Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta.

Dermal fibroblasts (dFBs) resist infection by locally differentiating into adipocytes and producing cathelicidin antimicrobial peptide in response to Staphylococcus aureus (S. aureus). Here, we show that neonatal skin was enriched with adipogenic dFBs and immature dermal fat that highly expressed cathelicidin. The pool of adipogenic and antimicrobial dFBs declined after birth, leading to an age-dependent loss of dermal fat and a decrease in adipogenesis and cathelidicin production in response to infection. Transforming growth factor beta (TGF-ß), which acted on uncommitted embryonic and adult dFBs and inhibited their adipogenic and antimicrobial function, was identified as a key upstream regulator of this process. Furthermore, inhibition of the TGF-ß receptor restored the adipogenic and antimicrobial function of dFBs in culture and increased resistance of adult mice to S. aureus infection. These results provide insight into changes that occur in the skin innate immune system between the perinatal and adult periods of life.

Oxygenate-induced structural evolution of high-entropy electrocatalysts for multifunctional alcohol electrooxidation integrated with hydrogen production.

High-entropy compounds have been emerging as promising candidates for electrolysis, yet their controllable electrosynthesis strategy remains a formidable challenge because of the ambiguous ionic interaction and codeposition mechanism. Herein, we report a oxygenates directionally induced electrodeposition strategy to construct high-entropy materials with amorphous features, on which the structural evolution from high-entropy phosphide to oxide is confirmed by introducing vanadate, thus realizing the simultaneous optimization of composition and structure. The representative P-CoNiMnWVOx shows excellent bifunctional catalytic performance toward alkaline hydrogen evolution reaction and ethanol oxidation reaction (EOR), with small potentials of -168 mV and 1.38 V at 100 mA cm-2, respectively. In situ spectroscopy illustrates that the electrochemical reconstruction of P-CoNiMnWVOx induces abundant Co-O species as the main catalytic active species for EOR and follows the conversion pathway of the C2 product. Theoretical calculations reveal the optimized electronic structure and adsorption free energy of reaction intermediates on P-CoNiMnWVOx, thereby resulting in a facilitated kinetic process. A membrane-free electrolyzer delivers both high Faradaic efficiencies of acetate and H2 over 95% and superior stability at100 mA cm-2 during 120 h electrolysis. In addition, the unique composition and structural advantages endow P-CoNiMnWVOx with multifunctional catalytic activity and realize multipathway electrosynthesis of formate-coupled hydrogen production.

Regulation Strategy of Nanostructured Engineering on Indium-Based Materials for Electrocatalytic Conversion of CO2.

Electrochemical carbon dioxide reduction (CO2 RR), as an emerging technology, can combine with sustainable energies to convert CO2 into high value-added products, providing an effective pathway to realize carbon neutrality. However, the high activation energy of CO2 , low mass transfer, and competitive hydrogen evolution reaction (HER) leads to the unsatisfied catalytic activity. Recently, Indium (In)-based materials have attracted significant attention in CO2 RR and a series of regulation strategies of nanostructured engineering are exploited to rationally design various advanced In-based electrocatalysts, which forces the necessary of a comprehensive and fundamental summary, but there is still a scarcity. Herein, this review provides a systematic discussion of the nanostructure engineering of In-based materials for the efficient electrocatalytic conversion of CO2 to fuels. These efficient regulation strategies including morphology, size, composition, defects, surface modification, interfacial structure, alloying, and single-atom structure, are summarized for exploring the internal relationship between the CO2 RR performance and the physicochemical properties of In-based catalysts. The correlation of electronic structure and adsorption behavior of reaction intermediates are highlighted to gain in-depth understanding of catalytic reaction kinetics for CO2 RR. Moreover, the challenges and opportunities of In-based materials are proposed, which is expected to inspire the development of other effective catalysts for CO2 RR.

Integrated lipid metabolomics and proteomics analysis reveal the pathogenesis of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level. METHODS: We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform. RESULTS: Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders. CONCLUSION: The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.

Identification of SUMOylation-related biomarkers in papillary thyroid carcinoma.

BACKGROUND: Small ubiquitin-like modifier (SUMO) modification is increasingly recognized as critical in tumorigenesis and progression. This study identifies biomarkers linked to SUMOylation in papillary thyroid carcinoma (PTC), aiming to advance therapeutic and prognostic strategies. METHODS: Employing PTC datasets and SUMO related genes (SRGs), we utilized univariate Cox regression for prognosis-related SRGs, conducted differential expression analyses, and integrated findings to pinpoint candidate genes. These genes underwent further validation through survival, gene set enrichment, immune infiltration, and drug sensitivity analyses, including external validation via quantitative RT-qPCR. In our final step, we conducted immunohistochemical staining on tumor samples from PTC patients at our center and integrated this with their clinical data to validate BMP8A's effectiveness in predicting recurrence in PTC. RESULTS: Three biomarkers-BMP8A, RGS8, and SERPIND1-emerged as significant. Gene Set Enrichment Analysis (GSEA) showed their involvement in immune-related pathways, with differential immune infiltration patterns and drug response correlations observed, underscoring their potential for targeted therapy. Lastly, we validated the efficacy of BMP8A in predicting the recurrence of PTC in patients using clinical and pathological data from our center. CONCLUSION: The study identifies BMP8A, RGS8, and SERPIND1 as key biomarkers associated with SUMOylation in PTC. Their linkage to immune response and drug sensitivity highlights their importance as targets for therapeutic intervention and prognosis in PTC research.

Identifying a survival-associated cell type based on multi-level transcriptome analysis in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a five-year survival rate of less than 40%. There is significant variability in survival time among IPF patients, but the underlying mechanisms for this are not clear yet. METHODS AND RESULTS: We collected single-cell RNA sequence data of 13,223 epithelial cells taken from 32 IPF patients and bulk RNA sequence data from 456 IPF patients in GEO. Based on unsupervised clustering analysis at the single-cell level and deconvolution algorithm at bulk RNA sequence data, we discovered a special alveolar type 2 cell subtype characterized by high expression of CCL20 (referred to as ATII-CCL20), and found that IPF patients with a higher proportion of ATII-CCL20 had worse prognoses. Furthermore, we uncovered the upregulation of immune cell infiltration and metabolic functions in IPF patients with a higher proportion of ATII-CCL20. Finally, the comprehensive decision tree and nomogram were constructed to optimize the risk stratification of IPF patients and provide a reference for accurate prognosis evaluation. CONCLUSIONS: Our study by integrating single-cell and bulk RNA sequence data from IPF patients identified a special subtype of ATII cells, ATII-CCL20, which was found to be a risk cell subtype associated with poor prognosis in IPF patients. More importantly, the ATII-CCL20 cell subtype was linked with metabolic functions and immune infiltration.

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

Phosphorus-Modified Amorphous High-Entropy CoFeNiCrMn Compound as High-Performance Electrocatalyst for Hydrazine-Assisted Water Electrolysis.

Exploiting highly active and bifunctional catalysts for both hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR) is a prerequisite for the hydrogen acquisition. High-entropy materials have received widespread attention in catalysis, but the high-performance bifunctional electrodes are still lacking. Herein, a novel P-modified amorphous high-entropy CoFeNiCrMn compound is developed on nickel foam (NF) by one-step electrodeposition strategy. The achieved CoFeNiCrMnP/NF delivers remarkable HER and HzOR performance, where the overpotentials as low as 51 and 268 mV are realized at 100 mA cm-2 . The improved cell voltage of 91 mV is further demonstrated at 100 mA cm-2 by assessing CoFeNiCrMnP/NF in the constructed hydrazine-assisted water electrolyser, which is almost 1.54 V lower than the HER||OER system. Experimental results confirm the important role of each element in regulating the bifuncational performance of high-entropy catalysts. The main influencing elements seem to be Fe and Ni for HER, while the P-modification and Cr metal may contribute a lot for HzOR. These synergistic advantages help to lower the energy barriers and improve the reaction kinetics, resulting in the excellent bifunctional activity of the CoFeNiCrMnP/NF. The work offers a feasible strategy to develop self-supporting electrode with high-entropy materials for overall water splitting.

Neuropilin-1 Facilitates Pseudorabies Virus Replication and Viral Glycoprotein B Promotes Its Degradation in a Furin-Dependent Manner.

Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through in vitro coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis; in vivo, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention. IMPORTANCE Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last, in vivo, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.

Comparative analysis of SARS-CoV-2 Omicron BA.2.12.1 and BA.5.2 variants.

The initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BA.1 and BA.2, are being progressively displaced by BA.5 in many countries. To provide insight on the replacement of BA.2 by BA.5 as the dominant SARS-CoV-2 variant, we performed a comparative analysis of Omicron BA.2.12.1 and BA.5.2 variants in cell culture and hamster models. We found that BA.5.2 exhibited enhanced replicative kinetics over BA.2.12.1 in vitro and in vivo, which is evidenced by the dominant BA.5.2 viral genome detected at different time points, regardless of immune selection pressure with vaccine-induced serum antibodies. Utilizing reverse genetics, we constructed a mutant SARS-CoV-2 carrying spike F486V substitution, which is an uncharacterized mutation that concurrently discriminates Omicron BA.5.2 from BA.2.12.1 variant. We noticed that the 486th residue does not confer viral replication advantage to the virus. We also found that 486V displayed generally reduced immune evasion capacity when compared with its predecessor, 486F. However, the surge of fitness in BA.5.2 over BA.2.12.1 was not due to stand-alone F486V substitution but as a result of the combination of multiple mutations. Our study upholds the urgency for continuous monitoring of SARS-CoV-2 Omicron variants with enhanced replication fitness.

Protocatechuic acid alleviates polycystic ovary syndrome symptoms in mice by PI3K signaling in granulosa cells to relieve ROS pressure and apoptosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complicated gynecological endocrine disease that occurs in women of childbearing age. Protocatechuic acid is a phenol-rich compound derived from herbs and owns vital functions in numerous diseases. Howbeit, protocatechuic acid's impact on PCOS is unknown. METHODS: A combination of in vivo and in vitro models was examined in this study. C57BL/6 mice were injected subcutaneously daily with dehydroepiandrosterone to establish a PCOS mouse model, and protocatechuic acid was intraperitoneally injected into PCOS mice. Granulosa cells of PCOS ovaries were also isolated. The function of protocatechuic acid was appraised using enzyme-linked immunosorbent assay, hematoxylin-eosin staining, reactive oxygen species (ROS) and LC3 levels analysis, flow cytometry, quantitative real-time PCR, and western blot. Meanwhile, the mechanism of protocatechuic acid was assessed with a series of molecular experiments. RESULTS: Protocatechuic acid owned no apparent toxic effect on mice. Functionally, protocatechuic acid owned a function of mitigating PCOS in vivo. Meanwhile, protocatechuic acid repressed ROS, autophagy, and apoptosis of PCOS ovarian granulosa cells in vitro. Mechanistically, rescue assays elucidated that the protective function of protocatechuic acid against PCOS was interrelated to the activation of the PI3K/AKT/mTOR axis. CONCLUSION: Protocatechuic acid alleviated PCOS symptoms in mice through PI3K signaling in granulosa cells to reduce ROS levels and apoptosis.

[p53 regulates primordial follicle activation through the mTOR signaling pathway].

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-µ (PFT-µ, 5 µmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 µmol/L), PFT-µ (5 µmol/L), PFT-µ (5 µmol/L) + RAP (1 µmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-µ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.

Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.

Aminopeptidase N Is an Entry Co-factor Triggering Porcine Deltacoronavirus Entry via an Endocytotic Pathway.

Porcine deltacoronavirus (PDCoV) is a recently discovered coronavirus that poses a potential threat to the global swine industry. Although we know that aminopeptidase N (APN) is important for PDCoV replication, it is unclear whether it is the primary functional receptor, and the mechanism by which it promotes viral replication is not fully understood. Here, we systematically investigated the roles of porcine APN (pAPN) during PDCoV infection of nonsusceptible cells, including in viral attachment and internalization. Using a viral entry assay, we found that PDCoV can enter nonsusceptible cells but then fails to initiate efficient replication. pAPN and PDCoV virions clearly colocalized with the endocytotic markers RAB5, RAB7, and LAMP1, suggesting that pAPN mediates PDCoV entry by an endocytotic pathway. Most importantly, our study shows that regardless of which receptor PDCoV engages, only entry by an endocytotic route ultimately leads to efficient viral replication. This knowledge should contribute to the development of efficient antiviral treatments, which are especially useful in preventing cross-species transmission. IMPORTANCE PDCoV is a pathogen with the potential for transmission across diverse species, although the mechanism of such host-switching events (from swine to other species) is poorly understood. Here, we show that PDCoV enters nonsusceptible cells but without efficient replication. We also investigated the key role played by aminopeptidase N in mediating PDCoV entry via an endocytotic pathway. Our results demonstrate that viral entry via endocytosis is a major determinant of efficient PDCoV replication. This knowledge provides a basis for future studies of the cross-species transmissibility of PDCoV and the development of appropriate antiviral drugs.

Interfacial engineering of cobalt sulfide/graphene hybrids for highly efficient ammonia electrosynthesis.

Electrocatalytic N2 reduction reaction (NRR) into ammonia (NH3), especially if driven by renewable energy, represents a potentially clean and sustainable strategy for replacing traditional Haber-Bosch process and dealing with climate change effect. However, electrocatalytic NRR process under ambient conditions often suffers from low Faradaic efficiency and high overpotential. Developing newly regulative methods for highly efficient NRR electrocatalysts is of great significance for NH3 synthesis. Here, we propose an interfacial engineering strategy for designing a class of strongly coupled hybrid materials as highly active electrocatalysts for catalytic N2 fixation. X-ray absorption near-edge spectroscopy (XANES) spectra confirm the successful construction of strong bridging bonds (Co-N/S-C) at the interface between CoS x nanoparticles and NS-G (nitrogen- and sulfur-doped reduced graphene). These bridging bonds can accelerate the reaction kinetics by acting as an electron transport channel, enabling electrocatalytic NRR at a low overpotential. As expected, CoS2/NS-G hybrids show superior NRR activity with a high NH3 Faradaic efficiency of 25.9% at -0.05 V versus reversible hydrogen electrode (RHE). Moreover, this strategy is general and can be extended to a series of other strongly coupled metal sulfide hybrids. This work provides an approach to design advanced materials for ammonia production.

Isobavachalcone inhibits Pseudorabies virus by impairing virus-induced cell-to-cell fusion.

Pseudorabies virus (PRV) is an important pathogen that threatens the global swine industry. Currently, there is no effective drug that can clinically prevent or treat PRV infections. Isobavachalcone (IBC), a natural chalcone compound derived from Psoralea corylifolia, displays multiple biological activities, such as antibacterial, antifungal, and anticancer activities. Recently, it was found that IBC exhibited antiviral activity against an RNA virus, porcine reproductive and respiratory syndrome virus (PRRSV), in vitro. In the current study, we further demonstrated for the first time that IBC has a strong inhibitory effect on PRV. Through a viral luciferase expression assay, we showed that the inhibition step occurs mainly in the late stage of viral replication. Finally, via a cell-to-cell fusion assay, we demonstrated that IBC inhibits PRV by blocking virus-mediated cell fusion. Thus, IBC may be a candidate for further therapeutic evaluation against PRV infection in vivo.

Phenylboronic acid-functionalized vertically ordered mesoporous silica films for selective electrochemical determination of fluoride ion in tap water.

The selective electrochemical determination of fluoride is reported by phenylboronic acid-functionalized vertically ordered mesoporous silica film attached to the indium tin oxide electrode, designed as PBA-VMSF/ITO. Fluoride ion can selectively bind to phenylboronic acid to generate boronate anions, leading to negative charges inside the ultrasmall nanochannel of VMSF and ultimately rejecting the access of potassium ferricyanide ions to the electrode surface. By recording the reduced electrochemical signal of potassium ferricyanide, determination of fluoride ion in aqueous solution was achieved with a fast response, wide response range, and high selectivity. Furthermore, with the specific recognition of PBA and anti-fouling ability of VMSF, the PBA-VMSF/ITO sensor has been successfully used to detect fluoride ion in tap water.

Surface/Interfacial Engineering of Inorganic Low-Dimensional Electrode Materials for Electrocatalysis.

Exploitation of highly active and cost-effective electrode materials for the design of new types of renewable energy storage and conversion systems has been tremendously stimulated by the higher attention being paid to global energy security and invention of alternative clean sustainable energy technologies. Low-dimensional solid materials with special atomic and electronic structures are deemed desirable platforms for establishing clear relationships between surface/interface structure characteristics and electrocatalytic activity, representing enormous potential in the pursuit of high-performance electrocatalysts. Recent achievements revealed that surface and interfacial atomic engineering is capable of achieving novel physical and chemical properties as well as superior synergistic effects in inorganic low-dimensional nanomaterials for electrocatalysis. Compared to bulk counterparts, the electronic structure in the surface of inorganic low-dimensional nanomaterials is more sensitive to and can thus be regulated more easily by surface and interfacial modification strategies, resulting in greatly optimized electrocatalytic performance. In this Account, we focus on recent progress in surface and interfacial modification strategies to efficaciously engineer the electrocatalytic performance of inorganic low-dimensional electrode materials. We summarize several important regulation strategies of dimensional confinement, incorporation, surface reconstruction, interface modulation, and defect engineering, which immensely optimize the spin configuration, electrical conductivity, catalytic active site exposure, and reaction energy barrier of inorganic electrode material. At dimensionally confined atomic-scale thickness, more surface-facet atoms are exposed as active sites, which provide an ideal platform for applying surface incorporation and defect engineering, subsequently producing more catalytic active sites and better adsorption free energy for the improvement of catalytic activity. Moreover, regulation of the interfacial character of electrode materials, such as the surface strain, contact area, and bridged bonds, can optimize the electron transfer capacity and reaction kinetics process. On the other hand, once exposed to a strong alkaline solution under oxidizing potentials, the real active layer of electrode materials (such as transition-metal sulfides, nitrides, and phosphides) could be activated by a surface reconstruction strategy, realizing a unique core-shell structure with a highly conductive electron transfer channel inside and highly active catalytic sites outside for electrocatalysis. Based on these points of view, focusing on inorganic low-dimensional electrode materials, the proper choice of surface and interfacial modification strategies would effectively modulate their electrocatalytic activity, realizing unlimited potential applications in promising areas of electrocatalytic water splitting, rechargeable metal batteries, and fuel cells. Overall, we anticipate that surface and interfacial regulation approaches can provide a new understanding of the design of inorganic electrode materials, facilitating the rapid promotion of electrocatalytic performance in electrode materials for electrocatalysis.

CRISPR/Cas9-mediated 2-sgRNA cleavage facilitates pseudorabies virus editing.

Several groups have used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) for DNA virus editing. In most cases, one single-guide RNA (sgRNA) is used, which produces inconsistencies in gene editing. In this study, we used a swine herpesvirus, pseudorabies virus, as a model to systematically explore the application of CRISPR/Cas9 in DNA virus editing. In our current report, we demonstrated that cotransfection of 2 sgRNAs and a viral genome resulted in significantly better knockout efficiency than the transfection-infection-based approach. This method could result in 100% knockout of ≤3500 bp of viral nonessential large fragments. Furthermore, knockin efficiency was significantly improved by using 2 sgRNAs and was also correlated with the number of background viruses. We also demonstrated that the background viruses were all 2-sgRNA-mediated knockout mutants. Finally, this study demonstrated that the efficacy of gene knockin is determined by the replicative kinetics of background viruses. We propose that CRISPR/Cas9 coupled with 2 sgRNAs creates a powerful tool for DNA virus editing and offers great potential for future applications.-Tang, Y.-D., Guo, J.-C., Wang, T.-Y., Zhao, K., Liu, J.-T., Gao, J.-C., Tian, Z.-J., An, T.-Q., Cai, X.-H. CRISPR/Cas9-mediated 2-sgRNA cleavage facilitates pseudorabies virus editing.