[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

Release potential, neglected leakage and reduction countermeasures of COD and Ammonia in MSWLs.

In order to eliminate the impact of the industrial revolution on the environment and improve the water ecological environment, pollutant discharge reduction is imperative. With the acceleration of global discharge reduction process, the huge pollutant release potential and potential environmental effects of municipal solid waste landfills gradually appear, but its release amount and intensity have not been quantitatively revealed. We propose a coupling method of parameter stochastic simulation and physical process model simulation to estimate the hidden leakage of large-scale regional municipal solid waste landfills, and provide a methodology for estimating the hidden leakage of landfills in other countries and even in the whole world by taking China, which has the largest amount of waste generation among developing countries, as an example. Prior to the implementation of stringent construction quality control and assurance management requirements, the average annual leachate generation potential over the entire life cycle of 2600 landfills in China was estimated to be 4.66 × 108 m3, in which the concentrations of COD and NH3-N are 5.38 × 102-6.48 × 104 mg/L and 6.10-3.50 × 103 mg/L, respectively, and the total amounts are 5.21 × 103-7.81 × 108 t and 8.09 × 102-6.65 × 107 t, respectively. About 14 % of these pollutants may leak into the environmental media through the landfill liner with the average number of holes of 21.5/ha. For different regions, the overall release, discharge and leakage of COD and NH3-N in East China account for 35.70 %, 36.68 % and 29.60 % respectively, making it the region with the highest potential for discharge and risk of leakage. Meanwhile, the implementation of mandatory regulations related to leachate generation and control has led to a significant reduction in the leakage of pollutants. For instance, comprehensively detecting and repair of holes in the impermeable liner has reduced the number of holes to 2/ha, resulting in a reduction of >90 % in the leakage of pollutants.

Multistimuli-Responsive Shape-Memory Composites with a Water-Assisted Self-Healing Function Based on Sodium Carboxymethyl Cellulose/Poly(vinyl alcohol)/MXene.

Recent advancements in artificial intelligence have propelled the development of shape-memory polymers (SMPs) with sophisticated, environment-sensitive capabilities. Despite the progress, most of the existing SMPs are limited to responding to a single stimulus and show poor functionality, which has severely hindered their future applications. Herein, we report a high-performance multistimuli-responsive shape-memory and self-healing composite film fabricated by embedding MXene nanosheets into a conventional shape-memory sodium carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) matrix. The incorporation of photothermal MXene nanosheets not only enhances the composite films' mechanical strength but also provides efficient solar-thermal conversion and robust light-actuated shape-memory properties. The resultant composite films exhibit an exceptional shape-memory response to various stimuli including heat, light, and water. Meanwhile, the interfacial interactions can be modulated by adjusting the MXene content, thereby enabling precise manipulation of the shape-memory performance. Moreover, thanks to the intrinsic hydrophilicity of the components and the unique physically cross-linked network, the composite films also demonstrate an effective water-assisted self-healing capability with an impressive healing efficiency of 85.7%. This work offers insights into the development of multifunctional, multistimuli-responsive shape-memory composites, opening up new possibilities for future applications in smart technologies.

Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

A Novel Multi-compartment Rotating Bioreactor for Improving ADSC--Spheroid Formation and its Application in Neurogenic Erectile Dysfunction.

OBJECTIVE: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED). METHODS: Firstly, an MCSRB was constructed using a centrifugal device and hinged trays. Secondly, influence factors (density, rotational speed) on the formation of ADSC-spheroids were explored. Finally, a neurogenic ED model was established to verify the effectiveness and safety of ADSC-spheroids for ED treatment. RESULTS: An MCSRB promoted ADSCs to gather microspheres, most of which were 90-130 µm in diameter. Supernatant from three-dimensional culture led to a significant increase in cytokine expression in ADSCs and migration rate in human umbilical vein endothelial cells (HUVECs) compared to control groups. The erectile function and pathological changes of the penis were improved in the ADSC-spheroids treatment group compared to the traditional ADSCs treatment group (p < 0.01). CONCLUSION: Efficient, batch, controlled and homogenized production of ADSC stem cell microspheres, and effective improvement of erectile dysfunction in neurogenic rats can be achieved using the MCSRB device.

Thiyl Radical Trapped by Cobalt Catalysis: An Approach to Markovnikov Thiol-Ene Reaction.

In the presence of a thiyl radical species, the catalytic Markovnikov thiol-ene reaction is challenging because it prefers to proceed via a radical pathway, thereby leading to anti-Markovnikov selectivity. In this work, a rare example of thiyl radical engaged in Markovnikov thiol-ene reaction enabled by cobalt catalysis is reported. This protocol features the avoidance of unique oxidants, exclusive regioselectivity, and broad substrate scope. Scalable synthesis and late-stage modification of complex molecules demonstrate the practicability of the protocol.

FAM3A Deficiency - Induced Mitochondrial Dysfunction Underlies Post-Infarct Mortality and Heart Failure.

Mitochondrial protein sequence similarity 3 gene family member A (FAM3A) plays important roles in the electron transfer chain, while its functions in the heart are still unknown. This study aims to explore the roles and mechanisms of FAM3A after myocardial infarction (MI). FAM3A-deficient (Fam3a-/-) mice were implemented with MI injury and showed lower survival rates at 4 weeks as well as decreased cardiac systolic function. Isolated cardiomyocytes of Fam3a-/- mice showed reduced basal, ATP-linked respiration and respiratory reserve compared to that of wild-type mice. Transmission electron microscopy studies showed Fam3a-/- mice had a larger size and elevated density of mitochondria. FAM3A deficiency also induced elevated mitochondrial Ca2+, higher opening level of mPTP, lower mitochondrial membrane potential and elevated apoptotic rates. Further analyses demonstrated that mitochondrial dynamics protein Opa1 contributed to the effects of FAM3A in cardiomyocytes. Our study discloses the important roles of mitochondrial protein FAM3A in the heart.

Metabolic improvements of novel microbial fermentation on black tea by Eurotium cristatum.

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The "golden flower" fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the "golden flower" fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (-)-epicatechin gallate were decreased by different degrees after the inoculation of the "golden flower" fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the "golden flower" fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by "golden flower" fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the "golden flower" fungi and black tea, and it provides important information for improving the quality of black tea.

Uric acid and evaluate the coronary vascular stenosis gensini score correlation research and in gender differences.

BACKGROUND AND AIMS: Recent studies have shown that the negative effect of uric acid (UA) on coronary arteries determines the severity of atherosclerotic disease. This study aims to explore the relationship between serum UA level and Gensini score, which reflects the severity of coronary artery disease. METHODS: A total of 860 patients with suspected coronary heart disease who were admitted to hospital due to angina pectoris or myocardial ischemia related symptoms and received coronary angiography were selected. Based on the findings of the angiography, they were categorized into two groups: the coronary heart disease (CHD) group (n = 625) and the control group (n = 235). The uric acid levels and other clinical data were compared between these groups. Additionally, the prevalence of coronary heart disease and Gensini score were compared between the groups, considering gender-specific quartiles of uric acid levels. The clinical baseline data were analyzed using appropriate statistical methods, and multivariate logistic regression analysis was conducted to identify independent risk factors for coronary heart disease. RESULTS: Of 860 patients (mean age, 63.97 ± 11.87 years), 528 were men (mean age, 62.06 ± 11.5 years) and 332 were women (mean age, 66.99 ± 10.11 years). The proportion of smoking, diabetes, hypertension, and hyperlipidemia in the coronary heart disease group was higher than that in the control group (P < 0.05). HbA1C, Gensini score, BMI, TG and hsCRP in the coronary heart disease group were higher than those in the control group (P < 0.05), and HDL-C was lower than that in the control group (P < 0.05). There were no significant differences in age, heart rate, Cr, TC and LDL-C between the two groups (P > 0.05).Multivariate logistic regression analysis showed that age, hypertension, hsCRP and SUA levels increased the risk of coronary heart disease, and the difference was statistically significant(OR = 1.034,95%CI 1.016-1.052, P = 0.001; OR = 1.469,95%CI 1.007-2.142, P = 0.046;OR = 1.064,95%CI 1.026-1.105, P = 0.001; OR = 1.011,95%CI 1.008-1.014, P < 0.001). CONCLUSION: Serum uric acid is positively correlated with Gensini score in patients with coronary heart disease, which is an independent factor for evaluating the degree of coronary artery stenosis and has a predictive effect.

BTSC-TNAS: A neural architecture search-based transformer for brain tumor segmentation and classification.

Glioblastoma (GBM), isolated brain metastasis (SBM), and primary central nervous system lymphoma (PCNSL) possess a high level of similarity in histomorphology and clinical manifestations on multimodal MRI. Such similarities have led to challenges in the clinical diagnosis of these three malignant tumors. However, many existing models solely focus on either the task of segmentation or classification, which limits the application of computer-aided diagnosis in clinical diagnosis and treatment. To solve this problem, we propose a multi-task learning transformer with neural architecture search (NAS) for brain tumor segmentation and classification (BTSC-TNAS). In the segmentation stage, we use a nested transformer U-shape network (NTU-NAS) with NAS to directly predict brain tumor masks from multi-modal MRI images. In the tumor classification stage, we use the multiscale features obtained from the encoder of NTU-NAS as the input features of the classification network (MSC-NET), which are integrated and corrected by the classification feature correction enhancement (CFCE) block to improve the accuracy of classification. The proposed BTSC-TNAS achieves an average Dice coefficient of 80.86% and 87.12% for the segmentation of tumor region and the maximum abnormal region in clinical data respectively. The model achieves a classification accuracy of 0.941. The experiments performed on the BraTS 2019 dataset show that the proposed BTSC-TNAS has excellent generalizability and can provide support for some challenging tasks in the diagnosis and treatment of brain tumors.

Mendelian randomization studies of depression: evidence, opportunities, and challenges.

BACKGROUND: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. METHODS: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. RESULTS: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. CONCLUSIONS: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.

Economical Production of Phenazine-1-carboxylic Acid from Glycerol by Pseudomonas chlororaphis Using Cost-Effective Minimal Medium.

Phenazine compounds are widely used in agricultural control and the medicine industry due to their high inhibitory activity against pathogens and antitumor activity. The green and sustainable method of synthesizing phenazine compounds through microbial fermentation often requires a complex culture medium containing tryptone and yeast extract, and its cost is relatively high, which greatly limits the large-scale industrial production of phenazine compounds by fermentation. The aim of this study was to develop a cost-effective minimal medium for the efficient synthesis of phenazine compounds by Pseudomonas chlororaphis. Through testing the minimum medium commonly used by Pseudomonas, an ME medium for P. chlororaphis with a high production of phenazine compounds was obtained. Then, the components of the ME medium and the other medium were compared and replaced to verify the beneficial promoting effect of Fe2+ and NH4+ on phenazine compounds. A cost-effective general defined medium (GDM) using glycerol as the sole carbon source was obtained by optimizing the composition of the ME medium. Using the GDM, the production of phenazine compounds by P. chlororaphis reached 1073.5 mg/L, which was 1.3 times that achieved using a complex medium, while the cost of the GDM was only 10% that of a complex medium (e.g., the KB medium). Finally, by engineering the glycerol metabolic pathway, the titer of phenazine-1-carboxylic acid reached the highest level achieved using a minimum medium so far. This work demonstrates how we systematically analyzed and optimized the composition of the medium and integrated a metabolic engineering method to obtain the most cost-effective fermentation strategy.

Diagnostic performance of resting full-cycle ratio in identifying coronary lesions causing myocardial ischaemia: a meta-analysis.

BACKGROUND: The resting full-cycle ratio (RFR), a new non-congestive resting index, is commonly used for physiological evaluations of coronary arteries. AIMS: This study aims to evaluate the accuracy of RFR in detecting coronary artery stenosis with hemodynamic significance using fractional flow reserve (FFR) as the reference standard. METHODS: Using 'RFR, resting full-cycle ratio' as the search term, we searched PubMed, Embase, Cochrane Library, and Web of Science databases, screening the literature according to the inclusion and exclusion criteria. By applying FFR ≤ 0.80 and RFR ≤ 0.89 as the diagnostic criteria for ischaemia, we analysed the synthetic sensitivity, specificity, and corresponding 95% confidence intervals, then synthesised the summary receiver operating characteristic curve (SROC). RESULTS: Three studies were included in this meta-analysis, comprising 1,084 patients with 1,312 lesions. When we used FFR ≤ 0.80 as the reference standard, the synthesised sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of RFR in the diagnosis of coronary ischaemia were 73%, 81%, 67%, 85%, 3.95, and 0.33, respectively. Besides, the area under the curve (AUC) was 0.8276. CONCLUSION: Using FFR as the reference standard, RFR has good diagnostic accuracy in detecting coronary ischaemic lesions and may be an effective alternative to FFR in the future, to some extent.

Development of a novel fluorescent aptasensor based on the interaction between hexagonal ß-Co(OH)2 nanoplates and nitrogen-doped carbon dots for ultrasensitive detection of patulin.

There is an urgent need to develop an economical and convenient method for the ultrasensitive detection of patulin (PAT), a mycotoxin that can potentially harm human health when it is found in fruits and their derivatives. In this study, we have developed a novel fluorescent aptasensor that utilizes nitrogen-doped carbon dots (N-CDs) as the fluorescent donor and hexagonal ß-Co(OH)2 nanoplates as the fluorescent acceptor. N-CDs were synthesized through the hydrothermal method, resulting in spherical particles with a diameter of 7.6 nm. These nanoparticles exhibited excellent water solubility and displayed a vibrant blue emission at 448 nm when excited at 360 nm. Cobalt hydroxide nanoplates with a beta crystal structure [ß-Co(OH)2] were synthesized using a simple co-precipitation method, exhibiting hexagonal plate-like shapes with uniform lateral sizes of 4-5 µm. The fluorescence of N-CDs can be efficiently quenched by hexagonal ß-Co(OH)2 nanoplates through Förster resonance energy transfer mechanism. The maximum quenching-recovery capability can be achieved when the concentrations of N-CDs-Apt and ß-Co(OH)2 nanoplates are 150 nmol/L and 100 µg/mL, respectively. The pH of the TE buffer should be 8.0, and the incubation time should be 10 min at 25 °C. The developed fluorescent aptasensor displayed an excellent selectivity for PAT determination with a detection limit of 0.57 pg/mL in the linear range of 1.25 pg/mL-100 ng/mL. The rapid PAT determination in fruit juice samples was realized with good recoveries (96.9-105.8%). The developed fluorescent aptasensor based on the interaction between N-CDs and hexagonal ß-Co(OH)2 nanoplates can be a promising method for the rapid and ultrasensitive detection of PAT in agricultural products.

[Progress of the application research of modern acupuncture anesthesia in perioperative period of thoracic surgery].

Modern acupuncture anesthesia is the application of acupuncture-related therapies to optimize the perioperative management which is based on the combined acupuncture-medicine anesthesia technology, and building a perioperative acupuncture anesthesia accelerated rehabilitation system. Based on the thoracic surgery, this paper analyzes and summarizes the application effects of modern acupuncture anesthesia, focusing on preoperative anxiety relief and advanced analgesia； reduce the dosage of anesthetics, stable respiration and hemodynamics, anti-stress and organ protection during surgery； postoperative analgesia, prevention of nausea, vomiting and cognitive impairment, improvement of gastrointestinal function, prevention of cognitive impairment, and enhancement of immunity. It is anticipated that this review may provide a basis for the further promotion and application of modern acupuncture anesthesia in clinical practice.

Development and validation of a radiomics-based prediction pipeline for the response to stereotactic radiosurgery therapy in brain metastases.

OBJECTIVES: The first treatment strategy for brain metastases (BM) plays a pivotal role in the prognosis of patients. Among all strategies, stereotactic radiosurgery (SRS) is considered a promising therapy method. Therefore, we developed and validated a radiomics-based prediction pipeline to prospectively identify BM patients who are insensitive to SRS therapy, especially those who are at potential risk of progressive disease. METHODS: A total of 337 BM patients (277, 30, and 30 in the training set, internal validation set, and external validation set, respectively) were enrolled in the study. 19,377 radiomics features (3 masks × 3 MRI sequences × 2153 features) extracted from 9 ROIs were filtered through LASSO and Max-Relevance and Min-Redundancy (mRMR) algorithms. The selected radiomics features were combined with 4 clinical features to construct a two-stage cascaded model for the prediction of BM patients' response to SRS therapy using SVM and an ensemble learning classifier. The performance of the model was evaluated by its accuracy, specificity, sensitivity, and AUC curve. RESULTS: Radiomics features were integrated with the clinical features of patients in our optimal model, which showed excellent discriminative performance in the training set (AUC: 0.95, 95% CI: 0.88-0.98). The model was also verified in the internal validation set and external validation set (AUC 0.93, 95% CI: 0.76-0.95 and AUC 0.90, 95% CI: 0.73-0.93, respectively). CONCLUSIONS: The proposed prediction pipeline could non-invasively predict the response to SRS therapy in patients with brain metastases thus assisting doctors to precisely designate individualized first treatment decisions. CLINICAL RELEVANCE STATEMENT: The proposed prediction pipeline combines the radiomics features of multi-modal MRI with clinical features to construct machine learning models that noninvasively predict the response of patients with brain metastases to stereotactic radiosurgery therapy, assisting neuro-oncologists to develop personalized first treatment plans. KEY POINTS: • The proposed prediction pipeline can non-invasively predict the response to SRS therapy. • The combination of multi-modality and multi-mask contributes significantly to the prediction. • The edema index also shows a certain predictive value.

Yu-Shiba-Rusinov states assisted by asymmetric Coulomb repulsion in a bipartite molecular device.

Interfacing magnetism with superconducting condensates are promising candidates holding Majorana bound states with which fault-tolerant quantum computation could be implemented. Within this field, understanding the detailed dynamics is important both for fundamental reasons and for the development of innovative quantum technologies. Herein, motivated by a molecular magnet Tb2Pc3interacting with a superconducting Pb(111) substrate, which results in spin-orbital Yu-Shiba-Rusinov (YSR) states, as is affirmed by a theoretical simulation with the aid of the numerical renormalization group technique (see Xiaet al2022Nat. Commun.136388), we study the YSR states and quantum phase transitions (QPTs) in a bipartite molecular device adsorbed on ans-wave superconducting substrate. We highlight the effect of asymmetric Coulomb repulsion by computing the spectrum function and spin correlation function in various parameter regimes. We demonstrate that if one impurity is non-interacting, there are no YSR states in both impurities with any repulsion value in the other impurity. Whereas if the repulsion in one impurity is strong, the YSR states are observed in both impurities, and a QPT arises as the repulsion in the other impurity sweeps, assisted by the competition between the superconducting singlet (Cooper pair) and the Kondo singlet. The evolution of YSR states distinguishes from the single impurity case and can be well interpreted by the energy scales of the isotropic superconducting gap parameter, as well as the two Kondo temperatures. Our findings provide theoretical insights into the phase diagram of two magnetic impurities on a superconducting host and shine light on the effects induced by asymmetric Coulomb repulsion on many-body interactions.

Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, p < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.

Hepatocyte-secreted FAM3D ameliorates hepatic steatosis by activating FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide; however, the underlying mechanisms remain poorly understood. FAM3D is a member of the FAM3 family; however, its role in hepatic glycolipid metabolism remains unknown. Serum FAM3D levels are positively correlated with fasting blood glucose levels in patients with diabetes. Hepatocytes express and secrete FAM3D, and its expression is increased in steatotic human and mouse livers. Hepatic FAM3D overexpression ameliorated hyperglycemia and steatosis in obese mice, whereas FAM3D-deficient mice exhibited exaggerated hyperglycemia and steatosis after high-fat diet (HFD)-feeding. In cultured hepatocytes, FAM3D overexpression or recombinant FAM3D protein (rFAM3D) treatment reduced gluconeogenesis and lipid deposition, which were blocked by anti-FAM3D antibodies or inhibition of its receptor, formyl peptide receptor 1 (FPR1). FPR1 overexpression suppressed gluconeogenesis and reduced lipid deposition in wild hepatocytes but not in FAM3D-deficient hepatocytes. The addition of rFAM3D restored FPR1's inhibitory effects on gluconeogenesis and lipid deposition in FAM3D-deficient hepatocytes. Hepatic FPR1 overexpression ameliorated hyperglycemia and steatosis in obese mice. RNA sequencing and DNA pull-down revealed that the FAM3D-FPR1 axis upregulated the expression of heterogeneous nuclear ribonucleoprotein U (hnRNP U), which recruits the glucocorticoid receptor (GR) to the promoter region of the short-chain acyl-CoA dehydrogenase (SCAD) gene, promoting its transcription to enhance lipid oxidation. Moreover, FAM3D-FPR1 axis also activates calmodulin-Akt pathway to suppress gluconeogenesis in hepatocytes. In conclusion, hepatocyte-secreted FAM3D activated the FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation in hepatocytes. Under obesity conditions, increased hepatic FAM3D expression is a compensatory mechanism against dysregulated glucose and lipid metabolism.