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The synthesis and modification of peptides occupy a unique position in the field of drug development, and the functionalization of amino acids is a valuable strategy as an alternative to peptide modification. Currently, the development of tyrosine (Tyr) as a target amino acid is a major challenge in the field of chemistry. Herein, we report an electrochemical radical coupling reaction of labeling tyrosine-containing active drugs and peptides with thiocarbamate derivatives for the first time. This tri-component, one-pot reaction can be performed smoothly under simple, gentle, and clean electrochemical conditions and is suitable for the functionalization of various Tyr-containing drug molecular derivatives and peptides.

Objectives: To summarize the clinical characteristics and investigate the efficacy of ethanol embolotherapy in the treatment of chest well arteriovenous malformation (AVM). Treatment-associated complications were also explored.Materials and Methods: Between March 2017 and August 2021, 32 consecutive patients (mean age, 23.7 years; age range, 5–54 years) who underwent ethanol embolotherapy for chest well AVMs under general anesthesia were included in this study. Embolization was performed through a direct puncture, transarterial catheterization, or a combination of the 2 procedures. The mean follow-up duration after the last treatment was 18.0 months (range, 3–42 months). The degree of devascularization on follow-up (assessed using angiography or computed tomography), and the clinical signs and symptoms of AVMs were evaluated as the therapeutic outcomes. The major and minor complications associated with the procedures were recorded.Results: A total of 103 embolization procedures (mean, 3.2; range, 2–7) comprising 101 ethanol embolization and 2 coil embolizations were performed on 32 patients with chest wall AVMs. The AVM nidus was accessed through the transarterial approach alone in 4 patients, by direct puncture in 11, and a combined procedure in 17 patients. Overall, more than 80% of the procedures were performed using the combined approach. Complete AVM devascularization was achieved in 12 (37.5%) patients. Moreover, 76% to 99% AVM was achieved in 18 patients (56.3%), and 50% to 75% in 2 patients (6.3%). Bleeding, pain, heart failure, and cosmetic deformities were the indications for treatment. For 3 patients (3/32, 9.4%) who had bleeding, the treatment stopped the hemorrhage. Complete pain relief was reported in 8 patients (8/32, 25.0%), whereas complete relief from congestive heart failure post-embolization was observed in 5 of the 6 patients with congestive heart failure (5/6, 83.3%). Complete correction of cosmesis deformities after embolization was achieved in 10 patients (10/32, 31.3%). Two patients who underwent surgery to correct persistent deformity after embolization only showed insignificant improvement. In addition, 6 (18.8%) patients developed 13 complications including blister, necrosis, hemothorax, transient hemoglobinuria, and transient pulmonary artery hypertension.Conclusions: Ethanol embolotherapy is a safe and effective procedure for chest well AVMs. Surgery is required for some patients with residual cosmesis deformity.Clinical Impact Currently, there is no standard treatment for chest well AVMs due to their rarity and high heterogeneity. The present study shows that thanol embolotherapy is a safe and clinically effective treatment procedure for the chest well AVMs. Transarterial embolization in combination with direct puncture embolization can reach the AVM nidus. Ethanol embolotherapy can achieve complete obliteration of the AVM nidus in the majority of patients. Surgery may still be needed to correct cosmetic deformity after embolization. The present study provides valuable evidence to inform clinical decision-making.

Co-cultivation of isopod-associated fungi Herpotrichiasp. SF09 and Trametes versicolorSF09A led to the reciprocal induction of thirteen new compounds (1–7and 9–13) with diverse architectures. Importantly, compounds 1and 2are rare fungal sesquiterpene-saccharide hybrids incorporating a xylopyranose moiety, compound (±)-3represents the first example of a natural linear sesquiterpene racemate, and compound 7is a rare α-pyrone derivative with a xylopyranose motif. Their structures were elucidated by analysis of NMR and mass spectrometry data, and their absolute configurations were determined by Mosher’s method, microscale derivatization, and single-crystal X-ray diffraction, as well as ECD calculations. All the isolated compounds ameliorated MPP+-induced oxidative damage in PC12 cells in a dose-dependent fashion. Among them, compounds 5and 15showed significant protective action against neuronal injury by MPP+at 5 μM. Meanwhile, transcriptome sequencing was performed to evaluate the molecular mechanism of the neuroprotective activity for compound 5. Results indicated that compound 5might mitigate MPP+-induced neuronal injury through the regulation of multiple signaling pathways, including the PI3K-Akt and MAPK pathways. Our findings suggested that compound 5could be a promising neuroprotective agent for the treatment of Parkinson’s disease.

The recent discovery of crystalline pentazolates marks a major advance in polynitrogen chemistry and raises prospects of making the long-touted potent propellant N5+N5–salt. However, despite the synthesis of cyclo-N5–anions in pentazolates, countercation cyclo-N5+remains elusive due to the strong oxidizing power of the pentazole ion; moreover, pure N5+N5–salt is known to be unstable. Here, we devise a new strategy for making rare cyclo-N5+cations and assembling the long-sought N5+N5–salt in tailored ionic compounds, wherein the negative/positive host ions act as oxidizing/reducing agents to form cyclo-N5+/N5–species. This strategy is implemented via an advanced computational crystal structure search, which identifies X N5N5F (X = Li, Na, and K) compounds that stabilize at high pressures and remain viable at ambient pressure–temperature conditions based on ab initio molecular dynamics simulations. This finding opens an avenue for creating and stabilizing the N5+N5–salt assembly in ionic compounds, where cyclo-N5species are oxidized/reduced via comatching with host ions of high/low electronegativity. The present results demonstrate novel polynitrogen chemistry, and these findings offer new insights and prospects for the design and synthesis of diverse chemical species that exhibit unusual charge states, bonding structures, and superior functionality.

Calcination of MgCO3is an important industrial reaction, but it causes significant and unfavorable CO2production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*→ COOH*trans→ COOH*cis→ CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O–CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O–CH2→ sur-O–CH3→ sur-O + CH4*).

Orthogonal time frequency space (OTFS) as a newly proposed two-dimensional modulation scheme outperforms the orthogonal frequency division multiplexing in high-speed scenarios. Most recent studies focus on off-grid channel estimation with the ideal pulse which needs to satisfy the bi-orthogonality robustness condition but does not exist. In this paper, we consider an OTFS system with rectangular pulses and propose a grid evolution based off-grid sparse Bayesian inference (GESBI) by updating the virtual delay-Doppler grid to improve the accuracy of the channel estimation. In particular, different from the recently proposed off-grid channel estimation algorithms in OTFS where the virtual grid is fixed and uniform, the proposed channel estimation method consists of an external and internal iteration, where the grid evolution method performs in the external iteration to update the virtual grid to be non-uniform by utilizing the estimated on-grid and the off-grid information in the internal iteration. In addition, the grid evolution-based efficient sparse Bayesian inference with the Student’s T distribution prior (T-GEESBI) is proposed to reduce the channel estimation complexity while improving the channel estimation accuracy. Specifically, the matrix inversion is avoided by approximating the posterior distribution. Then the equal non-convex problem is handled by utilizing the block coordinate descent method in a majorization-minimization framework. Furthermore, the two types of genie bounds on the mean squared error of the estimated channel coefficients are derived. Finally, both theoretical and numerical analyses demonstrate low complexity, convergence, and the efficiency of the proposed channel estimation approach.

Background: Placebo control plays an important role in evaluating the effectiveness of interventions. Specifying differential effects of various placebo controls on migraine prevention would be essential in the explanation of preventive treatment for migraine and the indirect comparison between different prophylactic therapeutics. Objectives: To access the impact of different non-pharmacologic placebo types on different outcomes in migraine patients. Methods: We searched PubMed, Cochrane Controlled Register of Trials, Embase, and Web of Science databases from the date of creation to June 19, 2023. Randomized controlled trials of migraine that included sham intervention of acupuncture or cognitive behavioural therapy (CBT) or non-invasive Vagus Nerve Stimulation (nVNS) or repetitive Transcranial Magnetic Stimulation (rTMS) or transcranial Direct Current Stimulation (tDCS) were conducted. The primary outcome was the migraine days, and the secondary outcomes were the number of migraine attacks, headache days, headache frequency, and responder’s rate. Placebo effects were assessed using five individual placebos for network meta-analysis, using mean differences to measure the relative effect of pair-wise comparisons between interventions. Result: A total of 50 trials with 4880 subjects were included. Twenty-seven trials were evaluated for low risk of bias. The results of indirect comparisons show that sham rTMS and sham tDCS had optimal and similar effects in reducing migraine days; sham acupuncture has the greatest effect on reducing the number of migraine attacks and relieving headache frequency; sham rTMS had a highly significant advantage in reducing headache days compared with the other placebo controls. Conclusion: Based on the network meta-analysis results, we found that sham acupuncture had the greatest effect on migraine prophylaxis. The strong placebo effect of sham acupuncture should be considered when assessing the therapeutic effect.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2were more predominant with CSF(+) while FAT4mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.

Perovskite-silicon (Si) tandem solar cells are the most prominent contenders to succeed single-junction Si cells that dominate the market today. Yet, to justify the added cost of inserting a perovskite cell on top of Si, these devices should first exhibit sufficiently high power conversion efficiencies (PCEs). Here, we present two key developments with a synergetic effect that boost the PCEs of our tandem devices with front-side flat Si wafers—the use of 2,3,4,5,6-pentafluorobenzylphosphonic acid (pFBPA) in the perovskite precursor ink that suppresses recombination near the perovskite/C60interface and the use of SiO2nanoparticles under the perovskite film that suppresses the enhanced number of pinholes and shunts introduced by pFBPA, while also allowing reliable use of Me-4PACz as a hole transport layer. Integrating these developments in an optically and electrically optimized tandem device (e.g., with a durable Si cell), reproducible PCEs of 30 ± 1%, and a certified maximum of 30.9% are achieved.

Numerous high-performance nanotechnologies have been developed, but their practical applications are largely restricted by the nanomaterials’ low stabilities and high operation complexity in aqueous substrates. Herein, we develop a simple and high-reliability hydrogel-based nanotechnology based on the in situformation of Au nanoparticles in molybdenum disulfide (MoS2)-doped agarose (MoS2/AG) hydrogels for electrophoresis-integrated microplate protein recognition. After the incubation of MoS2/AG hydrogels in HAuCl4solutions, MoS2nanosheets spontaneously reduce Au ions, and the hydrogels are remarkably stained with the color of as-synthetic plasmonic Au hybrid nanomaterials (Au staining). Proteins can precisely mediate the morphologies and optical properties of Au/MoS2heterostructures in the hydrogels. Consequently, Au staining-based protein recognition is exhibited, and hydrogels ensure the comparable stabilities and sensitivities of protein analysis. In comparison to the fluorescence imaging and dye staining, enhanced sensitivity and recognition performances of proteins are implemented by Au staining. In Au staining, exfoliated MoS2semiconductors directly guide the oriented growth of plasmonic Au nanostructures in the presence of formaldehyde, showing environment-friendly features. The Au-stained hydrogels merge the synthesis and recognition applications of plasmonic Au nanomaterials. Significantly, the one-step incubation of the electrophoretic hydrogels leads to high simplicity of operation, largely challenging those multiple-step Ag staining routes which were performed with high complexity and formaldehyde toxicity. Due to its toxic-free, simple, and sensitive merits, the Au staining integrated with electrophoresis-based separation and microplate-based high-throughput measurements exhibits highly promising and improved practicality of those developing nanotechnologies and largely facilitates in-depth understanding of biological information.

Extracellular vesicle (EV) molecular phenotyping offers enormous opportunities for cancer diagnostics. However, the majority of the associated studies adopted biomarker-based unimodal analysis to achieve cancer diagnosis, which has high false positives and low precision. Herein, we report a multimodal platform for the high-precision diagnosis of bladder cancer (BCa) through a multispectral 3D DNA machine in combination with a multimodal machine learning (ML) algorithm. The DNA machine was constructed using magnetic microparticles (MNPs) functionalized with aptamers that specifically identify the target of interest, i.e., five protein markers on bladder-cancer-derived urinary EVs (uEVs). The aptamers were hybridized with DNA-stabilized silver nanoclusters (DNA/AgNCs) and a G-quadruplex/hemin complex to form a sensing module. Such a DNA machine ensured multispectral detection of protein markers by fluorescence (FL), inductively coupled plasma mass spectrometry (ICP-MS), and UV–vis absorption (Abs). The obtained data sets then underwent uni- or multimodal ML for BCa diagnosis to compare the analytical performance. In this study, urine samples were obtained from our prospective cohort (n= 45). Our analytical results showed that the 3D DNA machine provided a detection limit of 9.2 × 103particles mL–1with a linear range of 4 × 104to 5 × 107particles mL–1for uEVs. Moreover, the multimodal data fusion model exhibited an accuracy of 95.0%, a precision of 93.1%, and a recall rate of 93.2% on average, while those of the three types of unimodal models were no more than 91%. The elevated diagnosis precision by using the present fusion platform offers a perspective approach to diminishing the rate of misdiagnosis and overtreatment of BCa.

Spectrum–structure correlation is playing an increasingly crucial role in spectral analysis and has undergone significant development in recent decades. With the advancement of spectrometers, the high-throughput detection triggers the explosive growth of spectral data, and the research extension from small molecules to biomolecules accompanies massive chemical space. Facing the evolving landscape of spectrum–structure correlation, conventional chemometrics becomes ill-equipped, and deep learning assisted chemometrics rapidly emerges as a flourishing approach with superior ability of extracting latent features and making precise predictions. In this review, the molecular and spectral representations and fundamental knowledge of deep learning are first introduced. We then summarize the development of how deep learning assist to establish the correlation between spectrum and molecular structure in the recent 5 years, by empowering spectral prediction (i.e., forward structure–spectrum correlation) and further enabling library matching and de novomolecular generation (i.e., inverse spectrum–structure correlation). Finally, we highlight the most important open issues persisted with corresponding potential solutions. With the fast development of deep learning, it is expected to see ultimate solution of establishing spectrum–structure correlation soon, which would trigger substantial development of various disciplines.

While process simulation tools offer immense potential in chemical engineering, effectively integrating them into the educational curriculum poses challenges. This work explored and practiced online–offline blended teaching in process simulation courses. The design of this blended course was based on a comparison of students’ performances in fully online courses, Massive Open Online Courses (MOOCs) and Small Private Online Course (SPOCs). Approximately 2000 students from academic institutions or industries have participated in these online courses since 2021. The comparison between MOOCs and SPOCs encompassed participation rates and scores, revealing a preference among participants for hands-on software lectures over theoretical ones in the process simulation course. Based on the outcomes of online learning, we redesigned the online–offline blended course to optimize course arrangements, leveraging the complementary advantages of both online and offline instruction. This blended approach manifested in two key aspects: first, the online segment served as a precursor to the offline component, with the offline component acting as an evaluative measure of the online segment; second, the two-unit project-based online learning led to the redesigned five-unit offline instruction, which served as both a supplement and expansion to the two-unit online teaching. Furthermore, offline activities, such as error-correction exercises and case studies conducted through group learning, enhanced students’ ability for open-ended and independent thinking and reinforced their understanding of innovation on process simulation, which was lacking in online learning.

The copolymerization of olefins with carbon monoxide (CO) affords aliphatic polyketones, which exhibit excellent mechanical strength, crystallinity, photodegradability, hydrophilicity, and surface and barrier properties. The chain-transfer copolymerization of ethylene with CO has offered an available method to regulate the molecular weight of polyketones that are amenable to conventional injection molding and extrusion. In this study, we investigated the copolymerization pathway using the [P,O]-Pd catalyst in a protonic environment. The key chain-propagating species are identified by state-of-the-art electrospray ionization mass spectrometry. These findings indicate that the copolymerization can be performed in different protonic solvents in a chain-transfer fashion; thus, the molecular weight of polyketone products can be regulated over the range of 8.13–238 kg/mol. In particular, such a chain-transfer method renders the formation of novel telechelic structures having a ketone backbone and diester chain ends selectively. The differences between [P,O]-Pd and diphosphine–Pd catalysts have been disclosed, and this study provides insights into the discovery and design of novel catalysts for this interesting copolymerization reaction.

Antiangiogenic therapy is an effective way to disrupt nutrient supply and starve tumors, but it is restricted by poor efficacy and negative feedback-induced tumor relapse. In this study, a neuropilin-1 (NRP-1)-targeted nanomedicine (designated as FPPT@Axi) is reported for spatiotemporal tumor suppression by combining photodynamic therapy (PDT) with antiangiogenesis. In brief, FPPT@Axi is prepared by utilizing an NRP-1-targeting chimeric peptide (Fmoc-K(PpIX)-PEG8-TKPRR) to encapsulate the antiangiogenic drug Axitinib (Axi). Importantly, the NRP-1-mediated targeting property enables FPPT@Axi to selectively concentrate at vascular endothelial and breast cancer cells, facilitating the production of reactive oxygen species (ROS) in situfor specific vascular disruption and enhanced cell apoptosis under light stimulation. Moreover, the codelivered Axi can further inhibit vascular endothelial growth factor receptor (VEGFR) to impair the negative feedback of PDT-induced tumor neovascularization. Consequently, FPPT@Axi spatiotemporally restrains the tumor growth through blocking angiogenesis, destroying tumor vessels, and inducing tumor apoptosis. Such an NRP-1-mediated targeting codelivery system sheds light on constructing an appealing candidate with translational potential by using clinically approved PDT and chemotherapy.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signaland will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

This paper proposes a digital twin (DT) modeling method for the lifecycle state evaluation of cable-stayed bridges, which cover a large time scale and simultaneously involve macroscopic and microcosmic exploration. First, the DT model at the design stage corresponds to the computer-aided design (CAD) model and then evolves to the computer-aided engineering (CAE) model during the construction stage. After that, the DT model for the operational stage starts from the completion model of the bridge and keeps evolving with the bridge physical entity in the long-term service. An information interaction media is used for the information interchange between the DT model and the bridge physical entity. And a fidelity index gives the quantitative estimation of similarity between the DT model and the bridge physical entity. Finally, the proposed method has been verified against a cable-stayed bridge model, whose DT model could reflect the actual state evolution of the physical entity.

AbstractThe in-plant use of recycled aggregate concrete derived from precast rejects (termed PRAC herein) can promote a circular economy in the precast industry. However, the environmental implications associated with this practice remain poorly understood. A refined life cycle assessment (LCA) model was therefore developed to highlight the environmental benefits of using PRAC compared to natural aggregate concrete and conventional recycled aggregate concrete. Some key factors influencing PRAC’s environmental performance were also examined. The results indicate that PRAC exhibits around 15% lower energy consumption and carbon dioxide emissions compared to other recycled materials. This reduction is attributed to the favourable quality of PRAC and the elimination of long-distance transport. However, emissions allocation and raw material prices play significant roles in determining the overall environmental impact of PRAC. The equivalent mortar volume mixing method is best suited for PRAC production, as it saves energy, reduces emissions, and maintains similar mechanical properties. Nevertheless, the high-temperature curing, which is often necessary in a precast factory setting, can be energy-intensive and thus diminishes the eco-friendliness of PRAC. Overall, the findings support the use of precast rework as recycled aggregate for cleaner production in the precast industry.

Periodontitis is a chronic inflammatory disease closely associated with reactive oxygen species (ROS) involvement. Eliminating ROS to control the periodontal microenvironment and alleviate the inflammatory response could potentially serve as an efficacious therapy for periodontitis. Melatonin (MT), renowned for its potent antioxidant and anti-inflammatory characteristics, is frequently employed as an ROS scavenger in inflammatory diseases. However, the therapeutic efficacy of MT remains unsatisfactory due to the low water solubility and poor bioavailability. Carbon dots have emerged as a promising and innovative nanomaterial with facile synthesis, environmental friendliness, and low cost. In this study, melatonin-derived carbon dots (MT-CDs) were successfully synthesized via the hydrothermal method. The MT-CDs have good water solubility and biocompatibility and feature excellent ROS-scavenging capacity without additional modification. The in vitroexperiments proved that MT-CDs efficiently regulated intracellular ROS, which maintained mitochondrial homeostasis and suppressed the production of inflammatory mediators. Furthermore, findings from the mouse model of periodontitis indicated that MT-CDs significantly inhibited the deterioration of alveolar bone and reduced osteoclast activation and inflammation, thereby contributing to the regeneration of damaged tissue. In terms of the mechanism, MT-CDs may scavenge ROS, thereby preventing cellular damage and the production of inflammatory factors by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. The findings will offer a vital understanding of the advancement of secure and effective ROS-scavenging platforms for more biomedical applications.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most widely studied herbicide targets and has gained significant attention. To identify potential effective HPPD inhibitors, a rational multistep virtual screening workflow was built, which included CBP models (based on the receptor–ligand interactions in the crystal complex), Hypogen models with activity prediction ability (according to the derivation of structure–activity relationships from a set of molecules with reported activity values), and a consensus docking procedure (consisting of LibDock, Glide, and CDOCKER). About 1 million molecules containing diketone or β-keto–enol substructures were filtered by Lipinski’s rules, CBP model, and Hypogen model. A total of 12 compounds with similar docking postures were generated by consensus docking. Eventually, four molecules were screened based on the specific binding pattern and affinity of the HPPD inhibitor. The biological evaluation in vivo displayed that compounds III-1and III-2exhibited comparable herbicidal activity to isoxaflutole and possessed superior safety on various crops (wheat, rice, sorghum, and maize). The ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that compound IIIpossessed relatively good toxicological results. This work provides a theoretical basis and valuable reference for the virtual screening and molecular design of novel HPPD inhibition herbicides.

A 1:8 physical water model was constructed to investigate the fluid flow and mixing phenomena in the basic oxygen furnace (BOF) converter. The particle image velocimetry was employed to measure the velocity distribution of the bath and the high-speed camera was applied to capture the cavity shape in the combined blowing BOF converter. The mixing time for varied operating conditions was measured by the stimulus-response approach. The cavity depth increased with the decrease in the lance height and the increase in the top gas flow rate while the bottom blowing gas had little influence on the cavity depth. The minimum cavity depth was obtained under the condition of a 69.8 m3/h top gas flow rate, a 287.5 mm lance height and a 0.93 m3/h bottom blowing gas flow rate, which was 161.2 mm. The mixing time decreased as the lance height decreased and the top blowing gas flow rate increased. The mixing time was first decreased and then increased with the increase in the bottom gas flow rate. With the condition of 69.8 m3/h gas flow rate of top blowing, the 287.5 mm lance height and the 0.93 m3/h gas flow rate of bottom blowing, the mixing time in the converter was 48.65 s. The empirical formula between the stirring power and the mixing time in the converter was calculated.

The construction of quaternary carbon centers via C–C coupling protocols remains challenging. The coupling of tertiary C(sp3) with secondary or tertiary C(sp3) counterparts has been hindered by pronounced steric clashes and many side reactions. Herein, we have successfully developed a type of bisphosphine ligand iron complex-catalyzed coupling reactions of tertiary alkyl halides with secondary alkyl zinc reagents and efficiently realized the coupling reaction between tertiary C(sp3) and secondary C(sp3) with high selectivity for the initial instance, which provided an efficient method for the construction of quaternary carbon centers with high steric hindrance. The combination of an iron catalyst and directing group of the substrate makes the great challenging transformation possible.

Ultracold polyatomic molecules offer opportunities1in cold chemistry2,3, precision measurements4and quantum information processing5,6, because of their rich internal structure. However, their increased complexity compared with diatomic molecules presents a challenge in using conventional cooling techniques. Here we demonstrate an approach to create weakly bound ultracold polyatomic molecules by electroassociation7(F.D. et al., manuscript in preparation) in a degenerate Fermi gas of microwave-dressed polar molecules through a field-linked resonance8–11. Starting from ground-state NaK molecules, we create around 1.1 × 103weakly bound tetratomic (NaK)2molecules, with a phase space density of 0.040(3) at a temperature of 134(3) nK, more than 3,000 times colder than previously realized tetratomic molecules12. We observe a maximum tetramer lifetime of 8(2) ms in free space without a notable change in the presence of an optical dipole trap, indicating that these tetramers are collisionally stable. Moreover, we directly image the dissociated tetramers through microwave-field modulation to probe the anisotropy of their wavefunction in momentum space. Our result demonstrates a universal tool for assembling weakly bound ultracold polyatomic molecules from smaller polar molecules, which is a crucial step towards Bose–Einstein condensation of polyatomic molecules and towards a new crossover from a dipolar Bardeen–Cooper–Schrieffer superfluid13–15to a Bose–Einstein condensation of tetramers. Moreover, the long-lived field-linked state provides an ideal starting point for deterministic optical transfer to deeply bound tetramer states16–18.

An efficient method to construct 4-aryl-substituted β-carbolines from indole-2-methyl-α-aminoketones via a TMSOTf-promoted annulation reaction was reported. High yield along with wide substrate scope and functional group tolerance make this reaction applicable to build various highly potential bioactive β-carboline derivatives.

Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Neutral nanomaterials functionalized with PEG or similar molecules have been popularly employed as nanomedicines. Compared to positive counterparts that are capable of harnessing the well-known proton sponge effect to facilitate their escape from lysosomes, it is yet unclear how neutral substances got their entry into the cytosol. In this study, by taking PEGylated, neutral Au nanospheres as an example, we systematically investigated their time-dependent translocation postuptake. Specifically, we harnessed dissipative particle dynamics simulations to uncover how nanospheres bypass lysosomal entrapment, wherein a mechanism termed as “squeezing-out” mode was discovered. We next conducted a comprehensive investigation on how nanomaterials implicate lysosomes in terms of integrity and functionality. By using single-molecule imaging, specific preservation of PEG-terminated with targeting moieties in lysosomes supports the “squeezing-out” mode as the mechanism underlying the lysosomal escape of nanomaterials. All evidence points out that such a process is benign to lysosomes, wherein the escape of nanomaterials proceeds at the expense of targeting moieties loss. Furthermore, we proved that by fine-tuning of the efficacy of nanomaterials escaping from lysosomes, modulation of distinct pathways and metabolic machinery can be achieved readily, thereby offering us a simple and robust tool to implicate cells.

The recycling of spent lithium-ion batteries is in urgent demand, while organic binders hinder the recovery of electrode materials. In this study, a pyrolysis-coupled mechanical milling method was proposed to recover electrode materials from a spent lithium-ion battery. The results showed that pyrolysis removed the organic binders inside the spent battery, and after the mechanical milling, the total recovery ratio of electrode materials increased from 38.91 to 93.70% under the conditions with a pyrolysis temperature of 650 °C, milling duration of 15 min, and grinding ball ratio of 2:3. Meanwhile, the recovery ratios of cathode metals and anode graphite reached 97.89 and 86.90%, respectively. On the basis of the characterization results, it was determined that the chemical valences of the recovered metals were reduced by the reductive pyrolysis gases, whereas the graphitization degree of the recovered graphite decreased dramatically as a result of the presence of pyrolysis char. The findings presented herein offered a simple and eco-friendly option for the recovery of electrode materials from a spent lithium-ion battery as well as recycling noble metals and graphite resources.

A radical 1,2,4-trifunctional reaction of thiosulfonate to unactivated olefin is achieved by a migration strategy under mild conditions. In this reaction, the more unstable primary free radicals are in situ generated after the migration of heteroaryl groups in the presence of DABCO. This trifunctionalization of unactivated olefins involves two C–S bond formations and one C–C bond formation.

ABSTRACTThe random inspection of the China Securities Regulatory Commission (CSRC) is an important policy for practicing “standardizing regulatory behavior and innovating management modes”. This study investigates how CSRC’s random affect capital market information efficiency from the perspective of stock price synchronicity. Using a sample of China’s non-financial A-share firms from 2013 to 2019, we find that random inspections significantly reduced the stock price synchronicity of inspected firms. Random inspections could increase the probability of releasing management earnings forecasts, media coverage and investor attention, and thereby improve information efficiency. Further study finds that the effect of random inspections on stock price synchronicity is stronger for non-state controlled firms, districts with more listed firms, and districts with more transparent government. This study enriches the literature on the consequences of random inspections and extends our knowledge of the relationship between regulatory innovations and the information efficiency of the capital market.

The GH4720Li alloy is one of the most widely used precipitation-strengthened nickel-based superalloy. However, systematic study about effect of strain rate on the plastic deformation behavior of GH4720Li alloy at intermediate temperature is lacking. The evolution of the tensile properties and plastic deformation mechanism of GH4720Li alloy with the strain rate at 650 °C were systematically studied with the help of transmission electron microscopy analysis. The results show that the tensile strength of the alloy increases and the plasticity decreases with the increase in strain rate. When the strain rate is 5 min−1, the tensile strength of the alloy is 1448 MPa and the tensile plasticity is 18%. As the strain rate increases from 0.05 to 0.5 min−1, the size and morphology of the primary γ′ phase of the alloy remain unchanged, with an average size of about 1.8 μm. However, when the strain rate further increases to 5 min−1, the average size of the primary γ′ phase increases to 2.5 μm. In addition, the increase of strain rate has no significant effect on the size and distribution of secondary and tertiary γ′ phases. As the strain rate increases from 0.05 to 5 min−1, the deformation mechanism of alloy gradually evolved from dislocation slip and twin to dislocation slip, indicating that the plastic deformation mechanism of the alloy presents a high strain rate sensitivity at 650 °C.

In this article, broadband dual-circularly polarized (dual-CP) antenna arrays with independent control of polarizations are proposed and demonstrated at the K-band. By introducing folded $\Gamma $ -shaped end loadings and corner truncation, a dual-CP magnetoelectric dipole (ME-dipole) element with a compact footprint and a broad bandwidth of 22.5% is realized. Based on such element, a $2\times2$ -element sequential rotation (SR) subarray is constructed. By employing a high dielectric constant substrate, a stacked array feeding configuration is devised by placing two sets of microstrip feeding circuits above and below the ground plane for independent dual-CP beamforming. Importantly, the feeding circuitry is fully confined within the area of the array elements without occupying any extra space. Furthermore, a $4\times4$ -element array is synthesized for obtaining dual-CP radiated beams over a broad bandwidth with improved CP purity and port isolation via exploiting the double-stage SR feeding strategy. The fabricated array prototype experimentally achieves a 3-dB axial ratio bandwidth of wider than 28.5%, a 3-dB gain bandwidth of about 23.2%, as well as a −10 dB impedance bandwidth of greater than 50% within which the port isolation is higher than 15 dB. Moreover, the dual-CP beamforming is also showcased by a second array example that generates an LHCP pencil beam and an RHCP vortex beam pointing at distinct directions, confirming the capability of independent control of polarization.

Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

In this brief, an optimization design of broadband Doherty power amplifier (DPA) is presented for the extension of bandwidth. A dual-state impedance objective function is utilized in the optimization of the carrier and peaking output matching networks (OMNs) to satisfy the load impedance constraints at back-off output power and saturation, respectively. Unlike conventional method, a novel impedance constraint strategy is proposed by employing an impedance constraint circle in Smith chart, which can more fully utilize the impedance region obtained from load-pull simulations. Moreover, to increase design flexibility, a fragment-type matching circuit is employed in the OMN optimization design together with the dual-state impedance objective function. Experimental results demonstrate a 1.2 to 2.6 GHz (74% fractional bandwidth) broadband DPA with a drain efficiency of 49.7%–53.5% measured at 6 dB back-off and a saturated output power of higher than 43 dBm.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The “block and lock” approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the “block and lock” strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the “block and lock” strategy in the pursuit of an HIV-1 cure.

A novel hybrid composite integrating conductive poly-3-methoxythiophene and PCN-222(Fe) (porphyrin-metal–organic frameworks) was synthesized using an in situpolymerization strategy. Leveraging the large specific area of MOFs and the low electrical resistance of conductive polymers, the modified electrode proved to be a promising candidate for the electrochemical detection of 4-nitrobenzaldehyde. The electrocatalytic response was measured using differential pulse voltammetry techniques and cyclic voltammetry, where the linear concentration range of analyte detection was estimated to be 0–900 μM and the detection limit was 0.233 μM with high selectivity toward the analyte. The sensor demonstrated repeatability and stability, allowing the direct electroanalytical measurement of 4-nitrobenzaldehyde in real samples with reliable recovery. This methodology expands the application of porphyrin MOFs for the electroanalytical sensing of environmental contaminants.

In this paper, a dual-band Doherty power amplifier (DPA) is proposed that can operate over two wide passbands, which is realized by multiple transmission zeros (TZs) in an all-pass response. The short/open stub loaded stepped-impedance transformers act as the output matching networks (OMNs) in both carrier and peaking paths. The shunted stubs not only generate TZs but also perform impedance conversion, simultaneously satisfying the load-pull requirements at both output back off (OBO) and saturation. This is achieved over two wide frequency ranges. The combination between the OMNs in the two paths realizes a dual-passband response, even though the number of TZs at saturation is one less than that at OBO. A prototype DPA is implemented based on two 10-W GaN transistors to validate the methodology. Measured lower and upper frequency bands are from 1.35 to 1.75 GHz and 3.05 to 3.45 GHz, respectively, with both having 400 MHz operating bandwidths. Measured results demonstrate a maximum saturated gain of 9.2 dB and an output power of 43.8 dBm. Maximum 6-dB OBO and saturated efficiencies ( $\eta$ ) are 58% and 72%, respectively. The circuit occupies a very compact size with an area of $0.5\lambda _{g} \times 0.43\lambda _{g}$ .