摘要：
STUDY QUESTION: Can a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth? SUMMARY ANSWER: We developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology with continuous scores, enabling finer differentiation between blastocysts with similar or same grades, with higher scores significantly correlating with higher live birth rates. WHAT IS KNOWN ALREADY: While the Gardner grading system is widely used by embryologists worldwide, blastocysts having similar or same ICM and TE grades cause challenges for embryologists in decision-making. Furthermore, human assessment is subjective and inconsistent in predicting which blastocysts have higher potential to result in live birth. STUDY DESIGN, SIZE, DURATION: The study design consists of three main steps. First, BlastScoringNet was developed using a grading dataset of 2760 blastocysts with majority-voted Gardner grades. Second, the model was applied to a live birth dataset of 15228 blastocysts with known live birth outcomes to generate blastocyst scores. Finally, the correlation between these scores and live birth outcomes was assessed. The blastocysts were collected from patients who underwent IVF treatments between 2016 and 2018. For external application study, an additional grading dataset of 1455 blastocysts and a live birth dataset of 476 blastocysts were collected from patients who underwent IVF treatments between 2021 and 2023 at an external IVF institution. PARTICIPANTS/MATERIALS, SETTING, METHODS: In this retrospective study, we developed BlastScoringNet, an interpretable deep-learning model which outputs expansion degree grade and continuous scores quantifying a blastocyst's ICM morphology and TE morphology, based on the Gardner grading system. The continuous ICM and TE scores were calculated by weighting each base grade's predicted probability and summing the predicted probabilities. To represent each blastocyst's overall potential for live birth, we combined the ICM and TE scores using their odds ratios (ORs) for live birth. We further assessed the correlation between live birth rates and the ICM score, TE score, and the OR-combined score (adjusted for expansion degree) by applying BlastScoringNet to blastocysts with known live birth outcomes. To test its generalizability, we also applied BlastScoringNet to an external IVF institution, accounting for variations in imaging conditions, live birth rates, and embryologists' experience levels. MAIN RESULTS AND THE ROLE OF CHANCE: BlastScoringNet was developed using data from 2760 blastocysts with majority-voted grades for expansion degree, ICM, and TE. The model achieved mean area under the receiver operating characteristic curve values of 0.997 (SD 0.004) for expansion degree, 0.903 (SD 0.031) for ICM, and 0.943 (SD 0.040) for TE, based on predicted probabilities for each base grade. From these predicted probabilities, BlastScoringNet generated continuous ICM and TE scores, as well as expansion degree grades, for an additional 15228 blastocysts with known live birth outcomes. Higher ICM and TE scores, along with their OR-combined scores, were significantly correlated with increased live birth rates (P < 0.0001). By fine-tuning, BlastScoringNet was applied to an external IVF institution, where higher OR-combined ICM and TE scores also significantly correlated with increased live birth rates (P = 0.00078), demonstrating consistent results across both institutions. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective nature. Further prospective randomized trials are required to confirm the clinical impact of BlastScoringNet in assisting embryologists in blastocyst selection. WIDER IMPLICATIONS OF THE FINDINGS: BlastScoringNet provides an interpretable and quantitative method for evaluating blastocysts, aligned with the widely used Gardner grading system. Higher OR-combined ICM and TE scores, representing each blastocyst's overall potential for live birth, were significantly correlated with increased live birth rates. The model's demonstrated generalizability across two institutions further supports its clinical utility. These findings suggest that BlastScoringNet is a valuable tool for assisting embryologists in selecting blastocysts with the highest potential for live birth. The code and pre-trained models are publicly available to facilitate further research and widespread implementation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Vector Institute and the Temerty Faculty of Medicine at the University of Toronto, Toronto, Ontario, Canada, via a Clinical AI Integration Grant, and the Natural Science Foundation of Hunan Province of China (2023JJ30714). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.
摘要：
Classic deep learning methods for human activity recognition (HAR) from wearable sensors struggle with cross-person and cross-position challenges due to nonidentical data distributions caused by context variations (e.g., user, sensor placement). Existing solutions show promise but usually require extensive labeled data from source and target contexts, which is often unavailable in real-world scenarios. To address these limitations, we introduce semi-supervised context agnostic representation learning without target (SCAGOT), a novel semi-supervised approach that learns context-agnostic activity representations without relying on target context data. SCAGOT uses a dual-stream architecture with adversarial disentanglement and a contrastive clustering mechanism. This effectively separates context features from context-agnostic activity features, maximizing intraclass compactness and interclass separability in the activity representation space. In addition, a new inverse cross-entropy loss further refines the representations by removing residual context information. Extensive evaluations on four benchmark datasets demonstrate that SCAGOT outperforms state-of-the-art methods in cross-person and cross-position HAR, offering a promising solution for robust real-world activity recognition.
摘要：
The design of complex reactor shielding structures requires consideration of neutron and photon radiation levels in various regions, as well as trade-offs in weight, volume, and cost, leading to a substantial increase in shielding calculation parameters and optimization objectives. This study introduces a high-dimensional multi-objective shielding optimization method based on a multi-parameter shielding calculation surrogate model, with significant improvements to the FCNN-NSGAIII shielding optimization method which integrates a neural network with a genetic algorithm. For the optimization of complex reactor shielding structures under diverse source item energy spectra, the multi-parameter surrogate model achieves a prediction error reduction of an order of magnitude to 3.65% compared to traditional neural networks. Furthermore, the k_NSGAIII optimization algorithm, enhanced with a knee-point strategy, demonstrates a greater relative set coverage indicator than the NSGAIII algorithm, indicating its ability to identify superior shielding design schemes.
The design of complex reactor shielding structures requires consideration of neutron and photon radiation levels in various regions, as well as trade-offs in weight, volume, and cost, leading to a substantial increase in shielding calculation parameters and optimization objectives. This study introduces a high-dimensional multi-objective shielding optimization method based on a multi-parameter shielding calculation surrogate model, with significant improvements to the FCNN-NSGAIII shielding optimization method which integrates a neural network with a genetic algorithm. For the optimization of complex reactor shielding structures under diverse source item energy spectra, the multi-parameter surrogate model achieves a prediction error reduction of an order of magnitude to 3.65% compared to traditional neural networks. Furthermore, the k_NSGAIII optimization algorithm, enhanced with a knee-point strategy, demonstrates a greater relative set coverage indicator than the NSGAIII algorithm, indicating its ability to identify superior shielding design schemes.
摘要：
The complexity of blood and its matrix in high-performance liquid chromatography (HPLC) glycated hemoglobin (HbA1c) assays is closely related to column performance. However, the available prefilters with a single structure or surface membrane materials are not ideal for column protection, andcoupled with the complexity of blood samples, leads to rapid degradation of column performance. Therefore, we have developed a new microprefilter with a three-stage filtration design and depth filter material to protect thecolumn. All filter materials used in the preparation of microprefilters were characterized, screened, and optimized, and then manufactured on the basis of optimized filter materials, which are depth filter material microprefilters. Based on the material and structural design, microprefilters were capable of filtering particulate matter from test samples on a step-by-step basis to avoid the plugging effect that occurs when all sizes of substances are gathered together. Moreover, all newly developed microprefilters can be tested more times, up to 600 times. Microprefilters with small-pore-size final filtration membranes of polyethersulfone, hydrophilic polytetrafluoroethylene, and mixed cellulose showed excellent column protection in terms of column efficiency, HbA1c retention time, number of column tests, and column backpressure, and prolonged column lifetime by as much as 20-30% compared with microprefilters with large-pore-size final membranes. Our study provides valuable depth filter material microprefilters with multistage filtration for chromatography columns, and showed excellent column protection and prolonged column lifetime. Meanwhile, microprefilters can be tested more times. The newly developed microprefilters with a small-pore-size final membrane are the optimal choice for column protection of the HbA1c assay.
作者机构：
[Yang, Gaojian; Usman, Rabia; He, Nongyue; Fang, Yile] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Digital Med Engn, Nanjing 210096, Peoples R China.;[Chen, Zhu; He, Nongyue] Hunan Univ Technol, Hunan Key Lab Biomed Nanomat & Devices, Zhuzhou 412007, Peoples R China.;[Li, Zhiyang] Nanjing Univ, Dept Clin Lab, Affiliated Drum Tower Hosp, Med Sch, Nanjing 210008, Peoples R China.;[Liu, Yuan; Li, Song; Deng, Yan; Chen, Zhu; Deng, Y; Chen, Hui] Univ South China, Inst Cytol & Genet, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Liu, Yuan; Li, Song; Deng, Yan; Chen, Zhu; Deng, Y; Chen, Hui] Univ South China, Inst Future Sci, Changsha 410000, Peoples R China.
通讯机构：
[Liu, Y; Deng, Y ] U;[He, NY ; Fang, YL] S;Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Digital Med Engn, Nanjing 210096, Peoples R China.;Hunan Univ Technol, Hunan Key Lab Biomed Nanomat & Devices, Zhuzhou 412007, Peoples R China.;Univ South China, Inst Cytol & Genet, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Peoples R China.
关键词：
Extracellular vesicles;Aptamer;Streptavidin magnetic beads;Nt.BbvCI;Detection
摘要：
The extracellular vesicles show great potential as a noninvasive biomarker for the early detection of cancer. Hence, there is an urgent requirement to create biosensors that are time-saving, simple, and easily scalable in order to accomplish rapid, sensitive, and quantitative detection of extracellular vesicles. In this study, we present a self-propelled DNA walker powered by endonuclease Nt.BbvCI, which enables the development of a “signal on” sensing platform for the rapid and highly sensitive detection of extracellular vesicles. The DNA motor employed tracks made of streptavidin magnetic beads, which consisted of substrate strands labeled with fluorescein and motor strands locked by aptamers. The aptamer recognition of the target protein on extracellular vesicles unlocked the motor strand, initiating the DNA motor process. After replacing the optimal buffer solution containing the endonuclease Nt.BbvCI, the motor strands autonomously moved along the streptavidin magnetic beads track, continuously releasing fluorescent molecules and producing detectable fluorescence signals. Under optimal conditions, the detection range was from 2×104 particles/mL to 2×109 particles/mL, with a detection limit of 2.9×103 particles/mL, demonstrating excellent selectivity. This method has demonstrated good selectivity in different tumor-derived extracellular vesicles and performs well in complex biological samples. The ability to effectively analyze surface proteins of extracellular vesicles in a short period of time gives our DNA walker a tremendous potential for developing simple and cost-effective clinical diagnostic devices.
The extracellular vesicles show great potential as a noninvasive biomarker for the early detection of cancer. Hence, there is an urgent requirement to create biosensors that are time-saving, simple, and easily scalable in order to accomplish rapid, sensitive, and quantitative detection of extracellular vesicles. In this study, we present a self-propelled DNA walker powered by endonuclease Nt.BbvCI, which enables the development of a “signal on” sensing platform for the rapid and highly sensitive detection of extracellular vesicles. The DNA motor employed tracks made of streptavidin magnetic beads, which consisted of substrate strands labeled with fluorescein and motor strands locked by aptamers. The aptamer recognition of the target protein on extracellular vesicles unlocked the motor strand, initiating the DNA motor process. After replacing the optimal buffer solution containing the endonuclease Nt.BbvCI, the motor strands autonomously moved along the streptavidin magnetic beads track, continuously releasing fluorescent molecules and producing detectable fluorescence signals. Under optimal conditions, the detection range was from 2×104 particles/mL to 2×109 particles/mL, with a detection limit of 2.9×103 particles/mL, demonstrating excellent selectivity. This method has demonstrated good selectivity in different tumor-derived extracellular vesicles and performs well in complex biological samples. The ability to effectively analyze surface proteins of extracellular vesicles in a short period of time gives our DNA walker a tremendous potential for developing simple and cost-effective clinical diagnostic devices.
摘要：
In this paper, a novel bifunctional molecule dialkyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DAHAOEP) containing both phosphoryl and hydroxamic groups was designed and synthesized, and used as a uranium extractant. The extraction properties of DAHAOEP were focused. Dihexyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DHHAOEP) was shown to have a better extraction effect on uranyl ions than dibutyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DBHAOEP) and diethyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DEHAOEP). Under the optimal extraction conditions, the extraction efficiency of DHHAOEP on uranyl ions could reach up to 98 %. Extraction saturation capacity, reusability and selectivity results indicated that the saturation capacity of DHHAOEP continuous extraction can reach 596 % after 10 times of extraction, DHHAOEP had been recycled more than 5 times, and exhibited a superior selectivity for uranyl ions. Slope method showed that DHHAOEP mainly coordinated with uranyl ions in a 1:2 coordination, i.e., monomolecular bidentate coordination M2L. FTIR and XPS analysis further confirmed that DHHAOEP combined with uranyl ions through it’s -C(=O)-NHOH and P = O groups to form a five-membered ring and P-O-U configuration, respectively.
In this paper, a novel bifunctional molecule dialkyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DAHAOEP) containing both phosphoryl and hydroxamic groups was designed and synthesized, and used as a uranium extractant. The extraction properties of DAHAOEP were focused. Dihexyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DHHAOEP) was shown to have a better extraction effect on uranyl ions than dibutyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DBHAOEP) and diethyl (2-(hydroxyamino)-2-oxoethyl) phosphonate (DEHAOEP). Under the optimal extraction conditions, the extraction efficiency of DHHAOEP on uranyl ions could reach up to 98 %. Extraction saturation capacity, reusability and selectivity results indicated that the saturation capacity of DHHAOEP continuous extraction can reach 596 % after 10 times of extraction, DHHAOEP had been recycled more than 5 times, and exhibited a superior selectivity for uranyl ions. Slope method showed that DHHAOEP mainly coordinated with uranyl ions in a 1:2 coordination, i.e., monomolecular bidentate coordination M2L. FTIR and XPS analysis further confirmed that DHHAOEP combined with uranyl ions through it’s -C(=O)-NHOH and P = O groups to form a five-membered ring and P-O-U configuration, respectively.
摘要：
The lung as an organ that is fully exposed to the external environment for extended periods, comes into contact with numerous inhaled microorganisms. Lung macrophages are crucial for maintaining lung immunity and operate primarily through signaling pathways such as toll-like receptor 4 and nuclear factor-κB pathways. These macrophages constitute a diverse population with significant plasticity, exhibiting different phenotypes and functions on the basis of their origin, tissue residence, and environmental factors. During lung homeostasis, they are involved in the clearance of inhaled particles, cellular remnants, and even participate in metabolic processes. In disease states, lung macrophages transition from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. These distinct phenotypes have varying transcriptional profiles and serve different functions, from combating pathogens to repairing inflammation-induced damage. However, macrophages can also exacerbate lung injury during prolonged inflammation or exposure to antigens. In this review, we delve into the diverse roles of pulmonary macrophages the realms in homeostasis, pneumonia, tuberculosis, and lung tumors.
摘要：
Histamine is catalyzed by histidine decarboxylase (HDC), which plays important roles in many physiological and pathological processes, but its role in angiogenesis has not been thoroughly clarified. Here we report that HDC is highly expressed in Ly6C(+) macrophages, rather than in endothelial cells using Hdc-GFP transgenic mice with hindlimb ischemia (HLI) mouse model. Given the whole-process promoting effect of macrophages on angiogenesis, a cluster of HDC(+)CXCR2(+) macrophages have been identified by single-cell sequencing technology in ischemic tissue. The inactivation of HDC leads to a lack of histamine and pro-angiogenic factor production in macrophages, inducing a harsh inflammatory microenvironment that is not conducive to the interaction between macrophages and endothelial cells. Moreover, HA-DA@histamine hydrogel has been designed and demonstrated to safely treat ischemic injury by modulating inflammation and angiogenesis. These data highlight the critical roles of HDC/histamine signaling in macrophage differentiation, angiogenesis, and muscle regeneration in the early stage of HLI.
摘要：
Epicanthus refers to the longitudinal curved skin folds that cover the medial canthus, which affect aesthetics due to covering the medial canthus angle and lacrimal mound. Various surgical methods exist for correcting epicanthus, each with its own set of advantages and disadvantages, and lacking a standardized operational protocol, making it difficult for beginners to master and for clinical promotion.This article aims to explore a standardized and simplified five-step procedure for treating epicanthus and report our clinical experience and effectiveness. A retrospective analysis was conducted from October 2019 to September 2022 at the Burn and Plastic Surgery Department of the Second Affiliated Hospital of South China University. A consistent team of doctors utilized a five-step method to correct the medial canthus in 306 patients with epicanthus. All patients were followed up for more than 6 months. We observed 306 patients and used iris diameter as a reference value to subjectively evaluate the clinical effect through photo evaluation and scar scoring.Objective evaluation of clinical efficacy was achieved through the inter canthal distance (ICD) and palpebral fissure length (PFL). The study included 295 females and 11 males, with an average follow-up time of 14.2 months.The average increase rate of PFL is 14.9%, and the average reduction rate of ICD is 8.6%. Two cases of bleeding and swelling were promptly treated, and no long-term complications were left. 85 cases of scar hyperplasia were treated with KELO-COTE® silicone gel, triamcinolone injection, and appropriate laser therapy in combination, and the scars gradually resolved after 12 months. 4 cases of recurrence and 2 cases of asymmetry underwent reoperation. Observing the satisfaction and effectiveness rate of 306 patients, the overall satisfaction and effectiveness rate reached over 95%. About 96.40% of patients were satisfied with the surgery and would recommend it to their family and friends. The paired t-test was used for statistical analysis, and the results showed statistical significance. The five-step method for correcting epicanthus proves to be a simple, efficient, and reliable technique that is easily mastered by beginners. It boasts high patient satisfaction and carries a low risk of scar formation.
作者机构：
[Yuexin Wang] Department of Anesthesiology, Cangzhou People’s Hospital, Cangzhou, China;[Jingli Chen] Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;[Xiaoling Hu] The First Affiliated Hospital of University of South China, Hengyang, China;[Huayong Jiang] Shaoxing People’s Hospital, Shaoxing, China;[Saiying Wang] The Third Xiangya Hospital of Central South University, Changsha, China
通讯机构：
[Xiangdong Chen; Min Yan] D;Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China;Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China<&wdkj&>Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
摘要：
HSK21542, a peripherally restricted kappa opioid receptor agonist, was evaluated for efficacy and safety in patients with postoperative pain following abdominal surgery. This was assessed in two phase 3, multicentre, randomized, double-blind, controlled trials (HSK21542-301 [ClinicalTrials.gov identifier, NCT04738357] and HSK21542-303 [ClinicalTrials.gov identifier, NCT05390905]) in China. HSK21542-301 was a dual-arm study comparing HSK21542 1.0 μg/kg with placebo, while HSK21542-303 involved three arms comparing HSK21542 1.0 μg/kg with tramadol 50 mg/dose and placebo. All treatments were administered intravenously. The primary endpoint was the time-weighted summed pain intensity differences over 24 h (SPID0-24 h). Both HSK21542-301 (least squares [LS] mean [± standard error], −39.1 [1.88] vs −27.4 [1.89]; P < 0.001) and HSK21542-303 (−64.0 [2.25] vs −45.9 [2.25]; P < 0.001) demonstrated superiority of HSK21542 over placebo in terms of SPID0-24 h, while HSK21542-303 showed non-inferiority to tramadol (LS mean difference, −1.1; 95% confidence interval, −7.4 to 5.1; P < 0.001). Furthermore, HSK21542 had a comparable safety profile to placebo, inducing fewer gastrointestinal adverse events compared with tramadol. Grade ≥3 treatment-emergent adverse events occurred in eight (5.9%) and three (2.3%) patients in the HSK21542 arm of HSK21542-301 and HSK21542-303, respectively. In conclusion, HSK21542 showed potent analgesic effect and was well tolerated in patients who underwent abdominal surgery and experienced postoperative pain. Commonly used opioids for pain management primarily target the mu opioid receptor. However, mu opioid receptor agonists often come with harmful side effects. Here, the authors report the results of two phase 3 trials of HSK21542 (anrikefon), a highly selective activator of peripheral kappa opioid receptor agonists, for postoperative pain treatment following abdominal surgery.
摘要：
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
期刊：
PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2025年27(5):2828-2833 ISSN：1463-9076
通讯作者：
Liu, Xichun;Lin, YW
作者机构：
[Han, Hui; Pan, Aiqun; Lin, Ying-Wu; Liu, Xichun; Liu, XC] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Gao, Shu-Qin; Lin, Ying-Wu] Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
通讯机构：
[Lin, YW ; Liu, XC] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
摘要：
Globin X is a newly discovered member of the globin family, while its structure and function are not fully understood. In this study, we performed protein modelling studies using Alphafold3 and molecular dynamics simulations, which suggested that the protein adopts a typical globin fold, with the formation of a potential disulfide bond of Cys65 and Cys141. To elucidate the role of this unique disulfide in protein structure and stability, we constructed a double mutant of C65S/C141S by mutating the two cysteine residues to serine. As suggested by protein mass, ultraviolet-visible (UV-Vis) and circular dichroism (CD) spectroscopy analyses, the potential disulfide bond has minimal effect on the overall protein structure, but its absence reduces the protein stability. Electron paramagnetic resonance (EPR) analysis also revealed an increase in the proportion of high-spin state heme iron, which accelerates the rate of heme degradation in reaction with H(2)O(2). This study highlights the critical role of the Cys65-Cys141 in maintaining the stability of globin X and the bis-His heme coordination state, providing insights into the structure-function relationship of the newly discovered globin.
摘要：
Advanced atherosclerosis is the pathological basis for acute cardiovascular events, with significant residual risk of recurrent clinical events despite contemporary treatment. The death of foamy macrophages is a main contributor to plaque progression, but the underlying mechanisms remain unclear. Bulk and single-cell RNA sequencing demonstrated that massive iron accumulation in advanced atherosclerosis promoted foamy macrophage ferroptosis, particularly in low expression of triggering receptor expressed on myeloid cells 2 (TREM2 low ) foamy macrophages. This cluster exhibits metabolic characteristics with low oxidative phosphorylation (OXPHOS), increasing ferroptosis sensitivity. Mechanically, upregulated heme oxygenase 1 (HMOX1)-lactate dehydrogenase B (LDHB) interaction enables Lon peptidase 1 (LONP1) to degrade mitochondrial transcription factor A (TFAM), leading to mitochondrial dysfunction and ferroptosis. Administration of the mitochondria-targeted reactive oxygen species (ROS) scavenger MitoTEMPO (mitochondrial-targeted TEMPO) or LONP1 inhibitor bortezomib restored mitochondrial homeostasis in foamy macrophages and alleviated atherosclerosis. Collectively, our study elucidates the cellular and molecular mechanism of foamy macrophage ferroptosis, offering potential therapeutic strategies for advanced atherosclerosis.
Advanced atherosclerosis is the pathological basis for acute cardiovascular events, with significant residual risk of recurrent clinical events despite contemporary treatment. The death of foamy macrophages is a main contributor to plaque progression, but the underlying mechanisms remain unclear. Bulk and single-cell RNA sequencing demonstrated that massive iron accumulation in advanced atherosclerosis promoted foamy macrophage ferroptosis, particularly in low expression of triggering receptor expressed on myeloid cells 2 (TREM2 low ) foamy macrophages. This cluster exhibits metabolic characteristics with low oxidative phosphorylation (OXPHOS), increasing ferroptosis sensitivity. Mechanically, upregulated heme oxygenase 1 (HMOX1)-lactate dehydrogenase B (LDHB) interaction enables Lon peptidase 1 (LONP1) to degrade mitochondrial transcription factor A (TFAM), leading to mitochondrial dysfunction and ferroptosis. Administration of the mitochondria-targeted reactive oxygen species (ROS) scavenger MitoTEMPO (mitochondrial-targeted TEMPO) or LONP1 inhibitor bortezomib restored mitochondrial homeostasis in foamy macrophages and alleviated atherosclerosis. Collectively, our study elucidates the cellular and molecular mechanism of foamy macrophage ferroptosis, offering potential therapeutic strategies for advanced atherosclerosis.
作者：
Yan Lou;Wei Jin;Zhiwei Huang;Yuanyuan Liang;Kongqiu Hu;...
期刊：
中国化学快报：英文版,2025年:111279 ISSN：1001-8417
通讯作者：
Changchun Zhao<&wdkj&>Lei Mei
作者机构：
[Changchun Zhao] School of Science, China University of Geosciences, Beijing (CUGB), Beijing 100083, China;[Wei Jin; Zhiwei Huang; Yuanyuan Liang; Kongqiu Hu; Liyong Yuan; Lei Mei] Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China;School of Nuclear Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China;[Lingling Su] School of Nuclear Science and Technology, University of South China, Hengyang 421001, China;[Yan Lou] School of Science, China University of Geosciences, Beijing (CUGB), Beijing 100083, China<&wdkj&>Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
通讯机构：
[Changchun Zhao] S;[Lei Mei] L;Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China<&wdkj&>School of Science, China University of Geosciences, Beijing (CUGB), Beijing 100083, China
摘要：
Hierarchical assembly provides a rational procedure to acquire complex supramolecular architectures from basic building blocks. In this work, a novel kind of double-stranded polyrotaxane motif was reported by Ag + -directed coordination-driven assembly following the preassembly of a four-connected pseudorotaxane (cpb) 2 -CB8 linker. Moreover, supramolecular isomerism is observed in crystalline compounds based on double-stranded polyrotaxane motifs due to differences in lattice stacking mode. Interestingly, the resultant supramolecular isomers, cross-Ag-DSP-1 and para-Ag-DSP-1, show dual thermo- and anion-responsiveness. Benefiting from high crystallinity of these coordination assemblies, a combination of characterization techniques, especially X-ray diffraction, were used to unveil precise molecular mechanism related to inherent dynamic behavior of these assemblies, which can be attributed to remarkable lattice rearrangement and crystal transformations as temperature increases or after anion exchange, reflecting the adaptive adjustment ability of these supramolecular architectures in response to external stimuli. Based on the anion exchange capability, these two supramolecular materials show fast removal kinetics and high sorption capacity for perrhenate (ReO 4 - ) anion, a surrogate of radioactive pertechnetate (TcO 4 - ) in nuclear waste eluents. This work provides a feasible way to supramolecular assemblies with customized structures and stimuli-responsiveness, and is helpful to design and synthesize more functional supramolecular systems with complex structures and tailored functions.
Hierarchical assembly provides a rational procedure to acquire complex supramolecular architectures from basic building blocks. In this work, a novel kind of double-stranded polyrotaxane motif was reported by Ag + -directed coordination-driven assembly following the preassembly of a four-connected pseudorotaxane (cpb) 2 -CB8 linker. Moreover, supramolecular isomerism is observed in crystalline compounds based on double-stranded polyrotaxane motifs due to differences in lattice stacking mode. Interestingly, the resultant supramolecular isomers, cross-Ag-DSP-1 and para-Ag-DSP-1, show dual thermo- and anion-responsiveness. Benefiting from high crystallinity of these coordination assemblies, a combination of characterization techniques, especially X-ray diffraction, were used to unveil precise molecular mechanism related to inherent dynamic behavior of these assemblies, which can be attributed to remarkable lattice rearrangement and crystal transformations as temperature increases or after anion exchange, reflecting the adaptive adjustment ability of these supramolecular architectures in response to external stimuli. Based on the anion exchange capability, these two supramolecular materials show fast removal kinetics and high sorption capacity for perrhenate (ReO 4 - ) anion, a surrogate of radioactive pertechnetate (TcO 4 - ) in nuclear waste eluents. This work provides a feasible way to supramolecular assemblies with customized structures and stimuli-responsiveness, and is helpful to design and synthesize more functional supramolecular systems with complex structures and tailored functions.
期刊：
Cancer Cell International,2025年25(1):1-14 ISSN：1475-2867
通讯作者：
Kuiyu Gong<&wdkj&>Guihua Wang
作者机构：
[Yanfang Liu; Sikai Wang; Jiangyan Chen; Yang Zhao; Kuiyu Gong; Guihua Wang] Department of Oncology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410021, China;[Yuanjun Zeng] Department of Pathology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China;[Zhouqi Wang] Traditional Chinese Medicine, Medical School of Shanxi Datong University, Datong, China
通讯机构：
[Kuiyu Gong; Guihua Wang] D;Department of Oncology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410021, China
摘要：
Platinum-based chemotherapy is the standard first-line cancer treatment. However, patients experience relapses due to chemoresistance. We found that long non-coding RNA 16 (lncRNA16) promotes platinum resistance and inhibits cell death in non-small cell lung cancer (NSCLC). However, the type of cell death inhibited by lncRNA16 remains unknown. The biological roles of lncRNA16 and microRNA 1827 (miRNA1827) in cell proliferation and colony formation were determined using functional experiments. Dual-luciferase reporter and RNA immunoprecipitation assays were performed to confirm the interactions between lncRNA16 and miRNA1827. In vivo patient-derived tumor xenograft (PDX) models were used to investigate the effects of miRNA1827 agomir on platinum resistance. Pyroptosis was inhibited in platinum-resistant NSCLC cells. LncRNA16 contributed to the expression of methyl-CpG binding domain protein 3 (MBD3) by sponging miRNA1827, thereby inhibiting gasdermin E (GSDME) expression, which inhibited pyroptosis in platinum-resistant NSCLC. The miRNA1827 agomir repressed platinum resistance in vitro experiments and in vivo PDX models. We identified a novel function of lncRNA16 in inhibiting pyroptosis and proposed an effective therapeutic drug, the miRNA1827 agomir, for chemosensitization. This study offers a potential strategy for treating patients with NSCLC, especially those with platinum resistance.
作者机构：
[Fan, Yuyun; Xu, Ye; Wang, Chunlong; Lang, Xiaodong; Wang, Xi] Deep Min Lab Shandong Gold Grp Co Ltd, Yantai, Peoples R China.;[Lin, QB; Lin, Qibin] Univ South China, Sch Resources Environm & Safety Engn, Hengyang, Peoples R China.
通讯机构：
[Lin, QB ] U;Univ South China, Sch Resources Environm & Safety Engn, Hengyang, Peoples R China.
摘要：
During the excavation of the shaft, the inlet air temperature undergoes seasonal variations and is influenced by geothermal effects and air compression heat. Merely augmenting the inlet air volume fails to mitigate the extreme temperatures encountered at the deep working face. Consequently, the implementation of refrigeration and cooling technologies becomes imperative to manage the heat-induced issues. To address the high-temperature challenge during shaft excavation at the Sanshandao Gold Mine, a ventilation system model was developed utilizing Fluent simulation software. This model facilitated the prediction of the temperature field dynamics at the working face, taking into account project progression and seasonal shifts. Through a comprehensive analysis of factors encompassing cooling capacity deterioration, energy consumption for cooling, and the installation and maintenance requirements of refrigeration units across various systems, a surface-based centralized refrigeration system was devised. Furthermore, a simulation analysis was conducted to evaluate the refrigeration technology, offering valuable technical insights for the calculation of cooling capacity, as well as the selection and application of appropriate refrigeration systems. The results indicated that subsequent to excavating the shaft to a depth of 1600 m, the working face temperature fluctuated with seasonal variations but consistently remained above 28 degrees C. At a depth of 1800 m, the temperature peaked, reaching a maximum of 40.19 degrees C. Following the implementation of the surface centralized refrigeration system, with an inlet air volume of 22.6 m3/s and an inlet air temperature maintained below 10 degrees C, the working face temperature was effectively reduced to below 27 degrees C. This study presents a comprehensive suite of refrigeration and cooling methodologies, encompassing temperature field prediction, refrigeration parameter calculation, simulation analysis of cooling performance, refrigeration system design, and their application in deep shaft excavation. These methods provide a technical foundation for mitigating heat-induced damage in deep shafts.
作者：
Ji, Hong-Tao;Lu, Yu-Han;Liu, Yan-Ting;Huang, Yu-Lin;Tian, Jiang-Feng;...
期刊：
中国化学快报：英文版,2025年36(2):110568 ISSN：1001-8417
通讯作者：
Zhang, YH;He, WM
作者机构：
[Liu, Yan-Ting; Liu, Feng; Ji, Hong-Tao; Huang, Yu-Lin; Zhang, Yong-Hong] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Ophthalmol, Hengyang 421001, Peoples R China.;[Zeng, Yan-Yan; Lu, Yu-Han; He, Wei-Min; Tian, Jiang-Feng; Ji, Hong-Tao; He, WM] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Yang, Hai-Yan] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp,Xiangya Sch Med, Dept Lung Canc & Gastroenterol, Changsha 410013, Peoples R China.
通讯机构：
[Zhang, YH ; He, WM ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Ophthalmol, Hengyang 421001, Peoples R China.;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
关键词：
Dual catalysis;Semiconductor;Chlorine;Redox catalyst;Hydrogen atom transfer
摘要：
The first example of Nd@C3N4-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed, which allows for the synthesis of various 4-alkylated cyclic sulfonyl ketimines. In this process, chlorine functions as both a redox and hydrogen atom transfer catalyst. The synergism of the reversible Nd2+/Nd3+ and Cl¯/Cl˙ redox pairs significantly enhances overall photocatalytic efficiency. The in vitro anticancer activity of 4-alkylated products was evaluated by using the CCK8 assay against both human choroidal melanoma (MUM-2B) and lung cancer (A549) cell. Compound 3da showed approximately triple the potency of 5-fluorouracil.
The first example of Nd@C3N4-photoredox/chlorine dual catalyzed alkylation with unactivated alkanes as the alkyl sources has been developed, which allows for the synthesis of various 4-alkylated cyclic sulfonyl ketimines. In this process, chlorine functions as both a redox and hydrogen atom transfer catalyst. The synergism of the reversible Nd2+/Nd3+ and Cl¯/Cl˙ redox pairs significantly enhances overall photocatalytic efficiency. The in vitro anticancer activity of 4-alkylated products was evaluated by using the CCK8 assay against both human choroidal melanoma (MUM-2B) and lung cancer (A549) cell. Compound 3da showed approximately triple the potency of 5-fluorouracil.
