POLQ inhibition attenuates the stemness and ferroptosis resistance in gastric cancer cells via downregulation of dihydroorotate dehydrogenase.

Gastric cancer (GC) contains subpopulations of cancer stem cells (CSCs), which are described as the main contributors in tumor initiation and metastasis. It is necessary to clarify the molecular mechanism underlying CSCs phenotype and develop novel biomarkers and therapeutic targets for gastric cancer. Here, we show that POLQ positively regulates stem cell-like characteristics of gastric cancer cells, knockdown of POLQ suppressed the stemness of GC cells in vitro and in vivo. Further mechanistic studies revealed that POLQ knockdown could downregulate the expression of dihydroorotate dehydrogenase (DHODH). DHODH overexpression rescued the reduced stemness resulted by POLQ knockdown. Furthermore, we found that POLQ expression correlated with resistance to ferroptosis, and POLQ inhibition renders gastric cancer cells more vulnerable to ferroptosis. Further investigation revealed that POLQ regulated DHODH expression via the transcription factors E2F4, thereby regulating ferroptosis resistance and stemness of gastric cancer cells. Given the importance of POLQ in stemness and ferroptosis resistance of GC, we further evaluated the therapeutic potential of POLQ inhibitor novobiocin, the results show that novobiocin attenuates the stemness of GC cells and increased ferroptosis sensitivity. Moreover, the combination of POLQ inhibitor and ferroptosis inducer synergistically suppressed MGC-803 xenograft tumor growth and diminished metastasis. Our results identify a POLQ-mediated stemness and ferroptosis defense mechanism and provide a new therapeutic strategy for gastric cancer.

A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress.

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease.

The expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice.

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of Echinococcus multilocularis (E. multilocularis) larvae. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) produces inhibitory signals and induces T cell exhaustion, thereby inhibiting the parasiticidal efficacy of the liver immune system. Therefore, the purpose of this study is to explore how T-cell exhaustion contributes to AE and whether blocking CTLA-4 could reverse T cell exhaustion. Here we discovered that the expression of CTLA-4 was increased in the infiltrating margin around the lesion of the liver from AE patients by using western blot and immunohistochemistry assay. Multiple fluorescence immunohistochemistry identified that CTLA-4 and CD4/CD8 molecules were co-localized. For in vitro experiments, it was found that the sustained stimulation of E. multilocularis antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For in vivo experiments, the expression of CTLA-4 was increased in the liver of E. multilocularis-infected mice, and the CTLA-4 and CD4/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4+ T cells and CD8+ T cells in the liver and peripheral blood were significantly increased and induced T exhaustion. When the mice were treated with anti-CTLA-4 antibodies, the number and weight of the lesions decreased significantly. Meanwhile, the flow cytometry results suggested that blocking CTLA-4 could effectively reverse T cell exhaustion and reactivate immune function. Our work reveals that blocking CTLA-4 could effectively reverse the T cell exhaustion caused by E. multilocularis and could be used as a novel target for the treatment of AE.

MSMTSeg: Multi-Stained Multi-Tissue Segmentation of Kidney Histology Images via Generative Self-Supervised Meta-Learning Framework.

Accurately diagnosing chronic kidney disease requires pathologists to assess the structure of multiple tissues under different stains, a process that is timeconsuming and labor-intensive. Current AI-based methods for automatic structure assessment, like segmentation, often demand extensive manual annotation and focus on single stain domain. To address these challenges, we introduce MSMTSeg, a generative self-supervised meta-learning framework for multi-stained multi-tissue segmentation in renal biopsy whole slide images (WSIs). MSMTSeg incorporates multiple stain transform models for style translation of inter-stain domains, a self-supervision module for obtaining pre-trained models with the domain-specific feature representation, and a meta-learning strategy that leverages generated virtual data and pre-trained models to learn the domain-invariant feature representation across multiple stains, thereby enhancing segmentation performance. Experimental results demonstrate that MSMTSeg achieves superior and robust performance, with mDSC of 0.836 and mIoU of 0.718 for multiple tissues under different stains, using only one annotated training sample for each stain. Our ablation study confirms the effectiveness of each component, positioning MSMTSeg ahead of classic advanced segmentation networks, recent few-shot segmentation methods, and unsupervised domain adaptation methods. In conclusion, our proposed few-shot cross-domain technology offers a feasible and cost-effective solution for multi-stained renal histology segmentation, providing convenient assistance to pathologists in clinical practice. The source code and conditionally accessible data are available at https://github.com/SnowRain510/MSMTSeg.

Novel cow dung-doped sludge biochar as an efficient ozone catalyst: Synergy between graphitic structure and defects induces free radical pathways.

A composite material, cow dung-doped sludge biochar (Zn@SBC-CD), was synthesized by one-step pyrolysis using ZnCl2 as an activating agent and applied to a catalytic ozonation process (COP) for methylene blue (MB) removal. SEM, XRD, FTIR, XPS and BET analyses were performed to characterize the biochar (BC) catalysts. Zn@SBC-CD had high graphitization degree, abundant active sites and uniform distribution of Zn on its surface. Complete removal of MB was achieved within 10 min, with a removal rate much higher than that of ozone alone (32.4%), implying the excellent ozone activation performance of Zn@SBC-CD. The influence of experimental parameters on MB removal efficiency was examined. Under the optimum conditions in terms of ozone dose 0.04 mg/mL, catalyst dose 400 mg/L and pH 6.0, COD was completely removed after 20 min. Electron paramagnetic resonance (EPR) analysis revealed radical and non-radical pathways were involved in MB degradation. The Zn@SBC-CD/O3 system generated superoxide anion radicals (•O2-), which were the main active species for MB removal, through adsorption, transformation, and transfer, Furthermore, Zn@SBC-CD exhibited good reusability and stability in cycling experiments. This study provides a novel approach for the utilization of cow dung and sludge in synthesis of functional biocatalysts and application in organic wastewater treatment.

Stabilization of heavy metals in solid waste and sludge pyrolysis by intercalation-exfoliation modified vermiculite.

Increasing amounts of solid waste and sludge have created many environmental management problems. Pyrolysis can effectively reduce the volume of solid waste and sludge, but there is still the problem of heavy metal contamination, which limits the application of pyrolysis in environmental management. The intercalated-exfoliated modified vermiculite (IEMV) by intercalators of sodium dodecylbenzene sulfonate, hexadecyltrimethylammonium bromide and octadecyltrimethylammonium bromide were used to control the release of Cd, Cr, Cu, Zn and Pb during pyrolysis process of sludge or solid waste. The retention of heavy metals in sludge was generally better than that in solid waste. The IEMV by octadecyltrimethylammonium bromide as the intercalator calcined 800 °C (STAB-800) was the best additive for heavy metal retention, and the retention of Cr, Cu and Zn was significantly better than that of Pb and Cd. Cr, Cu, Zn and Pb were at low risk, while Cd had considerable risk under certain circumstances. New models were proposed to comprehensively evaluate the results of the risk and forms of heavy metals, and the increasing temperature was beneficial in reducing the hazards of heavy metals by the addition of STAB-800. The reaction mechanism of heavy metals with vermiculite was revealed by simulation of reaction sites, Fukui Function and Frontier Molecular Orbital. Thermal activation-intercalated-exfoliated modified vermiculite (T-IEMV) is more reactive and had more active sites for heavy metals. Mg atoms and outermost O atoms are the main atoms for T-IEMV to react with heavy metals. The Cr, Cu and Zn have better adsorption capacity by T-IEMV than Pb and Cd. This study provides a new insight into managing solid waste and sludge and controlling heavy metal environmental pollution.

Multiscale reconfiguration induced highly saturated poling in lead-free piezoceramics for giant energy conversion.

The development of high-performance lead-free K0.5Na0.5NbO3-based piezoceramics for replacing commercial lead-containing counterparts is crucial for achieving environmentally sustainable society. Although the proposed new phase boundaries (NPB) can effectively improve the piezoelectricity of KNN-based ceramics, the difficulty of achieving saturated poling and the underlying multiscale structures resolution of their complex microstructures are urgent issues. Here, we employ a medium entropy strategy to design NPB and utilize texture engineering to induce crystal orientation. The developed K0.5Na0.5NbO3-based ceramics enjoys both prominent piezoelectric performance and satisfactory Curie temperature, thus exhibiting an ultrahigh energy harvesting performance as well as excellent transducer performance, which is highly competitive in both lead-free and lead-based piezoceramics. Comprehensive structural analysis have ascertained that the field-induced efficient multiscale polarization configurations irreversible transitions greatly encourages high saturated poling. This study demonstrates a strategy for designing high-performance piezoceramics and establishes a close correlation between the piezoelectricty and the underlying multiscale structures.

Mechanical enhancement and high linearity health monitoring of composite materials based on CNTs/PSF/PI film sensor with ultra-low SWCNTs doping content.

A new type of embedded composite material health monitoring nano-sensor is designed to ensure that the unique material advantages of nanofillers can be maximized. The carbon nanotubes (CNTs)/polysulfone (PSF)/polyimide (PI) thin film sensor in this paper is obtained by the self-assembly of a PSF/PI asymmetric porous membrane which is prepared by a phase inversion method through vacuum filtration of SWCNTs. It is a new structure for a practical CNT sensor that can take into account both 'composite health monitoring and damage warning' and 'composite mechanical enhancement'. The new structure of the CNTs/PSF/PI film sensor is divided into two parts. The upper part consists of small-aperture finger-like holes filled with SWCNTs (the SWCNT content is 0.0127 mg cm-2). The lower part consists of large-aperture cavities conducive to resin infiltration, which enhance the interface bonding force between the sensor and the composite material. This unique structure allows the CNTs/PSF/PI film sensor to change the influence of the embedded sensor from 'introducing defects' to 'local enhancement', and the mechanical strength of the enhanced specimen can reach up to 1.68 times that of the original specimen, and the service interval can reach 2.01 times that of the original specimen. In addition, the CNTs/PSF/PI film sensor also has good sensitivity (GF = 2.54) and extremely high linearity (R2 = 0.9995), and has excellent follow-up and interface bonding ability. It can also maintain excellent fatigue resistance and stability over 46 500 vibration cycles, which provides new research ideas and research methods for the field of composite-life monitoring sensors.

Interplay of CD36, autophagy, and lipid metabolism: insights into cancer progression.

CD36, a scavenger receptor B2 that is dynamically distributed between cell membranes and organelle membranes, plays a crucial role in regulating lipid metabolism. Abnormal CD36 activity has been linked to a range of metabolic disorders, such as obesity, nonalcoholic fatty liver disease, insulin resistance and cardiovascular disease. CD36 undergoes various modifications, including palmitoylation, glycosylation, and ubiquitination, which greatly affect its binding affinity to various ligands, thereby triggering and influencing various biological effects. In the context of tumors, CD36 interacts with autophagy to jointly regulate tumorigenesis, mainly by influencing the tumor microenvironment. The central role of CD36 in cellular lipid homeostasis and recent molecular insights into CD36 in tumor development indicate the applicability of CD36 as a therapeutic target for cancer treatment. Here, we discuss the diverse posttranslational modifications of CD36 and their respective roles in lipid metabolism. Additionally, we delve into recent research findings on CD36 in tumors, outlining ongoing drug development efforts targeting CD36 and potential strategies for future development and highlighting the interplay between CD36 and autophagy in the context of cancer. Our aim is to provide a comprehensive understanding of the function of CD36 in both physiological and pathological processes, facilitating a more in-depth analysis of cancer progression and a better development and application of CD36-targeting drugs for tumor therapy in the near future.

Medical errors, affected sites, and adverse consequences among patients in the orthopaedic department: Does age matter?

Background: Orthopaedics have become the focus of research on patient safety due to the high incidence of medical errors. Previous studies were based on all orthopaedic patients and rarely conducted empirical analyses from the perspective of age. This study aimed to fill the academic gap in the age variable by comparing medical errors, affected sites, and adverse consequences in orthopaedic patients. Methods: This retrospective study included 329 litigation claims against orthopaedists using data from China Judgments Online. First, we performed computer crawling and screened 5,237 litigation documents using keywords, including medical errors. Second, 2,536 samples were retained through systematic random sampling, and 549 irrelevant cases were deleted after manual reading. Finally, three clinicians from different medical departments selected 329 incidents related to orthopaedics for further analysis, according to the description of the lawsuits. Three other professional orthopaedists evaluated the patients' ages, affected sites of medical errors, and adverse consequences. Results: The greatest number of medical errors was observed in the joints (30.43%) for all orthopaedic patients. However, adult patients (aged 18-60 years) were most susceptible to errors in the extremities (30.42%). A higher rate of complications was associated with a higher rate of morbidity/mortality for the corresponding patients. Medical errors correlated with complications occurred in the following sites: joints (15.38%), extremities (12.50%), spine (16.95%), multiple sites (15.38%), and hands and feet (14.81%). In addition to surgical errors, over 10% of all orthopaedic patients experienced missed diagnoses. The incidence of insufficient adherence to informed consent obligations was 13.5% among adult patients and was much higher in paediatric and older adults patients. When orthopaedic patients suffered from medical technical errors, iatrogenic mortality/morbidity would decrease by 0.3% for one unit increase in age. Conclusion: Dividing patients into different ages demonstrated diverse results in terms of medical errors and affected sites. Negligence in diagnosis and examination can be fatal factors that endanger safety, and complications may cause morbidity/mortality. When patients suffered from technical errors, age is inversely proportional to mortality/morbidity. Special attention needs to be paid to technical errors in the younger older adults population (60-64 years old), which has inspired implications in promoting aging and public health.

Effective stabilization of heavy metals in solid waste and sludge pyrolysis using intercalated-exfoliated modified vermiculite: Experiment and simulation study.

Pyrolysis is effective in reducing the volume of solid waste and sludge, and produces less pollutants than incineration and landfill, but the process still suffers from heavy metal pollution. Four types of intercalated-exfoliated modified vermiculite (UIV, DIV, TIV and 3IV) were prepared using urea, dimethylsulfoxide, tributyl phosphate and 3-aminopropyltriethoxysilane as intercalators for the control of Cd, Cr, Cu, Pb and Zn in municipal sewage sludge (MSL), paper mill sludge (PML), municipal domestic waste (MWA) and aged refuse (AFE). The larger the interlayer spacing of the vermiculite, the more favorable the retention of heavy metals. 3IV was the most effective additive, with an average retention of more than 75 % of all heavy metals at 450 ℃ for the four raw materials. Cr, Cu, Pb and Zn were all at low potential ecological risk (Pr), while Cd was moderate or considerable Pr, and the addition of 3IV reduced the Pr. Distribution of intercalators between vermiculite interlayers was haphazard, and interlayer spacing results were close to those of the experiment (except for tributyl phosphate). The reactive electrons mainly flowed from the Highest Occupied Molecular Orbital (HOMO) of vermiculite flakes to the Lower Unoccupied Molecular Orbital (LUMO) of heavy metal chlorides. In contrast, the reactive electrons mostly flowed from the HOMO of heavy metal oxides to the LUMO of vermiculite flakes. Heavy metal oxides were more readily adsorbed on vermiculite flakes than heavy metal chlorides, and the adsorption capacity of Cr and Zn was stronger than that of Cd, Pb and Cu.

Circulating miR-423-5p levels are associated with carotid atherosclerosis in patients with chronic kidney disease.

BACKGROUND AND AIMS: Carotid atherosclerosis is associated with an elevated risk of stroke in patients with chronic kidney disease. However, the molecular basis for the incidence of carotid atherosclerosis in patients with CKD is poorly understood. Here, we investigated whether circulating miR-423-5p is a crucial link between CKD and carotid atherosclerosis. METHODS AND RESULTS: We recruited 375 participants for a cross-sectional study to examine the occurrence of carotid plaque and plaque thicknesses. Levels of miR-423-5p were determined by qPCR analysis. We found that non-dialysis CKD patients had higher circulating exosomal and plasma miR-423-5p levels, and dialysis-dependent patients had lower miR-423-5p levels than non-dialysis CKD patients. After excluding for the influence of dialysis patients, linear regression analysis indicated that levels of circulating miR-423-5p are negatively correlated with eGFR (P < 0.001). Higher plasma miR-423-5p levels were associated with the incidence and severity of carotid plaques. In parallel, we constructed a murine model of CKD with a 5/6 nephrectomy protocol and performed RNA sequencing studies of aortic tissues. Consistent with these findings in CKD patients, circulating exosomal miR-423-5p levels in CKD mice were elevated. Furthermore, our RNA-seq studies indicated that the putative target genes of miR-423-5p were related to oxidative stress functions for aorta of CKD mice. CONCLUSION: Levels of miR-423-5p are associated with the presence and severity of carotid plaque in CKD. Data from our mouse model suggests that miR-423-5p likely influences gene expression programs related to oxidative stress in aorta of CKD mice.

Low-level Nd:YAG laser inhibiting inflammation and oxidative stress in human gingival fibroblasts via AMPK/SIRT3 axis.

OBJECTIVE: Photobiomodulation is extensively employed in the management of chronic inflammatory diseases such as periodontitis because of its anti-inflammatory and antioxidant effects. This study used low-level Nd:YAG laser to investigate the mechanism of photobiomodulation as well as the role of adenosine monophosphate-activated protein kinase (AMPK) and Sirtuins (SIRT) 3 in it, providing new clues for the treatment of periodontitis. METHODS: Human gingival fibroblasts (HGFs) were extracted from gingiva and stimulated with LPS. The suitable parameters of Nd:YAG laser were chosen for subsequent experiments by detecting cell viability. We assessed the level of inflammation and oxidative stress as well as AMPK and SIRT3. The mechanism for AMPK targeting SIRT3 modulating the anti-inflammatory and antioxidant effects of photobiomodulation was explored by the AMPK inhibitor (Compound C) test, cell transfection, western blot, and immunofluorescence. RESULTS: HGFs were isolated and identified, followed by the identification of optimal Nd:YAG laser parameters (60 mJ, 15 Hz, 10s) for subsequent experimentation. With this laser, inflammatory factors (IL-6, TNF-α, COX2, and iNOS) decreased as well as the phosphorylation and nuclear translocation of NFκB-P65. SOD2 was up-regulated but reactive oxygen species (ROS) was down-regulated. The laser treatment exhibited enhancements in AMPK phosphorylation and SIRT3 expression. The above effects could all be reversed by Compound C. Silencing AMPK or SIRT3 by siRNA, the down-regulation of COX2, iNOS, and ROS by laser was inhibited. SIRT3 was down-regulated when the AMPK was silenced. CONCLUSION: Low-level Nd:YAG laser activated AMPK-SIRT3 signaling pathway, facilitating the anti-inflammatory and antioxidative activity.

Evaluation and optimization of ecological spatial resilience of Yanhe River Basin based on complex network theory.

The loess hilly and gully areas have broken terrain, vertical and horizontal ravines and fragile ecological environments. Improving the resilience of the regional ecological space is conducive to improving the quality of the local ecological environment. With the ecological space of the Yanhe River Basin selected as the research object, this paper constructs a research framework of "network identification topology-resilience evaluation-spatial optimization" and uses morphological spatial pattern analysis (MSPA) and the minimum cumulative resistance model (MCR) to identify ecological spatial networks. Based on circuit theory, the ecological pinch point is identified, the ecological spatial network is optimized, and scenario simulation is performed. Through complex network theory and related indicators, the ecological spatial resilience of the basin is evaluated, and the hierarchical optimization strategy of the ecological space is confirmed. According to the ecological function of the source area and the results of the resilience evaluation, the boundaries of the protected control area, guidance development area, remediation area, and maintenance and improvement area of the basin are delineated. The importance of ecological source and corridor protection is classified, and corresponding protection strategies are proposed. The research results can provide theoretical support and practical guidance for the territorial spatial planning and ecological space construction of the Yanhe River Basin and provide a reference for the ecological restoration, resource development and environmental governance of the Yanhe River Basin.

Strong Oxidizing Molten Salts for Strengthening Structural Restoration Enabling Direct Regeneration of Spent Layered Cathode.

As a mainstream technology for recycling spent lithium-ion batteries, direct regeneration is rapidly developed due to its high efficiency and green characteristics. However, efficient reuse of spent LiNix Coy Mn1- x - y O2 cathode is still a significant challenge, as the rock salt/spinel phase on the surface hinders the Li replenishment and phase transformation to the layered structure. In this work, the fundamental understanding of the repair mechanism is confirmed that the oxidizing atmosphere is the crucial factor that can greatly improve the rate and degree of phase restoration. Particularly, a ternary-component molten salt system (LiOH-Li2 CO3 -LiNO3 ) is proposed for direct regeneration of LiNi0.5 Co0.2 Mn0.3 O2 (NCM523), which can in situ generate the strong oxidizing intermediate of superoxide radicals. Additionally, it shows a liquid-like reaction environment at a lower temperature to acceclerate the transport rate of superoxide-ions. Therefore, the synergistic effect of LiOH-Li2 CO3 -LiNO3 system can strengthen the full restoration of rock salt/spinel phases and achieve the complete Li-supplement. As anticipated, the regenerated NCM523 delivers a high cycling stability with a retention of 91.7% after 100 cycles, which is even competitive with the commercial NCM523. This strategy provides a facile approach for the complete recovery of layer structure cathode, demonstrating a unique perspective for the direct regeneration of spent lithium-ion batteries.

Significant enhancement in antioxidant and antimicrobial activity of tragacanth gum through chemical modification using amino acids.

Herein, glutamic acid, lysine, arginine and glycine grafted tragacanth gum (TG) were synthesized and designated as TG-Glu, TG-Lys, TG-Arg, and TG-Gly, respectively. The corresponding degrees of substitution (DS) were 0.212, 0.255, 0.394, and 0.169. Thermal, antioxidant, and antibacterial properties of synthesized amino acid-grafted tragacanth gum (ATG) were investigated. The results suggested that the grafting of amino acids onto TG has the potential to alter its thermal properties. When compared with TG and amino acid alone, ATG exhibited significantly enhanced antioxidant and antibacterial properties, with these properties being concentration-dependent. At a concentration of 2 mg/mL for TG-Glu and 3 mg/mL for TG-Arg, TG-Gly, and TG-Lys, the scavenging rate for 2,2'-hypoazido-3-ethylbenzothiazoline sulfonate (ABTS) radical reached 100 %. On the other hand, the scavenging rate of TG-Glu for hydroxyl radical achieved 100 % even at a concentration as low as 1 mg/mL. These properties were accompanied by an increase in reducing force and a notable improvement in the ability to scavenge superoxide anion (O2-). Moreover, the combination of amino acids and TG represents a promising approach to enhance the antimicrobial activities of TG, with the bacteriostatic rate reaching 100 %. Consequently, ATG shows promise as a novel agent for both antioxidation and antimicrobial applications.

Synthesis and Evaluation of Imidazole Derivatives Bearing Imidazo[2,1-b] [1,3,4]thiadiazole Moiety as Antibacterial Agents.

BACKGROUND: Drug-resistant infections kill hundreds of thousands of people globally every year. In previous work, we found that tri-methoxy- and pyridine-substituted imidazoles show strong antibacterial activities. OBJECTIVE: The aim of this work was to investigate the antibacterial activities and bacterial resistances of imidazoles bearing an aromatic heterocyclic, alkoxy, or polycyclic moiety on the central ring. METHODS: Three series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4- yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (13a-e, 14a-d, and 15a-f) were synthesized and their antibacterial activity was evaluated. The structures were confirmed by their 1H NMR, 13C NMR, and HRMS spectra. All the synthesized compounds were screened against Gram-positive, Gramnegative, and multidrug-resistant bacterial strains. RESULTS: More than half of the compounds showed moderate or strong antibacterial activity. Among them, compound 13e (MICs = 1-4 µg/mL) showed the strongest activity against Gram-positive and drug-resistant bacteria as well as high selectivity against Gram-negative bacteria. Furthermore, it showed no cytotoxicity against HepG2 cells, even at 100 µM, and no hemolysis at 20 µM. CONCLUSION: These results indicate that compound 13e is excellent candicate for further study as a potential antibacterial agent.

Semantic-Preserving Surgical Video Retrieval With Phase and Behavior Coordinated Hashing.

Medical professionals rely on surgical video retrieval to discover relevant content within large numbers of videos for surgical education and knowledge transfer. However, the existing retrieval techniques often fail to obtain user-expected results since they ignore valuable semantics in surgical videos. The incorporation of rich semantics into video retrieval is challenging in terms of the hierarchical relationship modeling and coordination between coarse- and fine-grained semantics. To address these issues, this paper proposes a novel semantic-preserving surgical video retrieval (SPSVR) framework, which incorporates surgical phase and behavior semantics using a dual-level hashing module to capture their hierarchical relationship. This module preserves the semantics in binary hash codes by transforming the phase and behavior similarities into high- and low-level similarities in a shared Hamming space. The binary codes are optimized by performing a reconstruction task, a high-level similarity preservation task, and a low-level similarity preservation task, using a coordinated optimization strategy for efficient learning. A self-supervised learning scheme is adopted to capture behavior semantics from video clips so that the indexing of behaviors is unencumbered by fine-grained annotation and recognition. Experiments on four surgical video datasets for two different disciplines demonstrate the robust performance of the proposed framework. In addition, the results of the clinical validation experiments indicate the ability of the proposed method to retrieve the results expected by surgeons. The code can be found at https://github.com/trigger26/SPSVR.

Tumor-targeting hydroxyapatite nanoparticles for remodeling tumor immune microenvironment (TIME) by activating mitoDNA-pyroptosis pathway in cancer.

In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive "cold" tumor types into immuno-responsive "hot" ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.

Strain Sensors Made of MXene, CNTs, and TPU/PSF Asymmetric Structure Films with Large Tensile Recovery and Applied in Human Health Monitoring.

Designing flexible wearable sensors with a wide sensing range, high sensitivity, and high stability is a vulnerable research direction with a futuristic field to study. In this paper, Ti3C2Tx MXene/carbon nanotube (CNT)/thermoplastic polyurethane (TPU)/polysulfone (PSF) composite films with excellent sensor performance were obtained by self-assembly of conductive fillers in TPU/PSF porous films with an asymmetric structure through vacuum filtration, and the porous films were prepared by the phase inversion method. The composite films consist of the upper part with finger-like "cavities" filled by MXene/CNTs, which reduces the microcracks in the conductive network during the tensile process, and the lower part has smaller apertures of a relatively dense resin cortex assisting the recovery process. The exclusive layer structure of the MXene/CNTs/TPU/PSF film sensor, with a thickness of 46.95 µm, contains 0.0339 mg/cm2 single-walled carbon nanotubes (SWNTs) and 0.348 mg/cm2 MXene only, providing functional range (0-80.7%), high sensitivity (up to 1265.18), and excellent stability and durability (stable sensing under 2300 fatigue tests, viable to the initial resistance), endurably cycled under large strains with serious damage to the conductive network. Finally, the MXene/CNTs/TPU/PSF film sensor is usable for monitoring pulse, swallow, tiptoe, and various joint bends in real time and distributing effective electrical signals. This paper implies that the MXene/CNTs/TPU/PSF film sensor has broad prospects in pragmatic applications.