Design, synthesis, and biological evaluation of dual-site HIV-1 inhibitors simultaneously targeting the NNRTI binding pocket and an adjacent site with favorable resistance profiles.

Given high mutation rate of HIV-1 and its impact on NNRTIs' efficacy, targeting novel binding pockets has emerged as a viable strategy to overcome the drug resistance. In this study, we designed and synthesized 26 novel "dual-site" HIV-1 inhibitors that simultaneously target two distinct sites on reverse transcriptase (RT): the classical non-nucleoside inhibitor binding pocket (NNIBP) and a newly identified NNRTIs-adjacent site (NNIAS). Antiviral evaluation demonstrated that all compounds possessed potent activity against the wild-type (WT) HIV-1 strain, with EC values ranging from 4.

Stacking-controlled magnetic anisotropy switching in bilayer Janus MnClBr.

Bilayer Janus MnClBr exhibits intriguing tunable magnetic anisotropy energy (MAE), governed by stacking configurations and halogen-specific orbital interactions. Using density functional theory (DFT), we find that AA stacking in MnClBr induces a MAE transition from in-plane to out-of-plane orientation, which is absent in bilayer MnBrI and MnClI. This switching is driven by a compressed Mn-Br interlayer distance that amplifies the positive contribution of MAE from the p and p interaction of Br while suppressing the p-p contributions.

Discovery of novel diarypyrimidine derivatives as potent HIV-1 NNRTIs by exploiting the tolerant region I within NNRTI binding pocket.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) serve as an essential component of antiretroviral treatment regimens, but they encounter challenges such as resistance mutations, poor solubility, and adverse effects. This study presents the design, synthesis, and biological evaluation of novel diarylpyrimidine (DAPY)-typed derivatives targeting the tolerant region I within the NNRTI binding pocket (NNIBP). We introduced aliphatic ring structures with high Fsp value, aiming to enhance target affinity while simultaneously improving water solubility.

A patent review of anti-coronavirus agents targeting the spike-ACE2 interaction (2019-present).

Introduction: The Angiotensin-converting enzyme 2 (ACE2) receptor, crucial for coronavirus recognition of host cells, is a key target for therapeutic intervention against SARS-CoV-2 and related coronaviruses. Therefore, thoroughly investigating the interaction mechanism between ACE2 and the Spike protein (S protein), as well as developing targeted inhibitors based on this mechanism, is vital for effectively controlling the spread of SARS-CoV-2 and preventing potential future pandemics caused by other coronaviruses.

Areas Covered: This article comprehensively reviews the mechanisms underlying ACE2-S protein interaction that facilitate SARS-CoV-2 entry into host cells.

Spherical Nucleic Acids Meet Acoustic Levitation: A Breakthrough in Synthesis and Application.

Spherical nucleic acids (SNAs), with their densely packed nucleic acid shells and programmable functionalities, have become indispensable in nanomedicine and biosensing. Developed synthesis methods, including salt aging, pH modulation, freeze-thaw cycling, n-butanol dehydration, evaporation drying, and microwave heating, have enabled foundational advances but are constrained by slow kinetics, compromised structural uniformity and especially harsh reaction conditions, making them unsuitable for in situ tracking of biological events. This concept article introduces acoustic levitation synthesis as a groundbreaking alternative, uniquely addressing these limitations through a rapid, green, and highly controllable process.

Dion-Jacobson Perovskites with a Ferroelectrically Switchable Chiral Nonlinear Optical Response.

Electrically switchable second harmonic generation (SHG) is highly valuable in electro-optic modulators, which can be deployed in data communication and quantum optics. Coupling circular dichroism (CD) with an electrically controlled SHG process is advantageous because it enhances the signal transmission bandwidth and security while enabling multiple modulation modes for optical logic. However, ferroelectrically switchable chiral second-order nonlinearity is rarely reported.

FOXM1-activated IGF2BP3 promotes cell malignant phenotypes and M2 macrophage polarization in hepatocellular carcinoma by inhibiting ferroptosis via stabilizing RRM2 mRNA in an m6A-dependent manner.

Background: Ferroptosis has a crucial role in human carcinogenesis. N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) suppresses ferroptosis of hepatocellular carcinoma (HCC) cells. Here, we examined the effects and molecular determinants of IGF2BP3-mediated ferroptosis on malignant behaviors of HCC cells.

Discovery of novel fused-heterocycle-bearing diarypyrimidine derivatives as HIV-1 potent NNRTIs targeting tolerant region I for enhanced antiviral activity and resistance profile.

As an important part of anti-AIDS therapy, HIV-1 non-nucleoside reverse transcriptase inhibitors are plagued by resistance and toxicity issues. Taking our reported XJ-18b1 as lead compound, we designed a series of novel diarypyrimidine derivatives by employing a scaffold hopping strategy to discover potent NNRTIs with improved anti-resistance properties and drug-like profiles. The most active compound 3k exhibited prominent inhibitory activity against wild-type HIV-1 (EC = 0.

Two-dimensional chiral perovskites with large spin Hall angle and collinear spin Hall conductivity.

Two-dimensional hybrid organic-inorganic perovskites with chiral spin texture are emergent spin-optoelectronic materials. Despite the wealth of chiro-optical studies on these materials, their charge-to-spin conversion efficiency is unknown. We demonstrate highly efficient electrically driven charge-to-spin conversion in enantiopure chiral perovskites (R/S-MB)(MA)PbI (〈〉 = 4), where MB is 2-methylbutylamine, MA is methylamine, Pb is lead, and I is iodine.

An optimized impedance matching construction strategy: carbon nanofibers inlaid with Ni nanocrystals by electrospinning for high-performance microwave absorber.

With the widespread use of electronic goods, solving electromagnetic pollution has become one of the new challenges. Higher requirements for microwave-absorbing materials (MAM) have emerged to address this issue. The composite of carbon nanofiber (CNF) and magnetic nanoparticles is the material that effectively absorbs microwaves.

Neuroendoscopic Surgery Versus Stereotactic Aspiration in the Treatment of Supratentorial Intracerebral Hemorrhage: A Meta-Analysis.

Background: Debate persists over the relative merits of neuroendoscopic surgery (NS) compared to stereotactic aspiration (SA) for treating supratentorial intracerebral hemorrhage (ICH). Consequently, we undertook this meta-analysis to assess the efficacy and safety of NS versus SA.

Methods: We searched for the all-relevant studies systematically from English databases including PubMed, Embase, Web of Science, and the Cochrane Library.

Eosinophil Recovery Time Is Associated with Clinical Outcomes in Patients with Type A Acute Aortic Dissection: a Retrospective Cohort Study.

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month.

Acoustic Levitation Synthesis of Ultrahigh-Density Spherical Nucleic Acid Architectures for Specific SERS Analysis.

Controllably regulating the electrostatic bilayer of nanogold colloids is a significant premise for synthesizing spherical nucleic acid (SNA) and building ordered plasmonic architectures. We develop a facile acoustic levitation reactor to universally synthesize SNAs with an ultra-high density of DNA strands, which is even higher than those of various state-of-the-art methods. Results reveal a new mechanism of DNA grafting via acoustic wave that can reconfigure the ligands on colloidal surfaces.

LPCAT3 exacerbates early brain injury and ferroptosis after subarachnoid hemorrhage in rats.

Aims: Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is known to play a pivotal role in lipid metabolism, but its role in the early brain injury (EBI) following subarachnoid hemorrhage (SAH) remains unclear. This study provides insights into LPCAT3 expression alterations and functional implications in EBI following SAH.

Methods: SAH models of adult male Sprague-Dawley (SD) rats were established by intravascular perforation.

The relationship between ostracism and negative risk-taking behavior: the role of ego depletion and physical exercise.

Background: As a major public health problem globally, negative risk-taking behavior of college students may be related to their ostracism experience, but the reason for this association is unclear. Based on the limited resource theory, combined with the integrative model of athletic performance, we tested a moderated mediation model in which ego depletion mediated the association between ostracism and risk-taking, and physical exercise moderated the mediation process to examine the mechanisms underlying the association between ostracism and negative risk-taking behavior.

Methods: One thousand three hundred seven students (43% female) from four universities in China were recruited using cluster random sampling.

Efficacy and safety of eptinezumab for migraine: A systematic review and meta-analysis.

Background: Calcitonin gene-related peptides (CGRP) have been considered a new effective means to prevent and treat migraine. Eptinezumab is a new class of CGRP antagonists that has been ratified for clinical treatment. The purpose of this systematic review was to assess and contrast the therapeutic effect and safety of eptinezumab in the management of migraine in comparison with a placebo.

Recent Advances in Synthesis of Non-Alternating Polyketone Generated by Copolymerization of Carbon Monoxide and Ethylene.

The copolymers of carbon monoxide (CO) and ethylene, namely aliphatic polyketones (PKs), have attracted considerable attention due to their unique property and degradation. Based on the arrangement of the ethylene and carbonyl groups in the polymer chain, PKs can be divided into perfect alternating and non-perfect alternating copolymers. Perfect alternating PKs have been previously reviewed, we herein focus on recent advances in the synthesis of PKs without a perfect alternating structure including non-perfect alternating PKs and PE with in-chain ketones.

Multipiezo Effect in Altermagnetic VSeTeO Monolayer.

Strain engineering has been used as an efficient method to modulate various properties of quantum materials and electronic devices. One may establish piezo effects based on a disciplined response to the strain in multifunctional nanosystems. Inspired by a recent theoretical proposal on the interesting piezomagnetism and C-paired valley polarization in the VSeO monolayer, we predict a stable altermagnetic Janus monolayer VSeTeO using density functional theory calculations.

First-principles predictions of room-temperature ferromagnetism in orthorhombic MnX (X = O, S) monolayers.

Two-dimensional ferromagnets with high spin-polarization at ambient temperature are of considerable interest because they might be useful for making nanoscale spintronic devices. We report that even though bulk phases of MnO are generally antiferromagnetic with low ordering temperatures, the corresponding MnO and MnS monolayers are ferromagnetic, and MnS is a high temperature half metallic ferromagnet. Based on first-principles calculations, we find that the MnO monolayer is an intrinsic ferromagnetic semiconductor with a Curie temperature of ∼300 K, while the half-metallic MnS monolayer has a remarkably high of ∼1150 K.

Reconstruction of fractional vortex phase evolution by generative adversarial networks.

Digital signal coding based on the combination of vortex beam orbital angular momentum (OAM) and vortex optical phase information has made many achievements in optical communication. The accuracy of the vortex optical phase is the key to improving the efficiency of communication coding. In this regard, we propose a depth learning model based on the generative adversarial network (GAN) to accurately recover the phase image information of fractional vortex patterns at any diffraction distance, thus solving the problem that it is difficult to determine the phase information of fractional vortex patterns at different transmission distances due to the phase evolution.

Sources and hydrogeochemical processes of groundwater under multiple water source recharge condition.

Ecological water replenishment (EWR) is an essential approach for improving the quantity and quality of regional water. The Chaobai River is a major river in Beijing that is replenished with water from multiple sources, including reclaimed water (RW), the South-North Water Transfer Project (SNTP), reservoir discharge (RD). The effects of multiple water source recharge (MWSR) on groundwater quality remain unclear.

Restoring System xc- activity by xCT overexpression inhibited neuronal ferroptosis and improved neurological deficits after experimental subarachnoid hemorrhage.

Background: Ferroptosis is an important therapeutic target to alleviate early brain injury (EBI) after subarachnoid hemorrhage (SAH), yet the mechanism of neuronal ferroptosis after SAH remains unclear. System xc- dysfunction is one of the key pathways to induce ferroptosis. System xc- activity is mainly regulated by the expression of xCT.