Accuracy of 14 intraocular lens power calculation formulas in extremely long eyes.

PURPOSE: To compare the accuracy of 14 formulas in calculating intraocular lens (IOL) power in extremely long eyes with axial length (AL) over 30.0 mm. METHODS: In this retrospective study, 211 eyes (211 patients) with ALs > 30.0 mm were successfully treated with cataract surgery without complications. Ocular biometric parameters were obtained from IOLMaster 700. Fourteen formulas were evaluated using the optimized A constants: Barrett Universal II (BUII), Kane, Emmetropia Verifying Optical (EVO) 2.0, PEARL-DGS, T2, SRK/T, Holladay 1, Holladay 2, Haigis and Wang-Koch AL adjusted formulas (SRK/Tmodified-W/K, Holladay 1modified-W/K, Holladay 1NP-modified-W/K, Holladay 2modified-W/K, Holladay 2NP-modified-W/K). The mean prediction error (PE) and standard deviation (SD), mean absolute errors (MAE), median absolute errors (MedAE), and the percentage of prediction errors (PEs) within ± 0.25 D, ± 0.50 D, ± 1.00 D were analyzed. RESULTS: The Kane formula had the smallest MAE (0.43 D) and MedAE (0.34 D). The highest percentage of PE within ± 0.25 D was for EVO 2.0 (37.91%) and the Holladay 1NP-modified-W/K formulas (37.91%). The Kane formula had the highest percentage of PEs in the range of ± 0.50, ± 0.75, ± 1.00, and ± 2.00 D. There was no significant difference in PEs within ± 0.25, ± 0.50 ± 0.75 and ± 1.00 D between BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas (P > .05) by using Cochran's Q test. The Holladay 2modified-W/K formula has the lowest percentage of hyperopic outcomes (29.38%). CONCLUSIONS: The BUII, Kane, EVO 2.0 and Wang-Koch AL adjusted formulas have comparable accuracy for IOL power calculation in eyes with ALs > 30.0 mm.

Cyclodextrin-conjugated low-molecular-weight polyethyleneimine as a macromolecular contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone via host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist (r1 = 4.25 mM-1 s-1) used in clinic, the PC/Ad-PEG2000-PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity (r1 = 11.62 mM-1 s-1) with excellent biocompatibility. Furthermore, in vivo experiments demonstrated that PC/Ad-PEG2000-PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility in vivo. Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.

Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within T2N1M0 stage hormone receptor-positive, HER2-negative breast cancer: a retrospective cohort study based on SEER database.

BACKGROUND: Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients. MATERIALS AND METHODS: Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan-Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT. RESULTS: After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36-1.83) and BCSS (HR 1.70, 95% CI 1.44-2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR. CONCLUSION: Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.

A deep learning-based approach for fully automated segmentation and quantitative analysis of muscle fibers in pig skeletal muscle.

Muscle fiber properties exert a significant influence on pork quality, with cross-sectional area (CSA) being a crucial parameter closely associated with various meat quality indicators, such as shear force. Effectively identifying and segmenting muscle fibers in a robust manner constitutes a vital initial step in determining CSA. This step is highly intricate and time-consuming, necessitating an accurate and automated analytical approach. One limitation of existing methods is their tendency to perform well on high signal-to-noise ratio images of intact, healthy muscle fibers but their lack of validation on more complex image datasets featuring significant morphological changes, such as the presence of ice crystals. In this study, we undertake the fully automatic segmentation of muscle fiber microscopic images stained with myosin adenosine triphosphate (mATPase) activity using a deep learning architecture known as SOLOv2. Our objective is to efficiently derive accurate measurements of muscle fiber size and distribution. Tests conducted on actual images demonstrate that our method adeptly handles the intricate task of muscle fiber segmentation, yielding quantitative results amenable to statistical analysis and displaying reliability comparable to manual analysis.

Improving tumor sensitivity by the introduction of an ester chain to triaryl derivatives targeting PD-1/PD-L1.

PD-1/PD-L1 pathway blockade is a promising immunotherapy for the treatment of cancer. In this manuscript, a series of triaryl compounds containing ester chains were designed and synthesized based on the pharmacophore studies of the lead BMS-1. After several SAR iterations, 22 showed the best biochemical activity binding to hPD-L1 with an IC50 of 1.21 nM in HTRF assay, and a KD value of 5.068 nM in SPR analysis. Cell-based experiments showed that 22 effectively promoted A549 cell death by restoring T-cell immune function. 22 showed significant in vivo antitumor activity in a 4T1 mouse model without obvious toxicity, with a TGI rate of 67.8 % (20 mg/kg, ip). Immunohistochemistry data indicated that 22 activates the immune activity in tumors. These results suggest that 22 is a promising compound for further development of PD-1/PD-L1 inhibitor for cancer therapy.

Microplastics in three types of human arteries detected by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS).

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 µg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 µg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 µg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.

Genome-based classification of genera Halosegnis and Salella, and description of four novel halophilic archaea isolated from a tidal flat.

The current species of Halosegnis and Salella within the class Halobacteria are closely related based on phylogenetic, phylogenomic, and comparative genomic analyses. The Halosegnis species showed 99.8-100.0% 16S rRNA and 96.6-99.6% rpoB' gene similarities to the Salella species, respectively. Phylogenetic and phylogenomic analyses showed that Salella cibi CBA1133T, the sole species of Salella, formed a single tight cluster with Halosegnis longus F12-1T, then with Halosegnis rubeus F17-44T. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and average amino acid identity (AAI) values between Salella cibi CBA1133T and Halosegnis longus F12-1T were 99.2, 94.2, and 98.6%, respectively, much higher than the thresholds for species demarcation. This genome-based classification revealed that the genus Salella should be merged with Halosegnis, and Salella cibi should be a later heterotypic synonym of Halosegnis longus. Halophilic archaeal strains DT72T, DT80T, DT85T, and DT116T, isolated from the saline soil of a tidal flat in China, were subjected to polyphasic taxonomic characterization. The phenotypic, chemotaxonomic, phylogenetic, and phylogenomic features indicated that strains DT72T (= CGMCC 1.18925T = JCM 35418T), DT80T (= CGMCC 1.18926T = JCM 35419T), DT85T (= CGMCC 1.19049T = JCM 35605T), and DT116T (= CGMCC 1.19045T = JCM 35606T) represent four novel species of the genera Halorussus, Halosegnis and Haloglomus, respectively, for which the names, Halorussus caseinilyticus sp. nov., Halorussus lipolyticus sp. nov., Halosegnis marinus sp. nov., and Haloglomus litoreum sp. nov., are proposed.

Automated machine learning-based model for the prediction of pedicle screw loosening after degenerative lumbar fusion surgery.

The adequacy of screw anchorage is a critical factor in achieving successful spinal fusion. This study aimed to use machine learning algorithms to identify critical variables and predict pedicle screw loosening after degenerative lumbar fusion surgery. A total of 552 patients who underwent primary transpedicular lumbar fixation for lumbar degenerative disease were included. The LASSO method identified key features associated with pedicle screw loosening. Patient clinical characteristics, intraoperative variables, and radiographic parameters were collected and used to construct eight machine learning models, including a training set (80% of participants) and a test set (20% of participants). The XGBoost model exhibited the best performance, with an AUC of 0.884 (95% CI: 0.825-0.944) in the test set, along with the lowest Brier score. Ten crucial variables, including age, disease diagnosis: degenerative scoliosis, number of fused levels, fixation to S1, HU value, preoperative PT, preoperative PI-LL, postoperative LL, postoperative PT, and postoperative PI-LL were selected. In the prospective cohort, the XGBoost model demonstrated substantial performance with an accuracy of 83.32%. This study identified crucial variables associated with pedicle screw loosening after degenerative lumbar fusion surgery and successfully developed a machine learning model to predict pedicle screw loosening. The findings of this study may provide valuable information for clinical decision-making.

M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets.

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level. Among these modifications, N7-methylguanosine (m7G) stands out as one of the most prevalent. Over recent years, significant attention has been directed towards understanding the implications of m7G modification. This modification is present in diverse RNA molecules, including transfer RNAs, messenger RNAs, ribosomal RNAs, and other noncoding RNAs. Its regulation occurs through a series of specific methyltransferases and m7G-binding proteins. Notably, m7G modification has been implicated in various diseases, prominently across multiple cancer types. Earlier studies have elucidated the significance of m7G modification in the context of immune biology regulation within the tumor microenvironment. This comprehensive review culminates in a synthesis of findings related to the modulation of immune cells infiltration, encompassing T cells, B cells, and various innate immune cells, all orchestrated by m7G modification. Furthermore, the interplay between m7G modification and its regulatory proteins can profoundly affect the efficacy of diverse adjuvant therapeutics, thereby potentially serving as a pivotal biomarker and therapeutic target for combinatory interventions in diverse cancer types.

Alteration of chromosome structure impacts gene expressions implicated in pancreatic ductal adenocarcinoma cells.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a five-year survival rate of approximately 10%. Genetic mutations are pivotal drivers in PDAC pathogenesis, but recent investigations also revealed the involvement of non-genetic alterations in the disease development. In this study, we undertook a multi-omics approach, encompassing ATAC-seq, RNA-seq, ChIP-seq, and Hi-C methodologies, to dissect gene expression alterations arising from changes in chromosome accessibility and chromatin three-dimensional interactions in PDAC. RESULTS: Our findings indicate that chromosomal structural alterations can lead to abnormal expressions on key genes during PDAC development. Notably, overexpression of oncogenes FGFR2, FOXA2, CYP2R1, and CPOX can be attributed to the augmentation of promoter accessibility, coupled with long-range interactions with distal elements. Additionally, our findings indicate that chromosomal structural alterations caused by genomic instability can lead to abnormal expressions in PDACs. As an example, by analyzing chromosomal changes, we identified a putative oncogenic gene, LPAR1, which shows upregulated expression in both PDAC cell lines and clinical samples. The overexpression is correlated with alterations in LPAR1-associated 3D genome structure and chromatin state. We further demonstrated that high LPAR1 activity is required for enhanced PDAC cell migration in vitro. CONCLUSIONS: Collectively, our findings reveal that the chromosomal conformational alterations, in addition to the well-known genetic mutations, are critical for PDAC tumorigenesis.

Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea.

BACKGROUND: The objective of this study was to determine the independent and incremental values of advanced oxidative protein product (AOPP), interleukin 6 (IL-6), and growth differentiation factor 15 (GDF15) in identifying arteriosclerosis in patients with obstructive sleep apnea (OSA). METHODS: A total of 104 individuals diagnosed with OSA by polysomnography were recruited in our study. Arteriosclerosis was defined by measuring the ultrafast pulse wave velocity of the carotid artery. Peripheral venous blood samples were collected to analyze the levels of AOPP, IL-6, and GDF15 utilizing commercially available enzyme-linked immunosorbent assays. RESULTS: Compared to OSA patients without arteriosclerosis, those with arteriosclerosis exhibited significantly higher levels of AOPP, IL-6, and GDF15. GDF15 remained significantly associated with arteriosclerosis even after accounting for clinical factors such as age, gender, body mass index, systolic blood pressure, fasting blood glucose, smoking, and the apnea-hypoxia index (AHI). GDF15 demonstrated the largest area under the curve (AUC) for identifying arteriosclerosis in OSA patients (AUC, 0.85 [0.77-0.94]). The logistic regression model, combining clinical factors and AHI, was enhanced by the inclusion of AOPP and IL-6 (Chi-square = 25.06), and even further improved when GDF15 was added (Chi-square = 50.74). The integrated discrimination index increased by 0.06 to 0.16 when GDF15 was added to the models including clinical factors, AOPP, and IL-6. CONCLUSIONS: This study verified the independent and incremental value of GDF15 in identifying arteriosclerosis in OSA patients, surpassing clinical risk factors and other serum biomarkers such as AOPP and IL-6.

PS-MPs promotes the progression of inflammation and fibrosis in diabetic nephropathy through NLRP3/Caspase-1 and TGF-ß1/Smad2/3 signaling pathways.

BACKGROUND: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles. METHODS: In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5 µm PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis. RESULTS: The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-ß/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group. CONCLUSION: The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-ß1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.

Compound Danshen dripping pills prevent early diabetic retinopathy: roles of vascular protection and neuroprotection.

Introduction: Diabetic retinopathy (DR) represents a major cause of adult blindness, and early discovery has led to significant increase in the number of patients with DR. The drugs currently used for treatment, such as ranibizumab, mainly focus on the middle and late periods of DR, and thus do not meet the clinical need. Here, the potential mechanisms by which compound Danshen Dripping Pills (CDDP) might protect against early DR were investigated. Methods: Db/db mice were used to establish a DR model. The initial weights and HbA1c levels of the mice were monitored, and retinal pathology was assessed by hematoxylin-eosin (HE) staining. The vascular permeability of the retina and thickness of each retinal layer were measured, and electroretinogram were performed together with fundus fluorescein angiography and optical coherence tomography. The levels of inflammatory factors were examined in retinal tissue, as well as those of intercellular adhesion molecule 1 (ICAM-1), IL-6, and monocyte chemoattractant protein 1 (MCP-1) in the serum using ELISA. Immunohistochemistry was used to evaluate levels of vascular endothelial growth factor (VEGF), B-cell lymphoma 2 (Bcl-2), and Bclassociated X protein (Bax). Retinal cell injury and apoptosis were examined by TdT-mediated dUTP Nick End Labeling (TUNEL) assays. Results: The data showed that CDDP significantly improved cellular disarrangement. Imaging data indicated that CDDP could reduce vascular permeability and the amplitude of oscillatory potentials (OPs), and restore the thickness of the ganglion cell layer. Moreover, CDDP reduced the expression levels of inflammatory factors in both the retina and serum. Conclusion: These findings strongly suggest that CDDP prevents early DR through vascular and neuroprotection.

Characterization on vermicular graphite rate and tensile strength in vermicular graphite cast iron based on nonlinear ultrasonic technique.

Ultrasonic techniques have been widely used to detect the percentage of vermicular graphite, defects, etc. in vermicular graphite cast iron. The linear ultrasonic velocity method is the main ultrasonic method for characterizing vermicular graphite rate and tensile strength in the current study, however, it is often easy to misjudge the vermicular graphite rate due to its insignificant variation. This study explores the feasibility of using the nonlinear ultrasonic technique (NUT) to characterize the vermicular graphite rate and tensile strength. Based on the longitudinal critically refracted (LCR) wave detection model, an experimental study to detect the vermicular graphite rate and tensile strength of vermicular graphite cast iron is carried out using the nonlinear ultrasonic harmonic method, and compared with the ultrasonic velocity method. The experiment results show that the relative nonlinear parameter of the LCR wave decreases along with the increase of vermicular graphite rate and increases along with the increase of tensile strength, and it has higher detection sensitivity and resolution than ultrasonic velocity by analyzing the obtained data. The increase in the acoustic nonlinearity parameter (ANP) is related to the increase in the number of grain boundaries in the microstructure. Therefore, the relationship among microstructure, ANP, and mechanical properties of vermicular graphite cast iron can be established, and it's promising that a new approach might be developed for quickly detecting the vermicular graphite rate and corresponding tensile strength with the NUT.

Asymmetric and parallel subgenome selection co-shape common carp domestication.

BACKGROUND: The common carp (Cyprinus carpio) might best represent the domesticated allopolyploid animals. Although subgenome divergence which is well-known to be a key to allopolyploid domestication has been comprehensively characterized in common carps, the link between genetic architecture underlying agronomic traits and subgenome divergence is unknown in the selective breeding of common carps globally. RESULTS: We utilized a comprehensive SNP dataset in 13 representative common carp strains worldwide to detect genome-wide genetic variations associated with scale reduction, vibrant skin color, and high growth rate in common carp domestication. We identified numerous novel candidate genes underlie the three agronomically most desirable traits in domesticated common carps, providing potential molecular targets for future genetic improvement in the selective breeding of common carps. We found that independently selective breeding of the same agronomic trait (e.g., fast growing) in common carp domestication could result from completely different genetic variations, indicating the potential advantage of allopolyploid in domestication. We observed that candidate genes associated with scale reduction, vibrant skin color, and/or high growth rate are repeatedly enriched in the immune system, suggesting that domestication of common carps was often accompanied by the disease resistance improvement. CONCLUSIONS: In common carp domestication, asymmetric subgenome selection is prevalent, while parallel subgenome selection occurs in selective breeding of common carps. This observation is not due to asymmetric gene retention/loss between subgenomes but might be better explained by reduced pleiotropy through transposable element-mediated expression divergence between ohnologs. Our results demonstrate that domestication benefits from polyploidy not only in plants but also in animals.

Enhanced immunity against SARS-CoV-2 in returning Chinese individuals.

Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.

BANP Participates in the Chronic Intermittent Hypoxia-Induced Senescence of Vascular Endothelial Cells by Promoting P53 Phosphorylation and Nuclear Retention.

INTRODUCTION: The objective of this study was to examine the potential induction of senescence in vascular endothelial cells (VECs) by chronic intermittent hypoxia (CIH), a defining characteristic of obstructive sleep apnea (OSA). This investigation seeks to elucidate the underlying mechanisms that contribute to the development of cardiovascular diseases in patients with OSA, with a particular focus on CIH-induced vascular aging. METHODS: The BioSpherix-OxyCycler system was used to establish models of CIH in both rats and human umbilical vein endothelial cells (HUVECs). To assess VECs' senescence, various methods were employed including EdU incorporation assay, cell cycle analysis, senescence-associated ß-galactosidase (SA-ß-gal) staining, and senescence protein testing. Vascular aging was evaluated through measurements of carotid-femoral pulse wave velocity, intima-media thickness, and Ki67 immunohistochemical staining. In order to identify the molecular mechanisms associated with CIH-induced senescence in VECs, a bioinformatics study was conducted utilizing the Gene Expression Omnibus database. RESULTS: Under conditions of CIH, HUVECs exhibited inhibited proliferation, arrested cell cycle, increased activity of SA-ß-gal, and elevated expression levels of p53 and p21 compared to HUVECs under normoxic conditions. Similarly, rats exposed to CIH displayed increased carotid-femoral pulse wave velocity, intima-media thickness, vascular permeability, and SA-ß-gal activity in VECs, along with decreased expression of arterial Ki67. BTG3-associated protein (BANP) was found to be highly expressed in CIH-induced VECs. Furthermore, the overexpression of BANP resulted in the senescence of VECs, along with elevated levels of p53 phosphorylation and nuclear localization. CONCLUSIONS: These findings demonstrate that CIH can induce VECs senescence and contribute to vascular aging. Additionally, BANP can induce VECs senescence by promoting p53 phosphorylation and nuclear retention. These discoveries offer novel insights into the increased cardiovascular risk associated with OSA, thereby presenting new possibilities for therapeutic intervention.

Quantification of soft tissue artifacts using CT registration and subject-specific multibody modeling.

The potential use of gait analysis for quantitative preoperative planning in total hip arthroplasty (THA) has previously been demonstrated. However, the joint kinematic data measured through this process tend to be unreliable for surgical planning due to distortions caused by soft tissue artifacts (STAs). In this study, we developed a novel motion capture framework by combining computed tomography (CT)-based postural calibration and subject-specific multibody dynamics modeling to prevent the effect of STAs in measuring hip kinematics. Three subjects with femoroacetabular impingement syndrome were recruited, and CT data for each patient were collected by attaching marker clusters near the hip. A subject-specific multibody hip joint model was developed based on reconstructed CT data. Spring-dashpot network calculations were performed to minimize the distance between the anatomical landmark and its corresponding infrared reflective marker. The STAs of the thigh was described as six degrees of freedom viscoelastic bushing elements, and their parameter values were identified via smooth orthogonal decomposition. Least squares optimization was used to modify the pelvic rotations to compensate for the rigid components of STAs. The results showed that CT-assisted motion tracking enabled the successful identification of STA influences in gait and squat positions. Furthermore, STA effects were found to alter maximal pelvis tilt and hip rotations during a squat. Compared to other techniques, such as dual fluoroscopic imaging, the adopted framework does not require additional medical imaging for patients undergoing robot-assisted THA surgery and is thus a practical way of evaluating hip joint kinematics for preoperative surgical planning.

The association of SPARC with hypertension and its function in endothelial-dependent relaxation.

BACKGROUND AND AIMS: Secreted protein acidic and rich in cysteine (SPARC) is involved in the pathological processes of many metabolic diseases. However, studies on the relevance of SPARC to hypertension and its involvement in endothelial function are scarce. In this study, we aim to explore the relevance of SPARC to hypertension and investigate its role in endothelium-dependent relaxation (EDR). METHODS: 110 patients who met the criteria were recruited as participants. Serum SPARC concentrations were determined by Luminex assay. The correlation between SPARC levels and hypertension was analyzed. After treatment with SPARC ex vivo or in vivo, endothelial-dependent relaxation (EDR) was measured by wire myography. Western blotting was performed to detect the expression of proteins relevant to endothelial function. RESULTS: Our results showed that serum SPARC levels were significantly higher in the hypertensive group and were positively associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Functional results demonstrated that SPARC dramatically impaired EDR and induced the excess production of reactive oxygen species (ROS) in endothelial cells. Further experimental results confirmed that SPARC reduced angiotensin-converting enzyme 2 (ACE2) expression and ACE2 overexpression or activation completely abolished the impairing effect of SPARC on endothelial function. CONCLUSIONS: The present study reveals the correlation between elevated SPARC and hypertension and confirms its adverse effect on endothelial function, helping establish a comprehensive understanding of hypertension-related endothelial dysfunction in a new scope.

Breath volatile organic compounds for chronic kidney disease progression monitoring.

Breath analysis may provide a convenient and non-invasive method for clinical monitoring of chronic kidney disease (CKD) progression. However, few breath volatile organic compounds (VOCs) indicating progression of CKD have been reported. In this study, we used gas chromatography-mass spectrometry (GC-MS) for untargeted detection of breath VOCs in stage 1, 3, and 5 CKD patients. The results showed that, the levels of breath 4-heptanone, n-octane, and n-dodecane gradually increased from CKD stage 1 to stage 5, and their increasing rates from CKD stage 3 to stage 5 were higher than those from CKD stage 1 to stage 3. Gender, smoking habits, age, and body mass index (BMI) had insignificant impact on the levels of the three breath VOCs. The accuracies of the polynomial support vector machine (SVM) and K-nearest neighbour (KNN) models based on 4-heptanone + n-octane + n-dodecane combination in distinguishing CKD stages 1, 3, and 5 were 76.3% and 72.8%, respectively. The combination of 4-heptanone + n-octane + n-dodecane was superior to any single component for monitoring CKD progression. These discoveries have valuable implications for long-term clinical monitoring of CKD and improving our understanding of CKD.