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This note studies the stability problem of nonlinear positive differential-difference equations with unbounded time-varying delays. Under assumptions on the nonlinear vector fields, such as being homogeneous, cooperative, and order-preserving, conditions are derived for positivity and asymptotic stability of nonlinear differential-difference equations, which include the corresponding linear system as a special case. This work features three main contributions: first, a necessary and sufficient positivity condition is proposed for nonlinear differential-difference equations with delays. Then, utilizing the concept of homogeneity, a necessary and sufficient condition is provided for the global asymptotic stability of such positive nonlinear systems with unbounded delays. Finally, we analyze the global $\mu$-stability of the systems with unbounded time-varying delays to estimate the convergence rates of the system dynamics. The effectiveness of the obtained theoretical results is illustrated by numerical examples, including an analysis of nonlinear epidemic-spreading processes.

In this work, we propose a hierarchical motion planning framework for a swarm of collective vehicles with a lower maximum speed to race against a single adversary with a higher maximum speed, where the swarm gains a competitive advantage by collaborating. The proposed path planner framework consists of two planning layers: the decision layer and the execution layer. The racing strategy of the swarm is planned in the decision layer, which determines the discrete path and changes the formation of the cooperative vehicles according to the game's progress. A Gestalt Nash Game (GNG) framework is designed to depict the racing game and determine the strategy of each swarm member: cooperative block or all-full sprint. Then, an interaction-enhanced iterated best response algorithm is introduced to solve each vehicle's optimal trajectory and infer the adversary's planning path, searching the Nash equilibrium solution for this multi-vehicle racing. Furthermore, the execution layer employs the discrete trajectories obtained in the decision layer as the B-spline control points and considers the kinematic constraints to get smooth and feasible trajectories. We also combine the MPC method with the simplified Pacejka tire model to drive the vehicle motion. Illustrative simulation examples with different initial conditions are presented, showing that the slower group can beat the faster adversary with a higher probability using the proposed hierarchical path planner.

A current-efficient and fast-transient n-type low-dropout regulator (LDO) for high-frequency load transient in mobile phone applications is presented in this article. By using transconductance magnified MOS (TM-MOS), it reduces LDO’s output impedance with fast response speed and keeps high current efficiency. Moreover, based on load-current sensing of TM-MOS, active clamp strategy is implemented to optimize the driving dead zone (DDZ) of this NMOS LDO and achieve good high-frequency load transient performance. Robust loop stability for a wide load-current range is ensured as well with the help of revised Type-II frequency compensation. This circuit has been implemented in a 0.35- $\mu \text{m}$ standard CMOS process and occupies an active chip area of $470\times280\,\,\mu \text{m}^{2}$ . With a 1- $\mu \text{F}$ output cap and load steps between 0 A and 300 mA, experimental results show that it features 50/36 mV of undershoot/overshoot at low-frequency load transient and 68/36 mV of undershoot/overshoot at the high-frequency load transient (i.e., 10- $\mu \text{s}$ light-load duration). This regulator consumes 8.2- $\mu \text{A}$ quiescent current, achieving 99.68% equivalent current efficiency at 300-mA load current.

Object contour plays an important role in fields such as semantic segmentation and image classification. However, the extraction of contour is a difficult task, especially when the contour is incomplete or unclosed. In this paper, the existing contour detection approaches are reviewed and roughly divided into three categories: pixel-based, edge-based, and region-based. In addition, since the traditional contour detection approaches have achieved a high degree of sophistication, the deep convolutional neural networks (DCNNs) have good performance in image recognition, therefore, the DCNNs based contour detection approaches are also covered in this paper. Moreover, the future development of contour detection is analyzed and predicted.

This work deals with the distributed Byzantine-resilient observer (DBRO) design problem for continuous-time high-order integrator multiagent systems on directed graphs, which intends to estimate the leader states accurately in a finite-time interval. A new kind of edge-based DBRO is first formulated for the followers to estimate each order of the nonautonomous leader's state, which is implemented in a cascading manner. Then, the finite-time zero-error estimation performance of the above DBRO is guaranteed for both time-invariant and time-varying strongly $(2f+1)$-robust directed topologies, based on strictly nonsmooth analysis and mathematical induction method. Finally, the practicability and validity of this new DBRO are illustrated via a numerical simulation example.

This article delves into the distributed resilient output containment control of heterogeneous multiagent systems against composite attacks, including Denial-of-Service (DoS) attacks, false-data injection (FDI) attacks, camouflage attacks, and actuation attacks. Inspired by digital twin technology, a twin layer (TL) with higher security and privacy is employed to decouple the above problem into two tasks: 1) defense protocols against DoS attacks on TL and 2) defense protocols against actuation attacks on the cyber–physical layer (CPL). Initially, considering modeling errors of leader dynamics, distributed observers are introduced to reconstruct the leader dynamics for each follower on TL under DoS attacks. Subsequently, distributed estimators are utilized to estimate follower states based on the reconstructed leader dynamics on the TL. Then, decentralized solvers are designed to calculate the output regulator equations on CPL by using the reconstructed leader dynamics. Simultaneously, decentralized adaptive attack-resilient control schemes are proposed to resist unbounded actuation attacks on the CPL. Furthermore, the aforementioned control protocols are applied to demonstrate that the followers can achieve uniformly ultimately bounded (UUB) convergence, with the upper bound of the UUB convergence being explicitly determined. Finally, we present a simulation example and an experiment to show the effectiveness of the proposed control scheme.

This work solves the countermeasure design problems of distributed resilient output time-varying formation-tracking (TVFT) of heterogeneous multiagent systems (MASs) against general Byzantine attacks (GBAs). Inspired by the concept of Digital Twin, a hierarchical protocol equipped with a twin layer (TL) is proposed, which decouples the above problem into the defense against Byzantine edge attacks (BEAs) on the TL and the defense against Byzantine node attacks (BNAs) on the cyber-physical layer (CPL). First, a secure TL with respect to (w.r.t.) the high-order leader dynamics is designed, which achieves resilient estimation against BEAs. A trusted-node strategy against BEAs is proposed, which promotes network resilience by protecting almost the smallest fraction of crucial nodes on the TL. It is proven that strongly $(2f+1)$ -robustness w.r.t. the above trusted nodes is sufficient for the resilient estimation performance of the TL. Second, a decentralized adaptive and chattering-free controller against potentially unbounded BNAs is designed on the CPL. This controller has the merit of uniformly ultimately bounded (UUB) convergence and an assignable exponential decay rate when converging into the above UUB bound. To the best of our knowledge, this article is the first to achieve resilient output TVFT against GBAs, rather than under GBAs. Finally, the practicability and validity of this new hierarchical protocol are illustrated via a simulation example.

The harmonics and resonance of traction power supply systems (TPSSs) aggravate the electromagnetic interference (EMI) to adjacent metallic pipelines (MPs), which has aroused widespread concern. In this paper, an evaluation method on pipeline interference voltage under harmonic induction is presented. The results show that the Carson integral formula is more accurate in calculating the mutual impedance at higher frequencies. Then, an integrated train–network–pipeline model is established to estimate the influences of harmonic distortion and resonance on an MP. It is revealed that the higher the harmonic current distortion rate of the traction load, the larger the interference voltage on an MP. Particularly, the interference voltage is amplified up to 7 times when the TPSS resonates, which is worthy of attention. In addition, the parameters that affect the variation and sensitivity of the interference voltage are studied, namely, the pipeline coating material, locomotive position, and soil resistivity, indicating that soil resistivity and 3PE (3-layer polyethylene) anticorrosive coating are more sensitive to harmonic induction. Field test results show that the harmonic distortion can make the interference voltage more serious, and the protective measures are optimized.

This article studies the resilient formation tracking control problem for spacecraft swarm while considering actuation attacks and input saturation. A distributed Lyapunov-based model predictive controller (DLMPC) framework is designed for spacecraft swarm to track the target trajectory in a preset formation shape and achieve attitude consensus. To ensure formation safety, a collision avoidance term is introduced into the DLMPC framework. To guarantee the feasibility and stability of the DLMPC, we first construct the Lyapunov-based adaptive auxiliary controller and then use its stability to construct the stability constraint. The DLMPC inherits the characteristic of the Lyapunov-based adaptive auxiliary controller and employs online optimization to guarantee better formation tracking performance. As a novel framework for spacecraft formation control, the proposed DLMPC has the advantage of improving the formation tracking performance through persistently online optimization, especially, in adversarial dynamic environments. The simulation results validate the superiority and resilience of the DLMPC, and the proposed DLMPC framework shows improvement in formation tracking performance.

In this article, a resilient path planning scheme is proposed to navigate an unmanned aerial vehicle (UAV) to its planned (nominal) destination with minimum energy consumption in the presence of a strategic attacker. The UAV is equipped with the following two sensors: 1) a GPS sensor, which is vulnerable to spoofing attacks; 2) a well-functioning ultrawideband (UWB) sensor, which is possible to be deceived. It is shown that a covert attacker can significantly deviate the UAV's path without being detected by the UWB sensor by simultaneously corrupting the GPS signals and forging control inputs. The prerequisite for the attack occurrence is first discussed. Based on this prerequisite, an optimal attack scheme is proposed, which maximizes the deviation between the nominal destination and the real one. Correspondingly, an energy-efficient and resilient navigation scheme based on Pontryagin's maximum principle is formulated, which suppresses the above covert attacker effectively. Essentially, this problem can be seen as a Stackelberg game between a resilient path planner (defender) and a covert attacker. The effectiveness of our theoretical results is illustrated via two simulation examples.

The pyridine derivative, 4-(dimethylamino)pyridine (DMAP), is important in a surprisingly wide variety of applications spanning chemical, biological, and technological domains. Empirically, the protonation state of DMAP and how this protonation state is changed with adsorption on a solid surface are known to play a crucial role in many of these applications. However, direct spectroscopic evidence for bias-dependent DMAP (de)protonation at solid/aqueous interfaces is still very limited. Here, we employed surface-specific vibrational sum frequency (VSF) spectroscopy to study the (de)protonation process of DMAP(H+) on a polycrystalline gold electrode at neutral pH. Because VSF spectroscopy is interface-specific by its symmetry selection rules, its application allows us to distinguish adsorbed molecules from those close to, but not at, the interface and identify their speciation and orientation with respect to the surface normal. We find that the potential-induced (de)protonation of flat-lying DMAPH+molecules occurs at relatively low potentials but that both species adsorb horizontally on the surface. A horizontal-to-vertical phase transition occurs only at more positive biases. The physical picture these results suggest confirms and extends that inferred previously from electrochemical measurements and offers a general approach for characterizing interface-induced acid/base chemistry and its relation to interfacial molecular structures.

Objective: As reported, glioma progression is affected by altered FXR1, long non-coding RNA FGD5-AS1, and microRNA (miR)-124-3p. However, relationships among these genes remain unclear. Accordingly, this paper ascertains whether FXR1 manipulates glioma progression via the FGD5-AS1/miR-124-3p axis. Methods: Glioma tissues were harvested, in which FGD5-AS1 and miR-124-3p levels were examined with qRT-PCR and FXR1 level was assessed with qRT-PCR and western blot. The interaction of miR-124-3p with FGD5-AS1 was analyzed by dual-luciferase reporter, RIP, and Pearson correlation coefficient assays, and that of FXR1 with FGD5-AS1 was assessed by RIP and Pearson correlation coefficient assays. Glioma cells were obtained, followed by qRT-PCR detection of miR-124-3p expression. After gain- or loss-of-function assays, EdU, Transwell, and tubule formation assays were performed to determine cell proliferation, invasion and migration, and angiogenesis. Next, the intracranial in situ graft tumor model was established for in vivo verification. Results: FGD5-AS1 and FXR1 levels were high, but miR-124-3p level was low in glioma tissues. Likewise, glioma cells had downregulated miR-124-3p expression. Mechanistically, FGD5-AS1 negatively bound to miR-124-3p, and FXR1 was positively correlated and interacted with FGD5-AS1. miR-124-3p overexpression or FGD5-AS1 or FXR1 knockdown restricted cell invasion, proliferation, migration, and angiogenesis in gliomas. miR-124-3p inhibition abrogated the repressive impacts of FXR1 knockdown on the malignant progression of gliomas. Also, FXR1 constrained tumor growth and angiogenesis in mice, which was counterweighed by inhibiting miR-124-3p. Conclusion: FXR1 might act as an oncogene in gliomas by declining miR-124-3p through FGD5-AS1.

Multi-agent pickup and delivery (MAPD) is crucial in intelligent storage systems (ISSs), where multiple automated guided vehicles (AGVs) are assigned to various and potentially uncertain dynamic tasks. In this work, we consider a human–swarm hybrid system consisting of human workers and a swarm of AGVs collaborating to accomplish MAPD tasks. A human–swarm hybrid system pickup and delivery ((HS)$_{2}$PD) framework based on the receding-horizon prediction window is proposed, which facilities the development of future ISSs. This (HS)$_{2}$PD framework is essentially a two-layer hierarchical decision procedure, which takes the uncertainties of human behavior and the dynamic changes of tasks into account. The first layer is a two-level programming model handling the problems of mode assignment and task allocation. The second layer calculates each vehicle’s exact path by solving mixed-integer programmings. An integrated high-efficient algorithm for the (HS)$_{2}$PD problem is also proposed. The practicality and validity of the above algorithm are demonstrated via several groups of numerical simulations of (HS)$_{2}$PD tasks.

This work investigates the problem of joint localization and target tracking (JLATT) of multi-vehicle systems (MVSs) in the presence of Byzantine attacks (BAs). For MVSs, there may exist malicious and misbehaving vehicles, called Byzantine vehicles, which act as deceivers and pass false information to their neighbors. For the first time, we formulate a resilient JLATT framework to synthesize the hybrid problems of distributed cooperative localization and flock tracking in the presence of BAs. More specifically, we propose a covariance weighted mean-subsequence-filter (CW-MSF) algorithm to guarantee that the MVS achieves flock tracking w.r.t a target even in the presence of a certain fraction of Byzantine vehicles. Note that this resilient JLATT scheme does not require global information and thus it is fully distributed. The practicality and validity of this novel JLATT framework are verified via an illustrative numerical simulation example.

This paper is concerned with the optimization of the impulse-to-peak value of positive linear systems. Although the results of the analysis of the peak value of positive linear systems have been reported in the literature, the synthesis problem of impulse-to-peak value remains unresolved. To address this problem, in this paper we show that a cost-constrained minimization problem of the impulse-to-peak value of parameterized positive linear systems can be reduced to a DC (difference of convex functions) program. The derivation utilizes the log-log convexity of posynomial functions and a recent characterization of the impulse-to-peak value of positive systems via a linear program. To illustrate the effectiveness of our results, we study the optimization problem for minimizing the peak infection of networked epidemic spreading processes.

This paper studies the countermeasure design problems of distributed resilient time-varying formation-tracking control for multi-UAV systems with single-way communications against composite attacks, including denial-of-services (DoS) attacks, false-data injection attacks, camouflage attacks, and actuation attacks (AAs). Inspired by the concept of digital twin, a new two-layered protocol equipped with a safe and private twin layer (TL) is proposed, which decouples the above problems into the defense scheme against DoS attacks on the TL and the defense scheme against AAs on the cyber-physical layer. First, a topology-repairing strategy against frequency-constrained DoS attacks is implemented via a Zeno-free event-triggered estimation scheme, which saves communication resources considerably. The upper bound of the reaction time needed to launch the repaired topology after the occurrence of DoS attacks is calculated. Second, a decentralized adaptive and chattering-relief controller against potentially unbounded AAs is designed. Moreover, this novel adaptive controller can achieve uniformly ultimately bounded convergence, whose error bound can be given explicitly. The practicability and validity of this new two-layered protocol are shown via a simulation example and a UAV swarm experiment equipped with both Ultra-WideBand and WiFi communication channels.

This work deals with the optimal epidemics policy-seeking problem on networks-of-networks (NoN) in the presence of unknown malicious adding-edge attacks. This problem is investigated in a framework of games-of-games (GoG), in which the conflicts between each network policymaker and the attacker are captured by a series of the Stackelberg games, while all network policymakers together compose a Nash game. First, the tolerable maximum attack magnitude is investigated and given implicitly. Then, we prove the existence of the gestalt Nash equilibrium (GNE) under mild attacks bounded by the above magnitude. A Heuristic algorithm based on iterative geometric programming is proposed to seek the GNE of the above GoG, whose asymptotical convergence is verified. Correspondingly, a greedy Heuristic strategy for the malicious attacker to compromise the NoN topology is developed. The practicability and validity of the above theoretical results and algorithms are illustrated via a simulation example.

Under the strategy of “Northeast Revitalizing”, Northeast China must correctly handles the coupling relationship of coordinated development among economy, energy, environment, and technology if it insists on the concept of green development. In this paper, by establishing an appropriate evaluation index system and introducing ”kernel function density” analysis method, the coupling problem and it’s time evolution characteristics of the coordinated development of the economy–energy–environment–technology of Liaoning Province, Jilin Province, Heilongjiang Province and Inner Mongolia Autonomous Region in Northeast China were studied. It was found that the coordination degree of the quaternary systems was between 0.71 and 0.97, and it was good. The development degree was between 0.25 and 0.58, and it was very bad. The ”weakness” of low development degree results in the low coupling degree (between 0.46 and 0.70) of the quaternary system. The coordination degree of the quaternary systems in Northeast China was increasing year by year, and the differences between provinces (regions) were also shrinking. The development degree generally presented ”wave” fluctuation characteristics, and the regional difference showed an increasing trend. The coupling degree of Heilongjiang Province, Jilin Province and Liaoning Province basically maintained a steady state of improvement, and Inner Mongolia Autonomous Region improved significantly after 2017. Finally, the paper put forward some countermeasures and suggestions to improve the coupling degree of the coordinated development of economy, energy, environment and technology in Northeast China, so as to provide reference for the revitalization of Northeast China.

Plant biotic or abiotic stresses, such as pathogens, mechanical damage, or high temperature, can increase intracellular H2O2concentration, damaging proteins, lipids, and DNA. Most current H2O2detection methods require the separation or grinding of plant samples, inducing plant stresses, and the process is complicated and time-consuming. This paper constructed a metal–organic framework (MOF)-based biosensor for real-time, remote, and in situdetection of exogenous/endogenous H2O2in plant organs through color-to-thermal signal conversion. By simply spraying horseradish peroxidase, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and the precursor of zeolite imidazolate frameworks-8 (ZIF-8), ZIF-8 biosensors were formed in situon a plant root, petiole, or leaf. This biosensor could report sub-micromolar H2O2in plants since the oxidation products, ABTS• +, emitted heat when they absorbed energy from near-infrared (NIR) light. Due to the plant’s low absorption in the NIR region, the ZIF-8 biosensor allowed for remote thermal sensing of H2O2transport or biotic/abiotic stresses in plants with a high signal-to-noise ratio combining NIR laser and thermometer. Our biosensor can be used for the future development of plant sensors for monitoring plant signaling pathways and metabolism that are nondestructive, minimally invasive, and capable of real-time, in situanalysis.

The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF).

The heterostructure CdS/CdTe is one of the most important interfaces in solar energy cells, however, its exact structure is not well-known due to the large lattice mismatch, thus hindering the studies of interfacial properties. In this paper, we present a scheme to explore the interface structures by combining the differential evolution (DE) algorithm and the neural network potential. A high-accuracy neural network potential is trained to describe the interatomic interactions, and then the interfacial structures are searched using our DE program that started from a CdS/CdTe interface model that consists of about 1740 atoms. We identify a series of interfacial structures with defects and assess their stabilities by considering the interfacial energies. We find that the CdS-like interface I is generally energetically more favorable and prefers to be defect-free under the Cd-poor condition. Therefore, the Cd-poor condition might be beneficial for improving the solar cell efficiencies by suppressing possible defect recombination at the interface. Our work provides a general scheme to study structures of complex interfaces with a large number of atoms.

Viruses significantly influence local and global biogeochemical cycles and help bacteria to survive in different environments by encoding various auxiliary metabolic genes (AMGs) associated with energy acquisition, stress tolerance and degradation of xenobiotics. Here we studied whether bacterial (dsDNA) virus encoded AMGs are enriched in organochlorine pesticide (OCP) contaminated soil in China and if viral AMGs include genes linked to OCP biodegradation. Using metagenomics, we found that OCP-contaminated soils displayed a lower bacterial, but higher diversity of viruses that harbored a higher relative abundance of AMGs linked to pesticide degradation and metabolism. Furthermore, the diversity and relative abundance of AMGs significantly increased along with the severity of pesticide contamination, and several biodegradation genes were identified bioinformatically in viral metagenomes. Functional assays were conducted to experimentally demonstrate that virus-encoded L-2-haloacid dehalogenase gene (L-DEX) is responsible for the degradation of L-2-haloacid pesticide precursors, improving bacterial growth at sub-inhibitory pesticide concentrations. Taken together, these results demonstrate that virus-encoded AMGs are linked to bacterial metabolism and biodegradation, being more abundant and diverse in soils contaminated with pesticides. Moreover, our findings highlight the importance of virus-encoded accessory genes for bacterial ecology in stressful environments, providing a novel avenue for using viruses in the bioremediation of contaminated soils.

Viruses significantly influence local and global biogeochemical cycles and help bacteria to survive in different environments by encoding various auxiliary metabolic genes (AMGs) associated with energy acquisition, stress tolerance and degradation of xenobiotics. Here we studied whether bacterial (dsDNA) virus encoded AMGs are enriched in organochlorine pesticide (OCP) contaminated soil in China and if viral AMGs include genes linked to OCP biodegradation. Using metagenomics, we found that OCP-contaminated soils displayed a lower bacterial, but higher diversity of viruses that harbored a higher relative abundance of AMGs linked to pesticide degradation and metabolism. Furthermore, the diversity and relative abundance of AMGs significantly increased along with the severity of pesticide contamination, and several biodegradation genes were identified bioinformatically in viral metagenomes. Functional assays were conducted to experimentally demonstrate that virus-encoded L-2-haloacid dehalogenase gene (L-DEX) is responsible for the degradation of L-2-haloacid pesticide precursors, improving bacterial growth at sub-inhibitory pesticide concentrations. Taken together, these results demonstrate that virus-encoded AMGs are linked to bacterial metabolism and biodegradation, being more abundant and diverse in soils contaminated with pesticides. Moreover, our findings highlight the importance of virus-encoded accessory genes for bacterial ecology in stressful environments, providing a novel avenue for using viruses in the bioremediation of contaminated soils.

In pinhole integral imaging (PII)‐based hologram, each pinhole is regarded as a point light source to emit light rays in different directions to simulate light propagation from the reconstructed 3D information to the computer‐generated hologram (CGH). The PII‐based hologram presents at a working mode similar to resolution‐priority integral imaging (RPII). The depth of field (DOF) is inevitably limited. In this paper, we use twice close‐range capturing to enhance the DOF of this hologram. Twice close‐range capturing can ensure that the virtual objects with different depths are not far from their respective image reference planes, and the detailed information of the back object also can be preserved. Besides, we use a simple ray‐tracing method to solve the occlusion problems. Numerical and optical reconstruction verified that the proposed method can reconstruct clearer 3D images compared with the single capturing method. In addition, the proposed method can present a natural occlusion effect. Thus, the DOF is enhanced. Twice close‐range capturing can ensure that the objects with different depths are not far from their respective image referencing planes, and the detailed information of the back object also can be preserved. In addition, rays on the same path emitted from the front and back objects can be found by a simple ray‐tracing method to handle occlusion problem.

We have achieved an Ir(III)‐catalyzed temperature‐controlled divergent synthesis of tetrasubstituted alkenes and pyrrolo[1,2‐a]indole derivatives through C−H alkenylation/DG migration and [3+2] annulation, respectively. This method has various advantageous features: a) excellent regio‐ and stereoselectivity and good functional group tolerance, b) broad substrate scope and moderate to excellent yields, c) mild redox‐neutral reaction conditions and operational simplicity. We report an Ir(III)‐catalyzed temperature‐controlled divergent synthesisof tetrasubstituted alkenes and pyrrolo[1,2‐a]indole derivatives through C−H alkenylation/DG migration and [3+2] annulation, respectively. This protocol is characterized by excellent regio‐ and stereoselectivity, broad substrate scope, good functional group tolerance, moderate to excellent yields, mild redox‐neutral reaction conditions and operational simplicity.

Herein, we report the divergent synthesis of alkynylated imidazo[1,5-a]indoles and α,α-difluoromethylene tetrasubstituted alkenes through Rh(III)-catalyzed [4 + 1] annulation/alkyne moiety migration and C–H alkenylation/DG migration, respectively. This protocol features tunable product selectivity, excellent chemo-, regio-, and stereoselectivity, broad substrate scope, moderate to high yields, good tolerance of functional groups, and mild redox-neutral conditions.

ABSTRACTBiogenesis of autophagosomes is the early step of macroautophagy/autophagy and requires membrane acquisition mainly from ER-Golgi-sourced precursor vesicles. Matured autophagosomes fuse with lysosomes for final degradation. However, how this selective fusion is determined remains elusive. Here, we identified Sac1 by a high throughput screen in Saccharomyces cerevisiaeto show it was critical for autophagosome-lysosome fusion through its PtdIns4P phosphatase activity. Sac1 deficiency caused a dramatic increase of PtdIns4P at early Golgi apparatus and abnormal incorporation of PtdIns4P into Atg9 vesicles and autophagosomes, which caused failure to recruit SNARE proteins for autophagosome fusion with vacuoles. Sac1 function in autophagy was highly conserved from yeast to mammalian cells. Our work thus suggested that correct upstream lipid incorporation was important for downstream fusion step of autophagy and that Sac1 played a critical and ancient role in this surveillance of lipid integration.Abbreviations:Ape1: aminopeptidase Ι; ATG: autophagy related; EBSS: Earle’s balanced salt solution; ER: endoplasmic reticulum; ERGIC: Golgi apparatus and ER-Golgi intermediate compartment; HOPS: homotypic fusion and protein sorting complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns4K: phosphoinositide-4-kinase; PtdIns4P: phosphatidylinositol-4-phosphate; SD-N: nitrogen starvation medium; SNARE: soluble N-ethylamide-sensitive factor attachment protein receptor

Lookup table (LUT) and wavefront recording plane (WRP) methods are proposed to accelerate the computation of fully computed hologram stereograms (HSs). In the LUT method, we precalculate large and complete spherical wave phases with varying depths, and each complex amplitude distribution segment of the object point can be obtained quickly by cropping a specific and small part of the precalculated spherical wave phases. Then, each hologram element (hogel) can be calculated by superposing all the related segments. In addition, setting a WRP near the 3D scene can further accelerate computation and reduce storage space. Because the proposed methods only replace the complex calculation using referencing LUT, they are accurate and have no limitation on the size of hogel compared with some methods of paraxial approximation. Simulations and optical experiments verify that the proposed methods can reconstruct quality 3D images with reduced computational load.

In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities in vitroand in vivo. The structure–activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells in vitro, of which 3-(6-chloro-9H-purin-9-yl)dodecan-1-ol (9b) exhibited the most potent effect against the HCT-116 and SW480 cells with IC50values of 0.89 and 1.15 μM, respectively. Furthermore, all of the (R)-configured acyclic nucleoside derivatives displayed more potent anticancer activity compared to their (S)-counterparts. Mechanistic studies revealed that compound 9btriggered apoptosis in the cancer cell lines viadepolarization of the mitochondrial membrane and effectively inhibited colony formation. Importantly, compound 9binhibited the growth of the SW480 xenograft in a mouse model with low systemic toxicity. These results indicated that acyclic nucleoside compounds are viable as potent and effective anticancer agents, and compound 9bmay serve as a promising lead compound that merits further attention in future anticancer drug discovery.

Herein, we report the additive-controlled divergent synthesis of tetrasubstituted 1,3-enynes and alkynylated 3H-pyrrolo[1,2-a]indol-3-ones through rhodium-catalyzed C–H alkenylation/DG migration and [3+2] annulation, respectively. This protocol features rare directing group migration in 1,3-diyne-involved C–H activation, excellent regio- and stereoselectivity, excellent monofunctionalization over difunctionalization, broad substrate scope, moderate to high yields, good functional group compatibility, and mild redox-neutral conditions.

Human serine palmitoyltransferase (SPT) complex catalyzes the initial and rate-limiting step in the de novo biosynthesis of all sphingolipids. ORMDLs regulate SPT function, with human ORMDL3 being related to asthma. Here we report three high-resolution cryo-EM structures: the human SPT complex, composed of SPTLC1, SPTLC2 and SPTssa; the SPT–ORMDL3 complex; and the SPT–ORMDL3 complex bound to two substrates, PLP-l-serine (PLS) and a non-reactive palmitoyl-CoA analogue. SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core. SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity. ORMDL3 is located in the center of the complex, serving to stabilize the SPT assembly. Our structural and biochemical analyses provide a molecular basis for the assembly and substrate selectivity of the SPT and SPT–ORMDL3 complexes, and lay a foundation for mechanistic understanding of sphingolipid homeostasis and for related therapeutic drug development.