Augmented Electrochemical Oxygen Evolution by d-p Orbital Electron Coupling.

While high-entropy alloys, high-entropy oxides, and high-entropy hydroxides, are advanced as a novel frontier in electrocatalytic oxygen evolution, their inherent activity deficiency poses a major challenge. To achieve the unlimited goal to tailor the structure-activity relationship in multicomponent systems, entropy-driven composition engineering presents substantial potential, by fabricating high-entropy anion-regulated transition metal compounds as sophisticated oxygen evolution reaction electrocatalysts. Herein, a versatile 2D high-entropy metal phosphorus trisulfide is developed as a promising and adjustable platform. Leveraging the multiple electron couplings and d-p orbital hybridizations induced by the cocktail effect, the exceptional oxygen evolution catalytic activity is disclosed upon van der Waals material (MnFeCoNiZn)PS3, exhibiting an impressively low overpotential of 240 mV at a current density of 10 mA cm-2, a minimal Tafel slope of 32 mV dec-1, and negligible degradation under varying current densities for over 96 h. Density functional theory calculations further offer insights into the correlation between orbital hybridization and catalytic performance within high-entropy systems, underscoring the contribution of active phosphorus centers on the substrate to performance enhancements. Moreover, by achieving electron redistribution to optimize the electron coordination environment, this work presents an effective strategy for advanced catalysts in energy-related applications.

Tuning Crystal Phase of Palladium-Selenium Nanowires for Enhanced Ethylene Glycol Electrocatalytic Oxidation.

Alcohol electrooxidation is pivotal for a sustainable energy economy. However, designing efficient electrocatalysts for this process is still a formidable challenge. Herein, palladium-selenium nanowires featuring distinct crystal phases: monoclinic Pd7Se2 and tetragonal Pd4.5Se for ethylene glycol electrooxidation reaction (EGOR) are synthesized. Notably, the supported monoclinic Pd7Se2 nanowires (m-Pd7Se2 NWs/C) exhibit superior EGOR activity, achieving a mass activity (MA) and specific activity (SA) of 10.4 A mgPd -1 (18.7 mA cm-2), which are 8.0 (6.7) and 10.4 (8.2) times versus the tetragonal Pd4.5Se and commercial Pd/C and surpass those reported in the literature. Furthermore, m-Pd7Se2 NWs/C displays robust catalytic activity for other alcohol electrooxidation. Comprehensive characterization and density functional theory (DFT) calculations reveal that the enhanced electrocatalytic performance is attributed to the increased formation of Pd0 on the high-index facets of the m-Pd7Se2 NWs, which lowers the energy barriers for the C─C bond dissociation in CHOHCHOH* and the CO* oxidation to CO2*. This study provides palladium-based alloy electrocatalysts exhibiting the highest mass activity reported to date for the electrooxidation of ethylene glycol, achieved through the crystalline phase engineering strategy.

Efficacy and safety of 0.01% atropine combined with orthokeratology lens in delaying juvenile myopia: An observational study.

It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study, 172 adolescents aged 8 to 12 years who were admitted to the diopter department of Hengshui People Hospital from April 2021 to May 2022 were selected. According to the equivalent spherical diopter measured at the time of initial diagnosis, myopic patients were randomly divided into low myopia group (group A) and moderate myopia group (group B). At the same time, according to the different treatment methods, the patients were divided into the group wearing frame glasses alone (group c), the group wearing frame glasses with low-concentration Atropine (group d), the group wearing corneal shaping glasses alone at night (group e), and the group wearing corneal shaping glasses at night with low-concentration Atropine (group f). The control effect of myopia development and axial elongation in group f was better than that in groups d and e (P < .05). The effect of controlling myopia development and axial elongation in group f is with P > .05. The probability of postoperative adverse reactions in group f was lower and lower than that in the other groups. Low-concentration atropine combined with OK lens could effectively delay the development of juvenile myopia, and had a high safety. Low-concentration of Atropine would not have a significant impact on the basic tear secretion and tear film stability. Nightwear of OK lens also had no significant impact, but it would significantly reduce the tear film rupture time in the first 3 months, and at the same time, the tear film rupture time would be the same after 6 months as before treatment.

Regioselective epitaxial growth of metallic heterostructures.

Constructing regioselective architectures in heterostructures is important for many applications; however, the targeted design of regioselective architectures is challenging due to the sophisticated processes, impurity pollution and an unclear growth mechanism. Here we successfully realized a one-pot kinetically controlled synthetic framework for constructing regioselective architectures in metallic heterostructures. The key objective was to simultaneously consider the reduction rates of metal precursors and the lattice matching relationship at heterogeneous interfaces. More importantly, this synthetic method also provided phase- and morphology-independent behaviours as foundations for choosing substrate materials, including phase regulation from Pd20Sb7 hexagonal nanoplates (HPs) to Pd8Sb3 HPs, and morphology regulation from Pd20Sb7 HPs to Pd20Sb7 rhombohedra and Pd20Sb7 nanoparticles. Consequently, the activity of regioselective epitaxially grown Pt on Pd20Sb7 HPs was greatly enhanced towards the ethanol oxidation reaction; its activity was 57 times greater than that of commercial Pt/C, and the catalyst showed increased stability (decreasing by 16.3% after 2,000 cycles) and selectivity (72.4%) compared with those of commercial Pt/C (56.0%, 18.2%). This work paves the way for the design of unconventional well-defined heterostructures for use in various applications.

Balance between FeIV-NiIV synergy and Lattice Oxygen Contribution for Accelerating Water Oxidation.

Hydrogen obtained from electrochemical water splitting is the most promising clean energy carrier, which is hindered by the sluggish kinetics of the oxygen evolution reaction (OER). Thus, the development of an efficient OER electrocatalyst using nonprecious 3d transition elements is desirable. Multielement synergistic effect and lattice oxygen oxidation are two well-known mechanisms to enhance the OER activity of catalysts. The latter is generally related to the high valence state of 3d transition elements leading to structural destabilization under the OER condition. We have found that Al doping in nanosheet Ni-Fe hydroxide exhibits 2-fold advantage: (1) a strong enhanced OER activity from 277 mV to 238 mV at 10 mA cm-2 as the Ni valence state increases from Ni3.58+ to Ni3.79+ observed from in situ X-ray absorption spectra. (2) Operational stability is strengthened, while weakness is expected since the increased NiIV content with 3d8L2 (L denotes O 2p hole) would lead to structural instability. This contradiction is attributed to a reduced lattice oxygen contribution to the OER upon Al doping, as verified through in situ Raman spectroscopy, while the enhanced OER activity is interpreted as an enormous gain in exchange energy of FeIV-NiIV, facilitated by their intersite hopping. This study reveals a mechanism of Fe-Ni synergy effect to enhance OER activity and simultaneously to strengthen operational stability by suppressing the contribution of lattice oxygen.

Symmetry-Breaking of Nanoparticle Surface Function Via Conformal DNA Design.

Asymmetric surface functionalization of complex nanoparticles to control their directional self-assembly remains a considerable challenge. Here, we demonstrated a conformal DNA design strategy for flexible remodeling of the surface of complex nanoparticles, taking Au nanobipyramids (AuNBPs) as a model. We sheathed one or both tips of AuNBPs into conformal DNA origami with an exceptionally accurate orientation control. Such asymmetrically and symmetrically distributed surface patches possess regioselective, sequence, and site-specific DNA binding capabilities. As a result, we realized a series of prototypical multicomponent "colloidal molecules" made of AuNBPs and Au nanospheres (AuNSs) with defined directionality and number of "bonding valence" as well as 1D and 3D hierarchical assemblies, e.g., inverse core-satellites of AuNBPs and AuNSs, side-by-side and tip-to-tip linear assemblies of AuNBPs, and 3D helical superstructures of AuNBPs with tunable twists. These findings inspire new opportunities for nanoparticle surface engineering and the high-order self-assembly of nanoarchitectures with higher complexity and broadened functionalities.

An all-metallic nanovesicle for hydrogen oxidation.

Vesicle, a microscopic unit that encloses a volume with an ultrathin wall, is ubiquitous in biomaterials. However, it remains a huge challenge to create its inorganic metal-based artificial counterparts. Here, inspired by the formation of biological vesicles, we proposed a novel biomimetic strategy of curling the ultrathin nanosheets into nanovesicles, which was driven by the interfacial strain. Trapped by the interfacial strain between the initially formed substrate Rh layer and subsequently formed RhRu overlayer, the nanosheet begins to deform in order to release a certain amount of strain. Density functional theory (DFT) calculations reveal that the Ru atoms make the curling of nanosheets more favorable in thermodynamics applications. Owing to the unique vesicular structure, the RhRu nanovesicles/C displays excellent hydrogen oxidation reaction (HOR) activity and stability, which has been proven by both experiments and DFT calculations. Specifically, the HOR mass activity of RhRu nanovesicles/C are 7.52 A mg(Rh+Ru)-1 at an overpotential of 50 mV at the rotating disk electrode (RDE) level; this is 24.19 times that of commercial Pt/C (0.31 mA mgPt-1). Moreover, the hydroxide exchange membrane fuel cell (HEMFC) with RhRu nanovesicles/C displays a peak power density of 1.62 W cm-2 in the H2-O2 condition, much better than that of commercial Pt/C (1.18 W cm-2). This work creates a new biomimetic strategy to synthesize inorganic nanomaterials, paving a pathway for designing catalytic reactors.

Modulating 3d Charge State via Halogen Ions in Neighboring Molecules of Metal-Organic Frameworks for Improving Water Oxidation.

Modulating the coordination environment of the metal active center is an effective method to boost the catalytic performances of metal-organic frameworks (MOFs) for oxygen evolution reaction (OER). However, little attention has been paid to the halogen effects on the ligands engineering. Herein, a series of MOFs X─FeNi-MOFs (X = Br, Cl, and F) is constructed with different coordination microenvironments to optimize OER activity. Theoretical calculations reveal that with the increase in electronegativity of halogen ions in terephthalic acid molecular (TPA), the Bader charge of Ni atoms gets larger and the Ni-3d band center and O-2p bands move closer to the Fermi level. This indicates that an increase in ligand negativity of halogen ions in TPA can promote the adsorption ability of catalytic sites to oxygen-containing intermediates and reduce the activation barrier for OER. Experimental also demonstrates that F─FeNi-MOFs exhibit the highest catalytic activity with an ultralow overpotential of 218 mV at 10 mA cm-2, outperforming most otate-of-the-art Fe/Co/Ni-based MOFs catalysts, and the enhanced mass activity by seven times compared with that for the sample before ligands engineering. This work opens a new avenue for the realization of the modulation of NiFe─O bonding by halogen ion in TPA and improves the OER performance of MOFs.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

CRISPR-Cas13a-Triggered DNAzyme Signal Amplification-Based Colorimetric miRNA Detection Method and Its Application in Evaluating the Anxiety.

The development of a bio-sensing strategy based on CRISPR/Cas that is exceptionally sensitive is crucial for the identification of trace molecules. Colorimetric miRNA detection utilizing CRISPR/Cas13a-triggered DNAzyme signal amplification was described in this article. The developed strategy was implemented for miRNA-21 detection as a proof of concept. The cleavage activity of Cas13a was triggered when the target molecule bonded to the Cas13a-crRNA complex and cleaved uracil ribonucleotides (rU) in the substrate probe. As a consequence, the S chain was liberated from the T chain that had been modified on magnetic beads (MB). The G-rich sections were then exposed when the catalytic hairpin assembly between the H1 and H2 probes was activated by the released T@MB. G-rich section can fold into G-quadruplex. By catalyzing the formation of green ABTS3- via HRP-mimicking G-quadruplex/hemin complexes, colorimetric measurements of miRNA can be achieved visually through DNAzyme-mediated signal amplification. The method demonstrated a low limit of detection of 27 fM and a high selectivity towards target miRNA eventually. As a result, the developed strategy provides a clinical application platform for the detection of miRNAs that is both ultrasensitive and extremely specific.

Suppressing Structure Delamination for Enhanced Electrochemical Performance of Solid Oxide Cells.

Reversible solid oxide cells (rSOCs) have significant potential as efficient energy conversion and storage systems. Nevertheless, the practical application of their conventional air electrodes, such as La0.8Sr0.2MnO3-δ (LSM), Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF), and PrBa0.8Ca0.2Co2O5+δ (PBCC), remains unsatisfactory due to interface delamination during prolonged electrochemical operation. Using micro-focusing X-ray absorption spectroscopy (µ-XAS), a decrease (increase) in the co-valence state from the electrode surface to the electrode/electrolyte interface is observed, leading to the above delamination. Utilizing the one-pot method to incorporate an oxygen-vacancy-enriched CeO2 electrode into these air electrodes, the uniform distribution of the Co valence state is observed, alleviating the structural delamination. PBCC-CeO2 electrodes exhibited a degradation rate of 0.095 mV h-1 at 650 °C during a nearly 500-h test as compared with 0.907 mV h-1 observed during the 135-h test for PBCC. Additionally, a remarkable increase in electrolysis current density from 636 to 934 mA cm-2 under 1.3 V and a maximum power density from 912 to 989 mW cm-2 upon incorporating CeO2 into PBCC is also observed. BSCF-CeO2 and LSM-CeO2 also show enhanced electrochemical performance and prolonged stability as compared to BSCF and LSM. This work offers a strategy to mitigate the structural delamination of conventional electrodes to boost the performance of rSOCs.

Amorphous-crystalline RuTi nanosheets enhancing OH species adsorption for efficient hydrogen oxidation catalysis.

Anion exchange membrane fuel cells are a potentially cost-effective energy conversion technology, however, the electrocatalyst for the anodic hydrogen oxidation reaction (HOR) suffers from sluggish kinetics under alkaline conditions. Herein, we report that Ru-based nanosheets with amorphous-crystalline heterointerfaces of Ru and Ti-doped RuO2 (a/c-Ru/Ti-RuO2) can serve as a highly efficient HOR catalyst with a mass activity of 4.16 A mgRu-1, which is 19.8-fold higher than that of commercial Pt/C. Detailed characterization studies show that abundant amorphous-crystalline heterointerfaces of a/c-Ru/Ti-RuO2 nanosheets provide oxygen vacancies and unsaturated coordination bonds for balancing adsorption of hydrogen and hydroxyl species on Ru active sites to elevate HOR activity. Moreover, Ti doping can facilitate CO oxidation, leading to enhanced strength to CO poisoning. This work provides a strategy for enhancing alkaline HOR performance over Ru-based catalysts with heteroatom and heterointerface dual-engineering, which will attract immediate interest in chemistry, materials science and beyond.

Efficacy and safety of fundoplication in treating gastroesophageal reflux related chronic cough: A meta-analysis.

Gastroesophageal reflux related chronic cough (GERC), is a common type of chronic cough. Drug treatment is the first choice. But some patients are tired of taking medicine everyday and some patients can not benefit from drugs. For these patients, fundoplication may be the most effective method. However, the importance of fundoplication in treating GERC is undervalued, and there is very few meta-analysis looking into the effect and safety of fundoplication in treating GERC. To solve this question, we performed this meta-analysis. The PRISMA strategy was used for this study. Our study was registered with PROSPERO (ID: CRD42021251072). We searched PubMed, Medline, Web of Science, and the Cochrane databases from 1990 to December of 2022. The meta-analysis was performed with Review Manager 5.4 and Stata 14. After selection and exclusion, 15 articles out of 672 were included. The meta-analysis showed that the cure rate of laparoscopic fundoplication in treating GERC was 58% (95%CI: 52%-65%), with I2 = 45%; and the effective rate was 86% (95%CI: 80%-93%), with I2 = 0%. Laparoscopic fundoplication is effective for the most of GERC patients; however, when the goal is to cure GERC completely, a relatively conservative attitude should be taken. In terms of safety, laparoscopic fundoplication is quite reliable offered by skilled surgeons.

Unveiling the functional heterogeneity of cytokine-primed human umbilical cord mesenchymal stem cells through single-cell RNA sequencing.

BACKGROUND: Mesenchymal stem cells (MSCs) hold immense promise for use in immunomodulation and regenerative medicine. However, their inherent heterogeneity makes it difficult to achieve optimal therapeutic outcomes for a specific clinical disease. Primed MSCs containing a certain cytokine can enhance their particular functions, thereby increasing their therapeutic potential for related diseases. Therefore, understanding the characteristic changes and underlying mechanisms of MSCs primed by various cytokines is highly important. RESULTS: In this study, we aimed to reveal the cellular heterogeneity, functional subpopulations, and molecular mechanisms of MSCs primed with IFN-γ, TNF-α, IL-4, IL-6, IL-15, and IL-17 using single-cell RNA sequencing (scRNA-seq). Our results demonstrated that cytokine priming minimized the heterogeneity of the MSC transcriptome, while the expression of MSC surface markers exhibited only slight changes. Notably, compared to IL-6, IL-15, and IL-17; IFN-γ, TNF-α, and IL-4 priming, which stimulated a significantly greater number of differentially expressed genes (DEGs). Functional analysis, which included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, indicated that IFN-γ, TNF-α, and IL-4-primed hUC-MSCs are involved in interferon-mediated immune-related processes, leukocyte migration, chemotaxis potential, and extracellular matrix and cell adhesion, respectively. Moreover, an investigation of various biological function scores demonstrated that IFN-γ-primed hUC-MSCs exhibit strong immunomodulatory ability, TNF-α-primed hUC-MSCs exhibit high chemotaxis potential, and IL-4-primed hUC-MSCs express elevated amounts of collagen. Finally, we observed that cytokine priming alters the distribution of functional subpopulations of MSCs, and these subpopulations exhibit various potential biological functions. Taken together, our study revealed the distinct regulatory effects of cytokine priming on MSC heterogeneity, biological function, and functional subpopulations at the single-cell level. CONCLUSIONS: These findings contribute to a comprehensive understanding of the inflammatory priming of MSCs, paving the way for their precise treatment in clinical applications.

High-Pressure Synthesis of Semiconducting PbCu3Mn4O12 with Near-Room-Temperature Ferrimagnetic Order.

A transition-metal oxide of PbCu3Mn4O12 was prepared at 1523 K and 10 GPa. An A-site-ordered quadruple perovskite structure with the space group Im3̅ is assigned for this compound. Based on bond-valence-sum calculations and X-ray absorption spectroscopy, the charge combination is determined to be PbCu32+Mn44+O12. Due to Cu2+(↑)-Mn4+(↓) antiferromagnetic coupling, a near-room-temperature ferrimagnetic phase transition is observed at approximately 287 K. PbCu3Mn4O12 exhibits a semiconducting electric transport property with the energy band gap Eg ≈ 0.2 eV. In addition, considerable low-field magnetoresistance effects are observed at lower temperatures. This study provides an intrinsic near-room-temperature ferrimagnetic semiconductor that exhibits potential applications in next-generation spintronic devices.

High-Pressure Synthesis of Quadruple Perovskite Oxide CaCu3Cr2Re2O12 with a High Ferrimagnetic Curie Temperature.

An AA'3B2B'2O12-type quadruple perovskite oxide of CaCu3Cr2Re2O12 was synthesized at 18 GPa and 1373 K. Both an A- and B-site ordered quadruple perovskite crystal structure was observed, with the space group Pn-3. The valence states are verified to be CaCu32+Cr23+Re25+O12 by bond valence sum calculations and synchrotron X-ray absorption spectroscopy. The spin interaction among Cu2+, Cr3+, and Re5+ generates a ferrimagnetic transition with the Curie temperature (TC) at about 360 K. Moreover, electric transport properties and specific heat data suggest the presence of a half-metallic feature for this compound. The present study provides a promising quadruple perovskite oxide with above-room-temperature ferrimagnetism and possible half-metallic properties, which shows potential in the usage of spintronic devices.

Combined therapy of CAR-IL-15/IL-15Rα-T cells and GLIPR1 knockdown in cancer cells enhanced anti-tumor effect against gastric cancer.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has shown remarkable responses in hematological malignancies with several approved products, but not in solid tumors. Patients suffer from limited response and tumor relapse due to low efficacy of CAR-T cells in the complicated and immunosuppressive tumor microenvironment. This clinical challenge has called for better CAR designs and combined strategies to improve CAR-T cell therapy against tumor changes. METHODS: In this study, IL-15/IL-15Rα was inserted into the extracellular region of CAR targeting mesothelin. In-vitro cytotoxicity and cytokine production were detected by bioluminescence-based killing and ELISA respectively. In-vivo xenograft mice model was used to evaluate the anti-tumor effect of CAR-T cells. RNA-sequencing and online database analysis were used to identify new targets in residual gastric cancer cells after cytotoxicity assay. CAR-T cell functions were detected in vitro and in vivo after GLI Pathogenesis Related 1 (GLIPR1) knockdown in gastric cancer cells. Cell proliferation and migration of gastric cancer cells were detected by CCK-8 and scratch assay respectively after GLIPR1 were overexpressed or down-regulated. RESULTS: CAR-T cells constructed with IL-15/IL-15Rα (CAR-ss-T) showed significantly improved CAR-T cell expansion, cytokine production and cytotoxicity, and resulted in superior tumor control compared to conventional CAR-T cells in gastric cancer. GLIPR1 was up-regulated after CAR-T treatment and survival was decreased in gastric cancer patients with high GLIPR1 expression. Overexpression of GLIPR1 inhibited cytotoxicity of conventional CAR-T but not CAR-ss-T cells. CAR-T treatment combined with GLIPR1 knockdown increased anti-tumor efficacy in vitro and in vivo. CONCLUSIONS: Our data demonstrated for the first time that this CAR structure design combined with GLIPR1 knockdown in gastric cancer improved CAR-T cell-mediated anti-tumor response.

Rational design, synthesis and biological evaluation of novel HIV-1 protease inhibitors containing 2-phenylacetamide derivatives as P2 ligands with potent activity against DRV-Resistant HIV-1 variants.

A novel kind of potent HIV-1 protease inhibitors, containing diverse hydroxyphenylacetic acids as the P2-ligands and 4-substituted phenyl sulfonamides as the P2' ligands, were designed, synthesized and evaluated in this work. Majority of the target compounds exhibited good to excellent activity against HIV-1 protease with IC50 values below 200 nM. In particular, compound 18d with a 2-(3,4-dihydroxyphenyl) acetamide as the P2 ligand and a 4- methoxybenzene sulfonamide P2' ligand exhibited inhibitory activity IC50 value of 0.54 nM, which was better than that of the positive control darunavir (DRV). More importantly, no significant decline of the potency against HIV-1DRVRS (DRV-resistant mutation) and HIV-1NL4_3 variant (wild type) for 18d was detected. The molecular docking study of 18d with HIV-1 protease (PDB-ID: 1T3R, www.rcsb.org) revealed possible binding mode with the HIV-1 protease. These results suggested the validity of introducing phenol-derived moieties into the P2 ligand and deserve further optimization which was of great value for future discovery of novel HIV-1 protease.

Spectroscopic Evidence of Kondo-Induced Quasiquartet in CeRh_{2}As_{2}.

CeRh_{2}As_{2} is a new multiphase superconductor with strong suggestions for an additional itinerant multipolar ordered phase. The modeling of the low-temperature properties of this heavy-fermion compound requires a quartet Ce^{3+} crystal-field ground state. Here, we provide the evidence for the formation of such a quartet state using x-ray spectroscopy. Core-level photoelectron and x-ray absorption spectroscopy confirm the presence of Kondo hybridization in CeRh_{2}As_{2}. The temperature dependence of the linear dichroism unambiguously reveals the impact of Kondo physics for coupling the Kramer's doublets into an effective quasiquartet. Nonresonant inelastic x-ray scattering data find that the |Γ_{7}^{-}⟩ state with its lobes along the 110 direction of the tetragonal structure (xy orientation) contributes most to the multiorbital ground state of CeRh_{2}As_{2}.