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The first palladium-catalyzed direct ring-opening of mono-substituted phenyl and heteroaryl cyclopropyl ketones to obtain α,β-unsaturated ketones is described. The reaction features high stereoselectivity to obtain (E)-1-phenylbut-2-en-1-one derivatives.

Background: Dopamine dysregulationsyndrome (DDS) is a complication of Parkinson's disease (PD) that seriously affects the quality of life of PD patients. Currently, the risk factors for DDS are unknown, and it is critical to identify them in the early stages of PD. Objective: To explore the incidence of and risk factors for DDS in patients with early PD. Methods: A retrospective cohort study was conducted on the general data, clinical features and imaging data of patients with early PD in the PPMI database. Multivariate Cox regression analysis was performed to analyze the risk factors for the development of DDS in patients with early PD, and Kaplan‒Meier curves examined the frequency and predictors of incident DDS symptoms. Results: At baseline, 2.2% (n=6) of patients with early PD developed DDS, and the cumulative incidence rates of DDS during the 5-year follow-up period were 2.8%, 6.4%, 10.8%, 15.5% and 18.7%, respectively. In the multivariate Cox regression model controlling for age, sex and drug use, hypersexuality (HR=3.088; 95% CI: 1.416~6.732; P=0.005), compulsive eating (HR=3.299; 95% CI: 1.665~6.534; P=0.001), compulsive shopping (HR=3.899; 95% CI: 1.769~8.593; P=0.001), anxiety(HR=4.018; 95% CI: 2.136~7.599; PPConclusion: Early PD patients with a hypersexuality, compulsive eating, compulsive shopping, anxiety and lower H-Y stage were at increased risk for DDS. The occurrence of DDS may be related to the decrease in the average DAT uptake of the caudate and putamen.

The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of N-(hetero)aryl analogues (1-32) of the natural anti-Alzheimer's disease drug huperzine A (HPA) was prepared via palladium-catalyzed Buchwald-Hartwig cross-coupling reactions of HPA with various aryl bromides in good yields. Most of the N-aryl-huperzine A (N-aryl-HPA) analogues showed good acetylcholinesterase (AChE) inhibitory activity in in vitro experiments. Three arylated huperzine A analogues (14, 19, and 30) exhibited stronger anti-AChE activity than HPA. The 5-methoxy-2-pyridyl analogue (30) displayed the most potent AChE inhibition activity, with an IC50 value of 1.5 μM, which was 7.6-fold more active than HPA. Compound 30 also exhibited better neuroprotective activity for H2O2-induced damage in SH-SY5Y cells than HPA. Structure-activity relationship analysis suggested that the electron density of the installed aromatic ring or heteroaromatic ring played a significant role in inducing the AChE inhibition activity. Overall, compound 30 showed the advantages of easy synthesis, high potency and selectivity, and improved neuroprotection, making it a potential huperzine-type lead compound for Alzheimer's disease drug development.

Three new aconitine-type C19-diterpenoid alkaloid namely novolunines A (1), B (2), and C (3), along with fifteen known diterpenoid alkaloids were isolated from the roots of Aconitum novoluridum, whose phytochemical investigations have never been reported before. The structures of three new alkaloids were established on the basis of spectra data (high-resolution electrospray ionization (HR-ESI)-MS, IR, one dimensional (1D)- and 2D-NMR). Noteworthily, novolunines A (1) and B (2) are two diterpenoid alkaloids bearing conformational isomerism. In addition, the diterpenoid alkaloids 1-3 did not show any anti-acetylcholinesterase (AChE) or anti-inflammatory activities.

Two new premyrsinane-type diterpenes (2 and 3) as diastereomers were synthesized from lathyrane-type diterpene euphorbia factor L3 (1) for the first time via an efficient Fe(acac)3-catalyzed skeleton conversion process. This conversion features a biogenetically inspired strategy that relies on a concise reductive olefin coupling involving intramolecular Michael addition with free radicals. The structures of 2 and 3 were elucidated by a combination of the interpretation of their spectroscopic data and single-crystal X-ray diffraction analysis. The premyrsinane diterpenes 2 and 3 exhibited cytotoxic activity against the 4T1 breast cancer cell line, while the parent compound euphorbia factor L3 (1) was inactive. The current results not only confirmed the biogenetic relationship between lathyranes and premyrsinanes for the first time but also suggested a novel method for the preparation of naturally rare premyrsinane diterpenes with high bioactivity from the more abundant natural lathyrane diterpenes.

In parking edge computing, the service providers can engage the parking vehicles to provide computing services. The requesting vehicles can enjoy the advantages of the parking computing services with no need to build expensive equipment locally, whereas the parking vehicles can sell the computing resources to gain benefits. However, in an open parking computing system, the identity of each entity is easy to be counterfeited by other malicious entities, which may cause the leakage of privacy data of honest entities and the waste of parking computing resources. To address this issue, we propose an efficient authentication protocol between vehicle and roadside unit near the parking lot, which also allows two verified entities to generate a common key to enjoy the parking computing service confidentially. The protocol is extended to allow anonymous authentication so that the true identity would not be leaked to RSU during the authentication process, and malicious vehicle tracing if some forged or illegal authentication message is submitted to cheat the service provider or roadside unit. The security and efficiency analysis demonstrate that the proposed authentication protocols are secure and practical in applications.

Ensuring that a vehicle can obtain its real location in a high-precision prebuilt map is one of the most important tasks of the Autonomous Internet of Vehicles (AIoV). In this work, we show that the resampling of the particle filter (PF) algorithm is optimized by using the prior information of particles that shift real localizations to improve vehicle localization accuracy without changing the existing PF process, i.e., the particle shift filter (PSF). The number of particles is critical to their convergence efficiency. We perform quantitative and qualitative analyses of how to improve particle localization accuracy while ensuring timeliness, without increasing the number of particles. Moreover, the cumulative error of the particles increases with time, and the localization accuracy and robustness decrease. Our findings show that the initial particle density is 159 particles/m3, and the cumulative variance of the PSF particles is improved by 27%, 29%, and 82% at the x-, y-, and z-axes, respectively, under the same conditions as the PF algorithm, while the calculation time only increases by 10.6%. Moreover, the cumulative mean error is reduced by 0.74 m, 0.88 m, and 0.68 m at the x-, y-, and z-axes, respectively, indicating that the localization error of the PSF changes less with time. All experiments were performed using open-source software and datasets.

Hypoxic-ischemic encephalopathy (HIE) is a main cause of mortality and severe neurologic impairment in the perinatal and neonatal period. However, few satisfactory therapeutic strategies are available. Here, we reported that a rapid nuclear translocation of phosphatase and tensin homolog deleted on chromosome TEN (PTEN) is an essential step in hypoxic-ischemic brain damage (HIBD)- and oxygen-glucose deprivation (OGD)-induced neuronal injures both in vivo and in vitro. In addition, we found that OGD-induced nuclear translocation of PTEN is dependent on PTEN mono-ubiquitination at the lysine 13 residue (K13) that is mediated by neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1). Importantly, we for the first time identified α- and γ-adaptin binding protein (Aagab) as a novel NEDD4-1 regulator to regulate the level of NEDD4-1, subsequently mediating Pten nuclear translocation. Finally, we demonstrated that genetic upregulation of Aagab or application of Tat-K13 peptide (a short interference peptide that flanks K13 residue of PTEN) not only reduced Pten nuclear translocation, but also significantly alleviated the deficits of myodynamia, motor and spatial learning and memory in HIBD model rats. These results suggest that Aagab may serve as a regulator of NEDD4-1-mediated Pten nuclear translocation to promote functional recovery following HIBD in neonatal rats, and provide a new potential therapeutic target to guide the clinical treatment for HIE.

Five new aconitine-type C19-diterpenoid alkaloids, apetalrines A-E (1-5), were isolated from Aconitum apetalum. Their structures were determined by analysis of 1D and 2D NMR, IR, and HRESIMS data. Semisynthesis of apetalrine B (2) from its parent compound aconorine was achieved to confirm the structure proposed. Twenty derivatives of 2 (11a-11l, 12a, 12b, 12d, 12e, 12j, 12k, 12m, 12n) were synthesized via a unified approach relying on simple coupling reactions. The evaluation of neuroprotective effects of compounds (1-5, 11b, 11c, 11f-11i, 12a, 12b, 12d, 12e, 12k, 12m, 12n) with low cytotoxicity revealed compound 2 to exhibit good neuroprotective effects in H2O2-treated SH-SY5Y cells at a concentration of 50 μM. A series of studies using flow cytometry, staining, and Western blotting on 2 indicated that its neuroprotective effects may arise from inhibiting cell apoptosis.

A panel of unnatural base pairs is developed to expand genetic alphabets. One or more unnatural base pairs (UBPs) can be inserted to enlarge the capacity, diversity, and functionality of canonical DNA, so monitoring the multiple-UBPs-containing DNA by simple and convenient approaches is essential. Herein, we report a bridge-base approach to repurpose the capability of determining TPT3-NaM UBPs. The success of this approach depends on the design of isoTAT that can simultaneously pair with NaM and G as a bridge base, as well as the discovering of the transformation of NaM to A in absence of its complementary base. TPT3-NaM can be transferred to C–G or A–T by simple PCR assays with high read-through ratios and low sequence-dependent properties, permitting for the first time to dually locate the multiple sites of TPT3-NaM pairs. Then we show the unprecedented capacity of this approach to trace accurate changes and retention ratios of multiple TPT3-NaM UPBs during in vivo replications. In addition, the method can also be applied to identify multiple-site DNA lesions, transferring TPT3-NaM makers to different natural bases. Taken together, our work presents the first general and convenient approach capable of locating, tracing, and sequencing site- and number-unlimited TPT3-NaM pairs.

Unmanned Aerial Vehicles (UAVs) cooperative multi-task system has become the research focus in recent years. However, the existing network frameworks of UAVs are not flexible and efficient enough to deal with the complex multi-task scheduling, because they are not able to perceive the different features. In this paper, a novel cooperated UAVs network framework for multi-task scheduling is proposed. It is a three-layer network including a core layer, an aggregation layer and an execution layer, which enhances the efficiency of multi-task distribution, aggregation and transmission. Furthermore, an AggreGate Flow (AGFlow) based scheduler is dedicatedly designed to maximize the task completion rate, whose key point is to aggregate flows belonging to one task during the multi-task transmission of UAVs network and to allocate priority by calculating the urgency-level of each AGFlow. Simulation results demonstrate that, compared with that of state-of-the-art scheduler, the average task completion rate of AGFlow based scheduler is raised by 0.278.

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To reduce distribution risk and improve the efficiency of medical materials delivery under major public health emergencies, this paper introduces a drone routing problem with time windows. A mixed-integer programming model is formulated considering contactless delivery, total travel time, and customer service time windows. Utilizing Dantzig–Wolfe decomposition, the proposed optimization model is converted into a path-based master problem and a pricing subproblem based on an elementary shortest path problem with resource constraints. We embed the pulse algorithm into a column generation framework to solve the proposed model. The effectiveness of the model and algorithm is verified by addressing different scales of Solomon datasets. A case study on COVID-19 illustrates the application of the proposed model and algorithm in practice. We also perform a sensitivity analysis on the drone capacity that may affect the total distribution time. The experimental results enrich the research related to vehicle routing problem models and algorithms under major public health emergencies and provide optimized relief distribution solutions for decision-makers of emergency logistics.

The elongase of the very long-chain fatty acids (Elovls) gene family in fish has more diversity than in other vertebrates, which plays several critical roles in fatty acid synthesis and low-temperature stress adaptation. Gymnocypris przewalskii settles in plateau lakes with cold and resource-poor settings, and the evolution and function of Elovl genes in this fish are unknown. In the study, to identify the Elovl genes in G. przewalskii, the genome-wide identification and phylogenetic analysis of the gene members have been conducted with the expression profile of different tissues under cold stress. Fatty acid compositions, meanwhile, were detected in both the hepatopancreas and skeletal muscle during cold adaptation. A total of 21 Elovl members have been identified from the genome of G. przewalskii, belonging to Elovl1, Elovl2, Elovl4, Elovl5, Elovl6, Elovl7, and Elovl8 subgroups, with conserved ELO domain and four common motifs. Phylogenetic analysis revealed that subfamilies Elovl1 and Elovl7, Elov2, and Elovl5 have a closer genetic relationship, while the Elovl6 class was classed into an independent clade. Synteny analysis showed that whole-genome duplication, tandem duplicates, and gene conversion could drive the Elovls family expansion in G. przewalskii. The Ka/Ks and RELAX analysis showed distinguishing positive selection traces in ORF sequences of gpElovl2. Transcriptional data showed that different gpElovl subtypes exhibited a tissue-specific expression. Subtypes gpElovl1a, gpElovl2 and gpElovl6l were highly expressed induced by cold stress, as well as fatty acid metabolism-related genes, including Acyl-CoA synthetase long-chain gene (Ascl1a-1) and Stearyl-CoA desaturase gene (Scd1a-1). In addition, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) contents of the hepatopancreas and skeletal muscle were significantly increased under 15-day cold stress. These results provide a better understanding of fish Elovl genes and their roles in cold adaptation.

Background. Ferroptosis is a type of iron-dependent programmed cell death. Ferroptosis has been shown to be a significant factor for the pathogenesis of Parkinson’s disease (PD). However, the mechanism involved in ferroptosis has not been fully elucidated in PD. Methods. Repressor element-1 silencing transcription factor (REST) and specificity protein 1 (SP1) expressions were monitored by qRT-PCR. Cell viability, reactive oxygen species (ROS), and mitochondrial injury were validated by CCK-8, flow cytometry, and transmission electron microscope. The levels of neurons-related proteins and ferroptosis-associated proteins were identified by western blot and immunofluorescence assays. The interaction between miR-494-3p and REST or SP1 and ACSL4 was analyzed by luciferase, chromatin immunoprecipitation, or EMSA assay. Results. Erastin could dose-dependently induce neuron injury and ferroptosis of LUHMES cells. miR-494-3p overexpression induced ROS production, mitochondrial damage, ferroptosis, and neuron injury in erastin-induced LUHMES cells. Likewise, miR-494-3p inhibition had the opposite effects. We also showed that REST was a target gene of miR-494-3p and could repress erastin-induced ferroptosis, neuron injury, ROS, and mitochondrial injury via SP1 in LUHMES cells. Moreover, we demonstrated that SP1 could interact with ACSL4. We also confirmed that miR-494-3p could aggravate the pathological changes of substantia nigra and corpus striatum in the MPTP-induced PD mouse model. Conclusion. miR-494-3p significantly promotes ferroptosis by regulating the REST/SP1/ACSL4 axis in PD. Thus, our results open potential therapeutic targets for PD.

According to attentional control theory and processing efficiency theory, anxiety impairs top-down cognitive control and processing efficiency under threat-related stimuli conditions. However, what is the resulting pattern under an emotionally neutral condition? Therefore, the study examined whether individuals with social anxiety exhibited the cognitive control deficiency in absence of emotional information and how social anxiety modulated cognitive control performance by recording the N2, N450, and SP components in the Stroop task. Behavioral data showed that participants with high social anxiety (HSA) showed slower response times than low social anxiety (LSA). ERP data showed that in HSA participants, congruent trials elicited more negative N2 than incongruent trials, but this was not for LSA ones. The N450 was more negative under incongruent condition than congruent ones. This effect was noticeable in LSA participants, but not in HSA ones. The conflict SP was more positive under incongruent condition than congruent one in HSA participants but not in LSA ones. The significant group differences of the N450 and SP were found mainly for incongruent condition. The present findings indicate that individuals with HSA exhibited cognitive control deficiency for neutral stimuli and an individual's social anxiety modulates the neural correlates of conflict-driven cognitive control.

Underwater optical imaging has important application value, but it is also challenging. In traditional underwater imaging, the problems of uneven illumination, blurred texture details and low contrast often exist, in this paper we propose an underwater active polarization imaging algorithm based on low-rank sparse decomposition aiming to solve the problems above. According to the principle of underwater polarization imaging, the algorithm first performs target information enhancement on the acquired polarization images. Then combining with the low-rank characteristics of backscatter images in the scattered light field, the background information and target information could be separated from the captured images by the low-rank sparse decomposition principle, the high-quality image could be recovered from turbid water as a result. The results of experimental treatments with different turbidity levels demonstrate that the underwater polarization imaging algorithm based on low-rank sparse decomposition can improve the contrast of images, maintain the details of images and remove the background scattering at the same time. Moreover, the proposed method can effectively recover multiple targets and significantly improve the imaging quality which provides a new idea for underwater polarization clear imaging detection.

Nowadays, cultivated variants and adulterants of Astragali Radix (AR) have flooded the market, causing the quality assurance of AR to be challenging. To address this issue, we combined network pharmacology with chromatographic fingerprinting and multicomponent quantitative analysis for the quality evaluation of AR. Specifically, through network pharmacology, a complete understanding of the active components and pharmacological activities of AR was established. In addition, establishing fingerprint profiles and multicomponent quantitation by high-performance liquid chromatography (HPLC) is convenient and comprehensive, and can more fully reflect the overall situation of the distribution of various chemical components. To evaluate and differentiate AR from different origins, hierarchical cluster analysis and principal component analysis were performed. The result showed that AR acts synergistically through multiple targets and pathways. The content of chemical components in AR from different origins varied significantly. Combining network pharmacology and multicomponent quantification results, astragaloside II and IV and formononetin can be used as quality markers for the quality control of AR. This study provides a comprehensive and reliable strategy for the quality evaluation of AR and identifies its quality markers to ensure the quality of the herb.

The flow condensation heat transfer (FCHT) in plain channels has a variety of applications in many industrial sectors, and thus it is important to predict FCHT coefficients accurately. This paper compiled a large compound FCHT database containing 5607 data points and 30 fluids and presented a strategy for developing a new correlation of FCHT coefficients. The parameter range of the database is the hydraulic diameter D = 0.493–20 mm, vapor quality x = 0.003–0.992, mass flux G = 24–1533 kg/m2 s, heat flux q = 2.9–422 kW/m2, reduced pressure pr = 0.04–0.95, liquid Prandtl number Prl = 1.7–8.5, liquid Reynolds number Rel = 11.6–5.3 × 104, and gas Reynolds number Reg = 75.1–9.1 × 105. Based on the database and strategy, a new general correlation with substantially better accuracy was developed, which is applicable to plain channels of various sizes and a broad operational parameter range. It predicts the database with a mean absolute deviation (MAD) of 14.1%, while the best existing Δ T-independent correlation predicts the database with an MAD of 20.2%. The applicability of the new and 38 existing correlations to individual fluids was assessed. The new correlation performs best for 8 of the 14 fluids that have more than 50 data points in the entire database, while the most accurate existing one performs best only for 2 of them. The Fang number Fa plays an important role in the new correlation, implying that it relates to the fundamental mechanisms of both boiling and condensation heat transfer.

The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of

Three new aconitine-type C

In this study, the effect of social anxiety on item recognition memory was examined by adopting a study-test paradigm. Participants with high and low social anxiety (31 HSA vs. 30 LSA) memorized neutral target and threat target (NT vs. TT) words while threat distracters were simultaneously presented. The behavioral results did not exhibit group differences in recognition performance. The event-related potentials (ERP) results showed that the HSA and LSA participants all did not exhibit significant old/new effects for neutral targets, while only the LSA participants exhibited significant old/new effects for threat targets. For the distracters, the HSA participants did not exhibit evident old/new effects under the NT and TT conditions; while LSA participants showed a reversed LPC old/new effect for the threat distracters under the NT condition. The old/new effects for threat targets were impaired in HSA participants but presented in LSA participants. These findings suggest that social anxiety modulates the effect of recognition memory for social threat words.

Two new premyrsinane-type diterpenes (

With the repaid development of Internet of Vehicles (IoV), more available resources and energy-efficient optimizations in resources scheduling are exactly required for large-scale network implementation for sustainable development. We observe that parked vehicles (PVs) have rich and underutilized resources for task execution. By scheduling them as general computing nodes to undertake computation tasks, we introduce a new computing paradigm, named by parked vehicular computing (PVC). There exists some challenging issues to be addressed for the facilitation of PVC. In particular, an incentive mechanism is needed to offer optimized rewards for PVs with the consideration of their parking time and energy consumption. In this paper, we investigate an energy-efficient PVC paradigm, and we design a contract-based incentive mechanism to motivate PVs to contribute their idle on-board resources. The PVs are classified into different types according to their parking time. Then, the designed contracts are assigned to different types of PVs. To realize the incentive mechanism, the optimization problem with the contract design is formulated to maximize the utility of the service provider. For optimal contract design, we solve the simplified problem by using Lagrangian multiplier method. Numerical results indicate that the proposed PVC with optimal contract design outperforms existing work in improving social welfare of resource scheduling, which takes quality-of-service and overall energy consumption into consideration. We also demonstrate that the contract-based incentive mechanism is energy-efficient and effective.

In data center networks, MultiPath TCP (MPTCP) obtains both higher network utilization and fairer allocation of capacity by exploring multiple paths simultaneously. However, MPTCP experiences more queue oscillation in switch buffer with the increasing of the number of subflows. When using explicit congestion notification as the congestion indication to track the queue length in switch buffer, it is difficult for MPTCP to capture the accurate congestion state, resulting in wrong behavior in congestion control. Therefore, we propose an enhanced MPTCP protocol, namely, advanced MPTCP (AMP), which adjusts the time granularity of the congestion detection and control under a different number of subflows. The test results show that compared with Linked Increases Algorithm and eXplicit MultiPath, AMP achieves lower latency for small flows and higher throughput for large flows.

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare, and the clinical symptoms, test results, and imaging characteristics are nonspecific in most patients; thus, it is difficult to differentiate from other liver masses before surgery. Histopathology and immunohistochemistry are the main basis for the diagnosis. PHNETs and colon tumors co-occur in a patient and are non-homologous, as reported in the English-language literature for the first time.We present a case of a 60-year-old woman with right hepatic lobe mass accidentally discovered on abdominal ultrasonography during a routine examination. Preoperative liver contrast-enhanced computed tomography suggested hepatocellular carcinoma; then, surgery were performed. Pathological results revealed a Grade 2 neuroendocrine tumor of the liver. In search of the primary tumor, upper and lower endoscopy of the GI tract was performed and revealed a mass in the ascending colon. Ascending colon cancer was considered; then, laparoscopic right hemicolectomy was performed. Pathological results suggested tubular villous adenoma of the ascending colon. The final diagnosis was not colon cancer with liver metastases but was PHNETs with colon adenoma.PHNETs are rare cancers that are difficult to diagnose, requiring not only differentiation from other liver masses but also exclusion of metastases from extrahepatic sources. The pathological results play an important in making an accurate diagnosis.Pathology, postoperative follow-up, and comprehensive imaging examinations are powerful tools in the diagnosis of PHNETs. Currently, surgery is the best treatment to achieve a potential cure and prolong the patient's survival.