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A comprehensive and effective electrochemical methodology is introduced for the diverse hydrodechlorination of gem-dichlorocyclopropanes and the ring cleavage hydrodefluorination of gem-difluorocyclopropanes under uniform electrochemical conditions. Moreover, the water content allows for the adjustable monohydrodechlorination or dihydrodechlorination of gem-dichlorocyclopropanes with exceptional chemoselectivity. Additionally, the mildness and practicality of this protocol facilitate its application to the late-stage functionalization of bioactive molecules. Mechanistic analyses suggest that the proton source may originate from acetonitrile.

The exploitation of simply processed p-type semiconductors and photodetectors with promising optoelectrical properties remains challenging yet essential for current and future advanced optoelectronic applications. Transparent p-type CuI and Sn-doped CuI (Cu–Sn–I) films and their self-powered photodetectors have been successfully fabricated by the spraying method. It is found that the incorporation of Sn dopants enhances the optical, electrical, and photoelectric properties of CuI thin films as well as their corresponding self-powered heterojunction photodetectors. This improvement of the optoelectrical properties of the Cu–Sn–I film and its photodetector can be attributed to the adjustment of the acceptor defect level and increased hole concentration resulting from Sn doping. The Cu–Sn–I/n-Si photodetector exhibits a responsivity of 10.7 mA/W, a detectivity of 6.79 × 1011Jones, and a response time of 77 μs/30 μs (0 V bias). The response time exhibits the fastest rise and decay times compared with the other CuI-based self-powered UV photodetectors in recent years, showcasing promising applications in the realm of transparent electronics moving forward. This study also presents an effective strategy for enhancing the electrical properties of p-type semiconductors and devices through effective doping.

Directly assembling drugs into mesoporous nanoformulations will be greatly favored due to the combination of enhanced drug delivery efficiency and mesostructure-enabled nanobio interactions. However, such an approach is hindered due to the lack of understanding of polymer nanoparticles’ formation mechanism, especially the relationship between polymerization, self-assembly, and the nucleation process. Here, by investigating the levodopa and dopamine polymerization process, we identify π-cation interaction as pivotal in the self-assembly and nucleation control of dopa molecules. Thus, through manipulation of the π-cation interaction, we present the direct assembly of a commercial drug, levodopa, into mesoporous nanoformulations. The synthesized nanospheres, approximately 200 nm in diameter, exhibit uniform mesopores of around 8 nm. These nanoformulations, abundant in mesopores, enhance chiral phenylalanine interaction with α-synuclein (Syn), curbing aggregation, safeguarding neurons, and alleviating Parkinson’s pathology. When combating α-synuclein, the nanoformulation achieved ∼100% inhibition of protein aggregation and sustained neuron viability up to 300%. We believe that this study may advance mesoscale self-assembly knowledge, guiding future nanopharmaceutical developments.

With the development of smart grid, the introduction of blockchain technology provides a novel idea for secure power data sharing. The existing blockchain-based data aggregation schemes generally rely on a unique leader node to perform verification algorithms, but there may be a lazy leader node not performing aggregation data verification to save computation costs. In addition, in the existing verification mechanism, light nodes need to perform the same verification operations as the leader node, which results in resource-constrained light nodes being unable to bear. In this paper, we propose an efficient blockchain-based data aggregation scheme with privacy-preserving on the smart grid, called EC-ASPG, which implements a supervised mechanism for the lazy leader node, enhancing the security of the system. Furthermore, we propose a separable consensus verification mechanism, which can prevent other light nodes from performing duplicate verification operations like the leader node, effectively improving the efficiency of consensus verification. Finally, we present a formal security proof and comprehensive performance evaluations. The results show that our scheme is secure and outperforms the compared schemes in terms of performance analysis.

Herein, we present a prominent metal-free C–N cross-coupling platform that enables access to carbamoyl- and ketoazides from isocyanides or silyl enol ethers and trimethylsilyl azide (TMSN3) with an aid of iodine(III) promoter. This offers a rapid route to a diverse set of synthetically valuable azide decorated fragments with excellent substrate scope and good to excellent yields. The disclosed platform exemplifies the use of TMSN3for incorporation of the azide fragment without the loss of N2.

Progressive dysfunction of the retinal pigment epithelium (RPE) and the adjacent photoreceptor cells in the outer retina plays a pivotal role in the pathogenesis of diabetic retinopathy (DR). Here, we observed a marked increase in oxidative stress-induced apoptosis in parallel with higher expression of telomeric protein TIN2 in RPE cells under hyperglycemia in vivo and in vitro. Delving deeper, we confirm that high glucose-induced elevation of mitochondria-localized TIN2 compromises mitochondrial activity and weakens the intrinsic antioxidant defense, thereby leading to the activation of mitochondria-dependent apoptotic pathways. Mechanistically, mitochondrial TIN2 promotes the phosphorylation of FOXO1 and its relocation to the mitochondria. Such translocation of transcription factor FOXO1 not only promotes its binding to the D-loop region of mitochondrial DNA—resulting in the inhibition of mitochondrial respiration—but also hampers its availability to nuclear target DNA, thereby undermining the intrinsic antioxidant defense. Moreover, TIN2 knockdown effectively mitigates oxidative-induced apoptosis in diabetic mouse RPE by preserving mitochondrial homeostasis, which concurrently prevents secondary photoreceptor damage. Our study proposes the potential of TIN2 as a promising molecular target for therapeutic interventions for diabetic retinopathy, which emphasizes the potential significance of telomeric proteins in the regulation of metabolism and mitochondrial function.

Ru(PPh3)3Cl2reacts with Binn–from an ethylenediamine (en) solution of K5Bi4to yield a new architype of 13-vertex [Bi10{RuPPh3}3]−(1) composed of unprecedented incomplete cuboidal Bi73–and triangular Bi33–held together by {RuPPh3}2+.

The development of a bifunctional electrocatalyst with high efficiency, high stability, and low cost is of great significance in practical applications of electrocatalytic water splitting. Herein, a self-supporting bifunctional electrocatalyst with a NiFe layered double hydroxide/Fe2O3/Ni3S2heterostructure (NiFe LDH/Fe2O3/Ni3S2/IF) for hydrogen evolution and oxygen evolution reactions (HER/OER) is synthesized by the self-corrosion of iron foam (IF) and hydrothermal strategies. The constructed NiFe LDH/Fe2O3/Ni3S2/IF hierarchical heterostructure was not only beneficial to expose active sites and promote charge/mass transfer but also generate a superhydrophilic/superaerophobic surface, thereby accelerating the reaction kinetics to improve the HER/OER activity. Therefore, NiFe LDH/Fe2O3/Ni3S2/IF exhibited superior overpotentials of 226.2 and 162.8 mV for the OER and HER at 100 mA cm–2, respectively. NiFe LDH/Fe2O3/Ni3S2/IF was employed as both the cathode and the anode to assemble a device for overall water splitting and displayed a voltage of 1.55 V at 10 mA cm–2. The overall water splitting device was coupled with a solar cell to simulate a solar-powered water splitting system, resulting in a superior solar-to-hydrogen conversion efficiency of 15.16%. This work can promote the development of clean energy sources such as solar hydrogen production.

Manipulation of the spin state holds great promise to improve the electrochemical activity of transition metal-based catalysts. However, the underlying relationship between the nonplanar metal coordination environment and spin states remains to be explored. Herein, we report the precise regulation of nonplanar Fe atomic d-orbital energy level into an irregular tetrahedral crystal field configuration by introducing P atoms. With the increase of P coordination number, the spin magnetic moment decreases linearly from 3.8 μB to 0.2 μB, and the high spin content decreases linearly from 31% to 5%. Significantly, a volcanic curve between the spin states of Fe-based catalysts (Fe–NxPy) and oxygen reduction reaction (ORR) activity has been unequivocally established based on the thermodynamic results. Thus, the Fe–N3P1catalyst with a 19% medium spin state experimentally exhibits the optimal reaction activity with a high half-wave potential of 0.92 V. These findings indicate that regulating electron spin moments through coordination engineering is a promising catalyst design strategy, providing important insights into spin catalysis.

Purpose: The purpose of this paper is to investigate the impact of mechanical vibration on the heat transfer and pressure drop characteristics of semicircular channel printed circuit heat exchangers (PCHEs), while also establishing correlations between vibration parameters and thermal performance. Design/methodology/approach: By combining experimental and numerical simulation methods, the heat transfer coefficient and pressure drop characteristics of supercritical carbon dioxide (S-CO2) in a semicircular channel with a diameter of 2 mm under vibration conditions were studied. Reinforce the research by conducting computational fluid dynamics studies using ANSYS Fluent 22.0, the experimental results were compared with the numerical simulation results to verify the accuracy of the numerical method. Findings: The use of vibration has the potential to attenuate the degradation of wall heat transfer caused by buoyancy-induced PCHEs on the upward-facing surface. The heat transfer enhancement (HTE) was maximized by an increase of 18.2%, while the pressure drop enhancement (PDE) was elevated by over 25-fold. The capacity to enhance the heat exchange between S-CO2 and channel walls through increasing vibration intensity is limited, indicating maximum effectiveness in improving thermal performance. Originality/value: Conducting heat transfer experiments on PCHEs with mechanical vibration enhancement and verifying the accuracy of the vibration numerical model. The relation based on the dimensionless factor is derived. To provide theoretical support for using vibration to enhance the heat transfer capability of PCHEs. [ABSTRACT FROM AUTHOR]

The notion of constrained common invariant subspaces (CCISs) is proposed in this article as a generalization of the well-known invariant subspace to study the structural properties of multiple matrices. Specifically, some necessary and sufficient conditions for the existence of a CCIS are established to provide a methodology to compute such a CCIS. Then, the properties of CCISs and their relation to common eigenvectors are revealed. The existence of common eigenvectors leads to the existence of CCIS, but not vice versa, so the established CCIS can reveal the structural properties of multiple matrices better than common eigenvectors can. The established CCIS is applied to the reducibility of Fornasini–Marchesini (F-M) state-space models, i.e., the necessary and sufficient conditions and the related algorithm for reducibility of F-M models are developed. Finally, a gain-scheduled state-feedback control is proposed for a rational parameter system to further demonstrate the superiority of the established CCIS.

Double Toeplitz (shortly DT) codes are introduced here as a generalization of double circulant codes. The authors show that such a code is isodual, hence formally self-dual (FSD). FSD codes form a far-reaching generalization of self-dual codes, the most important class of codes of rate one-half. Self-dual DT codes are characterized as double circulant or double negacirculant. Likewise, even binary DT codes are characterized as double circulant. Numerical examples obtained by exhaustive search show that the codes constructed have best-known minimum distance, up to one unit, amongst formally self-dual codes, and sometimes improve on the known values. For q= 2, the authors find four improvements on the best-known values of the minimum distance of FSD codes. Over F4an explicit construction of DT codes, based on quadratic residues in a prime field, performs equally well. The authors show that DT codes are asymptotically good over Fq. Specifically, the authors construct DT codes arbitrarily close to the asymptotic Varshamov-Gilbert bound for codes of rate one half.

Actin fibers are an important part of the cytoskeleton, providing vital support for the plasma membrane. This function is driven by its ATPase (ATP: adenosine triphosphate) activity, i.e., ATP+H2O→ADP+Pi. This seemingly simple reaction has attracted much attention because the hydrolysis of ATP provides energy to support life processes. However, the reaction mechanism of ATP hydrolysis in actin is not clear. In order to gain deep insights into the functions of actin, it is essential to elucidate the reaction mechanism of the actin ATP hydrolysis. In this paper, we have studied the reaction mechanism of the ATP hydrolysis in actin by the combined quantum mechanical and molecular mechanics (QM/MM) calculations. Our results show that 1) bond cleavage of the Pγ—OSof ATP and bond formation between oxygen of the lytic water and Pγatoms take place simultaneously, and this is the rate-limiting step of the hydrolysis; 2) the proton on the lytic water transfers to the phosphate to form H2PγO4−viaone bridge water. The energy barrier of the complete reaction is 17.6 kcal/mol (1 kcal=4.184 kJ), which is in high agreement with the experimental value.

In situregeneration is a promising strategy for constructing tissue engineering heart valves (TEHVs). Currently, the decellularized heart valve (DHV) is extensively employed as a TEHV scaffold. Nevertheless, DHV exhibits limited blood compatibility and notable difficulties in endothelialization, resulting in thrombosis and graft failure. The red blood cell membrane (RBCM) exhibits excellent biocompatibility and prolonged circulation stability and is extensively applied in the camouflage of nanoparticles for drug delivery; however, there is no report on its application for large-scale modification of decellularized extracellular matrix (ECM). For the first time, we utilized a layer-by-layer assembling strategy to immobilize RBCM on the surface of DHV and construct an innovative TEHV scaffold. Our findings demonstrated that the scaffold significantly improved the hemocompatibility of DHV by effectively preventing plasma protein adsorption, activated platelet adhesion, and erythrocyte aggregation, and induced macrophage polarization toward the M2 phenotype in vitro. Moreover, RBCM modification significantly enhanced the mechanical properties and enzymatic stability of DHV. The rat models of subcutaneous embedding and abdominal aorta implantation showed that the scaffold regulated the polarization of macrophages into the anti-inflammatory and pro-modeling M2 phenotype and promoted endothelialization and ECM remodeling in the early stage without thrombosis and calcification. The novel TEHV exhibits excellent performance and can overcome the limitations of commonly used clinical prostheses.

Granulation is an effective method for improving the flowability of drugs, particularly when they are in needle form. Carbamazepine-hesperetin (CBZ-HPE) cocrystal is a needle-like crystal with low solubility and poor flowability, which limits its application. To address this issue, this study aimed to obtain CBZ-HPE microspheres using the quasi-emulsion solvent diffusion (QESD) technique. The preparation process was monitored using polarized light microscopy, and the formation mechanism was elucidated using the radial distribution function (RDF). The microspheres were extensively characterized using PXRD, DSC, TGA, and SEM. Furthermore, the effects of surfactants, contents, and rotational speeds on the morphology and particle size distribution of microspheres were analyzed to determine the optimal experimental conditions. Based on these findings, naringenin and quercetin, the active ingredients of traditional Chinese medicine, were chosen to successfully prepare CBZ-HPE multicomponent microspheres. This research provides a foundation for increasing drug powder properties and drug conjugation through the preparation of microspheres.

We describe a visible light-induced palladium-catalyzed radical germylative arylation of alkenes with easily accessible chlorogermanes. This protocol provides expedient access to germanium-substituted indolin-2-ones in good to excellent yields under mild reaction conditions. The key step for this strategy lies in the reductive activation of germanium–chloride bonds with an excited palladium complex under visible light irradiation. The involvement of germanium radicals was evidenced by electron paramagnetic resonance spectroscopy experiments.

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe’s efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.

A series of deeply reduced MoIV6-polyoxometalates (POMs), [MoIV6(bpy)6MoVI2O16S2]·10H2O (1) (bpy = 2,2′-bipyridine), [MoIV6(bpy)4(L-TrA)2MoV4(bpy)2O14S4]2·36.5H2O (2), and [MoIV6(bpy)4(D-TrA)2MoV4(bpy)2O14S4]2(3) (TrA = tartaric acid), were obtained from one-pot hydrothermal syntheses. They feature the bioxo-bridged [MoIV3O3S]4+incomplete cuboidal cores stabilized by strong triangular metal–metal bonds and datively chelated bpy π-ligands. The two apical MoVIO4in 12e-Mo8(1) and two [MoV2O3STrAbpy] in 16e-Mo10(2, 3) complete the octahedral coordination geometry of the deeply reduced MoIV, not counting the MoIV–MoIVd2–d2bonds. The aromatic planar bpy π ligands form a two-dimensional face-to-face π stacking supramolecular structure, which are further strengthened by point-to-face C–H···π interactions in the π stacked layers. 16e-Mo10(2, 3) has stronger intramolecular face-to-face π stacking interactions, which are interconnected by intermolecular C–H···π into a three-dimensional framework structure. These structural features account for their highly enhanced electronic conductivities (1, 6.19 × 10–8S cm–1; 2, 2.18 × 10–7S cm–1), providing a new way of thinking to improve electronic conductivity of POMs. 1-3have been described by first-principles density function theory (DFT) calculations and also characterized by elemental analyses, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), solid UV–visible spectra, and circular dichroic (CD) spectra.

Endogenous security has the ability to discover, eliminate, and solve internal security problems and hidden dangers within the network, and is a superior technology to ensure future network security. The $t/k$-diagnosis strategy, as a strong and adaptive self-diagnosis strategy, is an important part for ensuring endogenous security. Moreover, the folded hypercube ($FQ_{n}$) as a data transmission network (e.g., optical network) topology offers new potential for the construction of large-scale, high data throughput, and low-latency systems, such as computing network, human-cyber-physical systems, and smart grid. However, there are few studies on endogenous security based on $FQ_{n}$ networks. Therefore, this article designs an adaptive system-level fault self-diagnosis strategy, namely Fast t/k-Diagnosis Under Maeng-Malek Model (Ftk-DIAG-MM*) to diagnosis the faulty vertices in $FQ_{n}$ network under the Maeng-Malek model (MM* mod). Then, we provide a proof of the algorithm correctness theoretically by the fault tolerance of $FQ_{n}$ network. It is derived by theoretical derivation that the $t/k$-diagnosability inherent to the $FQ_{n}$ network is $(n+1)(k+1)-k(k+3)/2$. The simulation experiments demonstrate that the designed Ftk-DIAG-MM* strategy can correctly diagnose all vertices within the range allowed by the diagnosability, and still has a great performance when it exceeds the range allowed by the diagnosability. It greatly enhances the fault diagnosis capability of $FQ_{n}$ network in the circumstance of misdiagnosing a few vertices, which provides an important theoretical basis for the reliability and endogenous security of $FQ_{n}$ networks.

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 μM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.

Traditional underwater polarization differential imaging methods use a fixed polarization direction to suppress the background scattered light; however, the polarization angle of the background scattered light may change in different underwater environments, limiting their effectiveness and real-time performance. In this paper, an improved underwater polarization differential imaging method is proposed, in which the polarization angle with the highest frequency of occurrence is selected as the polarization angle of the backscattered light by Stokes vector analysis. Then, the polarization images of the two best orthogonal polarization directions are obtained by combining the polarizer Mueller matrix and processed differentially. Compared with the traditional method, this method can suppress the backscattered light more accurately and effectively and improve the quality and real-time performance of underwater imaging. This method will have an important impact on imaging applications in complex underwater scenes.

In this study, a Cu–Cu2O junction structure was grown in situ on the surface of Cu plates via chemical etching at room temperature. A novel dopamine (DA) electrochemical sensor based on Cu–Cu2O/glassy carbon electrode (Cu–Cu2O/GCE) was constructed. The Cu–Cu2O/GCE sensor exhibited a wide linear range of 0.03–2.45 mM and a low limit of detection of 7.1 nM (S/N = 3) for DA. The enhanced performance was due to the unique void structure, which increased catalytic active sites and electrochemical active surface areas. Moreover, the optimization of the Cu2O–to–Cu ratio allowed for the effective regulation of the electron configuration of the Cu–Cu2O junction structure. The Cu–Cu2O/GCE sensor also exhibited good reproducibility, stability, and anti-interference ability.

Extracellular vesicles (EVs) have garnered significant attention in biomedical applications. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the unbiased and rapid isolation of EVs in 20 min with ∼80% recovery in neutral conditions. Moreover, the approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, the isolated EVs could be directly applied for downstream protein and nucleic acid analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of both epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene mutation in clinical plasma samples. Our approach offers great possibilities for utilizing EVs in liquid biopsy, as well as in various other biomedical applications.

This article presents a Kalman–Koopman linear quadratic regulator (KKLQR) control approach to robotic systems. In the proposed approach, an optimal Koopman modeling method based on neural networks, in which continuous Koopman eigenfunctions are constructed without requiring any predefined dictionary, is proposed to obtain approximated linear models with high precision for robotic systems. Specifically, the linear model is constructed through a multistep prediction error minimization, which enables a long-term prediction capability. Furthermore, the Kalman filter is employed to alleviate the effects of disturbances in the KKLQR control approach. Experimental results show that the proposed KKLQR control approach achieves better prediction and control performance than other existing representative methods.

This article proposes a slot-loaded circularly polarized implantable antenna with wide bandwidth at 2.45 GHz, i.e., Industrial, Scientific, and Medical (ISM) band. This antenna is established with a compact size of 44.52 mm3based on 3D printing technology, and biocompatible material MED610 is adopted for human safety consideration. During the design, unilaterally shorted patch antenna loaded with T-slot is adopted, obtaining two closely spaced orthogonal modes with miniaturized antenna size. More importantly, to obtain wide impedance matching, a spiral slot is introduced around the feed, forming an L-section network consisted of a parallel capacitor and a series inductor. As a result, a wide circular polarization bandwidth of 28.7 % is realized for the proposed antenna. The measured results are well agreed with simulated results.

Galectin-3 (Gal-3) is a carbohydrate binding protein that has been implicated in the development and progression of fibrotic diseases. Proof-of-principal animal models have demonstrated that inhibition of Gal-3 is a potentially viable pathway for the treatment of fibrosis─with small molecule Gal-3 inhibitors advanced into clinical trials. We hereby report the discovery of novel galactose-based monosaccharide Gal-3 inhibitors comprising 2-methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (compound 20) and 4-phenyl-4H-1,2,4-triazole (compound 15). Notably, hindered rotation caused by steric interaction between the 3-thione and ortho-trifluoromethyl group of compounds 20, 21induced formation of thermodynamically stable atropisomers. Distinct X-ray cocrystal structures of 20and 21were obtained, which clearly demonstrated that the configuration of 21proscribes a key halogen bonding σ-hole interaction of 3-chloro with carbonyl oxygen of Gly182, thereby leading to significant loss in potency. Ultimately, 20and 15were evaluated in mouse pharmacokinetic studies, and both compounds exhibited oral exposures suitable for further in vivoassessment.

Based on the similarity between the working mechanism of memristors and the synapses of neural networks, a design scheme of perceptron neural networks based on memristors is proposed in this article. Using memristor based perceptron neurons as the basic unit, a single layer perceptron neural network based on memristors is implemented by adding perceptron neurons in parallel. A multilayer perceptron neural network based on memristors is implemented by serially adding a single layer perceptron neural network. The multiclassification function of the single layer perceptron neural network based on memristors was verified through experiments to determine the quadrant of points in a two-dimensional plane, with a classification accuracy of 96.67%. Through logical XOR operation experiments, the ability of the multilayer perceptron neural network based on memristors to handle linear indivisible problems is verified, and the error is zero. The experimental results of multiclassification and linear indivisibility problems confirm the feasibility of the memristor based perceptron network design scheme.

ABSTRACTIntroductionFocal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation.Areas coveredThere is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research.Expert OpinionFAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure–activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

An effective tool to assess embryo quality in the assisted reproduction clinical practice will enhance successful implantation rates and mitigate high risks of multiple pregnancies. Potential biomarkers secreted into culture medium (CM) during embryo development enable rapid and noninvasive methods of assessing embryo quality. However, small volumes, low biomolecule concentrations, and impurity interference collectively preclude the identification of quality-related biomarkers in single blastocyst CM. Here, we developed a noninvasive trace multiomics approach to screen for potential markers in individual human blastocyst CM. We collected 84 CM samples and divided them into high-quality (HQ) and low-quality (LQ) groups. We evaluated the differentially expressed proteins (DEPs) and metabolites (DEMs) in HQ and LQ CM. A total of 504 proteins and 189 metabolites were detected in individual blastocyst CM. Moreover, 9 DEPs and 32 DEMs were identified in different quality embryo CM. We also categorized HQ embryos into positive implantation (PI) and negative implantation (NI) groups based on ultrasound findings on day 28. We identified 41 DEPs and 4 DEMs associated with clinical implantation outcomes in morphologically HQ embryos using a multiomics analysis approach. This study provides a noninvasive multiomics analysis technique and identifies potential biomarkers for clinical embryo developmental quality assessment.

A silver-catalyzed protocol for the intermolecular radical umpolung cross-coupling protocol of silyl enol ethers with activated methylene compounds is disclosed. The protocol exhibits excellent functional group tolerance, enabling the expedient preparation of a variety of tricarbonyl compounds. Preliminary mechanistic investigations suggest that the reaction proceeds through a process involving free radicals in which silver oxide has a dual role, acting as both a catalyst and a base.

Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image‐enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white‐light imaging (WLI) in a high‐risk population. In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630–4.330]; p< 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p< 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. United States National Library of Medicine (https://www.clinicaltrials.gov), ID: NCT040720521.

The oxygen reduction reaction (ORR) holds significant importance in the electrochemical processes of energy conversion systems. The kinetics of the ORR are sluggish as it is involved in multistep reactions. It is imperative to investigate ORR electrocatalysts with outstanding performance and durability accelerating their kinetics. Manganese–nitrogen–carbon (Mn–N–C) materials offer significant advantages including efficient atom utilization and easily tunable coordination structures, rendering them promising candidates for enhancing ORR catalytic activity. The mini-review provides a concise overview of the fundamental principles underlying the ORR. Then, three strategies for regulating the coordination structure are summarized to improve the ORR catalytic activity of Mn–N–C catalysts: adjusting the coordination number of N atoms around Mn atoms, doping nonmetal atoms, and doping metal atoms. Finally, this mini-review outlines the challenges and prospects associated with the Mn–N–C catalyst for ORR. This mini-review is anticipated to deepen the comprehension of ORR electrocatalysts for readers by presenting targeted optimization methods to regulate the configuration of Mn–N–C catalysts.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18adipocyte-specific knockout (Rab18AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18AKO mice had a moderate increase without ER stress stimulation. Rab18AKO mice developed insulin resistance and systematic inflammation. Rab18AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Enzymes catalyze almost all material conversion processes within living organisms, yet their natural evolution remains unobserved. Short peptides, derived from proteins and featuring active sites, have emerged as promising building blocks for constructing bioactive supramolecular materials that mimic native proteins through self-assembly. Herein, we employ histidine-containing isomeric tetrapeptides KHFF, HKFF, KFHF, HFKF, FKHF, and FHKF to craft supramolecular self-assemblies, aiming to explore the sequence–activity landscapes of enzyme evolution. Our investigations reveal the profound impact of peptide sequence variations on both assembly behavior and catalytic activity as hydrolytic simulation enzymes. During self-assembly, a delicate balance of multiple intermolecular interactions, particularly hydrogen bonding and aromatic–aromatic interactions, influences nanostructure formation, yielding various morphologies (e.g., nanofibers, nanospheres, and nanodiscs). Furthermore, the analysis of the structure–activity relationship demonstrates a strong correlation between the distribution of the His active site on the nanostructures and the formation of the catalytic microenvironment. This investigation of the sequence–structure–activity paradigm reflects how natural enzymes enhance catalytic activity by adjusting the primary structure during evolution, promoting fundamental research related to enzyme evolutionary processes.

The antibodies in the natural biological world utilize bivalency/multivalency to achieve a higher affinity for antigen capture. However, mimicking this mechanism on the electrochemical sensing interface and enhancing biological affinity through precise spatial arrangement of bivalent aptamer probes still pose a challenge. In this study, we have developed a novel self-assembly layer (SAM) incorporating triblock polyA DNA to enable accurate organization of the aptamer probes on the interface, constructing a “lock-and-key-like” proximity hybridization assay (PHA) biosensor. The polyA fragment acts as an anchoring block with a strong affinity for the gold surface. Importantly, it connects the two DNA probes, facilitating one-to-one spatial proximity and enabling a controllable surface arrangement. By precisely adjusting the length of the polyA fragment, we can tailor the distance between the probes to match the molecular dimensions of the target protein. This design effectively enhances the affinity of the aptamers. Notably, our biosensor demonstrates exceptional specificity and sensitivity in detecting PDGF-BB, as confirmed through successful validation using human serum samples. Overall, our biosensor presents a novel and versatile interface for proximity assays, offering a significantly improved surface arrangement and detection performance.

As important π-skeletons, benzosiloles often possess unique electronic and optical properties and have been widely used in semiconductor materials. Therefore, great attention has been drawn to the area of developing novel synthetic methods for various benzosiloles. However, the synthesis of enantioenriched silicon-stereogenic benzosiloles is still at an early stage and remains to be explored. Herein, we performed systematic density functional theory studies on the recently reported nickel-catalyzed asymmetric synthesis of silicon-stereogenic benosiloles, which was enabled by an enantioselective desymmetrization of (2-alkenyl)aryl-substituted silacyclobutanes. Our computational study shows that the reaction mechanism involves ligand exchange, oxidative addition, alkene insertion, and hydrogen-transfer coupled reductive-demetalation steps. The proposed transmetalation and β-hydride elimination mechanism was not found, which might be due to the unfavorable ring strain of the multicyclic intermediates. The novel hydrogen-transfer coupled reductive-demetalation mechanism was shown to be reasonable for the generation of the silicon-stereogenic benzosilole. Noncovalent interactions (including C–H···π and hydrogen bonding) in the rate-determining alkene insertion transition state account for the origins of the enantioselectivity. Our computational study sheds light on the detailed reaction mechanism and also provides insights for the development of novel approaches for synthesis of high-value silicon-stereogenic compounds.

To understand the effect of particulate contaminants on pavement skid resistance, the friction numbers of three surfaces under different pollution conditions (particle size, coverage fraction, and shape factor) were measured using a British Pendulum Tester (BPT). The results show that less than 45% coverage fraction of the particles above 0.3 mm even results in almost 50% friction loss at a low speed of 10 km/h. In this situation, the rougher surface has a stronger holding particles capacity. Moreover, the particle size determining the lowest friction level gradually increases as the surface roughness increases. The particle size of 1.18–2.36 mm is the most typical size range leading to a low friction level. In addition, the friction first drops sharply and then increases slowly with the coverage fraction increases, which also conforms to the Stribeck curve.

The oriental fruit fly,Bactrocera dorsalis(Hendel), is a notorious pest of fruit crops, causing severe damage to fleshy fruits during oviposition and larval feeding. Gravid females locate suitable oviposition sites by detecting the host volatiles. Here, the oviposition preference of antenna-removed females and the electrophysiological response of ovipositors to benzothiazole indicated that both antennae and ovipositors are involved in perceiving benzothiazole. Subsequently, odorant receptors (ORs) expressed in both antennae and ovipositors were screened, and BdorOR43a-1 was further identified to respond to benzothiazole using voltage-clamp recording. Furthermore, BdorOR43a-1–/–mutants were obtained using the CRISPR/Cas9 system and their oviposition preference to benzothiazole was found to be significantly altered compared to WT females, suggesting that BdorOR43a-1 is one of the important ORs for benzothiazole perception. Our results not only demonstrate the important role of antennae and ovipositors in benzothiazole-induced oviposition but also elucidate on the OR responsible for benzothiazole perception in B. dorsalis.

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The permeability and selectivity of biological and artificial ion channels correlate with the specific hydration structure of single ions. However, fundamental understanding of the effect of ion–ion interaction remains elusive. Here, via non-contact atomic force microscopy measurements, we demonstrate that hydrated alkali metal cations (Na+and K+) at charged surfaces could come into close contact with each other through partial dehydration and water rearrangement processes, forming one-dimensional chain structures. We prove that the interplay at the nanoscale between the water–ion and water–water interaction can lead to an effective ion–ion attraction overcoming the ionic Coulomb repulsion. The tendency for different ions to become closely packed follows the sequence K+> Na+> Li+, which is attributed to their different dehydration energies and charge densities. This work highlights the key role of water molecules in prompting close packing and concerted movement of ions at charged surfaces, which may provide new insights into the mechanism of ion transport under atomic confinement.

Many endeavors in expressing a heterologous gene in microbial hosts rely on simply placing the gene of interest between a selected pair of promoters and terminator. However, although the expression efficiency could be improved by engineering the host cell, how modifying the expression cassette itself systematically would affect heterologous gene expression remains largely unknown. As the promoter and terminator bear plentiful cis-elements, herein using the Aspergillus nigermannanase with high application value in animal feeds and the eukaryotic filamentous fungus workhorse Trichoderma reeseias a model gene/host, systematic engineering of an expression cassette was investigated to decipher the effect of its mutagenesis on heterologous gene expression. Modifying the promoter, signal peptide, the eukaryotic-specific Kozak sequence, and the 3′-UTR could stepwise improve extracellular mannanase production from 17 U/mL to an ultimate 471 U/mL, representing a 27.7-fold increase in expression. The strategies can be generally applied in improving the production of heterologous proteins in eukaryotic microbial hosts.

Accurate prediction of enzyme optimal temperature (Topt) is crucial for identifying enzymes suitable for catalytic functions under extreme bioprocessing conditions. The optimal growth temperature (OGT) of microorganisms serves as a key indicator for estimating enzyme Topt, reflecting an evolutionary temperature balance between enzyme-catalyzed reactions and the organism’s growth environments. Existing OGT databases, collected from culture collection centers, often fall short as culture temperature does not precisely represent the OGT. Models trained on such databases yield inadequate accuracy in enzyme Topt prediction, underscoring the need for a high-quality OGT database. Herein, we developed AI-based models to extract the OGT information from the scientific literature, constructing a comprehensive OGT database with 1155 unique organisms and 2142 OGT values. The top-performing model, BioLinkBERT, demonstrated exceptional information extraction ability with an EM score of 91.00 and an F1 score of 91.91 for OGT. Notably, applying this OGT database in enzyme Topt prediction achieved an R2value of 0.698, outperforming the R2value of 0.686 obtained using culture temperature. This emphasizes the superiority of the OGT database in predicting the enzyme Topt and underscores its pivotal role in identifying enzymes with optimal catalytic temperatures.

Monochamus alternatusis an important stem-boring pest in forestry. However, the complex living environment of Monochamus alternatuscreates a natural barrier to chemical control, resulting in a very limited control effect by traditional insecticidal pesticides. In this study, a stable pesticide dendritic mesoporous silica-loaded matrine nanopesticide (MAT@DMSNs) was designed by encapsulating the plant-derived pesticide matrine (MAT) in dendritic mesoporous silica nanoparticles (DMSNs). The results showed that MAT@DMSNs, sustainable nanobiopesticides with high drug loading capacity (80%) were successfully constructed. The release efficiency of DMSNs at alkaline pH was slightly higher than that at acidic pH, and the cumulative release rate of MAT was about 60% within 25 days. In addition, the study on the toxicity mechanism of MAT@DMSNs showed MAT@DMSNs were more effective than MAT and MAT (0.3% aqueous solutions) in touch and stomach toxicity, which might be closely related to their good dispersibility and permeability. Furthermore, MAT@DMSNs are also involved in water transport in trees, which can further transport the plant-derived insecticides to the target site and improve its insecticidal effect. Meanwhile, in addition, the use of essential oil bark penetrants in combination with MAT@DMSNs effectively avoids the physical damage to pines caused by traditional trunk injections and the development of new pests and diseases induced by the traditional trunk injection method, which provides a new idea for the application of biopesticides in the control of stem-boring pests in forestry.

ABSTRACTCracking of the reinforced concrete (RC) slab is a critical problem for a composite beam subjected to a hogging moment, which hinders its application to indeterminate composite structural systems. An [...]

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1H-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in in vitroand in vivosettings. Results showed that small-molecule-modified surfaces significantly reduced the Staphylococcal epidermidisbiofilm formation compared to unmodified surfaces and decreased the nucleotide levels of c-di-AMP in biofilm cells, suggesting that the tethered small molecules interfere with intracellular nucleotide signaling and inhibit biofilm formation. The hemocompatibility assay showed that the modified polyurethane films did not induce platelet activation or red blood cell hemolysis but significantly reduced plasma coagulation and platelet adhesion. The cytocompatibility assay with fibroblast cells showed that small-molecule-modified surfaces were noncytotoxic and cells appeared to be proliferating and growing on modified surfaces. In a 7-day subcutaneous infection rat model, the polymer samples were implanted in Wistar rats and inoculated with bacteria or PBS. Results show that modified polyurethane significantly reduced bacteria by ∼2.5 log units over unmodified films, and the modified polymers did not lead to additional irritation/toxicity to the animal tissues. Taken together, the results demonstrated that small molecules tethered on polymer surfaces remain active, and the modified polymers are biocompatible and resistant to microbial infection in vitro and in vivo.