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Abstract Laser-lubricant interaction has been a critical reliability issue in a thermo-tribological system named heat-assisted magnetic recording, one of the next generation hard disk drive solutions to increasing data storage. The lubricant response under laser irradiation and the subsequent lubricant recovery are crucial to the system’s reliability and longevity, however, they cannot be diagnosed locally and timely so far. Here, we propose a thermal scheme to in-situ characterize the mechanical laser-lubricant interaction. The nanometer-thick lubricant has a thermal barrier effect on the near-field thermal transport in the system, according to which the lubricant thickness can be determined. As demonstrations, this paper reports the first quantitative in-situ measurements of the laser-induced lubricant depletion and the subsequent reflow dynamics. The proposed scheme shows a sub-angstrom resolution (~0.2 Å) and a fast response time within seconds, rendering in-situ real-time lubricant diagnosis feasible in the practical hard disk drive products.

Abstract Recent studies have suggested that mRNA internal m7G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m7G. Such interactions, especially IGF2BP3 with m7G, could promote the degradation of m7G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m7G modification, while IGF2BP1 prefers m6A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m7G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m7G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.

CO2 storage in basalt formation has received much attention as one of the new CO2 geological storage methods worldwide. It has been successfully implemented in Iceland and the United States. During the process of carbon storage in basalt, CO2 is transformed into solid minerals, which differs significantly from carbon storage in sandstone reservoirs in terms of CO2 injection method, burial depth, and physical property requirements of reservoir cap. Significant differences are also found in both monitoring schemes. By studying the Wallula basalt storage project in the United States and the Carbfix mineralization storage project in Iceland, this study compared and summarized the monitoring schemes of basalt storage for different CO2 injection phases (supercritical and gas dissolved state). The monitoring systems of basalt storage, saline aquifer storage, oil and gas reservoir storage were further compared. The storage monitoring system for sandstone reservoir focuses on the structural integrity of the CO2 reservoir and evaluating the change of CO2 concentration along the potential leakage path. The monitoring period is usually more than 50 years. In contrast, basalt mineralization and storage technology focus on the mineralization reaction of “water-CO2-basalt”. Its monitoring system is mainly to describe the property changing pattern of each substance from downhole fluid (chemical compositions, tracer concentrations, pH, etc.) during the storage cycle. Moreover, it evaluates the degree of mineralization reaction and the storage efficiency of basalt qualitatively and quantitatively. Finally, based on the systematic and comprehensive monitoring scheme of saline aquifer and oil and gas reservoir storage, the basalt-CO2 mineralization storage monitoring technology is analyzed systematically and a complete set of basalt-CO2 mineralization storage monitoring scheme and process is summarized. By comparing different CO2 storage monitoring systems, this study proposes a universal “subsurface-wellbore-surface-ground” monitoring scheme for basalt-CO2 mineralization: monitoring scope, purpose, program, and alert system. This provides basic information for the future basalt-CO2 mineralization storage demonstration project.

Abstract Silk nanofibrils (SNFs), the fundamental building blocks of silk fibers, endow them with exceptional properties. However, the intricate mechanism governing SNF assembly, a process involving both protein conformational transitions and protein molecule conjunctions, remains elusive. This lack of understanding has hindered the development of artificial silk spinning techniques. In this study, we address this challenge by employing a graphene plasmonic infrared sensor in conjunction with multi-scale molecular dynamics (MD). This unique approach allows us to probe the secondary structure of nanoscale assembly intermediates (0.8–6.2 nm) and their morphological evolution. It also provides insights into the dynamics of silk fibroin (SF) over extended molecular timeframes. Our novel findings reveal that amorphous SFs undergo a conformational transition towards β-sheet-rich oligomers on graphene. These oligomers then connect to evolve into SNFs. These insights provide a comprehensive picture of SNF assembly, paving the way for advancements in biomimetic silk spinning.

Abstract Polaritons are well-established carriers of light, electrical signals, and even heat at the nanoscale in the setting of on-chip devices. However, the goal of achieving practical polaritonic manipulation over small distances deeply below the light diffraction limit remains elusive. Here, we implement nanoscale polaritonic in-plane steering and cloaking in a low-loss atomically layered van der Waals (vdW) insulator, α-MoO3, comprising building blocks of customizable stacked and assembled structures. Each block contributes specific characteristics that allow us to steer polaritons along the desired trajectories. Our results introduce a natural materials-based approach for the comprehensive manipulation of nanoscale optical fields, advancing research in the vdW polaritonics domain and on-chip nanophotonic circuits.

Abstract With the continuous construction of urban traffic roads, more and more new roads are cut off by existing roads to form “dead end roads”. There is an urgent need for a trenchless method suitable for urban ultra-shallow overburden to build the undercrossing tunnel. To solve this problem, this paper proposed the micro pipe jacking and joint assembly structure (MPJ & JAS) method, which has the characteristics of shallow burial depth, low cost, short construction time, flexible cross-section setting and high space utilization. The MPJ & JAS method construct a large cross-section tunnel through assembling small cross-section elements, quite different from traditional methods. Therefore, this paper designed a CT-shaped integrated joint, the mechanical performance of which was verified and clarified by tensile test. The bending test and finite element (FE) analysis proved the reliability of MPJ & JAS tunnel structure, and confirmed the structure performances such as the failure models, crack behaviors, load–deflection response and stress–strain distribution. Moreover, the influences of the steel plate thickness, concrete strength and shear connector spacing were determined by the FE analysis. On the basis of test results and reasonable assumptions, a theoretical design method considering the influence of the CT-shaped integrated joint was proposed, which can effectively predict the bending strength of the MPJ & JAS tunnel structure with an error of less than 10%. Finally, in view of the characteristics of the MPJ & JAS method, the suitable micro pipe jacking machine, soil reinforcement measure, hydraulic traction construction technology, high-precision guidance system and concrete construction quality detection method based on the phased array ultrasonic imaging technology were developed, supporting the accurate and efficient construction of the MPJ & JAS tunnel.

Objectives: To investigate the factors influencing imipenem/cilastatin (IMI) and meropenem (MEM) concentrations in critically ill adult patients and the role of these concentrations in the clinical outcome. Methods: Plasma trough concentrations of IMI and MEM were detected by high-performance liquid chromatography. A target value of 100%-time above MIC was used for the drugs. Results: A total of 186 patients were included, with 87 receiving IMI and 99 receiving MEM. The percentages of patients reaching the target IMI and MEM concentrations were 44.8% and 38.4%, respectively. The proportions of patients infected with drug-resistant bacteria were 57.5% and 69.7% in the IMI group and MEM group, respectively. In the multivariate analysis, the risk factors for an IMI concentration that did not reach the target were infection with drug-resistant bacteria, and those for MEM were infection with drug-resistant bacteria, estimated glomerular filtration rate, and diabetes mellitus. A total of 47.1% of patients had good outcomes in the IMI cohort, and 38.1% of patients had good outcomes in the MEM cohort. The duration of mechanical ventilation and IMI concentration were associated with ICU stay in patients in the IMI cohort, while MEM concentration and severe pneumonia affected the clinical outcome of patients in the MEM cohort. Conclusion: Infection with drug-resistant bacteria is an important factor influencing whether IMI and MEM concentrations reach the target. Furthermore, IMI and MEM concentrations are associated with the clinical outcome, and elevated doses of IMI and MEM should be given to patients who are infected with drug-resistant bacteria.

Introduction It remains difficult for patients with spinal cord injury (SCI) to fully recover their sensory and motor functions; thus, they must rely on the assistance of caregivers to complete activities of daily living. This leads to psychological distress and decreased quality of life in patients and caregivers. Interventions for dyadic coping are a promising option. However, no studies have examined the effects of dyadic coping interventions on patients with SCI and their spouses. Therefore, our team constructed a dyadic coping intervention programme for couples with SCI.Method and analysis This two-arm, parallel-design, pilot randomised controlled trial will recruit 72 couples with SCI from two tertiary hospitals in Hefei, China. Couples will be randomly allocated to two arms. Couples randomly assigned to the intervention group will receive the usual care and the dyadic coping intervention. Couples randomly assigned to the control group will receive usual care only. The primary outcomes will be the feasibility and acceptability of the dyadic coping intervention for couples with SCI. Secondary outcomes will be quality of life, psychological distress, caregiver burden, marital satisfaction and dyadic coping. Outcomes will be collected at three time points: baseline (T0), post-intervention (T1) and after a follow-up period of 8 weeks (T2).Ethics and dissemination This study has been approved by the Research Ethics Committee of Anhui Medical University (84240008). The results will be published in a peer-reviewed journal.Trial registration number ChiCTR2300074556.

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).

Summary: In this protocol, we present a facile nanoscale thermal mapping technique for electronic devices by use of atomic force microscopy and a phase change material Ge2Sb2Te5. We describe steps for Ge2Sb2Te5 thin film coating, Ge2Sb2Te5 temperature calibration, thermal mapping by varying heater power, and thermal mapping by varying heating time. The protocol can be applied for resolving surface temperatures of various operational microelectronic devices with a nanoscale precision.For complete details on the use and execution of this protocol, please refer to Cheng et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Stacking order plays a crucial role in determining the crystal symmetry and has significant impacts on electronic, optical, magnetic, and topological properties. Electron-phonon coupling, which is central to a wide range of intriguing quantum phenomena, is expected to be intricately connected with stacking order. Understanding the stacking order-dependent electron-phonon coupling is essential for understanding peculiar physical phenomena associated with electron-phonon coupling, such as superconductivity and charge density waves. In this study, we investigate the effect of stacking order on electron-infrared phonon coupling in graphene trilayers. By using gate-tunable Raman spectroscopy and excitation frequency-dependent near-field infrared nanoscopy, we show that rhombohedral ABC-stacked trilayer graphene has a significant electron-infrared phonon coupling strength. Our findings provide novel insights into the superconductivity and other fundamental physical properties of rhombohedral ABC-stacked trilayer graphene, and can enable nondestructive and high-throughput imaging of trilayer graphene stacking order using Raman scattering.

The Gaussian sum extended Kalman filter (GSEKF), as a nonlinear non-Gaussian filter, disregards the impact of colored noise components in non-Gaussian noise engendered by external interference, which may compromise the estimation accuracy in global navigation satellite system/strapdown inertial navigation system (GNSS/SINS) tightly coupled positioning and attitude determination systems. To address this problem, an improved Gaussian sum extended Kalman filter with colored noise (colored-GSEKF) is proposed to refine the random model by approximating non-Gaussian noise using Gaussian mixture models and whitening the colored noise components within the non-Gaussian colored noise through state and measurement augmentation. This improved algorithm further enhances the accuracy and stability of the filtering estimation in non-Gaussian colored noise environments. Simulations and experimental results indicate that the proposed colored-GSEKF exhibits superior accuracy in modeling a random model in non-Gaussian colored noise environments. By applying this filter to GNSS/SINS tightly coupled positioning and attitude determination systems utilized on unmanned aerial vehicles influenced by non-Gaussian colored noise, the estimation accuracy and stability can be improved.

Although federated learning (FL) represents a distributed machine learning paradigm that ensures privacy protection, the failure of stragglers to upload local models in a timely manner results in an overall degradation of the global model’s performance, and the difficulty of accurately predicting whether clients will succeed in uploading a local model makes client selection still a challenge. To address this issue, existing works mainly focus on increasing the number of clients who participate in training within a fixed time, however, the fact is that the performance of a global model depends on the data used for training. Therefore, increasing the clients’ data contribution to the global model can effectively enhance the global model’s performance. To this end, we propose a Bayesian estimation based FL framework, named FedBoost, to enhance the performance of the model when straggler problem exists. Specifically, we formulate a long-term problem aimed at maximizing clients’ cumulative effective data contributions, while satisfying a long-term fairness constraints, which ensure a minimum selection frequency for clients. By analyzing the stability of virtual queues, we transform the long-term problem into a stepwise one via Lyapunov optimization, reducing its computational complexity. Due to the inability of the server to predict whether clients successfully upload the local model before receiving the actual upload, we use Bayesian estimation based on the observed frequency of successful uploads to estimate this probability. Last, extensive experimental results indicate that the average test accuracy of our FedBoost is up to 5.59% higher than both FedAvg and FedCS on three real-world datasets, and achieves test loss that are at most 0.1646 below the two baselines. Furthermore, the value of Lapunov function remains lower than 1.4, and at least 85% of the estimation of probabilities are in a reasonable range.

Abstract Anisotropic materials with oppositely signed dielectric tensors support hyperbolic polaritons, displaying enhanced electromagnetic localization and directional energy flow. However, the most reported hyperbolic phonon polaritons are difficult to apply for active electro-optical modulations and optoelectronic devices. Here, we report a dynamic topological plasmonic dispersion transition in black phosphorus via photo-induced carrier injection, i.e., transforming the iso-frequency contour from a pristine ellipsoid to a non-equilibrium hyperboloid. Our work also demonstrates the peculiar transient plasmonic properties of the studied layered semiconductor, such as the ultrafast transition, low propagation losses, efficient optical emission from the black phosphorus’s edges, and the characterization of different transient plasmon modes. Our results may be relevant for the development of future optoelectronic applications.

With the growing public attention to data privacy protection, the problem of data silos has been exacerbated, which makes it more difficult for crowd intelligence technologies to get off the ground. Meanwhile, Federated Learning (FL) has received great attention for its ability to break data silos and jointly build machine learning models. To crack the data silo problem in crowd intelligence, we propose a new Crowd Federated Learning (CFL) framework, which is a two-tier architecture consisting of a cloud server, model owners, and data collectors, that enables collaborative model training among individuals without the need for raw data interaction. However, existing work struggles to simultaneously ensure the balance of incentives among data collectors, model owners, and cloud server, which can affect the willingness of sharing and collaboration among subjects. To solve the above problem, we propose a hierarchical incentive mechanism named FedCom, i.e., Crowd Federated Learning for Contribution matching, to match participants’ contributions with rewards. We theoretically prove that FedCom has contribution matching fairness, and conduct extensive comparative experiments with five baselines on one simulated dataset and four real-world datasets. Experimental results validate that FedCom is able to reduce the computation time of contribution evaluation by about 8 times and improve the global model performance by about 2% while ensuring fairness.

Systemic blood circulation is one of life activity’s most important physiological functions. Continuous noninvasive hemodynamic monitoring is essential for the management of cardiovascular status. However, it is difficult to achieve systemic hemodynamic monitoring with the daily use of current devices due to the lack of multichannel and time-synchronized operation capability over the whole body. Here, we utilize a soft microfiber Bragg grating group to monitor spatiotemporal hemodynamics by taking advantage of the high sensitivity, electromagnetic immunity, and great temporal synchronization between multiple remote sensor nodes. A continuous systemic hemodynamic measurement technique is developed using all-mechanical physiological signals, such as ballistocardiogram signals and pulse waves, to illustrate the actual mechanical process of blood circulation. Multiple hemodynamic parameters, such as systemic pulse transit time, heart rate, blood pressure, and peripheral resistance, are monitored using skin-like microfiber Bragg grating patches conformally attached at different body locations. Relying on the soft microfiber Bragg grating group, the spatiotemporal hemodynamic monitoring technique opens up new possibilities in clinical medical diagnosis and daily health management.

Abstract The aim of this study was to validate the performance of the Ovarian-Adnexal Reporting and Data Systems (O-RADS) series models proposed by the American College of Radiology (ACR) in the preoperative diagnosis of adnexal masses (AMs). Two experienced sonologists examined 218 patients with AMs and gave the assessment results after the examination. Pathological findings were used as a reference standard. Of the 218 lesions, 166 were benign and 52 were malignant. Based on the receiver operating characteristic (ROC) curve, we defined a malignant lesion as O-RADS > 3 (i.e., lesions in O-RADS categories 4 and 5 were malignant). The area under the curve (AUC) of O-RADS (v2022) was 0.970 (95% CI 0.938–0.988), which wasn’t statistically significantly different from the O-RADS (v1) combined Simple Rules Risk (SRR) assessment model with the largest AUC of 0.976 (95% CI 0.946–0.992) (p = 0.1534), but was significantly higher than the O-RADS (v1) (AUC = 0.959, p = 0.0133) and subjective assessment (AUC = 0.918, p = 0.0255). The O-RADS series models have good diagnostic performance for AMs. Where, O-RADS (v2022) has higher accuracy and specificity than O-RADS (v1). The accuracy and specificity of O-RADS (v1), however, can be further improved when combined with SRR assessment.

Abstract Background Although stimuli-responsive nanoplatforms were developed to deliver immunogenic cell death (ICD) inducers to enhance cancer immunotherapy, the complete release of ICD inducers into the tumor microenvironment (TME) was limited by the inadequate supplementation of endogenous stimulus (e.g., reactive oxygen species (ROS)). To address this issue, we synthesized a self-responsive nanomaterial with self-supplied ROS, which mainly consists of a ROS responsive moiety HPAP and cinnamaldehyde (CA) as the ROS-generating agent. The endogenous ROS can accelerate the degradation of HPAP in materials to release docetaxel (DTX, an ICD inducer). In intracellular acidic environment, the pH-sensitive acetal was cleaved to release CA. The released CA in turn induces the generation of more ROS through mitochondrial damage, resulting in amplified DTX release. Using this self-cycling and self-responsive nanomaterial as a carrier, DTX-loaded pH/ROS dual-responsive nanoparticles (DTX/FA-CA-Oxi-αCD NPs) were fabricated and evaluated in vitro and in vivo. Results In vitro experiments validated that the NPs could be effectively internalized by FA-overexpressed cells and completely release DTX in acidic and ROS microenvironments to induce ICD effect. These NPs significantly blocked 4T1 cell migration and decreased cell invasion. In vivo experiments demonstrated that the tumor-targeted NPs significantly inhibited tumor growth and blocked tumor metastasis. More importantly, these NPs significantly improved immunotherapy through triggering effector T-cell activation and relieving the immunosuppressive state of the TME. Conclusions Our results demonstrated that DTX/FA-CA-Oxi-αCD NPs displayed great potential in preventing tumor metastasis, inhibiting tumor growth, and improving the efficacy of anti-PD-1antibody. Graphical Abstract

ABSTRACT: Objective: Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name medications, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin. Methods: The pharmacokinetic (PK) parameters (Cmax, AUC0∼24, Tmax, and t1/2), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment; the cumulative fraction of response) calculated by Monte Carlo simulation were investigated. Results: Our results demonstrated that compared with generics, brand-name levofloxacin not only had higher drug content, it also showed higher antimicrobial susceptibility, higher resistance to mutation ability, and higher percentage of each dosage interval wherein plasma concentration of antimicrobial agents exceeded the MPC90 (mutant prevention concentration to prevent the mutation of 90% strains) against various clinical isolates. Although the differences in AUC0∼24 between brand-name levofloxacin and generics were not statistically significant (P > 0.05, F test), Monte Carlo simulation results showed cumulative fraction of response values for PK/PD of brand-name medications were higher than generics. Conclusion: Our results indicated that PK or PD equivalence did not imply therapeutic equivalence; thus, we suggest including PK/PD analysis in the bioequivalence evaluation system, which benefits prediction of clinical outcome with high application value.

Abstract A main challenge in Heat-Assisted Magnetic Recording technology is the build-up of contaminants called smear on the near field transducer. In this paper, we investigate the role of optical forces originating from the electric field gradient in the formation of smear. First, based on suitable theoretical approximations, we compare this force with air drag and the thermophoretic force in the head-disk interface for two smear nanoparticle shapes. Then, we evaluate the force field’s sensitivity to the relevant parameter space. We find that the smear nanoparticle’s refractive index, shape, and volume significantly impact the optical force. Further, our simulations reveal that the interface conditions, such as spacing and the presence of other contaminants, also influence the magnitude of the force.

Abstract Activating transcription factor 4 (ATF4) is one of the key effectors of endoplasmic reticulum stress (ERS), ATF4/CHOP pathway-mediated ERS plays an important role in the progression of acute kidney disease (AKI). We have previously reported that Vitamin D receptor (VDR) exert renoprotection in rodent AKI models. However, whether ATF4, as well as ERS, is involved in the protective effect of VDR in ischemia-reperfusion (I/R) induced AKI is unknown. Herein, we showed that VDR agonist paricalcitol and VDR overexpression alleviated I/R-induced renal injury and cells apoptosis with decreased ATF4 and attenuated ERS, while VDR deletion significantly resulted in further increased ATF4, more drastic ERS and renal injury in I/R mice models. In addition, paricalcitol remarkably reduced Tunicamycin (TM) induced ATF4 and ERS with attenuated renal injury, while VDR deletion aggravated the above changes in TM mice models. Moreover, overexpression of ATF4 partially abolished the effect of paricalcitol against TM-induced ERS and apoptosis, while inhibition of ATF4 enhanced the protective effect of paricalcitol. Bioinformatics analysis indicated potential VDR binding sites on ATF4 promotor sequence which were further confirmed by ChIP-qPCR and dual-luciferase reporter gene assay. In conclusion, VDR attenuated I/R-induced AKI by suppressing ERS partly via transcriptional regulation of ATF4.

Abstract Cherenkov radiation (CR) excited by fast charges can serve as on-chip light sources with a nanoscale footprint and broad frequency range. The reversed CR, which usually occurs in media with the negative refractive index or negative group-velocity dispersion, is highly desired because it can effectively separate the radiated light from fast charges thanks to the obtuse radiation angle. However, reversed CR at the mid-infrared remains challenging due to the significant loss of conventional artificial structures. Here we observe mid-infrared analogue polaritonic reversed CR in a natural van der Waals (vdW) material (i.e., α-MoO3), whose hyperbolic phonon polaritons exhibit negative group velocity. Further, the real-space image results of analogue polaritonic reversed CR indicate that the radiation distributions and angles are closely related to the in-plane isofrequency contours of α-MoO3, which can be further tuned in the heterostructures based on α-MoO3. This work demonstrates that natural vdW heterostructures can be used as a promising platform of reversed CR to design on-chip mid-infrared nano-light sources.

Abstract Serotonin, also known as 5-hydroxytryptamine (5-HT), is a key messenger that mediates several central and peripheral functions in the human body. Emerging evidence indicates that serotonin is critical in tumorigenesis, but its role in colorectal cancer remains elusive. Herein, we report that serotonin transporter (SERT) transports serotonin into colorectal cancer cells, enhancing Yes-associated protein (YAP) expression and promoting in vitro and in vivo colon cancer cell growth. Once within the cells, transglutaminase 2 (TG2) mediates RhoA serotonylated and activates RhoA-ROCK1/2 signalling to upregulate YAP expression in SW480 and SW1116 cells. Blocking SERT with citalopram reversed the serotonin-induced YAP expression and cell proliferation, inhibiting serotonin’s effects on tumour formation in mice. Moreover, SERT expression was correlated with YAP in pathological human colorectal cancer samples and the levels of 5-HT were highly significant in the serum of patients with colorectal cancer. Together, our findings suggested that serotonin enters cells via SERT to activate RhoA/ROCK/YAP signalling to promote colon cancer carcinogenesis. Consequently, targeting serotonin-SERT-YAP axis may be a potential therapeutic strategy for colorectal cancer. Video abstract

Background Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). tRNA derived fragments (tRFs/tiRNAs) are groups of small noncoding RNAs derived from tRNAs. To date, the role of tRFs/tiRNAs in renal IRI has not been reported. Herein, we aimed to investigate the involvement of tRFs/tiRNAs in the occurrence and development of ischemia–reperfusion-induced AKI.Methods Moderate/severe renal IRI mouse models were established by bilateral renal pedicle clamping. The tRF/tiRNA profiles of healthy controls and moderate/severe IRI-stressed kidney tissues were sequenced by Illumina NextSeq 500. Candidate differentially expressed tiRNAs were further verified by RT-qPCR. Biological analysis was also performed.Results Overall, 152 tRFs/tiRNAs were differentially expressed in the moderate ischemic injury group compared with the normal control group (FC > 2, p 2, p

Abstract Background Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous. Methods A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan–Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states. Results MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan–Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p 0.05). Conclusions Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.

Background: The fruit of Terminalia chebula has been widely used for a thousand years for treating diarrhea, ulcers, and arthritic diseases in Asian countries. However, the active components of this Traditional Chinese medicine and their mechanisms remain unclear, necessitating further investigation.Objectives: To perform simultaneous quantitative analysis of five polyphenols in T. chebula and evaluate their anti-arthritic effects including antioxidant and anti-inflammatory activity in vitro.Materials and methods: Water, 50% water-ethanol, and pure ethanol were used as extract solvents. Quantitative analysis of gallic acid, corilagin, chebulanin, chebulagic acid, and ellagic acid in the three extracts was performed using high-performance liquid chromatography (HPLC). Antioxidant activity was assessed by the 2,2-diphenylpicrylhydrazyl (DPPH) radical-scavenging assay, and anti-inflammatory activity was evaluated by detecting interleukin (IL)-6 and IL-8 expression in IL-1β-stimulated MH7A cells.Results: The 50% water-ethanol solvent was the optimal solvent yielding the highest total polyphenol content, and the concentrations of chebulanin and chebulagic acid were much higher than those of gallic acid, corilagin, and ellagic acid in the extracts. The DPPH radical-scavenging assay showed that gallic acid and ellagic acid were the strongest antioxidative components, while the other three components showed comparable antioxidative activity. As for the anti-inflammatory effect, chebulanin and chebulagic acid significantly inhibited IL-6 and IL-8 expression at all three concentrations; corilagin and ellagic acid significantly inhibited IL-6 and IL-8 expression at high concentration; and gallic acid could not inhibit IL-8 expression and showed weak inhibition of IL-6 expression in IL-1β-stimulated MH7A cells. Principal component analysis indicated that chebulanin and chebulagic acid were the main components responsible for the anti-arthritic effects of T. chebula.Conclusion: Our findings highlight the potential anti-arthritic role of chebulanin and chebulagic acid from T. chebula.

Graphene plasmons hold potential for infrared optoelectronic devices, but the interaction with the substrate often degrades their quality. Here, the authors report the characterization of plasmons in suspended graphene with tunable suspension height, showing enhanced quality factors and propagation lengths at room temperature.

Background: Our previous study showed that vitamin D (VD)-vitamin D receptor (VDR) plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI.Objective: To investigate the role of VD-VDR in glucose metabolism reprogramming in LPS-induced AKI.Methods: We established a model of LPS-induced AKI in VDR knockout (VDR-KO) mice, renal proximal tubular-specific VDR-overexpressing (VDR-OE) mice and wild-type C57BL/6 mice. In vitro, human proximal tubular epithelial cells (HK-2 cells), VDR knockout and VDR overexpression HK-2 cell lines were used.Results: Paricalcitol (an active vitamin D analog) or VDR-OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in VDR-KO mice. In in vitro experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-PDHA1). Moreover, paricalcitol activated the phosphorylation of AMP-activated protein kinase (AMPK), and an AMPK inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells.Conclusion: VD-VDR alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of PDHA1 phosphorylation via the AMPK pathway.

Abstract Pseudouridine (Ψ) is an abundant mRNA modification in mammalian transcriptome, but its functions have remained elusive due to the difficulty of transcriptome-wide mapping. We develop a nanopore native RNA sequencing method for quantitative Ψ prediction (NanoPsu) that utilizes native content training, machine learning modeling, and single-read linkage analysis. Biologically, we find interferon inducible Ψ modifications in interferon-stimulated gene transcripts which are consistent with a role of Ψ in enabling efficacy of mRNA vaccines.

Abstract Background N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism and m6A dysregulation is implicated in various human diseases. In this study, we explored the potential role of RNA m6A modification in the pathogenesis of Alzheimer disease (AD). Methods We investigated the m6A modification and the expression of m6A regulators in the brain tissues of AD patients and determined the impact and underlying mechanism of manipulated expression of m6A levels on AD-related deficits both in vitro and in vivo. Results We found decreased neuronal m6A levels along with significantly reduced expression of m6A methyltransferase like 3 (METTL3) in AD brains. Interestingly, reduced neuronal m6A modification in the hippocampus caused by METTL3 knockdown led to significant memory deficits, accompanied by extensive synaptic loss and neuronal death along with multiple AD-related cellular alterations including oxidative stress and aberrant cell cycle events in vivo. Inhibition of oxidative stress or cell cycle alleviated shMettl3-induced apoptotic activation and neuronal damage in primary neurons. Restored m6A modification by inhibiting its demethylation in vitro rescued abnormal cell cycle events, neuronal deficits and death induced by METTL3 knockdown. Soluble Aβ oligomers caused reduced METTL3 expression and METTL3 knockdown exacerbated while METTL3 overexpression rescued Aβ-induced synaptic PSD95 loss in vitro. Importantly, METTL3 overexpression rescued Aβ-induced synaptic damage and cognitive impairment in vivo. Conclusions Collectively, these data suggested that METTL3 reduction-mediated m6A dysregulation likely contributes to neurodegeneration in AD which may be a therapeutic target for AD.

Breast cancer is the most common malignant tumor in women and is a big challenge to clinical treatment due to the high morbidity and mortality. The pH/ROS dual-responsive nanoplatforms may be an effective way to significantly improve the therapeutic efficacy of breast cancer. Herein, we report a docetaxel (DTX)-loaded pH/ROS-responsive NP that could achieve active targeting of cancer cells and selective and complete drug release for effective drug delivery. The pH/ROS-responsive NPs were fabricated using nanocarriers that consist of an ROS-responsive moiety (4-hydroxymethylphenylboronic acid pinacol ester, HPAP), cinnamaldehyde (CA, an aldehyde organic compound with anticancer activities) and cyclodextrin (α-CD). The NPs were loaded with DTX, modified with a tumor-penetration peptide (circular RGD, cRGD) and named DTX/RGD NPs. The cRGD could promote DTX/RGD NPs penetration into deep tumor tissue and specifically target cancer cells. After internalization by cancer cells through receptor-mediated endocytosis, the pH-responsive acetal was cleaved to release CA in the lysosomal acidic environment. Meanwhile, the high ROS in tumor cells induced the disassembly of NPs with complete release of DTX. In vitro cellular assays verified that DTX/RGD NPs could be effectively internalized by 4T1 cells, obviously inducing apoptosis, blocking the cell cycle of 4T1 cells and consequently, killing tumor cells. In vivo animal experiments demonstrated that the NPs could target to the tumor sites and significantly inhibit the tumor growth in 4T1 breast cancer mice. Both in vitro and in vivo investigations demonstrated that DTX/RGD NPs could significantly improve the antitumor effect compared to free DTX. Thus, the DTX/RGD NPs provide a promising strategy for enhancing drug delivery and cancer therapy.

Membranes with fast and selective ion transport are highly relevant for energy storage devices. Here, the authors report a layered double hydroxide membrane with high ionic selectivity and hydroxide ion conductivity for flow battery applications, and reveal the ions transport mechanism of the membrane.

Mapping local phonon dispersion in individual nanostructures reveals their thermal, optical, and mechanical properties but requires high detection sensitivity. Here, the authors present position-dependent phonon dispersion measurements in individual boron nitride nanotubes.

Abstract Background N6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain. Results We show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimer’s disease, which is correlated with reduced protein levels. Conclusions Our results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimer’s disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.

The integration of perovskite photodetectors with thin-film transistor (TFT) backplane or complementary metal-oxide-semiconductor CMOS circuit is a key step towards prototyping perovskite-based image sensors. Here, we demonstrate a pixel configuration for indirect X-ray detection comprising of IGZO TFTs and perovskite photodiodes (PDs). The perovskite photodiode is patterned by a two-step deposition method. Our integrated TFT/PD pixel shows a weak light detection capability down to 4 nW cm−2 and a fast-transient response to the pulse light and gate switching. Combining with a CsI scintillator, the integrated pixel achieves a specific X-ray sensitivity of 8.2 $8.2 \times 10^{2} \mu \mathrm{C} \mathrm{mGy}_{\text {air }}^{-1} \mathrm{~cm}^{-3}$ . Theoretically, with a state-of-the-art scintillator, the new pixel can provide a detectable signal for X-ray imaging at a dose rate as low as $10 \mu \mathrm{Gy}_{\text {air }} \mathrm{s}^{-1}$ . This work provides an advanced pixel design for high resolution, high sensitivity, and high frame-rate flat-panel imager.

Luteolin (Lut) is a natural flavonoid polyphenolic compound with multiple pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the poor aqueous solubility and low bioactivity of Lut restrict its clinical translation. Herein, we developed a reactive oxygen species (ROS)-responsive nanoplatforms to improve the bioactivity of Lut. Folic acid (FA) was employed to decorate the nanoparticles (NPs) to enhance its targeting ability. The size of Lut-loaded ROS-responsive nanoparticles (Lut/Oxi-αCD NPs) and FA-modified Lut/Oxi-αCD NPs (Lut/FA-Oxi-αCD NPs) is 210.5 ± 6.1 and 196.7 ± 1.8 nm, respectively. Both Lut/Oxi-αCD NPs and Lut/FA-Oxi-αCD NPs have high drug loading (14.83 ± 3.50 and 16.37 ± 1.47%, respectively). In vitro cellular assays verified that these NPs could be efficiently internalized by 4T1 cells and the released Lut from NPs could inhibit tumor cells proliferation significantly. Animal experiments demonstrated that Lut/Oxi-αCD NPs, especially Lut/FA-Oxi-αCD NPs obviously accumulated at tumor sites, and inhibited tumor growth ∼3 times compared to the Lut group. In conclusion, the antitumor efficacy of Lut was dramatically improved by targeting delivery with the ROS-responsive nanoplatforms.

Abstract Background The study was performed to assess the diagnostic capability of ECG on the cardiogenic shock (CS) in acute myocarditis. A new score was derived from the combination of the ECG parameters and the diagnostic value was also evaluated. Methods Total 103 consecutive patients with acute myocarditis admitted in Nanjing Drum Hospital were enrolled in the current study. The cohort was divided into fulminant myocarditis group (FM, n = 20) and non fulminant myocarditis group (NFM, n = 83). The demographic features, results of electrocardiography (ECG) and ultracardiography were compared. Logistic regression analysis was conducted to identify the relevant factors in ECG parameters. We created a new variable called “ECG score” by certain combination of ECG parameters. The diagnostic capability of ECG score for CS was compared with the existing diagnostic indices using regression model and receiver-operating characteristics (ROC) analysis. Results There were several changes on ECG significantly different between the two groups. Multivariate regression analysis demonstrated PR + QRS interval (P = 0.008), ventricular arrhythmia (P = 0.001) and pathological Q wave (P = 0.003) were the independent relevant factors of CS. The derived variable “ECG score” was identified as a significant relevant factor of CS by multivariate regression model. ROC analysis showed PR + QRS interval, ventricular arrhythmia and pathological Q wave all had equivalent diagnostic capability to left ventricular ejection fraction (LVEF) and shock index (SI). ECG score was equivalent to LVEF but superior to SI in diagnosing CS Conclusions ECG was valuable in diagnosing CS due to acute myocarditis. The ECG score was superior to the traditional diagnostic indices and could be used for an rapid recognition of CS.

BackgroundInhibition of sympathetic activity and renin–angiotensin system with renal denervation (RDN) was proved to be effective in managing refractory hypertension, and improving left ventricular (LV) performance in chronic heart failure. The inhibition of sustained sympathetic activation prevents or delays the development of cardiac fibrosis and dysfunction that occurs after myocardial infarction and ischemia–reperfusion (I/R) injury. The translational efficiency of RDN remains to be defined in preclinical animal studies.ObjectivesThis study investigated the therapeutic role of RDN in adverse remodeling and intramyocardial inflammation in myocardial ischemia–reperfusion (MI/R) injury.MethodsHerein, 15 minipigs were subjected to 90-min percutaneous occlusion of the left anterior descending artery followed by reperfusion. Eight animals received simultaneous RDN using catheter-based radiofrequency ablation (MI/R-RDN). Cardiac function and infarct volume were measured in vivo, followed by histological and biochemical analyses.ResultsThe infarct volume in I/R-RDN pigs reduced at 30 days postreperfusion, compared to I/R-Sham animals. The levels of catecholamine and cytokines in the serum, kidney cortex, the border, and infarcted regions of the heart were significantly reduced in I/R-RDN group. Moreover, the gene expression of collagen and the protein expression of adrenergic receptor beta 1 in heart were also decreased in I/R-RDN mice. Additionally, RDN therapy alleviated myocardial oxidative stress.ConclusionRDN is an effective therapeutic strategy for counteracting postreperfusion myocardial injury and dysfunction, and the application of RDN holds promising prospects in clinical practice.

Background: The inner association of inflammation with voriconazole (VCZ) metabolism has not been fully investigated. We intend to investigate the effects of inflammation on liver function, VCZ trough concentration (C0), C0/dose ratio and the ratio of VCZ to VCZ-N-oxide concentration (C0/CN) in adult and elderly patients.Methods: A single-center retrospective study was conducted among patients who were treated in our hospital between January 2018 and December 2021. For each eligible patient, demographic details, medical history, laboratory parameters, procalcitonin (PCT), C reactive protein (CRP), and interleukin-6 (IL-6) were collected from the medical chart. VCZ CN, TNF-α, IL-1β, IL-8, and IL-10 concentrations were detected in blood samples.Results: A total of 356 patients were included in our study, with 195 patients in the adult cohort (

ObjectiveTo establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method.MethodsA retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model.ResultsThree algorithms (SVR, GBRT, and RF) with high R2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors.ConclusionWe firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.

The global incidence of high myopia is increasing year by year. High myopia is closely related to cataract, but high myopia is accompanied by special pathological changes,which make the operative difficulty and the incidence of postoperative complications of high myopia with cataract is much higher than common cataract. With the advent of the era of refractive cataract, postoperative visual quality requirements of patients are higher, and the challenges to ophthalmologists are also greater. Therefore, we need to pay more attention to the management of patients with high myopia combined with cataract. In this paper, the surgical methods, preoperative biological measurements, common complications during and after the operation of high myopia with cataract were reviewed.

Abstract Objectives Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN). Methods We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up. Results The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0–10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod. Conclusions Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.

Low-cost flow batteries with high power density are promising for energy storage, but membranes with simultaneously high ion conductivity and selectivity should be developed. Here the authors report a thin-film composite membrane that breaks the trade-off between ion conductivity and selectivity.

Renal ischemia-reperfusion (IR) is one of the main causes of renal injury. In severe cases with serious consequences, IR-related renal damage progresses rapidly and can even lead to acute renal failure. Its clinical treatment is currently difficult. According to various studies at home and abroad, HMGB1 is released from the nucleus into the cytoplasm or extracellular space by damaged parenchymal cells during ischemia and hypoxia, and this plays an important role in the initiation of reperfusion injury as an early inflammatory factor and is closely related to the occurrence and development of renal diseases. In recent years, the protective effect of osthole on IR of tissues and organs has been a key topic among clinical researchers. Osthole can inhibit the inflammatory response, reduce cell apoptosis the progression, and improve the prognosis of IR, thus protecting the kidney. During the development of renal IR, finding a mechanism through which the osthole blocks the release of HMGB1 from the nucleus would be helpful in detecting targets for clinical treatment.

Abstract Optical‐field driven electron tunneling in nanojunctions has made demonstrable progress toward the development of ultrafast charge transport devices at subfemtosecond time scales, and have evidenced great potential as a springboard technology for the next generation of on‐chip “lightwave electronics.” Here, the empirical findings on photocurrent the high nonlinearity in metal–insulator–metal (MIM) nanojunctions driven by ultrafast optical pulses in the strong optical‐field regime are reported. In the present MIM device, a 14th power‐law scaling is identified, never achieved before in any known solid‐state device. This work lays important technological foundations for the development of a new generation of ultracompact and ultrafast electronics devices that operate with suboptical‐cycle response times.

Strong-field photoemission is the emission of electrons driven by a strong electric field of light. Here the authors demonstrate a highly non-linear strong-field photoemission, approaching the 40th power-law scaling, from carbon nanotubes, yielding a photoemission current with up to 100% carrier-envelope phase modulation depth.

Abstract Background Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs). Results MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H2O2. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs. Conclusions Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.

Identification of gas molecules is crucial in healthcare and security applications. Here the authors achieve label-free identification of SO2, NO2, N2O, and NO gas molecules by detecting their rotational-vibrational modes using graphene nanoribbon plasmons.

Abstract Background Enzymatic biodegradation of organophosphate pesticides (OPs) is a promising technology to remove these toxic compounds. However, its application in industrial washing was restricted by the lack of efficient immobilized enzymes that can work at high temperatures and high pHs in the presence of various detergents. Therefore, it is necessary to develop a simple method to prepare a robust immobilized enzyme for efficient degradation of OPs. Results An organophosphate hydrolase (OPH), PoOPHM9, was conjugated and immobilized with a commercially available polymer, Pluronic F127. The prepared cross-linked enzyme-polymer conjugate (CLEPC) displayed higher pH stability in the range from 7.0 to 11.0 and a higher optimal temperature (50 °C) than that of free PoOPHM9 (30 °C). Its half-life and apparent k cat/K M reached 12.8 h at 50 °C and 390.3 ± 7.8 mM−1 s−1, respectively, which were even better than that of the traditional cross-linked enzyme aggregates (CLEA, 7.2 h and 10.9 ± 1.7 mM−1 s−1). The activity of PoOPHM9 CLEPC was further enhanced up to 2.5-fold by the anionic, nonionic and biocompatible detergents, which was first observed. 0.15 mM Malathion was degraded completely by PoOPHM9 CLEPC after activation within 10 min in the presence of 0.1% (w/w) detergents of all types at pH 9.0 and 25 °C, demonstrating its capability in degrading OPs at practically relevant conditions. Conclusion The conjugation of Pluronic F127 in enzyme immobilization could effectively reduce the activity loss of immobilized enzymes and enhance their stability and activity at high temperatures and high pHs. In addition, the activity of CLEPC can be even enhanced in the presence of various detergents. This technology can be extended easily to produce other immobilized polymer-enzyme conjugates due to its simplicity.