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How to eliminate the background signal of the electrochemical aptasensor and improve its signal amplification efficiency is one of the key factors to build a highly sensitive and selective sensor. Herein, we developed a multi-signal amplified, zero background electrochemical aptasensor for rapid detection of tumor markers, with carcinoembryonic antigen (CEA) as a model analyte. A type of dendritic DNA scaffold labeled with a lead-based metal organic framework (HCR-Pb-MOF) was prepared by hybrid chain reaction as signal tags. After one-step replacement of the signal tags into the supernatant by the target, the inner Pb2+ ions in the replaced tags were detected by square-wave voltammetry (SWV) for qualification. The assay has some distinct advantages. Firstly, one HCR-Pb-MOF can load many Pb-MOFs, with each Pb-MOF containing large amounts of Pb2+; thus, multi-amplified signals from Pb2+ can be obtained after one-step replacement of the target. Secondly, Pb-MOF can also completely avoid the leakage of Pb2+, which is usually observed in the MOF probes electrostatically adsorbing metal ions, to achieve zero background. Thus, the aptasensor with a one-step replacement detection strategy can greatly improve sensitivity, with the detection limit of CEA being 0.333 pg mL−1. Finally, the stirring bar was employed after introducing the target into the system. Therefore, the whole sample detection time can be reduced to within 10 min. This aptasensor was successfully applied to rapidly and accurately analyze CEA in human serum, with results consistent to those of ELISA. All of these findings prove that this multi-signal amplified, rapid, zero background electrochemical aptasensor can meet the requirements for rapid and highly sensitive detection of tumor markers in human serum. Unlabelled Image • An enzyme-free and multi-signal amplified electrochemical aptasensor with DNA-Pb-MOF scaffold as signal tag was developed. • The employment of Pb-MOF can overcome the leakage of Pb2+ to bring zero background. • The detection based on one-step replacement of signal tags by target can greatly reduce the detection time. • The assay showed high sensitivity and specificity to detect 0.333 pg mL-1 CEA in serums. [ABSTRACT FROM AUTHOR]

An enzyme-free fluorometric assay is described that accomplishes dual signal amplification by making use of a two stirring bars. Two Y-shaped DNA probes were designed and placed on the bars. When the target (with chloramphenicol as model analyte) is added, it triggers target recycling and simultaneously catalyzes hairpin assembly (CHA). A large fraction of DNA primers is released by the analyte from the bar to the supernatant and open hairpins with G-quadruplex DNA sequence. The G-quadruplex can specifically bind thioflavin T (ThT) to emit fluorescence (with excitation/emission maxima at 445 and 485 nm) for quantification of chloramphenicol. An enzyme is not needed. ThT is added to the system as a fluorescent DNA probe. All this strongly reduces the cost for sensor construction and usage. The dual signal amplification steps occur simultaneously which reduces the detection time. The assay was successfully employed to the determination of CAP in spiked milk and fish samples within 60 min and with a 16 pM limit of detection (at S/N = 3).Schematic representation of a new method for the detection of chloramphenicol by using  two stirring bars. It is based on target recycling and catalyzed hairpin assembly amplification. CAP: chloramphenicol, ThT: thioflavin T, CHA: catalyzed hairpin assembly. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIOP) is a widespread disease characterized by low bone density. There remains a lack of effective means for osteoporosis. Rehmannioside A (ReA), an iridoid glycoside, exhibits various pharmacological activities. This study aimed to explore the role and mechanism of ReA in osteogenic differentiation of osteoblasts. Cell viability, reactive oxygen species (ROS) generation, and cell apoptosis were assessed using corresponding assay kits. Real-time quantitative polymerase chain reaction, Western blotting, and alkaline phosphatase (ALP) staining were performed to evaluate the osteogenic differentiation of MC3T3-E1 cells. Alizarin red S staining was used to assess the mineralization of MC3T3-E1 cells. Protein expression associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was analyzed using Western blotting. Micro-computed tomography, histopathological, and immunohistochemical analyses were performed to determine the therapeutic effect of ReA on GIOP in vivo.The results showed that ReA promoted the osteogenic differentiation of MC3T3-E1 cells by regulating the PI3K/AKT signaling pathway and protected mice against glucocorticoid-induced bone loss by promoting osteoblast-mediated bone formation in vivo. The findings of the current study revealed that ReA is a potential therapeutic agent for osteoporosis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In order to address the issue of low amino acid retention in the production of xylooligosaccharides (XOS) through hydrothermal pretreatment at high temperatures, a novel approach combining low temperature acid hydrolysis and enzymatic hydrolysis was employed. This innovative method not only allows for the production of amino acid-rich XOS, but also yields a valuable byproduct known as humic-like acid (HLA) from vinegar residue (VR). Under the optimal pretreatment conditions (89 °C, 6 h, 1.2 % sulfuric acid), the yield of XOS was 19.88 %. Furthermore, the hydrolyzate extracted from the acid pretreated VR had a content of 2.65 g/L amino acids (corresponding to the retention rate of 82.0 %), and the HLA yield of the sample was 10.51 %. Comprehensive analyses, such as Fourier transform infrared spectroscopy, elemental analysis, total acidic functional group, and nuclear magnetic resonance were employed to examine the structure and composition of the produced HLA, indicating that it was similar to that of natural commercial humic acid (CHA) extracted from minerals. Through this innovative approach, the production of amino acid-rich XOS and HLA from VR offers a sustainable solution that not only addresses the issue of low amino acid retention but also maximizes the potential of VR as a valuable resource., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

High-altitude polycythemia (HAPC) is a pathological state resulting from maladaptation to prolonged high-altitude exposure, posing significant risks to the cardiovascular health of highlanders. However, its influence on hypertension-mediated organ damages (HMODs) in hypertensive individuals remains unclear. We recruited hypertensive patients residing at altitudes above 2500 m for over 3 years. A case-control matching was conducted in a 1:1 ratio between hypertensive patients with and without HAPC, based on gender and age. Echocardiography, carotid artery ultrasound, and brachial flow-mediated dilation (FMD) were measured as HMODs. A total of 88 hypertensive patients were included in the analysis, with 44 with HAPC and 44 without HAPC. Patients with HAPC showed significantly higher hemoglobin (HGB) levels (217.82 ± 17.34 vs. 160.16 ± 13.25, P<0.001), a larger left atrium (LA) diameter (35.36 ± 4.25 vs. 33.09 ± 3.55, P = 0.008), and a higher proportion of impaired FMD (95.45% vs. 79.55%, P = 0.049) compared to those without HAPC. No significant differences were found between the two groups in diastolic function parameters, left ventricular mass index (LVMI), relative wall thickness (RWT), or intima-media thickness (IMT). After adjusting for age, gender, and other confounding factors, HGB remained significantly associated with LA diameter (β = 0.034, P = 0.023) and impaired FMD (OR = 1.034, 95% CI 1.001-1.069). After matching for age and gender, hypertensive patients with HAPC exhibited a significantly larger LA diameter and a higher prevalence of impaired FMD compared to those without HAPC. Additionally, HGB was identified as an independent risk factor for both increased LA diameter and impaired FMD in hypertensive patients with HAPC., (© 2024. The Author(s).)

The invasive Phytolacca americana L. poses a significant threat to local agroforestry ecosystems due to its allelopathic toxicity. However, the ecophysiological response mechanisms of crops to allelochemicals remain unclear. This study investigated the seedling growth, physiological, and biochemical responses of three gramineous crops to the root extracts of P. americana and identified potential allelochemicals of the invader. The germination and seedling growth of three crops were inhibited by extracts differently, with high-concentration extracts causing more severe inhibition on seedling roots in hydroponic (>57%) than soil culture experiments (>18%). This inhibition may be related to representative secondary metabolites such as fatty acyls, alkaloids, and phenols. Despite the significant inhibition of high-concentration extracts on seedling growth, the levels of soluble sugar, soluble protein, and antioxidant enzymes increased synergistically. Under allelopathic stress, three species enhanced antioxidant enzyme activities and metabolite contents at the cost of reducing their shoot, root biomass, and root/shoot ratio. This may be an ecophysiological growth-defense strategy to bolster their resistance to allelopathy. Interestingly, transgenic rice exhibited greater sensitivity to allelochemicals than wild-type rice, resulting in more pronounced growth inhibition and increased levels of most metabolites and antioxidant enzymes. This study highlights the adaptive strategies of three gramineous crops to the allelopathy of invasive P. americana .

Objectives: To study the relationship between the ablation range and applied energy of laser ablation (LA) and microwave ablation (MWA) in papillary thyroid microcarcinoma (PTMC)., Methods: A total of 201 PTMC patients were treated with LA (n = 102) or MWA (n = 99) with single-applicator fixed ablation. The ablation range was determined by contrast-enhanced ultrasound. The ratios of ablation volume, longitudinal diameter, and orthogonal diameter to ablation energy (R AV/E , R AL/E , R AO/E ) were analyzed and compared between MWA and LA. The effects of PTMC characteristics and Hashimoto's thyroiditis (HT) on ablation efficiency were evaluated by linear regression., Results: The R AV/E was 0.72 (0.65-0.84) mm 3 /J for MWA and 0.48 (0.39-0.54) mm 3 /J for LA. HT was significantly correlated with R AV/E of LA (coefficient =  - 0.367, p < 0.0001). R AL/E did not differ significantly between MWA and LA (MWA 0.026 mm/J, LA 0.025 mm/J; p = 0.957). However, MWA had a greater R AO/E than LA (MWA 0.014 mm/J, LA 0.012 mm/J; p < 0.0001). The plateau values of MWA and LA on the ablation orthogonal diameter were 10.7 mm and 8.69 mm, respectively., Conclusions: MWA showed a higher R AV/E than LA. More intuitively, MWA had a better ablation performance than LA on the orthogonal axis rather than the longitudinal axis. Theoretically, MWA and LA could achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. HT had a negative effect on LA but not on MWA., Clinical Relevance Statement: This study establishes strong connections between ablation energy and ablation range in papillary thyroid microcarcinoma (PTMC) in vivo, possibly contributing to the supplementation of the PTMC Ablation Consensus or Guidelines and providing a scientific basis for choosing clinical ablation parameters in PTMC., Key Points: • Both microwave ablation (MWA) and laser ablation (LA) have excellent performance on the ablation longitudinal axis (easily exceeding 10 mm) for papillary thyroid microcarcinoma (PTMC). • MWA performed much better than LA on the ablation orthogonal axis. • MWA and LA are expected to achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin., (© 2024. The Author(s).)

Table tennis training has been employed as an exercise treatment to enhance cognitive brain functioning in patients with mental illnesses. However, research on its underlying mechanisms remains limited. In this study, we investigated functional and structural changes in large-scale brain regions between 20 table tennis players (TTPs) and 21 healthy controls (HCs) using 7-Tesla magnetic resonance imaging (MRI) techniques. Compared with those of HCs, TTPs exhibited significantly greater fractional anisotropy (FA) and axial diffusivity (AD) values in multiple fiber tracts. We used the locations with the most significant structural changes in white matter as the seed areas and then compared static and dynamic functional connectivity (sFC and dFC). Brodmann 11, located in the orbitofrontal cortex, showed altered dFC values to large-scale brain regions, such as the occipital lobe, thalamus, and cerebellar hemispheres, in TTPs. Brodmann 48, located in the temporal lobe, showed altered dFC to the parietal lobe, frontal lobe, cerebellum, and occipital lobe. Furthermore, the AD values of the forceps minor (Fmi) and right anterior thalamic radiations (ATRs) were negatively correlated with useful field of view (UFOV) test scores in TTPs. Our results suggest that table tennis players exhibit a unique pattern of dynamic neural activity, this provides evidence for potential mechanisms through which table tennis interventions can enhance attention and other cognitive functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer, which is highly aggressive and incurable. Here, we proposed an ultrasound activatable bromodomain-containing protein 4 (BRD4) proteolysis targeting chimera (PROTAC) release strategy for the first time for precisely controlled protein degradation in preclinical TNBC model. Through combination of PROTAC and ultrasound-targeted microbubble destruction (UTMD) technology, the present strategy also aims to concurrently solve the major limitations of poor loading capacity of microbubbles and undesirable targeting and membrane permeability of PROTAC. PROTAC (ARV-825)-encapsulated microbubbles, ARV-MBs, were developed for the efficacious treatment of TNBC in vitro and in vivo. The microbubbles we synthesized showed ultrasound-responsive drug release ability, which could effectively promote the penetration of PROTAC into tumor site and tumor cell. Under ultrasound, ARV-MBs could play an effective antitumor effect by potentiating the ubiquitination and degradation of BRD4 in tumor. The current study may provide a new idea for promoting clinical translation of drug-loaded microbubbles and PROTAC, and offer a new efficacious therapeutic modality for TNBC., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Hongye He et al.)

Background: The clinical strategy of oral supplementation of Vitamin D (VD) as a preventive and therapeutic measure for warts needs further exploration., Methods: The clinical data of patients with skin diseases who visited the Children's Hospital affiliated with Chongqing Medical University from February 2018 to June 2024 were collected. The serum VD levels in patients with warts (common warts, flat warts, and plantar warts) and patients with other common skin diseases (atopic dermatitis, psoriasis, alopecia areata, vitiligo, and chronic urticaria) were compared. Two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate potential causal associations between VD and warts., Results: The average serum VD level of children with warts was 23.27 ± 7.07 ng/mL, which showed no statistically significant difference compared to children with other common skin diseases. The inverse variance weighted (IVW) method analysis indicated a positive causal relationship between VD and warts (Odds Ratio [OR] = 1.86, [95% CI: 1.19-2.92], p = 0.007). Sensitivity analysis did not show any indication of horizontal pleiotropy or heterogeneity. The MR-PRESSO method did not identify any outliers., Conclusion: The levels of serum VD in children with warts do not significantly decrease compared to children with other common skin conditions. The evidence from the MR analysis indicates a positive causal relationship between VD and warts, suggesting caution in supplementing VD for children with warts who have normal or elevated serum VD levels. Further clinical studies are needed for validation in the future., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Purpose: Osteosarcoma is a primary bone tumor lacking optimal clinical treatment options. Tumor-associated macrophages in the tumor microenvironment are closely associated with tumor development and metastasis. Studies have identified the macrophage receptor with collagenous structure (MARCO) as a specific receptor expressed in macrophages. This study aimed to investigate whether anti-MARCO mAb treatment can induce macrophage polarization in the tumor microenvironment and elicit anti-tumor effects., Methods: THP-1 cells were treated with 20 ng/mL phorbol 12-myristate 13-acetate and 80 ng/mL interleukin-4 for 48 h to induce macrophage polarization to alternatively activated macrophages (M2). Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, flow cytometry, and bioinformatic analyses were performed to evaluate macrophage polarization. The co-culture groups included a blank group, an M2 macrophage and U2OS co-culture group, and an anti-MARCO mAb-treated M2 macrophage group. Cell viability assays, cell scratch tests, apoptosis, and cell cycle analyses were performed to determine the effects of anti-MARCO mAb-treated macrophages on osteosarcoma cells., Results: It was demonstrated that anti-MARCO mAb can drive macrophages toward classically activated macrophage (M1) polarization. Anti-MARCO mAb promoted the secretion of pro-inflammatory factors by macrophages, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta, interleukin-6 and interleukin-23. Studies on in vitro co-culture models have revealed that macrophages treated with anti-MARCO mAb can suppress the growth and migration of osteosarcoma cells, induce cell apoptosis, and inhibit cell cycle progression of osteosarcoma cells through M1 polarization of macrophages in vitro., Conclusion: Anti-MARCO mAb treatment exerts anti-osteosarcoma effects by affecting macrophage polarization toward M1 macrophages, offering a potential new therapeutic approach for treating osteosarcoma., (© 2024. The Author(s).)

Glycosylation is the most structurally diverse form of post-translational modification (PTM) of proteins that affects a myriad of cellular processes. As a pivotal regulator of protein homeostasis, glycosylation notably impacts the function of proteins, spanning from protein localization and stability to protein-protein interactions. Aberrant glycosylation is a hallmark of cancer, and extensive studies have revealed the multifaceted roles of glycosylation in tumor growth, migration, invasion and immune escape Over the past decade, glycosylation has emerged as an immune regulator in the tumor microenvironment (TME). Here, we summarize the intricate interplay between glycosylation and the immune system documented in recent literature, which orchestrates the regulation of the tumor immune response through endogenous lectins, immune checkpoints and the extracellular matrix (ECM) in the TME. In addition, we discuss the latest progress in glycan-based cancer immunotherapy. This review provides a basic understanding of glycosylation in the tumor immune response and a theoretical framework for tumor immunotherapy.

As a pivotal subfield within the domain of time series forecasting, runoff forecasting plays a crucial role in water resource management and scheduling. Recent advancements in the application of artificial neural networks (ANNs) and attention mechanisms have markedly enhanced the accuracy of runoff forecasting models. This article introduces an innovative hybrid model, ResTCN-DAM, which synergizes the strengths of deep residual network (ResNet), temporal convolutional networks (TCNs), and dual attention mechanisms (DAMs). The proposed ResTCN-DAM is designed to leverage the unique attributes of these three modules: TCN has outstanding capability to process time series data in parallel. By combining with modified ResNet, multiple TCN layers can be densely stacked to capture more hidden information in the temporal dimension. DAM module adeptly captures the interdependencies within both temporal and feature dimensions, adeptly accentuating relevant time steps/features while diminishing less significant ones with minimal computational cost. Furthermore, the snapshot ensemble method is able to obtain the effect of training multiple models through one single training process, which ensures the accuracy and robustness of the forecasts. The deep integration and collaborative cooperation of these modules comprehensively enhance the model's forecasting capability from various perspectives. Ablation studies conducted validate the efficacy of each module, and through multiple sets of comparative experiments, it is shown that the proposed ResTCN-DAM has exceptional and consistent performance across varying lead times. We also employ visualization techniques to display heatmaps of the model's weights, thereby enhancing the interpretability of the model. When compared with the prevailing neural network-based runoff forecasting models, ResTCN-DAM exhibits state-of-the-art accuracy, temporal robustness, and interpretability, positioning it at the forefront of contemporary research.

Table tennis players have adaptive visual and sensorimotor networks, which are the key brain regions to acquire environmental information and generate motor output. This study examined 20 table tennis players and 21 control subjects through ultrahigh field 7 Tesla magnetic resonance imaging. First, we measured percentage amplitude of fluctuation across five different frequency bands and found that table tennis players had significantly lower percentage amplitude of fluctuation values than control subjects in 18 brain regions, suggesting enhanced stability of spontaneous brain fluctuation amplitudes in visual and sensorimotor networks. Functional connectional analyses revealed increased static functional connectivity between two sensorimotor nodes and other frontal-parietal regions among table tennis players. Additionally, these players displayed enhanced dynamic functional connectivity coupled with reduced static connectivity between five nodes processing visual and sensory information input, and other large-scale cross-regional areas. These findings highlight that table tennis players undergo neural adaptability through a dual mechanism, characterized by global stability in spontaneous brain fluctuation amplitudes and heightened flexibility in visual sensory networks. Our study offers novel insights into the mechanisms of neural adaptability in athletes, providing a foundation for future efforts to enhance cognitive functions in diverse populations, such as athletes, older adults, and individuals with cognitive impairments., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to explore the interactions between microbubbles and microwave ablation (MWA)., Methods: The study employed custom-made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 10 5 particles mL -1 ) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K-type thermocouple probes were used to monitor the MWA-induced temperature increase. Contrast-enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation-zone volumes were evaluated and compared between the groups with and without microbubbles., Results: In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA-induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble-defect region over the ablation time. An increase in the temperature caused microbubble destruction., Conclusions: Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature-dependent manner. Thus, the poor thermotolerance of microbubbles is a non-negligible barrier when using CEUS to monitor the ablation range during MWA in real-time., (© 2024 American Institute of Ultrasound in Medicine.)

Objectives: The aims of this study were to explore the incidence characteristics and trend prediction of lymphoma from 2005 to 2035, and to provide data basis for the prevention and control of lymphoma in China., Method: The data on lymphoma incidence in China from 2005 to 2017 were obtained from the Chinese Cancer Registry Annual Report. The Joinpoint regression model was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to reflect time trends. Age-period-cohort models were conducted to estimate age, period, and cohort effects on the lymphoma incidence. A Bayesian age-period-cohort model was used to predict lymphoma incidence trends from 2018 to 2035., Results: From 2005 to 2017, the incidence of lymphoma was 6.26/100,000, and the age-standardized incidence rate (ASIR) was 4.11/100,000, with an AAPC of 1.4% [95% confidence interval (CI): 0.3%, 2.5%]. The ASIR was higher in men and urban areas than in women and rural areas, respectively. The age effect showed that the incidence risk of lymphoma increased with age. In the period effect, the incidence risk of lymphoma in rural areas decreased first and then increased with 2010 as the cutoff point. The overall risk of lymphoma incidence was higher in the cohort before the 1970-1974 birth cohort than in the cohort after. From 2018 to 2035, the lymphoma incidence in men, women, and urban areas will show an upward trend., Conclusion: From 2005 to 2017, the incidence of lymphoma showed an increasing trend, and was different in regions, genders, and age groups in China. It will show an upward trend from 2018 to 2035. These results are helpful for the formulation and adjustment of lymphoma prevention, control, and management strategies, and have important reference significance for the treatment of lymphoma in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Shao, Cao, Lu, Lei, Chen, Tong, Lu, Yan, Zhang, Pan and Nong.)

Background: Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment., Results: Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis., Conclusions: Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings., (© 2024. The Author(s).)

Rapid, simultaneous, and sensitive detection of biomolecules has important application prospects in disease diagnosis and biomedical research. However, because the content of intracellular endogenous target biomolecules is usually very low, traditional detection methods can't be used for effective detection and imaging, and to enhance the detection sensitivity, signal amplification strategies are frequently required. The hybridization chain reaction (HCR) has been used to detect many disease biomarkers because of its simple operation, good reproducibility, and no enzyme involvement. Although HCR signal amplification methods have been employed to detect and image intracellular biomolecules, there are still false positive signals. Therefore, a target-triggered enzyme-free amplification system (GHCR system) was developed, as a fluorescent AND-gated sensing platform for intracellular target probing. The false positive signals can be well avoided and the accuracy of detection and imaging can be improved by using the design of the AND gate. Two cancer markers, GSH and miR-1246, were used as two orthogonal inputs for the AND gated probe. The AND-gated probe only works when GSH and miR-1246 are the inputs at the same time, and FRET signals can be the output. In addition to the use of AND-gated imaging, FRET-based high-precision ratiometric fluorescence imaging was employed. FRET-based ratiometric fluorescent probes have a higher ability to resist interference from the intracellular environment, they can avoid false positive signals well, and they are expected to have good specificity. Due to the advantages of HCR, AND-gated, and FRET fluorescent probes, the GHCR system exhibited highly efficient AND-gated FRET bioimaging for intracellular endogenous miRNAs with a lower detection limit of 18 pM, which benefits the applications of ratiometric intracellular biosensing and bioimaging and offers a novel concept for advancing the diagnosis and therapeutic strategies in the field of cancer.

Table tennis involves quick and accurate motor responses during training and competition. Multiple studies have reported considerably faster visuomotor responses and expertise-related intrinsic brain activity changes among table tennis players compared with matched controls. However, the underlying neural mechanisms remain unclear. Herein, we performed static and dynamic resting-state functional magnetic resonance imaging (rs-fMRI) analyses of 20 table tennis players and 21 control subjects using 7T ultra-high field imaging. We calculated the static and dynamic amplitude of low-frequency fluctuations (ALFF) of the two groups. The results revealed that table tennis players exhibited decreased static ALFF in the left inferior temporal gyrus (lITG) compared with the control group. Voxel-wised static functional connectivity (sFC) and dynamic functional connectivity (dFC) analyses using lITG as the seed region afforded complementary and overlapping results. The table tennis players exhibited decreased sFC in the right middle temporal gyrus and left inferior parietal gyrus. Conversely, they displayed increased dFC from the lITG to prefrontal cortex, particularly the left middle frontal gyrus, left superior frontal gyrus-medial, and left superior frontal gyrus-dorsolateral. These findings suggest that table tennis players demonstrate altered visuomotor transformation and executive function pathways. Both pathways involve the lITG, which is a vital node in the ventral visual stream. These static and dynamic analyses provide complementary and overlapping results, which may help us better understand the neural mechanisms underlying the changes in intrinsic brain activity and network organization induced by long-term table tennis skill training., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhao, Cao, Gao, Wang, Yun, Luo, Liu and Zheng.)

This paper addresses fixed-time output synchronization problems for two types of complex dynamical networks with multi-weights (CDNMWs) by using two types of adaptive control methods. Firstly, complex dynamical networks with multiple state and output couplings are respectively presented. Secondly, several fixed-time output synchronization criteria for these two networks are formulated based on Lyapunov functional and inequality techniques. Thirdly, by employing two types of adaptive control methods, fixed-time output synchronization issues of these two networks are dealt with. At last, the analytical results are verified by two numerical simulations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Immune checkpoint blockade (ICB) typified by anti-PD-1/PD-L1 antibodies as a revolutionary treatment for solid malignancies has been limited to a subset of patients due to poor immunogenicity and inadequate T cell infiltration. Unfortunately, no effective strategies combined with ICB therapy are available to overcome low therapeutic efficiency and severe side effects. Ultrasound-targeted microbubble destruction (UTMD) is an effective and safe technique holding the promise to decrease tumor blood perfusion and activate anti-tumor immune response based on the cavitation effect. Herein, we demonstrated a novel combinatorial therapeutic modality combining low-intensity focused ultrasound-targeted microbubble destruction (LIFU-TMD) with PD-L1 blockade. LIFU-TMD caused the rupture of abnormal blood vessels to deplete tumor blood perfusion and induced the tumor microenvironment (TME) transformation to sensitize anti-PD-L1 immunotherapy, which markedly inhibited 4T1 breast cancer's growth in mice. We discovered immunogenic cell death (ICD) in a portion of cells induced by the cavitation effect from LIFU-TMD, characterized by the increased expression of calreticulin (CRT) on the tumor cell surface. Additionally, flow cytometry revealed substantially higher levels of dendritic cells (DCs) and CD8 + T cells in draining lymph nodes and tumor tissue, as induced by pro-inflammatory molecules like IL-12 and TNF-α. These suggest that LIFU-TMD as a simple, effective, and safe treatment option provides a clinically translatable strategy for enhancing ICB therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Cao, Liu, Zhou, He, Tang, Wan, Wang, Xiong, Zhong and Li.)

As edge computing platforms need low power consumption and small volume circuit with artificial intelligence (AI), we design a compact and stable memristive visual geometry group (MVGG) neural network for image classification. According to characteristics of matrix-vector multiplication (MVM) using memristor crossbars, we design three pruning methods named row pruning, column pruning, and parameter distribution pruning. With a loss of only 0.41% of the classification accuracy, a pruning rate of 36.87% is obtained. In the MVGG circuit, both the batch normalization (BN) layers and dropout layers are combined into the memristive convolutional computing layer for decreasing the computing amount of the memristive neural network. In order to further reduce the influence of multistate conductance of memristors on classification accuracy of MVGG circuit, the layer optimization circuit and the channel optimization circuit are designed in this article. The theoretical analysis shows that the introduction of the optimized methods can greatly reduce the impact of the multistate conductance of memristors on the classification accuracy of MVGG circuits. Circuit simulation experiments show that, for the layer-optimized MVGG circuit, when the number of multistate conductance of memristors is 2 5 = 32 , the optimized circuit can basically achieve an accuracy of the full-precision MVGG. For the channel-optimized MVGG circuit, when the number of multistate conductance of memristors is 2 2 = 4 , the optimized circuit can basically achieve an accuracy of the full-precision MVGG.

Photothermal therapy (PTT), by converting light to thermal energy, has become a novel and noninvasive technique for tumor thermal ablation in clinical practice. However, as a result of phagocytosis of reticuloendothelial cells, current photothermal agents (PTAs) derived from exogenous materials suffer from incompetent tumor targeting and brief internal circulation time. The resulting poor accumulation of PTAs in the target area severely reduces the efficacy of PTT. In addition, the potential toxicity of PTAs, excessive laser exposure, and possibilities of tumor recurrence and metastasis following PTT are still intractable problems that severely influence patients' quality of life. Herein, a biomimetic pH-responsive nanoprobe was prepared via cancer cell membrane coating polydopamine (PDA)-CaCO 3 nanoparticles (CPCaNPs) for photoacoustic (PA)/ultrasonic (US)/thermal imaging-guided PTT. When CPCaNPs targeted and infiltrated into the tumor's acidic microenvironment, the decomposed CO 2 bubbles from homologous targeting CPCaNPs enhanced ultrasonic (US) signals obviously. At the same time, the PDA of CPCaNPs not only performed efficient PTT of primary tumors but also generated photoacoustic (PA) signals. In addition, an immune checkpoint pathway blockade was combined, which inhibited tumor recurrence and metastasis significantly and improved the immunosuppressive microenvironment after PTT to a large extent. Thus, these proposed biomimetic pH-responsive CPCaNPs provide a promising strategy for precise PTT immunotherapy under the intelligent guidance of PA/US/thermal imaging and show great potential for clinical translation.

Background: Even though PD-1/PD-L1 is an identified key "don't find me" signal to active adaptive immune system for cancer treatment, the overall response rate (ORR) for all cancer patients is still limited. Other effective therapeutic modalities to bridge the innate and adaptive immunity to improve ORR are urgently needed. Recently, CD47/SIRPα interaction is confirmed as a critical "don't eat me" signal to active innate immunity. However, the red blood cell (RBC) toxicity is the big concern for the development of CD47-based anti-cancer therapeutics. Methods: Here, we report the development of a CD47/PD-L1 bispecific antibody 6MW3211 to block both PD-1/PD-L1 and CD47/SIRPα signals, and studied the effects of 6MW3211 on anti-tumor immune functions in vitro and in vivo . The pharmacokinetic and toxicity profiles of 6MW3211 were evaluated in GLP non-human primate (NHP) studies. Results: The dual immune checkpoint inhibitory signaling blocker 6MW3211 shows high binding affinity to PD-L1 and low binding affinity to CD47. This inequivalent binding affinity design makes 6MW3211 preferentially bound to PD-L1 on tumor cells followed by disrupting the interaction of CD47/SIRPα. Complex structure determination and flow cytometry assay demonstrated that 6MW3211 has no binding to either human or rhesus monkey RBCs. 6MW3211 effectively blocked both PD-1/DP-L1 and CD47/SIRPα signaling and promoted macrophage phagocytosis of tumor cells. Potent therapeutic efficacies of 6MW3211 in three different mouse models were further observed. Moreover, 6MW3211 was demonstrated to have a fairly good safety profile in a GLP NHP study. In addition, multiplex fluorescent immunohistochemistry (mIHC) staining shows that PD-L1 and CD47 co-express on several different types of human tumor tissues. Conclusions: These results support the development of 6MW3211 for the treatment of PD-L1 and CD47 double positive cancers., Competing Interests: Competing Interests: Rongjuan Wang, Chang Zhang, Yuting Cao, Junchao Wang, Shasha Jiao, Jiao Zhang, Min Wang, Peipei Tang, Zijun Ouyang, Wenlu Liang, Yu Mao, An Wang, Gang Li, Jinchao Zhang, Mingzhu Wang, Shuang Wang and Xun Gui are employees of Mabwell (Shanghai) Bioscience Co., Ltd. and may hold shares in Mabwell (Shanghai) Bioscience Co., Ltd. The other authors declare no competing interests., (© The author(s).)

Background: High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment., Methods: M@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy., Results: Guided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU's killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8 + T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed., Conclusions: Our findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host's antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Alkaline pectate lyases have biotechnological applications in plant fiber processing, such as ramie degumming. Previously, we characterized an alkaline pectate lyase from Bacillus clausii S10, named BacPelA, which showed potential for enzymatic ramie degumming because of its high cleavage activity toward methylated pectins in alkaline conditions. However, BacPelA displayed poor thermo-alkaline stability. Here, we report the 1.78 Å resolution crystal structure of BacPelA in apo form. The enzyme has the characteristic right-handed β-helix fold of members of the polysaccharide lyase 1 family and shows overall structural similarity to them, but it displays some differences in the details of the secondary structure and Ca 2+ -binding site. On the basis of the structure, 10 sites located in flexible regions and showing high B-factor and positive Δ T m values were selected for mutation, aiming to improve the thermo-alkaline stability of the enzyme. Following site-directed saturation mutagenesis and screening, mutants A238C, R150G, and R216H showed an increase in the T 50 15 value at pH 10.0 of 3.0 °C, 6.5 °C, and 7.0 °C, respectively, compared with the wild-type enzyme, interestingly accompanied by a 24.5%, 46.6%, and 61.9% increase in activity. The combined mutant R150G/R216H/A238C showed an 8.5 °C increase in the T 50 15 value at pH 10.0, and an 86.1% increase in the specific activity at 60 °C, with approximately doubled catalytic efficiency, compared with the wild-type enzyme. Moreover, this mutant retained 86.2% activity after incubation in ramie degumming conditions (4 h, 60 °C, pH 10.0), compared with only 3.4% for wild-type BacPelA. The combined mutant increased the weight loss of ramie fibers in degumming by 30.2% compared with wild-type BacPelA. This work provides a thermo-alkaline stable, highly active pectate lyase with great potential for application in the textile industry, and also illustrates an effective strategy for rational design and improvement of pectate lyases.

Objective: The outcome of congenital clubfoot treatment is still challenging if the feet deformities are not completely corrected. Here we explore a minimal invasive procedure with an eight-plate implant to correct the residual forefoot adduction deformity after treatment of neglected or relapsed clubfoot., Methods: We retrospectively reviewed patients with residual forefoot adduction deformity after clubfoot treatment between January 2013 and June 2016. The patients underwent temporary epiphysiodesis of the lateral column of the mid-foot, which in detail, an eight-plate was placed on each side of the calcaneocuboid joint. The foot deformities were recorded according to the weight-bearing radiographic measurements including talo-first metatarsal angle, calcaneo-fifth metatarsal angle and medial-to-lateral column length., Results: A total of 13 patients (20 feet) with an average age of 7.8 years old were located with an average duration of 40.8 months follow-up (range, 28 to 54 months). The average talo-first metatarsal angle improved from 28.3° (range, 19° to 47°) preoperatively to 8.3° (range, 3° to 18°) and the calcaneo-fifth metatarsal angle improved from 29.1° (range, 19° to 40°) preoperatively to 8.4° (range, 0° to 21°) at final follow-up. The mean ratio of the medial-to-lateral column length improved from 1.14 ± 0.06 to 1.55 ± 0.09 with statistical significance (t = 3.566; P < 0.001)., Conclusions: Eight-plate epiphysiodesis is an easy and effective method for the correction of residual forefoot adduction deformity after clubfoot treatment in growing children without the need of osteotomy., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

The sinoatrial node (SAN) is the origin of the electrical signals for rhythmic heartbeats in mammals. The spontaneous firing of SAN pacemaker cells (SANPCs) triggers cardiac contraction. 'Local Ca 2+ release' (LCR), a unique cellular activity, acts as the 'engine' of the spontaneous firing of SANPCs. However, the mechanism of LCR initiation remains unclear. Here, we report that endogenous glutamate drives LCRs in SANPCs. Using a glutamate sensor, we unraveled a tight correlation between glutamate accumulation and LCR occurrence, indicating a potential relationship between glutamate and LCRs. Intracellular application of glutamate significantly enhanced the LCRs in both intact and permeabilized SANPCs. Mechanistically, we revealed that mitochondrial excitatory amino acid transporter 1 (EAAT1)-dependent mitochondrial glutamate import promoted ROS generation, which in turn led to the oxidation of Ca 2+ -handling proteins, ultimately resulting in enhanced LCRs. Importantly, EAAT1 depletion reduced both the spontaneous firing rates of isolated SANPCs and the heart rate in vitro and in vivo, suggesting the central role of EAAT1 as a glutamate transporter in the regulation of cardiac autonomic rhythm. In conclusion, our results indicate that glutamate serves as an LCR igniter in SANPCs, adding a potentially important element to the coupled-clock theory that explains the origin of spontaneous firing. These findings shed new light on the future prevention and treatment of cardiac pacemaker cell-related arrhythmias., (© 2022. The Author(s).)

In recent years, thermal ablation has played an increasingly important role in treating various tumors in the clinic. A practical thermochromic phantom model can provide a favorable platform for clinical thermotherapy training of young physicians or calibration and optimization of thermal devices without risk to animals or human participants. To date, many tissue-mimicking thermal phantoms have been developed and are well liked, especially the polyacrylamide gel (PAG)-based phantoms. This review summarizes the PAG-based phantoms in the field of thermotherapy, details their advantages and disadvantages and provides a direction for further optimization. The relevant physical parameters (such as electrical, acoustic, and thermal properties) of these phantoms are also presented in this review, which can assist operators in a deeper understanding of these phantoms and selection of the proper recipes for phantom fabrication., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Published by Elsevier Inc.)

Rupture of tendons and ligaments (T/L) is a major clinical challenge due to T/L possess anisotropic mechanical properties and hierarchical structures. Here, to imitate these characteristics, an approach is presented by fabricating hybrid nanofibrous composites. First, hybrid fiber-reinforced yarns are fabricated via successively electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) and gelatin (Ge) nanofibers onto polyethylene terephthalate (PET) fibers to improve biodurability and biocompatibility. Then, by comparing different manufacturing methods, the knitted structure succeeds in simulating anisotropic mechanical properties, even being stronger than natural ligaments, and possessing comfort compliance superior to clinically used ligament advanced reinforcement system (LARS) ligament. Moreover, after inoculation with tendon-derived stem cells and transplantation in vivo, hybrid nanofibrous composites are integrated with native tendons to guide surrounding tissue ingrowth due to the highly interconnected and porous structure. The knitted hybrid nanofibrous composites are also ligamentized and remodeled in vivo to promote tendon regeneration. Specifically, after the use of optimized anisotropic hybrid nanofibrous composites to repair tendon, the deposition of tendon-associated extracellular matrix proteins is more significant. Thus, this study indicates a strategy of manufacturing anisotropic hybrid nanofibrous composites with superior mechanical properties and good histocompatibility for clinical reconstruction., (© 2022 Wiley-VCH GmbH.)

This paper mainly focuses on the lag H ∞ synchronization problem of coupled neural networks with multiple state or delayed state couplings. On one hand, by exploiting state feedback controller and Lyapunov functional, a criterion of lag H ∞ synchronization for coupled neural networks with multiple state couplings (CNNMSCs) is insured, and lag H ∞ synchronization problem in CNNMSCs is also coped with based on the adaptive state feedback controller. On the other hand, we explore the lag H ∞ synchronization for coupled neural networks with multiple delayed state couplings (CNNMDSCs) by utilizing similar control strategies. At last, two numerical examples are presented to verify the effectiveness and correctness of lag H ∞ synchronization for CNNMSCs and CNNMDSCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cervical squamous cell carcinoma (CSCC) is a type of female cancer that affects millions of families worldwide. Human papillomavirus (HPV) infection is the main reason for CSCC formation, and squamous intraepithelial lesions (SILs) induced by high-risk HPV (HR-HPV) infection are considered precancerous lesions. A previous study reported that HPV-infected cancer cells were able to counteract lipid peroxidation for survival. Recent research has reported that ferroptosis acts in an iron-dependent lipid peroxidation manner to kill cancer cells, and it is proposed as a new approach for female cancer therapy. Here, we investigated the role of ferroptosis throughout SIL development into CSCC. We found that ferroptosis occurred in SIL, but anti-ferroptosis emerged in CSCC. Our data further indicated that an antiferroptotic effect was formed in response to persistent ferroptosis and then promoted oncogenesis. Altogether, we provide novel insight into ferroptosis in cervical SIL development and suggest a potential therapeutic target for the treatment of CSCC., (© 2022. The Author(s).)

Background: Stroke is a serious disease that threatens human health both in China and worldwide. Identifying and establishing its risk factors are prerequisites for intervention and evaluation of prognosis. Over the years, risk factors, such as age, diabetes, and hypertension, have gradually been established. However, at present, there is no consensus on the influence of sex on the prognosis of ischaemic stroke., Aims: The aims of our research was to analyse the correlation between sex and poststroke prognosis based on the results of the Third China National Stroke Registry [CNSR-III], as well as the influence of other risk factors that may be confounded by sex on ischaemic stroke and potential interventions., Methods: The CNSR-III recruited 14146 acute ischaemic stroke [AIS] patients between 2015 and 2018. Our study included 13,972 patients who had complete follow-up information. This research analysed basic information, socioeconomic status, lifestyle habits, medical history, and poststroke prognosis., Results: There was a conspicuous relationship between sex and functional prognosis, stroke recurrence and all-cause death due to ischemic stroke in univariate analysis. Male stroke patients had a better prognosis than female patients. In multivariate analysis, we found that age, atrial fibrillation [AF], diabetes, hypertension and the severity of stroke had adverse effects on ischemic stroke prognosis. After adjustment for other risk factors, the functional prognosis of female patients at 3 months was worse than that of male patients [odds ratio [OR] 1.16, 95% confidence interval [CI], 1.025- 1.314]. Sex had a nonsignificant association with stroke recurrence at 3 months [hazard ratio [HR] 1.141, 95% CI, 0.975-1.336]. Furthermore, compared to male patients, female stroke patients had a lower cumulative death rate at 12 months [HR 0.777, 95% CI, 0.628-0.963]., Conclusion: Our study identified sex differences in stroke-related disability, recurrence, and death and attempted to explain the causes of these differences. Our study clearly showed that a large proportion of this difference could be attributed to age, socioeconomic factors, lifestyle habits, and medical history, confounded by sex differences rather than sex per se., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To study the efficacy and safety of fractional 2940 nm laser-assisted drug delivery of timolol maleate 0.5% solution for the treatment of deep IHs., Methods: In this study, 30 deep IHs were included, and a fractional 2940 nm laser was applied with 2-weeks intervals. Topical timolol maleate 0.5% was applied under occlusion for 30 min four times/day for 24 weeks. The plasma concentration of timolol maleate was monitored for 0.5 h after the first treatment. The HAS scores and the depth, lateral diameter, vertical diameter of hemangiomas were evaluated before treatment, at 8 weeks and 24 weeks of treatment, and at 4 weeks after treatment., Results: Twenty-three patients (76.7%) demonstrated excellent regression, 4(13.3%) showed good response, and 3(10%) experienced moderate regression. The HAS score was declined from 3.6 ± 0.7 to 2.3 ± 0.6 at 8 weeks, and from 1.3 ± 0.5 to 0.8 ± 0.5 at 24 weeks ( p  < .05). Plasma timolol concentration was not detected in 11 infants, and the rest ranged from 1.580 pg/mL to 14.718 pg/mL, which were <1 ng/mL. No systemic complications were observed in any patients., Conclusion: Fractional 2940 nm laser-assisted drug delivery of timolol maleate 0.5% is considered to be an effective and safe method for treating deep IHs.

A ring-width series was developed from Dahurian larch (Larix gmelinii) in the northeastern forest area of Inner Mongolia, China. By analyzing the relationships between tree-ring data and climate records, an August-September mean maximum temperature (T 89 ) series during 1845 and 2012 was reconstructed based on a simple linear regression equation. This reconstructed series explained 40.9% variance of the observed temperature from 1959 to 2012. The reconstructed T 89 series was consistent with the historical disaster events caused by extreme climate (e.g., flood, frost disaster, and cold damage). Besides, the temperature comparisons showed that the year in which the warm months (April-September) in northeast China began to warm up has latitude differences. It started with a gradual delay from north to south, starting 1980 in the south region, after 1950 AD in the central region and after 1940 in the north region. Our study can enrich high-resolution temperature series in Northeast China and help clarify the characteristic of recent warming in northeast China., (© 2021. ISB.)

The full-length cDNA sequence of F3'5'H gene from the Brunfelsia acuminata was obtained by RT-PCR and RACE, whose GenBank accession number is JQ678765. The sequence contains a 1521 bp open reading frame, 120 bp 5'UTR and 61 bp 3'UTR, encoding a total of 506 amino acids. The molecular mass of the predicted protein is 56.47 kDa with an estimated pI of 8.78, respectively. Sequence alignment showed that the amino acid sequence of F3'5'H was 91%, 87% and 84% with that of Petunia × hybrida , Nierembergia sp ., Solanum tuberosum , respectively. Real-time quantitative PCR analysis showed that the expression of F3'5'H gene was different in petals of different days, which was the highest expression level on day 0 and significantly higher than other days. The results indicated that F3'5'H might play key role in flower color regulation and provide a theoretical reference for blue flower molecular breeding.

Objection: Cumulative studies have identified the effectiveness of cardiac shock wave therapy (CSWT) in treating heart failure after acute myocardial infarction (AMI), but little have been discussed with regard to the beneficial effects of CSWT on anti-fibrosis along with the underlying mechanism. In this study, we investigated whether CSWT could reduce post-AMI fibrosis and further explored the molecular mechanism. Methods: Rat heart failure (HF) models induced by ligating the left anterior descending coronary artery were established and validated by echocardiography. Eligible animals were randomly categorized into five groups: the sham group, the HF group, the HF + CSWT group, the HF + LY294002 group, and the HF + CSWT + LY294002 group. The cardiac weight, serum level of BNP, NT-pro BNP and echocardiography parameters were measured to assess cardiac function in different groups. Masson's trichrome staining was used to assess the proportions of the fibrotic area. The expression level of CD34, αSMA was measured by RT-PCR, Immunohistochemistry and Immunofluorescent analyses and the level of PI3K/Akt was quantified by Immunohistochemistry and Western blotting. Results: The application of CSWT significantly improved cardiac function and reduced myocardial fibrosis and level of CD34 and αSMA, compared to the HF group. CSWT led to significant elevations of p-PI3K and p-Akt expression levels compared to that of the HF group and the inhibition of the PI3K/Akt pathway abolished the observed beneficial effects of CSWT. Conclusion: CSWT can facilitate the alleviation of cardiac fibrosis induced by AMI through the activation of PI3K/Akt signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Tian, Cao, Ma, Shang, Li, Zhang, Deng, Li, Guo and Yang.)

Biological fluorescence imaging technologies have attracted a lot of attention and have been widely used in biomedical fields. Compared with other technologies, fluorescence imaging has a lower cost, higher sensitivity, and easier operation. However, due to the disadvantages of one-photon (OP) fluorescence imaging, such as low spatial and poor temporal resolution and poor tissue permeability depth, the application of OP fluorescence imaging has some limitations. Though two-photon (TP) fluorescence imaging can well overcome these shortcomings of OP, the single-mode imaging remains deficient. Therefore, dual-mode imaging combined with TP imaging and magnetic resonance imaging (MRI) can make up for the deficiency well, which make dual-mode imaging for the early diagnosis of diseases more accurate. Hence, a dual-mode nanoprobe TP-CQDs@MnO 2 was designed for probing the fluorescence/MR dual-mode imaging strategy of intracellular H + by using TP-CQDs (two photon-carbon quantum dots) and MnO 2 nanosheets. The MnO 2 nanosheets treated as fluorescence quenching agents of TP-CQDs exhibited a supersensitive response to H + , which made the fluorescence signals turn "off" to "on" for TP fluorescence imaging, in the meantime, large amounts of Mn 2+ were generated for MRI. A dual-mode nanoprobe TP-CQDs@MnO 2 can monitor intracellular wide pH (4.0-8.0), and the fluorescence intensity of TP-CQDs@MnO 2 has recovered up to more than six times and the corresponding results of MRI were satisfactory. TP fluorescence imaging of cells and tissues showed higher detection sensitivity and deeper tissue penetration (240.0 μm) than OP. The dual-mode imaging platform hold great promise for pH-related early diagnosis and treatment, which has great potential to improve clinical efficacy.

In this article, we investigate a class of memristive neural networks (MNNs) with time-varying delays and leakage delays via sliding mode control (SMC) with and without control disturbance. SMC is used to ensure MNNs' stability. According to the characteristics of the MNNs, we consider the following three models: the first is the MNNs with time-varying delays, the second is the MNNs with time-varying delays and the control disturbance, and the third is the MNNs with time-varying delays, leakage delays, and the control disturbance. We quote some assumptions and lemmas to ensure that our main results are true. The sliding surface, the corresponding sliding mode controller, and the Lyapunov functions are constructed in different models to ensure MNNs' stability. Finally, some examples and simulations verify the validity of our main results by solving linear matrix inequality (LMI), and the conclusions and analysis of the results are given.

This article investigates the synchronization problem of multiple memristive neural networks (MMNNs) in the case of switching communication topologies and parameter mismatch. First, the distributed event-triggered control under continuous sampling conditions is studied. Then, a periodic event-triggered control (PETC) model is proposed to substantially reduce control consumption. Using the Lyapunov method, the properties of M -matrix, and some inequalities, the sufficient criteria of synchronous control are derived. The results can be used in the analysis of other multiagent nonlinear systems. A norm-based threshold function is given to determine the update time of the controller, and it is proved that the trigger condition excludes the Zeno behavior. Subject to parameter mismatch, a quasisynchronous control strategy is proposed, which can be extended to complete synchronization provided that the system mismatch or disturbance disappears. It is worth mentioning that this article introduces the signal function into the controller, so that the theoretical error can be limited to an arbitrarily small range. Furthermore, this new controller is used in the PETC strategy which automatically avoids the Zeno behavior. Finally, one example is given to illustrate our results.

Over the past decade, cancer immunotherapy, such as immune checkpoint inhibitors (ICRs), has attained considerable progresses in clinical practice. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) act as next ICRs, and originally function as a co-inhibitory receptor expressed on interferon (IFN)-γ producing CD4+ and CD8+ T-cells. Furthermore, Tim-3 has also been found to express on innate immune cells and several types of tumors, signifying the pivotal role that Tim-3 plays in chronic viral infections and cancer. In addition, Tim-3 and multiple ICRs are concurrently expressed and regulated on dysfunctional or exhausted T-cells, leading to improved antitumor immune responses in preclinical or clinical cancer therapy through co-blockade of Tim-3 and other ICRs such as programmed cell death-1 (PD-1). In this review, the biological characteristics of Tim-3 and the function of Tim-3 in regulating tumorigenesis and inflammation have been summarized. The usage of a single blockade of Tim-3 or in combination with multiple immunotherapy regimens have drawn attention to antitumor potential as a target for immunotherapy.

Although exogenous melatonin can enhance the drought tolerance of plants, reports on the role of melatonin in drought tolerance in male reproductive organs are limited. To explore this, a pot experiment was conducted with cotton cultivar Yuzaomian 9110 to study the effects of exogenous melatonin (100, 200, and 1000 μM) on male fertility and related carbohydrate metabolism in anther under drought. Results showed that drought inhibited the translocation of carbon assimilates to anthers, however, melatonin application (100 and 200 μM) significantly improved the translocation of carbon assimilates to drought-stressed anthers. Drought reduced the deposition of starch, the hydrolysis of sucrose into hexoses, the generation of adenosine triphosphate (ATP) in anthers, restricting pollen viability and germination. Nevertheless, the appropriate melatonin concentrations (100 and 200 μM) increased the starch accumulation by enhancing ADP-glucose pyrophosphorylase and soluble starch synthases activities and accelerated the hydrolysis of sucrose by increasing sucrose synthase, acid and alkaline invertases activities in drought-stressed anthers. Appropriate melatonin concentrations (100 and 200 μM) also could help to generate more ATP for reproductive activities of drought-stressed anthers, finally increasing the pollen viability and germination of drought-stressed plants. These findings suggest that drought inhibited male fertility of cotton, but a precise melatonin application could regulate the carbohydrate balance of drought-stressed anthers to improve male fertility. This is the first report demonstrating the important role of exogenous melatonin in improving male fertility under drought conditions by regulating the carbohydrate metabolism in the male part of cotton., Competing Interests: Declaration of competing interest The authors claim no competing interests., (Copyright © 2020. Published by Elsevier Masson SAS.)

This paper investigates the global exponential synchronization problem of delayed memristive neural networks (MNNs) with reaction-diffusion terms. First, by utilizing the pinning control technique, two novel kinds of control methods are introduced to achieve synchronization of delayed MNNs with reaction-diffusion terms. Then, with the help of inequality techniques, pinning control technique, the drive-response concept and Lyapunov functional method, two sufficient conditions are obtained in the form of algebraic inequalities, which can be used for ensuring the exponential synchronization of the proposed delayed MNNs with reaction-diffusion terms. Moreover, the obtained results based on algebraic inequality complement and improve the previously known results. Finally, two illustrative examples are given to support the effectiveness and validity of the obtained theoretical results., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: To investigate the antitumor efficacy of microwave ablation combined with dendritic cell-derived exosomes (Dex) or dendritic cells (DC) in treating hepatocellular carcinoma using a tumor - bearing mouse model., Methods: We used a bilateral tumor - bearing mouse model treated with MWA, MWA + DC (DC-combined group) or MWA + Dex (Dex-combined group). Following tumor ablation on one side, the tumor volume on the contralateral side was monitored. The proportions of CD8 + (cytotoxic) T cells and regulatory T (Treg) cells in the spleen were analyzed by flow cytometry, and the number of CD8 + T cells and Treg cells in tumor sites was detected by immunohistochemistry. The concentration of interleukin-10 and interferon-γ in plasma was identified using enzyme-linked immunosorbent assay., Results: The combination therapy significantly inhibited tumor growth compared with MWA monotherapy. In addition, the tumor immune microenvironment was significantly improved in HCC mice in the combination therapy groups compared to MWA group demonstrated by an increased number of CD8 + T cells and a decreased number of Treg cells in tumor sites. A lower proportion of Treg cells were observed in the spleen in the combination therapy groups compared to MWA group. Moreover, the concentration of plasma IFN-γ increased, and the concentration of plasma IL-10 decreased in the combination therapy groups compared to the MWA group. However, there was no statistical difference between the Dex-combined group and the DC-combined group in the comparisons mentioned above., Conclusions: Our results provide evidence that MWA combined with Dex can significantly inhibit tumor growth and improve the immune microenvironment compared to MWA alone. Furthermore, the immune-enhancing effect of Dex and DC was equivalent in our combination therapy strategy.

This paper presents the theoretical results on sliding mode control (SMC) of neural networks via continuous or periodic sampling event-triggered algorithm. Firstly, SMC with continuous sampling event-triggered scheme is developed and the practical sliding mode can be achieved. In addition, there is a consistent positive lower bound for the time interval between two successive trigger events which implies that the Zeno phenomenon will not occur. Next, a more economical and realistic SMC technique is presented with periodic sampling event-triggered algorithm, which guarantees the robust stability of the augmented system. Finally, two illustrative examples are presented to substantiate the effectiveness of the derived theoretical results., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Multicolor fluorescence probes can show fluorescence of different colors when detecting different targets, and the excellent feature can create a highly differentiated multicolor sensing platform. However, most of the previously reported multicolor luminescent materials usually suffer from high toxicity and photobleaching, complex preparation procedures, and poor water solubility, which may not be conducive to bioanalytical applications. Two-dimensional metal organic frameworks (2D MOFs), which have large specific surface areas with long-range fluorescence quenching coupled with biomolecular recognition events, have encouraged innovation in biomolecular probing. Here, we propose a 2D-MOF-based multicolor fluorescent aptamer nanoprobe using a double stirring bar assisted target replacement system for enzyme-free signal amplification. It utilizes the interaction between 2D MOFs and DNA molecules to detect multiple antibiotics quickly, sensitively, and selectively. Since 2D MOFs have excellent quenching efficiency for luminescence of fluorescent-dye-labeled single-strand DNA (ssDNA), the background fluorescence can be largely reduced and the signal-to-noise ratio can be improved. When the adsorbed ssDNA formed double helix double-stranded DNA with its complementary ssDNA, its fluorescence can be almost fully recovered. The assay was tested by detecting chloramphenicol (CAP), oxytocin (OTC), and kanamycin (KANA) in biological samples. The developed aptasensor was sufficiently sensitive to detect the antibiotic residues as low as 1.5 pM CAP, 2.4 pM OTC, and 1 pM KANA (S/N = 3). It has been preliminarily used for multicolor imaging of three different antibiotics in fish tissue slices with satisfactory results.

In this paper, we investigate the synchronization problem on delayed memristive neural networks (MNNs) with leakage delay and parameters mismatch via event-triggered control. We divide MNNs with parameters mismatch into two categories for discussion. One is state-dependent and can achieve synchronization by designing a suitable controller. A novel Lyapunov functional is constructed to analyze the synchronization problem. Moreover, the triggering conditions are independent from the delay boundaries and can be static or dynamic. Another category of parameters mismatch is structure-dependent and can only achieve quasi-synchronization by appropriate controller. By using matrix measure method and generalized Halanay inequality, a quasi-synchronization criterion is established. The controllers in this paper are discrete state-dependent and can be updated under the event-based triggering condition, which is more simpler than the previous results. In the end of our paper, two illustrative examples are given to support our results., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The development of multiplex assays to simultaneously monitor multiclass chemical contaminants that commonly coexist in foods, such as heavy metal ions, antibiotics, and estrogen residues, is gaining attention. Here, a microfluidic chip (MC)-based multianalysis method coupled with magnetic encoded aptamer probes was used for simultaneous detection of kanamycin, 17β-estradiol, and lead ion (Pb 2+ ). Using this innovative strategy, the magnetic bead (MB)-based encoded probes labeled with aptamer hybrid chains were first used to selectively capture multiple targets, followed by generating single-stranded primers. The primers triggered a multibranched hybridization chain reaction (mHCR). Finally, three kinds of complementary strands (C-DNAs) with different lengths were hybridized with the arms of the mHCR products to form three types of multibranched DNA nanostructures. The decrement signals of C-DNAs were employed for qualification of targets. As the signal tags corresponded to different targets, the DNA nanostructures realized "one target for the decrease of massive C-DNAs" to improve sensitivity. The use of MB-based encoded probes could achieve magnetic separation to eliminate interference in the complex. The detection limits of this method were 1.76 × 10 -4 nM (kanamycin), 1.18 × 10 -4 nM (17β-estradiol), and 1.29 × 10 -4 nM (lead ion). Furthermore, the MC platform is reusable and can be used for more than 4000 samples. The assay combining the MC with MB-based encoded probes with multibranched DNA signal tags offers a universal, reusable, and high-throughput detection platform for screening multiclass chemical contaminants in food samples with complex matrices.