Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Mitophagy mediated by HIF-1α/FUNDC1 signaling in tubular cells protects against renal ischemia/reperfusion injury.

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

Characteristics of the time processing of adults' strongest sustained attentional bias toward neutral infant faces.

Previous studies have shown that adults exhibit the strongest attentional bias toward neutral infant faces when viewing faces with different expressions at different attentional processing stages due to different stimulus presentation times. However, it is not clear how the characteristics of the temporal processing associated with the strongest effect change over time. Thus, we combined a free-viewing task with eye-tracking technology to measure adults' attentional bias toward infant and adult faces with happy, neutral, and sad expressions of the same face. The results of the analysis of the total time course indicated that the strongest effect occurred during the strategic processing stage. However, the results of the analysis of the split time course revealed that sad infant faces first elicited adults' attentional bias at 0 to 500 ms, whereas the strongest effect of attentional bias toward neutral infant faces was observed at 1000 to 3000 ms, peaking at 1500 to 2000 ms. In addition, women and men had no differences in their responses to different expressions. In summary, this study provides further evidence that adults' attentional bias toward infant faces across stages of attention processing is modulated by expressions. Specifically, during automatic processing adults' attentional bias was directed toward sad infant faces, followed by a shift to the processing of neutral infant faces during strategic processing, which ultimately resulted in the strongest effect. These findings highlight that this strongest effect is dynamic and associated with a specific time window in the strategic process.

Z-Type Ligand Enables Efficient and Stable Deep-Blue Perovskite Light-Emitting Diodes.

During the synthesis of deep-blue perovskite quantum dots (PQDs), they generally emerge as a two-dimensional byproduct with poor yield and low photoluminescence quantum yield (PLQY) due to amine ligand enrichment-induced abundant surface defects. Herein, we provide a colloidal synthesis method to prepare deep-blue CsPbBr3 PQDs in a green nontoxic solvent via strategic Z-type ligand engineering. Z-type ligands of zinc octanoate enable the formation of robust coordination bonds with surface bromide ions of PQDs, maintaining acid-base equilibrium and reducing excess amine enrichment on the PQDs surface. Consequently, homogeneous and monodispersed PQDs with improved PLQY of 73% are successfully synthesized, achieving efficient deep-blue LEDs with a peak EQE of 5.46%, a maximum luminance of 847.6 cd/m2, and an operational half-lifetime of 14 min. The devices exhibit color coordinates of (0.137, 0.049), closely approximating the Rec. 2020 blue standard. Our work offers a potentially eco-friendly and viable route for realizing high-performance LEDs in the deep-blue region.

Joint Association of Lipoprotein(a) and a Family History of Coronary Artery Disease with the Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

AIM: No data are currently available regarding the association between Lp(a) and the cardiovascular outcomes in patients with coronary artery disease (CAD) according to their family history (FHx) of CAD. This study aimed to evaluate the significance of Lp(a) in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) with or without FHx. METHODS: A total of 6056 patients with CCS were enrolled. Information on FHx was collected, and the plasma Lp(a) levels were measured. All patients were followed up regularly. The independent and joint associations of Lp(a) and FHx with the risk of MACEs, including cardiovascular death, nonfatal myocardial infarction, and stroke, were analyzed. RESULTS: With over an average of 50.35±18.58 months follow-up, 378 MACEs were recorded. A Cox regression analysis showed an elevated Lp(a) level to be an independent predictor for MACEs in patients with [hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.38-5.54] or without FHx (HR: 1.35, 95% CI: 1.02-1.77). In comparison to subjects with non-elevated Lp(a) and negative FHx, patients with elevated Lp(a) alone were at a nominally higher risk of MACEs (HR: 1.26, 95% CI: 0.96-1.67), while those with both had the highest risk (HR: 1.93, 95% CI: 1.14-3.28). Moreover, adding Lp(a) to the original model increased the C-statistic by 0.048 in subjects with FHx (p=0.004) and by 0.004 in those without FHx (p=0.391). CONCLUSIONS: The present study is the first to suggest that Lp(a) could be used to predict MACEs in CCS patients with or without FHx; however, its prognostic significance was more noteworthy in patients with FHx.

Syringic Acid Attenuates the IL-1ß-Induced Akt Pathway in Chondrocyte ATDC5 Cells.

BACKGROUND: Osteoarthritis (OA) is a chronic progressive joint ailment that is largely predominant worldwide. However, it typically gets worse over time, occurs more frequently, and becomes more crippling. OBJECTIVES: Syringic acid (SA) is a well-known phenolic compound reported to suppress inflammation, cell proliferation, and apoptosis of various cancer cells. Since the role of SA in OA remains unknown, there is a need to hypothesize the anti-inflammatory activities of SA on IL- 1ß-induced ATDC5 chondrocyte­like cells and to elucidate its protective action against OA. METHODS: The cytotoxicity, inflammatory mediators, mRNA expression of MMPs, ADAMTS, COX-2, and Akt/NF-κB protein expression of SA activity on ATDC5 cells were examined through CCK-8 assay, ELISA, RT-qPCR, and western blot. It was found that SA (10, 20, and 30 µM) did not show any inhibitory effects on the viability of the ATDC5 cells in a concentrationdependent manner. RESULTS: SA markedly reduced the inflammatory mediators, cytokines, PGE2, MMPs, COX-2, and ADAMTS in a concentration-dependent manner. Likewise, SA expressively attenuated IL- 1ß-stimulated Akt phosphorylation and NF-κB activation as well as IL-1ß- induced ATDC5 chondrocytes. CONCLUSION: This study revealed that SA is a novel candidate applicable for the treatment of OA.

Cellular senescence in cancer: molecular mechanisms and therapeutic targets.

Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor-promoting effect of senescence is mainly elicited by a senescence-associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A "one-two-punch" therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field.

Harnessing Natural Evaporation for Electricity Generation using MOF-Based Nanochannels.

Functionalized nanochannels can convert environmental thermal energy into electrical energy by driving water evaporation. This process involves the interaction between the solid-liquid interface and the natural water evaporation. The evaporation-driven water potential effect is a novel green environmental energy capture technology that has a wide range of applications and does not depend on geographical location or environmental conditions, it can generate power as long as there is water, light, and heat. However, suitable materials and structures are needed to harness this natural process for power generation. MOF materials are an emerging field for water evaporation power generation, but there are still many challenges to overcome. This work uses MOF-801, which has high porosity, charged surface, and hydrophilicity, to enhance the output performance of evaporation-driven power generation. It can produce an open circuit voltage of ≈2.2 V and a short circuit current of ≈1.9 µA. This work has a simple structure, easy preparation, low-cost and readily available materials, and good stability. It can operate stably in natural environments with high practical value.

Color-Tunable Organic Light-Emitting Diodes with Single Pt (O

Color-tunable organic light-emitting diodes (CT-OLEDs) have a large color-tuning range, high efficiency and operational stability at practical luminance, making them ideal for human-machine interactive terminals of wearable biomedical devices. However, the device operational lifetime of CT-OLEDs is currently far from reaching practical requirements. To address this problem, a tetradentate Pt(II) complex named tetra-Pt-dbf, which can emit efficiently in both monomer and aggregation states, is designed. This emitter has high Td of 508 °C and large intermolecular bonding energy of -52.0 kcal mol⁻1, which improve its thermal/chemical stability. This unique single-emitter CT-OLED essentially avoids the "color-aging issue" and achieves a large color-tuning span (red to yellowish green) and a high external quantum efficiency （EQE） of ≈30% at 1000 cd m-2 as well as an EQE of above 25% at 10000 cd m-2. A superior LT90 operational lifetime of 520,536 h at a functional luminance of 100 cd m-2, which is over 20 times longer than the state-of-the-art CT-OLEDs, is estimated. To demonstrate the potential application of such OLEDs in wearable biomedical devices, a simple electromyography (EMG)-visualization system is fabricated using the CT-OLEDs.

A Load-Adaptive Driving Method for a Quasi-Continuous-Wave Laser Diode.

A quasi-continuous-wave (QCW) laser diode (LD) driver is commonly used to drive diode bars and stacks designed specifically for QCW operations in solid-state lasers. Such drivers are optimized to deliver peak current and voltage pulses to LDs while maintaining low average power levels. As a result, they are widely used in laser processing devices and laser instruments. Traditional high-energy QCW LD drivers primarily use capacitors as energy storage components and pulsed constant-current sources with op-amps and power metal-oxide-semiconductor field-effect transistors (MOSFETs) as their core circuits for generating repeated constant-current pulses. The drawback of this type of driver is that the driver's output voltage needs to be manually adjusted according to the operating voltage of the load before use to maximize driver efficiency while providing a sufficient current. Another drawback is its inability to automatically adjust the output voltage to maintain high efficiency when the load changes during the driver operation. Drastic changes in the load can cause the driver to fail to function properly in extreme cases. Based on the above traditional circuit structure, this study designed a stability compensation circuit and realized a QCW LD driver for driving a GS20 diode stack with a maximum repetition rate of 100 Hz, a constant current of approximately 300 A, a load voltage of approximately 10 V, and a pulse width of approximately 300 µs. In particular, a high-efficiency, load-adaptive driving method was used with the MOSFETs in the critical saturation region (i.e., between the linear and saturated regions), controlling its power loss effectively while achieving maximum output current of the driver. The experiments demonstrated that the driver efficiency could be maintained at more than 80% when the load current varied from 50 to 300 A.

Two-dimensional Cs3Sb2Br9 inducing transformation of three-dimensional CsPbBr3 to nanoplates.

This communication describes an effective morphological control strategy involving introducing two-dimensional (2D) Cs3Sb2Br9 to induce a transformation of three-dimensional (3D) CsPbBr3 to 2D nanoplates (NPLs). By tuning the Sb/Pb ratio, 2D CsPbBr3 NPLs exhibiting a deep-blue emission centered at a wavelength of 464 nm with an FWHM of 24 nm have been produced. The absence of organic ligands in these high-quality 2D NPLs mitigate the instability issue induced by organic ligand migration and penetration, and these NPLs exhibit 80% of the initial PL intensity after 55 days.

Bioresponsive nanocomplex integrating cancer-associated fibroblast deactivation and immunogenic chemotherapy for rebuilding immune-excluded tumors.

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.

Case report: Tall cell carcinoma with reversed polarity of the breast: an additional case and review of the literature.

Objective: The aim of this report was to comprehensively investigate the clinicopathological features, histological characteristics, and differential diagnosis of tall cell carcinoma with reversed polarity of the breast (TCCRP) to enhance the understanding of this tumour for precise therapeutic interventions. Methods: The clinicopathological characteristics and differential diagnosis of a patient with TCCRP were retrospectively analysed, and a systematic literature review was extracted from relevant published studies on PubMed. Results: All patients included in the study were female, with a median age of 51 years. Microscopically, the tumour cells exhibited a solid papillary growth pattern with tall columnar morphology and reversed nuclear polarity. Immunohistochemistry revealed that the tumours were triple-negative breast cancer (negative for ER, PR, and HER-2), with a low Ki-67 proliferation index. Different degrees of expression were observed for CK7, Calretinin, and S-100 markers; however, CK5/6 showed high expression levels. Conclusions: TCCRP is an uncommon invasive carcinoma subtype found in the breast. Its histological morphology resembles that of tall cell subtype papillary thyroid carcinoma. Accurate diagnosis requires the integration of histomorphological assessment along with immunohistochemistry and molecular genetics analysis.

Saikosaponin d protects pancreatic acinar cells against cerulein-induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS-STING pathway.

Acute pancreatitis represents an inflammatory disease featuring pancreatic necrosis and inflammation. Inflammatory injury of pancreatic acinar cells (PACs) is critically involved in the initiation and progression of acute pancreatitis. Pyroptosis, a new kind of programmed cell death concomitant with a low-grade inflammatory reaction, plays a function in acute pancreatitis pathology. It is unclear whether saikosaponin d (SSd), a pharmacologically active natural product, could protect PACs by regulating pyroptosis. Here, we established a PAC injury model in vitro using cerulein to treat AR42J cells. SSd restored viability and proliferation and lowered the release of pancreatic enzymes and inflammatory interleukins in cerulein-treated AR42J cells. Cerulein-induced pyroptosis was evidenced by typical ultrastructural changes and NLRP3/caspase-1 activation in AR42J cells, but SSd attenuated cerulein-induced pyroptosis and inhibited NLRP3/caspase-1 pathway. Mechanically, SSd reduced mitochondrial damage and mtDNA release, and blocked cGAS-STING signaling in AR42J cells treated with cerulein, contributing to the inhibition of NLRP3-mediated pyroptosis. Furthermore, SSd abolished cerulein-elevated oxidative stress in AR42J cells, leading to the mitigation of mitochondrial damage and inhibition of cGAS-STING signaling and pyroptosis. In conclusion, SSd protected PACs against cerulein-induced pyroptosis by alleviating mitochondrial damage and inhibiting the cGAS-STING pathway, and it could be a therapeutic candidate for acute pancreatitis.

Transcriptional regulation of SARS-CoV-2 receptor ACE2 by SP1.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation-a marker of its activity-and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters (Mesocricetus auratus) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection.

Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and ROS/RNS: Relevance to Parkinson's disease and therapeutic implications.

In this review, we explore how short-chain fatty acids (SCFAs) produced by the gut microbiome affect Parkinson's disease (PD) through their modulatory interactions with alpha-synuclein, neuroinflammation, and oxidative stress mediated by reactive oxygen and nitrogen species (ROS/RNS). In particular, SCFAs-such as acetate, propionate, and butyrate-are involved in gut-brain communication and can modulate alpha-synuclein aggregation, a hallmark of PD. The gut microbiome of patients with PD has lower levels of SCFAs than healthy individuals. Probiotics may be a potential strategy to restore SCFAs and alleviate PD symptoms, but the underlying mechanisms are not fully understood. Also in this review, we discuss how alpha-synuclein, present in the guts and brains of patients with PD, may induce neuroinflammation and oxidative stress via ROS/RNS. Alpha-synuclein is considered an early biomarker for PD and may link the gut-brain axis to the disease pathogenesis. Therefore, elucidating the role of SCFAs in the gut microbiome and their impact on alpha-synuclein-induced neuroinflammation in microglia and on ROS/RNS is crucial in PD pathogenesis and treatment.

The ever-lasting green tides: What can we do？.

Macroalgal blooms (Green tides) are occurring more frequently in many regions of the world because of the combined effects of increasingly intense human activity and climate change. In the last decade, the world's largest Ulva prolifera green tide has become a recurrent phenomenon, appearing every summer in the southern Yellow Sea, China. Green tides can hurt coastal tourism and eradicate aquaculture and artisanal fishing. Eutrophication in nearshore waters is the ultimate explanation for the explosive growth of the macroalgal biomass, but the specific course of each nearshore green tide is often complex and requires in-depth and extensive research to develop effective mitigation strategies. Researchers have undertaken extensive studies on the prevention, control and mitigation of large-scale green algal blooms, and felicitated the utilization of green tide harmful biomass through bio-refining, bioconversion and other measures. However, due to the large-scale and trans-regional nature of the green tide, the government's administrative coordination measures are also essential for effective control. Nevertheless, it is becoming increasingly urgent to prevent and control the bloom at the early stage, and efficiently salvage and use these valuable raw materials.

A new species of Amolops (Amphibia, Anura, Ranidae) from Guizhou Province, China.

The Torrent frogs of the genus Amolops are widely distributed in Nepal and northern India eastwards to southern China and southwards to Malaysia. The genus currently contains 84 species. Previous studies indicated underestimated species diversity in the genus. In the context, a new species occurring from the mountains in the northwestern Guizhou Province, China is found and described based on morphological comparisons and molecular phylogenetic analyses, Amolopsdafangensissp. nov. Phylogenetic analyses based on DNA sequences of the mitochondrial 16S rRNA and COI genes supported the new species as an independent lineage. The uncorrected genetic distances between the 16S rRNA and COI genes in the new species and its closest congener were 0.7% and 2.6%, respectively, which are higher than or at the same level as those among many pairs of congeners. Morphologically, the new species can be distinguished from its congeners by a combination of the following characters: body size moderate (SVL 43.2-46.8 mm in males); head length larger than head width slightly; tympanum distinct, oval; vocal sacs absent; vomerine teeth present; dorsolateral folds weak formed by series of glands; nuptial pads present on the base of finger I; heels overlapping when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level far beyond the tip of the snout when leg stretched forward.

Synergetic impact of lipoprotein(a) and fibrinogen on stroke in coronary artery disease patients.

BACKGROUND: Emerging data suggested that lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Previous studies indicated fibrinogen (Fib) had synergetic effect on Lp(a)-induced events. However, combined impact of Fib and Lp(a) on ischemic stroke has not been elucidated. METHODS: In this prospective study, we consecutively enrolled 8263 patients with stable coronary artery diseases (CAD) from 2011 to 2017. Patients were categorized into three groups according to tertiles of Lp(a) levels [Lp(a)-low, Lp(a)-medium, and Lp(a)-high] and further divided into nine groups by Lp(a) and Fib levels. All subjects were followed up for the occurrence of ischemic stroke. RESULTS: During a median follow-up of 37.7 months, 157 (1.9%) ischemic strokes occurred. Stroke incidence increased by Lp(a) (1.1 vs. 2.1 vs. 2.5%, Cochran-Armitage p < .001) and Fib (1.1 vs. 2.0 vs. 2.6%, Cochran-Armitage p < .001) categories. When further classified into nine groups by Lp(a) and Fib levels, the incidence of ischemic stroke in group 9 [Lp(a)-high and Fib-high] was significantly higher than that in group 1 [Lp(a)-low and Fib-low] (3.1 vs. 6%, p < .001). The group 9 was associated with a highest risk for ischemic stroke (adjusted HR 4.907, 95% CI: 2.154-11.18, p < .001), compared with individuals in the Lp(a)-high (adjusted HR 2.290, 95% CI: 1.483-3.537, p < .001) or Fib-high (adjusted HR 1.184, 95% CI: 1.399-3.410, p = .001). Furthermore, combining Lp(a) with Fib increased C-statistics by .045 (p = .004). CONCLUSIONS: Current study first demonstrated that elevated Lp(a) combining with Fib evaluation enhanced the risk of ischemic stroke in patients with CAD beyond Lp(a) or Fib alone.

DeepmdQCT: A multitask network with domain invariant features and comprehensive attention mechanism for quantitative computer tomography diagnosis of osteoporosis.

In the medical field, the application of machine learning technology in the automatic diagnosis and monitoring of osteoporosis often faces challenges related to domain adaptation in drug therapy research. The existing neural networks used for the diagnosis of osteoporosis may experience a decrease in model performance when applied to new data domains due to changes in radiation dose and equipment. To address this issue, in this study, we propose a new method for multi domain diagnostic and quantitative computed tomography (QCT) images, called DeepmdQCT. This method adopts a domain invariant feature strategy and integrates a comprehensive attention mechanism to guide the fusion of global and local features, effectively improving the diagnostic performance of multi domain CT images. We conducted experimental evaluations on a self-created OQCT dataset, and the results showed that for dose domain images, the average accuracy reached 91%, while for device domain images, the accuracy reached 90.5%. our method successfully estimated bone density values, with a fit of 0.95 to the gold standard. Our method not only achieved high accuracy in CT images in the dose and equipment fields, but also successfully estimated key bone density values, which is crucial for evaluating the effectiveness of osteoporosis drug treatment. In addition, we validated the effectiveness of our architecture in feature extraction using three publicly available datasets. We also encourage the application of the DeepmdQCT method to a wider range of medical image analysis fields to improve the performance of multi-domain images.