Jianing Li

• Renmin University of China

The pituitary adenylate cyclase-activating polypeptide receptor I (PAC1R) represents a highly sought-after therapeutic target for chronic pain, migraine, and post-traumatic stress. As a class B G protein-coupled receptor (GPCR), the PAC1R is highly expressed throughout the neuronal and central nervous system membranes, with the receptor subject to...

Event cameras, offering high temporal resolutions and high dynamic ranges, have brought a new perspective to address common challenges in monocular depth estimation (e.g., motion blur and low light). However, existing CNN-based methods insufficiently exploit global spatial information from asynchronous events, while RNN-based methods show a limited...

Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combin...

Geometric isomerism in mechanically interlocked systems—which arises when the axle of a mechanically interlocked molecule is oriented, and the macrocyclic component is facially dissymmetric—can provide enhanced functionality for directional transport and polymerization catalysis. We now introduce a kinetically controlled strategy to control geometr...

Different from visible cameras which record intensity images frame by frame, the biologically inspired event camera produces a stream of asynchronous and sparse events with much lower latency. In practice, visible cameras can better perceive texture details and slow motion, while event cameras can be free from motion blurs and have a larger dynamic...

Glutathione (GSH) is a critical component of the cellular redox system that combats oxidative stress. The glutamate-cystine antiporter, system x C ⁻ , is a key player in GSH synthesis that allows for the uptake of cystine, the rate-limiting building block of GSH. It is unclear whether GSH or GSH-dependent protein oxidation [protein S -glutathionyla...

DAVIS camera, streaming two complementary sensing modalities of asynchronous events and frames, has gradually been used to address major object detection challenges (e.g., fast motion blur and low-light). However, how to effectively leverage rich temporal cues and fuse two heterogeneous visual streams remains a challenging endeavor. To address this...

Protein-S-glutathionylation is a post-translational modification involving the conjugation of glutathione to protein thiols, which can modulate the activity and structure of key cellular proteins. Glutaredoxins (GLRX) are oxidoreductases that regulate this process by performing deglutathionylation. However, GLRX has five cysteines that are potentia...

DAVIS camera, streaming two complementary sensing modalities of asynchronous events and frames, has gradually been used to address major object detection challenges (e.g., fast motion blur and low-light). However, how to effectively leverage rich temporal cues and fuse two heterogeneous visual streams remains a challenging endeavor. To address this...

Two‐dimensional (2D) assemblies of water‐soluble block copolymers have been limited by a dearth of systematic studies that relate polymer structure to pathway mechanism and supramolecular morphology. Here, we employ sequence‐defined triblock DNA amphiphiles for the supramolecular polymerization of free‐standing DNA nanosheets in water. Our systemat...

Two‐dimensional (2D) assemblies of water‐soluble block copolymers have been limited by a dearth of systematic studies that relate polymer structure to pathway mechanism and supramolecular morphology. Here, we employ sequence‐defined triblock DNA amphiphiles for the supramolecular polymerization of free‐standing DNA nanosheets in water. Our systemat...

Molecules with bioactivity towards G protein-coupled receptors represent a subset of the vast space of small drug-like molecules. Here, we compare machine learning models, including dilated graph convolutional networks, that conduct binary classification to quickly identify molecules with activity towards G protein-coupled receptors. The models are...

Event cameras, offering high temporal resolutions and high dynamic ranges, have brought a new perspective to address common challenges (e.g., motion blur and low light) in monocular depth estimation. However, how to effectively exploit the sparse spatial information and rich temporal cues from asynchronous events remains a challenging endeavor. To...

We report a general synthetic route toward helical ladder polymers with varying spring constants, built with chirality‐assisted synthesis (CAS). Under tension and compression, these shape‐persistent structures do not unfold, but rather stretch and compress akin classical Hookean springs. Our synthesis is adaptable to helices with different pitch an...

Helical molecular springs built from chiral ladder polymers expand and contract without unfolding at room temperature. In their Communication (DOI: 10.1002/anie.202209772), Severin T. Schneebeli and co‐workers show that such helical ladder polymers can act like classical Hookean springs in solution with adjustable spring constants.

Molekulare Spiralfedern aus chiralen Leiterpolymeren expandieren und kontrahieren ohne Entfaltung bei Raumtemperatur. In ihrer Zuschrift (DOI: 10.1002/ange.202209772) zeigen Severin T. Schneebeli und Mitarbeiter, dass sich solche spiralförmigen Leiterpolymere in Lösung wie klassische Hooke′sche Federn mit einstellbaren Federkonstanten verhalten kön...

Establishing how polymeric vectors such as polyethylenimine (PEI) bind and package their nucleic acid cargo is vital toward developing more efficacious and cost-effective gene therapies. To develop a molecular-level picture of DNA binding, we examined how the Raman spectra of PEIs report on their local chemical environment. We find that the intense...

DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and noninvasive control of chemical processes for a wide range of applications. However, most current photoresponsive DNA switches are limited by either irreversible switching or reversible switching with impractically slow kinetics. Here, we re...

We report a general synthetic route toward freeform helical ladder polymers with varying spring constants, built with chirality‐assisted synthesis (CAS). Under tension and compression, these shape‐persistent structures do not unfold, but rather stretch and compress akin classical Hookean springs. Our synthesis is adaptable to helices with different...

Due to high-speed motion blur and challenging illumination, conventional frame-based cameras have encountered an important challenge in object detection tasks. Neuromorphic cameras that output asynchronous visual streams instead of intensity frames, by taking the advantage of high temporal resolution and high dynamic range, have brought a new persp...

G protein-coupled receptors (GPCRs) are currently appreciated to be routed to diverse cellular platforms to generate both G protein-dependent and -independent signals. The latter has been best studied with respect to β-arrestin-associated receptor internalization and trafficking to signaling endosomes for extracellular signal-regulated kinase (ERK)...

The lack of biologically relevant protein structures can hinder rational design of small molecules to target G protein-coupled receptors (GPCRs). While ensemble docking using multiple models of the protein target is a promising technique for structure-based drug discovery, model clustering and selection still need further investigations to achieve...

DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and non-invasive control of chemical processes for a wide range of applications. However, most current photo-responsive DNA switches are limited either by irreversible switching or reversible switching with impractically slow kinetics. Here, we...

Peptide binding to membranes is common and fundamental in biochemistry and biophysics and critical for applications ranging from drug delivery to the treatment of bacterial infections. However, it is largely unclear, from a theoretical point of view, what peptides of different sequences and structures share in the membrane-binding and insertion pro...

Event cameras, offering extremely high temporal resolution and high dynamic range, have brought a new perspective to addressing common object detection challenges (e.g., motion blur and low light). However, how to learn a better spatio-temporal representation and exploit rich temporal cues from asynchronous events for object detection still remains...

In digital cameras, we find a major limitation: the image and video form inherited from a film camera obstructs it from capturing the rapidly changing photonic world. Here, we present vidar, a bit sequence array where each bit represents whether the accumulation of photons has reached a threshold, to record and reconstruct the scene radiance at any...

Neuromorphic vision sensor is a new bio-inspired imaging paradigm emerged in recent years. It uses the asynchronous spike signals instead of the traditional frame-based manner to achieve ultra-high speed sampling. The spike camera was developed recently to perceive fine textures by simulating a small retinal region called fovea. For this new type o...

Neuromorphic vision sensor is a new bio-inspired imaging paradigm that reports asynchronous, continuously per-pixel brightness changes called `events' with high temporal resolution and high dynamic range. So far, the event-based image reconstruction methods are based on artificial neural networks (ANN) or hand-crafted spatiotemporal smoothing techn...

In digital cameras, we find a major limitation: the image and video form inherited from a film camera obstructs it from capturing the rapidly changing photonic world. Here, we present vidar, a bit sequence array where each bit represents whether the accumulation of photons has reached a threshold, to record and reconstruct the scene radiance at any...

We reported a redesign of a physical chemistry laboratory course (CHEM 166) for our chemistry majors at the University of Vermont carried out during the COVID-19 pandemic. We started to teach this course after a curriculum reform, which split an upper-division undergraduate laboratory course into physical and analytical chemistry laboratories. To a...

Spike camera is a new type of bio-inspired vision sensor, each pixel of which perceives the brightness of the scene independently, and finally outputs 3-dimensional spatiotemporal spike streams. To bridge the spike camera and traditional frame-based vision, there is some works to reconstruct spike streams into regular images. However, the low spati...

Short peptides with antimicrobial activity have therapeutic potential for treating bacterial infections. Mechanisms of actions for antimicrobial peptides require binding the biological membrane of their target, which often represents a key mechanistic step. A multitude of data-driven approaches have been developed to predict potential antimicrobial...

Background Interleukin-1-dependent increases in glycolysis promote allergic airways disease in mice and disruption of pyruvate kinase M2 (PKM2) activity is critical herein. Glutathione-S-transferase P (GSTP) has been implicated in asthma pathogenesis and regulates the oxidation state of proteins via S-glutathionylation. We addressed whether GSTP-de...

Structure-based drug design targeting the SARS-CoV-2 virus has been greatly facilitated by available virus-related protein structures. However, there is an urgent need for effective, safe small-molecule drugs to control the spread of the virus and variants. While many efforts are devoted to searching for compounds that selectively target individual...

We synthesized some of the longest unimolecular oligo(p-phenylene ethynylenes) (OPEs), which are fully substituted with electron-withdrawing ester groups. An iterative convergent/divergent (a.k.a. iterative exponential growth – IEG) strategy based on Sonogashira couplings was utilized to access these sequence-defined macromolecules with up to 16 re...

Large-scale conformational transitions in the spike protein S2 domain are required during host cell infection of the SARS-CoV-2 virus. Although conventional molecular dynamics simulations have been extensively used to study therapeutic targets of SARS-CoV-2, it is still challenging to gain molecular insight into the key conformational changes due t...

DNA nanostructures are highly addressable and compatible with biological systems but often require hundreds of unique strands for their assembly. On the other hand, nature can assemble complex structures from identical building blocks by compartmentalizing the process: assembling molecules into sub-components and bringing these together across mult...

This work presents the first transition metal-free synthesis of oxygen-linked aromatic polymers by integrating iterative exponential polymer growth (IEG) with nucleophilic aromatic substitution (SNAr) reactions. Our approach applies methyl sulfones as the leaving groups, which eliminate the need for a transition metal catalyst, while also providing...

Antibiotic resistance is a critical public health problem. Each year ∼2.8 million resistant infections lead to more than 35 000 deaths in the U.S. alone. Antimicrobial peptides (AMPs) show promise in treating resistant infections. However, applications of known AMPs have encountered issues in development, production, and shelf-life. To drive the de...

Event cameras as bioinspired vision sensors have shown great advantages in high dynamic range and high temporal resolution in vision tasks. Asynchronous spikes from event cameras can be depicted using the marked spatiotemporal point processes (MSTPPs). However, how to measure the distance between asynchronous spikes in the MSTPPs still remains an o...

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21986-8

The related neuropeptides PACAP and VIP, and their shared PAC1, VPAC1 and VPAC2 receptors, regulate a large array of physiological activities in the central and peripheral nervous systems. However, the lack of comparative and molecular mechanistic investigations hinder further understanding of their preferred binding selectivity and function. PACAP...

Shape-morphing uses a single actuation source for complex-task-oriented multiple patterns generation, showing a more promising way than reconfiguration, especially for microrobots, where multiple actuators are typically hardly available. Environmental stimuli can induce additional causes of shape transformation to compensate the insufficient space...

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. 24 Through its capacity to sense temperature and other environmental factors, H-NS allows 25 pathogens like Salmonella to adapt their gene expression to their presence inside or outside 26 warm-blooded hosts. To investigate how this sensing mechanism may have ev...

Antibiotic resistance is a critical public health problem. Each year ~2.8 million resistant infections lead to more than 35,000 deaths in the U.S. alone. Anti-microbial peptides (AMPs) show promise in treating resistant infections. But, applications of known AMPs have encountered issues in development, production, and shelf-life. To drive the devel...

By integrating various simulation and experimental techniques, we discovered that antimicrobial peptides (AMPs) may achieve synergy at an optimal concentration and ratio, which can be caused by aggregation of the synergistic peptides. On multiple time and length scales, our studies obtain novel evidence of how peptide coaggregation in solution can...

Antimicrobial peptides (AMPs) are peptides with promising applications for healthcare, veterinary, and agriculture industries. Despite prior success in AMP design using physics- or knowledge-based approaches, there is still a critical need to create new methodologies to design peptides with a low false positive rate and high AMP activity and select...

By integrating various simulation and experimental techniques, we discovered that antimicrobial peptides (AMPs) may achieve synergy at an optimal concentration and ratio, which can be caused by aggregation of the synergistic peptides. On multiple time and length scales, our studies obtain novel evidence of how peptide co-aggregation in solution can...

Selective monofunctionalization of substrates with distant, yet equally reactive functional groups is difficult to achieve, as it requires the second functional group to selectively modulate its reactivity once the first functional group has reacted. We now show that mechanically interlocked catalytic rings can effectively regulate the reactivity o...

It's good to talk: Distant ends in rotaxanes can talk to each other in a reaction-history-dependent manner with the help of a catalytic ring, which shuttles freely between the ends. With this kinetically controlled information transfer mechanism, one end knows whether the other end has reacted, and if yes, with what reagent. The end receiving this...

Selective catalysis at the molecular level represents a cornerstone of chemical synthesis. However, it still remains an open question how to elevate tunable catalysis to larger length scales to functionalize whole polymer chains in a selective manner. We now report a hydrazone-linked tetrahedron with wide openings, which acts as a catalyst to size-...

Recent advances in computer hardware and software, particularly the availability of machine learning (ML) libraries, allow the introduction of data-based topics such as ML into the biophysical curriculum for undergraduate and graduate levels. However, there are many practical challenges of teaching ML to advanced level students in biophysics majors...

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression, and hence toxicity and biological responses, to their presence inside or outside warm-blooded hosts. To investigate h...

Temporal cues embedded in videos provide important clues for person Re-Identification (ReID). To efficiently exploit temporal cues with a compact neural network, this work proposes a novel 3D convolution layer called Multi-scale 3D (M3D) convolution layer. The M3D layer is easy to implement and could be inserted into traditional 2D convolution netw...

Magnetic microrobots have been developed for various biomedical applications. Magnetic motion on substrate surface is required for indirect magnetic manipulation and assembly of non-magnetic targets, where the drag force and friction force presents as the main resistance for actuation. Inspired by human walking, a novel magnetic microrobot with two...

Objective: Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice. Approach and Results: We adapted our protocol for biliary cholesterol secretion with published methods for measuring transintestinal cholesterol elimination. Bile was diverted and biliary lipid secretion maintained by infus...

This paper proposes the Global-Local Temporal Representation (GLTR) to exploit the multi-scale temporal cues in video sequences for video person Re-Identification (ReID). GLTR is constructed by first modeling the short-term temporal cues among adjacent frames, then capturing the long-term relations among inconsecutive frames. Specifically, the shor...

While virtual reality (VR) is emerging as an interactive tool for chemical education, its application and assessment for chemical education are still limited. Thus, an educational VR activity based on interactive molecular dynamics in virtual reality (iMD-VR), which allows for real-time, immersive interactions with a dynamic molecular world, was no...

This paper proposes a two-stream convolution network to extract spatial and temporal cues for video based person ReIdentification (ReID). A temporal stream in this network is constructed by inserting several Multi-scale 3D (M3D) convolution layers into a 2D CNN network. The resulting M3D convolution network introduces a fraction of parameters into...

The large pose variations and misalignment errors exhibited by person images significantly increase the difficulty of person Re-Identification (ReID). Existing works commonly apply extra operations like pose estimation, part segmentation, etc., to alleviate those issues and improve the robustness of pedestrian representations. While boosting the Re...

The pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor (PAC1R, ADCYAP1R1) is a member of the vasoactive intestinal peptide (VIP)/secretin/glucagon family of G protein-coupled receptors (GPCRs). PAC1R has been shown to play crucial roles in the central and peripheral nervous systems. The activation of PAC1R initiates...

Shapeshifters, in common mythology, are entities that can undergo multiple physical transformations. As our understanding of G protein-coupled receptors (GPCRs) has accelerated and been refined over the last two decades, we now understand that GPCRs are not static proteins, but rather dynamic structures capable of moving from one posture to the nex...

Designed microtissues that replicate highly ordered three-dimensional (3D) multicellular in vivo structures have shown huge potential in biomedical research and drug discovery. Through microencapsulation and microfluidic techniques, cell-laden microcapsules have been widely used as pathological or pharmacological models. However, most conventional...

Magnetic micromachines as wireless end-effectors have been widely applied for drug discovery and regenerative medicine. Yet, the magnetic assembly of arbitrarily shaped cellular microstructures with high efficiency and flexibility still remains a big challenge. Here, a novel clamp-shape micromachine using magnetic nanoparticles was developed for th...

Class B G protein-coupled receptors (GPCRs) comprise a family of 15 peptide-binding members, which are crucial targets for endocrine, metabolic, and stress-related disorders. While their protein structures and dynamics remain largely unclear, computer modeling and simulations represent a promising means to help solve such puzzles. Herein, we presen...

Modeling peptide assembly from monomers on large time and length scales is often intractable at the atomistic resolution. To address this challenge, we present a new approach which integrates coarse-grained (CG), mixed-resolution, and all atom (AA) modeling in a single simulation. We simulate the initial encounter stage with the CG model, while the...

As an environment-dependent pleiotropic gene regulator in Gram-negative bacteria, the H-NS protein is crucial for adaptation and toxicity control of human pathogens such as Salmonella, Vibrio cholerae or enterohaemorrhagic Escherichia coli. Changes in temperature affect the capacity of H-NS to form multimers that condense DNA and restrict gene expr...

Molecular crane arms deliver nitronium ions to specific locations of concave, polyaromatic systems in a stereoselective manner. In their Communication (DOI: 10.1002/anie.201811517), S. T. Schneebeli and co‐workers now describe how the first enantioselective aromatic nitration reactions have been achieved with the help of such crane arms. These find...

Molekulare Kranausleger bringen in stereoselektiver Weise Nitroniumionen zu spezifischen Stellen konkaver polyaromatischer Systeme. S. T. Schneebeli und Mitarbeiter beschreiben in ihrer Zuschrift (DOI: 10.1002/ange.201811517), wie die ersten enantioselektiven Nitrierungsreaktionen mithilfe solcher Kranausleger erreicht wurden. Die Ergebnisse stelle...

Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality‐assisted synthesis (CAS). Reported here is an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, and it provides an enantioselective synthesis of a C3v‐symmetric tribenzotriquinacene (TBTQ). These axially‐chiral structur...

Cells use membrane proteins as gatekeepers to transport ions and molecules, catalyze reactions, relay signals, and interact with other cells. DNA nanostructures with lipidic anchors are promising as membrane protein mimics because of their high tuneability. However, the design features specifying DNA nanostructure’s functions in lipid membranes are...

This paper proposes a two-stream convolution network to extract spatial and temporal cues for video based person Re-Identification (ReID). A temporal stream in this network is constructed by inserting several Multi-scale 3D (M3D) convolution layers into a 2D CNN network. The resulting M3D convolution network introduces a fraction of parameters into...

Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality‐assisted synthesis (CAS). We now report an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, which provides an enantioselective synthesis of a C3v‐symmetric tribenzotriquinacene (TBTQ). These axially‐chiral structures a...

The incorporation of synthetic molecules as corner units in DNA structures has been of interest over the last two decades. In this work, we present a facile method for generating branched small molecule‐DNA hybrids with controllable valency, different sequences, and directionalities (5′–3′) using a “printing” process from a simple 3‐way junction st...

The Src kinase controls aspects of cell biology and its activity is regulated by intramolecular structural changes induced by protein interactions and tyrosine phosphorylation. Recent studies indicate that Src is additionally regulated by redox-dependent mechanisms, involving oxidative modification(s) of cysteines within the Src protein, although t...