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Abstract Background Neonatal hypoxic ischemic encephalopathy (HIE) leads to different degrees of neurological sequelae. The incidence of HIE is relatively high, and the causal pathways leading to HIE are still controversial. This study aimed to investigate the risk factors associated with HIE comparing differences between genders. Methods A cross-sectional study of 196 neonates diagnosed with HIE was conducted. Based on the severity of clinical findings, HIE was classified as mild, moderate or severe. For mild HIE, the outcomes were relatively less severe, whereas moderate to severe HIE could suffer serious consequences, including death, cerebral palsy, epilepsy. T-test, chi-square test and logistic regression were used to analyze data. Results Among the 196 neonatal HIE, 39 (19.9%) had mild HIE,157 (80.1%) had moderate or severe HIE. The logistic regression analysis showed that gender was a specific stratified characteristic of moderate or severe HIE. In the male neonates group, emergency cesarean section, abnormal labor stage and amniotic fluid contamination were associated with an increased risk of moderate or severe HIE, where the adjusted odds ratios (ORs) were 4.378 (95% confidence intervals (CI):2.263–6.382), 2.827 (95% CI:1.743–5.196) and 2.653 (95%CI:1.645–3.972), respectively. As expected, a significant additive effect was found in the interactions between emergency cesarean section and abnormal labor stage, as well as between emergency cesarean section and amniotic fluid contamination, where the relative excess risk of interaction was 2.315(95%CI:1.573–3.652) and 1.896(95%CI: 1.337–3.861) respectively. Conclusion Emergency cesarean section, abnormal labor stage and amniotic fluid contamination were risk factors of moderate or severe HIE in neonates, and the associations were significantly correlated with male gender. Notably, coinciding incidences of emergency cesarean section with abnormal labor stage, or emergency cesarean section with amniotic fluid contamination were possibly synergistic in increasing the risk of moderate or severe HIE. These findings may assist clinicians in strengthening their awareness on risks affecting HIE and help reduce the incidence of moderate or severe HIE in clinical practice.

In-situ experimental observation cannot be an effective method in the impact process of metal cavitation erosion, and the impact damage energy prediction theory has not been established based on a detailed mathematical and physical model. Research has shown that the metal material can be regarded as a sensor to reflect the impact parameters. Soft metal materials such as industrial pure copper with a single α-phase microstructure can be a suitable sensor to detect cavitation erosion effects, revealing the impact behaviors of the cavitation jet through the depth, width and spatial distribution of cavitation pits on the surface. In this scenario, volume loss of cavitation pits on a macro/mesoscale are obtained by three-dimensional surface measurement. A coupled fluid-solid simulation model calculating the impact damage energy on a macro/mesoscale is established based on the Smoothed Particle Hydrodynamics (SPH) and the Crystal Plasticity Finite Element Method (CPFEM). Python programming is used to set the trajectory of SPH particles to determine the macro cavitation flow field. IFEM methods were used to construct the prediction theory of cavitation impact energy in a relatively simple exponential equation, establishing the quantitative relationship between cavitation impact damage energy and measured volume of cavitation pits. Compared with conventional measurement and simulation, the present multiscale approaches are assumed as a further step advancement towards calculating the impact damage energy of cavitation water jet.

Abstract We aimed to assess long-term disease progression in patients with severe keratoconus (KC). Clinical records of 125 patients (201 eyes) with severe KC followed-up for > 12 months were retrospectively analyzed. From these, 28 patients (31 eyes) were included. Corneal topography parameters evaluated included thinnest corneal thickness (TCT), maximum keratometry (Kmax), anterior and posterior mean corneal radii of 3 mm (aKM, pKM), steep keratometry, and KC screening indices. All patients wore rigid gas permeable contact lenses (RGPCLs) for an extended period. The median patient age and follow-up period were 20 (interquartile range [IQR] 17–22) years and 25 (15–38) months, respectively. Compared to baseline, the aKM, Kmax, and KC screening indices on the anterior corneal surface were reduced at the final follow-up (P

Abstract Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

Abstract Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2, as well as aquaporin 1 and β2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or aquaporin 1 and β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

Abstract Background Optimization of a highly efficient transient expression system is critical for the study of gene function, particularly in those plants in which stable transformation methods are not widely available. Agrobacterium tumefaciens‑mediated transient transformation is a simple and low-cost method that has been developed and applied to a wide variety of plant species. However, the transient expression in spinach (Spinacia oleracea L.) is still not reported. Results We developed a transient expression system in spinach leaves of the Sp75 and Sp73 varieties. Several factors influencing the transformation efficiency were optimized such as Agrobacterium strain, spinach seedling stage, leaf position, and the expression time after injection. Agrobacterium strain GV3101 (pSoup-p19) was more efficient than AGL1 in expressing recombinant protein in spinach leaves. In general, Sp75 leaves were more suitable than Sp73 leaves, regardless of grow stage. At four-leaf stage, higher intensity and efficiency of transient expression were observed in group 1 (G1) of Sp75 at 53 h after injection (HAI) and in G1 of Sp73 at 64 HAI. At six-leaf stage of Sp75, group 3 (G3) at 72 HAI were the most effective condition for transient expression. Using the optimized expression system, we detected the subcellular localization of a transcriptional co-activator SoMBF1c and a NADPH oxidase SoRbohF. We also detected the interaction of the protein kinase SoCRK10 and the NADPH oxidase SoRbohB. Conclusion This study established a method of highly efficient transient expression mediated by Agrobacterium in spinach leaves. The transient expression system will facilitate the analysis of gene function and lay a solid foundation for molecular design breeding of spinach.

Abstract This study aimed to explore naringin’s potential to promote the osteogenic differentiation of MC3T3-E1 under oxidative stress. It delved into Nar’s connection with the Wnt/β-catenin and PI3K/Akt signaling pathways. Initially, 2911 OP-related genes were analyzed, revealing close ties with the PI3K/Akt and Wnt pathways alongside oxidative stress. Nar’s potential targets—ESR1, HSP90AA1, and ESR2—were identified through various databases and molecular docking studies confirmed Nar’s affinity with ESR1 and HSP90AA1. Experiments established optimal concentrations for Nar and H2O2. H2O2 at 0.3 mmol/L damaged MC3T3-E1 cells, alleviated by 0.1 µmol/L Nar. Successful establishment of oxidative stress models was confirmed by DCFH-DA probe and NO detection. Nar exhibited the ability to enhance osteogenic differentiation, counteracting oxidative damage. It notably increased osteoblast-related protein expression in MC3T3-E1 cells under oxidative stress. The study found Nar’s positive influence on GSK-3β phosphorylation, β-catenin accumulation, and pathway-related protein expression, all critical in promoting osteogenic differentiation. The research concluded that Nar effectively promotes osteogenic differentiation in MC3T3-E1 cells under oxidative stress. It achieved this by activating the Wnt/β-catenin and PI3K/Akt pathways, facilitating GSK-3β phosphorylation, and enhancing β-catenin accumulation, pivotal in osteogenesis.

Abstract Background Powdery mildew, caused by Eeysiphe heraclei, seriously threatens Heracleum moellendorffii Hance. Plant secondary metabolites are essential to many activities and are necessary for defense against biotic stress. In order to clarify the functions of these metabolites in response to the pathogen, our work concentrated on the variations in the accumulation of secondary metabolites in H. moellendorffii during E. heraclei infection. Results Following E. heraclei infection, a significant upregulation of coumarin metabolites—particularly simple coumarins and associated genes was detected by RNA-seq and UPLC-MS/MS association analysis. Identifying HmF6’H1, a Feruloyl CoA 6’-hydroxylase pivotal in the biosynthesis of the coumarin basic skeleton through ortho-hydroxylation, was a significant outcome. The cytoplasmic HmF6’H1 protein was shown to be able to catalyze the ortho-hydroxylation of p-coumaroyl-CoA and caffeoyl-CoA, resulting in the formation of umbelliferone and esculetin, respectively. Over-expression of the HmF6’H1 gene resulted in increased levels of simple coumarins, inhibiting the biosynthesis of furanocoumarins and pyranocoumarins by suppressing PT gene expression, enhancing H. moellendorffii resistance to powdery mildew. Conclusions These results established HmF6’H1 as a resistance gene aiding H. moellendorffii in combatting E. heraclei infection, offering additional evidence of feruloyl-CoA 6’-hydroxylase role in catalyzing various types of simple coumarins. Therefore, this work contributes to our understanding of the function of simple coumarins in plants’ defense against powdery mildew infection.

Abstract Background Over the past three decades, China has experienced significant changes in urban-rural, gender, and age-specific suicide mortality patterns. This study aimed to investigate the long-term trends in suicide mortality in China from 1987 to 2020. Methods Suicide mortality data were obtained from China’s National Health Commission. Joinpoint regression analysis was used to examine changes in trends and age-period-cohort modeling to estimate age, period, and cohort effects on suicide mortality from 1987 to 2020. Net drift, local drift, longitudinal age curves, and period relative risks were also calculated. Results Crude and age-standardized suicide mortality in China showed continuing downward trends from 1987 to 2020, with a more pronounced decrease in rural areas (net drift = -7.07%, p

Abstract The role of SLC35A2 in breast cancer remains poorly understood, with limited available information on its significance. This study aimed to investigate the expression of SLC35A2 and clinicopathological variables in breast cancer patients. Immunohistochemical analysis of SLC35A2 protein was conductedon 40 adjacent non-neoplastic tissues and 320 breast cancer tissues. The study also assesed the association between SLC35A2 expression and breast cancer clinicopathological features of breast cancer, as well as its impact on overall survival. In comparison to adjacent non-neoplastic tissues, a significantly higher expression of SLC35A2 was observed in breast cancer tissues (P = 0.020), and this expression was found to be independently correlated with HER2 positivity (P = 0.001). Survival analysis indicated that patients with low SLC35A2 expression had a more favorable prognosis in HER2-positive subtype breast cancer (P = 0.017). These results suggest that SLC35A2 is overexpressed in breast cancer tissues compared to adjacent non-neoplastic tissues and may serve as a potential prognostic marker for HER2-positive subtype breast cancer. Furthermore, breast cancer patients with the HER2 positive subtype who exhibited decreased levels of SLC35A2 expression demonstrated improved long-term prognostic outcomes.

Abstract Background This study investigates the relationship between triglyceride-glucose (TyG) index trajectories and the results of ablation in patients with stage 3D atrial fibrillation (AF). Methods A retrospective cohort study was carried out on patients who underwent AF Radiofrequency Catheter Ablation (RFCA) at the Cardiology Department of the Fourth Affiliated Hospital of Zhejiang University and Taizhou Hospital of Zhejiang Province from January 2016 to December 2022. The main clinical endpoint was determined as the occurrence of atrial arrhythmia for at least 30 s following a 3-month period after ablation. Using a latent class trajectory model, different trajectory groups were identified based on TyG levels. The relationship between TyG trajectory and the outcome of AF recurrence in patients was assessed through Kaplan-Meier survival curve analysis and multivariable Cox proportional hazards regression model. Results The study included 997 participants, with an average age of 63.21 ± 9.84 years, of whom 630 were males (63.19%). The mean follow-up period for the participants was 30.43 ± 17.75 months, during which 200 individuals experienced AF recurrence. Utilizing the minimum Bayesian Information Criterion (BIC) and the maximum Entropy principle, TyG levels post-AF RFCA were divided into three groups: Locus 1 low-low group (n = 791), Locus 2 low-high-low group (n = 14), and Locus 3 high-high group (n = 192). Significant differences in survival rates among the different trajectories were observed through the Kaplan-Meier curve (P

Objective: The main objective of this study was to create and assess a detailed diagnostic model with an optimizing feature selection algorithm that combines computed tomography (CT) imaging characteristics, demographic information, and genetic markers to enhance the accuracy of benign and malignant classification of osteosarcoma. This research seeks to enhance the early identification and categorization of benign and malignant of osteosarcoma, ultimately enabling more personalized and efficient treatment approaches. Methods: Data from 225 patients diagnosed with osteosarcoma at two different medical institutions between June 2018 and June 2021 were gathered for this research study. A novel feature selection approach that combined Principal Component Analysis (PCA) with Improved Particle Swarm Optimization (IPSO) was utilized to analyze 1743 image-derived features. The performance of the resulting model was evaluated using metrics such as area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE), and compared to models developed using conventional feature selection methods. Results: The proposed model showed promising predictive performance with an AUC of 0.87, accuracy of 0.80, sensitivity of 0.75, and specificity of 0.85. These results suggest improved predictive ability compared to models built using traditional feature selection techniques, particularly in terms of accuracy and specificity. However, there is room for improvement in enhancing sensitivity. Conclusion: Our study introduces a novel predictive model for distinguishing between benign and malignant osteosarcoma., emphasizing its potential significance in clinical practice. Through the utilization of CT imaging features, our model shows improved accuracy and specificity, marking progress in the early detection and classification of osteosarcoma as either benign or malignant. Future investigations will concentrate on enhancing the model’s sensitivity and validating its effectiveness on a larger dataset, aiming to boost its clinical relevance and support personalized treatment approaches for osteosarcoma.

ObjectiveThis study aims to investigate the image quality of a high-resolution, low-dose coronary CT angiography (CCTA) with deep learning image reconstruction (DLIR) and second-generation motion correction algorithms, namely, SnapShot Freeze 2 (SSF2) algorithm, and its diagnostic accuracy for in-stent restenosis (ISR) in patients after percutaneous coronary intervention (PCI), in comparison with standard-dose CCTA with high-definition mode reconstructed by adaptive statistical iterative reconstruction Veo algorithm (ASIR-V) and the first-generation motion correction algorithm, namely, SnapShot Freeze 1 (SSF1).MethodsPatients after PCI and suspected of having ISR scheduled for high-resolution CCTA (randomly for 100 kVp low-dose CCTA or 120 kVp standard-dose) and invasive coronary angiography (ICA) were prospectively enrolled in this study. After the basic information pairing, a total of 105 patients were divided into the LD group (60 patients underwent 100 kVp low-dose CCTA reconstructed with DLIR and SSF2) and the SD group (45 patients underwent 120 kVp standard-dose CCTA reconstructed with ASIR-V and SSF1). Radiation and contrast medium doses, objective image quality including CT value, image noise (standard deviation), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) for the aorta, left main artery (LMA), left ascending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) of the two groups were compared. A five-point scoring system was used for the overall image quality and stent appearance evaluation. Binary ISR was defined as an in-stent neointimal proliferation with diameter stenosis ≥50% to assess the diagnostic performance between the LD group and SD group with ICA as the standard reference.ResultsThe LD group achieved better objective and subjective image quality than that of the SD group even with 39.1% radiation dose reduction and 28.0% contrast media reduction. The LD group improved the diagnostic accuracy for coronary ISR to 94.2% from the 83.8% of the SD group on the stent level and decreased the ratio of false-positive cases by 19.2%.ConclusionCompared with standard-dose CCTA with ASIR-V and SSF1, the high-resolution, low-dose CCTA with DLIR and SSF2 reconstruction algorithms further improves the image quality and diagnostic performance for coronary ISR at 39.1% radiation dose reduction and 28.0% contrast dose reduction.

Abstract Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV‐SpCas9/sgRNA‐VEGFA system is demonstrated which blocks suture‐induced expression of VEGFA, CD31, and α‐smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Traditional methods for water quality assessment often overlook the uncertainty of water quality data during the sample collection process, leading to limitations in their application. Therefore, this study combines the comprehensive water quality index (CWQI) method and the improved CWQI method based on CRITIC with the Monte Carlo method to evaluate the water quality in the Weishui Reservoir watershed. The results indicate that (1) there is a noticeable difference in water quality between the Shaxiping and Dayanzui sampling points. The water quality at the Shaxiping sampling point is excellent, with a water quality classification of Class I. In contrast, the water quality at the Dayanzui sampling point is comparatively poorer, with an average water quality classification of Class III. (2) Sensitivity analysis shows that TN, NH4+-N, and TP are more sensitive than other indicators, suggesting that they are the primary factors influencing the evaluation results. (3) Compared to the traditional CWQI method, combining the CRITIC-based improved CWQI method with the Monte Carlo method is more scientifically rigorous. It considers the variety of evaluation indicators, allocates weights rationally, and provides evaluation results that align better with seasonal variations, resulting in higher discriminative power. HIGHLIGHTS A new model integrating Monte Carlo simulation, CRITC methods, and CWQI was proposed to assess water quality in Weishui Reservoir.; Compared with the conventional model (CWQI), the new model leads to more reasonable results.; The key parameters affecting water quality in Weishui Reservoir are TN, TP, and NH4+-N.;

Abstract In recent years, due to the shortage of blood products, some extensive burn patients were forced to adopt an “ultra-restrictive” transfusion strategy, in which the hemoglobin levels of RBC transfusion thresholds were 0.05). Among the ultra-restrictive transfusion group, patients with RBC transfusion threshold

Abstract Background Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown. Methods HIGD1A expression was determined in 24 pairs of human HCC samples and para-tumorous tissues. Loss-of-function experiments were conducted both in vivo and in vitro to explore the role of HIGD1A in HCC proliferation and metastasis. Results Increased HIGD1A expression was found in HCC tissues and cell lines, which was induced by hypoxia or low-glucose condition. Moreover, HIGD1A knockdown in HCC cells arrested the cell cycle at the G2/M phase and promoted hypoxia-induced cell apoptosis, resulting in great inhibition of cell proliferation, migration, and invasion, as well as tumor xenograft formation. Interestingly, these anti-tumor effects were not observed in normal hepatocyte cell line L02. Further, HIGD1A knockdown suppressed the expression of ornithine decarboxylase 1 (ODC1), a rate-limiting enzyme of polyamine metabolism under c-Myc regulation. HIGD1A was found to bind with the c-Myc promoter region, and its knockdown decreased the levels of polyamine metabolites. Consistently, the inhibitory effect on HCC phenotype by HIGD1A silencing could be reversed by overexpression of c-Myc or supplementation of polyamines. Conclusions Our results demonstrated that HIGD1A activated c-Myc–ODC1 nexus to regulate polyamine synthesis and to promote HCC survival and malignant phenotype, implying that HIGD1A might represent a novel therapeutic target for HCC.

Abstract Background To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression. Methods A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (Sw), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility. Results The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus. Conclusions This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.

Background: Chronic ankle instability (CAI) has been considered a neurophysiological disease, having as symptoms dysfunction in somatosensory and motor system excitability. Rehabilitation has been considered an effective treatment for CAI. However, few studies have explored the effects of rehabilitation on neuroplasticity in the CAI population. Objective: The purpose of this study was to investigate the effects of rehabilitation on cortical activities for postural control in CAI patients and to find the correlation between the change in cortical activities and patient-reported outcomes (PROs). Methods: Thirteen participants with CAI (6 female, 7 male, age = 33.8 ± 7.7 years, BMI = 24.7 ± 4.9 kg/m2) received a home exercise program for about 40 min per day, four days per week and six weeks, including ankle range-of-motion exercise, muscle strengthening, and balance activities. Cortical activation, PROs and Y-balance test outcomes were assessed and compared before and after rehabilitation. Cortical activation was detected via Functional near-infrared spectroscopy (fNIRS) while the participants performed single-leg stance tasks. Results: The participants had better PROs and Y balance test outcomes after rehabilitation. Greater cortical activation was observed in the primary somatosensory cortex (S1, d = 0.66, p = 0.035), the superior temporal gyrus (STG, d = 1.06, p = 0.002) and the middle temporal gyrus (MTG, d = 0.66, p = 0.035) in CAI patients after rehabilitation. Moreover, significant positive correlations were observed between the recovery of ankle symptoms and the change of cortical activation in S1 (r = 0.74, p = 0.005) and STG (r = 0.72, p = 0.007) respectively. Conclusion: The current study reveals that six weeks of rehabilitation can cause greater cortical activation in S1, STG and MTG. This increase in cortical activation suggested a better ability to perceive somatosensory stimuli and may have a compensatory role in function improvement.

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27S15/78/82A) and Hsp27S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27S15A and Hsp27S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2Apro) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27S82A. However, Hsp27S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.

Dynamic PET allows quantification of physiological parameters through tracer kinetic modeling. For dynamic imaging of brain or head and neck cancer on conventional PET scanners with a short axial field of view, the image-derived input function (ID-IF) from intracranial blood vessels such as the carotid artery (CA) suffers from severe partial volume effects. Alternatively, optimization-derived input function (OD-IF) by the simultaneous estimation (SIME) method does not rely on an ID-IF but derives the input function directly from the data. However, the optimization problem is often highly ill-posed. We proposed a new method that combines the ideas of OD-IF and ID-IF together through a kernel framework. While evaluation of such a method is challenging in human subjects, we used the uEXPLORER total-body PET system that covers major blood pools to provide a reference for validation. Methods: The conventional SIME approach estimates an input function using a joint estimation together with kinetic parameters by fitting time activity curves from multiple regions of interests (ROIs). The input function is commonly parameterized with a highly nonlinear model which is difficult to estimate. The proposed kernel SIME method exploits the CA ID-IF as a priori information via a kernel representation to stabilize the SIME approach. The unknown parameters are linear and thus easier to estimate. The proposed method was evaluated using 18F-fluorodeoxyglucose studies with both computer simulations and 20 human-subject scans acquired on the uEXPLORER scanner. The effect of the number of ROIs on kernel SIME was also explored. Results: The estimated OD-IF by kernel SIME showed a good match with the reference input function and provided more accurate estimation of kinetic parameters for both simulation and human-subject data. The kernel SIME led to the highest correlation coefficient (R = 0.97) and the lowest mean absolute error (MAE = 10.5 %) compared to using the CA ID-IF (R = 0.86, MAE = 108.2 %) and conventional SIME (R = 0.57, MAE = 78.7 %) in the human-subject evaluation. Adding more ROIs improved the overall performance of the kernel SIME method. Conclusion: The proposed kernel SIME method shows promise to provide an accurate estimation of the blood input function and kinetic parameters for brain PET parametric imaging.

Liver fibrosis occurs in response to chronic damage and inflammation to the liver. Leaving untreated, it can lead to decreased liver function and can eventually progress to cirrhosis, a more advanced and irreversible state of liver damage. Clinical investigations showed that chronic liver disease associated with neurological symptoms including anxiety, depression, and cognitive decline. However, few therapeutic options are available for treating liver and related brain pathologies simultaneously. In this study, we aim to find therapeutic candidates that target the liver-brain axis. Gossypetin, a flavonoid from sedum, shows promising capability in treating liver and brain pathologies in CCl4-induced mouse model. Short term of gossypetin administration is sufficient to ameliorate impaired liver function and pre-existing liver fibrosis, suppress MKK3/6-p38 MAPK and p53 activation, and abolish the activation of hepatic stellate cells and Kupffer cells. Although we observe no neuronal loss in the brain of mice with liver fibrosis, we do observe astrogliosis and microglial activation in certain brain regions, especially the hippocampus. Brief gossypetin administration also shows potential in alleviating neuroinflammation in these regions. These results suggest that gossypetin can target the liver-brain axis and be a promising candidate for treating chronic liver fibrosis patients with neurological symptoms.

Background: Rising clarithromycin resistance undermines Helicobacter pylori (H. pylori) treatment efficacy. We aimed to determine clarithromycin's minimum inhibitory concentration (MIC) levels and identify specific mutation sites in the 23S ribosomal subunit (23S rRNA) that predict treatment outcomes in a 14-day regimen of clarithromycin bismuth quadruple therapy (amoxicillin 1g, clarithromycin 500 mg, rabeprazole 10 mg, and colloidal bismuth pectin 200 mg). Materials and methods: We included adult H. pylori patients who hadn't previously undergone clarithromycin-based treatment, either as initial or rescue therapy. Exclusions were made for penicillin allergy, recent use of related medications, severe illnesses, or inability to cooperate. Patients underwent a 14-day clarithromycin bismuth quadruple therapy. Gastric mucosa specimens were obtained during endoscopy before eradication. MIC against amoxicillin and clarithromycin was determined using the E-test method. The receiver operating characteristic (ROC) curve helped to find the optimal clarithromycin resistance MIC breakpoint. Genetic sequences of H. pylori 23S rRNA were identified through Sanger Sequencing. (ChiCTR2200061476) Results: Out of 196 patients recruited, 92 met the inclusion criteria for the per-protocol (PP) population. The overall intention-to-treat (ITT) eradication rate was 80.00 % (84/105), while the modified intention-to-treat (MITT) and PP eradication rates were 90.32 % (84/93) and 91.30 % (84/92) respectively. No amoxicillin resistance was observed, but clarithromycin resistance rates were 36.19 % (38/105), 35.48 % (33/93), and 34.78 % (33/92) in the ITT, MITT, and PP populations respectively. Compared with the traditional clarithromycin resistance breakpoint of 0.25 μg/mL, a MIC threshold of 12 μg/mL predicted better eradication. Among 173 mutations on 152 sites in the 23S rRNA gene, only the 2143A > G mutation could predict eradication outcomes (p G mutation has limited specificity in predicting eradication outcomes, necessitating further investigation into additional mutation sites associated with clarithromycin resistance.

Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is expansion of the intronic hexanucleotide repeat (GGGGCC) n in C9orf72. Here, we investigate the formation of nucleic acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of ALS/FTD. We observe significant aggregation of the hexanucleotide sequence (GGGGCC) n , which we associate to the formation of multimolecular G-quadruplexes (mG4s) by using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions leads to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validate the biological relevance of our findings by detecting an increased prevalence of G4-structures in C9orf72 mutant human motor neurons when compared to healthy motor neurons by staining with a G4-selective fluorescent probe, revealing signal in putative condensates. Our findings strongly suggest that RNA G-rich repetitive sequences can form protein-free condensates sustained by multimolecular G-quadruplexes, highlighting their potential relevance as therapeutic targets for C9orf72 mutation-related ALS/FTD.

Abstract Introduction The aim of this work is to evaluate the intraobserver repeatability and interobserver reproducibility of corneal power measurements obtained with a swept-source optical coherence tomographer (CASIA 2, Tomey, Japan) in healthy subjects. Methods A total of 67 right eyes from 67 healthy subjects were enrolled. Two experienced observers measured each eye three times consecutively with the CASIA 2. Corneal power values were recorded as simulated keratometry, anterior, posterior, and total corneal power. Parameters were flattest keratometry (K f), steepest keratometry (K s), mean keratometry (K m), astigmatism magnitude, astigmatism power vectors J 0 and J 45. Intraobserver repeatability and interobserver reproducibility of the CASIA 2 were assessed by the within-subject standard deviation (S w), test–retest repeatability (TRT), coefficients of variation (CoV), and intraclass correlation coefficients (ICCs). Double-angle plots were used for astigmatism vector analysis. Results The CASIA 2 had high repeatability for all corneal power values, with S w values ≤ 0.17 diopters (D), TRT ≤ 0.46 D, and ICCs ranging from 0.866 to 0.998. Interobserver reproducibility was also high, showing all S w values ≤ 0.10 D, TRT ≤ 0.27 D, and ICCs ≥ 0.944. The reproducibility of the average of three consecutive measurements (S w 0.01–0.10 D, TRT 0.03–0.27 D, ICC 0.944–0.998) was higher than the reproducibility of single measurements (S w 0.01–0.17 D, TRT 0.03–0.47 D, ICC 0.867–0.996). Conclusions The CASIA 2 showed high intraobserver repeatability and interobserver reproducibility for anterior, posterior, and total corneal power measurements in 6.0-mm diameter area. In addition, we suggest that using the average of three consecutive measurements can improve reproducibility between observers, compared to single measurements only.

In this study, amino-modified micro-mesoporous silica (NH2-MMS) with hierarchical pores was prepared by modifying micro-mesoporous silica ZSM-5 with 3-aminopropyltriethoxysilane and used as an adsorbent in solid-phase extraction to analyze free fatty acids (FFAs) in krill oil during storage for an initial time. The Brunner Emmet Teller adsorption experiment and Fourier transform infrared spectroscopy demonstrate that NH2-MMS, with a hierarchical pore structure, was successfully synthesized. The adsorption experiments, especially static adsorption, indicate that the absorption ability of the prepared NH2-MMS, with a hierarchical pore structure, toward FFAs was better than that of traditional amino-modified mesoporous silica (SBA-15) with a mesoporous structure at all temperature and concentrations. Fairly low limits of detection (0.06–0.15 μg g−1), acceptable recoveries (85.16–94.31%), and precision (0.08–5.26%) were attained under ideal circumstances. Moreover, NH2-MMS has the advantages of easy preparation and being environmentally friendly. As a result, this method offers an alternative to the current method for determining FFAs in different kinds of oil specimens.

Pathogenic microorganisms play a crucial role in the global disease burden due to their ability to cause various diseases and spread through multiple transmission routes. Immunity tests identify antigens related to these pathogens, thereby confirming past infections and monitoring the host’s immune response. Traditional pathogen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs), are often labor-intensive, slow, and reliant on sophisticated equipment and skilled personnel, which can be limiting in resource-poor settings. In contrast, the development of microfluidic technologies presents a promising alternative, offering automation, miniaturization, and cost efficiency. These advanced methods are poised to replace traditional assays by streamlining processes and enabling rapid, high-throughput immunity testing for pathogens. This review highlights the latest advancements in microfluidic systems designed for rapid and high-throughput immunity testing, incorporating immunosensors, single molecule arrays (Simoas), a lateral flow assay (LFA), and smartphone integration. It focuses on key pathogenic microorganisms such as SARS-CoV-2, influenza, and the ZIKA virus (ZIKV). Additionally, the review discusses the challenges, commercialization prospects, and future directions to advance microfluidic systems for infectious disease detection.

The 6G technology has identified the frequency range of 0.1 to 1 THz as the communication band, with a particular focus on ultrafast modulation and multi-dimensional resolution coding technology. To advance the applications of THz photonics, there is a critical need for high-performance active optoelectronic THz devices. One potential solution involves the utilization of electrically controlled semi-metallic based THz modulators, which can provide suitable modulation depth and a wide modulation bandwidth. In this research, a semi-metallic TiS2 nanofilm device was developed using femtosecond laser direct ablation. The combination of structural effects and TiS2 absorption has significantly improved active modulation. These findings indicate that TiS2-based devices are well-suited for applications in THz photonics.

Abstract Introduction This study evaluated the differences and agreement between a new Scheimpflug camera (Scansys) and a swept-source anterior segment optical coherence tomographer (CASIA 2) for measurements of the anterior segment of the eye in normal subjects. Methods This prospective study included 84 eyes from 84 normal adult subjects who underwent three consecutive measurements with the Scansys and the CASIA 2 in random order. The mean keratometry (Km), astigmatism magnitude (AST), J 0, and J 45 vectors for both anterior and posterior corneal surfaces, central corneal thickness (CCT), thinnest corneal thickness (TCT), and anterior chamber depth (ACD) were obtained by both devices. The difference between these two devices was assessed using paired t test and violin plots. Bland–Altman plots and 95% limits of agreement (LoAs) were used to evaluate agreement. Results No statistically significant differences between the two devices were found for the anterior AST, anterior J 45, and posterior J 45 (P > 0.05). The remaining parameters were statistically significant (P ≤ 0.05), but the differences not clinically significant. The violin plots showed that the distribution and probability density of the measured parameters were similar for both devices. Bland–Altman plots revealed high agreement for the measured parameters between the Scansys and CASIA 2, with narrow 95% LoAs. Conclusions In terms of assessing parameters for the anterior segment, our study indicated that Scansys and CASIA 2 generally showed significant agreement. The two devices used in this study’s assessment of all the parameters can be used interchangeably in refractive analysis.

Abstract The crucial role of interferon (IFN) signaling is well known in the restriction or eradication of pathogen invasion. Viruses take a variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades. However, the way by viruses target IFN-signaling extracellularly has not been discovered. Infection by both coronavirus SARS-CoV-2 and enterovirus 71 (EV71 or EV-A71) can cause severe diseases such as neurological disorders and even death in children.1–3 Here, we show evidence that the protease of SARS-CoV-2 (3CLpro) and EV71 (2Apro) upregulates the expression and secretion of LDL-receptor-related protein-associated protein 1 (LRPAP1). As a ligand, the N-terminus of secreted LRPAP1 binds with the extracellular domain of IFNAR1 that triggers the receptor ubiquitination and degradation and promotes virus infection both in vitro, ex vivo in the mouse brain, and in vivo in newborn mice. A small peptide from the N-terminus of LRPAP1 effectively binds and causes IFNAR1 degradation that enhances both DNA and RNA viral infections, including herpesvirus HSV-1, hepatitis B virus (HBV), EV71, and beta-coronavirus HCoV-OC43; whereas α2M, a LRPAP1 inhibitor, arrests virus infections by stabilizing IFNAR1. Our study demonstrates a new mechanism used by viruses for evading host cell immunity, supporting a strategy for developing pan-antiviral drugs.

The electrochemical reduction of CO2 is an extremely potential technique to achieve the goal of carbon neutrality, but the development of electrocatalysts with high activity, excellent product selectivity, and long-term durability remains a great challenge. Herein, the role of metal-supports interaction (MSI) between different active sites (including single and bimetallic atom sites consisting of Cu and Ni atoms) and carbon-based supports (including C2N, C3N4, N-coordination graphene, and graphdiyne) on catalytic activity, product selectivity, and thermodynamic stability towards CO2 reduction reaction (CRR) is systematically investigated by first principles calculations. Our results show that MSI is mainly related to the charge transfer behavior from metal sites to supports, and different MSI leads to diverse magnetic moments and d-band centers. Subsequently, the adsorption and catalytic performance can be efficiently improved by tuning MSI. Notably, the bimetallic atom supported graphdiyne not only exhibits a better catalytic activity, higher product selectivity, and higher thermodynamic stability, but also effectively inhibits the hydrogen evolution reaction. This finding provides a new research idea and optimization strategy for the rational design of high-efficiency CRR catalysts.

Recycled carbon fibers are primarily utilized as reinforcement in the production of composite materials, and they have steadily become a hot topic in the twenty-first century. However, the presence of large amount of residual resin, crack damage and graphitized surface layer on the surface of recycled carbon fibers leads to the reduction of their mechanical properties. In this study, Cu matrix composites reinforced with carbon fiber were created using the spark plasma sintering process at 700–850 °C sintering temperature. The surface coating treatment was done to recycled carbon fiber in order to enhance the interfacial bonding between the carbon fiber and Cu matrix, and the ideal surface Ag plating parameters were investigated and established. Results have shown that the Ag coating on the fiber surface diffuses at different sintering temperatures, forming a Ag–Cu solid solution, which has a solid solution-strengthening effect on the substrate. When the sintering temperature is below 800 °C, some Ag atoms will precipitate out of the matrix, forming a small amount of Ag precipitation phase. As the sintering temperature increases, the tensile strength of the composite increases and then decreases, the compressive strength gradually decreases and the flexural strength gradually increases.

In this study, Al–7Si–Cu alloys with different contents of Cu were prepared by ultrasonic agitation casting method. The microstructures were characterized by scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS). Dry sliding friction and wear properties with different Cu contents and loads were investigated. The results indicated that the alloy with 3.0 wt% Cu content revealed the optimal microstructure, comprehensive mechanical properties, and tribological properties. The hardness, tensile strength, and yield strength were enhanced by 83%, 57%, and 59%, respectively. The friction coefficient and wear rate reduced by 33% and 24% at 40 N load, respectively. The wear mechanism of Al–7Si–Cu alloy was mainly abrasive wear and delamination wear accompanied by oxidation wear. The improvement of the tribological properties of the alloy was attributed to the combined improvement of the microstructure and mechanical properties.

Abstract Background In the study, we aimed to evaluate the ability of micro‐histology combined with cytology to improve the quality of slides and diagnose endometrial lesions. Methods Endometrial specimens were collected from Li Brushes. Every specimen was prepared for micro‐histological and cytological slides, using cell block (CB) and liquid‐based cytology (LBC) technologies. Semi‐quantitative scoring system was used to evaluate the qualities of slides. CB slides were assessed by 5‐category scoring system. Diagnostic accuracy was calculated in LBC, CB, and LBC + CB groups based on the histological gold standard. Endometrial atypical hyperplasia, and endometrial cancer were considered positive, whereas others were considered negative. Results A total of 167 patients were enrolled. CB slides were inferior to LBC slides only in cellularity (p

Cardiovascular diseases are the most common causes of mortality and disability worldwide. Eicosanoids are a group of bioactive metabolites that are mainly oxidized by arachidonic acid. Eicosanoids play a diverse role in cardiovascular diseases, with some exerting beneficial effects while others have detrimental consequences. However, a causal relationship between eicosanoid levels and cardiovascular disease remains unclear. Six single nucleotide polymorphisms (SNPs) with strong associations with plasma eicosanoid levels were selected. Summary-level data for cardiovascular disease were obtained from publicly available genome-wide association studies. A two-sample MR analysis identified that plasma eicosanoid levels were inversely correlated with unstable angina pectoris (OR 1.06; 95% CI 1–1.12; p = 0.04), myocardial infarction (OR 1.05; 95% CI 1.02–1.09; p = 0.005), ischemia stroke (OR 1.05; 95% CI 1–1.11; p = 0.047), transient ischemic attack (OR 1.03; 95% CI 1–1.07; p = 0.042), heart failure (OR 1.03; 95% CI 1.01–1.05; p = 0.011), and pulmonary embolism (OR 1.08; 95% CI 1.02–1.14; p = 1.69 × 10−6). In conclusion, our data strongly suggest a genetic causal link between high plasma eicosanoid levels and an increased cardiovascular disease risk. This study provides genetic evidence for treating cardiovascular diseases.

Within the fields of infectious disease diagnostics, microfluidic-based integrated technology systems have become a vital technology in enhancing the rapidity, accuracy, and portability of pathogen detection. These systems synergize microfluidic techniques with advanced molecular biology methods, including reverse transcription polymerase chain reaction (RT-PCR), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR), have been successfully used to identify a diverse array of pathogens, including COVID-19, Ebola, Zika, and dengue fever. This review outlines the advances in pathogen detection, attributing them to the integration of microfluidic technology with traditional molecular biology methods and smartphone- and paper-based diagnostic assays. The cutting-edge diagnostic technologies are of critical importance for disease prevention and epidemic surveillance. Looking ahead, research is expected to focus on increasing detection sensitivity, streamlining testing processes, reducing costs, and enhancing the capability for remote data sharing. These improvements aim to achieve broader coverage and quicker response mechanisms, thereby constructing a more robust defense for global public health security.

Abstract The cytidine deaminase, Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B, herein termed A3B), is a critical mutation driver that induces genomic instability in cancer by catalyzing cytosine-to-thymine (C-to-T) conversion and promoting replication stress (RS). However, the detailed function of A3B in RS is not fully determined and it is not known whether the mechanism of A3B action can be exploited for cancer therapy. Here, we conducted an immunoprecipitation-mass spectrometry (IP-MS) study and identified A3B to be a novel binding component of R-loops, which are RNA:DNA hybrid structures. Mechanistically, overexpression of A3B exacerbated RS by promoting R-loop formation and altering the distribution of R-loops in the genome. This was rescued by the R-loop gatekeeper, Ribonuclease H1 (RNASEH1, herein termed RNH1). In addition, a high level of A3B conferred sensitivity to ATR/Chk1 inhibitors (ATRi/Chk1i) in melanoma cells, which was dependent on R-loop status. Together, our results provide novel insights into the mechanistic link between A3B and R-loops in the promotion of RS in cancer. This will inform the development of markers to predict the response of patients to ATRi/Chk1i.

Abstract Background The Hypoxia inducible gene domain family member 2A (HIGD2A) protein is indispensable for the assembly of the mitochondrial respiratory supercomplex, which has been implicated in cell proliferation and cell survival under hypoxic conditions. Because the liver has a naturally low oxygen microenvironment, the role of HIGD2A in the development of hepatocellular carcinoma (HCC) remains largely unknown. Methods Gene expression data and clinical information were obtained from multiple public databases. A lentivirus-mediated gene knockdown approach was conducted to explore the function and mechanism of HIGD2A activity in HCC cells. In vivo and in vitro assays were performed to investigate the biological roles of HIGD2A. Results HIGD2A was overexpressed in HCC tissues and cell lines and was associated with a worse prognosis. Silencing HIGD2A expression significantly attenuated cell proliferation and migration, caused S-phase cell cycle arrest, and decreased tumor formation in nude mice. Mechanistically, HIGD2A depletion greatly decreased cellular ATP levels by disrupting mitochondrial ATP production. Moreover, HIGD2A knockdown cells displayed impaired mitochondrial function, such as mitochondrial fusion, increased expression of the mitochondrial stress response protein, and decreased oxygen consumption. Furthermore, knockdown of HIGD2A markedly attenuated the activation of the MAPK/ERK pathway. Conclusions HIGD2A promoted liver cancer cell growth by fueling mitochondrial ATP synthesis and activating the MAPK/ERK pathway, suggested that targeting HIGD2A may represent a new strategy for HCC therapy.

When installed in deep tunnel systems, the cover of the vortex dropshaft may be partially or fully sealed. With air exchange restricted through the cover, the air supply to the dropshaft through the inflow channel might not be adequate. Hence, further investigation is required to examine the effect of the restricted air passage through the cover on the flow regimes and hydraulic performance of the scroll vortex dropshaft. This study aims to quantify the head-discharge relationship, air-water distribution, and minimum air core size with different cover opening conditions. The 3D model of a fully open scroll vortex dropshaft is constructed, and numerical simulations are carried out and validated using experiment data. The results show that the effect is generally small when the ratio of the opening and dropshaft area is larger than 1%. When the cover is fully sealed, the minimum air core size reduces by ~5% of the dropshaft area which can have a serious implication to the design of the scroll vortex dropshaft. The present study provides a practical evaluation of the effect of the opening condition in the cover of the vortex chamber on the performance of scroll vortex dropshafts for underground water drainage systems..

A quantitative structure-activity relationship (QSAR) study was conducted to predict the anti-colon cancer and HDAC inhibition of triazole-containing compounds. Four descriptors were selected from 579 descriptors which have the most obvious effect on the inhibition of histone deacetylase (HDAC). Four QSAR models were constructed using heuristic algorithm (HM), random forest (RF), radial basis kernel function support vector machine (RBF-SVM) and support vector machine optimized by particle swarm optimization (PSO-SVM). Furthermore, the robustness of four QSAR models were verified by K-fold cross-validation method, which was described by Q2. In addition, the R2 of the four models are greater than 0.8, which indicates that the four descriptors selected are reasonable. Among the four models, model based on PSO-SVM method has the best prediction ability and robustness with R2 of 0.954, root mean squared error (RMSE) of 0.019 and Q2 of 0.916 for the training set and R2 of 0.965, RMSE of 0.017 and Q2 of 0.907 for the test set. In this study, four key descriptors were discovered, which will help to screen effective new anti-colon cancer drugs in the future.

BackgroundUsual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia that is caused by different etiologies. This study aimed to investigate the transplant-free survival (TFS) and the decline in forced vital capacity (FVC) of the patients with UIP and probable UIP patterns on CT caused by various underlying conditions.MethodsA retrospective cohort study was conducted, enrolling patients with interstitial lung disease exhibiting a CT pattern consistent with UIP or probable UIP. Clinical and prognostic data of patients categorized by the etiology were compared.ResultsA total of 591 patients were included and classified into the following groups: idiopathic pulmonary fibrosis (IPF) (n = 320), connective tissue disease (CTD)-UIP (n = 229), asbestosis-UIP (n = 28), and hypersensitivity pneumonitis (HP)-UIP (n = 14). Advanced age, elevated levels of serum cytokeratin fraction 21-1 and percentage of neutrophils in bronchoalveolar lavage were observed in all groups. IPF patients showed a more rapid decline in FVC (133.9 mL/year) compared to CTD-UIP (24.5 mL/year, p = 0.001) and asbestosis-UIP (61.0 mL/year, p = 0.008) respectively. Sub-analysis of CTD-UIP revealed that patients with rheumatoid arthritis (RA)-UIP (88.1 mL/year) or antineutrophil cytoplasmic antibody-associated vasculitis (AAV)-UIP (72.9 mL/year) experienced a faster deterioration in FVC compared to those with primary Sjögren’s syndrome (pSS)-UIP (25.9 mL/year, p

To determine whether existing exercise therapies can restore the joint position sense (JPS) deficits of patients with chronic ankle instability (CAI) when compared with controlled non-training patients. Seven databases were searched using ankle, injury, proprioception, and exercise-therapy-related terms. Peer-reviewed human studies in English that used the absolute errors score of joint position reproduction (JPR) test to compare the JPS of injured ankles in CAI patients before and after exercise therapy and non-training controls were included and analyzed. Demographic information, sample size, description of exercise therapies, methodological details of the JPR test, and absolute error scores were extracted by two researchers independently. Meta-analysis of the differences in JPS changes (i.e., absolute errors after treatment minus the baseline) between the exercise therapies and non-training controls was performed with the weighted mean difference (WMD) and 95% confidence interval (CI). Seven studies were finally included. Meta-analyses revealed significantly higher improvements in passive JPS during inversion with, WMD ​= ​−1.54° and eversion, of, WMD ​= ​−1.80°, after exercise therapies when compared with non-training controls. However, no significant changes in the impaired side active JPS were observed with regard to inversion and eversion. Existing exercise therapies may have a positive effect on passive JPS during inversion and eversion, but do not restore the active JPS deficits of injured ankles in patients with CAI when compared with non-training controls. Updated exercise components with a longer duration that focus on active JPS with longer duration are needed to supplement the existing content of exercise therapies.

Abstract Background To assess agreement of measurements between a new optical low coherence reflectometry (OLCR) biometer (SW-9000, Suoer, Tianjin, China) and a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in healthy subjects. Methods A total of 66 right eyes from 66 healthy subjects were enrolled in this prospective study. Three consecutive measurements were randomly obtained with both devices by the same experienced operator to assess agreement. Bland-Altman plots and 95% limits of agreement (LoA) were used to verify the agreement between the devices. Results are presented as mean ± standard deviation (SD). Results The SD-OCT/Placido tomographer showed high agreement with the OLCR biometer for all parameters included in this study. The mean differences of central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), mean keratometry (Km) and corneal diameter (CD) were 2.21 ± 2.67 μm (P

Background: Our study aimed to investigate the association between multimorbidity and the cognitive decline related functional limitations. Methods: Data were obtained from the 2011–2018 China Health and Retirement Longitudinal Study, and generalized estimating equation models were used for estimation. A Chinese multimorbidity-weighted index (CMWI) was used to quantify the cumulative disease burden of multimorbidity. A margin plot was used to show the probability of functional limitations by global cognitive function and CMWI. Then, subgroup analysis was performed by demographic factors, the severity of functionally impaired ADL/IADL, and the trajectories of cognitive function. Results: Multimorbidity was demonstrated to be associated cognitive decline related functional limitations over 8 years, with the coefficient of the interaction of cognitive function −0.001 (−0.001, −0.001). This moderating effect was only significant in the relationship between cognitive function and ≥2-item impaired ADL/IADL (coefficient = −0.008, 95% CI: 0.009, −0.007) but was not significant in the relationship between cognitive function and 1-item impaired ADL/IADL. The accelerated role of multimorbidity associated with more severe function limitations than the relatively mild limitations attributed to cognitive decline, and the role of multimorbidity was stronger in individuals with continuously high function of cognitive trajectories and gradually declining cognitive function than in those with low level of cognitive trajectories. Conclusions: Effectively managing multimorbidity is important for preventing cognitive decline. Preventing the onset and progression of multimorbidity may be one potential strategy for early prevention and intervention to reverse or postpone cognitive decline and its further dementia risk.

A rational investor always pursues a portfolio with the greatest possible return and the least possible risk. Therefore, a core issue of investment decision analysis is how to make an optimal investment choice in the market with fuzzy information and realize the balance between maximizing the return on assets and minimizing the risk. In order to find optimal investment portfolios of financial assets with high volatility, such as gold and Bitcoin, a mathematical model for formulating investment strategies based on the long short-term memory time series and the dynamic programming model combined with the greedy algorithm has been proposed in this paper. The model provides the optimal daily strategy for the five-year trading period so that it can achieve the maximum expected return every day under the condition of a certain investment amount and a certain risk. In addition, a reasonable risk measure based on historical increases is established while considering the weights brought by different investment preferences. The empirical analysis results show that the optimal total assets and initial capital obtained by the model change in the same proportion, and the model is relatively stable and has strong adaptability to the initial capital. Therefore, the proposed model has practical reference value and research significance for investors and promotes a better combination of computer technology and financial investment decision.

Abstract Purpose To systematically compare and rank ocular measurements with optical and ultrasound biometers based on big data. Methods PubMed, Embase, the Cochrane Library and the US trial registry ( www.ClinicalTrial.gov ) were used to systematically search trials published up to October 22nd, 2020. We included comparative studies reporting the following parameters measured by at least two devices: axial length (AL), flattest meridian keratometry (Kf), steepest meridian keratometry (Ks), mean keratometry (Km), astigmatism (AST), astigmatism vectors J0 and J45, anterior chamber depth (ACD), aqueous depth (AQD), central corneal thickness (CCT), corneal diameter (CD) and lens thickness (LT). A network-based big data analysis was conducted using STATA version 13.1. Results Across 129 studies involving 17,181 eyes, 12 optical biometers and two ultrasound biometers (with both contact and immersion techniques) were identified. A network meta-analysis for AL and ACD measurements found that statistically significant differences existed when contact ultrasound biometry was compared with the optical biometers. There were no statistically significant differences among the four swept-source optical coherence tomography (SS-OCT) based devices (IOLMaster 700, OA-2000, Argos and ANTERION). As for Ks, Km and CD, statistically significant differences were found when the Pentacam AXL was compared with the IOLMaster and IOLMaster 500. There were statistically significant differences for CCT when the OA-2000 was compared to Pentacam AXL, IOLMaster 700, Lenstar, AL-Scan and Galilei G6. Conclusion For AL and ACD, contact ultrasound biometry obtains the lower values compared with optical biometers. The Pentacam AXL achieves the lowest values for keratometry and CD. The smallest value for CCT measurement is found with the OA-2000.

The mesic-origin species Robinia pseudoacacia L. (black locust) is widely planted in the semiarid and sub-humid areas of the Loess Plateau for the reforestation of vegetation-degraded land. Under the scenario of changing precipitation patterns, exploring the response of photosynthesis to drought allows us to assess the risk to sustainable development of these plantations. In this study, paired plots were established including the control and a treatment of 30% exclusion of throughfall (since 2018). The photosynthetic characteristics were investigated using a portable photosynthesis system for four periods in the full-leaf growing season of 2021–2022, the fourth and fifth years, on both treated and controlled sampling trees. Leaf gas exchange parameters derived from diurnal changing patterns, light response curves, and CO2 response curves showed significant differences except for period II (9–11 September 2021) between the two plots. The photosynthetic midday depression was observed in 2022 in the treated plot. Meanwhile, the decline of net photosynthetic rate in the treated plot was converted from stomatal limitation to non-stomatal limitation. Furthermore, we observed that black locust adapted to long-term water deficiency by reducing stomatal conductance, increasing water use efficiency and intrinsic water use efficiency. The results demonstrate that reduction in precipitation would cause photosynthesis decrease, weaken the response sensitivity to light and CO2, and potentially impair photosynthetic resilience of the plantations. They also provide insights into the changes in photosynthetic functions under global climate change and a reference for management of plantations.

The molecular structure models of asphalt binder, ethanol additive, and ethanol-based foamed asphalt were constructed through the Molecular Dynamics (MD) method. The standard ethanol-based foamed asphalt model was employed to describe the modifier with its different compositions, including 10%, 20%, and 30% ethanol. The simulation calculations were done for the ethanol-based foamed asphalt molecular models under the NPT and NVT ensembles. The density, glass transition temperature, and radial distribution function of ethanol-based foamed asphalt molecular models were obtained to verify the rationalization of asphalt models and analyze the variation of density parameters with temperature and ethanol content for ethanol-based foamed asphalt molecular models. The results show that the simulated densities of the asphalt binder and three ethanol-based foamed asphalt molecular models remained constant with the increase of simulation steps. The simulated density values of basic and 10%-ethanol-based foamed asphalt molecular models are close to 0.9 g cm ^−3 . The simulated densities of 20%-ethanol-based and 30%-ethanol-based foamed asphalt molecular models were 0.8 g cm ^−3 and 0.75 g cm ^−3 . Meanwhile, the simulated density values of both asphalt binder and all ethanol-based foamed asphalt decreased with the increase in temperature and ethanol additive dosage. The glass transition temperatures of basic asphalt binder, 10%-ethanol-based, 20%-ethanol-based, and 30%-ethanol-based foamed asphalt occurred in the range of 275–295 K, 330–350 K, 330–350 K, and 320–340 K, respectively. In contrast, the glass transition temperature of ethanol-based foamed asphalt increased with the increase of ethanol additive dosage, indicating that adding ethanol additive significantly improved the high-temperature resistance of matrix asphalt. In the radial distribution function diagrams of all samples, the first strong peak appeared at 0.85–1.3 Å, and the second strong peak appeared at 1.95–2.35 Å. Moreover, both peaks increased with the increase of ethanol additive dosage, suggesting that the contact between ethanol molecules and asphalt molecules was closer with the rise of ethanol additive dosage.

Microwave intermittent drying was carried out on newly harvested corn kernels to study the effects of different microwave intermittent powers (900 W, 1800 W, 2700 W, and 3600 W) on the structural and functional properties of zein in corn kernels. The results showed that microwave drying could increase the thermal stability of zein in corn kernels. The solubility, emulsification activity index, and surface hydrophobicity increased under 1800 W drying power, which was due to the unfolding of the molecular structure caused by the increase in the content of irregular structure and the decrease in the value of particle size. At a drying power of 2700 W, there was a significant increase in grain size values and β-sheet structure. This proves that at this time, the corn proteins in the kernels were subjected to the thermal effect generated by the higher microwave power, which simultaneously caused cross-linking and aggregation within the proteins to form molecular aggregates. The solubility, surface hydrophobicity, and other functional properties were reduced, while the emulsification stability was enhanced by the aggregates. The results of the study can provide a reference for the in-depth study of intermittent corn microwave drying on a wide range of applications of zein in corn kernels.