Aptamer-based assembly systems for SARS-CoV-2 detection and therapeutics.

Nucleic acid aptamers are oligonucleotide chains with molecular recognition properties. Compared with antibodies, aptamers show advantages given that they are readily produced via chemical synthesis and elicit minimal immunogenicity in biomedicine applications. Notably, aptamer-encoded nucleic acid assemblies further improve the binding affinity of aptamers with the targets due to their multivalent synergistic interactions. Specially, aptamers can be engineered with special topological arrangements in nucleic acid assemblies, which demonstrate spatial and valence matching towards antigens on viruses, thus showing potential in the detection and therapeutic applications of viruses. This review presents the recent progress on the aptamers explored for SARS-CoV-2 detection and infection treatment, wherein applications of aptamer-based assembly systems are introduced in detail. Screening methods and chemical modification strategies for aptamers are comprehensively summarized, and the types of aptamers employed against different target domains of SARS-CoV-2 are illustrated. The evolution of aptamer-based assembly systems for the detection and neutralization of SARS-CoV-2, as well as the construction principle and characteristics of aptamer-based DNA assemblies are demonstrated. The typically representative works are presented to demonstrate how to assemble aptamers rationally and elaborately for specific applications in SARS-CoV-2 diagnosis and neutralization. Finally, we provide deep insights into the current challenges and future perspectives towards aptamer-based nucleic acid assemblies for virus detection and neutralization in nanomedicine.

Tuning A-Site Cation Deficiency in Pr0.5La0.5BaCo2O5+ δ Perovskite to Realize Large-Scale Hydrogen Evolution at 2000 mA cm-2.

Industrial-level hydrogen production from the water electrolysis requires reducing the overpotential (η) as much as possible at high current density, which is closely related to intrinsic activity of the electrocatalysts. Herein, A-site cation deficiency engineering is proposed to screen high-performance catalysts, demonstrating effective Pr0.5- xLa0.5BaCo2O5+ δ (P0.5- xLBC) perovskites toward alkaline hydrogen evolution reaction (HER). Among all perovskite compositions, Pr0.4La0.5BaCo2O5+ δ (P0.4LBC) exhibits superior HER performance along with unique operating stability at large current densities (J = 500-2000 mA cm-2 geo). The overpotential of ≈636 mV is achieved in P0.4LBC at 2000 mA cm-2 geo, which outperforms commercial Pt/C benchmark (≈974 mV). Furthermore, the Tafel slope of P0.4LBC (34.1 mV dec-1) is close to that of Pt/C (35.6 mV dec-1), reflecting fast HER kinetics on the P0.4LBC catalyst. Combined with experimental and theoretical results, such catalytic activity may benefit from enhanced electrical conductivity, enlarged Co-O covalency, and decreased desorption energy of H* species. This results highlight effective A-site cation-deficient strategy for promoting electrochemical properties of perovskites, highlighting potential water electrolysis at ampere-level current density.

Visible-Light-Responsive Polyoxometalate@Metal-Organic Frameworks Involving Ir Metalloligands for Highly Selective Photocatalytic Oxidation of Sulfides to Sulfoxide.

The synthesis of highly efficient visible-light-responsive photocatalysts is fundamental to solving the problems of low efficiency and poor selectivity in photocatalytic organic synthesis reactions. We synthesized a crystalline polyoxometalate @metal-organic framework material {Zn4 (H2 O)8 [Ir(ppy)2 (dcbpy)]4 [SiW12 O40 ]} ⋅ 4H2 O (Ir-SiW) by self-assembly of Ir metalloligands with POMs. The introduction of Ir metalloligands extends the light absorbing range to visible light, improving the efficient utilization of solar energy. The transfer of photogenerated electrons from Ir metalloligands to SiW12 was observed under visible light irradiation, which boosted the carrier separation efficiency. The synergistic effect of the two components increased the photocatalytic thioether oxidation activity, and the product methyl phenyl sulfoxide for 2.5 h under visible light irradiation (λ >400 nm) reached 99.5 %, which was higher than those of other POM-based photocatalysts. Meanwhile, the yield of methyl phenyl sulfoxide was still higher than 97 % after three cycles, demonstrating the high stability and reusability of Ir-SiW.

{Ru(C6 H6 )}-Decorating Heteropolymolybdate for Highly Activity Photocatalytic Oxidation of Benzyl Alcohol to Benzaldehyde.

An unclassical structure of {Ru(C6 H6 )}-based polyoxometalate, Cs6 H4 [Te2 Mo12 O46 {Ru(C6 H6 )}] ⋅ 16.5H2 O (1), has been successfully constructed from {Te2 Mo12 O46 }-type heteropolymolybdate and {Ru(C6 H6 )} group, which structure type was discovered for the first time. Compound 1 not only possesses strong light-harvesting ability, but also exhibits high carrier separation efficiency and lower charge transfer resistance. Under visible light irradiation, compound 1 displayed excellent catalytic activity and circularity in the conversion of benzyl alcohol to benzaldehyde (yield=94 %; turnover number=500; turnover frequency=20.8 h-1 ). Finally, the electron paramagnetic resonance measurement and energy level matching analysis provide theoretical basis for the derivation of the reaction mechanism.

MiR-24-3p regulates the differentiation of adipose-derived stem cells toward pericytes and promotes fat grafting vascularization.

Adipose-derived stem cells (ADSCs) enhance fat graft survival by promoting neovascularization. The mechanism that promotes ADSCs differentiation toward pericytes was not known. We treated ADSCs with conditional medium (CM) from endothelial cells (ECs) or human recombinant transforming growth factor ß (TGF-ß) to induce differentiation into pericytes. Pericytes markers, including platelet-derived growth factor receptor ß (PDGFRß), alpha-smooth muscle actin (α-SMA), and desmin, were examined. Pericytes differentiation markers, migration, and their association with ECs were examined in ADSCs transfected with miR-24-3p mimics and inhibitors. Bioinformatics target prediction platforms and luciferase assays were used to investigate whether PDGFRß was directly targeted by miR-24-3p. In vivo, fat mixed with ADSCs transfected with miR-24-3p mimics or inhibitors was implanted subcutaneously on the lower back region of nude mice. Fat grafts were harvested and analyzed at 2, 4, 6, and 8 weeks. Results showed that endogenous TGF-ß derived from CM from EC or human recombinant TGF-ß promoted migration, association with ECs, and induced expression of pericyte markers (PDGFRß, α-SMA, Desmin) in ADSCs. MiR-24-3p directly targeted PDGFRß in ADSCs by lucifer reporter assays. Inhibition of miR-24-3p promoted pericytes differentiation, migration, and association with ECs in ADSCs. Inhibition of miR-24-3p in ADSCs promoted survival, integrity, adipocyte viability, vascularization, pericytes association with ECs, and reduced fibrosis, whereas overexpression of miR-24-3p in ADSCs yielded the opposite results. Collectively, TGF-ß released by ECs induced ADSCs differentiation toward pericytes through miR-24-3p. Downregulation of miR-24-3p in ADSCs induced survival, integrity, adipocyte viability, vascularization, pericytes association with ECs, and reduced fibrosis after fat grafting.

Tetra-Ln3+-Implanted Tellurotungstates Covalently Modified by dl-Malic Acid: Proton Conduction and Photochromic Properties.

Three unique dl-malic acid covalently modified tetra-Ln3+-implanted tellurotungstates [H2(CH3)2]9NaH9[Ln4(H2O)14W6O13(OH)5(Mal)2(B-α-TeW9O33)4]·48H2O [Ln = La3+ (1), Ce3+ (2), Pr3+ (3); H3Mal = dl-malic acid] were fabricated by reacting Na2TeO3, Na2WO4·2H2O, Mal, and LnCl3·6H2O with dimethylamine hydrochloride in an aqueous solution. The most prominent architectural feature of these compounds is the covalent connection mode of an organic ligand and a polyoxometallate backbone, which is relatively rare in the realm of polyoxotungstates. The tetrameric polyanion can be deemed as four [TeW9O33]8- fragments fused together via an intriguing hexanuclearity [W6O13(OH)5(Mal)2Ln4(H2O)14]13+ cluster. Impedance measurements manifest that all three complexes display splendid proton conduction properties, with an exceptional conductivity for 2 up to 2.48 × 10-2 S·cm-1 under 85 °C and 95% relative humidity. Moreover, compounds 1 and 3 exhibited fast reversible photochromic properties with allochroic half-life periods t1/2 of 1.046 and 0.544 min, respectively.

A High Nucleus Cu-Incorporated Giant Phosphotungstate with Photocatalytic Oxidation C-H of Toluene.

Exploring a novel photocatalyst for catalytic oxidation of toluene is a sustainable strategy for energy conversion in times of an energy crisis. However, designing an effective photocatalyst for the conversion of toluene remains challenging. Herein, a novel organic monophosphonate-modified high nucleus Cu-incorporated polyoxotungstate, K8H33[{Cu0.5(H2O)4}{Cu2(O3PCH2COO)(1,4,9-α-P2W15O56)}]4·Cl·60H2O (1), has been intentionally synthesized by a self-assembly process utilizing conventional aqueous method. It reveals that 1 contains a polyanion of [{Cu0.5(H2O)}4{Cu2(O3PCH2COO)(1,4,9-α-P2W15O56)}]440- composed of four Dawson-type {1,4,9-α-P2W15} subunits, forming an oval-shaped structure and further connecting into a three-dimensional (3D) framework by lateral {Cu(H2O)4}2+. Interestingly, the trivacant {1,4,9-α-P2W15} subunits were observed in the organophosphonate acid-functionalized polyoxometalates for the first time. Notably, 1 exhibits a wonderful performance in catalytic oxidation of the recalcitrant C(sp3)-H bond of toluene to benzoic acid with a conversion as high as 97% under visible light utilizing O2 as an oxidant.

Controlled Assembly of a Dawson-like Antimoniotungstate-Supported Trefoil-type Trimer with Good Proton Conductivity Performance.

With the excellent properties of POM in the field of proton conductivity, the preparation of POM-based proton-conductive materials has burst into life. Herein, an unprecedented Sb-templated all-inorganic trimer Na8H18.64[(SbW14O52)3(Sb2W6.12Ru5.88O18)]·85H2O (1), which is based on tetravacant Dawson-like [SbW14O52]17- blocks and exhibits a trefoil type with D3 symmetry, has been successfully designed and synthesized by the assembly of simple materials with a one-pot hydrothermal method under acidic conditions. Also, compound 1 is systematically characterized by single-crystal X-ray diffraction, PXRD, ESI-MS, IR spectroscopy, UV-vis, elemental analysis, and TGA. Crystal structure data analysis demonstrates that compound 1 is constructed by a hexagonal prismatic heterometallic {Sb2W6.12Ru5.88O18} core and three equivalent {SbW14} units bridged through µ2-O atoms in periphery. Subsequently, further property experiments show that compound 1 exhibits high proton conductivity with a conductivity value (σ) of 3.07 × 10-2 S cm-1 at 75 °C and 80% relative humidity (RH). The activation energy of compound 1 evaluated by the Arrhenius plots is 0.22 eV, which indicates that the Grotthuss mechanism is dominant during the process of proton transfer.

Photocatalytic Reduction of Nitrobenzene to Aniline by an Intriguing {Ru(C6H6)}-Based Heteropolytungstate.

In this paper, we have successfully synthesized a structurally novel heteropolytungstate via coordination of four {Ru(C6H6)} and trivacant {TeW9O33} clusters, formulated as Cs4Na2H2[Te2W20O72(H2O){(C6H6)Ru}4]·12H2O (1). Compound 1 inherited the strong absorption of [Ru(C6H6)Cl2]2 in the visible region and {TeW9O33} in the UV region, providing a good basis for photocatalysis. As expected, compound 1 showed good photocatalytic activity in the visible-light-driven reduction of nitrobenzene using N2H4·H2O as a reductant with a yield of 99.8%, a high turnover number (TON = 330), and a high turnover frequency (TOF = 24 h-1). The cyclic experiment of nitrobenzene reduction indicated that compound 1 was an effective and stable heterogeneous catalyst. Finally, the nitrobenzene reduction pathway was affirmed using condensation with azobenzene as a reaction intermediate based on control experiments.

Synthesis and Characterization of 6-Ti-Substituted Polyoxomolybdate with High Catalytic Activity for Sulfide Oxidation.

A 6-Ti-substituted polyoxometalate, (NH4)5Cs7Na3H2[Cs@(Ti2GeMo10O39)3]·34H2O (1), was synthesized by reacting (NH4)6Mo7O24·4H2O, GeO2, and TiOSO4 through the conventional aqueous method. Polyanion 1a is composed of three {Ti2GeMo10} segments linked by Ti-O-Ti linkages and shows a trefoil-shaped structure. Furthermore, one Cs+ cation is encapsulated in the cavity of 1a. Notably, it possesses the highest number of Ti centers among the reported polyoxomolybdates. In addition, serving as a high-efficiency heterogeneous catalyst, 1 enables the conversion of methyl phenyl sulfide within 20 min, yielding 96.4% of the corresponding sulfoxide with good recyclability.

Intensifying Photocatalytic Baeyer-Villiger Oxidation of Ketones with the Introduction of Ru Metalloligands and Bimetallic Units in POM@MOF.

The synthesis of visible light-responsive and efficient photocatalysts toward green Baeyer-Villiger oxidation organic synthesis is of extraordinary significance. In this work, we have synthesized two examples of visible light responsive crystalline polyoxometalate@metal-organic framework materials Ru-NiMo and Ru-CoMo by introducing Ru metalloligands and {CdM3O12} bimetallic units (M = Ni or Co). This is the first report of metalloligand-modified polyoxometalate@metal-organic framework materials with bimetallic nodes, and the materials form a three-dimensional framework directly through coordination bonds between {CdM3O12} bimetallic units and metalloligands. In particular, Ru-NiMo can achieve efficient photocatalytic conversion of cyclohexanone to ε-caprolactone in yields as high as 95.5% under visible light excitation in the range of λ > 400 nm, achieving a turnover number and turnover frequency of 955 and 440 h-1, respectively, which are the best known photocatalysts for Baeyer-Villiger oxidation, while apparent quantum yield measured at 485 nm is 4.4%. Moreover, Ru-NiMo exhibited excellent structural stability and recyclability, producing a 90.8% yield after five cycles of recycling.

Treatment outcomes of retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis.

BACKGROUND: About 8% of TB cases worldwide are estimated to have rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), ranging from 5 to 11% regions. However, Hr-TB has not received much attention while comparing to be given high priority to the management of rifampicin-resistant tuberculosis (RR-TB). This study aimed to compare the differences of treatment effects for Hr-TB and RR-TB, so as to intensify the treatment and management of Hr-TB. METHODS: A retrospective study was used to collect bacteriologically positive retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis, who were conducted at 29 tuberculosis control institutions in China from July 2009 to June 2021. We assessed effectiveness and safety of retreated patients with isoniazid/ rifampicin resistant pulmonary tuberculosis. RESULTS: A total of 147 with either positive smear or cultures were enrolled, and 80 cases were in Hr-TB group and 67 cases were in RR-TB group. There was no significant difference in terms of age, sex, body mass, type of retreatment and comorbid diabetes between the two groups (P > 0.05). The rate of number of lesions involving lung fields ≥ 3 in Hr-TB group 75.9% (60/79) was significantly higher than RR-TB group 56.7% (38/67) (χ2 = 6.077, P = 0.014). There was no statistically significant difference (P = 0.166) with regard to the treatment outcomes of the two groups, the cure rates were 54.7% (41/75) and 53.6% (30/56), respectively, and the failure rate in Hr-TB group 22.7% (17/75) was 10% higher than RR-TB group 10.7% (6/56). The rate of negative sputum smear at the end of the second month (65.7%) in the Hr-TB group was significantly lower than that in the RR-TB group (85.7%) (P = 0.025). There were no significant differences in the incidences of serious adverse reactions and chest X-ray changes between the two groups (P > 0.05). During the 5-year follow-up, recurrence in the Hr-TB group (7 cases, 14.9%) was no significantly lower than that in the RR-TB group (4 cases, 11.8%) (P = 0.754). CONCLUSION: The treatment of retreated Hr-TB patients was difficult and could be statistically similar or considerably worse than RR-TB. It's urgent to conduct further evaluation of the treatment status quo to guide the guideline development and clinical practice of Hr-TB patients.

James Watt, of Steam Engine Fame, Offered Inhaled Carbon Monoxide for Putative Therapeutic Action.

James Watt (1736-1819) is remembered as a steam engine innovator and industrial magnate. A polymath, he was also a hands-on contributor to the Medical Pneumatic Institution of Thomas Beddoes. Watt recruited Humphry Davy, who there discovered analgesic action of inhaled nitrous oxide in 1799. Watt also built pneumatic equipment, and he introduced a gas mixture, dubbed hydro-carbonate, as a medical tonic. The bioactive component was carbon monoxide, a readily-lethal inhibitor of the transport and utilization of respiratory oxygen. Despite appreciable toxicity, carbon monoxide is an endogenous product of heme catabolism, and low doses of the gas are under laboratory investigation for therapeutic purposes. However, Watt's hydro-carbonate constituted a setback in the development of pharmacologically useful gases.

Contribution of immune cells to cancer-related neuropathic pain: An updated review.

Given that the incidence of cancer is dramatically increasing nowadays, cancer-related neuropathic pain including tumor-related and therapy-related pain gradually attracts more attention from researchers, which basically behaves as a metabolic-neuro-immune disorder with worse clinical outcomes and prognosis. Among various mechanisms of neuropathic pain, the common underlying one is the activation of inflammatory responses around the injured or affected nerve(s). Innate and adaptive immune reactions following nerve injury together contribute to the regulation of pain. On the other hand, the tumor immune microenvironment involving immune cells, as exemplified by lymphocytes, macrophages, neutrophils and dendritic cells, inflammatory mediators as well as tumor metastasis have added additional characteristics for studying the initiation and maintenance of cancer-related neuropathic pain. Of interest, these immune cells in tumor microenvironment exert potent functions in promoting neuropathic pain through different signaling pathways. To this end, this review mainly focuses on the contribution of different types of immune cells to cancer-related neuropathic pain, aims to provide a comprehensive summary of how these immune cells derived from the certain tumor microenvironment participate in the pathogenesis of neuropathic pain. Furthermore, the clarification of roles of various immune cells in different tumor immune microenvironments associated with certain cancers under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction, and thereby provides more opportunities for novel approaches for the prevention and treatment of cancer-related neuropathic pain.

Proline-rich 11 (PRR11) promotes the progression of cutaneous squamous cell carcinoma by activating the EGFR signaling pathway.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignancies, and its incidence rate is increasing worldwide. Proline-rich 11 (PRR11) has been reported to be involved in the occurrence and development of various tumors. However, the role of PRR11 in cSCC remains unknown. In the present study, we observed upregulated expression of PRR11 in cSCC tissues and cell lines. Knockdown of PRR11 in the cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing cell cycle arrest during the G1/S phase transition, promoted cell apoptosis, and reduced cell migration and invasion in vitro. Conversely, overexpression of PRR11 promoted cell proliferation, decreased cell apoptosis, and enhanced cell migration and invasion. PRR11 knockdown also inhibited cSCC tumor growth in a mouse xenograft model. Mechanistic investigations by RNA sequencing revealed that 891 genes were differentially expressed genes between cells with PRR11 knockdown and control cells. Enrichment analysis of different genes showed that the epidermal growth factor receptor (EGFR) signaling pathway was the top enriched pathway. We further validated that PRR11 induced EGFR pathway activity, which contributed to cSCC progression. These data suggest that PRR11 may serve as a novel therapeutic target in cSCC.

A Hexameric Ruthenium(III)-Containing Tungstoantimonate with Good Proton Conductivity Performance.

A novel Ru(III)-containing tungstoantimonate Na16H22[(B-ß-SbW9O33)6(W3RuO7)2(W4O11)]·118H2O (1) hexamer was successfully synthesized using the hydrothermal synthesis method. Analysis by single-crystal X-ray diffraction revealed that the polyanion comprises six trivacant Keggin-type [B-ß-SbW9O33]9- units interconnected by six {WO6} and six Ru/W disorder octahedra, resulting in an intriguing cyclohexane boat-like conformation. Compound 1 exhibits favorable proton conductivity, with a measured conductivity (σ) of 5.41 × 10-3 S cm-1 at 333 K and 55% relative humidity (RH). The activation energy (Ea) of compound 1 was determined to be 0.40 eV, providing evidence that its proton conductivity conforms to the Grotthus mechanism.

Discovery and Isolation of Two Arsenotungastate Species: [As4W48O168]36- and [As2W21O77(H2O)3]22.

Two novel arsenotungstate species, [As4W48O168]36- (1a) and [As2W21O77(H2O)3]22- (2a), have been successfully isolated under a one-pot synthetic method. 1a is the second largest arsenotungstate cluster and is constructed from four {AsW12} clusters combined together. 2a can be described as lacunary sites of {As2W19} filled by {W2O8} units. Compounds 1 and 2 exhibit proton conductivity properties, and the conductivity value of 1 is 5.0 × 10-3 S cm-1 at 98% relative humidity and 75 °C. This work proves that the lattice water molecules and polyoxoanions can participate in the formation of a hydrogen bond, acting as effective pathway for intermolecular proton conduction.

Fabrication of Polyoxometalate-Based Metal-Organic Frameworks Integrating Paddlewheel Rh2(OAc)4 for Visible-Light-Driven Oxidative Coupling of Amines.

The development of visible-light-responsive, environmentally friendly, and reusable photocatalysts for organic oxidation reactions is of vital significance. Herein, four polyoxometalate-based metal-organic frameworks (POMOFs) were synthesized and systematically characterized by assembling the paddlewheel complex Rh2(OAc)4 and various polyoxometalates (POMs). Single-crystal X-ray diffraction analysis revealed that the four POMOFs were isomorphic and possessed rare structural features among the POMOFs, with POMs as nodes and Rh2(OAc)4 as linkers. As expected, the activities of the four POMOFs for the photocatalytic oxidative coupling of benzylamine were better than that of Rh2(OAc)4 or POMs individually, which was ascribed to the synergistic effect between them, and the intrinsic reasons for the difference in the activity were explained via electrochemical measurements. In particular, the product imine yield reached 96.1% with NaRh-SiW12 as the catalyst and a turnover number and a turnover frequency of 480.5 and 120.5 h-1, respectively, while the product yield remained as high as 92% after three repetitions, evidencing its high stability. Moreover, the higher activities of the four POMOFs for the selective epoxidation of various alkenes reaffirm the synergistic effect between Rh2(OAc)4 and POMs.

Organic Hybrid Antimoniotungstate Layered Ionic Crystal: Synthesis, Structure, and Interlayer-Confined Proton Conduction.

A synchronous crystal- and microstructure-dependent strategy was implemented to synthesize the organic hybrid antimoniotungstate layered ionic crystal Na5.5H6.5[(SbW9O33)2{WO2(OH)}2{WO2}RuC7H3NO4]·36H2O, and the layered structure was constructed through the Na+ bridged sheet and the hydrogen-bonded layers. It displayed an effective proton conductivity of 2.97 × 10-2 S cm-1 at 348 K and 75% RH, owing to the complete interlayer confined hydrogen-bond network formed by the hydrogens of interlayer crystal waters, organic ligands ({RuC7H3NO4}2+, {C7H3NO4} is formed by the hydrolysis of pyridine 2,5-dicarboxylic acid (C7H5NO4)), and acidic protons (H+), along with the interlayer domain as a transport channel. Furthermore, the hydrogen-bond network originating from interlayer organic ligands and acidic protons was more stable at a higher temperature of 423 K, preserving a high conductivity of 1.99 × 10-2 S cm-1.

Beyond Anion Template: Polyoxometalate as a Property Influencer in High-Nuclearity Silver Thiolate Cluster.

Two 48-nuclei silver nanocages with similar structures and compositions were synthesized by using Keggin-type polyoxometalates (POMs) BW12 and SiW11Ni as anionic templates. However, their photoluminescence and photocurrent properties showed obvious differences. These results suggest that POMs not only serve as anion templates in constructing silver clusters but also influence their properties.