMB capillary column enabled the baseline separation of positional isomers such as ethylbenzene and xylene, chlorotoluene, carbon chain isomers such as butylbenzene and ethyl butanoate, and cis-trans isomers 1,3-dichloropropene. The hydrogen-bonding, dipole, and π-π interactions as well as the structure of COF significantly contribute to the isomer separation. This work provides a new strategy for designing functional 2D COFs for the efficient separation of isomers.

Although polycrystalline covalent organic frameworks (PCOFs) have already shown great potential as stationary phases for chromatography, irregular shape and size distribution of PCOFs make regulation of particle size of PCOFs for high separation performance impossible, which is accessible by the application of single-crystalline COFs (SCOFs). Herein, we showed preparation of three-dimensional SCOF (SCOF-303) bonded capillaries (SCOF-303-capillary) with different particle sizes (about 0.4-1.6 μm) and further investigated gas chromatographic separation ability of these SCOF-303-capillaries for isomers of xylene, dichlorobenzene, and pinene. It was found resolution and column efficiency of SCOF-303-capillaries for isomers decreased with the increase in particle size, mainly resulting from the weaker size-exclusion effect and higher mass transfer resistance of the larger particle size of flexible SCOF-303. The obtained SCOF-303-capillary (particle size of ∼0.4 μm) offered baseline separation of xylene isomers with the high resolution of 2.26-3.52, great efficiency of 7879 plates m -1 for p -xylene, better than PCOF-303-capillary, and commercial DB-5 and HP-FFAP capillary columns as well as many reported capillaries. This work not only shows the great potential of SCOFs for gas chromatography but also provides the theoretical direction for the design of the efficient COF based stationary phase by adjusting the particle sizes.

The valid management of inflammation and precise inhibition of smooth muscle cells (SMCs) is regarded as a promising strategy for regulating vascular responses after stent implantation, yet posing huge challenges to current coating constructions. Herein, we proposed a spongy cardiovascular stent for the protective delivery of 4-octyl itaconate (OI) based on a "spongy skin" approach, and revealed the dual-regulation effects of OI for improving vascular remolding. We first constructed a "spongy skin" onto poly-l-lactic acid (PLLA) substrates, and realized the protective loading of OI with the highest dosage of 47.9 μg/cm 2 . Then, we verified the remarkable inflammation mediation of OI, and surprisingly revealed that the OI incorporation specifically inhibited SMC proliferation and phenotype switching, which contributed to the competitive growth of endothelial cells (EC/SMC ratio ∼ 5.1). We further demonstrated that OI at a concentration of 25 μg/mL showed significant suppression of the TGF-β/Smad pathway of SMCs, leading to the promotion of contractile phenotype and reduction of extracellular matrix. In vivo evaluation indicated that the successful delivery of OI fulfilled the inflammation regulation and SMCs inhibition, therefore suppressing the in-stent restenosis. This "spongy skin" based OI eluting system may serve as a new strategy for improving vascular remolding, and provides a potential concept for the treatment of cardiovascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Electronic devices with tactile and pressure-sensing capabilities are becoming increasingly popular in the automatic industry, human motion/health monitoring, and artificial intelligence applications. Inspired by the natural nanotopography of the cicada wing, we propose here a straightforward strategy to fabricate a highly sensitive tactile sensor through nanotexturing of erected polyaniline (PANI) nanoneedles on a conductive and elastic three-dimensional (3D) carbon skeleton. The robust and compressible carbon networks offer a resilient and conducting matrix to catering complex scenarios; the biomimetic PANI nanoneedles firmly and densely anchored on a 3D carbon skeleton provide intimate electrical contact under subtle deformation. As a result, a piezoresistive tactile sensor with ultrahigh sensitivity (33.52 kPa -1 ), fast response/recovery abilities (97/111 ms), and reproducible sensing performance (2500 cycles) is developed, which is capable of distinguishing motions in a wide pressure range from 4.66 Pa to 60 kPa, detecting spatial pressure distribution, and monitoring various gestures in a wireless manner. These excellent performances demonstrate the great potential of nature-inspired tactile sensors for practical human motion monitoring and artificial intelligence applications.

A formal [4 + 2] cycloaddition of 3-nitroindoles with ortho -aminophenyl p -quinone methides via a dearomatization process was developed. This method provides a facile approach for preparing tetrahydro-5 H -indolo[2,3- b ]quinolones with good results. With the bifunctional Cinchona alkaloid-squaramide as the catalyst, the asymmetric version of the reaction successfully afforded the corresponding chiral products with moderate to good enantioselectivities. This work represents the first dearomative cycloaddition of electron-deficient heteroarenes triggered by aza-Michael addition from p -QMs.

Nanosilicon applications have been shown to increase plant defenses against both abiotic and biotic stresses. Silicon quantum nanodots (Si NDs), a form of nanosilicon, possess excellent biological and physiochemical properties ( e.g. , minimal size, high water solubility, stability, and biocompatibility), potentially making them more efficient in regulating plant responses to stress than other forms of silicon. However, to date, we still lack mechanistic evidence for how soil-applied Si NDs alter the regulation of plant physical and chemical defenses against insect herbivores. To address this gap, we compared the effect of fluorescent amine-functionalized Si NDs (5 nm) and the conventional fertilizer sodium silicate on maize ( Zea mays L.) physical and chemical defenses against the oriental armyworm ( Mythimna separata , Walker) caterpillars. We found that 50 mg/kg Si NDs and sodium silicate additions inhibited the growth of caterpillars the most (35.7% and 22.8%, respectively) as compared to other application doses (0, 10, and 150 mg/kg). Both Si NDs and silicate addition activated biosynthesis genes responsible for chemical (benzoxazinoids) and physical (lignin) defense production. Moreover, Si NDs upregulated the gene expression of antioxidant enzymes (SOD, CAT, and POD) and promoted the antioxidant metabolism (flavonoids) in maize leaves under M. separata attack. Finally, we show that, under field conditions, Si ND addition increased maize cob weight (28.7%), cob grain weight (40.8%), and 100-grain weight (26.5%) as compared to the control, and more so than the conventional silicon fertilizer. Altogether, our findings highlight the potential for Si NDs to be used as an effective and ecofriendly crop protection strategy in agroecosystems.

Background: The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms, among which transcriptional regulation is one of the most important components. Alternative splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell cycle. However, the patterns of transcript isoform expression in the cell cycle are unclear. Therapies targeting cell cycle checkpoints are commonly used as anticancer therapies, but none of them have been designed or evaluated at the alternative splicing transcript level. The utility of these transcripts as markers of cell cycle-related drug sensitivity is still unknown, and studies on the expression patterns of cell cycle-targeting drug-related transcripts are also rare., Methods: To explore alternative splicing patterns during cell cycle progression, we performed sequential transcriptomic assays following cell cycle synchronization in colon cancer HCT116 and breast cancer MDA-MB-231 cell lines, using flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples, and we developed a new algorithm to describe the periodic patterns of transcripts fluctuating during the cell cycle. Genomics of Drug Sensitivity in Cancer (GDSC) drug sensitivity datasets and Cancer Cell Line Encyclopedia (CCLE) transcript datasets were used to assess the correlation of genes and their transcript isoforms with drug sensitivity. We identified transcripts associated with typical drugs targeting cell cycle by determining correlation coefficients. Cytotoxicity assays were used to confirm the effect of ENST00000257904 against cyclin dependent kinase 4/6 (CDK4/6) inhibitors. Finally, alternative splicing transcripts associated with mitotic (M) phase arrest were analyzed using an RNA synthesis inhibition assay and transcriptome analysis., Results: We established high-resolution transcriptome datasets of synchronized cell cycle samples from colon cancer HCT116 and breast cancer MDA-MB-231 cells. The results of the cell cycle assessment showed that 43,326, 41,578 and 29,244 transcripts were found to be periodically expressed in HeLa, HCT116 and MDA-MB-231 cells, respectively, among which 1280 transcripts showed this expression pattern in all three cancer cell lines. Drug sensitivity assessments showed that a large number of these transcripts displayed a higher correlation with drug sensitivity than their corresponding genes. Cell cycle-related drug screening showed that the level of the CDK4 transcript ENST00000547281 was more significantly associated with the resistance of cells to CDK4/6 inhibitors than the level of the CDK4 reference transcript ENST00000257904. The transcriptional inhibition assay following M phase arrest further confirmed the M-phase-specific expression of the splicing transcripts. Combined with the cell cycle-related drug screening, the results also showed that a set of periodic transcripts, for example, ENST00000314392 (a dolichyl-phosphate mannosyltransferase polypeptide 2 isoform transcript), was more associated with drug sensitivity than the levels of their corresponding gene transcripts., Conclusions: In summary, we identified a panel of cell cycle-related periodic transcripts and found that the levels of transcripts of drug target genes showed different values for predicting drug sensitivity, providing novel insights into alternative splicing-related drug development and evaluation., (© 2022. The Author(s).)

Objective: To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods: The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, β-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results: By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27±2.73)%, P <0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells ( P =0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells ( P <0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of β-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58±0.25, P =0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells ( P >0.05). Conclusions: This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing β-CHK2 to promote DNA repair.

Thermally stable three-dimensional covalent organic frameworks (3D COFs) with rich pores of channels and cages are promising as stationary phases for gas chromatography (GC), which has not been explored. Here we synthesize the first amino-based 3D COF and its covalently bonded capillary via building-block exchange for GC separation of isomers.

The separation of amino acid (AA) enantiomers shows significance for chemistry, food, and biology, but remains challenging due to their similar properties. A promising nanoporous chiral covalent organic framework (COF) as a stationary phase for high-performance liquid chromatography (HPLC) suffers from the irregularity and widely distributed particle size of the chiral COF. Herein, we show the facile preparation of a chiral COF-monolith as a stationary phase for HPLC enantiomeric separation of AAs via orthogonal experiments. The CTzDa-monolith is prepared by the incorporation of the model chiral COF named CTzDa into the porous poly(ethylene dimethacrylate-co-methacrylate) monolith and reveals great permeability and mechanical stability. The corresponding CTzDa-monolithic column gives better chiral HPLC separation of AAs than the commercial Poroshell 120 chiral-T column. Thermal dynamic analysis and molecular docking calculations imply the involvement of stereoscopic hydrogen, π-π, and van der Waals interactions between the CTzDa and AAs during HPLC enantioseparation. The facile incorporation of the chiral COF into the porous monolith will promote the potential of a chiral COF as a stationary phase for HPLC., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Incorporation of highly selective and stable adsorbent with facile extraction technology is desired in practical analysis. Here we show the rational preparation of a urea-linked covalent organic framework functionalized polytetrafluoroethylene film (COF-117-PTFE) with ordered porous structure, rich functional groups, and large surface area-to-volume ratio as the effective adsorbent for convenient, selective and rapid thin film microextraction (TFME) of rhodamine B (RB). The COF-117-PTFE based TFME coupled with high performance liquid chromatography-fluorescence detector (HPLC-FLD) successfully realized the determination of RB with the limit of detection of 0.007 μg L - 1 , the linear range of 0.1 - 100 μg L - 1 . The relative standard deviation (RSD) of intraday (n = 5) and interday (n = 5) for the determination of 10 μg L - 1 RB were 2.3% and 6.8%, respectively. The absolute recoveries were 80.3%, 71.2% and 67.9% in river water, chili powder and Sichuan pepper powder, respectively. The recoveries for RB spiking in complicated real samples (dry chili, chili powder, dry Sichuan pepper, Sichuan pepper powder and river water) ranged from 90.4% to 107.5%. The developed COF-117-PTFE based TFME-HPLC-FLD method is promising in practical application. This work reveals the high potential of functionalized COF film as the adsorbent for effective extraction of trace contaminants in complicated samples., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022. Published by Elsevier B.V.)

The wide utilization of organophosphorus pesticides (OPPs) results in a potential threat to ecosystem and human health. The essential extraction process in practical OPPs analysis always suffers from the low efficiency due to the limited accessible active sites and interactions in the adsorbents. Here, we report a rational design and synthesis of a novel hydroxyl-functionalized three-dimensional covalent organic framework (3D COF-OH) named JNU-6 with ordered porous structure and multiple interactions as the adsorbent for rapid and selective dispersive solid phase extraction (DSPE) of OPPs. The 3D COF-OH based DSPE was coupled with gas chromatography-flame thermionic detection (GC-FTD) for the determination of four selected OPPs with low limits of detection of 0.15-0.39 ng mL -1 , wide linear range of 1-1100 ng mL -1 . The developed method gave good precision (relative standard deviation of 1.6-8.5% (n = 5)) and recoveries of 86-106% for the determination of OPPs in complicated fruit and vegetable samples. This work reveals the high practical potential of functionalized 3D COFs as adsorbents for effective extraction of trace contaminants in complicated samples., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Separation of isomers is important in diverse areas such as life science, chemical industry, pharmaceutical and environmental science, but still challenging due to their similar physicochemical properties. Development of new stationary phases is an effective way to improve the performance of chromatography for the separation of isomers. Here, we report the post-modification of a new hydroxyl-functionalized covalent organic framework (COF) TzDHNDA with [(1-phenylethyl)amino]acetic acid (PEAA) via esterification reaction to construct PEAA functionalized COF (TzDHNDA-PEAA). The prepared TzDHNDA-PEAA was stable up to 380 °C and used as stationary phase to make TzDHNDA-PEAA coated capillary column for gas chromatographic separation of isomers. The TzDHNDA-PEAA coated capillary column showed a high column efficiency for n-dodecane (12417 plates m -1 , 120 °C) and high resolution separation of the isomers of fluoroaniline (R m -/ o - =3.2, R p -/ m - =2.4), chloroaniline (R m -/ o - =5.7, R p -/ m - =1.8), nitrotoluene (R p -/o- =2.2, R m -/ p - =1.7), pinene (R β -/ α - =2.4), ionone (R β -/ α - =4.8) and 1,3-dichloropropene (R E -/ Z - =2.0). The fabricated column offered better separation of chloroaniline isomers than commercial capillary columns InertCap WAX, InertCap 1701 and InertCap 5. The introduced benzene ring, secondary amine and carbonyl groups of PEAA into the COF TzDHNDA significantly improved the resolution of isomers due to the enhanced hydrogen-bonding and π-π interactions. This work shows that post-modification strategy is an effective way to prepare novel COFs for chromatographic separation of isomers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Grafting specific recognition moieties onto solid-state nanofluidic channels is a promising way for selective and sensitive sensing of analytes. However, the time-consuming interaction between recognition moieties and analytes is the main hindrance to the application of nanofluidic channel-based sensors in rapid detection. Here, we show the integration of ordered two-dimensional covalent organic frameworks (2D COFs) to solid-state nanofluidic channels to achieve rapid, selective, and sensitive detection of contaminants. As a proof of concept, a thiourea-linked 2D COF (JNU-3) as the recognition unit is covalently bonded on the stable artificial anodic aluminum oxide nanochannels (AAO) to fabricate a JNU-3@AAO-based nanofluidic sensor. The rapid and selective interaction of Hg(II) with the highly ordered channels of JNU-3 allows the JNU-3@AAO-based nanofluidic sensor to realize ultrafast and precise determination of Hg(II) (90 s) with a low limit of detection (3.28 fg mL -1 ), wide linear range (0.01-100 pg mL -1 ), and good precision (relative standard deviation of 3.8% for 11 replicate determination of 10 pg mL -1 ). The developed method was successfully applied to the determination of mercury in a certified reference material A072301c (rice powder), real water, and rice samples with recoveries of 90.4-99.8%. This work reveals the great potential of 2D COFs-modified solid-state nanofluidic channels as a sensor for the rapid and precise detection of contaminants in complicated samples.

Development of novel functionalized covalent organic frameworks (COFs) as adsorbent for removal of mercury from environment is of great significance, but the conventional strategies for functionalizing COFs always sacrifice porous properties and suppress the exposure of functional sites, which goes against the rapid adsorption of Hg(II). Here, we show the rational design and preparation of the first thiourea-linked COFs via engineering the COFs linkage as functional moiety for ultrafast and selective adsorption of Hg(II). Two thiourea-linked COFs JNU-3 and JNU-4 were prepared via tautomerism reaction of 1,3,5-triformylphloroglucinol with 1,4-phenylenebis(thiourea) and 1,4-biphenylenebis(thiourea), respectively. The thiourea serves as not only linkage to connect the building block into irreversible crystalline structure, but also functional moiety to give no occupation of the COF pore and full exposure to Hg(II) with strong affinity, offering the JNU-3 and JNU-4 large adsorption capacity (960 and 561 mg g -1 , respectively) and ultrafast kinetics (equilibrium time of 10 s) for Hg(II). The proposed strategy for the design of functional COFs with inherent linkage as functional moiety largely promotes the performance of COFs for diverse applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM)., Methods: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated., Results: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity., Conclusion: BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

Porous surfaces have attracted tremendous interest for customized incorporation of functional agents on biomedical devices. However, the versatile preparation of porous structures on complicated devices remains challenging. Herein, we proposed a simple and robust method to fabricate "spongy skin" on diversified polymeric substrates based on non-solvent-induced phase separation (NIPS). Through the swelling and the subsequent phase separation process, interconnected porous structures were directly formed onto the polymeric substrates. The thickness and pore size could be regulated in the ranges of 5-200 and 0.3-0.75 μm, respectively. The fast capillary action of the porous structure enabled controllable loading and sustained release of ofloxacin and bovine albumin at a high loading dosage of 79.9 and 24.1 μg/cm 2 , respectively. We verified that this method was applicable to diversified materials including polymethyl methacrylate, polystyrene, thermoplastic polyurethane, polylactide acid, and poly(lactic- co -glycolic acid) and can be realized onto TCPS cell culture plates. This NIPS-based method is promising to generate porous surfaces on medical devices for incorporating therapeutic agents.

Sensitive and precise determination of chloramphenicol (CAP) is of great significance for human health due to its high risk in trace amounts. Solid-state artificial nanochannels are expected to be highly promising sensing devices owing to single-molecule sensitivity, target-specific selectivity, and portability. Herein, we report an aptamer self-assembly-functionalized artificial nanochannel-based sensor for highly sensitive and precise determination of CAP. Aptamer self-assembly (AAs) served as the specific recognition component and were in situ grown on the surface of stable anodic aluminum oxide (AAO) nanochannels to develop an AAs@AAO nanochannel-based sensor. Selective interaction with CAP led to the disassembly of AAs and sensitive current change of AAs@AAO nanochannels, allowing sensitive and precise sensing of CAP in complex food samples. The developed AAs@AAO nanochannel-based sensor showed a wide linear range from 0.32 to 1600 pg. mL -1 , low limit of detection (LOD) of 0.1 pg. mL -1 , high precision with relative standard deviation of 2.9%, and quantitative recoveries of 93.4-102.2% for CAP in milk, milk powder, and honey samples. This work proposes a versatile nanochannel-based platform for facile, sensitive, and precise sensing of hazardous residues in food samples.

Photodynamic therapy (PDT) received great attention in cancer therapy due to the advantages of negligible drug resistance, low side effects, and minimal invasiveness. Development of theranostic nanoprobes with specific imaging-guided PDT is of great significance in the field. Herein we report the fabrication of a novel theranostic nanoprobe porphyrin/G-quadruplex conjugated gold/persistent luminescence nanocomposites for imaging-guided PDT. The developed nanoprobe contains NIR-emitting persistent luminescent nanoparticles (PLNP) as the core for autofluorescence-free bioimaging and Au coating on PLNP for facile subsequent DNA conjugation. The DNA sequence is designed to contain G-rich AS1411 aptamer for recognizing the over-expressed cellular nucleolin of cancer cell and forming a G-quadruplex structure to combine with tetrakis (4-carboxyphenyl) porphyrin (TCPP) to realize PDT. The AS1411 aptamer-contained DNA conjugated Au-coated PLNP is rapidly prepared via a freezing method with high content of DNA and good aqueous stability. Meanwhile, TCPP is easily loaded into the G-quadruplex structure formed from G-rich AS1411 aptamer on the surface of Au/PLNP in presence of K + . The theranostic nanoprobe gives integrated merits of PLNP for autofluorescence-free bioimging, TCPP for PDT and AS1411 aptamer-contained DNA for specific binding to cancer cells. This work provides a new specially designed imaging-guided PDT nanoplatform for theranostics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Preparation of porphyrin-based covalent organic frameworks (Por-COFs) with high photosensitizing activity for photodynamic inactivation of bacteria is of great challenge, but significant for economy and human health. Herein, we show a conjugation-regulating strategy to design and synthesize Por-COFs with high photosensitizing activity for the photodynamic inactivation of bacteria. Terephthalaldehyde (Da), 2,5-Dihydroxyterephthalaldehyde (Dha), and 2,5-Diethoxyterephthalaldehyde (Deta) with different conjugation degrees are selected to condense with 5,10,15,20-Tetrakis(4-aminophenyl)porphyrin (Tph) to synthesize COF-366, DhaTph, and JNU-2, respectively. The higher conjugation of Dha and Deta than Da leads to the higher conjugation of DhaTph and JNU-2, respectively. Moreover, the hydroxyl group in Dha and the ethoxy group in Deta further expand the conjugation of DhaTph and JNU-2 via the formation of intralayer extended π-cloud delocalization and p-π conjunction, respectively. The extension of conjugation for DhaTph and JNU-2 results in the increase of intersystem crossing process and significantly improves their photosensitizing activity. Furthermore, JNU-2 with the highest photosensitizing activity exhibits superior antibacterial effects toward Staphylococcus aureus (99.1%) and Escherichia coli (96.8%). This study offers a new conjugation-regulating strategy for designing high photosensitizing activity of Por-COFs for the inactivation of bacteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Reprogramming of cellular metabolism is a hallmark of cancer. Mitochondrial ATP synthase (MAS) produces most of the ATP that drives the cell. High expression of the MAS-composing proteins is found during cancer and is linked to a poor prognosis in glioblastoma, ovarian cancer, prostate cancer, breast cancer, and clear cell renal cell carcinoma. Cell surface-expressed ATP synthase, translocated from mitochondrion to cell membrane, involves the angiogenesis, tumorigenesis, and metastasis of cancer. ATP synthase has therefore been considered a therapeutic target. We review recent various ATP synthase inhibitors that suppress tumor growth and are being tested for the clinic., Competing Interests: The authors declare no competing interest., (© 2021 The Author(s).)

Nowadays, due to increasing carbon dioxide released, water acidification poses a series of serious impacts on aquatic organisms. To evaluate the effects of water acidification on crustaceans, we focused on the Chinese mitten crab Eriocheir sinensis, which is a spawning migration and farmed species in China. Based on histological and oocyte transparent liquid observation, we found that the acidified environment significantly delayed the ovarian maturation of E. sinensis. Moreover, RNA-seq was applied to obtain gene expression profile from the crab's gills and ovaries in response to acidified environment. Compared with control groups, a total of 5471 differentially expressed genes (DEGs) were identified in acidified gills and 485 DEGs were identified in acidified ovaries. Enrichment analysis indicated that some pathways also responded to the acidified environment, such as PI3K-Akt signaling pathway, Chemokine signaling pathway, apoptosis, and toll-like receptor signaling pathway. Subsequently, some DEGs involved in immune response (ALF, Cathepsin A, HSP70, HSP90, and catalase) and ovarian maturation (Cyclin B, Fem-1a, Fem-1b, and Fem-1c) were selected to further validate the influence of water acidification on gene expression by qRT-PCR. The results showed that the expression level of immune-related genes was significantly increased to response to the water acidification, while the ovarian maturation-related genes were significantly decreased. Overall, our data suggested that E. sinensis was sensitive to the reduced pH. This comparative transcriptome also provides valuable molecular information on the mechanisms of the crustaceans responding to acidified environment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Facile synthesis of nano porous organic cages with small size and good fluorescence property is highly desirable, but still challenging and scarce for their sensing applications. Here we report a rapid room-temperature recrystallization method for the preparation of nano porous organic cages with ultra-small size as a fluorescent probe for copper ion. The prepared nano porous organic cages gave the diameter of 2.49 ± 0.04 nm, and exhibited stable emission at 535 nm with absolute quantum yield of 0.68%. On the basis of the coordination interaction and charge transfer between the nano porous organic cages and copper ion, a simple fluorescent probe for copper ion in aqueous solution was developed. The developed method gave a calibration function of QE = 0.4815lg[Cu 2+ ] + 0.5847 (where QE is the quenching efficiency; [Cu 2+ ] in μM) (R 2 = 0.9987) in a concentration range of 0.1-2 μM, the limit of detection (3s) of 8 nM, and the relative standard deviation of 0.36% for 10 replicate determinations of 0.5 μM copper ion. The recoveries of spiked copper ion in tap water samples ranged from 96.8% to 103.0%. The proposed method possesses good sensitivity, selectivity and accuracy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Periodic porous structures have been introduced into functional films to meet the requirements of various applications. Though many approaches have been developed to generate desired structures in polymeric films, few of them can effectively and dynamically achieve periodic porous structures. Here, a facile way is proposed to introduce periodic stratified porous structures into polyelectrolyte films. A photo-crosslinkable polyelectrolyte film of poly(ethylenimine) (PEI) and photoreactive poly(acrylic acid) derivative (PAA-N 3 ) is prepared by layer-by-layer (LbL) self-assembly. Stratified crosslinking of the PEI/PAA-N 3 film is generated basing on standing-wave optics. The periodic stratified porous structure is constructed by forming pores in noncrosslinked regions in the film. Thanks to the dynamic mobility of polyelectrolytes, this structural controlment can be repeated several times. The size of pores corresponding to the layer spacing of the film contributes to the structural colors. Furthermore, structural color patterns are fabricated in the film by selective photo-crosslinking using photomasks. Although the large-scale structural controlment in thick (micron-scale and above) films needs to be explored further, this work highlights the periodic structural controlment in polymeric films and thus presents an approach for application potentials in sensor, detection, and ink-free printing., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The in-stent restenosis (IRS) after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation. MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells (EC) and smooth muscle cells (SMC) in response to vascular injury, providing a promising therapeutic candidate to inhibit IRS. However, the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings. Here, we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) triblock copolymer spongy network. The miR-22 was used as a model microRNA to regulate SMC. The dynamic porous coating realized the uniform and controllable loading of miR-22, reaching the highest dosage of 133 pmol cm -2 . We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC, thus leading to the EC dominating growth at an EC/SMC ratio of 5.4. More importantly, the PCEC@miR-22 coated stents showed reduced inflammation, low switching of SMC phenotype, and low secretion of extracellular matrix, which significantly inhibited IRS. This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent, which may extend to other combination medical devices, and facilitate practical application of bioactive agents in clinics., Competing Interests: The authors declare no conflicts of interest regarding the publication of this paper., (© 2021 The Authors.)

Aim: To conduct a systematic review to understand the experiences of foreign-educated nurses in Japan., Background: The experiences of foreign nurses in host countries, and the challenges they face, have been widely investigated around the world. However, no systematic review has focused on the experience of foreign-educated nurses in Japan., Methods: A systematic literature review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. Japan Medical Abstract Society, Citation Information by National Institute of Informatics, Cumulative Index to Nursing and Allied Health Literature, and PubMed databases were used for the literature search. Inclusion criteria were research articles published between 2013 and 2020 written in Japanese or English. A quality assessment was performed using Version 2018 of the Mixed Methods Appraisal Tool. Selected articles were read repeatedly, and relevant contents were extracted and summarized thematically., Results: Twenty-five studies were selected for the review. The themes generated included (1) reasons for nurses to come to Japan, (2) experiences and current situations among the Economic Partnership Agreement nurses/nurse candidates living in Japan, and (3) experiences and current situation of nurses who had returned to their home countries. The second theme was classified into four categories: language and communication barriers, low pass rates for the national qualification exam, adaptation to workplaces and social environments, and psychological distress., Conclusion: Foreign nurses in Japan face various challenges and difficulties, even after they return to their home countries. Solving these problems may improve the wellbeing of foreign-educated nurses in Japan., Implications for Nursing Policy: The results from the current review highlight the necessity for immediate intervention by policymakers to improve the current support system for Economic Partnership Agreement nurses/nurse candidates. A thorough pre-arrival orientation should be provided for the nurse candidates to able them to make a well-informed choice., (© 2020 International Council of Nurses.)

In this article, the characterization, synthesis, as well as the photocatalysis dye degradation performance of two novel silver(I) coordination polymers, namely, [Ag(L)(Hbdc)] n (1, L = 1,4-Bis(5,6-dimethylbenzimidazol-1-yl)butane, H 2 bdc = 1,4-Benzenedicarboxylic acid) and [Ag 2 (L)(hip)] n (2, H 2 hip = 5-Hydroxyisophthalic acid), were investigated. Fascinatingly, the photocatalytic performance of Complexes 1 and 2 have been investigated, wherein Complex 2 is considered an excellent photocatalyst for degrading Rhodamine B/methyl violet/methylene blue mixed organic dyes. Furthermore, the treatment activities of Complexes 1 and 2 on Tic disorder (TD) were assessed when used with haloperidol, and biochemical studies were conducted to reveal the mechanism in detail. Initially, the enzyme-linked immunosorbent assay was carried out to determine the dopamine and high vanillic acid contents in the striatum of the TD animal model. Subsequently, the reverse transcription-polymerase chain reaction was utilized to determine the relative expression of dopamine 1 and 2 receptor.