Simultaneously Geometrical and Electronic Modulation of L10-PtZn by Trace Ge Boosts High-performance Oxygen Reduction Reaction.

Developing a highly active, durable, and low-platinum-based electrocatalyst for the cathodic oxygen reduction reaction (ORR) is for breaking the bottleneck of large-scale applications of proton exchange membrane fuel cells (PEMFCs). Herein, ultrafine PtZn intermetallic nanoparticles with low Pt-loading and trace germanium (Ge) involvement confined in the nitrogen-doped porous carbon (Ge-L10-PtZn@N-C) are reported. The Ge-L10-PtZn@N-C exhibit superior ORR activity with a mass activity of 3.04 A mg-1 Pt and specific activity of 4.69 mA cm-2, ≈12.2- and 10.2-times improvement compared to the commercial Pt/C (20%) at 0.90 V in 0.1 m KOH. The cathodic catalyst Ge-L10-PtZn@N-C assembled in the PEMFC shows encouraging peak power densities of 316.5 (at 0.86 V) and 417.2 mW cm-2 (at 0.91 V) in alkaline and acidic fuel-cell, respectively. The combination of experiment and density functional theory calculations (DFT) results robustly reveal that the participation of trace Ge can not only trigger a "growth site locking effect" to effectively inhibit nanoparticle growth, bring miniature nanoparticles, enhance dispersion uniformity, and achieve the exposure of the more electrochemical active site, but also effectively modulates the electronic structure, hence optimizing the adsorption/desorption of the oxygen intermediates.

Utilizing serum metabolomics for assessing postoperative efficacy and monitoring recurrence in gastric cancer patients.

OBJECTIVE: (1) This study aims to identify distinct serum metabolites in gastric cancer patients compared to healthy individuals, providing valuable insights into postoperative efficacy evaluation and monitoring of gastric cancer recurrence; (2) Methods: Serum samples were collected from 15 healthy individuals, 16 gastric cancer patients before surgery, 3 months after surgery, 6 months after surgery, and 15 gastric cancer recurrence patients. T-test and analysis of variance (ANOVA) were performed to screen 489 differential metabolites between the preoperative group and the healthy control group. Based on the level of the above metabolites in the recurrence, preoperative, three-month postoperative, and six-month postoperative groups, we further selected 18 significant differential metabolites by ANOVA and partial least squares discriminant analysis (PLS-DA). The result of hierarchical clustering analysis about the above metabolites showed that the samples were regrouped into the tumor-bearing group (comprising the original recurrence and preoperative groups) and the tumor-free group (comprising the original three-month postoperative and six-month postoperative groups). Based on the results of PLS-DA, 7 differential metabolites (VIP > 1.0) were further selected to distinguish the tumor-bearing group and the tumor-free group. Finally, the results of hierarchical clustering analysis showed that these 7 metabolites could well identify gastric cancer recurrence; (3) Results: Lysophosphatidic acids, triglycerides, lysine, and sphingosine-1-phosphate were significantly elevated in the three-month postoperative, six-month postoperative, and healthy control groups, compared to the preoperative and recurrence groups. Conversely, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol were significantly reduced in the three-month postoperative, six-month postoperative, and healthy control groups compared to the preoperative and recurrence groups. However, these substances did not show significant differences between the preoperative and recurrence groups, nor between the three-month postoperative, six-month postoperative, and healthy control groups; (4) Conclusions: Our findings demonstrate the presence of distinct metabolites in the serum of gastric cancer patients compared to healthy individuals. Lysophosphatidic acid, triglycerides, lysine, sphingosine-1-phosphate, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol hold potential as biomarkers for evaluating postoperative efficacy and monitoring recurrence in gastric cancer patients. These metabolites exhibit varying concentrations across different sample categories.

Promoting CO2 Dynamic Activation via Micro-Engineering Technology for Enhancing Electrochemical CO2 Reduction.

Optimizing the coordination structure and microscopic reaction environment of isolated metal sites is promising for boosting catalytic activity for electrocatalytic CO2 reduction reaction (CO2 RR) but is still challenging to achieve. Herein, a newly electrostatic induced self-assembly strategy for encapsulating isolated Ni-C3 N1 moiety into hollow nano-reactor as I-Ni SA/NHCRs is developed, which achieves FECO  of 94.91% at -0.80 V, the CO partial current density of ≈-15.35 mA cm-2 , superior to that with outer Ni-C2 N2 moiety (94.47%, ≈-12.06 mA cm-2 ), or without hollow structure (92.30%, ≈-5.39 mA cm-2 ), and high FECO of ≈98.41% at 100 mA cm-2 in flow cell. COMSOL multiphysics finite-element method and density functional theory (DFT) calculation illustrate that the excellent activity for I-Ni SA/NHCRs should be attributed to the structure-enhanced kinetics process caused by its hollow nano-reactor structure and unique Ni-C3 N1 moiety, which can enrich electron on Ni sites and positively shift d-band center to the Fermi level to accelerate the adsorption and activation of CO2 molecule and *COOH formation. Meanwhile, this strategy also successfully steers the design of encapsulating isolated iron and cobalt sites into nano-reactor, while I-Ni SA/NHCRs-based zinc-CO2 battery assembled with a peak power density of 2.54 mW cm--2 is achieved.

Monitoring Electron Flow in Nickel Single-Atom Catalysts during Nitrogen Photofixation.

An efficient catalytic system for nitrogen (N2) photofixation generally consists of light-harvesting units, active sites, and an electron-transfer bridge. In order to track photogenerated electron flow between different functional units, it is highly desired to develop in situ characterization techniques with element-specific capability, surface sensitivity, and detection of unoccupied states. In this work, we developed in situ synchrotron radiation soft X-ray absorption spectroscopy (in situ sXAS) to probe the variation of electronic structure for a reaction system during N2 photoreduction. Nickel single-atom and ceria nanoparticle comodified reduced graphene oxide (CeO2/Ni-G) was designed as a model catalyst. In situ sXAS directly reveals the dynamic interfacial charge transfer of photogenerated electrons under illumination and the consequent charge accumulation at the catalytic active sites for N2 activation. This work provides a powerful tool to monitor the electronic structure evolution of active sites under reaction conditions for photocatalysis and beyond.

Mesenchymal Stem Cell-Derived Exosomes in Cardioprotection: A Novel Application to Prevent Myocardial Injury.

Perioperative myocardial injury is a common complication caused by major surgery. Many pharmacological and nonpharmacological studies have investigated perioperative cardioprotection. However, the methods are insufficient to meet the increasing clinical needs for cardioprotection. The application of Mesenchymal Stem Cell-Derived Exosomes (MSC-Exos) is a novel cell-free therapeutic strategy and has significantly benefitted patients suffering from various diseases. In this review, we comprehensively analyzed the application of MSC-Exos to prevent myocardial infarction/injury by regulating inflammatory reactions, inhibiting cardiomyocyte apoptosis and autophagy, promoting angiogenesis, and mediating cardiac remodeling. Finally, we assessed the therapeutic effects and the challenges associated with the application of MSC-Exos from a clinical perspective.

Element-dependent effects of alkali cations on nitrate reduction to ammonia.

Catalytic conversion of nitrate (NO3-) pollutants into ammonia (NH3) offers a sustainable and promising route for both wastewater treatment and NH3 synthesis. Alkali cations are prevalent in nitrate solutions, but their roles beyond charge balance in catalytic NO3- conversion have been generally ignored. Herein, we report the promotion effect of K+ cations in KNO3 solution for NO3- reduction over a TiO2-supported Ni single-atom catalyst (Ni1/TiO2). For photocatalytic NO3- reduction reaction, Ni1/TiO2 exhibited a 1.9-fold NH3 yield rate with nearly 100% selectivity in KNO3 solution relative to that in NaNO3 solution. Mechanistic studies reveal that the K+ cations from KNO3 gradually bonded with the surface of Ni1/TiO2, in situ forming a K-O-Ni moiety during reaction, whereas the Na+ ions were unable to interact with the catalyst in NaNO3 solution. The charge accumulation on the Ni sites induced by the incorporation of K atom promoted the adsorption and activation of NO3-. Furthermore, the K-O-Ni moiety facilitated the multiple proton-electron coupling of NO3- into NH3 by stabilizing the intermediates.

Antiviral activity of vitamin D derivatives against severe fever with thrombocytopenia syndrome virus in vitro and in vivo.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that causes the severe fever thrombocytopenia syndrome, which manifests as fever and haemorrhage, accompanied by severe neurological complications. To date, no specific antiviral drugs have been approved for this indication. Herein, we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo. An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication, plaque formation, and protein expression in a dose-dependent manner. Subsequently, in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood. Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection. However, cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5, and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice. Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects. To expand the application of vitamin D derivatives, in vitro and in vivo drug combination assays were performed, which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV. The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice. This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.

Antiviral Activity of Selective Estrogen Receptor Modulators against Severe Fever with Thrombocytopenia Syndrome Virus In Vitro and In Vivo.

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection.

In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection.

Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

New ß-phospholactam as a carbapenem transition state analog: Synthesis of a broad-spectrum inhibitor of metallo-ß-lactamases.

In an effort to test whether a transition state analog is an inhibitor of the metallo-ß-lactamases, a phospholactam analog of carbapenem has been synthesized and characterized. The phospholactam 1 proved to be a weak, time-dependent inhibitor of IMP-1 (70%), CcrA (70%), L1 (70%), NDM-1 (53%), and Bla2 (94%) at an inhibitor concentration of 100µM. The phospholactam 1 activated ImiS and BcII at the same concentration. Docking studies were used to explain binding and to offer suggestions for modifications to the phospholactam scaffold to improve binding affinities.

A Research Investigation into the Impact of Reinforcement Distribution and Blast Distance on the Blast Resilience of Reinforced Concrete Slabs.

Reinforcement is one of the important factors affecting the anti-blast performance of reinforced concrete (RC) slabs. In order to study the impact of different reinforcement distribution and different blast distances on the anti-blast performance of RC slabs, 16 model tests were carried out for RC slab members with the same reinforcement ratio but different reinforcement distribution and the same proportional blast distance but different blast distances. By comparing the failure patterns of RC slabs and the sensor test data, the impact of reinforcement distribution and blast distance on the dynamic response of RC slabs was analyzed. The results show that, under contact explosion and non-contact explosion, the damage degree of single-layer reinforced slabs is more serious than that of double-layer reinforced slabs. When the scale distance is the same, with the increase of distance, the damage degree of single-layer reinforced slabs and double-layer reinforced slabs increases first and then decreases, and the peak displacement, rebound displacement and residual deformation near the center of the bottom of RC slabs gradually increase. When the blast distance is small, the peak displacement of single-layer reinforced slabs is smaller than that of double-layer reinforced slabs. When the blast distance is large, the peak displacement of double-layer reinforced slabs is smaller than that of single-layer reinforced slabs. No matter how large the blast distance, the rebound peak displacement of the double-layer reinforced slabs is smaller, and the residual displacement is larger. The research in this paper provides a reference for the anti-explosion design, construction and protection of RC slabs.

Modulation of Local Charge Distribution Stabilized the Anionic Redox Process in Mn-Based P2-Type Layered Oxides.

An anionic redox reaction is an extraordinary method for obtaining high-energy-density cathode materials for sodium-ion batteries (SIBs). The commonly used inactive-element-doped strategies can effectively trigger the O redox activity in several layered cathode materials. However, the anionic redox reaction process is usually accompanied by unfavorable structural changes, large voltage hysteresis, and irreversible O2 loss, which hinders its practical application to a large extent. In the present work, we take the doping of Li elements into Mn-based oxide as an example and reveal the local charge trap around the Li dopant will severely impede O charge transfer upon cycling. To overcome this obstacle, additional Zn2+ codoping is introduced into the system. Theoretical and experimental studies show that Zn2+ doping can effectively release the charge around Li+ and homogeneously distribute it on Mn and O atoms, thus reducing the overoxidation of O and improving the stability of the structure. Furthermore, this change in the microstructure makes the phase transition more reversible. This study aimed to provide a theoretical framework for further improve the electrochemical performance of similar anionic redox systems and provide insights into the activation mechanism of the anionic redox reaction.

Investigation of novel 5'-amino adenosine derivatives with potential anti-Zika virus activity.

The Zika virus (ZIKV) infections remains a global health threat. However, no approved drug for treating ZIKV infection. We previously found TZY12-9, a 5'-amino NI analog, that showed anti-ZIKV activity without chemical phosphorylation. Here, a series of 5'-amino NI analogs were synthesized and evaluated. The compound XSJ2-46 exhibited potent in vitro activity without requiring chemical phosphorylation, favorable pharmacokinetic and acute toxicity profiles. Preliminary mechanisms of anti-ZIKV activity of XSJ2-46 were investigated via a series of ZIKV non-structural protein inhibition assays and host cell RNA-seq. XSJ2-46 acted at the replication stage of viral infection cycle, and exhibited reasonable inhibition of RNA-dependent RNA polymerases (RdRp) with an IC50 value of 8.78 µM, while not affecting MTase. RNA-seq analysis also revealed differential expression genes involved in cytokine and cytokine receptor pathway in ZIKV-infected U87 cells treated with XSJ2-46. Importantly, treatment with XSJ2-46 (10 mg/kg/day) significantly enhanced survival protection (70% survival) in ZIKV-infected ICR mice. Additionally, XSJ2-46 administration resulted in a significant decrease in serum levels of ZIKV viral RNA in the IFNα/ß receptor-deficient (Ifnar-/-) A129 mouse model. Therefore, the remarkable in vitro and in vivo anti-ZIKV activity of compound XSJ2-46 highlights the promising research direction of utilizing the 5'-amino NI structure skeleton for developing antiviral NIs.

Scalable and switchable CO2-responsive membranes with high wettability for separation of various oil/water systems.

Smart membranes with responsive wettability show promise for controllably separating oil/water mixtures, including immiscible oil-water mixtures and surfactant-stabilized oil/water emulsions. However, the membranes are challenged by unsatisfactory external stimuli, inadequate wettability responsiveness, difficulty in scalability and poor self-cleaning performance. Here, we develop a capillary force-driven confinement self-assembling strategy to construct a scalable and stable CO2-responsive membrane for the smart separation of various oil/water systems. In this process, the CO2-responsive copolymer can homogeneously adhere to the membrane surface by manipulating the capillary force, generating a membrane with a large area up to 3600 cm2 and excellent switching wettability between high hydrophobicity/underwater superoleophilicity and superhydrophilicity/underwater superoleophobicity under CO2/N2 stimulation. The membrane can be applied to various oil/water systems, including immiscible mixtures, surfactant-stabilized emulsions, multiphase emulsions and pollutant-containing emulsions, demonstrating high separation efficiency (>99.9%), recyclability, and self-cleaning performance. Due to robust separation properties coupled with the excellent scalability, the membrane shows great implications for smart liquid separation.

In situ Observation of Structural Evolution and Phase Engineering of Amorphous Materials during Crystal Nucleation.

The nucleation pathway determines the structures and thus properties of formed nanomaterials, which is governed by the free energy of the intermediate phase during nucleation. The amorphous structure, as one of the intermediate phases during nucleation, plays an important role in modulating the nucleation pathway. However, the process and mechanism of crystal nucleation from amorphous structures still need to be fully investigated. Here, in situ aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) is employed to conduct real-time imaging of the nucleation of ultrathin amorphous nanosheets (NSs). The results indicate that their nucleation contains three distinct stages, i.e., aggregation of atoms, crystallization to form lattice-expanded nanocrystals, and relaxation of the lattice-expanded nanocrystals to form final nanocrystals. In particular, the crystallization processes of various amorphous materials are investigated systematically to form corresponding nanocrystals with unconventional crystalline phases, including face-centered-cubic (fcc) Ru, hexagonal-close-packed (hcp) Rh, and a new intermetallic IrCo alloy. In situ electron energy-loss spectroscopy (EELS) analysis unveils that the doped carbon in the original amorphous NSs can migrate to the surface during the nucleation process, stabilizing the obtained unconventional crystal phases transformed from the amorphous structures, which is also proven by density functional theory (DFT) calculations.

Binding of 2-(Triazolylthio)acetamides to Metallo-ß-lactamase CcrA Determined with NMR.

Metallo-ß-lactamase (MBL)-producing bacteria resistant to ß-lactam antibiotics are a serious threat to human health. Despite great efforts and important progress in the discovery of MBL inhibitors (MBLIs), there is none in clinical use. Herein, inhibitor complexes of the MBL CcrA were investigated by NMR spectroscopy to provide perspectives on the further development of 2-(triazolylthio)acetamide-type MBLIs. By using the NMR-based chemical shift perturbation (CSP) and direction of CSP methodologies together with molecular docking, the spatial orientation of three compounds in the CcrA active site was investigated (4-6). Inhibitor 6 showed the best binding affinity (K d ≈ 2.3 ± 0.3 µM), followed by 4 (K d = 11 ± 11 µM) and 5 (K d = 34 ± 43 µM), as determined from the experimental NMR data. Based on the acquired knowledge, analogues of other MBLIs (1-3) were designed and evaluated in silico with the purpose of examining a strategy for promoting their interactions with the catalytic zinc ions.

Azolylthioacetamide: A Highly Promising Scaffold for the Development of Metallo-ß-lactamase Inhibitors.

A new scaffold, azolylthioacetamide, was constructed and assayed against metallo-ß-lactamases (MßLs). The obtained molecules specifically inhibited MßL ImiS, and 1c was found to be the most potent inhibitor, with a K i = 1.2 µM using imipenem as substrate. Structure-activity relationships reveal that the aromatic carboxyl improves inhibitory activity of the inhibitors, but the aliphatic carboxyl does not. Compounds 1c-d and 1h-i showed the best antibacterial activities against E. coli BL21(DE3) cells producing CcrA or ImiS, resulting in 32- and 8-fold reduction in MIC values, respectively; 1c and 1f-j resulted in a reduction in MIC against P. aeruginosa. Docking studies revealed that 1a, 1c, and 1d fit tightly into the substrate binding site of CphA as a proxy for ImiS with the aromatic carboxylate forming interactions with Lys224, the Zn(II) ion, the backbone of Asn233, and hydrophobic portions of the inhibitors aligning with hydrophobic patches of the protein surface.