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Purpose: Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs. Methods: Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model. Results: The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity. Conclusion: The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.

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Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.86-fold) and in vivo (3.74-fold), significantly decreasing the intake of distomers. Additionally, synthesized fluorescent probe enantiomers visualized enantioselective process of CMIP. Furthermore, investigations of molecular mechanism indicated that dependence on spatial conformation was dominant. On one hand, imprinted cavity of MIP with D-isomer and stronger chiral interaction with R-enantiomers led to more specific adsorption. On the other hand, L-isomer of PSA controlled the release of S-enantiomers by multiple interaction including chiral H-bond, π-π interaction and Van der Waals force. Tthus, the innovatively designed transdermal patch with enantioselective ability released eutomers of racemate and simultaneously inhibited release of distomers, significantly improving therapeutical efficiency and avoiding overdose.

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Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.

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Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT.

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INTRODUCTION: Volatile organic compounds (VOCs) in breath serve as a source of biomarkers for medical conditions relevant to warfighter health including Corona Virus Disease and other potential biological threats. Electronic noses are integrated arrays of gas sensors that are cost-effective and miniaturized devices that rapidly respond to VOCs in exhaled breath. The current study seeks to qualify healthy breath baselines of exhaled VOC profiles through analysis using a commercialized array of metal oxide (MOX) sensors. MATERIALS AND METHODS: Subjects were recruited/consented through word of mouth and using posters. For each sample, breath was analyzed using an array of MOX sensors with parameters that were previously established. Data were also collected using a lifestyle questionnaire and from a blood test to assess markers of general health. Sensor data were processed using a feature extraction algorithm, which were analyzed through statistical approaches to identify correlations with confounding factors. Reproducibility was also assessed through relative standard deviation values of sensor features within a single subject and between different volunteers. RESULTS: A total of 164 breath samples were collected from different individuals, and 10 of these volunteers provided an additional 9 samples over 6 months for the longitudinal study. First, data from different subjects were analyzed, and the trends of the 17 extracted features were elucidated. This revealed not only a high degree of correlation between sensors within the array but also between some of the features extracted within a single sensor. This helped guide the removal of multicollinear features for multivariate statistical analyses. No correlations were identified between sensor features and confounding factors of interest (age, body mass index, smoking, and sex) after P-value adjustment, indicating that these variables have an insignificant impact on the observed sensor signal. Finally, the longitudinal replicates were analyzed, and reproducibility assessment showed that the variability between subjects was significantly higher than within replicates of a single volunteer (P-value = .002). Multivariate analyses within the longitudinal data displayed that subjects could not be distinguished from one another, indicating that there may be a universal healthy breath baseline that is not specific to particular individuals. CONCLUSIONS: The current study sought to qualify healthy baselines of VOCs in exhaled breath using a MOX sensor array that can be leveraged in the future to detect medical conditions relevant to warfighter health. For example, the results of the study will be useful, as the healthy breath VOC data from the sensor array can be cross-referenced in future studies aiming to use the device to distinguish disease states. Ultimately, the sensors may be integrated into a portable breathalyzer or current military gear to increase warfighter readiness through rapid and noninvasive health monitoring.

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Reactive Oxygen Species (ROS) and the redoxin system regulate the redox environment. Thus, they mediate various physiological and pathological processes involved in tumor occurrence and development by activating redox-sensitive genes and regulating redox signaling pathways, including tumor cell proliferation, migration, invasion, and various cell death types. Therefore, the mechanism underlying redox environment regulation must be clarified to accurately target this mechanism and improve the effect of tumor treatment. This review introduces redox-sensitive transcription factors and their activated downstream signaling pathways, and the application of inhibitors targeting related transcription factors in tumor therapy.

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SUN5, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that Sun5 is involved in mRNA export. In Sun5-knockout mice ( Sun5 -/-), poly(A) + RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of Sun5, heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A) + RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that Sun5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that Sun5 regulates mRNA export through an Nxf1-dependent pathway. In Sun5 -/- mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.

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BACKGROUND: Poly L-lactic acid (PLLA) can stimulate fibrous tissue regeneration to exert a filling effect. However, severe inflammatory reactions and unsatisfactory effects remain a concern. OBJECTIVE: Herein, we describe the mechanism of action, efficacy, and safety of PLLA microspheres in suspension (PLLA-b-PEG/HA) for facial contouring and soft tissue augmentation. METHODS: PLLA-b-PEG/HA, ssynthesized by copolymerization with ethylene glycol, were suspended in hyaluronic acid (HA). Physiological verification was performed using scanning electron microscopy and X-ray computed tomography. PLLA-b-PEG/HA were subcutaneously injected into the dorsal region of 4-month-old rabbits. Ultrasound assessed volumetric capacity at 3 days and 1, 2, 4, and 12 weeks. The inflammatory response, collagen production, and HA degradation were evaluated. A retrospective case series of 10 patients who received PLLA-b-PEG/HA injections was conducted to assess long-term efficacy and safety. RESULTS: PLLA-b-PEG exhibited a spherical structure with a smooth surface (20-45 µm diameter). In rabbits, implant site volume increased within 4 weeks, gradually decreasing thereafter. Fibrous capsules, microvessel density, and new collagen fiber formation progressively increased at 4, 12, and 26 weeks after injection. Clinical data demonstrated significant improvements in face contouring at months 3 and 12 after injection. All patients showed improved internal contours based on the Global Aesthetic Improvement Scale. After 12 months, 90% of the patients retained good shaping and support effects with minimal adverse reactions. CONCLUSIONS: PLLA-b-PEG/HA demonstrated superior biocompatibility and facial regeneration potential, with outstanding dual collagen-stimulating properties. The clinical efficacy and safety of PLLA-b-PEG/HA have been validated and established as a promising therapeutic option.

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Although the current surgical hematoma removal treatment saves patients' lives in critical moments of intracerebral hemorrhage (ICH), the lethality and disability rates of ICH are still very high. Due to the individual differences of patients, postoperative functional improvement is still to be confirmed, and the existing drug treatment has limited benefits for ICH. Recent advances in biomaterials may provide new ideas for the therapy of ICH. This review first briefly describes the pathogenic mechanisms of ICH, including primary and secondary injuries such as inflammation and intracerebral edema, and briefly describes the existing therapeutic approaches and their limitations. Secondly, existing nanomaterials and hydrogels for ICH, including exosomes, liposomes, and polymer nanomaterials, are also described. In addition, the potential challenges and application prospects of these biomaterials for clinical translation in ICH treatment are discussed.

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Proteoforms, which arise from post-translational modifications, genetic polymorphisms and RNA splice variants, play a pivotal role as drivers in biology. Understanding proteoforms is essential to unravel the intricacies of biological systems and bridge the gap between genotypes and phenotypes. By analysing whole proteins without digestion, top-down proteomics (TDP) provides a holistic view of the proteome and can decipher protein function, uncover disease mechanisms and advance precision medicine. This Primer explores TDP, including the underlying principles, recent advances and an outlook on the future. The experimental section discusses instrumentation, sample preparation, intact protein separation, tandem mass spectrometry techniques and data collection. The results section looks at how to decipher raw data, visualize intact protein spectra and unravel data analysis. Additionally, proteoform identification, characterization and quantification are summarized, alongside approaches for statistical analysis. Various applications are described, including the human proteoform project and biomedical, biopharmaceutical and clinical sciences. These are complemented by discussions on measurement reproducibility, limitations and a forward-looking perspective that outlines areas where the field can advance, including potential future applications.

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H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.

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BACKGROUND: Programmed cell death ligand 1 (PD-L1), as a reliable predictive biomarker, plays an important role in guiding immunotherapy of lung cancer. To investigate the value of CT-based deep learning radiomics signature to predict PD-L1 expression in non-small cell lung cancers(NSCLCs). METHODS: 259 consecutive patients with pathological confirmed NSCLCs were retrospectively collected and divided into the training cohort and validation cohort according to the chronological order. The univariate and multivariate analyses were used to build the clinical model. Radiomics and deep learning features were extracted from preoperative non-contrast CT images. After feature selection, Radiomics score (Rad-score) and deep learning radiomics score (DLR-score) were calculated through a linear combination of the selected features and their coefficients. Predictive performance for PD-L1 expression was evaluated via the area under the curve (AUC) of receiver operating characteristic, the calibration curves, and the decision curve analysis. RESULTS: The clinical model based on Cytokeratin 19 fragment and lobulated shape obtained an AUC of 0.767(95% CI: 0.673-0.860) in the training cohort and 0.604 (95% CI:0.477-0.731) in the validation cohort. 11 radiomics features and 15 deep learning features were selected by LASSO regression. AUCs of the Rad-score were 0.849 (95%CI: 0.783-0.914) and 0.717 (95%CI: 0.607-0.826) in the training cohort and validation cohort, respectively. AUCs of DLR-score were 0.938 (95%CI: 0.899-0.977) and 0.818(95%CI:0.727-0.910) in the training cohort and validation cohort, respectively. AUCs of the DLR-score were significantly higher than those of the Rad-score and the clinical model. CONCLUSION: The CT-based deep learning radiomics signature could achieve clinically acceptable predictive performance for PD-L1 expression, which showed potential to be a surrogate imaging biomarker or a complement of immunohistochemistry assessment.

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Infant birth sizes are vital clinical parameters to predict poor growth and micronutrient deficiency in early life. However, their effects on childhood anemia remain unclear. We aimed to explore the associations between birth weight, crown-heel length, and head circumference with anemia in early childhood, as well as potential modification factors. This population-based prospective cohort study included 204,556 participants with singleton live births delivered at gestational ages of 28-42 weeks. A logistic regression model was used to estimate the associations of the measures of infant birth size and their Z-score with anemia under five years old. There were 26,802 (13.10%) children under five years old who were diagnosed has having anemia. Compared with children who did not have anemia, children who had anemia had a lower birth weight and smaller head circumference and a longer crown-heel length (all p-values < 0.05). After adjusting for confounders, not only birth weight (ß coefficient, -0.008; 95% CI, -0.011--0.004; p < 0.001) and head circumference (ß coefficient, -0.004; 95% CI, -0.007--0.001; p = 0.009), but also the related Z-scores were negatively associated with childhood anemia, while the trends for crown-heel length were the opposite. We further found significant interactions of folic acid use and maternal occupation with infant birth sizes. In conclusion, infants having abnormal sizes at birth are significantly associated with the risk for childhood anemia, which can be modified by folic acid use during pregnancy and maternal occupation.

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As an important reservoir of antibiotic resistance genes (ARGs), the sludge discharged from wastewater treatment plants is the key intermediate for ARG transport into the environment. Bdellovibrio-and-like organisms (BALOs) are predatory bacteria that are expected to attack antibiotic-resistant bacteria (ARB). In this study, the screened BALOs (C3 & D15) were mixed with the sludge for biolysis to achieve the satisfying removal efficiencies of six tet genes, two sul genes, and one mobile genetic element (intl 1). Among them, tet(Q) demonstrated the highest reduction rate in relative abundance at 87.3 ± 1.0 %, while tet(X) displayed the lowest of 11.7 ± 0.2 %. The microorganisms, including Longilinea, Methanobacterium, Acetobacterium, Sulfurimonas, allobaculum, Gaiella, AAP99, Ellin6067, Rhodoferax, Ferruginibacter and Thermomonas, were expected to play a dual role in the reduction of ARGs by serving as ARB and BALOs' preferred prey. Meanwhile, BALOs consortium improved ARGs reduction efficiency via the expansion of the prey profile. Additionally, BALOs decreased the relative abundance of not only pathogens (Shinella, Rickettsia, Burkholderia, Acinetobacter, Aeromonas, Clostridium, Klebsiella and Pseudomonas), but also the ARGs' host pathogens (Mycobacterium, Plesiocystis, Burkholderia, and Bacteroides). Therefore, the application of BALOs for sludge biolysis are promising to decrease the sludge's public health risks via limiting the spread of ARGs and pathogens into the environment.

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INTRODUCTION: Perioperative anaphylaxis (POA) can lead to significant complications. Therefore, accurate identification of allergens for POA patients is critical to ensure the safety of future surgical and anaesthetic procedures. Existing perioperative allergen detection methods face challenges in sensitivity and specificity. The passive mast cell activation test (pMAT) has recently emerged as a potential diagnostic tool. Our study aims to evaluate the diagnostic efficacy of pMAT for identifying perioperative allergens, with a focus on non-depolarising neuromuscular blocking agents, the most common culprits of POA. METHODS AND ANALYSIS: This prospective diagnostic accuracy study will measure the diagnostic accuracy of pMAT in POA patients. Participants will undergo skin testing (ST), basophil activation testing (BAT) and pMAT. The diagnostic validity of pMAT will be assessed based on the results of ST and BAT. The assessment of diagnostic accuracy will include sensitivity, specificity, likelihood ratios, and false-positive and false-negative rates while measurement of the consistency rate will assess reliability. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of China-Japan Friendship Hospital (2023-KY-247). Results will be disseminated through academic presentations and peer-reviewed journal publications and will provide valuable scientific data and some new insights into the diagnostic accuracy of pMAT.

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BACKGROUND AND AIM: The association between the Triglyceride-glucose (TyG) index and depression has been observed, yet its confirmation within peri- and postmenopausal demographics remains elusive. Consequently, the principal aim of this investigation is to explore the nexus between TyG-related indicators and depressive symptoms among pre- and postmenopausal women. METHODS: The data utilized in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted from 2013 to 2016. The patients were divided into three groups based on TyG, Triglyceride-Glucose-Body Mass Index (TyG-BMI), Triglyceride-Glucose-Waist Circumference (TyG-WC), and Triglyceride-Glucose-Waist-to-Height Ratio (TyG-WHtR): Q1 (1st quintile), Q2 (2nd quintile), and Q3 (3rd quintile). Further exploration of the differences between these groups was conducted. Employing logistic regression, stratified analysis, restricted cubic splines, and subgroup analyses, we scrutinized the correlation between TyG-related indicators and depressive symptoms in both premenopausal and postmenopausal women. Furthermore, sensitivity analyses were conducted to assess the durability and uniformity of this relationship. RESULTS: In premenopausal women, there was a consistent independent positive correlation between TyG-BMI, TyG-WC, and TyG-WHtR with depressive symptoms across all three models, while TyG itself did not show a significant association. In Models 1 and 2, TyG-BMI exhibited a higher odds ratio (OR) value than the other two indicators [Model 1, Q3 OR (95 % confidence interval, CI) = 3.37 (1.91-5.94); Model 2, Q3 OR (95 % CI) = 3.03 (1.67-5.52)]. In Models 3, TyG-WHtR demonstrates a more significant association with depressive symptoms [Model 3, Q3 OR (95 % CI) = 2.85 (1.55-5.27)]. This correlation does not manifest in menopausal women. CONCLUSIONS: In premenopausal women, TyG-BMI, TyG-WC, and TyG-WHtR exhibited a positive and linear relationship with depressive symptoms. Furthermore, the analysis revealed that the combined measures of TyG-BMI, TyG-WC, and TyG-WHtR offered greater precision and sensitivity in assessing this association compared to TyG alone.

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PURPOSE: Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. METHODS: Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. RESULTS: In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. CONCLUSION: Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

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Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.

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Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i.e., zygotic genome activation (ZGA), clearance of maternal mRNAs, and initiation of cellular differentiation and organogenesis. MZT is modulated by many proteins at multiple levels in a collaborative fashion, i.e., transcription factors, histones, histone-modifying enzymes, RNA helicases, and P-body proteins. Significant discrepancies were discovered between zebrafish proteome and transcriptome profiles during the MZT. The proteome dynamics database will be a valuable resource for bettering our understanding of MZT.

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The timely and accurate diagnosis of breast cancer is pivotal for effective treatment, but current automated mammography classification methods have their constraints. In this study, we introduce an innovative hybrid model that marries the power of the Extreme Learning Machine (ELM) with FuNet transfer learning, harnessing the potential of the MIAS dataset. This novel approach leverages an Enhanced Quantum-Genetic Binary Grey Wolf Optimizer (Q-GBGWO) within the ELM framework, elevating its performance. Our contributions are twofold: firstly, we employ a feature fusion strategy to optimize feature extraction, significantly enhancing breast cancer classification accuracy. The proposed methodological motivation stems from optimizing feature extraction for improved breast cancer classification accuracy. The Q-GBGWO optimizes ELM parameters, demonstrating its efficacy within the ELM classifier. This innovation marks a considerable advancement beyond traditional methods. Through comparative evaluations against various optimization techniques, the exceptional performance of our Q-GBGWO-ELM model becomes evident. The classification accuracy of the model is exceptionally high, with rates of 96.54 % for Normal, 97.24 % for Benign, and 98.01 % for Malignant classes. Additionally, the model demonstrates a high sensitivity with rates of 96.02 % for Normal, 96.54 % for Benign, and 97.75 % for Malignant classes, and it exhibits impressive specificity with rates of 96.69 % for Normal, 97.38 % for Benign, and 98.16 % for Malignant classes. These metrics are reflected in its ability to classify three different types of breast cancer accurately. Our approach highlights the innovative integration of image data, deep feature extraction, and optimized ELM classification, marking a transformative step in advancing early breast cancer detection and enhancing patient outcomes.

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