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This study investigated the effects of high-hydrostatic-pressure (HHP) treatment of varying intensity (100-600 MPa) and duration (10-30 min) on polyphenols and volatile aromatic compounds in Marselan red wine. The types and concentrations of polyphenols and volatile aromatic compounds were compared before and after HHP treatment; the results indicated that HHP treatment at 300 MPa for 20 min significantly increased the total polyphenol content to 369.70 mg/L, a rise of 35.82%. The contents of key polyphenols, such as resveratrol and protocatechuic acid, were significantly enhanced. Furthermore, while the total content of volatile aromatic compounds did not change significantly under this condition compared to the untreated samples, the concentration of ester compounds significantly increased to 1.81 times that of the untreated group, thereby enriching the floral and fruity aromas of the wine and effectively improving its aromatic profile and sensory quality. Principal component analysis (PCA) further validated the positive impact of HHP treatment on the flavor characteristics of Marselan red wine. These findings provide technical support for the use of HHP in improving wine quality.
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Accurate diagnosis of white blood cells from cytopathological images is a crucial step in evaluating leukaemia. In recent years, image classification methods based on fully convolutional networks have drawn extensive attention and achieved competitive performance in medical image classification. In this paper, we propose a white blood cell classification network called ResNeXt-CC for cytopathological images. First, we transform cytopathological images from the RGB color space to the HSV color space so as to precisely extract the texture features, color changes and other details of white blood cells. Second, since cell classification primarily relies on distinguishing local characteristics, we design a cross-layer deep-feature fusion module to enhance our ability to extract discriminative information. Third, the efficient attention mechanism based on the ECANet module is used to promote the feature extraction capability of cell details. Finally, we combine the modified softmax loss function and the central loss function to train the network, thereby effectively addressing the problem of class imbalance and improving the network performance. The experimental results on the C-NMC 2019 dataset show that our proposed method manifests obvious advantages over the existing classification methods, including ResNet-50, Inception-V3, Densenet121, VGG16, Cross ViT, Token-to-Token ViT, Deep ViT, and simple ViT about 5.5-20.43% accuracy, 3.6-23.56% F1-score, 3.5-25.71% AUROC and 8.1-36.98% specificity, respectively.
Subject(s)
Leukocytes , Humans , Leukocytes/cytology , Neural Networks, Computer , Image Processing, Computer-Assisted/methods , Leukemia/pathology , Leukemia/classification , Algorithms , Deep LearningABSTRACT
Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.
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PURPOSE: This study aimed to explore relationship between lifestyle and depressive symptoms and evaluated the mediating effect of menopausal symptoms. METHODS: This was a secondary analysis of a survey in Hunan Province, China. We selected 3190 women aged 40 to 55 into final analyses. Menopausal and depressive symptoms were assessed by the Kupperman Menopausal Index and the 9-item Patient Health Questionnaire, respectively. A self-administered questionnaire was used to collect demographic and lifestyle information. RESULTS: The prevalence of depressive symptoms was 19.5%. After adjusting for demographic variables, passive smoking, drinking, and intensity of physical activity were positively associated with depressive symptoms. Frequency of exercise was a protective factor for depressive symptoms (AOR = 0.783, 95%CI: 0.446-0.991). Excess or restricted sleep duration was associated with higher probability of having depressive symptoms (AOR = 1.746, 95% CI: 1.324-2.304). Menopausal symptoms partially mediated the relationship between lifestyle and depressive symptoms. CONCLUSION: Findings highlighted the importance of menopausal symptoms in the relationship between the lifestyle and depressive symptoms, and provided a possibility that active lifestyle might improve depression symptoms among women at perimenopause through changes in sex hormones.
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Dissolved organic matter (DOM) plays a critical role in driving the development of biogeochemical functions in revegetated metal smelting slag sites, laying a fundamental basis for their sustainable rehabilitation. However, the DOM composition at the molecular level and its interaction with the microbial community in such sites undergoing long-term direct revegetation remain poorly understood. This study investigated the chemodiversity of DOM and its association with the bacterial community in the rhizosphere and non-rhizosphere slags of four plant species (Arundo donax, Broussonetia papyrifera, Cryptomeria fortunei, and Robinia pseudoacacia) planted at a zinc smelting slag site for 10 years. The results indicated that the relative abundance of lipids decreased from 18 % to 5 %, while the relative abundance of tannins and lignins/CRAM-like substances increased from 4 % to 10 % and from 44 % to 64 % in the revegetated slags, respectively. The chemical stability of the organic matter in the rhizosphere slag increased due to the retention of recalcitrant DOM components, such as lignins, aromatics, and tannins. As the diversity and relative abundance of the bacterial community increased, particularly within the Proteobacteria, there was better utilization of recalcitrant components (e.g., lignins/CRAM-like compounds), but this utilization was not invariable. In addition, potential preference associations between specific bacterial OTUs and DOM molecules were observed, possibly stimulated by heavy metal bioavailability. Network analysis revealed complex connectivity and strong interactions between the bacterial community and DOM molecules. These specific interactions between DOM molecules and the bacterial community enable adaptation to the harsh conditions of the slag environment. Overall, these findings provide novel insights into the transformation of DOM chemodiversity at the molecular level at a zinc smelting slag sites undergoing long-term revegetation. This knowledge could serve as a crucial foundation for developing direct revegetation strategies for the sustainable rehabilitation of metal smelting slag sites.
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The capability to excite, probe, and manipulate vibrational modes is essential for understanding and controlling chemical reactions at the molecular level. Recent advancements in tip-enhanced Raman spectroscopies have enabled the probing of vibrational fingerprints in a single molecule with Ångström-scale spatial resolution. However, achieving controllable excitation of specific vibrational modes in individual molecules remains challenging. Here, we demonstrate the selective excitation and probing of vibrational modes in single deprotonated phthalocyanine molecules utilizing resonance Raman spectroscopy in a scanning tunneling microscope. Selective excitation is achieved by finely tuning the excitation wavelength of the laser to be resonant with the vibronic transitions between the molecular ground electronic state and the vibrational levels in the excited electronic state, resulting in the state-selective enhancement of the resonance Raman signal. Our approach contributes to setting the stage for steering chemical transformations in molecules on surfaces by selective excitation of molecular vibrations.
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BACKGROUND: Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear. METHODS: We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018. RESULTS: We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo. CONCLUSIONS: Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.
Subject(s)
B7-H1 Antigen , CD8-Positive T-Lymphocytes , Chemokine CXCL5 , Lung Neoplasms , Neutrophils , Proto-Oncogene Proteins c-akt , Humans , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Animals , Neutrophils/metabolism , Neutrophils/immunology , Chemokine CXCL5/metabolism , Chemokine CXCL5/genetics , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphorylation , Signal Transduction , Up-Regulation , Female , Male , Chemotaxis , Mice, Inbred NOD , Mice, SCIDABSTRACT
Rock-climbing robots have significant potential in fieldwork and planetary exploration. However, they currently face limitations such as a lack of stability and adaptability on extreme terrains, slow locomotion, and single functionality. This study introduces a novel multimodal and adaptive rock-climbing robot (MARCBot), which addresses these limitations through spiny grippers that draw inspiration from morpho-functionalities observed in beetles, arboreal birds, and hoofed animals. This hybrid bioinspired design enables high attachment strength, passive adaptability to different terrains, and quick attachment on rock surfaces. The multimodal functionality of the gripper allows for attachment during climbing and support during walking. A novel control strategy using dynamics and quadratic programming (QP) optimizes attachment wrench distribution, reducing cost-of-transport by 20.03% and 6.05% compared to closed-loop inverse kinematic (CLIK) and virtual model control (VMC) methods, respectively. MARCBot achieved climbing speeds of 0.15 m min-1 on a vertical discrete rock surface under gravity and trotting speeds of up to 0.21 m s-1 on various complex terrains. It is the first robot capable of climbing on rock surfaces and trotting in complex terrains without the need for switching end-effectors. This study highlights significant advancements in climbing and multimodal locomotion for robots in extreme environments.
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OBJECTIVES: To investigate the protective effects of 2-methoxyestradiol (2ME) against hypoxic pulmonary hypertension (HPH) in neonatal rats. METHODS: Ninety-six Wistar neonatal rats were randomly divided into a normoxia group, a hypoxia group, and a hypoxia + 2ME group, with each group further subdivided into 3-day, 7-day, 14-day, and 21-day subgroups, containing eight rats each. The hypoxia and hypoxia + 2ME groups received daily subcutaneous injections of saline and 2ME (240 µg/kg), respectively, while the normoxia group was raised in a normoxic environment with daily saline injections. Right ventricular systolic pressure (RVSP) was measured using the direct pressure method. Pulmonary vascular morphology was assessed using hematoxylin and eosin staining, with metrics including the percentage of medial thickness of small pulmonary arteries relative to the external diameter (MT%) and the cross-sectional area of the media of small pulmonary arteries relative to the total cross-sectional area (MA%). Immunohistochemistry was used to detect the expression levels of hypoxia-inducible factor-1α (HIF-1α) and proliferating cell nuclear antigen (PCNA) proteins, while real-time quantitative PCR was used to to assess HIF-1α and PCNA mRNA levels. RESULTS: Compared to the normoxia group, the hypoxia and hypoxia + 2ME groups showed increased RVSP and upregulated HIF-1α and PCNA protein and mRNA expression levels at 3, 7, 14, and 21 days after hypoxia (P<0.05). Furthermore, at 7, 14, and 21 days after hypoxia, the hypoxia group showed increased MT% and MA% (P<0.05). In comparison to the hypoxia group, the hypoxia + 2ME group exhibited reduced RVSP and downregulated HIF-1α and PCNA protein and mRNA expression levels, along with decreased MT% and MA% at 7, 14, and 21 days after hypoxia (P<0.05). CONCLUSIONS: 2ME may protect against HPH in neonatal rats by inhibiting the expression of HIF-1α and PCNA and reducing pulmonary vascular remodeling. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 757-764.
Subject(s)
2-Methoxyestradiol , Animals, Newborn , Hypertension, Pulmonary , Hypoxia-Inducible Factor 1, alpha Subunit , Hypoxia , Proliferating Cell Nuclear Antigen , Pulmonary Artery , Rats, Wistar , Animals , 2-Methoxyestradiol/pharmacology , Rats , Hypertension, Pulmonary/prevention & control , Hypertension, Pulmonary/drug therapy , Proliferating Cell Nuclear Antigen/analysis , Proliferating Cell Nuclear Antigen/genetics , Hypoxia/complications , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Pulmonary Artery/drug effects , Male , Female , Estradiol/pharmacology , Estradiol/analogs & derivatives , RNA, Messenger/analysisABSTRACT
In the catalytic transformation of bio-oil into liquid fuels having alkanes via hydrodeoxygenation (HDO), the acid and metal sites in the catalyst are pivotal for promoting the HDO of lignin-derived phenolic compounds. This study introduces a novel bifunctional catalyst comprising phosphomolybdenum-vanadium heteropolyacids (H4PMo11VO40) coupled with Ni/C. The HDO reaction of the model compound guaiacol was carried out under reaction conditions of 230 °C, revealing the superior performance of H4PMo11VO40 with Ni/C catalysts compared to the conventional acids, even at low dosage. The Keggin structure of H4PMo11VO40 provided a solid catalyst with strong acidic and redox properties, alongside advantages such as ease of synthesis, cost-effectiveness, and tunable acid and redox properties at the molecular level. Characterization of Ni/C and the prepared acid demonstrated favorable pore structure with a mesopore volume of 0.281 cm3/g and an average pore size of 3.404 nm, facilitating uniform distribution and catalytic activity of Ni-metal. Incorporating acid enhances the acidic sites, fostering synergistic interactions between metal and acidic sites within the catalyst, thereby significantly enhancing HDO performance. Guaiacol conversion at 230 °C reached 100%, with a cyclohexane selectivity of 89.3%. This study presents a promising pathway for converting lignin-derived phenolic compounds.
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Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.
Subject(s)
Ferroptosis , Melatonin , Mice, Knockout , Sleep Deprivation , Animals , Mice , Melatonin/metabolism , Melatonin/pharmacology , Sleep Deprivation/metabolism , Male , Reactive Oxygen Species/metabolism , Mice, Inbred C57BL , Lipid Peroxidation , Arachidonate 15-Lipoxygenase/metabolism , Arachidonate 15-Lipoxygenase/genetics , Arachidonate 12-LipoxygenaseABSTRACT
Prostate-specific membrane antigen (PSMA) is an excellent target for cancer detection and therapy. Hypoxia is prevalent in solid tumors, and various nitroimidazole (NI) radioligands can be trapped inside hypoxic cells for diagnosis and therapy. To enhance tumor uptake and retention, we designed bivalent agents (compounds 1-8) incorporating a hypoxia-sensitive NI-moiety and a PSMA-targeting group. Ligands 1-8 were successfully prepared and labeled with 68Ga or 177Lu. Among them, [68Ga]Ga-8 ([68Ga]Ga-AAZTA-NI-PSMA-093) demonstrated significantly higher cellular accumulation under hypoxic conditions than under normoxic conditions, suggesting hypoxia-selective trapping by the introduction of NI group. PET/CT imaging at 60 min postinjection of [68Ga]Ga-8 revealed high tumor uptake (SUVmax: 10.68%ID/mL) in the tumor-bearing mice model. SPECT/CT imaging of [177Lu]Lu-8 at 24 and 48 h postinjection demonstrated excellent accumulation and retention. Preliminary studies indicate that [68Ga]Ga/[177Lu]Lu-8 may be promising bivalent agents targeting hypoxia and PSMA binding for diagnosis and radiotherapy.
Subject(s)
Antigens, Surface , Gallium Radioisotopes , Glutamate Carboxypeptidase II , Lutetium , Prostatic Neoplasms , Male , Gallium Radioisotopes/chemistry , Animals , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Humans , Glutamate Carboxypeptidase II/metabolism , Mice , Antigens, Surface/metabolism , Lutetium/chemistry , Radioisotopes/chemistry , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Cell Line, Tumor , Tissue Distribution , Mice, Nude , Tumor HypoxiaABSTRACT
(1) Background: Matou goats, native to Hunan and Hubei provinces in China, are renowned for their exceptional meat and skin quality. However, a comprehensive whole-genome-based exploration of the genetic architecture of this breed is scant in the literature. (2) Methods: To address this substantial gap, we used whole-genome sequences of 20 Matou goats and compared them with published genomic data of 133 goats of different breeds across China. This comprehensive investigation sought to assess genetic diversity, population structure, and the presence of genomic selection signals. (3) Results: The whole genome of Matou goat populations yielded a substantial catalog of over 19 million single nucleotide polymorphisms (SNPs), primarily distributed within intergenic and intron regions. The phylogenetic tree analysis revealed distinct clades corresponding to each goat population within the dataset. Notably, this analysis positioned Matou goats in a closer genetic affinity with Guizhou White goats, compared to other recognized goat breeds. This observation was corroborated by principal component analysis (PCA) and admixture analysis. Remarkably, Matou goats exhibited diminished genetic diversity and a notable degree of inbreeding, signifying a reduced effective population size. Moreover, the study employed five selective sweep detection methods (including PI, CLR, PI-Ratio, Fst, and XP-EHH) to screen top signal genes associated with critical biological functions, encompassing cardiomyocytes, immunity, coat color, and meat quality. (4) Conclusions: In conclusion, this study significantly advances our understanding of the current genetic landscape and evolutionary dynamics of Matou goats. These findings underscore the importance of concerted efforts in resource conservation and genetic enhancement for this invaluable breed.
Subject(s)
Goats , Polymorphism, Single Nucleotide , Selection, Genetic , Whole Genome Sequencing , Animals , Goats/genetics , Whole Genome Sequencing/methods , Polymorphism, Single Nucleotide/genetics , Phylogeny , China , Breeding , Genome/genetics , Genetic VariationABSTRACT
Breast cancer, globally the most common cancer in women, presents significant challenges in treatment. Breast-conserving surgery (BCS), a less traumatic and painful alternative to radical mastectomy, not only preserves the breast's appearance but also supports postsurgical functional recovery. However, accurately identifying tumors, precisely delineating margins, and thoroughly removing metastases remain complex surgical challenges, exacerbated by the limitations of current imaging techniques, including poor tumor uptake and low signal contrast. Addressing these challenges, our study developed a series of GnRHR-targeted probes (YQGN-n) for fluorescence imaging and surgical navigation of breast cancer through a drug repositioning strategy. Notably, YQGN-7, with its high cellular affinity (Kd of 217.8 nM), demonstrates exceptional selectivity and specificity for breast cancer tumors, surpassing traditional imaging agents like ICG in tumor uptake and pharmacokinetic properties. Furthermore, YQGN-7's effectiveness in surgical navigation, both for primary breast tumors and metastases, highlights its potential as a revolutionary tool in BCS.
Subject(s)
Breast Neoplasms , Fluorescent Dyes , Gonadotropin-Releasing Hormone , Female , Humans , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Fluorescent Dyes/chemistry , Animals , Gonadotropin-Releasing Hormone/chemistry , Mice , Optical Imaging , Drug Repositioning , Cell Line, Tumor , Mice, Nude , Receptors, LHRH/metabolism , Neoplasm Metastasis , Mice, Inbred BALB CABSTRACT
Miscanthus is a common pioneer plant with abundant genetic variation in abandoned mines in southern China. However, the extent to which genetic differentiation among species modulates rhizosphere bacterial communities remains unclear. Miscanthus samples were collected from 26 typical abandoned heavy-metal mines with different soil types in southern China, tested using 14 pairs of simple sequence repeats (SSR) primers, and classified into two genotypes based on Nei's genetic distance. The structure and diversity of rhizosphere bacterial communities were examined using 16 S rRNA sequencing. The results showed that among the factors affecting the rhizosphere bacterial community structure of Miscanthus samples, the role of genotype was not significant, and geographical conditions were the most important factors, followed by pH and total organic carbon (TOC). The process of rhizospheric community assembly varied among different genotypes; however, the recruited species and their abundances were similar. Collectively, we provided an approach based on genetic differentiation to quantify the relative contribution of genotypes to the rhizosphere bacterial community, demonstrating that genotypes contribute less than soil conditions. Our findings provide new insights into the role of host genetics in the ecological processes of plant rhizosphere bacterial communities in abandoned mines and provide theoretical support for microbe-assisted phytoremediation.
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STUDY QUESTION: Does vitrification cryopreservation of embryos for more than 5 years affect the pregnancy outcomes after frozen embryo transfer (FET)? SUMMARY ANSWER: Vitrification cryopreservation of good-quality blastocysts for more than 5 years is associated with a decrease in the implantation rate (IR) and live birth rate (LBR). WHAT IS KNOWN ALREADY: Previous studies have predominantly focused on embryos cryopreserved for relatively short durations (less than 5 years), yet the impact of extended cryopreservation duration on pregnancy outcomes remains a controversial issue. There is a relative scarcity of data regarding the efficacy and safety of storing embryos for 5 years or longer. STUDY DESIGN, SIZE, DURATION: This retrospective study involved 36 665 eligible vitrified-thawed embryo transfer cycles from 1 January 2016 to 31 December 2022, at a single fertility center in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into three groups according to embryo storage time: Group 1 consisted of 31 565 cycles, with storage time of 0-2 years; Group 2 consisted of 4458 cycles, with a storage time of 2-5 years; and Group 3 included 642 cycles, with storage time exceeding 5 years. The main outcome measures were IR and LBR. Secondary outcome variables included rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage, as well as neonatal outcomes. Reproductive outcomes were analyzed as binary variables. Multivariate logistic regression analysis was used to explore the effect of preservation time on pregnancy outcomes after correcting for confounding factors. In addition, we also assessed neonatal outcomes, such as large for gestational age (LGA) and small for gestational age (SGA). MAIN RESULTS AND THE ROLE OF CHANCE: IRs in the three groups (0-2, 2-5, and >5 years) were 37.37%, 39.03%, and 35.78%, respectively (P = 0.017), and LBRs in the three groups were 37.29%, 39.09%, and 34.91%, respectively (P = 0.028). After adjustment for potential confounding factors, compared with the 0-2 years storage group, prolonged embryo vitrification preservation time (2-5 years or >5 years) did not affect secondary outcomes such as rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage (P > 0.05). But cryopreservation of embryos for more than 5 years reduced the IR (adjusted odds ratio (aOR) 0.82, 95% CI 0.69-0.97, P = 0.020) and LBR (aOR 0.76, 95% CI 0.64-0.91, P = 0.002). Multivariate stratified analysis also showed that prolonging the cryopreservation time of blastocysts (>5 years) reduced the IR (aOR 0.78, 95% CI 0.62-0.98, P = 0.033) and LBR (aOR 0.68, 95% CI 0.53-0.87, P = 0.002). However, no effect on cleavage embryos was observed (P > 0.05). We further conducted stratified analyses based on the number and quality of frozen blastocysts transferred, and the results showed that the FET results after transfers of good-quality blastocysts in the >5 years storage group were negatively affected. However, the storage time of non-good-quality blastocysts was not significantly associated with pregnancy outcomes. Regarding the neonatal outcomes (of singletons), embryo vitrification preservation time had no effect on preterm birth rates, fetal birth weight, or neonatal sex ratios. However, as the storage time increased, rates of SGA (5.60%, 4.10%, and 1.18%) decreased, while rates of LGA (5.22%, 6.75%, and 9.47%) increased (P < 0.05). After adjusting for confounding factors, the increase in LGA and the decrease in SGA were significantly correlated with the duration of storage time. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study using data from a single fertility center, even though the data had been adjusted, our findings still need to be validated in further studies. WIDER IMPLICATIONS OF THE FINDINGS: With the full implementation of the two-child policy in China, there may be more patients whose embryos have been frozen for a longer time in the future. Patients should be aware that the IR and LBR of blastocysts are negatively affected when the cryopreservation time is longer than 5 years. Couples may therefore consider shortening the time until FET treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Nature Science Foundation of China (No. 82101672), Science and Technology Projects in Guangzhou (No. 2024A03J0180), General Guidance Program for Western Medicine of Guangzhou Municipal Health Commission (No. 20231A011096), and the Medical Key Discipline of Guangzhou (2021-2023). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ecliptea herba, a traditional Chinese herbal medicine for hair loss, was first recorded in the Tang Dynasty's 'Qian Jin Yue Ling', of which the active ingredients and mechanisms of action in the treatment of chemotherapy-induced hair loss remain poorly investigated. AIM OF THE STUDY: To investigate the effects of the petroleum ether extract of Eclipta (PEE) on alopecia and follicle damage and elucidate its potential therapeutic mechanisms using the integration of network pharmacology, bioinformatics, and experimental validation. MATERIALS AND METHODS: UPLC-MS was used to analyse the chemical composition of PEE. A network pharmacology approach was employed to establish the 'components-targets-pathways' network of PEE to explore potential therapeutic pathways and targets. Molecular docking was used for validation, and the mechanism of PEE in treating chemotherapy-induced alopecia (CIA) was elucidated using in vitro and in vivo on CIA models. RESULTS: UPLC-MS analysis of PEE revealed 185 components, while network pharmacology and molecular docking analyses revealed potential active compounds and their target molecules, suggesting the involvement of core genes, such as TP53, ESR1, AKT1, IL6, TNF, and EGFR. The key components included wedelolactone, dimethyl-wedelolactone, luteoloside, linarin, and hispidulin. In vivo, PEE promoted hair growth, restored the number of hair follicles, and reduced follicle apoptosis. Conversely, in vitro, PEE enhanced cell viability, reduced apoptosis, and protected HaCaT cells from damage induced by 4-hydroperoxycyclophosphamide (4-HC). CONCLUSIONS: PEE alleviated hair follicle damage in CIA mice by inhibiting the P53/Fas pathway, which may be associated with inhibiting hair follicle cell apoptosis. This study provides a novel therapeutic strategy for treating cyclophosphamide-induced hair loss.
Subject(s)
Alopecia , Eclipta , Signal Transduction , Animals , Humans , Male , Mice , Alkanes , Alopecia/chemically induced , Alopecia/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Cyclophosphamide/toxicity , Eclipta/chemistry , HaCaT Cells , Hair Follicle/drug effects , Hair Follicle/metabolism , Molecular Docking Simulation , Network Pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/geneticsABSTRACT
Accurate intracellular visualization of human telomerase RNA (hTR) is imperative for early diagnosis and treatment monitoring of hepatocellular carcinoma (HCC). While isothermal amplification-based DNA cascade strategies are promising, challenges persist in achieving great intake efficiency of detection probes within tumor cells and enhancing intracellular reaction efficiency. This study introduces a SA@Comb-HCR nanosystem, a highly effective approach for in situ hTR detection in HCC cells. Sodium alginate-coated liposomes ensures efficient nanoprobe delivery, which are then combined with proximity effect-inspired signal amplification. The coating of sodium alginate facilitates receptor-mediated endocytosis, prevents serum protein adhesion, and mitigates cationic liposome cytotoxicity. The designed Comb-like consolidated hairpin probe enhances the concentration of the local reactant, resulting in cascade amplification upon hTR activation. This technique achieves precision detection of intracellularly overexpressed hTR in HCC cells with a remarkable detection limit of 0.7 pM. This approach holds great promise for advancing targeted and sensitive early clinical diagnosis of HCC.
Subject(s)
Biosensing Techniques , Carcinoma, Hepatocellular , Liver Neoplasms , RNA , Telomerase , Humans , Telomerase/genetics , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Biosensing Techniques/methods , RNA/chemistry , RNA/genetics , Cell Line, Tumor , Nucleic Acid Amplification Techniques/methods , Limit of Detection , Liposomes/chemistryABSTRACT
Hydrogenation-Disproportionation-Desorption-Recombination (HDDR) Nd2Fe14B particles have excellent magnetic properties, but the magnetic properties of powder are not uniform across different particle sizes. The remanence and maximum magnetic energy products of samples with a particle size of 120 µm are 14.0 kGs and 41.35 MGOe, while the products of samples with a particle size of 60 µm are only 13.3 kGs and 36.31 MGOe. The macroscopic morphology of HDDR Nd2Fe14B particles and the gradient distribution of microstructures in different micro-regions were observed. By modifying the macroscopic morphology of the particles, the poorly oriented clusters on the surface of the particles were precisely eliminated, and the remanence and maximum magnetic energy products of the particles increased to 14.5 kGs and 45 MGOe, respectively. Compared with the original particles, the samples after mechanical grinding had better grain arrangement. The effects of the nanocrystalline c-axis and field misalignment angle θ on the magnetic properties of HDDR Nd2Fe14B particles were investigated through micromagnetic simulation. The targeted removal of macroscopic defects on the particle surface contributed to a 3.6% increase in remanence and an 8.8% increase in the maximum magnetic energy product, offering a promising approach to enhance the microstructure of high-performance HDDR Nd2Fe14B particles.
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In the field of armored vehicles, up to 70% of accidents are associated with low levels of situational awareness among the occupants, highlighting the importance of situational awareness in improving task performance. In this study, we explored the mechanisms influencing situational awareness by simulating an armored vehicle driving platform with 14 levels of experimentation in terms of five factors: experience, expectations, attention, the cueing channel, and automation. The experimental data included SART and SAGAT questionnaire scores, eye movement indicators, and electrocardiographic and electrodermal signals. Data processing and analysis revealed the following conclusions: (1) Experienced operators have higher levels of situational awareness. (2) Operators with certain expectations have lower levels of situational awareness. (3) Situational awareness levels are negatively correlated with information importance affiliations and the frequency of anomalous information in non-primary tasks. (4) Dual-channel cues lead to higher levels of situational awareness than single-channel cues. (5) Operators' situational awareness is lower at high automation levels.