Use of combined chemotherapy and immunotherapy improves pulmonary arterial hypertension.

Treatment modalities for pulmonary arterial hypertension (PAH) improve quality of life and walk distance. However, none of these therapies alter the structural/functional pulmonary vascular integrity that results in vascular remodeling. PAH smooth muscle cells share biological characteristics with cancer cells, which may be potential therapeutic targets for PAH. We present a case of a patient with connective tissue disease (CTD)-associated PAH treated on triple therapy who developed metastatic lung adenocarcinoma. While on PAH triple-therapy, she received a combination of carboplatin, pemetrexed, and pembrolizumab. She eventually had a complete pathologic response, no evidence of cancer recurrence, and significant improvement of PAH/overall clinical status. After discontinuation of neoplastic therapy, her clinical status worsened, she eventually passed away, and lung biopsy findings revealed evidence of severe pulmonary smooth muscle cell hypertrophy and pulmonary veno-occlusive disease. This report suggests that combined chemotherapy and immunotherapy may influence the efficacy of PAH therapies and improve clinical status.

Construction and verification of a risk prediction model for cognitive frailty in older patients with chronic obstructive pulmonary disease and diabetes mellitus.

OBJECTIVE: We explored risk factors for cognitive frailty in older patients with chronic obstructive pulmonary disease (COPD) and diabetes mellitus to develop and verify a risk prediction model for cognitive frailty. METHODS: This was a cross-sectional study. Convenience sampling was used to randomly select 378 patients hospitalized between February 2022 and December 2023. We allocated 265 patients who visited between February 2022 and February 2023 to a modeling group to analyze risk factors for cognitive frailty and create a logistic regression model for risk prediction. Another 113 patients who visited between March 2023 and December 2023 were included in a validation group for model verification. RESULTS: The cognitive frailty incidence in the 265 patients was 35.09% (93/265). Regression analysis showed that age >80 years (odds ratio [OR] = 4.576), regular exercise (OR = 0.390, polypharmacy (OR = 3.074), depression (OR = 2.395) duration of COPD combined with diabetes (OR = 1.902), Family APGAR index score (OR = 0.428), and chronic pain (OR = 2.156) were factors influencing the occurrence of cognitive frailty in older patients with COPD accompanied by diabetes. CONCLUSIONS: The constructed risk prediction model for cognitive frailty in older patients with COPD and diabetes showed good predictive value, aiding in the clinical identification of high-risk patients and facilitating timely intervention and guidance.

A novel hybrid Wireless Integrated Sensing Detector for simultaneous EEG and MRI (WISDEM).

Concurrent recording of EEG/fMRI signals reveals cross-scale neurovascular dynamics that are crucial for elucidating fundamental linkage between function and behaviors. However, MRI scanners generate tremendous artifacts for EEG detection. Despite existing denoising methods, cabled connections to EEG receivers are susceptible to environmental fluctuations inside MRI scanners, creating baseline drifts that complicate EEG signal retrieval from the noisy background. Here, a Wireless Integrated Sensing Detector for simultaneous EEG and MRI (WISDEM) is developed to encode fMRI and EEG signals on distinct sidebands of the detector oscillation carrier wave for detection by a standard MRI console over the entire duration of fMRI sequence. Local field potential (LFP) and fMRI maps are retrieved through low-pass and high-pass filtering of frequency-demodulate signals. From optogenetically-stimulated somatosensory cortex, the positive correlation between evoked LFP and fMRI signals validates strong neurovascular coupling, enabling cross-scale brain mapping with this 2-in-1 transducer as a research and diagnostic tool.

Urine complement proteins are associated with kidney disease progression of type 2 diabetes in Korean and American cohorts.

Background: Mechanisms of progression of diabetic kidney disease (DKD) are not completely understood. This study uses untargeted and targeted mass spectrometry-based proteomics in two independent cohorts on two continents to decipher the mechanisms of DKD in patients with type 2 diabetes. Methods: We conducted untargeted mass spectrometry on urine samples collected at the time of kidney biopsy from Korean patients with type 2 diabetes and biopsy-proven diabetic nephropathy at Seoul National University Hospital (SNUH-DN cohort; n = 64). These findings were validated using targeted mass spectrometry in urine samples from a Chronic Renal Insufficiency Cohort subgroup with type 2 diabetes and DKD (CRIC-T2D; n = 282). Urinary biomarkers/pathways associated with kidney disease progression (doubling of serum creatinine, ≥50% decrease in estimated glomerular filtration rates, or the development of end-stage kidney disease) were identified. Results: SNUH-DN patients had an estimated glomerular filtration rate (eGFR) of 55 mL/min/1.73 m 2 (interquartile range [IQR], 44-75) and random urine protein-to-creatinine ratio of 3.1 g/g (IQR, 1.7-7.0). Urine proteins clustered into two groups, with cluster 2 having a 4.6-fold greater hazard (95% confidence interval [CI], 1.9-11.5) of disease progression than cluster 1 in multivariable-adjusted, time-to-event analyses. Proteins in cluster 2 mapped to 10 pathways, four of the top five of which were complement or complement-related. A high complement score, constructed from urine complement protein abundance, was strongly correlated to 4 of 5 histopathologic DN features and was associated with a 2.4-fold greater hazard (95% CI, 1.0-5.4) of disease progression than a low complement score. Targeted mass spectrometry of the CRIC-T2D participants, who had an eGFR of 42 mL/min/1.73 m 2 (IQR, 37-49) and 24-hr urine protein of 0.48 g (IQR, 0.10-1.87), showed that the complement score similarly segregated them into rapid and slow DKD progression groups. In both cohorts, the complement score had a linear association with disease progression. Conclusions: Urinary proteomic profiling confirms the association between the complement pathway and rapid DKD progression in two independent cohorts. These results suggest a need to further investigate complement pathway inhibition as a novel treatment for DKD.

Contrasting presentations of children with ADHD and subthreshold ADHD.

BACKGROUND: We aimed to explore the differences and relationships in body composition, social function, and comorbidities between children with attention-deficit/hyperactivity disorder (ADHD) and subthreshold ADHD. METHODS: A case-control study was conducted to analyze the differences between children with ADHD and subthreshold ADHD. Logistic regression models were used to analyze the factors influencing social functional impairments and comorbidities. RESULTS: Children with ADHD and subthreshold ADHD had a higher fat mass index than healthy children (p < 0.05). The scores of all six social functional domains were higher in the subthreshold ADHD and ADHD groups than in the control group (p < 0.05). The prevalence of comorbidity was higher in children with subthreshold ADHD and ADHD compared to the control group (p < 0.05). Inattention and comorbid anxiety/depression increased the risk of functional impairments in children with ADHD (full syndrome/subthreshold), whereas a higher fat-free mass index reduced the risk. The severity of hyperactivity was associated with a higher risk of comorbidity in children with ADHD (full syndrome/subthreshold). CONCLUSION: Children with subthreshold ADHD and ADHD had more fat mass and higher rates of social functional impairments and comorbidities than healthy children. There were clinical correlations between body composition, social functional impairments, and comorbidities in ADHD. IMPACT: 1. Children with subthreshold ADHD and ADHD had higher fat mass levels than normal children. 2. The social function impairments and comorbidities of children with subthreshold ADHD were similar to those with ADHD. 3. Inattentiveness and anxiety/depression increased the risk of functional impairments in children with ADHD (full syndrome/subthreshold), while a higher fat-free mass index and skeletal muscle-to-body fat ratio reduced the risk.

The activities of daily living partially mediate the relationship between rapid eye movement sleep behavior disorder and depressive symptoms in Parkinson's disease.

Objective: A longitudinal study was conducted to investigate whether rapid eye movement sleep behavior disorder affect depression in patients with Parkinson's disease through activities of daily living. Methods: A total of 387 Parkinson's disease patients' six-year follow-up data (one follow-up per year) were obtained from the Parkinson's Progression Markers Initiative. To allow causal effects to manifest, this study increased the lag period and divided the data from the six follow-ups into two groups: wave 1 (wave refers to time points), wave 3, and wave 5 as one group, and wave 2, wave 4, and wave6 as the other group. The time interval between two time points in each group was two years. To comprehensively and deeply analyze the dynamic relationships between variables, accurately infer causal relationships, control for individual differences, and detect the stability of these relationships, this study constructed the fixed effects cross-lagged panel model (CLPM), the random effects CLPM (RE-CLPM) model, and the Equating CLPM and Equating RE-CLPM models with applied restriction conditions. Additionally, a reverse path was added to verify the reverse prediction effect. The most suitable data analysis model was selected to explore the relationships between the study variables. Furthermore, the longitudinal mediating effect of daily living activities between rapid eye movement sleep behavior disorder and depression was investigated. Results: In the models, Equating cross-lagged panel model was the best. The lag effect was positive and significant. In wave 1, 3, 5, activities of daily living mediated 11.82% on the path from rapid eye movement sleep behavior disorder to depression; in wave 2, 4, 6, it mediated 13.13%. Therefore, attention should be paid to the treatment of activities of daily living. Conclusion: Longitudinal changes in activities of daily living have indirect effects on the relationship between rapid eye movement sleep behavior disorder and depression, which highlights the importance of changes in activities of daily living ability in Parkinson's disease patients with rapid eye movement sleep behavior disorder.

Pan-genome analysis of 13 Spinacia accessions reveals structural variations associated with sex chromosome evolution and domestication traits in spinach.

Structural variations (SVs) are major genetic variants that can be involved in the origin, adaptation and domestication of species. However, the identification and characterization of SVs in Spinacia species are rare due to the lack of a pan-genome. Here, we report eight chromosome-scale assemblies of cultivated spinach and its two wild species. After integration with five existing assemblies, we constructed a comprehensive Spinacia pan-genome and identified 193 661 pan-SVs, which were genotyped in 452 Spinacia accessions. Our pan-SVs enabled genome-wide association study identified signals associated with sex and clarified the evolutionary direction of spinach. Most sex-linked SVs (86%) were biased to occur on the Y chromosome during the evolution of the sex-linked region, resulting in reduced Y-linked gene expression. The frequency of pan-SVs among Spinacia accessions further illustrated the contribution of these SVs to domestication, such as bolting time and seed dormancy. Furthermore, compared with SNPs, pan-SVs act as efficient variants in genomic selection (GS) because of their ability to capture missing heritability information and higher prediction accuracy. Overall, this study provides a valuable resource for spinach genomics and highlights the potential utility of pan-SV in crop improvement and breeding programmes.

LncRNA SNHG1 knockdown attenuates lipopolysaccharide-induced acute lung injury via regulating miR199a-3p/ROCK2 axis.

Acute lung injury (ALI) is a significant health condition with notable rates of morbidity and mortality globally. Long non-coding ribose nucleic acids (lncRNAs) play vital roles in mitigating various inflammation-related diseases, including ALI. The study aimed to investigate the functional role and molecular mechanisms of lncRNA SNHG1 on ALI in lipopolysaccharide (LPS)-treated A549 cells and in LPS-induced ALI mice. The expression of SNHG1 was initially examined in LPS-treated A549 cells. We further demonstrated the critical function of SNHG1 through various cellular assessments following SNHG1 knockdown, including cell counting kit (CCK)-8 assay, flow cytometry analysis, as well as enzyme-linked immunosorbent assay (ELISA). Reducing SNHG1 levels hindered the negative effects of LPS on cell viability, apoptosis, and inflammation. Moreover, SNHG1 acted as a negative regulator for miR-199a-3p, which targeted downstream ROCK2. Depletion of miR-199a-3p or enhanced expression of ROCK2 abolished the protective effects of SNHG1 knockdown on LPS-induced apoptosis and inflammation. Consistently, silencing SNHG1 alleviated LPS-induced lung injury in mice, demonstrating its potential therapeutic benefits in managing ALI. Overall, this study sheds light on the role of SNHG1 in modulating inflammation and apoptosis in ALI through the miR-199a-3p/ROCK2 pathway, offering new insights for the treatment of this condition.

Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements.

Type 1 diabetes (T1D) is a devastating autoimmune disease for which advanced mass spectrometry (MS) methods are increasingly used to identify new biomarkers and better understand underlying mechanisms. For example, integration of MS analysis and machine learning has identified multimolecular biomarker panels. In mechanistic studies, MS has contributed to the discovery of neoepitopes, and pathways involved in disease development and identifying therapeutic targets. However, challenges remain in understanding the role of tissue microenvironments, spatial heterogeneity, and environmental factors in disease pathogenesis. Recent advancements in MS, such as ultra-fast ion-mobility separations, and single-cell and spatial omics, can play a central role in addressing these challenges. Here, we review recent advancements in MS-based molecular measurements and their role in understanding T1D.

Fusiform nanoparticle boosts efficient genetic transformation in Sclerotinia sclerotiorum.

BACKGROUND: Sclerotinia sclerotiorum is a highly destructive phytopathogenic fungus that poses a significant threat to a wide array of crops. The current constraints in genetic manipulation techniques impede a thorough comprehension of its pathogenic mechanisms and the development of effective control strategies. RESULTS: Herein, we present a highly efficient genetic transformation system for S. sclerotiorum, leveraging the use of fusiform nanoparticles, which are synthesized with FeCl3 and 2,6-diaminopyrimidine (DAP). These nanoparticles, with an average longitude length of 59.00 nm and a positively charged surface, facilitate the direct delivery of exogenous DNA into the mycelial cells of S. sclerotiorum, as well as successful integration with stable expression. Notably, this system circumvents fungal protoplast preparation and tedious recovery processes, streamlining the transformation process considerably. Furthermore, we successfully employed this system to generate S. sclerotiorum strains with silenced oxaloacetate acetylhydrolase-encoding gene Ss-oah1. CONCLUSIONS: Our findings demonstrate the feasibility of using nanoparticle-mediated delivery as a rapid and reliable tool for genetic modification in S. sclerotiorum. Given its simplicity and high efficiency, it has the potential to significantly propel genetic research in filamentous fungi, offering new avenues for elucidating the intricacies of pathogenicity and developing innovative disease management strategies.

A Trapping-Micro-LC-FAIMS/dCV-MS Strategy for Ultrasensitive and Robust Targeted Quantification of Protein Drugs and Biomarkers.

The sensitivity of LC-MS in quantifying target proteins in plasma/tissues is significantly hindered by coeluted matrix interferences. While antibody-based immuno-enrichment effectively reduces interferences, developing and optimizing antibodies are often time-consuming and costly. Here, by leveraging the orthogonal separation capability of Field Asymmetric Ion Mobility Spectrometry (FAIMS), we developed a FAIMS/differential-compensation-voltage (FAIMS/dCV) method for antibody-free, robust, and ultrasensitive quantification of target proteins directly from plasma/tissue digests. By comparing the intensity-CV profiles of the target vs coeluted endogenous interferences, the FAIMS/dCV approach identifies the optimal CV for quantification of each target protein, thus maximizing the signal-to-noise ratio (S/N). Compared to quantification without FAIMS, this technique dramatically reduces endogenous interferences, showing a median improvement of the S/N by 14.8-fold for the quantification of 17 representative protein drugs and biomarkers in plasma or tissues and a 5.2-fold median increase in S/N over conventional FAIMS approach, which uses the peak CV of each target. We also discovered that the established CV parameters remain consistent over months and are matrix-independent, affirming the robustness of the developed FAIMS/dCV method and the transferability of the method across matrices. The developed method was successfully demonstrated in three applications: the quantification of monoclonal antibodies with subng/mL LOQ in plasma, an investigation of the time courses of evolocumab and its target PCSK9 in a preclinical setting, and a clinical investigation of low abundance obesity-related biomarkers. This innovative and easy-to-use method has extensive potential in clinical and pharmaceutical research, particularly where sensitive and high-throughput quantification of protein drugs and biomarkers is required.

A multi-ancestry GWAS meta-analysis of facial features and its application in predicting archaic human features.

Facial morphology, a complex trait influenced by genetics, holds great significance in evolutionary research. However, due to limited fossil evidence, the facial characteristics of Neanderthals and Denisovans have remained largely unknown. In this study, we conducted a large-scale multi-ethnic meta-analysis of the genome-wide association study (GWAS), including 9674 East Asians and 10,115 Europeans, quantitatively assessing 78 facial traits using 3D facial images. We identified 71 genomic loci associated with facial features, including 21 novel loci. We developed a facial polygenic score (FPS) that enables the prediction of facial features based on genetic information. Interestingly, the distribution of FPSs among populations from diverse continental groups exhibited relevant correlations with observed facial features. Furthermore, we applied the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and aligned predictions with the fossil records. Our results suggested that Neanderthals and Denisovans likely shared similar facial features, such as a wider but shorter nose and a wider endocanthion distance. The decreased mouth width was characterized specifically in Denisovans. The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.

Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae after acute COVID-19.

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target.

Warning Function of Frank's Sign in Pre-Existing Cardiac Disease Patients: A Case Report.

Frank's sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient's chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.

Genome-Wide Identification and Characterization of U-Box Gene Family Members and Analysis of Their Expression Patterns in Phaseolus vulgaris L. under Cold Stress.

The common bean (Phaseolus vulgaris L.) is an economically important food crop grown worldwide; however, its production is affected by various environmental stresses, including cold, heat, and drought stress. The plant U-box (PUB) protein family participates in various biological processes and stress responses, but the gene function and expression patterns of its members in the common bean remain unclear. Here, we systematically identified 63 U-box genes, including 8 tandem genes and 55 non-tandem genes, in the common bean. These PvPUB genes were unevenly distributed across 11 chromosomes, with chromosome 2 holding the most members of the PUB family, containing 10 PUB genes. The analysis of the phylogenetic tree classified the 63 PUB genes into three groups. Moreover, transcriptome analysis based on cold-tolerant and cold-sensitive varieties identified 4 differentially expressed PvPUB genes, suggesting their roles in cold tolerance. Taken together, this study serves as a valuable resource for exploring the functional aspects of the common bean U-box gene family and offers crucial theoretical support for the development of new cold-tolerant common bean varieties.

Ultrasound-guided serratus anterior plane block enhances postoperative analgesia and recovery in thoracoscopic surgery.

BACKGROUND: The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management. AIM: To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation. METHODS: Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation. RESULTS: The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group. CONCLUSION: Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.

Age over sex: evaluating gut microbiota differences in healthy Chinese populations.

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the "healthy" population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia-Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

A fast and sensitive size-exclusion chromatography method for plasma extracellular vesicle proteomic analysis.

Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 min. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals who underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts.

Vinorelbine administration impedes the timely progression of meiotic maturation and induces aneuploidy in mouse oocytes.

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.

Multi-branch attention Raman network and surface-enhanced Raman spectroscopy for the classification of neurological disorders.

Surface-enhanced Raman spectroscopy (SERS), a rapid, low-cost, non-invasive, ultrasensitive, and label-free technique, has been widely used in-situ and ex-situ biomedical diagnostics questions. However, analyzing and interpreting the untargeted spectral data remains challenging due to the difficulty of designing an optimal data pre-processing and modelling procedure. In this paper, we propose a Multi-branch Attention Raman Network (MBA-RamanNet) with a multi-branch attention module, including the convolutional block attention module (CBAM) branch, deep convolution module (DCM) branch, and branch weights, to extract more global and local information of characteristic Raman peaks which are more distinctive for classification tasks. CBAM, including channel and spatial aspects, is adopted to enhance the distinctive global information on Raman peaks. DCM is used to supplement local information of Raman peaks. Autonomously trained branch weights are applied to fuse the features of each branch, thereby optimizing the global and local information of the characteristic Raman peaks for identifying diseases. Extensive experiments are performed for two different neurological disorders classification tasks via untargeted serum SERS data. The results demonstrate that MBA-RamanNet outperforms commonly used CNN methods with an accuracy of 88.24% for the classification of healthy controls, mild cognitive impairment, Alzheimer's disease, and Non-Alzheimer's dementia; an accuracy of 90% for the classification of healthy controls, elderly depression, and elderly anxiety.