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Immunomodulation in biotechnological processes requires an adequate level of specific, high-affinity recombinant antibodies expressed in the affected cells. Here, we report a new strategy to obtain a sensitive nanobody against the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide. Unlike the previous methods that used total peripheral blood lymphocytes, specific peripheral lymphocytes stained with a fluorescein isothiocyanate-labeled 2,4-D coating antigen were isolated via fluorescence-activated cell sorting and used for phage display library construction. This strategy significantly reduced interference of anticarrier protein nanobody phages to small-molecule nanobody development and required only two cycles of panning to obtain the desired positive clones. Nb4-11, one of the most sensitive phage clones, showed good sensitivity and specificity against 2,4-D. Compared with previously reported 2,4-D nanobodies, the sequence of Nb4-11 exhibited completely different complementarity-determining regions (CDRs). The half-maximum inhibition concentration of the Nb4-11-based ic-ELISA was 29.3 ± 1.9 ng/mL. The Nb4-11 gene was subsequently transferred into Arabidopsis thaliana to confer herbicide resistance, and homozygous transgenic T3 lines were obtained. Stable expression of the 2,4-D nanobody in the model plant was confirmed via PCR, ic-ELISA, and Western blot analysis. In the dose-response bioassay, the transgenic T3 lines were resistant to 2 g of 2,4-D ai/ha. This work offers a new way to sort specific peripheral lymphocytes, efficiently develop nanobodies against small molecules, and create a novel mechanism for herbicide resistance based on the expression of nanobodies in plants.

The design and synthesis of high-efficiency electrochemiluminescence (ECL) emitters hold great promise for a wide range of analytical applications. In this study, we developed a rapid and straightforward strategy to fabricate a self-luminous Cd-based metal-organic framework (Cd-MOF) using individual aggregation-induced emission ligands, specifically 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethane (TPPE), within a few seconds. The rigid and directionally enriched metal node of Cd, along with the organic ligands, is formed within the Cd-MOF via coordination, effectively constraining the intramolecular free motions of TPPE and suppressing nonradiative relaxation. Additionally, the unique porous structure combined with the catalytic activity resulting from the incorporation of Cd 2+ , endow the Cd-MOF with 90-fold ECL enhancement compared to individual TPPE as more chromophores are electro-excited and more coreactants are catalyzed to produce luminescence. The as-made Cd-MOF amplifies the ECL performance by integrating ECL emitters and coreactant accelerators into a single entity, simplifying the sensing process. Leveraging the excellent ECL performance, we constructed a sensitive ECL sensor for hydroquinone based on competitive reactions, with a wide linear range from 200 nM to 1 mM and a satisfying detection limit as low as 80 nM.

High-performance Ga 2 O 3 solar-blind photodetectors are critical for applications due to their selective solar-blind ultraviolet sensitivity. The quality of the Ga 2 O 3 film has a significant impact on the performance of photodetectors. This study presents an innovative approach to enhancing the quality of Ga 2 O 3 films through the introduction of a naturally graded buffer layer, which is formed by the oxidation of a metallic Ga film and significantly improves interface stability by accommodating lattice mismatches and reducing defects. The structural and compositional characteristics of Ga 2 O 3 films were comprehensively analyzed using UV-vis (ultraviolet-visible) spectroscopy, AFM (Atomic Force Microscope), PL (Photoluminescence Spectroscopy), TEM (Transmission Electron Microscope), and XPS (X-ray Photoelectron Spectroscopy). The photodetectors fabricated from these films demonstrate responsivity of 99.8 mA/W and a solar-blind UV/UV ratio of 1.17 × 10 3 , with significant improvement compared to direct deposited films. This research highlights the potential of natural buffering layers to advance the performance of Ga 2 O 3 -based solar-blind UV detectors.

With the advancement of modern medical and brain-computer interface devices, flexible artificial nociceptors with tactile perception hold significant scientific importance and exhibit great potential in the fields of wearable electronic devices and biomimetic robots. Here, a bioinspired artificial intelligent nociceptive alarm system integrating sensing monitoring and transmission functions is constructed using a silk fibroin (SF) fibrous memristor. This memristor demonstrates high stability, low operating power, and the capability to simulate synaptic plasticity. As a result, an artificial pressure nociceptor based on the SF fibrous memristor can detect both fast and chronic pain and provide a timely alarm in the event of a fall or prolonged immobility of the carrier. Further, an array of artificial pressure nociceptors not only monitors the pressure distribution across various parts of the carrier but also provides direct feedback on the extent of long-term pressure to the carrier. This work holds significant implications for medical support in biological carriers or targeted maintenance of electronic carriers.

Lomefloxacin hydrochloride (LMFX) and sodium salicylate (SS) are important targets for real-time detection due to their widespread uses in daily life; accurate and portable monitoring of LMFX and SS is crucial for human health concerns accordingly. Developing a precise and smart platform for determination of the above analytes remains a significant challenge. Herein, a high-sensitivity platform incorporating a luminescence electrospinning film, self-designed smart-phone app, and portable 3D printing device has been developed to identify LMFX and SS. In this work, two heterometallic coordination polymers with two-dimensional layer structures have been synthesized based on 2,2'-oxidiacetic acid ligand (H 2 oda), namely, [LnPb(oda) 2 (CH 3 COO)] n [Ln = Eu ( IMU-1 ); Tb ( IMU-2 )]. IMU-1 and IMU-2 were ratio-dependent luminescence probes, which could selectively and sensitively sense with LMFX and SS, respectively. Additionally, the synthesized electrospinning films incorporating IMU-1 and IMU-2 were employed to identify LMFX and SS. Both films could rapidly photograph and color-capture through a portable 3D printing device, along with a self-designed smart-phone app that enabled convenient and quick determination of the concentrations of the above analytes. Remarkably, the mechanism exploration indicated that electron transfer from ligands to analytes affected the antenna effect and further utilized the intrinsic luminescence of analytes along with the luminescence quenching of Ln 3+ ions. Furthermore, a strategy for constructing ratio-based fluorescent probes by exploiting the luminescence of analytes and Ln 3+ ions in host coordination polymers is proposed. This work provides a new insight by combining luminescence probes, portable devices, and a smart-phone app for real-time detection of drugs and food additives.

Mechanochemistry by milling has recently attracted considerable interest for its ability to drive solvent-free chemical transformations exclusively through mechanical energy and at ambient temperatures. Despite its popularity and expanding applications in different fields of chemistry, its impact on Food Science remains limited. This review aims to demonstrate the specific benefits that mechanochemistry can provide in performing controlled glycation, and in "activating" sugar and amino acid mixtures, thereby allowing for continued generation of colors and aromas even after termination of milling. The generated mechanical energy can be tuned under specific conditions either to form only the corresponding Schiff bases and Amadori compounds or to generate their degradation products, as a function of the frequency of the oscillations in combination with the reactivity of the selected substrates. Similarly, its ability to initiate the Strecker degradation and generate pyrazines and Strecker aldehydes was also demonstrated when proteogenic amino acids were milled with glyoxal.

In planta expression of recombinant antibodies has been proposed as a strategy for herbicide resistance but is not well advanced yet. Here, an atrazine nanobody gene fused with a green fluorescent protein tag was transformed to Arabidopsis thaliana , which was confirmed with PCR, ELISA, and immunoblotting. High levels of nanobody accumulation were observed in the nucleus, cytoderm, and cytosol. The nanobody expressed in the plant had similar affinity, sensitivity, and selectivity as that expressed in Escherichia coli . The T3 homozygous line showed resistance in a dose-dependent manner up to 380 g ai/ha of atrazine, which is approximately one-third of the recommended field application rate. This is the first report of utilizing a nanobody in plants against herbicides. The results suggest that utilizing a high-affinity herbicide nanobody gene rather than increasing the expression of nanobodies in plants may be a technically viable approach to acquire commercial herbicide-resistant crops and could be a useful tool to study plant physiology.

Mucosal vaccines can prevent viruses from infecting the respiratory mucosa, rather than only curtailing infection and protecting against the development of disease symptoms. The SARS-CoV-2 spike receptor-binding domain (RBD) is a compelling vaccine target but is undermined by suboptimal mucosal immunogenicity. Here, we report a SARS-CoV-2-mimetic extracellular-vesicle vaccine developed using genetic engineering and dendritic cell membrane budding. After mucosal immunization, the vaccine recruits antigen-presenting cells rapidly initiating a strong innate immune response. Notably, it obviates the need for adjuvants and can induce germinal center formation through both intramuscular and intratracheal vaccination. It not only elicits high levels of RBD-specific antibodies but also stimulates extensive cellular immunity in the respiratory mucosa. A sequential immunization strategy, starting with an intramuscular injection followed by an intratracheal booster, significantly bolsters mucosal immunity with high levels of IgA and tissue-resident memory T cell responses, thereby establishing a formidable defense against pseudovirus infection.

We report the structural defects in Zr-metal-organic framework (MOFs) for achieving highly efficient CO 2 reduction under visible light irradiation. A series of defective Zr-MOF- X ( X = 160, 240, 320, or 400) are synthesized by acid-regulated defect engineering. Compared to pristine defect-free Zr-MOF (NNU-28), N 2 uptake increases for Zr-MOF- X synthesized with the HAc modulator, producing a larger pore space and Brunauer-Emmett-Teller surface area. The pore size distribution demonstrates that defective Zr-MOF- X exhibits mesoporous structures. Electrochemistry tests show that defective Zr-MOF- X possesses a more negative reduction potential and a higher photocurrent responsive signal than that of pristine NNU-28. Consequently, the defective samples exhibit a significantly higher efficiency in the photoreduction of CO 2 to formate. Transient absorption spectroscopies manifest that structural defects modulate the excited-state behivior of Zr-MOF- X and improve the photogenerated charge separation of Zr-MOF- X . Furthermore, electron paramagnetic resonance and in-suit X-ray photoelectron spectroscopy provide additional evidence of the high photocatalytic performance exhibited by defective Zr-MOF- X . Results demonstrate that structural defects in Zr-MOF- X also improve the charge transfer, producing abundant Zr(III) catalytically active sites, exhibiting a slower decay process than defect-free Zr-MOF. The long-lifetime Zr(III) species in defective Zr-MOF- X are fully exposed to a high-concentration CO 2 atmosphere, thereby enhancing the photocatalytic efficiency of CO 2 reduction.

Self-assembled nanostructures such as those formed by peptide amphiphiles (PAs) are of great interest in biological and pharmacological applications. Herein, a simple and widely applicable chemical modification, a urea motif, was included in the PA's molecular structure to stabilize the nanostructures by virtue of intermolecular hydrogen bonds. Since the amino acid residue nearest to the lipid tail is the most relevant for stability, we decided to include the urea modification at that position. We prepared four groups of molecules (13 PAs in all), with varying levels of intermolecular cohesion, using amino acids with distinct β-sheet promoting potential and/or containing hydrophobic tails of distinct lengths. Each subset contained one urea-modified PA and nonmodified PAs, all with the same peptide sequence. The varied responses of these PAs to variations in pH, temperature, counterions, and biologically related proteins were examined using microscopic, X-ray, spectrometric techniques, and molecular simulations. We found that the urea group contributes to the stabilization of the morphology and internal arrangement of the assemblies against environmental stimuli for all peptide sequences. In addition, microbiological and biological studies were performed with the cationic PAs. These assays reveal that the addition of urea linkages affects the PA-cell membrane interaction, showing the potential to increase the selectivity toward bacteria. Our data indicate that the urea motif can be used to tune the stability of a wide range of PA nanostructures, allowing flexibility on the biomaterial's design and opening a myriad of options for clinical therapies.

Nanostructured activated carbon (AC) adsorbents derived from woody biomass have garnered attention for their potential usage to remove toxic substances from the environment due to their high specific surface area, superior micro/mesoporosity, and tunable surface chemistry profile. However, chemical dopants widely used to enhance the chemical reactivity with heavy metals would pollute the environment and conflict with the vision of a cleaner and sustainable environment. Herein, we report a facile, green, and sustainable approach using fungi modification combined with alkali activation to produce AC for heavy metal removal. The decayed wood-derived AC (DAC) exhibited a high specific surface area of 2098 m 2 /g, and the content of O and N functional groups was 18 and 2.24%, respectively. It showed remarkable adsorption capacity toward Cd 2+ of 148.7 mg/g, which was much higher than most reported Cd 2+ adsorbents. Such excellent adsorption capacity was primarily based on enhanced physical adsorption (pore filling, π-π) and chemical adsorption (functional group complexation, ion exchange, and precipitation). Additionally, the DAC showed rapid kinetics and remarkable applicability in both dynamic environments and actual water samples. These results suggest that decayed wood has excellent potential for efficient use in the removal of Cd 2+ from wastewater. Furthermore, these results indicate that decayed wood can be cleanly produced into high efficiency heavy metal adsorbents to realize value-added utilization of decayed wood.

Selective recognition of 1,3-butadiene from complex olefin isomers is vital for 1,3-butadiene purification, but the lack of porous materials with suitable pore structures results in poor selectivity and low capacity in C4 olefin separation. Herein, two sulfonate-functionalized organic frameworks, ZU-601 and ZU-602, are designed and show impressive separation performance toward C4 olefins. Benefiting from the suitable aperture size caused by the flexibility of coordinated organic ligand, ZU-601, ZU-602 that are pillared with different sulfonate anions could discriminate C4 olefin isomers with high uptake ratio: 1,3-butadiene/1-butene (207), 1,3-butadiene/ trans -2-butene (10.1). Meanwhile, their layer-stacked structure enables the utilization of both intra- and interlayer space, enhancing the accommodation of guest molecules. ZU-601 exhibits record high 1,3-butadiene adsorption capacity of 2.90 mmol g -1 (0.5 bar, 298 K) among the reported flexible porous materials with high 1,3-butadiene/1-butene selectivity. The breakthrough experiments confirm their superior separation ability even for all five C4 olefin isomers, and the molecular-level structural change is well elucidated via powder, crystal analysis, and simulation studies. The work provides ideas toward advanced materials design with simultaneous high separation capacity and high separation selectivity for challenging separations.

Our prior investigations have evidenced that bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study aims to conduct a comprehensive analysis of the proteomics between BMSCs and BMSCs-Exos, and to further elucidate the potential therapeutic effect of BMSCs-Exos on RA, so as to establish a theoretical framework for the prevention and therapy of BMSCs-Exos on RA. The 4D label-free LC-MS/MS technique was used for comparative proteomic analysis of BMSCs and BMSCs-Exos. Collagen-induced arthritis (CIA) rat model was used to investigate the therapeutic effect of BMSCs-Exos on RA. Our results showed that some homology and differences were observed between BMSCs and BMSCs-Exos proteins, among which proteins highly enriched in BMSCs-Exos were related to extracellular matrix and extracellular adhesion. BMSCs-Exos can be taken up by chondrocytes, promoting cell proliferation and migration. In vivo results revealed that BMSCs-Exos significantly improved the clinical symptoms of RA, showing a certain repair effect on the injury of articular cartilage. In short, our study revealed, for the first time, that BMSCs-Exos possess remarkable efficacy in alleviating RA symptoms, probably through shuttling proteins related to cell adhesion and tissue repair ability in CIA rats, suggesting that BMSCs-Exos carrying expressed proteins may become a useful biomaterial for RA treatment.

The cell membrane exhibits a remarkable complexity of lipids and proteins that dynamically segregate into distinct domains to coordinate various cellular functions. The ability to manipulate the partitioning of specific membrane proteins without involving genetic modification is essential for decoding various cellular processes but highly challenging. In this work, by conjugating cholesterols or tocopherols at the three bottom vertices of the DNA tetrahedron, we develop two sets of nanodevices for the selective targeting of lipid-order (Lo) and lipid-disorder (Ld) domains on the live cell membrane. By incorporation of protein-recognition ligands, such as aptamers or antibodies, through toehold-mediated strand displacement, these DNA nanodevices enable dynamic translocation of target proteins between these two domains. We first used PTK7 as a protein model and demonstrated, for the first time, that the accumulation of PTK7 to the Lo domains could promote tumor cell migration, while sequestering it in the Ld domains would inhibit the movement of the cells. Next, based on their modular nature, these DNA nanodevices were extended to regulate the process of T cell activation through manipulating the translocation of CD45 between the Lo and the Ld domains. Thus, our work is expected to provide deep insight into the study of membrane structure and molecular interactions within diverse cell signaling processes.

Three hydrophobic porphyrin titanium-based metal-organic frameworks (MOFs) (HPA/DGIST-1, DPA/DGIST-1, and OPA/DGIST-1) were synthesized through a postsynthetic coordination reaction by using alkylphosphonic acid of different lengths (HPA, hexylphosphonic acid; DPA, dodecylphosphonic acid; OPA, octadecylphosphonic acid). Compared with the hydrophilic DGIST-1, modified DGIST-1 exhibits excellent hydrophobicity and presents good stability in humid atmospheres. Due to the introduction of porphyrin ligands, HPA/DGIST-1, DPA/DGIST-1, and OPA/DGIST-1 showed good visible-light absorption (380-700 nm) and sensitive photogenerated charge responses. When acted as catalysts, these hydrophobic Ti-MOFs can selectively reduce CO 2 to HCOO - under visible-light irradiation with average reaction rates of 150.9, 178.5, and 228.3 μmol·h -1 ·g -1 , where these values are 1.3-2.0 times higher than the system mediated by the initial porphyrin Ti-MOF catalyst. 13 C NMR spectroscopy demonstrates that the catalytic product HCOO - anion originates from the reactant CO 2 . The photocatalytic experiments, electron paramagnetic resonance, and photoluminescence spectra tests showed that porphyrin ligands and Ti-O units can act as catalytic activity centers to realize the conversion of CO 2 to HCOO - . This work demonstrated that the combination of porphyrin titanium-based MOF and alkyl hydrophobic groups is an effective way to enhance the stability of titanium-based MOFs and maintain their high photocatalytic performance.

Modulating the photon emission of the luminophore for boosting chemiluminescence (CL) response is very crucial for the construction of highly sensitive sensors via the introduction of functionalized materials. Herein, the integration of the emitter and coreactant accelerator into one entity is realized by simply assembling cucurbit[7]uril (CB[7]) on the surface of gold nanoparticles (AuNPs) through simple assembly via a Au-O bond. The loaded CB[7] on the AuNPs improves their catalytic capacity for the generation of hydroxyl radicals( • OH). Moreover, the host-guest recognition interaction between luminol and CB[7] enables the capture of luminol on AuNPs efficiently. Also, the intramolecular electron-transfer reaction between the luminol and • OH enables the CL response more effectively in the entity, which greatly boosts photon emission ca 100 folds compared with the individual luminol/H 2 O 2 . The host-guest recognition between luminol and CB[7] is revealed by Fourier transform infrared spectroscopy, electrochemical, and thermogravimetric characterization. Moreover, the proposed CL system is successfully used for the sensitive and selective determination of dopamine (DA) based on a synergistic quenching mechanism including the competition quenching and radical-scavenging effect from DA. The present amplified strategy by integrating recognized and amplified elements within one entity simplifies the sensing process and holds great potential for sensitive analysis based on the self-enhanced strategies.

In this study, four isostructural aluminum-based porphyrin metal-organic frameworks [Al-TCPP(M), M = H 2 and Zn] with different morphologies and sizes were synthesized by the hydrothermal method. By adjusting the hydrothermal reaction time and the types of porphyrin ligands, Al-TCPP(M) MOFs exhibited diverse morphologies including tetragonal, rectangular, and carambola-like phase. In view of the introduction of porphyrin ligands and the strong coordination effect of Al-O units, Al-TCPP(M) MOFs exhibited good chemical stability, broad visible light harvesting capability, and fast photogenerated charge response. Four Al-TCPP(M) MOFs exhibited excellent photocatalytic activities for Cr(VI) in aqueous solution. Notably, the regulation to the nanoscale carambola-like morphology of Al-TCPP MOFs and metallization of the porphyrin ligand promoted the Cr(VI) photoreduction reaction where the catalytic activity of metallic carambola-like Al-TCPP increased 1.7 times compared to that of nonmetallic tetragonal MOFs. With the assistance of sonophotocatalysis, the Cr(VI) average reduction rates reached 0.658, 0.542, 0.785, and 0.629 mg·L -1 ·min -1 for Al-TCPP(H 2 )-24h, Al-TCPP(H 2 )-72h, Al-TCPP(Zn)-24h, and Al-TCPP(Zn)-72h, which are 1.2-1.4 times higher than that of photocatalysis. UV-vis absorption spectroscopy, electronic spin resonance, and fluorescence spectroscopy experiments demonstrated that the synergistic effect of photochemistry and sonochemistry promoted the transfer of photogenerated electrons from Al-TCPP(M) to Cr(VI), thus enhancing the catalytic activity. The combination of the sonophotocatalytic technology with aluminum-porphyrin MOFs may become an effective strategy to improve MOF-based photocatalytic systems.

Highly selective capture of cesium (Cs + ) from complex aqueous solutions has become increasingly important owing to its ( 133 Cs) indispensable role in some cutting-edge technologies and the environmental mobility of radioactive nuclide ( 137 Cs) from nuclear wastewater. Herein, we report the development of cation-intercalated lamellar MoS 2 as an effective Cs + adsorbent with the advantages of facile synthesis and highly tunable layer spacing. Two types of cations, including Na + and NH 4 + , were employed for the intercalations between adjacent layers of MoS 2 . The results demonstrated that the adsorption capacity of the NH 4 + -intercalated material (M-NH 4 + , 134 mg/g) for Cs + clearly outperformed the others due to higher loading percentages of cations and larger layer spacing. The cesium partition coefficients for M-NH 4 + in the presence of 100-fold competing ions all exceed 1 × 10 3 mL/g. A simulated complex aqueous solution containing 15.37 mg/L Cs + and highly excess of competing ions Li + , Na + , K + , Mg 2+ , and Ca 2+ (20-306 times higher) was introduced to prove the practical application potential using our best-performing M-NH 4 + , showing a good to excellent partition ability of Cs + among other cations, especially for Cs/K and Cs/Na with separation factors of 58 and 212, respectively. The adsorption and selectivity mechanisms were clearly elucidated using various advanced techniques, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. These results revealed that the good selectivity for Cs + can be ascribed to the differences in Lewis acidities, hydration energy, cation sizes, and in particular, the divergence of coordination modes which was successfully achieved after tuning the layer distance via the cation intercalation strategy. In addition, the material has fast kinetics (<30 min), wide range of pH tolerance (4-10), and good reusability. Overall, our studies point out that the tunable lamellar MoS 2 -based materials are promising adsorbents for Cs + capture and separation.

Paclitaxel-induced peripheral neuropathy (PIPN) is one of the common adverse effects during the paclitaxel (PTX) treatment of cancer. In this study, we investigated the neuroprotective effects and mechanisms of thymoquinone (TQ) in the PIPN model. Through pain behavioral assays and histological assessment, we demonstrated that TQ significantly alleviated the nociceptive behavior, modulated the pathological changes in peripheral nerves, and decreased the expression of inflammatory factors TNF-α, IL-1β, and IL-6 induced by PIPN in mice. In addition, TQ significantly reversed the reduced viability and inflammatory response of primary DRG neurons caused by PTX. Moreover, the gene expression of related pathways was detected by Western blot, qPCR, and immunofluorescence, and the results showed that TQ exerts neuroprotective effects by regulating TLR4/MyD88 and its downstream NF-κB and MAPKs inflammatory pathways in vivo and in vitro . The treatment with TLR4 antagonist TAK-242 further indicated the important role of the TLR4/MyD88 signaling pathway in PIPN. Furthermore, molecular docking and a cellular thermal shift assay were used to confirm the interaction of TQ with TLR4. In summary, our study shows that TQ can inhibit inflammatory responses against PIPN by regulating TLR4 and MyD88 and its downstream inflammatory pathways.

mRNA vaccines encoding a single spike protein effectively prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the emergence of SARS-CoV-2 variants leads to a wide range of immune evasion. Herein, a unique trivalent mRNA vaccine based on ancestral SARS-CoV-2, Delta, and Omicron variant spike receptor-binding domain (RBD) mRNAs was developed to tackle the immune evasion of the variants. First, three RBD mRNAs of SARS-CoV-2, Delta, and Omicron were coencapsulated into lipid nanoparticles (LNPs) by using microfluidic technology. After that, the physicochemical properties and time-dependent storage stability of the trivalent mRNA vaccine nanoformulation were tested by using dynamic light scattering (DLS). In vitro , the trivalent mRNA vaccine exhibited better lysosomal escape ability, transfection efficiency, and biocompatibility than did the commercial transfection reagent Lipo3000. In addition, Western blot analyses confirmed that the three RBD proteins can be detected in cells transfected with the trivalent mRNA vaccine. Furthermore, ex vivo imaging analysis indicated that the livers of BALB/c mice had the strongest protein expression levels after intramuscular (IM) injection. Using a prime-boost strategy, this trivalent vaccine elicited robust humoral and T-cell immune responses in both the high-dose and low-dose groups and showed no toxicity in BALB/c mice. Three specific IgG antibodies in the high-dose group against SARS-CoV-2, Delta, and Omicron variants approached ∼1/1,833,333, ∼1/1,866,667, and ∼1/925,000, respectively. Taken together, two doses of inoculation with the trivalent mRNA vaccine may provide broad and effective immunization responses against SARS-CoV-2 and variants.

Developing high-performance electrocatalysts for oxygen evolution reaction (OER) is of importance for improving the overall efficiency of water splitting. Herein, the CoFe/(Co x Fe 1- x ) 3 Mo 3 C heterojunction is purposely designed as an OER catalyst, which displays a low overpotential of 293 mV for affording a current density of 10 mA cm -2 and a small Tafel slope of 48 mV/dec. Various characterization results demonstrate that the significant work-function difference between CoFe and (Co x Fe 1- x ) 3 Mo 3 C can induce interfacial charge redistribution, which results in the formation of Co and Fe sites with a high-spin state, thus stimulating the surface phase reconstruction of CoFe/(Co x Fe 1- x ) 3 Mo 3 C to corresponding active oxyhydroxide. Meanwhile, the electrochemical leaching of Mo ions from the initial structure can contribute to the formation of defective sites, further benefiting OH - adsorption and surface oxidation. Moreover, the remaining CoFe can accelerate electron migration during the electrocatalytic process. This study presents new insights into constructing efficient OER electrocatalysts with an optimized spin-state configuration via interfacial engineering.

Gray mold caused by Botrytis cinerea leads to huge economic losses to the kiwifruit ( Actinidia chinensis ) industry. Elucidating the molecular mechanism responding to B. cinerea is the theoretical basis for the resistance to molecular breeding of kiwifruit. Previous studies have shown that miR160 regulates plant disease resistance through the indole-3-acetic acid (IAA) signaling pathway. In this study, kiwifruit "Hongyang" was used as the material, and Ac-miR160d and its target genes were identified and cloned. Overexpression and virus-induced gene silencing (VIGS) technology combined with RNA-seq were adopted to analyze the regulatory role of Ac-miR160d in kiwifruit resistance to B. cinerea . Silencing Ac-miR160d ( AcMIR160d -KN) increased kiwifruit sensitivity to B. cinerea , whereas overexpression of Ac-miR160d ( AcMIR160d -OE) increased kiwifruit resistance to B. cinerea , suggesting that Ac-miR160d positively regulates kiwifruit resistance to B. cinerea . In addition, overexpression of Ac-miR160d in kiwifruit increased antioxidant enzyme activities, such as catalase (CAT) and superoxide dismutase (SOD), and endogenous phytohormone IAA and salicylic acid (SA) content, in response to B. cinerea -induced stress. RNA-seq identified 480 and 858 unique differentially expressed genes in the AcMIR160d -KN vs CK and AcMIR160d -OE vs CK groups, respectively, with fold change ≥2 and false discovery rate <0.01. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that families associated with "biosynthesis of secondary metabolites" are possibly regulated by Ac-miR160d. "Phenylpropanoid biosynthesis", "flavonoid biosynthesis", and "terpenoid backbone biosynthesis" were further activated in the two comparison groups upon B. cinerea infection. Our results may reveal the molecular mechanism by which miR160d regulates kiwifruit resistance to B. cinerea and may provide gene resources for molecular breeding in kiwifruit resistance.

Our understanding is limited concerning the interaction mechanism between widespread phthalate esters and staple crops, which have strong implications for human exposure. Therefore, this study was aimed at illuminating the transformation pathways of di- n -butyl phthalate (DnBP) in rice using an untargeted screening method. UPLC-QTOF-MS identified 16 intermediate transformation products formed through hydroxylation, hydrolysis, and oxidation in phase I metabolism and further by conjugation with amino acids, glutathione, and carbohydrates in phase II metabolism. Mono-2-hydroxy- n -butyl phthalate-l-aspartic acid (MHBP-asp) and mono-2-hydroxy- n -butyl phthalate-d-alanyl-β-d-glucoside (MHBP-ala-glu) products were observed for the first time. The proteomic analysis demonstrated that DnBP upregulated the expression of rice proteins associated with transporter activity, antioxidant synthesis, and oxidative stress response and downregulated that of proteins involved in photosynthesis, photorespiration, chlorophyll binding, and mono-oxygenase activity. Molecular docking revealed that DnBP can affect protein molecular activity via pi-sigma, pi-alkyl, and pi-pi interactions or by forming carbon-hydrogen bonds. The metabolomic analysis showed that key metabolic pathways including citrate cycle, biosynthesis of aminoacyl-tRNA, and metabolism of amino acids, sphingolipids, carbohydrates, nucleotides, and glutathione were activated in rice plants exposed to DnBP and its primary metabolite mono- n -butyl phthalate (MnBP). Furthermore, exposure to 80 ng/mL MnBP significantly perturbed the metabolic profile and molecular function in plants, with downregulation of the levels of beta-alanine (0.56-fold), cytosine (0.48-fold), thymine (0.62-fold), uracil (0.48-fold), glucose (0.59-fold), and glucose-1-phosphate (0.33-fold), as well as upregulation of the levels of l-glutamic acid (2.97-fold), l-cystine (2.69-fold), and phytosphingosine (38.38-fold). Therefore, the degradation intermediates of DnBP pose a potentially risk to plant metabolism and raise concerns for crop safety related to plasticizer pollution.

Room-temperature phosphorescence (RTP) is a photophysical phenomenon typically associated with a long-lived emission that can be detected by the unaided eye. Several natural proteins display RTP, as do certain artificial polymers. In both cases, the RTP is ascribed to effective intramolecular through-space electronic communication. However, small molecules with internal electronic communication that enable RTP are relatively rare. Herein, we describe an alkyl halide-responsive RTP system consisting of a meta -formylphenyl-bearing pillar[5]arene derivative that supports effective through-space charge transfer (TSCT) within the pillararene cavity. Treatment with bromoethane, a heavy atom-containing guest for the pillar[5]arene host, serves to enhance the emission. An isomeric para -formylphenyl-bearing pillar[5]arene system proved ineffective in producing an RTP effect. Quantum chemical calculations based on single-crystal X-ray diffraction analyses provided insights into the structural determinants governing TSCT between the 1,4-dimethoxybenzene donor units and the formylphenyl groups of the pillar[5]arene, as well as the associated energy gaps and intersystem crossing channels. We believe that the present system and the associated mechanistic analysis provide the foundation for design of new small molecule with tunable RTP features.

A series of methane-vented explosions were experimentally investigated in a 4.5 m 3 rectangular chamber at P 0 = 100 kPa and T 0 = 298 K, and the effects of ignition positions and vent areas on the external flame and temperature characteristics were studied. The results indicate that the vent area and ignition position significantly affect external flame and temperature changes. The external flame is portioned into three stages: an external explosion, a violent flame jet with a blue flame, and a yellow flame venting. The temperature peak first rises and then reduces with increasing distance. Rear ignition produces the largest flame lengths and highest temperature, while front ignition leads to the shortest flame and smallest temperature peak. The maximum flame diameter occurs at central ignition. As vent areas increase, the coupling effect of the pressure wave and the internal flame front weakens and the diameter and peak of the high-temperature peak increase. These results can offer scientific guidance for designing disaster prevention measures and evaluating explosion accidents in buildings., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Flavor molecules are commonly used in the food industry to enhance product quality and consumer experiences but are associated with potential human health risks, highlighting the need for safer alternatives. To address these health-associated challenges and promote reasonable application, several databases for flavor molecules have been constructed. However, no existing studies have comprehensively summarized these data resources according to quality, focused fields, and potential gaps. Here, we systematically summarized 25 flavor molecule databases published within the last 20 years and revealed that data inaccessibility, untimely updates, and nonstandard flavor descriptions are the main limitations of current studies. We examined the development of computational approaches (e.g., machine learning and molecular simulation) for the identification of novel flavor molecules and discussed their major challenges regarding throughput, model interpretability, and the lack of gold-standard data sets for equitable model evaluation. Additionally, we discussed future strategies for the mining and designing of novel flavor molecules based on multi-omics and artificial intelligence to provide a new foundation for flavor science research.

In this work, an urchin-like Ni@Ni 2 P@NiCoP (Ni@NP@NCP) composite was prepared on nickel foam by a simple hydrothermal treatment process. Using the prepared NiO nanosheets as templates, the NiCo precursor was prepared in the presence of three solvothermal systems of water/dimethylformamide (DMF)/dimethyl sulfoxide (DMSO) by the hydrothermal process. After mixing and calcining with sodium hypophosphite under a nitrogen atmosphere at a high temperature for phosphating, an urchin-like Ni@NP@NCP(F/SO/H) nanostructured catalyst was obtained with superior hydrogen evolution and oxygen evolution performance. To further explore their efficiency in seawater splitting. Ni@NP@NCP(F/SO/H) composites were used as the cathode and anode of an electrolytic cell, which delivered 1.822 V potential at 300 mA cm -2 in simulated seawater (1 M KOH and 0.5 M NaCl). This may provide an effective way of developing clean energy.

Docetaxel (DTX), a semisynthetic analogue of paclitaxel, is often used to treat cancers. Owing to its poor aqueous solubility, the current formulation of DTX for clinical applications involves using high surfactant and ethanol concentrations, causing hypersensitivity reactions. To overcome this issue, we developed a reduction-responsive DTX prodrug encapsulated within human serum albumin (HSA) nanoparticles (DTX-SS-COOH/HSA NPs). First, the DTX prodrug was conjugated to undecanoic acid through a disulfide bond (DTX-SS-COOH) via a four-step reaction. Subsequently, DTX-SS-COOH/HSA NPs were prepared via the desolvation method. The NPs exhibited a spherical structure with a diameter range of 140-220 nm, as revealed by dynamic light scattering and transmission electron microscopy. Fluorescence quenching analysis confirmed the formation of DTX-SS-COOH/HSA, which was ascribed to electrostatic interactions and hydrophobic forces. Notably, NPs with a feed mole ratio corresponding to DTX-SS-COOH/HSA = 9:1 demonstrated high drug-loading and encapsulation efficiency of 12.84 and 93.11%, respectively, alongside good stability. Moreover, the reduced responsiveness experiment revealed an accelerated DTX release in the presence of glutathione. An in vivo pharmacokinetic study indicated that DTX-SS-COOH/HSA NPs demonstrated considerably a prolonged circulation time (6.2-fold) compared to that of free DTX. Ultimately, the antitumor test of MDA-MB-231 tumor-bearing mice revealed that DTX-SS-COOH/HSA NPs were superior to DTX/HSA NPs for tumor growth inhibition. Thus, DTX-SS-COOH/HSA NPs represent a promising DTX nanoformulation for clinical application.

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell receptor (BCR)-mediated signaling as well as the downstream signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell malignancies by interfering with BCR signaling has been clinically validated by some covalent inhibitors, but suboptimal kinase selectivity may lead to some adverse effects, which also makes the clinical development of autoimmune disease therapy more challenging. The structure-activity relationship (SAR) starting from zanubrutinib ( BGB - 3111 ) leads to a series of highly selective BTK inhibitors, in which BGB - 8035 is located in the ATP binding pocket and has similar hinge binding to ATP but exhibits high selectivity over other kinases (EGFR, Tec, etc.). With an excellent pharmacokinetic profile as well as demonstrated efficacy studies in oncology and autoimmune disease models, BGB - 8035 has been declared a preclinical candidate. However, BGB - 8035 showed an inferior toxicity profile compared to that of BGB - 3111 .

Genipin (GP), the reactive metabolite of geniposide (GE), is responsible for GE-induced hepatotoxicity. As a potential detoxification pathway, the inactivation of GP by glutathione S-transferases (GSTs) has not yet been characterized. In this study, the thiol-GSH conjugates of GP, M532-1 and M532-2 were first identified and the catalytic activities of GSTs were investigated both in vitro and in vivo. GSTA1-1 and GSTA4-4 showed high activity in the formation of both thiol-GSH conjugates, whereas GSTA4-4 specifically catalyzed M532-2 formation in vitro. The active GST isoforms protect against alkylation of N -acetylcysteine (NAC), a classic model nucleophile. GST inhibition attenuated M532-1 formation in rat bile, confirming the in vivo catalytic role of GSTs. In conclusion, this study demonstrated the inactivation of GP by GSTs and implied that interindividual variability of GSTs may be a risk factor for susceptibility to GE-induced hepatotoxicity.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic and swift approval of two mRNA vaccines have put nucleic acid therapeutics in the spotlight of both the scientific community and the general public. Actually, in addition to mRNAs, multiple nucleic acid therapeutics have been successively commercialized over the past few years. The rapid development of nucleic acid drugs not only demonstrates their superior potency but also marks a new era of the field. Compared with conventional treatments targeting proteins rather than the root causes of diseases at the genetic level, nucleic acids are capable of achieving long-standing or even curative effects against undruggable disorders by modulating gene expression via inhibition, editing, addition, or replacement. This offers a terrific arsenal for expanding therapeutic access to diseases lacking current treatment options and developing vaccines to provide swift responses to emerging global health threats.Despite the stunning success and recent resurgence of interest in the field, the unfavorable physicochemical characteristics (i.e., the negative charge, large molecular weight, and hydrophilicity), susceptibility to nuclease degradation, off-target toxicity, and immunogenicity are a brake for moving nucleic acid therapeutics from bench to bedside. Currently, developing technologies to improve the circulation stability, targeting affinity, cellular entry, endolysosomal escape, efficacy, and safety of nucleic acid drugs still remains a major pharmaceutical bottleneck.In this Account, we outline the research efforts from our group on the development of technology platforms to overcome the pharmaceutical bottlenecks for nucleic acid therapeutics. We have engineered a variety of intelligent delivery platforms such as synthetic nanomaterials (i.e., lipid nanoparticles, polymers, and inorganic nanoparticles), physical delivery methods (i.e., electroporation), and naturally derived vehicles (i.e., extracellular vesicles), aiming at endowing nucleic acids with improved circulation stability, targeting affinity, and cellular internalization (Get in) and stimuli responsive endolysosomal escape capability (Get out). Moreover, we will discuss our progress in developing a series of modification strategies for sequence engineering of nucleic acids to endow them with enhanced nuclease resistance, translation efficiency, and potency while alleviating their off-target toxicity and immunogenicity (Sequence engineering). Integrating these technologies may promote the development of nucleic acid therapeutics with potent efficacy and improved safety (Efficacy & safety). With this Account, we hope to offer insights into rational design of cutting-edge nucleic acid therapeutic platforms. We believe that the continuing advances in nucleic acid technologies together with academic-industry collaborations in the clinic, will promise to usher in more clinically translatable nucleic acid therapeutics in the foreseeable future.

Substrate selectivity is one of the most attractive features of natural enzymes from their "bind-to-catalyze" working flow and is thus a goal for the development of synthetic enzyme mimics that mediate abiotic transformations. However, despite the recent success in the preparation of substrate-selective enzyme mimics based on single-chain nanoparticles, examples extending such selectivity into living systems have been absent. In this article, we report the in cellulo substrate selectivity of an enzyme-mimicking macromolecular catalyst based on a cationic dense-shell nanoparticle (DSNP) scaffold. With a systematic study on DSNP's structure-activity relationship, we demonstrate that the DSNP has excellent membrane affinity that is governed by several contributing factors, namely, charge density, type of charge, and particle size, and the best-performing phosphonium-rich DSNP can be used as a membrane-embedded catalyst (MEC) for efficient on-membrane synthesis. Importantly, the DSNP catalyst retains its selectivity toward lipophilic and anionic substrates when working as an MEC for on-membrane ligation. The usefulness of such substrate selectivity and on-membrane catalysis strategy was exemplified with several molecules of interest with low cell permeability and anionic nature, which were successfully transported into eukaryotic cells by after their formation directly on the cell membrane.

Pterostilbene (PTE), a dietary derivative of resveratrol, displayed pleiotropic health-promoting activities. This study aimed to explore the metabolic profiles and species differences of the phase I metabolism of PTE and to investigate subsequent detoxification after PTE bioactivation. PTE was found to be biotransformed to two pharmacologically active metabolites, pinostilbene and 3'-hydroxypterostilbene, in vivo and in vitro with substantial species differences. Human CYP1A2 was proved to be mainly responsible for the demethylation and 3'-hydroxylation of PTE, with its contribution to a demethylation of 94.5% and to a 3'-hydroxylation of 97.9%. An in vitro glutathione trapping experiment revealed the presence of an ortho -quinone intermediate formed by further oxidation of 3'-hydroxypterostilbene. Human glutathione S -transferase isoforms A2, T1, and A1 inactivated the ortho -quinone intermediate by catalyzing glutathione conjugation, implicating a potential protective pathway against PTE bioactivation-derived toxicity. Overall, this study provided a comprehensive view of PTE phase I metabolism and facilitated its further development as a promising nutraceutical.

Protein kinase N3 (PKN3), by virtue of its abnormal expression in prostate cells, has been widely used as a target of RNAi (shRNA, siRNA, miRNA) therapy. The major challenges of PKN3 RNAi therapy lie in how to design effective interference sequences and delivery systems. Herein, new PKN3 shRNA sequences (shPKN3-2459 and shPKN3-3357) were designed, and bioreducible, biodegradable, ionizable lipid-based nanoparticles were developed for shPKN3 delivery. First, an ionizable lipid (DDA-SS-DMA) bridged with disulfide bond and ester bonds was synthesized by a three-step reaction and confirmed by MS, 1 H NMR, and 13 C NMR. The ionizable lipid was mixed with cholesterol, DSPC, PEG-lipid, and shPKN3 by a microfluidic mixer to prepare lipid nanoparticles (LNP-shPKN3) which were characterized by DLS and TEM. Afterward, the pH and glutathione (GSH)-responsiveness of the DDA-SS-DMA based LNP delivery system were investigated by lysosome escape and gel electrophoresis assays. Compared with the commercial transfection reagent Lipo2000, the DDA-SS-DMA based delivery system showed higher transfection efficiency and lower toxicity. Western blot analysis, invasion tests, and migration assays were performed to evaluate the silencing effect of shPKN3 in vitro . In in vivo studies, high tumor suppression (65.8%) and treatment safety were evident in the LNP-shPKN3-2459 treatment group. Taken together, the DDA-SS-DMA based delivery system encapsulating shPKN3-2459 showed significant antitumor efficacy and might be a promising formulation for the treatment of prostate cancer.

Ball milling at ambient temperatures can accelerate the formation and accumulation of early-stage Maillard reaction intermediates considered important precursors of aromas and antioxidants. In this study, using chemical and biological assays, we explored the potential of sequential milling and heating to enhance the antioxidant and aroma-generating capacity of Maillard model systems. Milling (30 Hz/30 min) followed by dry heating (90 °C/30 min) of glycine or lysine with glucose significantly increased not only the intensity of their aroma-active compounds as analyzed by headspace-gas chromatography/mass spectrometry (HS-GC/MS) but also their free radical scavenging capacity as assessed by 2,2'-azino-bis-(3-ethylbenzothiazoneline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assays. This was attributed to the increased formation of redox-active endiol moieties and precursors of N , N -dialkyl-pyrazinium radical cation in the lysine system assessed by electrospray ionization-quadrupole time-of-flight/tandem mass spectrometry (ESI-QqTOF/MS/MS) analysis. The test samples also inhibited NO generation and cellular oxidative stress in RAW 264.7 murine macrophage cells, indicating size reduction induced by milling promoted paracellular absorption.

In this work, we synthesized and characterized four titanium-porphyrin metal-organic frameworks (MOFs) [DGIST-1(M), M = Co(II), Fe(III), Zn(II), and H 2 ] and used them as visible-light-driven catalysts for sonophotocatalytic Cr(VI) reduction. DGIST-1(M) exhibited open-framework, broad light absorption stemmed from ligand and sensitive photocurrent responses owing to the integration of one-dimensional Ti-oxo chains and 4-connected conjugated TCPP ligand (TCPP = tetrakis(4-carboxyphenyl)-porphyrin). DGIST-1(M) presented efficient reduction of Cr(VI) to Cr(III) in aqueous solution when used as sonophotocatalytic catalysts. The average reduction rates upon Cr(VI) were 0.920, 0.476, 0.377, and 0.194 mg·L -1 ·min -1 for DGIST-1(H 2 ), DGIST-1(Zn), DGIST-1(Co), and DGIST-1(Fe), which are 1.15-2.45 times higher than those in photocatalysis. Sonophotocatalytic experiments and electron paramagnetic resonance measurement proved that Ti-oxo chain units and porphyrin ligand in the structures of DGIST-1(M) existed as catalytic active centers for sonophotocatalytic reduction of Cr(VI). Photoluminescence and UV absorption spectra revealed that the unity of photocatalysis and sonochemistry strengthened the migration of photogenerated electrons from DGIST-1(M) to Cr(VI), which improved the activities of catalysts. This study suggested that the association of titanium-porphyrin MOFs and sonophotocatalytic technology is an impactful program for enhancing MOF-based photocatalytic systems.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Due to the development of drug resistance to traditional chemotherapies and high relapse rate, AML still has a low survival rate and there is in an urgent need for better treatment strategies. CD123 is widely expressed by AML cells, also associated with the poor prognosis of AML. In this study, we fabricated nanomicelles loaded with a lab-designed CD123 antagonistic peptide, which were referred to as m PO-6. The antagonistic and therapeutic effects were investigated with CD123 + AML cell lines and a refractory AML mouse (AE and CKIT D816V ) model. Results show that m PO-6 can specifically bind to the CD123 + AML cells and inhibit the cell viability effectively. Intravenous administration of m PO-6 significantly reduces the percentage of AML cells' infiltration and prolongs the median survival of AML mice. Further, the efficiency of m PO-6 is demonstrated to interfere with the axis of CD123/IL-3 via regulating the activation of STAT5, PI3K/AKT, and NF-κB signaling pathways related to cell proliferation or apoptosis at the level of mRNA and protein in vivo and in vitro . In conclusion, the novel CD123 antagonistic peptide micelle formulation m PO-6 can significantly enhance apoptosis and prolong the survival of AML mice by effectively interfering with the axis of CD123/IL-3 and therefore is a promising therapeutic candidate for the treatment of refractory AML.

All-inorganic halide perovskite nanocrystals with their fascinating optical properties have drawn increasing attention as promising nanoemitters. However, due to the intrinsic poor colloidal stability against the external environment, the practical applications are greatly limited. Herein, a facile and effective strategy for the in situ encapsulation of CsPbBr 3 NCs into highly dense multichannel polyacrylonitrile (PAN) nanofibers via a uniaxial electrospinning strategy is presented. Such a facile uniaxial electrospinning strategy enables the in situ formation of CsPbBr 3 NCs in PAN nanofibers without the introduction of stabilizers. Significantly, the obtained CsPbBr 3 nanofibers not only display intense fluorescence with a high quantum yield (≈48%) but also present high stability when exposed to water and air owing to the peripheral protecting matrix of PAN. After immersing CsPbBr 3 @PAN nanofiber films in water for 100 days, the quantum yield of CsPbBr 3 @PAN nanofibers maintained 87.5% of the original value, which was much higher than that using CsPbBr 3 NCs. Furthermore, based on the spectral overlap between the electrochromic material of ruthenium purple and fluorescence of CsPbBr 3 @PAN nanofiber films with excellent water stability, a reversible fluorescence switch is constructed with good fatigue resistance, suggesting their promising applications.

A transition-metal-free catalytic system was designed to address the dehydrative cross-coupling of unactivated primary/secondary alcohols with amines/amides under environmentally benign conditions. Mg 2+ and counteranion (PF 6 - ) worked synergistically to realize C-OH bond cleavage and concomitant C-N bond formation. A wide range of allylic alcohols and amines/amides were tolerated well in this transformation, which allowed C-N bond construction with high efficiency.

We report herein an exploration of the straightforward one-pot dual-catalysis strategy, i.e., direct combination of a photoactive coordination polymer (CP) with another metal catalyst, for carrying out the desirable photoinduced organic transformation. The strategy overcomes the necessity of the presynthesis of the metal/CP composite that has been demonstrated to be invalid in our case. A new two-dimensional CP showing the desirable properties of wide-range visible-light absorption and efficient photoinduced charge generation was synthesized via a solvothermal reaction. The synthesized CP was successfully applied to the photocatalytic C-C cross-coupling reaction via the one-pot dual-catalysis method, in combination with the simple and ligand-free palladium salt of Pd(OAc) 2 as a metal catalyst. The reaction features a short reaction time, mild reaction conditions, good recyclability, and a high yield of Heck products from a broad variety of substrates. A comparative experiment showed the presynthesized Pd/CP composite was invalid for the reaction, demonstrating the significance of the one-pot dual-catalysis strategy. Mechanistic studies suggest the one-pot reaction depends on the synergy between the photocatalysis of a synthesized CP to generate reactive aryl radicals and Pd catalysis to generate target products, in which the interfacial electron transfer has been demonstrated to be vital for producing the transient and catalytically active Pd(0) species near the surface of the CP. The study shows the direct combination of a CP photocatalyst and a metal catalyst is a highly feasible method for the photochemical reaction and enhances the prospects of application of photoactive CPs.

Photochemical treatment of highly toxic Cr(VI) is a desirable and ecofriendly method to protect the environment and human beings. In this study, a MOF-based sonophotocatalytic system is established, in which visible-light-driven sonophotocatalytic reduction of toxic Cr(VI) to Cr(III) in water is investigated using zirconium-porphyrin metal-organic frameworks (MOFs) structured as PCN-222(M) [M = H 2 , Zn(II), Fe(III), Co(II)]. In the view of the synergistic effect of sonochemistry and photocatalysis, PCN-222(M) exhibited enhanced activities for Cr(VI) reduction compared with the photocatalytic process. Kinetic studies showed that apparent reaction rate constants in the sonophotocatalytic system of PCN-222(M) are 1.5-3.3 times higher than those in photocatalysis. Fluorescence and UV-vis absorption spectra measurements demonstrate that the sonophotocatalytic process promotes the transfer of photoinduced electrons from PCN-222(M) to Cr(VI), thus enhancing the catalytic performance. The innovative combination of porous MOFs and sonophotocatalytic technology might become a feasible strategy to improve the existing MOF-based photocatalytic systems.

Electrostatic generators as a kind of effective energy harvesters have attracted intensive attention. However, the output of the generators is highly dependent on the charge density. Here, we demonstrate an all-in-one rotary electrostatic nanogenerator based on the charge pumping and voltage multiplying strategy (CV-ESG), which achieves high output power in SF 6 atmosphere. CV-ESG integrates a pumping electret generator, a main generator, and a voltage multiplying and stabilization circuit on a pair of rotator and stator. We analyze the breakdown effect and its influence on the insulating layer covered on the electrodes through experiments. The breakdown voltage is high in SF 6 atmosphere, and the maximum average power of CV-ESG in SF 6 is 37.29 mW at 750 rpm, which is 3.29 times that in air. There is no surface friction in CV-ESG, which avoids abrasion and reduces friction damping. And the pumping generator is integrated with the main generator, making CV-ESG compact and easy to assemble. This work provides the design strategy for a high-power rotary electrostatic generator with good performance.

Marrubiin, a furanoid compound, is a well-known diterpenoid lactone isolated from Marrubium vulgare , which displays a wide spectrum of pharmacological effects and potential hepatotoxicity. Considering that marrubiin contains a structural alert, furan ring, metabolic activation may be one of the major metabolic pathways, and the reactive metabolite may be involved in the hepatotoxicity. The present study was carried out to investigate the bioactivation mechanism of marrubiin in rats and humans. Marrubiin was initially metabolized into cis -butene-1,4-dial intermediate, which was readily trapped by glutathione (GSH) and N -acetyl-lysine (NAL) in the microsomal incubations supplemented with NADPH. A total of nine conjugates were detected and identified by high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. M1-M3 and M6 and M7 were characterized as mono-GSH conjugates, and M4 and M5 were identified as bis-GSH conjugates. M8 and M9 were identified as NAL conjugates. In rat bile, five GSH conjugates (M1-M3; M6 and M7) were detected. M1, M8, and M9 were chemically synthesized, and their structures were characterized by 13 C NMR. Sulfaphenazole, ticlopidine, and ketoconazole displayed significant inhibitory effect on the bioactivation of marrubiin. Further phenotyping revealed that CYP2C9, CYP2C19, and CYP3A4 were the primary enzymes catalyzing the bioactivation of marrubiin. The current study provides evidence for the CYP-dominated bioactivation of marrubiin to the corresponding cis -butene-1,4-dial intermediate, which enables us to better understand the potential side effects caused by marrubiin.

Separating trace propyne from propylene is of great importance in the petrochemical industry but difficult because of very close molecular sizes and physicochemical properties, which promotes the development of high-performance porous materials with great stability in practical adsorptive separation; however, a limited number of efficient adsorbents have been reported. Here, a class of robust functionalized ionic ultramicroporous polymers (IUPs) with different branched structures that feature high-density preferential anionic binding sites and outstanding thermal and water stability is systematically studied for the separation of propyne and propylene for the first time. The functionalized pore environment of IUPs achieves the highest selectivity of propyne and propylene (126.5) for the 1/99 (v/v) mixture among porous organic polymers, as well as excellent and recyclable dynamic separation performance. Modeling studies reveal that strong basic sites of IUPs with abundant ultramicroporosity facilitate the efficient removal of propyne from propylene. This study provides important clues for the design of robust functionalized adsorbents and thus expands the currently limited dictionary of adsorbents for the separation of important gas mixtures.

Elaborating the development of functional materials with excellent performance for supercapacitors is important in energy storage devices. In the present study, nanoflower-like MCoP (M = Ni and Fe) composites were successfully fabricated on Ni foam (denoted as NF@MCoP) by a cost-effective hydrothermal and low-temperature phosphating method. Simultaneously, the unique three-dimensional structure, nanoflower morphology, and the conductive substrate provide a favorable large electroactive area, shorter electron transfer distance, and rapid electron conductivity. The as-synthesized nanoflower-like MCoP composites exhibit outstanding energy density, power density, and long-term cycling stability. These results show that the developed electrode materials with excellent performance have great application prospects in the field of supercapacitor applications.

Baculiferins are a group of marine sponge-derived polycyclic alkaloids with anti-HIV (human immunodeficiency virus) activities. To identify additional baculiferin-based congeners for SAR analysis and to investigate the mode of action, a total of 18 new baculiferin-type derivatives were synthesized. The inhibitory activities of the congeners against the HIV-1 virus were evaluated in vitro , and the relevant SAR was discussed. Compound 18 exerted the most potent activity toward VSV-G-pseudotyped HIV-1 (IC 50 of 3.44 μM) and HIV-1 strain SF33 (IC 50 of 2.80 μM) in vitro . To identify the cellular targets, three photoaffinity baculiferin probes were simultaneously synthesized. Photoaffinity labeling experiments together with LC-MS/MS data identified aspartate-tRNA ligase (DARS) as a putative target protein of 18 . The overexpression and knockdown of DARS in HEK293T cells provided additional data to demonstrate that DARS is a potential target protein in the regulation of HIV virus infection. The modes of antiviral baculiferins 13 and 18 binding to DARS were determined by a molecular docking simulation. Thus, baculiferin 18 is considered a promising lead as a new molecular target for the development of anti-HIV agents.

Supramolecular nanostructures with tunable properties can have applications in medicine, pharmacy, and biotechnology. In this work, we show that the self-assembly behavior of peptide amphiphiles (PAs) can be effectively tuned by replacing the carboxylic acids exposed to the aqueous media with isosteres, functionalities that share key physical or chemical properties with another chemical group. Transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering studies indicated that the nanostructure's morphologies are responsive to the ionization states of the side chains, which are related to their p K a values. Circular dichroism studies revealed the effect of the isosteres on the internal arrangement of the nanostructures. The interactions between diverse surfaces and the nanostructures and the effect of salt concentration and temperature were assessed to further understand the properties of these self-assembled systems. These results indicate that isosteric replacements allow the pH control of supramolecular morphology by manipulating the p K a of the charged groups located on the nanostructure's surface. Theoretical studies were performed to understand the morphological transitions that the nanostructures underwent in response to pH changes, suggesting that the transitions result from alterations in the Coulomb forces between PA molecules. This work provides a strategy for designing biomaterials that can maintain or change behaviors based on the pH differences found within cells and tissues.

Herein, a novel metal-organic framework (MOF) with a pillared-layer structure was rationally synthesized to initiate intermolecular atom-transfer radical addition (ATRA) via photoinduced electron transfer activation of haloalkanes. The MOF synthesized via the controllable pillared-layer method is of excellent visible-light absorption and high chemical stability. Photocatalytic experiments show the atom transfer of various alkyl halides (R-X, X = Cl/Br/I) onto diverse olefins was successfully achieved to produce functional ATRA products. The mechanism and experimental investigations reveal the prepared MOF serves as an efficient photocatalyst with strong reduction potential to activate haloalkane substrates via photoinduced electron transfer, generating a highly reactive alkyl radical to trigger the ATRA reaction. Key events in the ATRA reaction, including alkyl radical photogeneration as well as halide transfer, have been further regulated to achieve preferable photocatalytic performance with higher yields, shorter reaction time, and desirable cycling capability. It is notable that the work is the first report on photoinduced electron transfer activation of halides by a MOF photocatalyst for the ATRA reaction, providing a new blueprint for MOFs to develop photoinduced radical reactions.

A chemical fixation strategy originating from single-atom-anchoring with metal-organic frameworks as a carrying matrix was proposed for solid-state electrochemiluminescence (ECL). Herein, UiO-67(N) with the exposure of 2,2'-bipyridine (bpy) ligands could coordinate with Ru 2+ to form a local structure of [Ru(bpy) 3 ] 2+ (Ru-UiO). The influence of the steric effect induced with different Ru sources was discussed. The as-obtained Ru-UiO exhibits high ECL intensity and outstanding stability in the presence of a coreactant at low concentrations. The proposed synthesis strategy may hold great potential for the synthesis of solid-state ECL materials and their further utilization in ECL analysis.

Metal-organic framework (MOF) materials are intriguing photocatalysts to trigger radical-mediated chemical transformations. We report herein the synthesis and characterization of a series of isomorphic MOFs which show a novel structure, wide visible-light absorption, high chemical stability, and specific redox potential. The prepared MOFs were explored for the photoinduced single-electron oxidation of thiol compounds, generating reactive thiyl radicals to afford thioethers via a convenient thiol-olefin reaction. Importantly, we provide a widely applicable strategy by combing a photoactive MOF with phosphine to modulate the generation of thiyl radical in the reaction, thereby producing a single product of the thioether without the formation of a disulfide byproduct due to the dimerization of thiyl radicals. The photocatalytic reaction takes advantage of this strategy, showing great generality where tens of thiols and olefins have been examined as coupling partners. In addition, the strategy has also been demonstrated to be effective for the reactions catalyzed by other MOFs. Mechanism studies reveal that the selective synthesis of C-S products relies on a synergy between the photoinduced generation of a thiyl radical over the MOF and the in situ cleavage of S-S bond into a S-H bond by phosphine. It is notable that the synthesized MOFs show advanced performance in comparison with classical MOFs. The work not only provides a series of novel MOF photocatalysts that are capable of photoinduced thiol-olefin coupling but also indicates the great potential of MOFs for photochemical transformations mediated by reactive radicals.