Carboxymethylcellulose sodium-derived carbon aerogels for solar-driven water purification.

Recycling polluted water via different techniques has become one of the most feasible ways to solve the freshwater crisis. We describe a novel method to prepare reusable and efficient photothermal energy conversion materials for water purification. Using crosslinked xerogels as precursor, the porous and interconnected carboxymethylcellulose sodium-derived carbon aerogels (abbreviated as CCAs) with good hydrophilic performance and strong light absorption capability are firstly fabricated through pyrolysis. Photothermal measurement results show that CCA15 exhibit excellent solar steam generation rate of 2.31 kg m-2 h-1 with high light-to-vapor conversion efficiency of 95.9% under 1 sun illumination. In addition, the feasible application of CCA15 for efficient water purification under 1 sun irradiation using a homemade water treatment device has been demonstrated successfully. The as-prepared CCAs shown in here can be a continuable solution to mitigate the global freshwater crisis.

Human transferrin receptor can mediate SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.

High-order sensory processing nanocircuit based on coupled VO2 oscillators.

Conventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics.

Pharmacokinetics of toltrazuril and its metabolite, toltrazuril sulfone, in suckling piglets following oral and intramuscular administrations.

Toltrazuril (TZR) is currently the only registered chemotherapeutic drug in the European Union for the treatment of Cystoisospora suis. This study investigated the comparative pharmacokinetics and tissue concentration-time profiles of TZR and its active metabolite, toltrazuril sulfone (TZR-SO2 ), after oral (per os, p.o.) and intramuscular (i.m.) administration to suckling piglets. Following a single administration of TZR orally at 50 mg/piglet or intramuscularly at 45 mg/piglet, higher concentrations of TZR and TZR-SO2 were observed in all three investigated tissues after p.o. administration. The mean TZR concentration in serum peaked at 14 µg/mL (34.03 h) and 5.36 µg/mL (120 h), while TZR-SO2 peaked at 14.12 µg/mL (246 h) and 9.92 µg/mL (330 h) after p.o. and i.m. administration, respectively. TZR was undetectable in the liver after p.o. administration (18 days) and in the jejunum (24 days) after i.m. injection, while TZR-SO2 was still detectable in all three tissues after 36 days regardless of administration routes. This study showed that p.o. formulation exhibited faster absorption and higher serum/tissue TZR/TZR-SO2 concentrations than i.m. formulation. Both formulations generated sufficient therapeutic concentrations in the serum and jejunum, and sustained enough time to protect against Cystoisospora suis infection in the piglets.

BrainPy, a flexible, integrative, efficient, and extensible framework for general-purpose brain dynamics programming.

Elucidating the intricate neural mechanisms underlying brain functions requires integrative brain dynamics modeling. To facilitate this process, it is crucial to develop a general-purpose programming framework that allows users to freely define neural models across multiple scales, efficiently simulate, train, and analyze model dynamics, and conveniently incorporate new modeling approaches. In response to this need, we present BrainPy. BrainPy leverages the advanced just-in-time (JIT) compilation capabilities of JAX and XLA to provide a powerful infrastructure tailored for brain dynamics programming. It offers an integrated platform for building, simulating, training, and analyzing brain dynamics models. Models defined in BrainPy can be JIT compiled into binary instructions for various devices, including Central Processing Unit, Graphics Processing Unit, and Tensor Processing Unit, which ensures high-running performance comparable to native C or CUDA. Additionally, BrainPy features an extensible architecture that allows for easy expansion of new infrastructure, utilities, and machine-learning approaches. This flexibility enables researchers to incorporate cutting-edge techniques and adapt the framework to their specific needs.

Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 µg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from the Poecilobdella manillensis Leech.

When Poecilobdella manillensis attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of P. manillensis, but the substance that produces the paralyzing effect in P. manillensis is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of P. manillensis. This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activity, but had no effect on FXa, trypsin, or thrombin activity. Furthermore, poeciguamerin exhibited analgesic activity in the foot-licking and tail-withdrawal mouse models and anticoagulant activity in the FeCl3-induced carotid artery thrombosis mouse model. In this study, poeciguamerin was found to be a promising elastase inhibitor with potent analgesic and antithrombotic activity for the inhibition of pain and thrombosis after surgery or in inflammatory conditions.

Multifunctional 3D magnetic carbon aerogel for adsorption separation and highly sensitive SERS detection of malachite green.

This work presents a novel strategy for the synthesis of a recyclable aerogel and its multifunctional application as effective adsorption material for organic pollutants and as a high-quality SERS substrate for on-site detection measurement. Silver nanoparticles (Ag NPs) were uniformly dispersed and adsorbed on the surface of an Fe3C-loaded carbon aerogel, resulting in the formation of a three-dimensional Ag-Fe3C-MCA (magnetic carbon aerogel) composite. The substrate preparation led to Ag-Fe3C-MCA with a mesoporous structure for high adsorption capacity, together with magnetic properties for easy separation capability. The Ag-Fe3C-MCA composite demonstrated an efficient removal ability for malachite green (MG), with an adsorption capacity of 296.7 mg g-1. Moreover, Ag-Fe3C-MCA composite provided ultrasensitive surface-enhanced Raman scattering detection for MG molecules, obtaining a limit of detection (LOD) of 3 × 10-10 M. Aquaculture water samples with spiked MG concentrations were used to simulate practical scenarios. The Ag-Fe3C-MCA presented has a significant potential for the removal of hazardous residues in wastewater, together with an efficient and sensitive method of quantification, all on the same substrate.

Blood-brain barrier injury and neuroinflammation induced by SARS-CoV-2 in a lung-brain microphysiological system.

In some patients, COVID-19 can trigger neurological symptoms with unclear pathogenesis. Here we describe a microphysiological system integrating alveolus and blood-brain barrier (BBB) tissue chips that recapitulates neuropathogenesis associated with infection by SARS-CoV-2. Direct exposure of the BBB chip to SARS-CoV-2 caused mild changes to the BBB, and infusion of medium from the infected alveolus chip led to more severe injuries on the BBB chip, including endothelial dysfunction, pericyte detachment and neuroinflammation. Transcriptomic analyses indicated downregulated expression of the actin cytoskeleton in brain endothelium and upregulated expression of inflammatory genes in glial cells. We also observed early cerebral microvascular damage following lung infection with a low viral load in the brains of transgenic mice expressing human angiotensin-converting enzyme 2. Our findings suggest that systemic inflammation is probably contributing to neuropathogenesis following SARS-CoV-2 infection, and that direct viral neural invasion might not be a prerequisite for this neuropathogenesis. Lung-brain microphysiological systems should aid the further understanding of the systemic effects and neurological complications of viral infection.

Design, Synthesis, and Biological Evaluation of Marine Lissodendrins B Analogues as Modulators of ABCB1-Mediated Multidrug Resistance.

Multidrug resistance (MDR) caused by ATP-Binding Cassette Subfamily B Member 1 (ABCB1, P-glycoprotein, P-gp) is a major barrier for the success of chemotherapy in clinics. In this study, we designed and synthesized a total of 19 Lissodendrins B analogues and tested their ABCB1-mediated MDR reversal activity in doxorubicin (DOX)-resistant K562/ADR and MCF-7/ADR cells. Among all derivatives, compounds D1, D2, and D4 with a dimethoxy-substituted tetrahydroisoquinoline fragment possessed potent synergistic effects with DOX and reversed ABCB1-mediated drug resistance. Notably, the most potent compound D1 merits multiple activities, including low cytotoxicity, the strongest synergistic effect, and effectively reversing ABCB1-mediated drug resistance of K562/ADR (RF = 1845.76) and MCF-7/ADR cells (RF = 207.86) to DOX. As a reference substance, compound D1 allows for additional mechanistic studies on ABCB1 inhibition. The synergistic mechanisms were mainly related to the increased intracellular accumulation of DOX via inhibiting the efflux function of ABCB1 rather than from affecting the expression level of ABCB1. These studies suggest that compound D1 and its derivatives might be potential MDR reversal agents acting as ABCB1 inhibitors in clinical therapeutics and provide insight into a design strategy for the development of ABCB1 inhibitors.

Peptide Stapling through Site-Directed Conjugation of Triazine Moieties to the Tyrosine Residues of a Peptide.

Peptide stapling is a strategy for improving the biological properties of peptides. Herein, we report a novel method for stapling peptides that utilizes bifunctional triazine moieties for two-component conjugation to the phenolic hydroxyl groups of tyrosine, which enables efficient stapling of unprotected peptides. In addition, we applied this strategy to the RGD peptide that can target integrins and demonstrated that the stapled RGD peptide had significantly improved plasma stability and integrin-targeting ability.

Triazine-pyridine chemistry for protein labelling on tyrosine.

Herein, we discover the new reactivity of the 1,3,5-triazine moiety reacting with a phenol group and report the development of biocompatible and catalyst-free triazine-pyridine chemistry (TPC) for tyrosine labelling under physiological conditions and profiling in the whole proteome. TPC exhibited high tyrosine chemoselectivity in biological systems after cysteine blocking, displayed potential in tyrosine-guided protein labelling, and had bio-compatibility in live cells.

Using Digital Technology to Design a Simple Interactive System for Nostalgic Gaming to Promote the Health of Slightly Disabled Elderly People.

An interactive digital gaming system with simple tangible interfaces is proposed for use by slightly disabled elderly people to promote their health and enjoyment of playful aging. The system simulates a rice threshing machine with nostalgic and entertaining functions expected to bring better life quality to older adults. Initially, pieces of literature were reviewed to derive relevant design principles. A prototype system was constructed accordingly and refined according to the invited older users' comments. The refined system was performed subsequently by slightly disabled elderly people, followed by a questionnaire survey conducted to collect their opinions. The opinion data were analyzed statistically by SPSS and AMOS to be reliable and valid. In addition, interviews were conducted with the users and experts were invited to collect comments on the system's usability, which were then evaluated to reveal several findings about the system's effectiveness: (1) digital products related to life experiences are more acceptable to slightly disabled elderly people, promoting their willingness to play games to achieve active aging; (2) simple system interfaces requiring no complicated limb functions are appropriate for the slightly disabled elderly people; and (3) digital gaming has the effects of training slightly disabled elderly peoples' cognitive and motor abilities as well as strengthening their body and mind.

Analysis of the Neuron Dynamics in Thalamic Reticular Nucleus by a Reduced Model.

Strategically located between the thalamus and the cortex, the inhibitory thalamic reticular nucleus (TRN) is a hub to regulate selective attention during wakefulness and control the thalamic and cortical oscillations during sleep. A salient feature of TRN neurons contributing to these functions is their characteristic firing patterns, ranging in a continuum from tonic spiking to bursting spiking. However, the dynamical mechanism under these firing behaviors is not well understood. In this study, by applying a reduction method to a full conductance-based neuron model, we construct a reduced three-variable model to investigate the dynamics of TRN neurons. We show that the reduced model can effectively reproduce the spiking patterns of TRN neurons as observed in vivo and in vitro experiments, and meanwhile allow us to perform bifurcation analysis of the spiking dynamics. Specifically, we demonstrate that the rebound bursting of a TRN neuron is a type of "fold/homo-clinic" bifurcation, and the tonic spiking is the fold cycle bifurcation. Further one-parameter bifurcation analysis reveals that the transition between these discharge patterns can be controlled by the external current. We expect that this reduced neuron model will help us to further study the complicated dynamics and functions of the TRN network.

Preparation and characterization of carboxymethylcellulose based citric acid cross-linked magnetic aerogel as an efficient dye adsorbent.

A low-cost, collectable, and efficient material is essential for adsorbing water pollution, such as dyes and heavy metal ions pollution. In this work, we proposed a novel strategy for the preparation of an efficient and collectable magnetic aerogel as adsorbent for dye. The magnetic aerogels were prepared from sodium carboxymethylcellulose (CMC) hydrogel using citric acid (CA) as the crosslinker, followed by vacuum freeze-drying technique to obtain aerogels. The effects of magnetic Fe3O4 nanoparticle contents on the adsorption properties of the aerogels were investigated. The results show that the as-prepared magnetic composite aerogels exhibit porous structure and display good adsorption and collectable performance for methylene blue (MB) in water with the removal rate of 97.5% in 6 h. The maximum compress strength and absorption capacity of the magnetic aerogel with 1 wt% Fe3O4 nanoparticle loading for MB is 0.13 MPa and 83.6 mg/g, respectively. Aerogels with Fe3O4 nanoparticles exhibited magnetism which enables the aerogels to easily collect. This excellent structure stability and collectability guarantees long-term integrity and floatability of the magnetic aerogels in water.

RNF220 mediates K63-linked polyubiquitination of STAT1 and promotes host defense.

STAT1 is a master regulator that orchestrates type 1 and 2 interferon (IFN)-induced IFN-stimulated gene (ISG) expression. The mechanisms by which STAT1 is phosphorylated and activated upon IFN signaling remain elusive. Our work demonstrated that ubiquitination of STAT1 mediated by the E3 ligase RNF220 contributed significantly to STAT1 activation and innate immune responses. Rnf220 gene deficiency resulted in the downregulation of IFN signaling and decreased expression of ISGs in response to type 1 and 2 IFNs stimulation and Acinetobacter baumannii and HSV-1 infection. Mechanistically, RNF220 interacted with STAT1 and mediated the K63-linked polyubiquitination of STAT1 at residue K110, which promoted the interaction between STAT1 and the kinase JAK1. The expression of RNF220 was induced by pathogenic infection and IFN signaling. RNF220 promoted STAT1 ubiquitination and phosphorylation through a positive feedback loop. RNF220 haploinsufficiency impaired IFN signaling, and RNF220-defective mice were more susceptible to A. baumannii and HSV-1 infection than WT mice. Our work offers novel insights into the mechanisms of STAT1 modulation and provides potential therapeutic targets against bacterial and viral infection and inflammatory diseases.

SiO2 prompts host defense against Acinetobacter baumannii infection by mTORC1 activation.

Host-pathogen interactions in the setting of chronic pulmonary inflammation remain unclear, and the occurrence of pneumonia is increased in patients with chronic obstructive pulmonary disease who use immunosuppressive drugs. We performed Acinetobacter baumannii infection in mice with chronic pulmonary inflammation after intranasal administration of SiO2 and found SiO2 treatment increased host defense against A. baumannii infection. Innate immune responses initiated by NF-κB, type 1 interferon, NLRP3 and AIM2 inflammasomes were dispensable for SiO2-mediated host defense. SiO2 treatment activated the mTORC1 signaling, and mTORC1 was crucial for host defense against A. baumannii infection. Our study highlights the protective role of mTORC1 signaling in host defense against bacterial infection, offers novel insights into understanding the mechanisms of immunosuppressive drug-related pneumonia, and provides potential host-directed therapeutics to treat bacterial infections.

A Neural Network Model With Gap Junction for Topological Detection.

Visual information processing in the brain goes from global to local. A large volume of experimental studies has suggested that among global features, the brain perceives the topological information of an image first. Here, we propose a neural network model to elucidate the underlying computational mechanism. The model consists of two parts. The first part is a neural network in which neurons are coupled through gap junctions, mimicking the neural circuit formed by alpha ganglion cells in the retina. Gap junction plays a key role in the model, which, on one hand, facilitates the synchronized firing of a neuron group covering a connected region of an image, and on the other hand, staggers the firing moments of different neuron groups covering disconnected regions of the image. These two properties endow the network with the capacity of detecting the connectivity and closure of images. The second part of the model is a read-out neuron, which reads out the topological information that has been converted into the number of synchronized firings in the retina network. Our model provides a simple yet effective mechanism for the neural system to detect the topological information of images in ultra-speed.

HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection.

The mechanism by which inflammasome activation is modulated remains unclear. In this study, we identified an AIM2-interacting protein, the E3 ubiquitin ligase HUWE1, which was also found to interact with NLRP3 and NLRC4 through the HIN domain of AIM2 and the NACHT domains of NLRP3 and NLRC4. The BH3 domain of HUWE1 was important for its interaction with NLRP3, AIM2, and NLRC4. Caspase-1 maturation, IL-1ß release, and pyroptosis were reduced in Huwe1-deficient bone marrow-derived macrophages (BMDMs) compared with WT BMDMs in response to stimuli to induce NLRP3, NLRC4, and AIM2 inflammasome activation. Furthermore, the activation of NLRP3, NLRC4, and AIM2 inflammasomes in both mouse and human cells was remarkably reduced by treatment with the HUWE1 inhibitor BI8622. HUWE1 mediated the K27-linked polyubiquitination of AIM2, NLRP3, and NLRC4, which led to inflammasome assembly, ASC speck formation, and sustained caspase-1 activation. Huwe1-deficient mice had an increased bacterial burden and decreased caspase-1 activation and IL-1ß production upon Salmonella, Francisella, or Acinetobacter baumannii infection. Our study provides insights into the mechanisms of inflammasome activation as well as a potential therapeutic target against bacterial infection.