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Photothermal therapy (PTT) shows promise in cancer treatments due to its good spatiotemporal selectivity and minimal invasiveness. However, PTT has some problems such as excessive heat damage to normal tissues, tumor thermo-resistance caused by heat shock proteins (HSPs), and limited efficacy of monotherapy. Here, we construct a patch named “partitioned microneedles” (PMN-SNAP/CuS), which separates the “catalyst” bovine serum albumin-based copper sulfide nanoparticles (CuS@BSA NPs) and the “reactant” S-nitroso-N-acetylpenicillamine (SNAP) into different regions of microneedles, for enhancing mild PTT (mPTT) of melanoma. PMN-SNAP/CuS showed an excellent photothermal effect, Fenton-like catalytic activity, and nitric oxide (NO) generation ability. The combination of NO and reactive oxygen species (ROS) produced by PMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source and enhanced the efficacy of mPTT. Both in vitro and in vivo results proved that PMN-SNAP/CuS significantly enhanced the inhibition of melanoma under 808 nm laser irradiation. In conclusion, our partitioned microneedle strategy based on the combination of enhanced mPTT and gas therapy (GT) provides a promising approach to enhance the therapeutic effect on melanoma.

Hydrogels are promising materials for wound protection, but in wet, or underwater environments, the hydration layer and swelling of hydrogels can seriously reduce adhesion and limit their application. In this study, inspired by the structural characteristics of strong barnacle wet adhesion and combined with solvent exchange, a robust wet adhesive hydrogel (CP-Gel) based on chitosan and 2-phenoxyethyl acrylate was obtained by breaking the hydration layer and resisting swelling. As a result, CP-Gel exhibited strong wet adhesion to various interfaces even underwater, adapted to joint movement and skin twisting, resisted sustained rushing water, and sealed damaged organs. More importantly, on-demand detachment and controllable adhesion were achieved by promoting swelling. In addition, CP-Gel with good biosafety significantly promotes seawater-immersed wound healing and is promising for use in water-contact wound care, organ sealing, and marine emergency rescue.

Small extracellular vesicles (sEVs) hold considerable promise for drug delivery due to their natural origin and inherent qualities. However, their clinical application is impeded by two main challenges: low yield and potential side effects. Therefore, it is crucial to obtain substantial quantities of sEVs that adhere to rigorous biosafety standards to ensure successful translation into clinical practice. To address this need, we propose exploring optimized methods for sourcing and separating sEVs, taking inspiration from clinical blood transfusion. In particular, we have identified blood sEVs as a viable alternative and developed a novel separation technique for their isolation. Our approach involves incubating dopamine solution with serum, resulting in the formation of polydopamine (PDA) nanoparticles on the surface of blood sEVs. These nanoparticles have minimal impact on blood sEVs, facilitating their easy separation under standard centrifugal conditions with high purity. This innovative technique enables the development of nanocarriers using blood sEVs with efficient drug-loading capabilities and enhanced pharmacokinetics. Additionally, the incorporation of PDA nanoparticles imparts a photothermal effect to the nanomedicines, enabling the integration of chemotherapy and photothermal therapy. Moreover, the photothermal effect holds the potential to facilitate the membrane fusion of sEVs and cells. In summary, our straightforward surface functionalization technique utilizing PDA effectively isolates blood sEVs and enables chemo-thermal tumor therapy. This approach significantly enhances the feasibility of translating sEV-based nanomedicines into clinical applications.

The energy conversion efficiency of a triboelectric nanogenerator (TENG) is severely limited by the charge density of triboelectric materials, while drastic and unavoidable charge decay happens during contact due to the insufficient charge retention capacity of positive triboelectric materials. Here, elaborately synthesized acid-ion-doped pyridine-based polybenzimidazole processing with strong charge retention capability is demonstrated to couple with negatively corona-polarized electrets. As illustrated by thermal stimulation and an ion mass spectrometer, the formation of acid-ion chimerism processes high activation energy for stored charges, and the selective anion migration can compensate the escape of polarized charge. Accordingly, the charge density can reach up to 596 μC m–2and the charge retention rate reaches 49.7%, which is so far the highest intrinsic charge density obtained in the open air. Thus, the ionic chimerism strategy provides an effective way to suppress the charge escaping in the open air and gives a great expandable avenue for the material challenges of TENG’s practical deployment.

In recent years, the full-touch human–machine interface (HMI) mode has been widely used in vehicles built by Tesla. This interaction mode replaces the conventional physical interaction modality with a screen, and it has a good sense of technological experience. However, it is unclear whether this mode will make the driver's lateral control more challenging than the conventional mode (CM). To investigate this issue, two most common secondary tasks were designed: dialing and navigation entry tasks and real-world road experiments were conducted using two instrumented vehicles. The vehicle operating parameters and the driver manual data were collected in different modes, respectively. Interestingly, the opposite results were found regarding the effect of the full-touch mode (FTM) on the driver's lateral control ability in different secondary tasks. Compared with the CM, the lateral control ability decreased less during the dialing task relative to the baseline driving in the FTM, while the lateral control ability decreased more in the FTM during the navigation entry task. In addition, drivers’ lateral control decreased further as task difficulty and driving speed increased regardless of mode. This study provides a theoretical basis for the development of laws and regulations regarding full-touch HMI mode.

A novel photochemical difluoromethylation of quinoxalin-2(1H)-ones under catalyst-free conditions was achieved with difluoroacetic anhydride and pyridine N-oxide. The green and mild reaction conditions as well as readily attainable difluoroacetic anhydride provide a useful protocol to prepare C3-difluoromethylated quinoxalin-2(1H)-ones.

Metal–organic frameworks (MOFs) are network-like frameworks composed of transition metals and organic ligands containing oxygen or nitrogen. Because of its highly controllable composition and ordered porous structure, it has broad application prospects in the field of material synthesis. In this work, Zn4(PYDC)4(DMF)2∙3DMF (ZPD) was synthesized via a hydrothermal method. Self-doped nitrogen porous carbon ZPDC-T was then prepared by one-step carbonization. The results show that the self-doped nitrogen porous carbon ZPDC-850 has a micro/mesoporous structure with a specific surface area of 1520 m2g−1and a nitrogen content of 6.47%. When a current density is 1.0 A g−1, its specific capacitance is 265.1 F g−1. After 5000 times of constant current charging and discharging, the capacitance retention rate was 79.2%. Thus, self-doped nitrogen porous carbon ZPDC-850 exhibits excellent electrochemical properties and good cyclic stability. Therefore, the self-doped nitrogen porous carbon derived from MOFs can be a promising electrode material for supercapacitors.

This study investigates the open-circuit fault diagnosis problem in the inverter of the inductive power transfer (IPT) systems. A novel rough-set-theory-based (RST-based) method is proposed to diagnose and locate the open-circuit faults for the first several attempts. First, the system structure of the IPT systems and the operation principle of the inverter are described. Then, by using the proposed rough-sets-theory-based method, a minimum set of necessary variables is obtained from some measurable parameters, which are used to generate the diagnostic rules. Implemented through a set of basic logic units, these rules result in a digital logic circuit for diagnosing inverter open-circuit faults in IPT systems. It should be emphasized that the proposed method not only enables fault diagnosis but also facilitates fault localization. Importantly, it is not constrained by inverter parameters or types. Finally, the simulation and experiment examples are carried out and the results show the effectiveness of the proposed methods.

Let Abe an infinite dimensional simple unital stably finite C*-algebra and Bbe a large subalgebra of A. In this paper, we show that Bhas local weak comparison if Ahas local weak comparison, and Ahas local weak comparison if M2(B)has local weak comparison. As a consequence, we are able to prove that Ahas weak comparison if and only if Bhas weak comparison.

The dynamics of the teleconnection between the Indian Ocean Dipole (IOD) in the tropical Indian Ocean and El Niño-Southern Oscillation (ENSO) in the tropical Pacific Ocean at the time lag of one year are investigated using lag correlations between the oceanic anomalies in the southeastern tropical Indian Ocean in fall and those in the tropical Indo-Pacific Ocean in the following winter-fall seasons in the observations and in high-resolution global ocean model simulations. The lag correlations suggest that the IOD-forced interannual transport anomalies of the Indonesian Throughflow generate thermocline anomalies in the western equatorial Pacific Ocean, which propagate to the east to induce ocean-atmosphere coupled evolution leading to ENSO. In comparison, lag correlations between the surface zonal wind anomalies over the western equatorial Pacific in fall and the Indo-Pacific oceanic anomalies at time lags longer than a season are all insignificant, suggesting the short memory of the atmospheric bridge. A linear continuously stratified model is used to investigate the dynamics of the oceanic connection between the tropical Indian and Pacific Oceans. The experiments suggest that interannual equatorial Kelvin waves from the Indian Ocean propagate into the equatorial Pacific Ocean through the Makassar Strait and the eastern Indonesian seas with a penetration rate of about 10%–15% depending on the baroclinic modes. The IOD-ENSO teleconnection is found to get stronger in the past century or so. Diagnoses of the CMIP5 model simulations suggest that the increased teleconnection is associated with decreased Indonesian Throughflow transports in the recent century, which is found sensitive to the global warming forcing.

Neuronal cell damage is a major cause of cognitive impairment in Alzheimer’s disease (AD). Multiple factors, such as amyloid deposition, tau hyperphosphorylation, and neuroinflammation, can lead to neuronal cell damage. Therefore, the development of multi-target drugs with broad neuroprotective effects may be an effective strategy for the treatment of AD. Natural products have become an important source of drug discovery because of their good pharmacological activity, multiple targets, and low toxicity. In this study, we screened a natural compound library and found that the fat-soluble sesquiterpene natural compound isolinderalactone (Iso) extracted from the dried root pieces of Lindera aggregatahad the ability to alleviate cellular damage induced by β-amyloid-1–42 (Aβ1–42). The role and mechanism of Iso in AD have not yet been reported. Herein, we demonstrated that Iso significantly reduced the level of apoptosis in PC12 cells. Besides, Iso treatment reduced amyloid deposition, neuron apoptosis, and neuroinflammation, ultimately improving the cognitive dysfunction of APP/PS1 (APPswe/PSEN 1dE9) mice. Notably, Iso-10 mg/kg showed superior improved effects in APP/PS1 mice compared with the positive control drug donepezil-5 mg/kg. Mechanistically, the results of RNA sequencing combined with Western blots showed that Iso exerted its therapeutic effect by inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. Taken together, our findings suggest that Iso is a potential drug candidate for the treatment of AD.

• The C-BiOCl/Bi 2 S 3 (C-BOC/BS) composites are successfully prepared. • C-BOC/BS show good photoelectrochemical (PEC) and photocatalytic (PC) properties. • The optimized 5C-BOC/5BS composite is used as a PEC sensor for Cr(VI) detection. • Efficient Cr(VI) removal is achieved via adsorption and PC reduction by 5C-BOC/5BS. Novel C-BiOCl/Bi 2 S 3 composites are prepared by hydrothermal C doping in BiOCl and in-situ growth of Bi 2 S 3 on C-BiOCl. Compared with BiOCl, C-BiOCl has a larger exposed surface area and can effectively absorb visible light. The construction of a heterojunction in C-BiOCl/Bi 2 S 3 further promotes the separation and transfer of photogenerated carriers. With improved photoelectric properties, the optimized 5C-BiOCl/5Bi 2 S 3 is applied as a dual-functional composite for photoelectrochemical (PEC) detection and photocatalytic (PC) reduction of Cr(VI). The 5C-BiOCl/5Bi 2 S 3 shows a linear range of 0.02–80 μM for PEC cathodic detection of Cr(VI) with a detection limit of 0.01628 μM. Additionally, 99.5% of Cr(VI) can be removed via absorption and PC reduction by 5C-BiOCl/5Bi 2 S 3 , with the reduction rate constant (k) 336 times higher than that of BiOCl. [ABSTRACT FROM AUTHOR]

The encapsulation of various guest molecules into the pores of metal–organic frameworks (MOFs) to form hybrid materials has attracted significant attention due to their unique spatial distribution and certain preferential geometry of the guests inside the MOFs. This arrangement often results in the guests exhibiting unique physical and chemical properties due to their intramolecular interactions with the host. In this article, five viologen derivatives were introduced as guests in a Zn-MOF with different benzene ring lengths, resulting in the formation of host–guest three-dimensional (3D) MOFs. The five compounds exhibited guest-dependent emission wavelength, color, and excellent photochromic behavior upon ultraviolet (UV) light radiation due to the distinct electronic transfer and π···π stacking interactions between the viologen guests and the host framework. This study provides a host–guest strategy for designing color-tunable luminescent and highly sensitive photochromic materials.

In recent years, neuromorphic processors are widely used in many scenarios, showing extreme energy efficiency over traditional architectures. However, almost all existing neuromorphic hardware are following the heterogeneous computing methodology without Instruction Set Architecture (ISA), leading to inflexibility in programming. In this paper, we first propose a RISC-V Neuromorphic Extension (RVNE) to enable fine-grained and flexible homogeneous programming for neuromorphic algorithms while utilizing SNN sparsity from different levels of granularity and computing flows. Based on RVNE, we next implement a neuromorphic micro-architecture that is tightly coupled to the CPU pipeline to accelerate neuromorphic computing. To demonstrate the proposed homogeneous neuromorphic architecture, we implement a prototype processor called NeuroRVcore based on RISC-V ISA and an open-source RISC-V core. The evaluation results show that RVNE achieves a 2.8 × −4.3 × reduction in code density compared with the general-purpose ISAs. Compared with the state-of-the-art neuromorphic processor, the proposed homogeneous computing reduces energy consumption by 3.4%−22.5% while enabling fine-grained and flexible homogeneous programming.

Video-based human-object interaction recognition is a challenging task since the state of objects as well as their correlations change constantly in the video. Existing methods mainly use 3DCNN or use separate components (e.g., GCN + RNN) to model the spatial correlation or the temporal correlation respectively, but ignore modeling spatio-temporal correlations simultaneously and long-term temporal dynamics of objects. In this paper, we propose a novel model, named Spatio-Temporal Interaction Graph Parsing Networks (STIGPN), for human-object interaction recognition in videos. STIGPN captures both spatial and temporal correlations simultaneously and thus can capture intra-frame and inter-frame dependencies efficiently and effectively. To model long-term temporal dynamics of objects, we introduce spatio-temporal feature enhancement, which can improve the detection of the salient human-object interaction pairs. We explore three types of spatio-temporal graph convolutions to simultaneously capture the spatio-temporal correlations and assess their effectiveness as the basic building block of STIGPN. Extensive experiments on CAD-120, Something-Else and Charades datasets show that our proposed solution leads to competitive results compared with the state-of-the-art methods. Code for STIGPN is available at: https://github.com/NingWang2049/STIGPN2

Background: Herpes simplex keratitis (HSK) is the most common but serious infectious keratitis with high recurrence. It is predominantly caused by herpes simplex virus type 1 (HSV-1). The spread mechanism of HSV-1 in HSK is not entirely clear. Multiple publications indicate that exosomes participate in the intercellular communication process during viral infections. However, there is rare evidence that HSV-1 spreads in HSK by exosomal pathway. This study aims to investigate the relationship between the spread of HSV-1 and tear exosomes in recurrent HSK. Methods: Tear fluids collected from total 59 participants were included in this study. Tear exosomes were isolated by ultracentrifugation, then identified by silver staining and western blot. The size was determined by dynamic light scattering (DLS). The viral biomarkers were identified by western blot. The cellular uptake of exosomes was studied using labelled exosomes. Results: Tear exosomes were indeed enriched in tear fluids. Collected exosomes own normal diameters consistent with related reports. The exosomal biomarkers existed in tear exosomes. Labelled exosomes were successfully taken up by human corneal epithelial cells (HCEC) in large numbers in a short time. After cellular uptake, HSK biomarkers were detectable by western blot in infected cells. Conclusions: Tear exosomes should be the latent sites of HSV-1 in recurrent HSK and might be involved in the spread of HSV-1. Besides, this study verifies HSV-1 genes can be indeed transferred between cells by exosomal pathway, providing new inspiration for the clinical intervention and treatment as well as the drug discovery of recurrent HSK.

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Although the biosynthesis of rifamycin has been studied for three decades, the biosynthetic formation of the naphthalenic ring remains unclear. In this study, by deletion of all post-PKS modification genes, we identified macrolactam precursors released from rifPKS. Isolated prorifamycins (M3and M4) have a benzenic chromophore and exist in two sets of macrocyclic atropisomers. The transformation from prorifamycins to benzenoid (5) and naphthalenoid (6) was suggested to be a non-enzymatic process, which is an off-PKS assembly.

The internet of things (IoT) has become a key support object for Chinese strategic emerging industries. It is of great practical significance to promote the construction of the internet of things. Driven by national policies, the development of the internet of things in China has achieved certain results, but it also faces many problems. For example, there are few theoretical and empirical studies on the internet of things economy. In this context, from the perspective of big data, this paper studies the development model and influencing factors of the internet of things economy, and takes Jiangsu Province as an example to put forward development strategies. This article studies the three-stage development model of the IoT economic big data ecosystem: the primary stage, the growth and maturity stage, and the integration stage. On the basis of the research on the development model, the general evaluation method of the economic development model of the internet of things from the perspective of big data is studied, and the general model of strategy selection is established.

In this article, the chance-constrained $H_{\infty }$ state estimation problem is investigated for a class of time-varying neural networks subject to measurements degradation and randomly occurring deception attacks. A novel energy-constrained deception attack model is proposed, in which both the occurrence of the attack and the selection of released faked packet are random and the energy of the deception attack is introduced, calculated, and analyzed quantitatively. The main purpose of the addressed problem is to design an $H_{\infty }$ estimator such that the prefixed probabilistic constraints of the system error dynamics are satisfied and the $H_{\infty }$ performance is also ensured. Subsequently, the explicit expression of the estimator gains is derived by solving a minimization problem subjected to certain recursive inequality constraints. Finally, a numerical example and a practical three-tank system are utilized to demonstrate the correctness and effectiveness of the proposed estimation scheme.

Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO3) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO2bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H2O2) supplementation and promotes the sustained production of ROS. BPMN-CuS/DOX significantly inhibits melanoma both in vitroand in vivoby the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies.

The DNA damage repair of tumor cells limits the effect of photothermal therapy (PTT), and high temperatures induced by PTT can damage adjacent normal tissues. To overcome these limitations, we developed a novel composite hydrogel (OLA-Au-Gel) based on chitosan (CS) and β-glycerophosphate (β-GP), which encapsulated olaparib-liposomes (OLA-lips) and CS-capped gold nanoparticles (CS-AuNPs). OLA-Au-Gel achieved the combination of mild PTT (mPTT) by CS-AuNPs and tumor DNA damage repair inhibition by OLA. The hydrogel showed good biocompatibility, injectability, and photothermal response. Under near-infrared laser irradiation, OLA-Au-Gel inhibited the proliferation of tumor cells, induced the generation of reactive oxygen species in vitro, and effectively inhibited the growth of breast tumors in vivo. OLA-Au-Gel shows a promising application prospect for inhibiting tumor development and improving the antitumor effect. Collectively, we propose a novel strategy for enhanced antitumor therapy based on the combination of mPTT and DNA damage repair inhibition.

SHR-A1201 is an antibody–drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

An accurate description for the shape of the graphene bubbles is essential for research and application of these gas bubbles in tuning electronic, magnetic, and optical properties of the two-dimensional nano materials. The present work reveals that the structural parameters of the bubble can not be described by the theoretical model based on the ideal gas law, which underestimates the structure parameters by 48%. The invalidity of the ideal gas law is due to the extremely large pressure of the gas inside the bubble that can be as high as 1 gigapascal, far beyond the applicability condition of the ideal gas law. To capture this effect, we develop an improved van der Waals equation with the quadratic nonlinear term of the gas density, which is found to provide an accurate description for the shape of the bubble. Further molecular dynamics simulations show high coincidence with the above van der Waals equation model for both graphene bubbles and MoS2bubbles.

Antibiotic resistance reduces the effectiveness of infected wound healing, and it is necessary to develop a new strategy to promote infected wound healing without using antibiotics. Here, we develop a Chlorin e6 (Ce6)-loaded zinc-metal–organic framework (MOF) thermosensitive hydrogel (Ce6@MOF-Gel) based on alginate and poly(propylene glycol) 407, which enhances antibacterial effects and promotes infected wound healing by a novel strategy of combining zinc-MOF with photodynamic therapy (PDT). Zinc-MOF can realize acid-responsive release of Ce6 and improve antibacterial performance without drug resistance by destroying the integrity of bacterial cell membranes and enhancing the production of bacterial reactive oxygen species (ROS). Additionally, Ce6@MOF-Gel enhances the stability, solubility, and photodynamic properties of Ce6. More importantly, Ce6@MOF-Gel reduces inflammation and promotes collagen deposition and re-epithelialization to facilitate infected wound healing. Collectively, the photodynamic MOF-based hydrogel provides a new, efficient, and safe way for accelerated healing of infected wounds.

ABSTRACTPromoting mobility behavior can benefit individuals’ well-being and regional economic vitality. This study focuses on the role of a new ICT-related factor, smartphone usage feedback in promoting users’ mobility behavior. Though smartphone usage feedback is designed to help users to regulate their smartphone use, we find it also has the potential to increase their mobility. According to cognitive dissonance theory, smartphone usage feedback may make users realize that they are more addicted to smartphones in the digital world than they perceive, which causes users to experience dissonance and guilt. To relieve the dissonance and guilt, users may put more cognitive resources into the physical world and perform more life activities, possibly leading to higher-level mobility. Using large-scale smartphone data, findings verify that smartphone usage feedback encourages users to increase stopping- and moving-related mobility behavior. Besides, users with lower-level historical stopping-related mobility are less likely to increase their mobility.

ABSTRACT The corrosive-cracking behavior of two types of reinforced concrete accelerated by a potentiostat and sustained compressive load was studied. The corrosion-rate function of steel bar in reinforced concrete based [...]

Deep cutaneous fungal infection (DCFI) is difficult to be treated by the traditional topical application due to low drug transdermal efficiency, poor fungicidal effect, and easy to develop drug resistance. Here, we report a novel biodegradable microneedle patch (CuS/PAF-26 MN) for DCFI treatment. CuS/PAF-26 MN is composed of hyaluronic acid (HA) and sodium carboxymethylcellulose (CMC-Na), which can simultaneously deliver copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26). CuS NE catalyzes hydrogen peroxide to produce reactive oxygen species (ROS), and PAF-26 directly destroys the cell membrane of fungi. The combination of ROS toxicity produced by CuS NE and the destruction of fungal membrane by PAF-26 shows strong antifungal activities without drug resistance. The antifungal effect of CuS/PAF-26 MN is significantly superior to that of traditional ointment, CuS MN or PAF-26 MN in a DCFI mouse model. Therefore, CuS/PAF-26 MN shows a promising application prospect for treating DCFI.

The low value of recycled products is the main roadblock for sustainable development of polymers. In this work, waste polypropylene and waste polyethylene were chosen to be recycled for value-added thermal management with the addition of hexagonal boron nitride (hBN). Through specific design of melt flow indexes (MFIs), we proposed a novel pressure-induced, flow-enhanced segregated structurization (PiF-SS) process. The segregated structures were visually confirmed by various microscopies at different scales. The highest in-plane thermal conductivities of ∼7.48 W/mk was obtained for the sample with a low hBN loading of 20 wt %. Ultimately, we evaluated the thermal management performance of all samples with various compositions. In this work, we believe that the concept of combinational utilization of a high-MFI polymer and a low-MFI polymer to perform PiF-SS can not only work for the sustainable reuse of waste polymers but also be used for manufacturing advanced functional materials.

To investigate the accuracy of ultrasonic diagnosis using the tele‐ultrasound robot in Leishen Shan Hospital. Twenty‐two patients with novel coronavirus pneumonia from Leishen Shan Hospital voluntarily participated in this study. Their thyroids, neck vessels, hepatobiliaries and kidneys were scanned by both a tele‐ultrasound robot manufactured by Imabot Co., Ltd, Wuhan and conventional method. The ultrasound diagnosis of each patient was compared, and the ultrasound images obtained by the two methods were mixed together and double‐blindly diagnosed by an experienced ultrasound radiologist. There were 44 positive lesions in 110 sites of 22 patients. Of which the two methods, 40 positive lesions were detected by the robotic method with 4 lesions missed (2 small polyps of gallbladder, 1 small hemangioma of liver and 1 small cyst of kidney) and 1 lesion misdiagnosed (normal carotid artery was misdiagnosed as carotid atherosclerotic plaque); 44 positive lesions were detected by conventional method with 1 small cyst of the liver was missed. There was no statistically significant difference in the accuracy rate between the robotic method and the conventional method using the chi‐square test of the four‐grid data (P>.05). The application of tele‐ultrasound robot meets the standard of patient care during the pandemic. The method is feasible to provide adequate ultrasound information to diagnose common abdominal, vascular, superficial organ pathologies in patients with COVID‐19 with acceptable accuracy compared with a conventional ultrasound scan.

Tridacna squamosa, Lamarck, 1819 (Bivalvia Cardiida Cardiidae, known as the fluted giant clam) is one of the largest-sized bivalve shells, which is equipped with a strong and tough bioceramic shell to effectively protect itself from the attack of predators. To better understand the mechanical defense mechanism, the relationship between the microstructure, composition, and mechanical properties of the Tridacna squamosashell was investigated. We find that the Tridacna squamosashell is composed of aragonite CaCO3and a small portion of organic matter, which are well-arranged, assembling a multiscale, inhomogeneous, and anisotropic structure. Three levels of microstructure units are identified, including the smallest aragonite rods, medium sheets, and block-like lamellae. Such multiscale structures are the main contributor to creating abundant fracture surfaces much larger than the case for single mineral components, leading to multiple toughening mechanisms observed in Vickers indentation experiments, such as pulled-out of mineral platelet and crack deflection. The material inhomogeneity in the cross-sectional direction indicates that the material is stronger at the inner layer than that at the outer layer, which also facilitates an effective defense against the predator attack. This study may provide insights into the design of biomaterials with the desired mechanical properties.

We report a metal-free trifluoromethylthiolation and trifluoromethylselenolation of 1,4-dihydropyridines with S-(trifluoromethyl) 4-methylbenzenesulfonothioate and Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate under visible light irradiation. This transformation was tolerated with a wide range of functional groups and provided an alternative and green strategy for the synthesis of trifluoromethylthioesters and trifluoromethylselenoesters.

A visible-light-induced difluoroalkylation of unactivated alkenes by fluoro-containing hypervalent iodine-based difluoroalkylation reagent was achieved for the first time under photo-catalyst-free conditions. Moreover, the same reaction conditions were applicable to the difluoroalkylation of alkynes to give the hydrodifluoroalkylation products in moderate to excellent yields. The readily available reagent, broad substrate scope, and photo-catalyst-free conditions make this protocol an efficient and environmental friendly method for the hydrodifluoroalkylation of alkenes and alkynes.

ABSTRACTBackgroundApixaban is a superior direct oral anticoagulant exihibiting interindividual variability in concentration and response in the real world. The present study aimed to identify genetic biomarkers associated with pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban in healthy Chinese subjects.MethodsThis multicenter study included 181 healthy Chinese adults taking a single dose of 2.5 mg or 5 mg apixaban and assessed their PK and PD parameters. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using the Affymetrix Axiom CBC_PMRA Array. Candidate gene association analysis and genome-wide association study were conducted to identify genes with a predictive value for PK and PD parameters of apixaban.ResultsSeveral ABCG2variants were associated with Cmaxand AUC0-tof apixaban (p < 6.12 × 10−5) and also presented significant differences of anti-Xa3hactivity and dPT3haccording to different ABCG2genotypes (p < 0.05). Besides, ABLIM2variants were found to be associated with PK characteristics and F13A1and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10−8).ConclusionABCG2variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. ABLIM2, F13A1and C3were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.

The design and synthesis of artificial molecular containers for the encapsulation of hydrocarbon gases to study their host-guest chemistry are highly important for potential application in gas storage, separation, and understanding of their biological functions. In this work, we report the subcomponent self-assembly of four cubic Zn8L12Br4(HL = N-(4-R)-1-(5-methyl-1H-imidazole-4-yl)methanimine) cages with good solubility in chloroform, which are capable of binding hydrocarbon gases including methane, ethane, and ethene in solution at ambient temperature. Two types of gas binding sites (one is in the cavity, and the other is at the window) are discovered in these cages, which are documented by nuclear magnetic resonance (NMR) spectra and density functional theory (DFT) calculations. Their performance of encapsulation of hydrocarbon gases can be tuned by carefully adjusting substituent groups. These metal-organic cages containing two types of binding sites provide new artificial models to mimic the structures and functions of biological systems in binding and transforming hydrocarbon gases.

Background and Objectives: Vedolizumab is a humanized monoclonal antibody, indicated for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD), that specifically binds to the α4β7 integrin. The aim of this study was to assess the pharmacokinetics, safety, and tolerability of vedolizumab following a single intravenous (IV) infusion in healthy adult Chinese subjects. Methods: Sixteen participants received a single IV infusion of vedolizumab (300 mg). Blood samples were collected to measure vedolizumab serum concentrations. The safety of all subjects was monitored. Results: The pharmacokinetic analysis showed that vedolizumab reached the maximum observed serum concentration (Cmax) at approximately 1.32 hours. The meanCmaxand area under the concentration–time curve from time 0 to time of the last quantifiable concentration (AUC0–t) and to infinity (AUC0–∞) were 137.25 µg/mL, 2360 days·µg/mL, and 2395 days·µg/mL, respectively. The elimination of vedolizumab was relatively slow, with a mean terminal disposition phase half-life elimination (t1/2) of 20.23 days. Six subjects were positive for anti-vedolizumab antibodies (AVAs) on day 106 and day 127. Finally, 4 out of 16 subjects (25.0%) had treatment-emergent adverse events (TEAEs), all of which were upper respiratory tract infections. Conclusion: Vedolizumab was well tolerated in healthy Chinese subjects when administered as a single-dose IV 300 mg infusion. In this study, the rate of AVA positivity was 37.5%, which occurred near the end of the study; no significant differences in pharmacokinetic profiles were observed between the AVA-positive and AVA-negative groups. Clinical Trial Registration: http://www.chinadrugtrials.org.cn: CTR20171528.

Passengers generate travel behaviours on public transit, whose variations deserve an exploration with an aim to guide daily-updated managements. In this study, we investigate temporal variability in travel patterns for over 3.3 million passengers across 120 days who use public transit in Beijing. Temporal variability is characterized by a series of features in terms of space coverage, travel distance and travel frequency, based on which, passengers are clustered into two types, that is, commuters with daily travel routines, and non-commuters who do not. How, and to which extent, they change travel patterns over time are examined, with using approaches concerning multivariate regression and curve fitting. Results show that, (1) commuters are more likely to travel longer but cover less territory than non-commuters on weekdays, while the opposite patterns occur on weekends. The variation of day of week affects commuters less, compared to non-commuters, due to more fixed schedules, as expected; (2) travel distance and frequency are found to increase faster, more linearly, than space-coverage features, the last of which experience a progressive decreasing of marginal increases before reaching a plateau. The above findings facilitate transport practitioners to design sound management schemes for passengers in different categories.

ABSTRACTAerosol loadings and their spatial distribution are among the most important atmospheric information needed for a range of applications such as air quality monitoring, climate research, and public health. A key measure of aerosol quantity is aerosol optical depth (AOD) and it has been routinely observed from space by Earth observing satellites/instrument, especially the Moderate Resolution Imaging Spectroradiometer (MODIS). Despite its global coverage and daily temporal resolution, the MODIS Multi-Angle Implementation of Atmospheric Correction (MAIAC) AOD product is fraught with missing values, severely limiting its use. A gap-filling method which is suitable for large-area application with high efficiency to obtain gapless AOD with reasonable spatial pattern and complete coverage is still lacking. Here, we proposed a novel spatiotemporal fitting algorithm to gap-fill the daily MODIS AOD product. Our algorithm is a multi-stage method aimed to address the non-stationary nature of AOD time series. First, the trend of daily AOD in a year in each pixel was fitted via smoothing splines and the residual was derived based on the original data and the trend. Second, the residual was spatially interpolated, leveraging the spatial correlation between the target pixel and the neighboring pixels. Third, the actual AOD was calculated as the sum of the trend and interpolated residual. We tested the algorithm against ground-based AOD data from 2011 to 2018 in China and further evaluated it via cross-validation at the global scale based on 10 selected MODIS tiles. Compared to the ground-reference AOD, the RMSE of our gapless datasets were 0.24 and 0.27 for Terra and Aqua, respectively; and the cross-validation showed a RMSE ranging from 0.045 to 0.055 (Terra) and 0.047 to 0.057 (Aqua) under different missing ratios. The novel gap-filling method outperforms the Interpolation-based Correlation Weighting (ICW) and Inverse Distance Weighting (IDW) algorithms in accuracy. Meanwhile, the gapless AOD using the novel algorithm shows lower accuracy than original MAIAC AOD, similar accuracy with the AOD from the Long-term Gap-free High-resolution Air Pollutants (LGHAP) concentration dataset, higher accuracy than the AOD from the Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2). Overall, the accuracy of gapless AOD using this algorithm meets the need of typical applications in relevant studies. The proposed algorithm is transferable to other regions, with the potential to be used even operationally and efficiently for generating accurate gapless global daily AOD datasets with the input of only MODIS MAIAC AOD data.

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from Knoxia valerianoidesexhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (1–9) and two known ones (10and 11). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC50values ranging from 1.05 to 13.74 μM. Compounds 4and 8exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds 4and 7behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.

Neurotoxicity can be resulted from many diverse clinical drugs, which has been a cause of concern to human populations across the world. The detection of drug-induced neurotoxicity (DINeurot) potential with biological experimental methods always required a lot of budget and time. In addition, few studies have addressed the structural characteristics of neurotoxic chemicals. In this study, we focused on the computational modeling for drug-induced neurotoxicity with machine learning methods and the insights into the structural characteristics of neurotoxic chemicals. Based on the clinical drug data with neurotoxicity effects, we developed 35 different classifiers by combining five different machine learning methods and seven fingerprint packages. The best-performing model achieved good results on both 5-fold cross-validation (balanced accuracy of 76.51%, AUC value of 0.83, and MCC value of 0.52) and external validation (balanced accuracy of 83.63%, AUC value of 0.87, and MCC value of 0.67). The model can be freely accessed on the web server DINeuroTpredictor (http://dineurot.sapredictor.cn/). We also analyzed the distribution of several key molecular properties between neurotoxic and non-neurotoxic structures. The results indicated that several physicochemical properties were significantly different between the neurotoxic and non-neurotoxic compounds, including molecular polar surface area (MPSA), AlogP, the number of hydrogen bond acceptors (nHAcc) and donors (nHDon), the number of rotatable bonds (nRotB), and the number of aromatic rings (nAR). In addition, 18 structural alerts responsible for chemical neurotoxicity were identified. The structural alerts have been integrated with our web server SApredictor (http://www.sapredictor.cn). The results of this study could provide useful information for the understanding of the structural characteristics and computational prediction for chemical neurotoxicity.

This paper proposes a convex reformulation for the non-linear optimal water-power flow (OWPF) problem to optimize the operation cost of the integrated electricity–water network (IEWN). Due to the significant challenge in seeking the optimal solution of non-convex problems, the original OWPF problem is reformulated as a tractable mixed-integer second-order cone programming (MISOCP) problem. For the power distribution network, a second-order cone (SOC) relaxation is employed to address the non-linear branch power flow equation. For the water distribution network, a big-M trick is introduced to handle the unknown direction of water flow, then SOC relaxations and convex envelopes are employed to deal with quadratic and bilinear terms in non-convex constraints, respectively. To enhance the approximation accuracy of the proposed MISOCP model, a convex combination method and a sequential convexification approach are developed. Numerical results demonstrate that the proposed method outperforms the original non-linear formulation and linearized reformulation in accuracy, efficiency, and robustness.

Seeking sustainable energy solutions for bioelectronic devices, high-performance, multifunctional biopolymer-based triboelectric nanogenerators (TENGs) are proving to be essential for biomedical applications. This study presents an innovative fabrication method for establishing secondary electron transport paths, resulting in biopolymer-based nanocomposites (poly (lactic acid) (PLA)/carbon nanotube (CNT)@expanded graphite (EG)) with inherent electron pathways. By integrating conductive biopolymer nanocomposites with polytetrafluoroethylene (PTFE) films, we developed a contact-separation mode TENG (CS-TENG) that demonstrates outstanding energy-harvesting efficiency. The CS-TENG displays an impressive charge density of 280 μC/m2, accompanied by an open circuit voltage (Voc) of 100.5 V and short circuit current density (Isc) values of 47.25 mA/m2. Moreover, the essential conductive network guarantees the CS-TENG’s stability across different humidity levels and serves as a moisture barrier. In addition to energy harvesting, the fabricated biopolymer nanocomposite films exhibit effective electromagnetic interference (EMI) shielding and Joule heating capabilities, rendering the CS-TENG suitable for use in diverse application scenarios. Our results emphasize the crucial role of conductive network architecture in creating high-performance biopolymer PLA-based TENGs. The innovative fabrication method and our CS-TENG's capabilities reveal the significant potential of biopolymer-based composites to transform energy harvesting, thermal management, and EMI shielding in bioelectronics.

The Chinese government has implemented a clean heating policy to alleviate the severe air pollution and high energy consumption associated with winter heating in northern China. However, the promotion of clean heating technology paths (CHTPs) is limited by the problems of rising energy prices and insufficient supply capacity. To quantitatively study the promotion scope of each CHTP, this paper adopts the K-means clustering method in machine learning to analyze the clean heating methods suitable for the characteristics of each region in northern China based on 37 pilot cities. The results show that the 10 CHTPs based on coal, electricity and natural gas as energy, the most widely applied is Air-source heat pump technology, accounting for 86.7 % in cities. The least number of cities suitable for application are water-source heat pumps and sewage-source heat pumps due to economic constraints, with a proportion of 44 %. The 3 kinds of CHTPs applying solar, biomass and geothermal energy, accounted for more than 60 %, among them, ground-source heat pumps are recommended to promote the smallest scope, concentrated in Hebei, Henan, Shandong, and Heilongjiang provinces. This study is of great significance in guiding the selection of CHTPs on a large spatial scale.

ABSTRACTInvestigating the function of delicate mammalian eyes often requires chemical fixation, histological sectioning, immunohistochemistry (IHC) and in situhybridization (ISH). One of the long-standing challenges in the ocular histology field is the limited success of maintaining intact morphology via cryo- or paraffin procedures. Although our latest protocol significantly improved the morphology of mouse eyeball sections, the window technique is time-consuming and requires extensive practice to avoid damage while making windows. In this study, we present a novel glyoxal fixative that is suitable for a freeze-substitution approach to improve both morphology and molecular target preservation of mouse eyes. The method prevents morphology distortion in all tested eyeballs. Therefore, it suits a variety of research needs from morphological examination to investigation of single-molecule RNA expression, using hematoxylin and eosin (H&E) stain, IHC, and ISH assays on either frozen (cryo) or paraffin-infiltrated tissue sections. In addition, this method can be easily performed in many histology laboratories.

Various functional polydopamine (PDA) nanoparticles have been developed to treat biofilms in recent years; however, in-depth knowledge of how the physicochemical properties of the nanoparticles impact their penetration and accumulation in biofilms is lacking. In this work, PDA nanoparticles of 15, 60, 90, and 200 nm sizes were synthesized and carboxyl, methoxy, and amine groups were introduced to the particle surface to control their surface charges, and then the penetration and accumulation of these PDA nanoparticles in S. aureusbiofilms were investigated. The PDA nanoparticles of approximately 60 nm size (PDA60) showed higher penetration and accumulation abilities than nanoparticles of other sizes, and the positively charged amine groups introduced onto the surfaces of PDA60 nanoparticles were more effective than carboxyl or methoxy groups in promoting the interactions of the nanoparticles with the biofilm. The PDA60 nanoparticles with amine surface groups exhibited good photothermal properties, and confocal laser scanning microscopy revealed that they were able to accumulate in the biofilm in significant amounts, which upon irradiation with a laser of 808 nm wavelength showed a high bactericidal rate (97.1%) against the biofilm. The findings of this work provide guidance for the design and development of nanoparticles for antibiofilm application.

Hydraulic transients occur frequently due to flow control operations in a hydraulic system, which may lead to adverse impacts on the system equipment. However, the existing researches on the power–water flow problem of the integrated electricity–water system (IEWS) are mainly based on steady-state hydraulic models, and few efforts have been spent investigating the effect of hydraulic transients on the IEWS. This paper incorporates the hydraulic transients of water distribution systems (WDSs) into the power–water flow analysis of the IEWS and proposes an extended-period quasi-steady-state IEWS model to evaluate the short-term operation of the system. The proposed model is theoretically analyzed and numerically validated based on a single-pipe WDS and a test IEWS composed of the IEEE-13 power distribution system and a 5-node WDS.