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Abstract Background Cognitive fusion MRI-guided targeted biopsy (cTB) has been widely used in the diagnosis of prostate cancer (PCa). However, cTB relies heavily on the operator’s experience and confidence in MRI readings. Our objective was to compare the cancer detection rates of MRI artificial intelligence-guided cTB (AI-cTB) and routine cTB and explore the added value of using AI for the guidance of cTB. Methods This was a prospective, single-institution randomized controlled trial (RCT) comparing clinically significant PCa (csPCa) and PCa detection rates between AI-cTB and cTB. A total of 380 eligible patients were randomized to the AI-cTB group (n = 191) or the cTB group (n = 189). The AI-cTB group underwent AI-cTB plus systematic biopsy (SB) and the cTB group underwent routine cTB plus SB. The primary outcome was the detection rate of csPCa. The reference standard was the pathological results of the combination of TB (AI-cTB/cTB) and SB. Comparisons of detection rates of csPCa and PCa between groups were performed using the chi-square test or Fisher’s exact test. Results The overall csPCa and PCa detection rates of the whole inclusion cohort were 58.8% and 61.3%, respectively. The csPCa detection rates of TB combined with SB in the AI-cTB group were significantly greater than those in the cTB group at both the patient level (58.64% vs. 46.56%, p = 0.018) and per-lesion level (61.47% vs. 47.79%, p = 0.004). Compared with cTB, the AI-cTB could detect a greater proportion of patients with csPCa at both the per-patient level (69.39% vs. 49.71%, p

Abstract Multi‐organ segmentation from abdominal CT scans is crucial for various medical examinations and diagnoses. Despite the remarkable achievements of existing deep‐learning‐based methods, accurately segmenting small organs remains challenging due to their small size and low contrast. This article introduces a novel knowledge‐guided cascaded framework that utilizes two types of knowledge—image intrinsic (anatomy) and clinical expertise (radiology)—to improve the segmentation accuracy of small abdominal organs. Specifically, based on the anatomical similarities in abdominal CT scans, the approach employs entropy‐based registration techniques to map high‐quality segmentation results onto inaccurate results from the first stage, thereby guiding precise localization of small organs. Additionally, inspired by the practice of annotating images from multiple perspectives by radiologists, novel Multi‐View Fusion Convolution (MVFC) operator is developed, which can extract and adaptively fuse features from various directions of CT images to refine segmentation of small organs effectively. Simultaneously, the MVFC operator offers a seamless alternative to conventional convolutions within diverse model architectures. Extensive experiments on the Abdominal Multi‐Organ Segmentation (AMOS) dataset demonstrate the superiority of the method, setting a new benchmark in the segmentation of small organs.

Abstract Background Influenza outbreaks have occurred frequently these years, especially in the summer of 2022 when the number of influenza cases in southern provinces of China increased abnormally. However, the exact evidence of the driving factors involved in the prodrome period is unclear, posing great difficulties for early and accurate prediction in practical work. Methods In order to avoid the serious interference of strict prevention and control measures on the analysis of influenza influencing factors during the COVID-19 epidemic period, only the impact of meteorological and air quality factors on influenza A (H3N2) in Xiamen during the non coronavirus disease 2019 (COVID-19) period (2013/01/01-202/01/24) was analyzed using the distribution lag non-linear model. Phylogenetic analysis of influenza A (H3N2) during 2013–2022 was also performed. Influenza A (H3N2) was predicted through a random forest and long short-term memory (RF-LSTM) model via actual and forecasted meteorological and influenza A (H3N2) values. Results Twenty nine thousand four hundred thirty five influenza cases were reported in 2022, accounting for 58.54% of the total cases during 2013–2022. A (H3N2) dominated the 2022 summer epidemic season, accounting for 95.60%. The influenza cases in the summer of 2022 accounted for 83.72% of the year and 49.02% of all influenza reported from 2013 to 2022. Among them, the A (H3N2) cases in the summer of 2022 accounted for 83.90% of all A (H3N2) reported from 2013 to 2022. Daily precipitation(20–50 mm), relative humidity (70–78%), low (≤ 3 h) and high (≥ 7 h) sunshine duration, air temperature (≤ 21 °C) and O3 concentration (≤ 30 µg/m3, > 85 µg/m3) had significant cumulative effects on influenza A (H3N2) during the non-COVID-19 period. The daily values of PRE, RHU, SSD, and TEM in the prodrome period of the abnormal influenza A (H3N2) epidemic (19–22 weeks) in the summer of 2022 were significantly different from the average values of the same period from 2013 to 2019 (P

Abstract Introduction Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. Methods RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. Results CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. Conclusion Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.

Objective To explore the intervention effect of health education based on the concept of Oren's self-care theory in elderly patients with acute ischemic stroke. Methods A total of 138 elderly acute ischemic stroke patients admitted to Handan Central Hospital from November 2021 to November 2023 were selected and randomly separated into two groups using a random number table method, each had 69 cases. The control group received routine health education, while the research group received health education based on the concept of Oren's self-care theory on the top of control group. Rehabilitation compliance, self-care ability, limb function, 10-meter walk test (10MWT), Timed up and go test (TUGT), healthy behavior, and self-care ability were compared between two groups. Results The compliance rate of research group was higher than that in control group (P

Abstract Background and objective The value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA. Methods The data derived from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA. Results In the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P

The recent mpox outbreak (in 2022–2023) has different clinical and epidemiological features compared with previous outbreaks of the disease. During this outbreak, sexual contact was believed to be the primary transmission route of the disease. In addition, the community of men having sex with men (MSM) was disproportionately affected by the outbreak. This population is also disproportionately affected by HIV infection. Given that both diseases can be transmitted sexually, the endemicity of HIV, and the high sexual behavior associated with the MSM community, it is essential to understand the effect of the two diseases spreading simultaneously in an MSM population. Particularly, we aim to understand the potential effects of HIV on an mpox outbreak in the MSM population. We develop a mechanistic mathematical model of HIV and mpox co-infection. Our model incorporates the dynamics of both diseases and considers HIV treatment with anti-retroviral therapy (ART). In addition, we consider a potential scenario where HIV infection increases susceptibility to mpox, and investigate the potential impact of this mechanism on mpox dynamics. Our analysis shows that HIV can facilitate the spread of mpox in an MSM population, and that HIV treatment with ART may not be sufficient to control the spread of mpox in the population. However, we showed that a moderate use of condoms or reduction in sexual contact in the population combined with ART is beneficial in controlling mpox transmission. Based on our analysis, it is evident that effective control of HIV, specifically through substantial ART use, moderate condom compliance, and reduction in sexual contact, is imperative for curtailing the transmission of mpox in an MSM population and mitigating the compounding impact of these intertwined epidemics.

AbstractContext Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear.Objective We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles.Materials and methods Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days’ administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed.Results 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%).Discussion and conclusion The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.

Lipopolysaccharide (LPS) plays an important role in Raw264.7 macrophage ferroptosis and inflammation. Purine-rich element-binding protein B (Purb) influences cellular processes by regulating gene expression as a transcription factor. However, the effect and molecular mechanism of Purb in regulating Raw264.7 macrophage ferroptosis is still unknown. In this study, we used malondialdehyde, glutathione (GSH) assays, Fe2+ fluorescence, reactive oxygen species staining, and western blotting to determine the effect of Purb on LPS-induced Raw264.7 macrophage ferroptosis. Pharmacological inhibitor of ferroptosis was utilized to explore its potential effects for inflammation by reverse transcription-quantitative polymerase chain reaction analysis. Meanwhile, chromatin immunoprecipitation was performed to verify the binding of Purb and the GSH-dependent peroxidase 4 (Gpx4). The results showed that LPS-induced inflammation in Raw264.7 macrophages was inhibited by ferroptosis inhibitor Fer-1 treatment. LPS inhibited the expression of Purb in Raw264.7 macrophages. In addition, Purb overexpression relieved the ferroptosis, and inflammatory response of Raw264.7 macrophages induced by LPS. Mechanistically, the binding of Purb to the Gpx4 promoter was decreased after LPS stimulation. Therefore, we concluded for the first time that Purb played a critical role in LPS-induced ferroptosis and inflammatory response by regulating the transcription of Gpx4. These results provide a theoretical basis for further research on the macrophage ferroptosis and inflammation.

Abstract Objective At different times, public health faces various challenges and the degree of intervention measures varies. The research on the impact and prediction of meteorology factors on influenza is increasing gradually, however, there is currently no evidence on whether its research results are affected by different periods. This study aims to provide limited evidence to reveal this issue. Methods Daily data on influencing factors and influenza in Xiamen were divided into three parts: overall period (phase AB), non-COVID-19 epidemic period (phase A), and COVID-19 epidemic period (phase B). The association between influencing factors and influenza was analysed using generalized additive models (GAMs). The excess risk (ER) was used to represent the percentage change in influenza as the interquartile interval (IQR) of meteorology factors increases. The 7-day average daily influenza cases were predicted using the combination of bi-directional long short memory (Bi-LSTM) and random forest (RF) through multi-step rolling input of the daily multifactor values of the previous 7-day. Results In periods A and AB, air temperature below 22 °C was a risk factor for influenza. However, in phase B, temperature showed a U-shaped effect on it. Relative humidity had a more significant cumulative effect on influenza in phase AB than in phase A (peak: accumulate 14d, AB: ER = 281.54, 95% CI = 245.47 ~ 321.37; A: ER = 120.48, 95% CI = 100.37 ~ 142.60). Compared to other age groups, children aged 4–12 were more affected by pressure, precipitation, sunshine, and day light, while those aged ≥ 13 were more affected by the accumulation of humidity over multiple days. The accuracy of predicting influenza was highest in phase A and lowest in phase B. Conclusions The varying degrees of intervention measures adopted during different phases led to significant differences in the impact of meteorology factors on influenza and in the influenza prediction. In association studies of respiratory infectious diseases, especially influenza, and environmental factors, it is advisable to exclude periods with more external interventions to reduce interference with environmental factors and influenza related research, or to refine the model to accommodate the alterations brought about by intervention measures. In addition, the RF-Bi-LSTM model has good predictive performance for influenza.

Abstract Background The efficacy of dapagliflozin in patients with acute heart failure remains unclear. Objective To investigate the impact of dapagliflozin (DAPA) on loop diuretics use and 90-day readmission in patients with acute heart failure. Methods In a retrospective cohort study, patients diagnosed with acute heart failure or chronic heart failure with acute exacerbation admitted to Fuyang People’s Hospital from January 2021 to April 2023, this study used DAPA (at a dose of 10 mg once daily) in combination with standard treatment. The patients were divided into DAPA group and DAPA-Free group based on whether they used DAPA in acute heart failure. To minimize the influence of confounding factors and ensure comparability between groups, we used propensity score matching (PSM). Results A total of 399 patients were included, with 206 patients (51.63%) in the DAPA group and 193 patients (48.37%) in the DAPA-Free group. PSM produced 160 pairs. After PSM, there were no statistically significant differences between the DAPA and DAPA-Free groups in terms of readmission of all causes (16.88% vs. 18.12%, OR 0.9141, 95% CI 0.5385–1.552, log rank P = 0.739) or readmission for heart failure (11.88% vs. 15.0%, OR 0.9077, 95% CI 0.4441–1.469, log rank P = 0.484) after 90-day follow-up. Patients in the DAPA group had a lower mean daily dose of intravenous loop diuretics compared to the DAPA-Free group (20 mg/d vs. 30.00 mg/d, P

Objective: Endoscopic injection is one of the simplest minimally invasive methods for the treatment of gastroesophageal diseases. However, the safety of injection material limits its clinical application. We investigated the feasibility, safety and efficacy of endoscopic autogenous fat transplantation (EAFT) in the lower part of esophagus in the treatment of gastroesophageal reflux disease in New Zealand albino rabbits. Methods: Eight New Zealand albino rabbits were used for autogenous fat transplantation. The dynamic pH value of the lower esophagus was monitored before and one week after fat transplantation in two rabbits. The local retention of fat was observed by endoscopy, and the pathological analysis was made at the junction of esophagus and stomach after two weeks of fat transplantation in six albino rabbits. During the experiment, the weight, dietary habit and infection of albino rabbits were monitored. Results: Endoscopic autogenous fat transplantation of the lower esophagus was successfully performed in 8 albino rabbits. The average pH value of the esophagus increased from 5.6 to 7.5 and 7.4 to 7.9, respectively in two rabbits one week after transplantation. The fat barrier of the lower esophagus was remained locally and observed by endoscopy two weeks after transplantation in six rabbits. Pathology showed that the adipocytes survived in the submucosa with neovascularization. No complications of bleeding, perforation and infection occurred. All albino rabbits kept normal dietary habit. No significant changes in weight were observed. Conclusion: Endoscopic autogenous fat transplantation in lower esophagus is considered as a safe and feasible method by preliminary animal experiments, which can provide a new option in the treatment of gastroesophageal reflux disease (GERD) and is worth further study.

Objective To investigate the relationship between serum miR-340-5p and stimulator of interferon gene (STING) levels in elderly patients with acute ischemic stroke and their condition and prognosis. Methods A total of 113 elderly patients with acute ischemic stroke admitted to Handan Central Hospital from May 2020 to May 2022 were selected as the study group, and 113 normal healthy patients during the same period were selected as the control group, according to the neurological impairment was assessed according to the National Institutes of Health Stroke Scale (NIHSS) score on the day of admission (< 6 scores as mild, 6- moderate > mild (P

Abstract Background Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). Methods The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). Results The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. Conclusions These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

Setting time as the fourth dimension, 4D printing allows us to construct dynamic structures that can change their shape, property, or functionality over time under stimuli, leading to a wave of innovations in various fields. Recently, 4D printing of smart biomaterials, biological components, and living cells into dynamic living 3D constructs with 4D effects has led to an exciting field of 4D bioprinting. 4D bioprinting has gained increasing attention and is being applied to create programmed and dynamic cell-laden constructs such as bone, cartilage, and vasculature. This review presents an overview on 4D bioprinting for engineering dynamic tissues and organs, followed by a discussion on the approaches, bioprinting technologies, smart biomaterials and smart design, bioink requirements, and applications. While much progress has been achieved, 4D bioprinting as a complex process is facing challenges that need to be addressed by transdisciplinary strategies to unleash the full potential of this advanced biofabrication technology. Finally, we present future perspectives on the rapidly evolving field of 4D bioprinting, in view of its potential, increasingly important roles in the development of advanced dynamic tissues for basic research, pharmaceutics, and regenerative medicine.

Abstract Objectives To develop and validate a deep learning (DL) model for automated segmentation of hepatic and portal veins, and apply the model in blood-free future liver remnant (FLR) assessments via CT before major hepatectomy. Methods 3-dimensional 3D U-Net models were developed for the automatic segmentation of hepatic veins and portal veins on contrast-enhanced CT images. A total of 170 patients treated from January 2018 to March 2019 were included. 3D U-Net models were trained and tested under various liver conditions. The Dice similarity coefficient (DSC) and volumetric similarity (VS) were used to evaluate the segmentation accuracy. The use of quantitative volumetry for evaluating resection was compared between blood-filled and blood-free settings and between manual and automated segmentation. Results The DSC values in the test dataset for hepatic veins and portal veins were 0.66 ± 0.08 (95% CI: (0.65, 0.68)) and 0.67 ± 0.07 (95% CI: (0.66, 0.69)), the VS values were 0.80 ± 0.10 (95% CI: (0.79, 0.84)) and 0.74 ± 0.08 (95% CI: (0.73, 0.76)), respectively No significant differences in FLR, FLR% assessments, or the percentage of major hepatectomy patients were noted between the blood-filled and blood-free settings (p = 0.67, 0.59 and 0.99 for manual methods, p = 0.66, 0.99 and 0.99 for automated methods, respectively) according to the use of manual and automated segmentation methods. Conclusion Fully automated segmentation of hepatic veins and portal veins and FLR assessment via blood-free CT before major hepatectomy are accurate and applicable in clinical cases involving the use of DL. Critical relevance statement Our fully automatic models could segment hepatic veins, portal veins, and future liver remnant in blood-free setting on CT images before major hepatectomy with reliable outcomes. Key Points Fully automatic segmentation of hepatic veins and portal veins was feasible in clinical practice. Fully automatic volumetry of future liver remnant (FLR)% in a blood-free setting was robust. No significant differences in FLR% assessments were noted between the blood-filled and blood-free settings. Graphical Abstract

Abstract Microbes are extensively present among various cancer tissues and play critical roles in carcinogenesis and treatment responses. However, the underlying relationships between intratumoral microbes and tumors remain poorly understood. Here, a MIcrobial Cancer‐association Analysis using a Heterogeneous graph transformer (MICAH) to identify intratumoral cancer‐associated microbial communities is presented. MICAH integrates metabolic and phylogenetic relationships among microbes into a heterogeneous graph representation. It uses a graph transformer to holistically capture relationships between intratumoral microbes and cancer tissues, which improves the explainability of the associations between identified microbial communities and cancers. MICAH is applied to intratumoral bacterial data across 5 cancer types and 5 fungi datasets, and its generalizability and reproducibility are demonstrated. After experimentally testing a representative observation using a mouse model of tumor‐microbe‐immune interactions, a result consistent with MICAH's identified relationship is observed. Source tracking analysis reveals that the primary known contributor to a cancer‐associated microbial community is the organs affected by the type of cancer. Overall, this graph neural network framework refines the number of microbes that can be used for follow‐up experimental validation from thousands to tens, thereby helping to accelerate the understanding of the relationship between tumors and intratumoral microbiomes.

Background Unveiling pro‐proliferation genes involved in crosstalk between pulmonary artery endothelial cells and pulmonary artery smooth muscle cells (PASMCs) are important to improving the therapeutic outcome of pulmonary hypertension (PH). Although growing studies have shown that super‐enhancers (SEs) play a pivotal role in pathological and physiological processes, the SE‐associated genes in PH and their impact on PASMC proliferation remain largely unexplored. Methods and Results We used serotype 5 adenovirus‐associated virus to interfere with syndecan‐4 and constructed an SU5416 combined with hypoxia–PH model. Chromatin immunoprecipitation sequencing analysis, chromatin immunoprecipitation quantitative polymerase chain reaction, and bioinformatics were used to confirm early growth response 1 was involved in regulating syndecan‐4‐associated SE in PASMCs. The effects of syndecan‐4 and its underlying mechanisms were subsequently elucidated using Western blot, coimmunoprecipitation, and cell coculture assays. Herein, we identified a novel SE‐associated gene, syndecan‐4, in hypoxia‐exposed PASMCs. Syndecan‐4 was transcriptionally driven by early growth response 1 via an SE and was significantly overexpressed in hypoxic PASMCs and plasma from patients with PH. Mechanism studies revealed that syndecan‐4 induces PASMC proliferation by interacting and regulating protein kinase C α ubiquitination. In addition, syndecan‐4 was enriched in exosomes secreted from hypoxic PASMCs, which subsequently transported and led to pulmonary artery endothelial cell dysfunction. Syndecan‐4 inhibition in hypoxia by serotype 5 adenovirus‐associated virus treatment attenuated the pulmonary artery remodeling and development of PH in vivo. Conclusions Taken together, our results demonstrate that an SE‐driven syndecan‐4 modulates crosstalk of PASMCs and pulmonary artery endothelial cells and promotes vascular remodeling via the protein kinase C α and exosome pathway, thus providing potential targets for the early diagnosis and treatment of hypoxic PH.

Purpose: To evaluate incision-related astigmatism (IRA) on the anterior and total cornea after implantable collamer lens (ICL) implantation through superior and temporal corneal incisions. Methods: The retrospective study included 141 eyes of 80 consecutive patients who underwent ICL implantation. An ocular examination was performed preoperatively and at 1 and 6 months postoperatively. The magnitude and axis of corneal astigmatism were assessed with keratometry (AstigK) and total corneal refractive power (TCRP, AstigTCRP) using a Scheimpflug camera, while the IRA obtained from keratometry (IRAK) and TCRP (IRATCRP) were evaluated using vector analysis. Results: At 6 months, AstigK significantly decreased from 1.45 ± 0.72 D to 1.15 ± 0.75 D in the superior incision group, whereas it increased from 1.70 ± 0.74 D to 1.88 ± 0.79 D in the temporal incision group (both P < 0.001). AstigTCRP significantly decreased from 1.32 ± 0.74 D to 1.09 ± 0.80 D in the superior incision group, while it increased from 1.61 ± 0.78 D to 1.83 ± 0.86 D in the temporal incision group (both P < 0.001). IRAK was 0.55 ± 0.30 D and 0.35 ± 0.25 D in the superior and temporal incision groups, respectively, while IRATCRP was 0.50 ± 0.28 D and 0.40 ± 0.26 D in the superior and temporal incision groups, respectively. IRAK was larger in the superior incision group than in the temporal incision group for both low- (P = 0.009) and high-astigmatism (P = 0.017). Conclusions: Incisions in ICL surgery cause corneal flattening in the meridian of the incision. The superior incision had a greater IRAK compared to the temporal incision.

Animals guide their behaviors through internal representations of the world in the brain. We aimed to understand how the macaque brain stores such general world knowledge, focusing on object color knowledge. Three functional magnetic resonance imaging (fMRI) experiments were conducted in macaque monkeys: viewing chromatic and achromatic gratings, viewing grayscale images of their familiar fruits and vegetables (e.g., grayscale strawberry), and viewing true- and false-colored objects (e.g., red strawberry and green strawberry). We observed robust object knowledge representations in the color patches, especially the one located around TEO: the activity patterns could classify grayscale pictures of objects based on their memory color and response patterns in these regions could translate between chromatic grating viewing and grayscale object viewing (e.g., red grating-grayscale images of strawberry), such that classifiers trained by viewing chromatic gratings could successfully classify grayscale object images according to their memory colors. Our results showed direct positive evidence of object color memory in macaque monkeys. These results indicate the perceptually grounded knowledge representation as a conservative memory mechanism and open a new avenue to study this particular (semantic) memory representation with macaque models.

IntroductionAconiti Lateralis Radix Praeparata (lateral roots of Aconitum carmichaelii Debeaux, Fuzi), is commonly used to treat various cardiovascular diseases, particularly heart failure. However, its strong cardiotoxicity limits its clinical applicability. Glycyrrhizae radix et rhizoma, (the root of Glycyrrhiza uralensis Fisch., Gancao), is known to synergistically increase the cardiotonic effects of Fuzi and alleviate the myocardial injury caused by Fuzi to some extent. However, the detailed mechanism via which the combination of Fuzi and Gancao reduces toxicity and increases or preserves the efficacy of Fuzi requires further investigation.MethodsOxidative stress injury models in H9C2 cells and mice with acute heart failure were established to evaluate the optimal synergistic protective concentration of Fuziline and Glycyrrhetinic acid (GA). A GA probe was then synthesized and used for target fishing using chemical and biological methods. Finally, the target and its function were verified using fluorescence co-localization, Western blotting, protein interaction analysis, molecular docking, and calcium ion imaging.ResultsThe best pharmacodynamic potential was achieved with a 1:1 or 2:1 ratio of Fuziline and GA concentrations. At these ratios, they regulated the protein levels of the downstream players of the Ca2+ signaling pathway via MDH2 and CALR, thereby balancing Ca2+ homeostasis in the myocardial tissue and mitigating the effects of heart failure.ConclusionThis study aimed to investigate the compatibility of Fuziline and GA, the active metabolites of a traditional Chinese medicine (TCM) pair, in exerting their cardiac effects, identify the direct biological targets and verify the mechanism of compatibility.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges. Conventional strategies always exhibit the insufficiencies in overall coverage, analytical efficiency, and degree of automation, and the results highly rely on the personal knowledge and experience. The goal of this work was to establish a software-aided approach, by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) and in-house high-definition MS2 library, to enhance the identification of prototypes and metabolites of the compound formulae in vivo, taking Sishen formula (SSF) as a template. Seven different MS2 acquisition methods were compared, which demonstrated the potency of a hybrid scan approach (namely high-definition data-independent/data-dependent acquisition (HDDIDDA)) in the identification precision, MS1 coverage, and MS2 spectra quality. The HDDIDDA data for 55 reference compounds, four component drugs, and SSF, together with the rat bio-samples (e.g., plasma, urine, feces, liver, and kidney), were acquired. Based on the UNIFI™ platform (Waters), the efficient data processing workflows were established by combining mass defect filtering (MDF)-induced classification, diagnostic product ions (DPIs), and neutral loss filtering (NLF)-dominated structural confirmation. The high-definition MS2 spectral libraries, dubbed in vitro-SSF and in vivo-SSF, were elaborated, enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples. Consequently, 118 prototypes and 206 metabolites of SSF were identified, with the identification rate reaching 80.51% and 79.61%, respectively. The metabolic pathways mainly involved the oxidation, reduction, hydrolysis, sulfation, methylation, demethylation, acetylation, glucuronidation, and the combined reactions. Conclusively, the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Summary: The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4.

Background: To prospectively assess the individual and joint effects of birth weight and the life’s essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life. Methods: In 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids. Results: Low birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02–1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71–11.15), P

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Significantly activated uridine nucleotide and fatty acid metabolism in HCC cells promote malignant proliferation and immune evasion. Herein, it is demonstrated that the tripartite motif 65 (TRIM65) E3 ubiquitin‐protein ligase, O‐GlcNAcylated via O‐GlcNAcylation transferase, is highly expressed in HCC and facilitated metabolic remodeling to promote the accumulation of products related to uracil metabolism and palmitic acid, driving the progression of HCC. Mechanistically, it is showed that TRIM65 mediates ubiquitylation at the K44 residue of neurofibromatosis type 2 (NF2), the key protein upstream of classical Hippo signaling. Accelerated NF2 degradation inhibits yes‐associated protein 1 phosphorylation, inducing aberrant activation of related metabolic enzyme transcription, and orchestrating metabolic and immune advantages. In conclusion, these results reveal a critical role for the TRIM family molecule TRIM65 in supporting HCC cell survival and highlight the therapeutic potential of targeting its E3 ligase activity to alter the regulation of proteasomal degradation.

Solid Rocket Motors (SRMs) rely on solid propellants, directly impacting the energy capacity of launch vehicles. High energy density material (HEDM) propellant exhibits superior energy density owing to the incorporation of a substantial quantity of energetic particles. However, the elevated particle fill ratio makes the formation of pores more prevalent during the manufacturing process of propellants. These pores, representing default defects, are indispensable factors in the investigation of mechanical properties of propellants. This study investigated default defects effects on HEDM propellants, analyzing both microscopic and macroscopic perspectives. Utilizing micro-CT imaging, the microstructure and default defects were characterized. Subsequently, using the cohesive zone model (CZM), microscopic damage evolution was depicted with the representative volume element (RVE) model, allowing in-depth analysis. Furthermore, a damage constitutive model, based on microscopic damage, was developed, with its softening function calibrated using microscopic damage evolution characteristics. Implemented into ABAQUS via user-defined material subroutine (UMAT), this model enabled the prediction of the mechanical response of HEDM propellants with different defects. The results demonstrate that the developed model accurately predicts the mechanical responses of HEDM propellants with different defects, showcasing the potential of macro-microscopic approaches in analyzing propellants with default defects.

The development of tissue engineering and regeneration research has created new platforms for bone transplantation. However, the preparation of scaffolds with good fiber integrity is challenging, because scaffolds prepared by traditional printing methods are prone to fiber cracking during solvent evaporation. Human skin has an excellent natural heat-management system, which helps to maintain a constant body temperature through perspiration or blood-vessel constriction. In this work, an electrohydrodynamic-jet 3D-printing method inspired by the thermal-management system of skin was developed. In this system, the evaporation of solvent in the printed fibers can be adjusted using the temperature-change rate of the substrate to prepare 3D structures with good structural integrity. To investigate the solvent evaporation and the interlayer bonding of the fibers, finite-element analysis simulations of a three-layer microscale structure were carried out. The results show that the solvent-evaporation path is from bottom to top, and the strain in the printed structure becomes smaller with a smaller temperature-change rate. Experimental results verified the accuracy of these simulation results, and a variety of complex 3D structures with high aspect ratios were printed. Microscale cracks were reduced to the nanoscale by adjusting the temperature-change rate from 2.5 to 0.5 °C s−1. Optimized process parameters were selected to prepare a tissue engineering scaffold with high integrity. It was confirmed that this printed scaffold had good biocompatibility and could be used for bone-tissue regeneration. This simple and flexible 3D-printing method can also help with the preparation of a wide range of micro- and nanostructured sensors and actuators.

Objective To explore the impacts of health empowerment model combined with binary coping intervention on neurological function,coping style,and hope level in elderly stroke patients. Methods A total of 144 elderly stroke patients admitted to Handan Central Hospital from October 2020 to October 2022 were selected as the research subjects,they were randomly separated into a reference group and an observation group,with 72 cases in each group.The reference group received routine nursing intervention,while observation group received health empowerment combined with binary coping intervention,The neurological function [National Institutes of Health Stroke Scale(NIHSS)] ,coping style [Simplified coping style questionnaire(SCSQ)] ,and hope level [Herth hope index(HHI)] of both groups were evaluated before and after intervention. Results There was no statistically significant difference in NIHSS scores,SCSQ scores,and HHI scores between the two groups before intervention(P>0.05).After intervention,the NIHSS scores of the observation group were lower than those in the control group(P

Abstract Collagen possesses high biocompatibility with all tissue and cell types in the body, enabling the creation of multifunctional composite materials for medical applications. In biomedical engineering, naturally-sourced collagen is often combined with diverse organic and inorganic bioactive components to eliminate defects and disorders in fields including orthopedics, dermatology, and more. At the same time, medical-related infection issues and the precise treatment needs of patients require collagen composite biomaterials to have antibacterial properties and customized structures. This paper reviews the antibacterial functionalization of collagen composite biomaterials in recent years, including the combination with inorganic or organic antibacterial agents, which is beneficial for preventing and controlling biological contamination in medical applications. Then, the existing problems and future development directions for the architecturalization of collagen composite materials with 3D printing were discussed, providing guidance for personalized customization of multifunctional materials to meet the specific needs of patients in the future. Graphical Abstract

Abstract The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively (P > 0.05). These values were significantly different at 1 and 5 years postoperatively (P

Abstract Background Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions. Methods We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3–18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models. Results The study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R 2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807–0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia. Conclusions The XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3–18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.

Abstract Reduced graphene oxide (rGO) films suffer from low capacitance for inner unreduced oxygen functional groups, restacking of sheets and high contact resistance. Herein, carbon spheres derived from renewable xylan were added to graphene oxide with large sheet area to fabricate film by gelation and filtration, followed by in situ reduction for high-performance flexible supercapacitor. rGO film with transverse size about 13 μm showed a good specific capacitance of 967 mF/cm2 at a scanning rate of 5 mV/s and increased to 1786 mF/cm2 by in situ reducing its inner part, which generally remained oxidized due to outer hindering from hydrophobic graphene. Then, by hydrothermal carbonization of xylan and activation with KOH, activated carbon sphere (aXCS) was prepared, which had a diameter of 150–200 nm and a specific capacitance of 270 F/g. The aXCS acted as spacer and connector to avoid restacking of graphene sheets and decrease interlayer contact resistance, resulting 94% increase in capacitance performance from rGO film to aXCS/rGO film. Therefore, combined in situ reduction and enhancement through compositing aXCS, the final film (aXCS/rGO-AA) showed a boosted specific capacitance of 755 mF/cm2 at 1 mA/cm2 in double electrode system, power density of 22.5–2250 mW/cm2, and energy density of 11.88–25.2 mWh/cm2. Meanwhile, aXCS/rGO-AA had outstanding cycling stability that its specific capacitance maintained 108.7% after 10,000 cycles of charge–discharge, showing promising potential in wearable and portable electronics. Graphical abstract

ObjectiveThis study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV.MethodsCytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity.ResultsWe identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse.ConclusionA group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

In this study, a trisodium citrate (TSC)-assisted hydrothermal method is utilized to prepare three-dimensional hydroxyapatite (3D HA). Understanding the role of TSC in the preparation of 3D HA crystals may provide valuable methods to design advanced biomaterials. As one of the indexes of solution supersaturation, the initial pH (ipH) value can not only directly affect the nucleation rate, but also affect the growth of HA crystals. In this work, the effect of the ipH on the microstructure, particle size distribution, and specific surface area of the 3D HA is explored. Results showed that the morphology of 3D HA transformed from a bundle to a dumbbell ball and then a dumbbell with an increase in the ipH. A corresponding mechanism of such a structural evolution was proposed, providing inspiration for the fabrication of innovative 3D HA structures with enhanced biological functionality and performance.

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause significant economic losses to the global swine industry, yet effective prevention and control measures remain elusive. The development of novel antivirals is thus urgently needed. Rifampicin (RFP), a semisynthetic derivative of rifamycin, has been previously reported to inhibit the replication of certain mammalian DNA viruses as well as RNA viruses. In this study, we unveil RFP as a potent inhibitor of PRRSV both in Marc-145 cells (half-maximal inhibitory concentration 61.26 μM) and porcine alveolar macrophages (half-maximal inhibitory concentration 53.09 μM). The inhibitory effect of RFP occurred during viral replication rather than binding, internalization and release. We also demonstrated that RFP inhibits PRRSV proteins production in the early stage of infection, without inhibiting host protein synthesis. Moreover, RFP effectively restricted porcine epidemic diarrhea virus (PEDV) and porcine enteric alphacoronavirus (PEAV) infection in Vero cells. In summary, these findings indicate the promising potential of RFP as a therapeutic agent for PRRSV, PEDV and PEAV infection in pig farms.

Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.

Background: The COVID-19 pandemic has exposed healthcare workers (HCWs) to serious risk of infection. The aims of our study were to investigate the epidemiological characteristics and risk factors of SARS-CoV-2 infection among HCWs, and evaluate the vaccine effectiveness (VE) during the Omicron pandemic in Shanghai, China. Methods: Active surveillance of COVID-19 was performed among HCWs who worked in Shanghai General Hospital from December 2022 to January 2023. A case-control study was conducted by questionnaire survey to analyse the infection-related risk factors. A retrospective cohort study was explored to evaluate VE against primary infection. Results: During the Omicron outbreak, 2,008 of 2,460 (81.6%) HCWs were infected with SARS-CoV-2. The infection rate was higher in women, younger age groups, nurses and medical technicians. Among the 1,742 participants in the questionnaire, 1,463 (84.0%) were tested positive, and 95.1% of them developed symptoms. Most of the infections (53.0%) were acquired outside the hospital. The risk factors associated with higher odds of infection were working in the emergency department (aOR 3.77, 95% CI 1.69–8.38) and medical examination area (aOR 2.47, 95% CI 1.10–5.51). The protective factors associated with lower odds of infection were previous infection with SARS-CoV-2 (aOR 0.01, 95% CI 0–0.07) and receiving four doses of vaccines (aOR 0.40, 95% CI 0.17–0.97). For frontline HCWs, those who had oral-nasal exposure to coworkers were more likely to be infected (aOR 1.74, 95% CI 1.21–2.51). In VE analysis, the risk of primary infection was lower in HCWs who received the emergency heterologous booster (the fourth dose) during the epidemic (aHR 0.25, 95% CI 0.15–0.40), resulting in an adjusted-VE of 75.1%. Conclusions: In response to future pandemic, it is important for public health policies to aim at protecting HCWs through risk-differentiated infection control measures, strengthening personal protection and recommending vaccination to vulnerable individuals before the arrival of Omicron wave.

Microstructural void formation during the processing of continuous fibre-reinforced polymer composites are a significant limitation of processes such as 3D printing, as voids inhibit resultant mechanical properties. Traditional optical microscopy approaches to void characterisation are tedious and are prone to errors due to non-ideal but realistic image conditions, including low contrast typical of microscopic images. This paper proposes a novel application of automated computer vision image processing techniques (i.e. a contrast-limited adaptive histogram equalisation (CLAHE) algorithm and Otsu's method) for detailed void characterisation of continuous fibre-reinforced composites. Microstructural void fraction was determined for both unidirectional and bi-axial laminates of a variety of thicknesses. The void characterisation by computer vision was shown to produce comparable results with manual contrast/brightness control, but with significantly less standard deviation. The computer vision software used in void characterisation is made freely available online at https://github.com/Xiao-ying/VoidDetector.

Abstract This paper introduces the concept of complex quadratic Diophantine fuzzy sets (CQDFS) which serves as a robust framework for effectively dealing with uncertainty within decision-making challenges. The study comprehensively explores the properties and characteristics of CQDFS by conducting a systematic comparative analysis to demonstrate its superiority over existing techniques in managing complex fuzzy information. This foundation contributes to the theoretical understanding of CQDFS and also provides valuable practical insights into a wide range of transportation strategies and economic efficiency. These insights offer practical solutions to enhance decision-making within these important and interconnected domains. The proposed complex information system serves as a versatile and adaptive tool, significantly strengthening the flexibility available for addressing complex decision-making challenges, particularly in contexts such as the management of GPS-enabled cargo vehicles and cargo loading operations, where precision and efficiency are of great importance.

Abstract Background China is implementing the family doctor (FD) system to reform the primary healthcare (PHC). The family doctor contract service (FDCS) policy plays a crucial role in this system implementation, aiming to transform the doctor-patient relationship and enhance PHC quality. This study aims to investigate the impact of FDCS on the doctor-patient relationship in PHCs using field research methodology. Method The field research methodology was employed to address the research questions. Quantitative methods were utilized for data collection and analysis. A structure questionnaire was used to collect data based on the research questions. Our investigation encompassed twenty-five village clinics across three counties in China. A total of 574 subjects helped us to finish this investigation in the study. The collected data was analyzed using statistical analysis including ordinary least squares (OLS) model and propensity scores matching model (PSM) to estimate the relationship. Result The findings from ordinary least squares (OLS) regression revealed that FDCS had a positive influence on patient trust in doctors within PHCs, with patients who participated the FDCS exhibiting higher levels of trust compared to those who did not participate. Propensity score matching (PSM) analysis further confirmed these results by accounting for selection bias. Conclusions The implementation of family doctor contract service has brought about significant transformation in the doctor-patient relationship within rural Chinese PHCs. In essence, it has revolutionized the service model of doctor in PHC, playing a pivotal role in improving primary health quality and enhance the service capability of doctors in PHC. This transformative process has been crucial for carrying out hierarchical diagnosis and treatment policy, which aims to adjust the medical service structure and optimizing the health service system. Therefore, it is imperative for government authorities and health administration departments to ensure continuous support for this essential service through appropriate formulation.

Soft hydrogels are excellent candidate materials for repairing various tissue defects, yet the mechanical strength, anti-swelling properties, and biocompatibility of many soft hydrogels need to be improved. Herein, inspired by the nanostructure of collagen fibrils, we developed a strategy toward achieving a soft but tough, anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles. Specifically, the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan (HM) with laponite (LAP) to form nanoparticles, followed by the inter-nanoparticle bonding through photo-crosslinking. The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques. Due to the unique structure of the crosslinked nanoparticles, the nanocomposite hydrogels exhibited low stiffness (G’< 2 kPa), high compressive strength (709 kPa), and anti-swelling (swelling ratio of 1.07 in PBS) properties. Additionally, by harnessing the photo-crosslinking ability of the nanoparticles, the nanocomposite hydrogels were processed as microgels, which can be three-dimensionally (3D) printed into complex shapes. Furthermore, we demonstrated that these nanocomposite hydrogels are highly biocompatible, biodegradability, and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing. This work presents a promising approach to develop biomimetic, nanofibrillar soft hydrogels for regenerative medicine applications.

In the field of network security attack and defense, attackers frequently utilize network monitoring to analyze traffic features and obtain user privacy. Most defense methods employ feature-based traffic morphing techniques. However, the existing traffic camouflage method based on the Wasserstein Generative Adversarial Network (WGAN) exhibits limited defensive effectiveness, as the transformed traffic can still be detected due to the inherent limitations of the model and algorithm. In this paper, we propose a Wasserstein Generative Adversarial Network model with a Self-Attention mechanism (SA-WGAN) and adjust the parameter of the discriminator. Simultaneously, in the traffic generation algorithm, a constraint on padding packets was added: the Jaccard Index of the set of statistical features of the generated traffic must reach a threshold of 0.25, while ensuring the inclusion of three-way handshake packets to optimize the camouflage effect. To verify the camouflage effectiveness of the optimized defense method, we conduct a series of adversarial attacks. Experimental results show that the feature defense method based on SA-WGAN can significantly reduce the detection accuracy of monitored traffic. Compared to the feature defense method based on WGAN, it decreases the classification accuracy by 9.15% under the Panchenko attack, effectively enhancing the defensive capability and successfully increasing the difficulty for attackers to penetrate network traffic.

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.

Abstract Rare cell populations are key in neoplastic progression and therapeutic response, offering potential intervention targets. However, their computational identification and analysis often lag behind major cell types. To fill this gap, we introduce MarsGT: Multi-omics Analysis for Rare population inference using a Single-cell Graph Transformer. It identifies rare cell populations using a probability-based heterogeneous graph transformer on single-cell multi-omics data. MarsGT outperforms existing tools in identifying rare cells across 550 simulated and four real human datasets. In mouse retina data, it reveals unique subpopulations of rare bipolar cells and a Müller glia cell subpopulation. In human lymph node data, MarsGT detects an intermediate B cell population potentially acting as lymphoma precursors. In human melanoma data, it identifies a rare MAIT-like population impacted by a high IFN-I response and reveals the mechanism of immunotherapy. Hence, MarsGT offers biological insights and suggests potential strategies for early detection and therapeutic intervention of disease.

Abstract Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. Methods We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. Results The most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. Conclusions Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1 P409L , ADGRA2 and ADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

Meteorological prediction is crucial for various sectors, including agriculture, navigation, daily life, disaster prevention, and scientific research. However, traditional numerical weather prediction (NWP) models are constrained by their high computational resource requirements, while the accuracy of deep learning models remains suboptimal. In response to these challenges, we propose a novel deep learning-based model, the Spatiotemporal Fusion Model (STFM), designed to enhance the accuracy of meteorological predictions. Our model leverages Fifth-Generation ECMWF Reanalysis (ERA5) data and introduces two key components: a spatiotemporal encoder module and a spatiotemporal fusion module. The spatiotemporal encoder integrates the strengths of convolutional neural networks (CNNs) and recurrent neural networks (RNNs), effectively capturing both spatial and temporal dependencies. Meanwhile, the spatiotemporal fusion module employs a dual attention mechanism, decomposing spatial attention into global static attention and channel dynamic attention. This approach ensures comprehensive extraction of spatial features from meteorological data. The combination of these modules significantly improves prediction performance. Experimental results demonstrate that STFM excels in extracting spatiotemporal features from reanalysis data, yielding predictions that closely align with observed values. In comparative studies, STFM outperformed other models, achieving a 7% improvement in ground and high-altitude temperature predictions, a 5% enhancement in the prediction of the u/v components of 10 m wind speed, and an increase in the accuracy of potential height and relative humidity predictions by 3% and 1%, respectively. This enhanced performance highlights STFM’s potential to advance the accuracy and reliability of meteorological forecasting.

Nutritional supplementation enriched with protein and antioxidants has been demonstrated to effectively strengthen skeletal muscle function and mitigate the risk of sarcopenia. Dietary protein has also been a common carrier to establish bioactive delivery system. Therefore, in this study, a Pickering emulsion delivery system for rutin was constructed with whey protein, and its structural characteristics, bioaccessibility, and molecular interactions were investigated. In the in vivo study, zebrafish (n = 10 in each group), which have a high genetic homology to humans, were treated with dexamethasone to induce sarcopenia symptoms and were administered with rutin, whey protein and the Pickering emulsion, respectively, for muscle movement ability evaluation, and zebrafish treated with or without dexamethasone was used as the model and the control groups, respectively. Results showed that the Pickering emulsion was homogeneous in particle size with a rutin encapsulation rate of 71.16 ± 0.15% and loading efficiency of 44.48 ± 0.11%. Rutin in the Pickering emulsion exhibited a significantly higher bioaccessibility than the free form. The interaction forces between rutin and the two components of whey proteins (α-LA and β-LG) were mainly van der Waals forces and hydrogen bonds. After treatment for 96 h, the zebrafish in Picking emulsion groups showed a significantly increased high-speed movement time and frequency, an increased level of ATP, prolonged peripheral motor nerve length, and normalized muscular histological structure compared with those of the model group (p < 0.05). The results of this study developed a new strategy for rutin utilization and provide scientific evidence for sarcopenia prevention with a food-derived resource.

Deep learning-based super-resolution (SR) techniques play a crucial role in enhancing the spatial resolution of images. However, remote sensing images present substantial challenges due to their diverse features, complex structures, and significant size variations in ground objects. Moreover, recovering lost details from low-resolution remote sensing images with complex and unknown degradations, such as downsampling, noise, and compression, remains a critical issue. To address these challenges, we propose ConvMambaSR, a novel super-resolution framework that integrates state-space models (SSMs) and Convolutional Neural Networks (CNNs). This framework is specifically designed to handle heterogeneous and complex ground features, as well as unknown degradations in remote sensing imagery. ConvMambaSR leverages SSMs to model global dependencies, activating more pixels in the super-resolution task. Concurrently, it employs CNNs to extract local detail features, enhancing the model’s ability to capture image textures and edges. Furthermore, we have developed a global–detail reconstruction module (GDRM) to integrate diverse levels of global and local information efficiently. We rigorously validated the proposed method on two distinct datasets, RSSCN7 and RSSRD-KQ, and benchmarked its performance against state-of-the-art SR models. Experiments show that our method achieves SOTA PSNR values of 26.06 and 24.29 on these datasets, respectively, and is visually superior, effectively addressing a variety of scenarios and significantly outperforming existing methods.

The occurrence and development of myocardial dysfunction are associated with damage in the cardiac microvascular endothelial cells (CMECs), which can regulate nutrient exchange and oxy-gen-carbon cycling to protect cardiomyocytes. Interventions targeting microRNAs (miRNAs) can effectively mitigate CMEC injury and thus improve cardiovascular diseases. MiRNAs are a class of noncoding single-strand RNA molecules typically 21–23 nucleotides in length that are encoded by endogenous genes. They are critical regulators of organism development, cell differentiation, metabolism, and apoptosis. Current clinical trials on miRNA drugs indicate that patient-specific miRNA levels are now being used as one of the criteria for predicting heart disease. However, the cellular process of various miRNAs in CMECs in cardiovascular diseases has not been fully elucidated. These mechanisms are a field that immediately requires further investigation. Accordingly, this review summarizes the roles and mechanisms of various miRNAs in CMECs in cardiovascular disease and includes the process of CMEC crosstalk between miRNAs and other cell types in the heart. Our study serves as a theoretical basis for the formal introduction of miRNA use into the treatment of cardiovascular diseases in the future.