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seco-pregnane C21steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21steroids and the structure–activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5lwith higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1and NtHsp70-061. Computational simulations indicated that 5ldisplayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind= −56.2 kcal/mol) compared with Ribavirin (ΔGbind= −47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

We herein reported a sustainable synthesis of 3,3-disubstituted oxindoles viaa Michael-type reaction based on the CuBr-catalysed capture of carboxylic oxonium ylides with isatylidene malononitrile. The reaction is characterized by a high atom economy and low economic constraints. The catalyst CuBr could be conveniently recyclized. The products of the reaction were found to be inhibitory against Na ion channels. We expect the reaction to shed the light on synthesis of biologically interesting molecules directed by principles of green chemistry.

Here we report a carbene-catalyzed enantio- and diastereoselective [4+2] cycloaddition reaction of cyclobutenones with isatins for the quick and efficient synthesis of spirocyclic δ-lactones bearing a chiral chlorine. A broad range of substrates with various substitution patterns proceed smoothly in this reaction, with the spirooxindole δ-lactone products afforded in generally good to excellent yields and optical purities under mild reaction conditions.

We present a relativistic equation-of-motion coupled-cluster with single and double excitation formalism within the exact two-component framework (X2C-EOM-CCSD), where both scalar relativistic effects and spin–orbit coupling are variationally included at the reference level. Three different molecular mean-field treatments of relativistic corrections, including the one-electron, Dirac–Coulomb, and Dirac–Coulomb–Breit Hamiltonian, are considered in this work. Benchmark calculations include atomic excitations and fine-structure splittings arising from spin–orbit coupling. Comparison with experimental values and relativistic time-dependent density functional theory is also carried out. The computation of the oscillator strength using the relativistic X2C-EOM-CCSD approach allows for studies of spin–orbit-driven processes, such as the spontaneous phosphorescence lifetime.

In this work, we designed a Mn-based hexacyanoferrate with partial substitution of MnIIIby FeII. The presence of FeIIat the low-spin position in Na2Mn1/6Fe5/6Fe(CN)6plays an important role in inhibiting the Jahn–Teller effect and reducing the dissolution of Mn2+, contributing to the robustness of the crystal structure. As a result, Na2Mn1/6Fe5/6Fe(CN)6can be qualified as an electrode material for aqueous nickel-ion batteries. A series of electrochemical evaluations show that it can achieve a charge capacity of 76.1 mAh g–1at 100 mA g–1, as well as an excellent cycling performance with 69.1% capacity retention upon 500 cycles. Besides, the reversible insertion/extraction mechanism of Ni2+in Na2Mn1/6Fe5/6Fe(CN)6is investigated by in situ/ex situ methods, demonstrating its stability and reversibility for electrochemical energy storage. In summary, Fe2+substitution enhances the structural integrity and electrochemical stability of Na2Mn1/6Fe5/6Fe(CN)6as a host material for nickel-ion storage.

Viscoelasticity is a crucial property of cells, which plays an important role in label-free cell characterization. This paper reports a model-fitting-free viscoelasticity calculation method, correcting the effects of frequency, surface adhesion and liquid resistance on AFM force-distance (FD) curves. As demonstrated by quantifying the viscosity and elastic modulus of PC-3 cells, this method shows high self-consistency and little dependence on experimental parameters such as loading frequency, and loading mode (Force-volume vs. PeakForce Tapping). The rapid calculating speed of less than 1ms per curve without the need for a model fitting process is another advantage. Furthermore, this method was utilized to characterize the viscoelastic properties of primary clinical prostate cells from 38 patients. The results demonstrate that the reported characterization method a comparable performance with the Gleason Score system in grading prostate cancer cells, This method achieves a high average accuracy of 97.6% in distinguishing low-risk prostate tumors (BPH and GS6) from higher-risk (GS7-GS10) prostate tumors and a high average accuracy of 93.3% in distinguishing BPH from prostate cancer.

The strength and plasticity trade-off in metal materials can be effectively addressed by Eutectic High-Entropy Alloys (EHEAs) through the realization of heterogeneous biphase layered structures at both micrometer and nanometer scales. In this work, a series of (CoCrFeNi)88NbxW(12-x)EHEAs were prepared, and the effects of the synergistic of Nb and W elements on the microstructure and mechanical properties of CoCrFeNi High-Entropy Alloys (HEAs) were investigated. With the increase of Nb content and the decrease of W content, the microstructure of the alloy underwent three changes, from Face Center Cubic (FCC) + μ biphase to FCC + μ + Laves triple phase, and finally to FCC + Laves biphase. The strength of the alloy increases, but the compression rate decreases. Among these alloys, (CoCrFeNi)88Nb10W2alloy exhibits exceptional mechanical properties. The synergistic effect of precipitation strengthening and grain boundary strengthening makes the yield strength, fracture strength, and plastic strain of the alloy are 1568 MPa, 2516 MPa, and 32 % respectively. In addition, in the CoCrFeNi HEAs, the weighted average atomic radius ratio (rm‾/rQ) is used to further precise the phase selection law of Laves phase and μ phase. When rm‾/rQ< 1.112, HEAs forms the μ phase, when 1.112 ≤ rm‾/rQ≤ 1.14, HEAs forms the Laves + μ biphase, when rm‾/rQ> 1.14, HEAs forms the Laves phase. The results can provide a basis for synergistic strengthening and phase selection of CoCrFeNi HEAs.

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A novel tactic to synthesize unsymmetrical 3-aryladipic acid esters has been developed via magnesium-promoted reductive coupling of ethyl cinnamates with methyl acrylate. In the present methodology, 3-aryladipic acid derivatives were prepared with good functional group tolerance and a wide substrate scope under very mild reaction conditions in good yields. The application of this reaction to dienic acid esters led to the successful control of the reaction to give 5-aryl-oct-3-enedioic acid esters with high regioselectivity.

The Cholesky decomposition technique is commonly used to reduce the memory requirement for storing two-particle repulsion integrals in quantum chemistry calculations that use atomic orbital bases. However, when quantum methods use multicomponent bases, such as nuclear–electronic orbitals, additional challenges are introduced due to asymmetric two-particle integrals. This work proposes several multicomponent Cholesky decomposition methods for calculations using nuclear–electronic orbital density functional theory. To analyze the errors in different Cholesky decomposition components, benchmark calculations using water clusters are carried out. The largest benchmark calculation is a water cluster (H2O)27where all 54 protons are treated quantum mechanically. This study provides energetic and complexity analyses to demonstrate the accuracy and performance of the proposed multicomponent Cholesky decomposition method.

Cardiovascular diseases (CVDs) are the leading cause of human death worldwide. Exosomes act as endogenous biological vectors; they possess advantages of low immunogenicity and low safety risks, also providing tissue selectivity, including the inherent targeting the to heart. Therefore, exosomes not only have been applied as biomarkers for diagnosis and therapeutic outcome confirmation but also showed potential as drug carriers for cardiovascular targeting delivery. This review aims to summarize the progress and challenges of exosomes as novel biomarkers, especially many novel exosomal noncoding RNAs (ncRNAs), and also provides an overview of the improved targeting functions of exosomes by unique engineered approaches, the latest developed administration methods, and the therapeutic effects of exosomes used as the biocarriers of medications for cardiovascular disease treatment. Also, the possible therapeutic mechanisms and the potentials for transferring exosomes to the clinic for CVD treatment are discussed. The advances, in vivoand in vitroapplications, modifications, mechanisms, and challenges summarized in this review will provide a general understanding of this promising strategy for CVD treatment.

A novel and highly stereoselective acyclic 1,3-difunctionalization of vinyl metal carbene species has been developed via Rh(II)/chiral phosphoric acid co-catalyzed three-component reactions of vinyldiazoacetates with alcohols and imines. This innovative approach features excellent regio-, diastereo-, and enantioselectivities, demonstrating a broad scope and functional group compatibility. Notably, this is the first example of three-component asymmetric acyclic 1,3-difunctionalization with in situ-formed vinyl metal carbenes.

Conventional phototrophic cultivation for microalgae production suffers from low and unstable biomass productivity due to limited and unreliable light transmission outdoors. Alternatively, the use of a renewable lignocellulose-derived carbon source, cellulosic hydrolysate, offers a cost-effective and sustainable pathway to cultivate microalgae heterotrophically with high algal growth rate and terminal density. In this study, we evaluate the feasibility of cellulosic hydrolysate-mediated heterotrophic cultivation (Cel-HC) for microalgae production by performing economic and environmental comparisons with phototrophic cultivation through techno-economic analysis and life cycle assessment. We estimate a minimum selling price (MSP) of 4722 USD/t for producing high-purity microalgae through Cel-HC considering annual biomass productivity of 300 t (dry weight), which is competitive with the conventional phototrophic raceway pond system. Revenues from the lignocellulose-derived co-products, xylose and fulvic acid fertilizer, could further reduce the MSP to 2976 USD/t, highlighting the advantages of simultaneously producing high-value products and biofuels in an integrated biorefinery scheme. Further, Cel-HC exhibits lower environmental impacts, such as cumulative energy demand and greenhouse gas emissions, than phototrophic systems, revealing its potential to reduce the carbon intensity of algae-derived commodities. Our results demonstrate the economic and environmental competitiveness of heterotrophic microalgae production based on renewable bio-feedstock of lignocellulose.

Chili pepper is an important spice and a model plant for fruit development studies. Large-scale omics information on chili pepper plant development continues to be gathered for understanding development as well as capsaicin biosynthesis. In this study, a full-spectrum transcriptome data of eight chili pepper tissues at five growth stages using the Oxford Nanopore long-read sequencing approach was generated. Of the 485 351 transcripts, 35 336 were recorded as reference transcripts (genes), while 450 015 were novel including coding, lnc, and other non-coding RNAs. These novel transcripts belonged to unknown/intergenic (347703), those retained introns (26336), and had multi-exons with at least one junction match (20333). In terms of alternative splicing, retained intron had the highest proportion (14795). The number of tissue-specific expressed transcripts ranged from 22 925 (stem) to 40 289 (flower). The expression changes during fruit and placenta development are discussed in detail. Integration of gene expression and capsaicin content quantification throughout the placental development clarifies that capsaicin biosynthesis in pepper is mainly derived from valine, leucin, and isoleucine degradation as well as citrate cycle and/or pyrimidine metabolism pathways. Most importantly, a user-friendly Pepper Full-Length Transcriptome Variation Database (PFTVD 1.0) (http://pepper-database.cn/) has been developed. PFTVD 1.0 provides transcriptomics and genomics information and allows users to analyse the data using various tools implemented. This work highlights the potential of long-read sequencing to discover novel genes and transcripts and their diversity in plant developmental biology.

The hybridization of liposome with stem cell membranes is an emerging technology to prepare the nanovehicle with the capacity of disease‐responsive targeting. However, the long‐term storage of this hybrid liposome has received limited attention in the literature, which is essential for its potential applicability in the clinic. Therefore, the preservation of long‐term activity of stem cell‐hybrid liposome using freeze‐drying is investigated in the present study. Mesenchymal stem cell‐hybrid liposome is synthesized and its feasibility for freeze‐drying under different conditions is examined. Results reveal that pre‐freezing the hybrid liposome at −20 °C in Tris buffer solution (pH 7.4) containing 10% trehalose can well preserve the liposomal structure for at least three months. Notably, major membrane proteins on the hybrid liposome are protected in this formulation and CXCR4‐associated targeting capacity is maintained both in vitro and in vivo. Consequently, the hybrid liposome stored for three months demonstrates a comparable tumor inhibition as the fresh‐prepared one. The present study provides the first insights into the long‐term storage of stem cell hybrid liposome using lyophilization, which may make an important step forward in enhancing the long‐term stability of these promising biomimetic nanovehicle and ease the logistics and the freeze‐storage in the potential clinical applications. A lyophilizable mesenchymal stem cell‐hybrid biomimetic liposome is developed that can be stored for at least 3 months with stable liposomal structure and membrane protein expression. The capacity of targeted drug delivery of this biomimetic liposome can be well preserved after the freeze storage, providing a possible solution to overcome the poor stability of biomimetic nanovehicles in practical use.

Asthma is a widespread public health concern, with an increasing incidence. Despite the implementation of current treatment strategies, asthma control, particularly for severe cases, remains suboptimal. Recent research has revealed the encouraging prospects of extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) as a viable therapeutic option for alleviating asthma symptoms. Therefore, the present review aims to provide an overview of the current progress and the therapeutic mechanisms of using MSC-derived EVs (MSC-EVs) for asthma treatment. Additionally, different administration approaches for EVs and their impacts on biodistribution and the curative outcomes of EVs are summarized. Notably, the potential benefits of nebulized inhalation of MSC-EVs are addressed. Also, the possibilities and challenges of using MSC-EVs for asthma treatment in clinics are highlighted. Overall, this review is intended to give new insight into the utilization of MSC-EVs as a potential biological drug for asthma treatment.

Direct reductive carboxylation of easily prepared aryl vinyl ketones under the atmosphere of carbon dioxide led to the selective formation of γ-keto carboxylic acids in 38–86% yields. The reaction is characterized by the carbon–carbon bond formation of carbon dioxide at the β-position of enone, with the use of magnesium turnings that can be easily handled as the reducing agent and the eco-friendly reaction conditions such as no pressuring, no lower or higher reaction temperature, and short reaction time. This protocol showed a wide substrate scope and provided a useful and convenient alternative to access biologically important γ-keto carboxylic acids.

Study Design: A retrospective study.Objectives: To identify if there is a link between sacral agenesis (SA) and post-operative coronal imbalance in patients with congenital lumbosacral deformities.Methods: This study reviewed a consecutive series of patients with congenital lumbosacral deformities. They had a minimum follow-up of 2 years. According to different diagnosis, they were divided into SA and non-SA group. Comparison analysis was performed between patients with and without post-operative coronal imbalance and risk factors were identified.Results: A total of 45 patients (18 in SA group and 27 in non-SA group) were recruited into this study, among whom 33 patients maintained coronal balance while 12 demonstrated postoperative coronal imbalance at last follow-up (14.32 ± 7.67 mm vs 35.53 ± 3.91 mm, P < 0.001). Univariate analysis showed that preoperative lumbar Cobb angle, immediate postoperative coronal balance distance and diagnosis of SA were significantly different between patients with and without post-operative coronal imbalance (P < 0.05). Binary logistic regression analysis showed that SA was an independent risk factor for postoperative coronal imbalance.Conclusions: As an independent risk factor for postoperative coronal imbalance, high level of suspicion of SA should be aware in children with congenital lumbosacral deformities. Sufficient bone grafts at sacroiliac joint are recommended for SA patients to prevent postoperative coronal imbalance.

The Tibetan Plateau, characterized by complicated geological structures, is sensitive to climate change and human activities. The vulnerable environmental balance of the Tibetan Plateau has witnessed substantial alterations, emphasizing the urgency to comprehend and protect its ecosystem quality. In this study, we aim to quantify the ecosystem quality of the Tibetan Plateau, portray its spatiotemporal dynamics, and analyze the spatial heterogeneity of climatic and anthropogenic influences. We employed the entropy weight method (EWM) to construct a comprehensive index, termed the Ecosystem Quality Comprehensive Assessment Index (EQCAI). The historical spatiotemporal patterns and trends of EQCAI were subsequently identified. Our results revealed a gradient of decreasing ecosystem quality from the southeast to the northwest of the Tibetan Plateau, while the mitigation of ecosystem quality degradation displayed an improving trend from the southwest to the northeast. We further detected the spatial heterogeneity of factors influencing changes in ecosystem quality through the multiscale geographically weighted regression (MGWR) method. Precipitation emerged as the primary positive factor, exerting a profound influence on the ecosystem quality of the southeastern Tibetan Plateau. Conversely, evapotranspiration, elevation, and human activities negatively affected the western Tibetan Plateau. This study proposes targeted conservation efforts for forestry regions with high ecosystem quality in the southeastern Tibetan Plateau. Additionally, we suggest that the positive impact of human activities on the ecosystem quality of the Tibetan Plateau should be further strengthened. Our findings contribute valuable insights for informed decision-making in the sustainable management and preservation of the Tibetan Plateau's fragile ecosystem.

To discover celastrol (CEL) derivatives with enhanced Hsp90–Cdc37 inhibition, C-20-COOH was introduced with various substituted imidazoles, which might affect the Michael addition of CEL by nucleophilic attack. The most potent compound 9, which showed higher antiproliferation, covalent-binding ability, and Hsp90–Cdc37 inhibition than CEL, was selected from 28 new target compounds. Then, the binding sites and the docking mode of 9to Hsp90 and Cdc37 were studied. Furthermore, the activity of 9sharply decreased or even disappeared in the Hsp90- and/or Cdc37-overexpressing A549 cells, indicating that the activity was related to its combination with Hsp90 and Cdc37. Moreover, 9could more effectively induce apoptosis and inhibit tumor growth than CEL in vivo. This study first found that imidazoles linked to C-20 of CEL might affect its Michael addition, which will provide support of CEL or even the other Michael acceptors for the development as antitumor agents.

A practical protocol for the regioselective preparation of 3-phenylpropargylsilanes and 3-phenylallylsilanes in yields of 36–77 and 48–86%, respectively, from readily accessible 3-phenylpropargyl and 1-phenylallyl pivalates was developed through reductive C(sp3)–O bond cleavage. This method represents the first example of the direct application of vastly abundant calcium granules to a reductive coupling reaction. A broad range of propargylsilanes and allylsilanes are simply prepared using easy-to-handle pivalates and chlorotrimethylsilane under mild catalyst-free and additive-free conditions.

The coronavirus disease 2019 (COVID-19) pandemic continues to threaten lives and the economy around the world. Estimating the risk of COVID-19 can help in predicting spreading trends, identifying risk areas, and making public health decisions. In this study, we proposed a comparative risk assessment method to estimate comprehensive and dynamic COVID-19 risks by considering the pandemic severity and the healthcare system pressure and then employing the z-order curve and fractal theory. We took the COVID-19 cases from January 19–March 10, 2020 in China as our research object. The results and analysis revealed that (1) the proposed method demonstrated its feasibility to assess and illustrate pandemic risk; (2) the temporal patterns of the daily relative risk indices of 31 provinces were clustered into four groups (high-value, fluctuating-increase, inverted U-shaped, and low-stable); (3) the spatial distribution of the relative pandemic risk indicated a significant circular pattern centered on Hubei Province; and (4) healthcare system capacity is the key to reducing relative pandemic risk, and cases imported from abroad should be given more attention. The methods and results of this study will provide a methodological basis and practical guidance for regional pandemic risk assessment and public health decision-making.

Four-component Dirac–Hartree–Fock is an accurate mean-field method for treating molecular systems where relativistic effects are important. However, the computational cost and complexity of the two-electron interaction make this method less common, even though we can consider the Dirac–Hartree–Fock Hamiltonian the “ground truth” of the electronic structure, barring explicit quantum electrodynamical effects. Being able to calculate these effects is then vital to the design of lower scaling methods for accurate predictions in computational spectroscopy and properties of heavy element complexes that must include relativistic effects for even qualitative accuracy. In this work, we present a Pauli quaternion formalism of maximal component and spin separation for computing the Dirac–Coulomb–Gaunt Hartree–Fock ground state, with a minimal floating point operation count algorithm. This approach also allows one to explicitly separate different spin physics from the two-body interactions, such as spin–free, spin–orbit, and spin–spin contributions. Additionally, we use this formalism to examine relativistic trends in the periodic table and analyze the basis set dependence of atomic gold and gold dimer systems.

As quantum chemistry calculations deal with molecular systems of increasing size, the memory requirement to store electron-repulsion integrals (ERIs) greatly outpaces the physical memory available in computing hardware. The Cholesky decomposition of ERIs provides a convenient yet accurate technique to reduce the storage requirement of integrals. Recent developments of a two-step algorithm have drastically reduced the memory operation (MOP) count, leaving the floating operation (FLOP) count as the last frontier of cost reduction in the Cholesky ERI algorithm. In this report, we introduce a dynamic integral tracking, reusing, and compression/elimination protocol embedded in the two-step Cholesky ERI method. Benchmark studies suggest that this technique becomes particularly advantageous when the basis set consists of many computationally expensive high-angular-momentum basis functions. With this dynamic-ERI improvement, the Cholesky ERI approach proves to be a highly efficient algorithm with minimal FLOP and MOP count.

Designing of PPy hydrogel precursor containing molecular-scale grids (diameter ∼2.0 nm) allows for homogeneous N,O-codoping into the porous carbon with tailored pore structures through carbonization-activation, which renders abundant sub-nanopores on their surface to increase the specific capacitance as extra capacitance sites.

Reductive silylation of benzofurans with an electron-withdrawing group by a magnesium metal and the subsequent oxidative rearomatization by DDQ gave the selective formation of less reported 3-silylated benzofurans in moderate to good yields under mild reaction conditions with wide substituent scope. The silyl group introduced on the five-membered ring by the reductive coupling could survive with no elimination throughout the oxidation process. The silylated heteroaromatic skeleton is useful as an intermediate in organic synthesis, and its practical utility was also demonstrated by several transformation reactions.

AbstractLipoxygenases (LOXs; EC1.13.11.12) are widely involved in plant growth, development, maturation, senescence and stress resistance. LOXs have been studied in many crop species but not in Tartary buckwheat [Fagopyrum tataricum(L.) Gaertn.]. This study aimed to systematically identify and analyze LOXgenes in Tartary buckwheat. Eight LOXgenes, which were unevenly distributed on five chromosomes, were identified in the Pinu1 Genome database. The data indicated that during long evolution, FtLOXgenes were subjected to purifying selection. The conservation of motifs within the 9-LOX and 13-LOX subfamilies supported the results of phylogenetic analyses. All FtLOX proteins contained the LOX family-specific His-(X)4-His-(X)4-His-(X)17-His-(X)8-His motif, suggesting that this motif is essential for protein function. Analyses of physical and chemical properties showed that FtLOX6 might function under both acidic and alkaline conditions. The FtLOXgene promoters contained many light-responsive elements, and transcriptome data further suggested their roles in growth regulation and the response to light. Quantitative real-time polymerase chain reaction analysis of expression differences in plants exposed to different wavelengths of light confirmed that FtLOX1and FtLOX4–7could respond to light. Genes co-expressed with FtLOXgenes were involved in the photoreaction-related pathway. This study provides a basis for further functional research in order to better understand the biological role of individual LOX gene in Tartary buckwheat.

Over the past decade, nanopore sequencing has experienced significant advancements and changes, transitioning from an initially emerging technology to a significant instrument in the field of genomic sequencing. However, as advancements in next-generation sequencing technology persist, nanopore sequencing also improves. This paper reviews the developments, applications, and outlook on nanopore sequencing technology. Currently, nanopore sequencing supports both DNA and RNA sequencing, making it widely applicable in areas such as telomere-to-telomere (T2T) genome assembly, direct RNA sequencing (DRS), and metagenomics. The openness and versatility of nanopore sequencing have established it as a preferred option for an increasing number of research teams, signaling a transformative influence on life science research. As nanopore sequencing technology advances, it provides a faster, more cost-effective approach with extended read lengths, demonstrating the significant potential for complex genome assembly, pathogen detection, environmental monitoring, and human disease research, offering a fresh perspective in sequencing technologies.

We present several schemes based on the spin-separation of the Dirac–Coulomb–Breit Hamiltonian for the perturbative treatment of relativistic four-component Hamiltonians within the state interaction framework. While state interaction approaches traditionally use zeroth-order scalar-relativistic states, we develop augmented zeroth-order Hamiltonians with increasing accuracy and investigate convergence to the variational limit as a function of the choice of zeroth-order Hamiltonian. The state interaction schemes developed in this work are benchmarked using ground-state fine-structure splitting of late-row atoms and diatomic hyrides. Although the scalar-relativistic zeroth-order Hamiltonian exhibits significant errors in ground-state fine-structure splitting, the predictive accuracy can be improved by augmenting the zeroth-order Hamiltonian with one- and two-electron vector-relativistic operators (e.g., spin–orbit, spin–spin, orbit–orbit). This work lays the theoretical foundation for the development of low-scaling, high-accuracy perturbative relativistic methods suitable for late-row elements.

We have implemented noniterative triples corrections to the energy from coupled-cluster with single and double excitations (CCSD) within the 1-electron exact two-component (1eX2C) relativistic framework. The effectiveness of both the CCSD(T) and the completely renormalized (CR) CC(2,3) approaches are demonstrated by performing all-electron computations of the potential energy curves and spectroscopic constants of copper, silver, and gold dimers in their ground electronic states. Spin–orbit coupling effects captured via the 1eX2C framework are shown to be crucial for recovering the correct shape of the potential energy curves, and the correlation effects due to triples in these systems change the dissociation energies by about 0.1–0.2 eV or about 4–7%. We also demonstrate that relativistic effects and basis set size and contraction scheme are significantly more important in Au2than in Ag2or Cu2.

Reductive introduction of a fluorine-containing carbon block to readily available conjugated ynones, followed by intramolecular cyclization, successfully gave the corresponding trifluoromethylated cyclopentenones or trifluoromethylated furans in good yields through a simple two-step protocol. The key compound in carbon–carbon bond formation by magnesium-promoted reduction is ethyl trifluoroacetate, which has been rarely used as a fluorine-containing carbon source, especially to electron-deficient carbon atoms in organic synthesis.

Magnesium-promoted reductive introduction of a trifluoroacetyl group to coumarin in the presence of ethyl trifluoroacetate and the subsequent treatment with trifluoroacetic acid led to simple access to a trifluoromethylated benzofurofuranone at 8a-position with a high regio- and stereoselectivity. Trifluoromethylated or difluoromethylated benzofurofuranone derivatives were also prepared from coumarins including naturally occurring ones only in two successive steps, which might have potential bioactivity in medicinal chemistry.

This study examines several techniques to improve the efficiency of the linearized multireference driven similarity renormalization group truncated to one- and two-body operators [MR-LDSRG(2)]. We propose a sequential MR-LDSRG(2) [sq-MR-LDSRG(2)] scheme, in which one-body substitutions are folded exactly into the Hamiltonian. This new approach is combined with density fitting (DF) to reduce the storage cost of two-electron integrals. To further avoid storage of large four-index intermediates, we propose a noninteracting virtual orbital (NIVO) approximation of the Baker–Campbell–Hausdorff series that neglects commutators terms with three and four virtual indices. The NIVO approximation reduces the computational prefactor of the MR-LDSRG(2), bringing it closer to that of coupled cluster with singles and doubles (CCSD). We test the effect of the DF and NIVO approximations on the MR-LDSRG(2) and sq-MR-LDSRG(2) methods by computing properties of eight diatomic molecules. The diatomic constants obtained by DF-sq-MR-LDSRG(2)+NIVO are found to be as accurate as those from the original MR-LDSRG(2) and coupled cluster theory with singles, doubles, and perturbative triples. Finally, we demonstrate that the DF-sq-MR-LDSRG(2)+NIVO scheme can be applied to chemical systems with more than 550 basis functions by computing the automerization energy of cyclobutadiene with a quintuple-ζ basis set. The predicted automerization energy is found to be similar to the value computed with Mukherjee’s state-specific multireference coupled cluster theory with singles and doubles.

An approach to trifluoroacetylation of aromatic conjugated esters successfully led to the efficient and selective introduction of trifluoroacetyl group to the electron‐deficient β‐ or δ‐carbon atom of ester under mild reaction conditions by magnesium‐promoted reduction, followed by deacetalization with trifluoroacetic acid in moderate to good yields. A variety of fluorinated keto esters derived from ethyl cinnamates and β, γ‐ or γ‐, δ‐unsaturated fluorinated keto esters from aromatic dienoesters with a longer conjugation system were synthesized through this simple methodology utilizing ethyl trifluoroacetate as a fluorine‐containing carbon source. Simple and selectiveintroduction of a trifluoroacetyl group into the electron‐deficient β‐ or δ‐carbon atom of aromatic conjugated esters was achieved by use of ethyl trifluoroacetate in good yields through magnesium‐promoted trifluoroacetylation, followed by deacetalization with trifluoroacetic acid.

Pulmonary inflammation is one of the most reported tissue inflammations in clinic. Successful suppression of inflammation is vital to prevent further inevitably fatal lung degeneration. Glucocorticoid hormone, such as methylprednisolone (MP), is the most applied strategy to control the inflammatory progression yet faces the challenge of systemic side effects caused by the requirement of large‐dosage and frequent administration. Highly efficient delivery of MP specifically targeted to inflammatory lung sites may overcome this challenge. Therefore, the present study develops an inflammation‐targeted biomimetic nanovehicle, which hybridizes the cell membrane of mesenchymal stem cell with liposome, named as MSCsome. This hybrid nanovehicle shows the ability of high targeting specificity toward inflamed lung cells, due to both the good lung endothelium penetration and the high uptake by inflamed lung cells. Consequently, a single‐dose administration of this MP‐loaded hybrid nanovehicle achieves a prominent treatment of lipopolysaccharide‐induced lung inflammation, and negligible treatment‐induced side effects are observed. The present study provides a powerful inflammation‐targeted nanovehicle using biomimetic strategy to solve the current challenges of targeted inflammation intervention. The biomimetic nanovehicle hybridized mesenchymal stem cell membrane and liposome (MSCsome) can recognize the inflamed pulmonary vascular endothelium and pass through the endothelial barrier efficiently and integrally. Consequently, an accurate and efficient delivery of methylprednisolone target to inflamed lung cells is achieved.

Mesenchymal Stem Cell‐Hybrid Nanovehicles In article 2300376, Donghang Xu, Tianyuan Zhang, Jianqing Gao and co‐workers develop a biomimetic nanovehicle hybridizing the cell membrane of mesenchymal stem cell with a liposome. This hybrid nanovehicle shows advantages of both highly efficient inflammation targeting and good drug‐loading capacity, resulting in a specifically targeted delivery of methylprednisolone to inflammatory damaged lung cells. A single‐dose administration of this hybrid nanovehicle achieves a prominent lung inflammation suppression, showing promising potential for the treatment against acute lung injury with reduced side effects.

Psi4NumPydemonstrates the use of efficient computational kernels from the open-source Psi4 program through the popular NumPylibrary for linear algebra in Python to facilitate the rapid development of clear, understandable Python computer code for new quantum chemical methods, while maintaining a relatively low execution time. Using these tools, reference implementations have been created for a number of methods, including self-consistent field (SCF), SCF response, many-body perturbation theory, coupled-cluster theory, configuration interaction, and symmetry-adapted perturbation theory. Furthermore, several reference codes have been integrated into Jupyter notebooks, allowing background, underlying theory, and formula information to be associated with the implementation. Psi4NumPytools and associated reference implementations can lower the barrier for future development of quantum chemistry methods. These implementations also demonstrate the power of the hybrid C++/Python programming approach employed by the Psi4 program.

Simultaneous translation is to translate a sentence before people finish it, to understand the speaker's intention in real-time. At present, simultaneous machine translation still relies on text-to-text data resources. However, the output information from the encoder side is used for the decoder as the input data recourse in the pure text translation system. This information is only derived from the text content, and the input information is single, causing a shortage of decoding information at the decoder and the vocabulary is missed in translation. The translator will also visually capture the information of the surrounding scenes to assist himself in the translation work, based on this feature, we propose a multi-modal simultaneous machine translation of fusion image information. We extract information from the image, add the information to the decoder side of the translation system, increase the input data resource of the decoder, and help the system improve the translation quality. We use the Multi30K dataset for experimental verification. Compared with the translation system of plain text, the method we propose can translate more complete sentences, richer content, and better translation results.

Existing only-text NMT (neural machine translation) systems can benefit from explicitly modelling target future contexts as recurrent states. However, the modelled target future context is implicit in the conventional only-text NMT as the target is invisible in inference. For the Multi-modal Neural Machine Translation (MNMT), the visual annotation presents the content described in the bilingual parallel sentence pair, so-called multi-modal consistency. This consistency provides an advantage that future target context can be simulated in visual features. This paper proposes a novel translation model that allows MNMT to encode the future target context from the visual annotation in auto-regressive decoding. Our model uses visual-target consistency to enhance the target generation. Moreover, we use the multi-modal consistency that fully uses the visual annotation to encourage the semantic agreement between bilingual parallel sentences and the pivoted visual annotation. Empirical results on several recent multi-model translation datasets demonstrated the MNMT model which we proposed significantly improved translation performance on a strong baseline, especially achieving new state-of-the-art results on all three language pairs with visual annotations. Our code will be available after acceptance.

In this work we propose a novel approach to solve the Schrödinger equation which combines projection onto the ground state with a path-filtering truncation scheme. The resulting projector configuration interaction (PCI) approach realizes a deterministic version of the full configuration interaction quantum Monte Carlo (FCIQMC) method [Booth, G. H.; Thom, A. J. W.; Alavi, A. J. Chem. Phys.2009, 131, 054106]. To improve upon the linearized imaginary-time propagator, we develop an optimal projector scheme based on an exponential Chebyshev expansion in the limit of an infinite imaginary time step. After writing the exact projector as a path integral in determinant space, we introduce a path filtering procedure that truncates the size of the determinantal basis and approximates the Hamiltonian. The path filtering procedure is controlled by one real threshold that determines the accuracy of the PCI energy and is not biased toward any determinant. Therefore, the PCI approach can equally well describe static and dynamic electron correlation effects. This point is illustrated in benchmark computations on N2at both equilibrium and stretched geometries. In both cases, the PCI achieves chemical accuracy with wave functions that contain less than 0.5% determinants of full CI space. We also report computations on the ground state of C2with up to quaduple-ζ basis sets and wave functions as large as 200 million determinants, which allow a direct comparison of the PCI, FCIQMC, and density matrix renormalization group (DMRG) methods. The size of the PCI wave function grows modestly with the number of unoccupied orbitals, and its accuracy may be tuned to match that of FCIQMC and DMRG.

ABSTRACTDespite the extensive in vitrocharacterization of CPAF (chlamydial protease/proteasome-like activity factor), its role in chlamydial infection and pathogenesis remains unclear. We now report that a Chlamydia trachomatisstrain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficient C. trachomatisstrain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2-5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF-dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promoting C. trachomatissurvival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity.

ABSTRACTChlamydiahas been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarumspreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarumcan spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarumstrain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivoimaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of the C. muridarumorganisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridaruminoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract.

The inhibition of angiogenesis represents a potential strategy for antitumor therapy. A novel synthetic fusion protein VTF, composed of bioactive fragments from two different angiogenesis inhibitors, vasostatin and tumstatin with a (Gly–Ser–Gly)2bridge, was generated using the pET-15b expression vector. The fusion protein VTF showed significantly enhanced efficacy in inhibiting human endothelial cell proliferation and tube formation and neovascularization on chick embryo chorioallantoic membrane. Moreover, VTF suppressed the growth of B16 melanoma and the formation of tumor blood vessels potently in vivo. These results indicated that the fusion protein containing the bioactive fragments of multiple angiogenesis inhibitors might be a promising therapeutic agent for tumor treatment.

A structurally novel acetyl-CoA carboxylase (ACC) inhibitor is identified from high-throughput screening. A preliminary structure−activity relationship study led to the discovery of potent dual ACC1/ACC2 and ACC2 selective inhibitors against human recombinant ACC1 and ACC2. Selective ACC2 inhibitors exhibited IC50 < 20 nM and >1000-fold selectivity against ACC1. (S)-Enantiomer 9p exhibited high ACC2 activity and lowered muscle malonyl-CoA dose-dependently in acute rodent studies, whereas (R)-enantiomer 9o was weak and had no effect on the malonyl-CoA level.

Human (H-) CCR5 is the primary coreceptor for ENV-mediated fusion by R5 strains of human immunodeficiency virus type 1, whereas mouse (M-) CCR5 lacks this function. An array of 23 H/M-CCR5 hybrids containing increasing amounts of H-CCR5 extending from the N terminus generated by random chimeragenesis had a biphasic pattern of coreceptor activity with JRFL and 89.6, revealing active regions in the N-terminal extracellular domain (N-ED) and at the junction of cytoplasmic loop 3. The M-CCR5 mutant in which divergent residues were replaced with the corresponding H-CCR5 N-ED sequence (NyYTsE) gained coreceptor function in fusion but not infection experiments. A M-CCR5 double mutant with substitution of human sequences for divergent residues from the N-ED and cytoplasmic loop 3 had augmented coreceptor activity in fusion assays and gain of function in infection experiments. The SIV-251 ENV utilized H- and M-CCR5 and variants. Flow cytometric analysis of M-CCR5 mutants and bifunctional receptors composed of CD4 domains fused to M-CCR5 mutants excluded the possibility that differences in coreceptor activity resulted from variations in cell surface expression. These results demonstrate that the coreceptor activity of the H-CCR5 N-ED is modulated by intracellular residues, illustrating the complexity of CCR5 requirements for interaction with ENV.

Real‐time effective traffic flow big data prediction network has important application significance. Over the past few years, traffic flow data have been exploding and we have entered the big data era. The key challenge of traffic flow prediction network is how to construct an adaptive model relying on historical data. Existing big data‐driven traffic flow prediction networking approaches mainly use shallow learning, and there are unsatisfying for many realistic applications, which inspire us to rethink the traffic flow big data prediction problem with deep learning. In this paper, we propose a novel prediction approach based on machine learning. In addition to the minimum prediction error as the goal, we present the long short‐term memory model, which is a typical machine learning algorithm with deep learning network. This method is applied into the real‐world traffic big data from performance measurement system. Experimental results show that the proposed machine learning algorithm has more applicability and higher performance, compared with shallow machine learning prediction network. Real‐time effective traffic flow big data prediction network has important application significance. Over the past few years, traffic flow data have been exploding and we have entered the big data era. This paper proposes a novel traffic flow prediction approach based on machine learning. Different from general deep learning models, LSTM network can learn long‐term dependence information. Experimental results show that the proposed Machine Learning algorithm has more applicability and higher performance, compared with shallow machine learning prediction network.