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Many behavioural interactions in real life involve three individuals. When each individual has two alternative strategies, they can be abstracted into mathematical models by means of [Formula: see text] asymmetric games. In this paper, we explore a special class of [Formula: see text] asymmetric games satisfying fixed conditions. Firstly, we analyse two solitary interior equilibrium points and provide the judgement condition for their instability based on the Jacobi matrix local stability analysis method. Secondly, we analyse the interior equilibrium points that are continuously distributed within a line and probe into their stability conditions based on generalized Hamiltonian systems theory. Under the circumstances, the stable interior equilibrium point is surrounded by closed orbits in phase space, which presents an observable stable state where two strategies coexist and fluctuate in each of the three game populations. This work enriches the study of [Formula: see text] asymmetric games’ evolutionary dynamics.

BackgroundMajor depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC).MethodsIn this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4–8 Hz; alpha, 8–12 Hz; beta1, 12–16 Hz; beta2, 16–24 Hz; and beta3, 24–40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17).ResultsDuring the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked.ConclusionOur study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression.LimitationsThe study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD.

With safety and efficacy demonstrated over hundreds of clinical trials in the last 30 years, along with at least six recent global marketing authorizations achieved since 2017, recombinant adeno-associated viruses (rAAVs) have been established as the leading therapeutic gene transfer vector for rare, monogenic diseases. Significant advances in manufacturing technology have been made in the last few decades to address challenges with GMP production of rAAV products, although yield, cost, scalability, and quality remain a challenge. With transient transfection processes established as a manufacturing platform for multiple commercial AAV products, there remains significant yield, cost, robustness, and scalability constraints that need to be resolved to enable a reliable supply of rAAV products for global patient access. The development of stable producer cell lines for rAAV products has enabled scalability and, in some cases, improvements in productivity. Herein we describe a novel AAV perfusion-enhanced expression (APEX) process, resulting in higher maximum cell densities in the production bioreactor with a 3- to 6-fold increase in volumetric productivity. This process has been successfully demonstrated across multiple serotypes in large scale cell culture with titers approaching 1 × 1012 GC/mL. The APEX production platform marks a significant leap forward in the efficient and effective manufacturing of rAAV vector products.

Previous research has indicated that students’ academic engagement is related to their emotional support from teachers. However, there is scarce evidence on how teacher emotional support relates to students’ academic engagement. Given the potential role of positive academic emotions in learning, this study investigated the mediating role of students’ positive academic emotions in the relationship between teacher emotional support and academic engagement among Chinese college students. Additionally, this study examined how mastery-approach goals moderated positive academic emotions. A survey instrument containing teacher emotional support, positive academic emotions, mastery-approach goals, and academic engagement was administered to 464 Chinese college students. The results demonstrated that students’ emotional support from their teachers positively influenced their academic engagement. Positive academic emotions mediated the relationship between teacher emotional support and students’ academic engagement. Furthermore, the mastery-approach goals moderated the mediating role of positive academic emotions. Finally, the implications for teachers in teaching for practice and the application prospects are discussed.

Abstract Background Anticoagulation is recommended as a standardized therapy for COVID-19 patients according to the WHO guidelines. However, bleeding events have also been reported. Hemorrhage or hematoma was observed in sites including the retroperitoneum, brain, alimentary tract, muscles, and soft tissues. Reduction or suspension of anticoagulants is a common intervention. Transfusion, endoscopic hemostasis, and vascular interventional therapy have been used to improve the condition. Case presentation In this article, we present two cases of concurrent multisite hematomas and bleeding at other sites in patients with SARS-CoV-2 infection. Both patients were treated with heparins and experienced bleeding after the anticoagulation therapy. Both patients were older with more than two comorbidities, and critical COVID-19. Laboratory tests revealed a considerable decrease in hemoglobin levels and alterations in the coagulation system. In the first patient, the main intervention was embolization using angiography. However, we only adjusted the anticoagulation strategy in the second case. The first patient recovered and was discharged; however, the second died of other causes. This study provides a retrospective review of typical hemorrhagic cases during anticoagulation in COVID-19 patients over the course of four years. A relatively comprehensive search was performed in Pubmed by constructing MeSH subject terms on limiting the search period and specific contents. It summarizes and synthesizes the research related to heparins and other novel anticoagulants in the context of COVID-19 from the onset of the pandemic to the present disseminated phase. This study aimed to offer valuable insights and reference points for developing anticoagulation treatment strategies for patients with COVID-19. Conclusions Anticoagulation is a crucial treatment option for patients with COVID-19. The difference in anticoagulant effects is related to the severity of COVID-19. Nafamostat can reduce thrombosis in the extracorporeal circuits in critically ill patients with COVID-19. The efficacy and safety of novel anticoagulants require further clinical data. Routine bedside assessments and real-time laboratory monitoring are essential for early identification of bleeding events during anticoagulant therapy and administering intervention.

Abstract Ancient textile images have a variety of styles and themes, and the classification of different types of textiles provides a reliable reference for the protection and restoration of cultural relics. Due to the low efficiency of traditional classification methods and the low accuracy of classification, the image restoration of textiles takes longer and the repair effect is poor. Therefore, this paper takes ancient textile images as the research object and selects YOLOv4–ViT collaborative identification network (YOLOv4–ViT network) and generative adversarial networks (GAN) restoration model from a variety of network models to classify and restore ancient textile images. In this work, YOLOv4–ViT network is used to recognize and classify pattern elements in ancient textile images. Then, according to the classification results, restoration training of ancient textiles was carried out using an improved GAN restoration model, for which the final classification accuracy reached 92.78% and the repair result even took only 1.5 s. On this basis, a reliable retrieval and restoration system is designed to realize the repair of damaged textile images, reduce the difficulty of repair, and help users retrieve and browse different categories of ancient textile images, thus solve the problems of slow retrieval speed in traditional retrieval methods and poor restoration effect of ancient textile images.

Abstract In China, the prevalence of diabetic retinopathy (DR) is increasing, so it is necessary to provide convenient and effective community outreach screening programs for DR, especially in rural and remote areas. The purpose of this study was to use the results of ophthalmologists as the gold standard to evaluate the accuracy of community general practitioners' judgement and grading of DR to find a feasible and convenient DR screening method to reduce the risk of visual impairment and blindness in known diabetes patients. Retinal images of 1646 diabetic patients who underwent DR screening through teleophthalmology at Nanchang First Hospital were collected for 30 months (January 2020 to June 2022). Retinal images were collected without medication for mydriasis, stored by community general practitioner, and diagnosed by both community general practitioner and ophthalmologist of our hospital through teleophthalmology. The grading of ophthalmologist was used as a reference or gold standard for comparison with that of community general practitioner. A total of 1646 patients and 3185 eyes were examined, including 2310 eyes with DR. The evaluation by the community general practitioner had a Kappa value of 0.578, sensitivity of 80.58%, specificity of 89.94%, and accuracy of 83.38%% in 2020; a Kappa value of 0.685, sensitivity of 95.43%, specificity of 78.55%, and accuracy of 90.77% in 2021; and a Kappa value of 0.744, sensitivity of 93.99%, specificity of 88.97%, and accuracy of 92.86% in 2022. Teleophthalmology helped with large-scale screening of DR and made it possible for community general practitioner to grade images with high accuracy after appropriate training. It is possible to solve the current shortage of eye care personnel, promote the early recognition of disease and reduce the impact of diabetes-associated blindness.

Abstract Background Disrupted sleep is believed to contribute to short- and long-term neurodevelopmental problems in very preterm infants (VPIs). This study presents a protocol for an evaluator-blinded, randomized crossover trial. It aims to assess the sleep efficiency of hospitalized VPIs by providing multisensory stimulation bundles. Furthermore, it aims to observe the intervention impacts on sleep during hospitalization of the VPIs and their sleep and neurodevelopmental outcomes during the first year of post-discharge follow-up. Methods The study will be conducted in the neonatology department of a tertiary pediatric teaching hospital. All the eligible VPIs will undergo two types of care in random order: “standard care” (2 weeks) and “standard care plus multisensory stimulation bundles,” each lasting 2 weeks. A generated list of random numbers will be used for case sequence allocation. Sleep outcomes will be evaluated using the Actiwatch-2 Actigraph. Moreover, the amplitude-integrated electroencephalography and the Griffiths Mental Development Scales will be used to measure the neurodevelopmental outcomes during hospitalization and in the first year of follow-up of the VPIs. Discussion The intervention protocol of this study differs from that of other traditional interventions by producing precise and consistent supportive stimulations, similar to maternal tactile, auditory, posture, and visual effects for hospitalized VPIs. This protocol could be an effective measure to facilitate sleep and early neurodevelopment of VPIs. The expected outcomes will help confirm the implementation and generalization of the multisensory stimulation bundles’ care protocol in neonatology departments. We expect that the study will positively impact hospitalized VPIs, especially in their sleep and early neurodevelopmental outcomes. It will also provide a new perspective regarding parent and infant interaction strategies, particularly for newborn intensive care units that limit visits because of the global spread of COVID-19. Trial registration Chinese Clinical Trial Registry ChiCTR 2200059099. Registered on 25 April 2022, https://www.chictr.org.cn/showproj.html?proj=166980 ; the Hospital Research Ethics Committee (approval number: SCMCIRB-K2021086-1, Version 01), approved on 21 January 2022.

Plain carbon steel is the most widely applied steel in current engineering construction. With the increased application property needs, the service life of plain carbon steel has been severely tested. As one of the most destructive failure modes, corrosion resistance of carbon steel has attracted wide attention. Rare earth La, as the microalloying element, was employed in plain carbon steel, Q355, to improve its corrosion resistance. As the content of La increased, the microstructure was refined. The fraction of pearlite decreased, while the content of acicular increased. Within the La addition of 230 ppm, the tensile strength and impact energy were jointly improved. Furthermore, the microalloying element of La modified the inclusion types and refined the inclusion size. The modified microstructure and inclusions by La co-improved the corrosion resistance. The formula of effective La content was proposed to estimate the effect of La on corrosion. As the effective content of La increased, the relative corrosion rate decreased. La3+ promoted the protective rust layer to increase corrosion resistance.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for coronavirus disease 2019 (COVID‐19), a complex and multifaceted illness. COVID‐19 is associated with various ocular manifestations including conjunctivitis, retinal vein occlusion and optic neuritis. However, the case of Vogt‐Koyanagi‐Harada (VKH) disease associated with SARS‐CoV‐2 is infrequent, and the specific association is still unclear. Case Presentation In the present study, a 35‐year‐old female patient without any significant medical history presented with 1 week of bilateral blurred vision, occurring 2 weeks after a clinical course of COVID‐19. Upon examination, both eyes exhibited bullous serous retinal detachments. She was diagnosed with incomplete VKH disease. Early diagnosis and treatment of VKH disease are essential for the visual prognosis of this aggressive disease. In this particular patient, ocular inflammatory signs and visual acuity improved via corticosteroid therapy. It is worth noting that the occurrence of VKH disease associated with SARS‐CoV‐2 is uncommon, and the specific connection between the two remains unknown. We review and summarize the clinical characteristics of VKH disease following SARS‐CoV‐2 infection, and discuss the potential mechanisms that may explain this phenomenon, based on similar studies previously reported. Conclusion Despite the unclear causality, it is important for ophthalmologists and physicians to be recognizant of the possible association between VKH disease and COVID‐19. SARS‐CoV‐2 may play a potential immunological triggering role in VKH disease. However, further in‐depth research is necessary to investigate the clinical and epidemiological features, as well as the underlying mechanisms of this association.

ObjectiveThe aim of this study was to investigate the impact of early life adversity on cognitive function in patients with schizophrenia, with a focus on social cognition (SC).MethodsTwo groups of patients with schizophrenia were recruited and matched on sociodemographic and clinical characteristics. One group consisted of 32 patients with a history of childhood trauma (SCZ-ct), and the other group consisted of 30 patients without a history of childhood trauma (SCZ-nct). In addition, 39 healthy controls without a history of childhood trauma (HC-nct) were also recruited. The intelligence of the three groups was assessed using the Wechsler Abbreviated Scale of Intelligence (WAIS—RC) short version. The cognitive function evaluation was conducted using the MATRICS Consensus Cognitive Battery (MCCB), and early life adversity was measured using the Childhood Trauma Questionnaire-Short Form (CTQ) and Bullying Scale for Adults (BSA).ResultsPatients with schizophrenia endosed significantly higher scores on the CTQ (F=67.61, p

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related death worldwide. Hepatectomy remains the first‐line treatment for patients with resectable HCC. However, the reported recurrence rate of HCC at 5 years after surgery is between 50% and 70%. Tumor‐related factors, including tumor size, number and differentiation, and underlying liver disease are well‐known risk factors for recurrence after treatment. In addition to tumor‐related factors, ever‐increasing amounts of studies are finding that the tumor microenvironment also plays an important role in the recurrence of HCC, including systemic inflammatory response and immune regulation. Based on this, some inflammatory and immune markers were used in predicting postoperative cancer recurrence. These include neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, cytotoxic T cells, and regulatory T cells, among others. In this review, we summarized the inflammatory and immune markers that affect recurrence after HCC resection in order to provide direction for adjuvant therapy after HCC resection and ultimately achieve the goal of reducing recurrence.

BackgroundMajor Depressive Disorder (MDD) is a pervasive mental health issue with significant diagnostic challenges. Electroencephalography (EEG) offers a non-invasive window into the neural dynamics associated with MDD, yet the diagnostic efficacy is contingent upon the appropriate selection of EEG features and brain regions.MethodsIn this study, resting-state EEG signals from both eyes-closed and eyes-open conditions were analyzed. We examined band power across various brain regions, assessed the asymmetry of band power between the hemispheres, and integrated these features with clinical characteristics of MDD into a diagnostic regression model.ResultsRegression analysis found significant predictors of MDD to be beta2 (16–24 Hz) power in the Prefrontal Cortex (PFC) with eyes open (B = 20.092, p = 0.011), beta3 (24–40 Hz) power in the Medial Occipital Cortex (MOC) (B = −12.050, p

Abstract Objective Accurate quantification of the root surface area (RSA) plays a decisive role in the advancement of periodontal, orthodontic, and restorative treatment modalities. In this study, we aimed to develop a dynamic threshold-based computer-aided system for segmentation and calculation of the RSA of isolated teeth on cone-beam computed tomography (CBCT) and to assess the accuracy of the measured data. Method We selected 24 teeth to be extracted, including single-rooted and multi-rooted teeth, from 22 patients who required tooth extraction. In the experimental group, we scanned 24 isolated teeth using CBCT with a voxel size of 0.3 mm. We designed a computer-aided system based on a personalized dynamic threshold algorithm to automatically segment the roots of 24 isolated teeth in CBCT images and calculate the RSA. In the control group, we employed digital intraoral scanner devices to perform optical scanning on 24 isolated teeth and subsequently manually segmented the roots using 3-matic software to calculate the RSA. We used the paired t-test (P 0.05). As per the Bland-Altman plot, the results were evenly distributed within the region of ± 1.96 standard deviations of the mean, with no increasing or decreasing trends and good consistency. Conclusion In this study, we designed a computer-aided root segmentation system based on a personalized dynamic threshold algorithm to automatically segment the roots of isolated teeth in CBCT images with a voxel size of 0.3 mm. We found that the RSA calculated using this approach was highly accurate, and a voxel of 0.3 mm in size could accurately display the surface area data in CBCT images. Overall, our findings in this study provide a foundation for future work on accurate automatic segmentation of tooth roots in full-mouth CBCT images and the computation of RSA.

Abstract The Hippo pathway is a master regulator of organ growth, stem cell renewal, and tumorigenesis, its activation is tightly controlled by various post-translational modifications, including ubiquitination. While several E3 ubiquitin ligases have been identified as regulators of Hippo pathway, the corresponding E2 ubiquitin-conjugating enzymes (E2s) remain unknown. Here, we performed a screen in Drosophila to identify E2s involved in regulating wing overgrowth caused by the overexpression of Crumbs (Crb) intracellular domain and identified Bruce as a critical regulator. Loss of Bruce downregulates Hippo target gene expression and suppresses Hippo signaling inactivation induced tissue growth. Unexpectedly, our genetic data indicate that Bruce acts upstream of Expanded (Ex) but in parallel with the canonical Hippo (Hpo) -Warts (Wts) cascade to regulate Yorkie (Yki), the downstream effector of Hippo pathway. Mechanistically, Bruce synergizes with E3 ligase POSH to regulate growth and ubiquitination-mediated Ex degradation. Moreover, we demonstrate that Bruce is required for Hippo-mediated malignant tumor progression. Altogether, our findings unveil Bruce as a crucial E2 enzyme that bridges the signal from the cell surface to regulate Hippo pathway activation in Drosophila.

Abstract Background Sexual problems are common among women with pelvic floor disorders (PFD). Few studies have explored the relationship between obesity and sexual function in women with PFD. This study aimed to prove that obesity was a risk factor for worse sexual function in women with PFD, and to investigate the mediating role of menstrual irregularity. Methods This was a cross-sectional study involving 783 women with PFD from Shandong Province, China between June 2020 and February 2021. Female sexual function was assessed using the Pelvic Organ Prolapse/UI Sexual Questionnaire-12 (PISQ-12). Obesity was defined as BMI ≥ 28.0. Menstrual irregularity was defined as menstrual cycles ≥ 35 or menstrual cycles

Background: Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40–69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32–1.62] and 1.11 [1.04–1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

A lightweight forest fire detection model based on YOLOv8 is proposed in this paper in response to the problems existing in traditional sensors for forest fire detection. The performance of traditional sensors is easily constrained by hardware computing power, and their adaptability in different environments needs improvement. To balance the accuracy and speed of fire detection, the GhostNetV2 lightweight network is adopted to replace the backbone network for feature extraction of YOLOv8. The Ghost module is utilized to replace traditional convolution operations, conducting feature extraction independently in different dimensional channels, significantly reducing the complexity of the model while maintaining excellent performance. Additionally, an improved CPDCA channel priority attention mechanism is proposed, which extracts spatial features through dilated convolution, thereby reducing computational overhead and enabling the model to focus more on fire targets, achieving more accurate detection. In response to the problem of small targets in fire detection, the Inner IoU loss function is introduced. By adjusting the size of the auxiliary bounding boxes, this function effectively enhances the convergence effect of small target detection, further reducing missed detections, and improving overall detection accuracy. Experimental results indicate that, compared with traditional methods, the algorithm proposed in this paper significantly improves the average precision and FPS of fire detection while maintaining a smaller model size. Through experimental analysis, compared with YOLOv3-tiny, the average precision increased by 5.9% and the frame rate reached 285.3 FPS when the model size was only 4.9 M; compared with Shufflenet, the average precision increased by 2.9%, and the inference speed tripled. Additionally, the algorithm effectively addresses false positives, such as cloud and reflective light, further enhancing the detection of small targets and reducing missed detections.

Soil moisture is the most direct evaluation index for agricultural drought. It is not only directly affected by meteorological conditions such as precipitation and temperature but is also indirectly influenced by environmental factors such as climate zone, surface vegetation type, soil type, elevation, and irrigation conditions. These influencing factors have a complex, nonlinear relationship with soil moisture. It is difficult to accurately describe this non-linear relationship using a single indicator constructed from meteorological data, remote sensing data, and other data. It is also difficult to fully consider environmental factors using a single drought index on a large scale. Machine learning (ML) models provide new technology for nonlinear problems such as soil moisture retrieval. Based on the multi-source drought indexes calculated by meteorological, remote sensing, and land surface model data, and environmental factors, and using the Cubist algorithm based on a classification decision tree (CART), a comprehensive agricultural drought monitoring model at 10 cm, 20 cm, and 50 cm depth in Gansu Province is established. The influence of environmental factors and meteorological factors on the accuracy of the comprehensive model is discussed, and the accuracy of the comprehensive model is evaluated. The results show that the comprehensive model has a significant improvement in accuracy compared to the single variable model, which is a decrease of about 26% and 28% in RMSE and MAPE, respectively, compared to the best MCI model. Environmental factors such as season, DEM, and climate zone, especially the DEM, play a crucial role in improving the accuracy of the integrated model. These three environmental factors can comprehensively reduce the average RMSE of the comprehensive model by about 25%. Compared to environmental factors, meteorological factors have a slightly weaker effect on improving the accuracy of comprehensive models, which is a decrease of about 6.5% in RMSE. The fitting accuracy of the comprehensive model in humid and semi-humid areas, as well as semi-arid and semi-humid areas, is significantly higher than that in arid and semi-arid areas. These research results have important guiding significance for improving the accuracy of agricultural drought monitoring in Gansu Province.

Background: The development of novel therapies holds significance in improving the prognosis of ovarian cancer (OC). This study aimed to prepare 177Lu-FA-DOTA-PEG-PLGA nanoparticles and evaluate their antitumor efficacy in OC. Methods: To obtain nanoparticles with both targeting and degradable properties, we employed folate receptor (FR) as the targeting molecule, the biodegradable material polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) as the carrier matrix, and diethylene triamine pentaacetic acid (DOTA) as the metal chelating agent to prepare 177Lu-FA-DOTA-PEG-PLGA nanoparticles. The labeling yield and radiochemical purity were determined. Healthy Institute of Cancer Research (ICR) mice and Bagg albino strain C (BALB/c) nude mice bearing subcutaneously transplanted SKOV3 human OC tumors were given 18.5 Mbq of 177Lu-FA-DOTA-PEG-PLGA nanoparticles for histological distribution analysis and micro-single-photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging, respectively. Twelve BALB/c nude mice bearing subcutaneously transplanted tumors or 12 BALB/c nude mice bearing intraperitoneal metastatic tumors were assigned to control (received 0.1 mL saline solution), chemotherapy (received twice 3 mg/kg cisplatin per week), and nanoparticle groups (received 18.5 Mbq nanoparticles via tail vein or intraperitoneal injection) (n = 4 per group). Tumor growth inhibition (TGI) and ascitic fluid volume were calculated to investigate antitumor efficiency. Hematoxylin and eosin (HE) staining was performed to evaluate the safety of nanoparticles. Results: The 177Lu-FA-DOTA-PEG-PLGA nanoparticles (labeling yield: 97–98%; radiochemical purity: 96–98%) exhibited a long blood circulation time and a low renal radioactivity uptake (1.646 %ID/g). Micro-SPECT/CT imaging revealed the highest tumor-to-muscle uptake ratio of 2.81 at 24 h. After tail vein injection of nanoparticles, the tumor growth in the chemotherapy and nanoparticle groups was inhibited compared with the control group. Upon intraperitoneal injection, fluorescence intensities of intraperitoneal metastatic tumors in the control, chemotherapy and nanoparticle groups showed a statistical difference (F = 6.09, p = 0.029). Ascitic fluid volumes in the chemotherapy and nanoparticle groups were significantly lower than that in the control group (F = 13.43, p = 0.006). HE staining results showed no obvious abnormalities in the small intestine and colon tissues of the mice in the nanoparticle group compared to the control group. Conclusions: We successfully developed 177Lu-FA-DOTA-PEG-PLGA nanoparticles with a long blood circulation time and low renal radioactivity uptake. These nanoparticles could inhibit OC tumor growth and intraperitoneal metastasis, suggesting a potential novel therapy for OC patients.

Enzyme-production microorganisms typically occupy a dominant position in composting, where cellulolytic microorganisms actively engage in the breakdown of lignocellulose. Exploring strains with high yields of cellulose-degrading enzymes holds substantial significance for the industrial production of related enzymes and the advancement of clean bioenergy. This study was inclined to screen cellulolytic bacteria, conduct genome analysis, mine cellulase-related genes, and optimize cellulase production. The potential carboxymethylcellulose-hydrolyzing bacterial strain Z2.6 was isolated from the maturation phase of pig manure-based compost with algae residuals as the feedstock and identified as Bacillus velezensis. In the draft genome of strain Z2.6, 31 related cellulolytic genes were annotated by the CAZy database, and further validation by cloning documented the existence of an endo-1,4-β-D-glucanase (EC 3.2.1.4) belonging to the GH5 family and a β-glucosidase (EC 3.2.1.21) belonging to the GH1 family, which are predominant types of cellulases. Through the exploration of ten factors in fermentation medium with Plackett–Burman and Box–Behnken design methodologies, maximum cellulase activity was predicted to reach 2.98 U/mL theoretically. The optimal conditions achieving this response were determined as 1.09% CMC-Na, 2.30% salinity, and 1.23% tryptone. Validation under these specified conditions yielded a cellulose activity of 3.02 U/mL, demonstrating a 3.43-fold degree of optimization. In conclusion, this comprehensive study underscored the significant capabilities of strain Z2.6 in lignocellulolytic saccharification and its potentialities for future in-depth exploration in biomass conversion.

Abstract To assess the inter-relationships between residual depressive symptoms (RDS) and Internet addiction (IA) using network analysis among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic. RDS and IA were assessed using the Patient Health Questionnaire-9 (PHQ-9) and the Internet Addiction Test (IAT), respectively. Central symptoms and bridge symptoms in the network model were examined. A total of 1,454 adolescents met the study criteria and were included in the analyses. The prevalence of IA was 31.2% (95% CI: 28.8%-33.6%). In the network analysis, the nodes IAT15 (“Preoccupation with the Internet”), PHQ2 (“Sad mood”), and PHQ1 (“Anhedonia”) were the most central symptoms in the IA-RDS network model. Bridge symptoms included IAT10 (“Sooth disturbing about your Internet use”), PHQ9 (“Suicide ideation”), and IAT3 (“Prefer the excitement online to the time with others”). Additionally, PHQ2 (“Sad mood”) was the main node linking “Anhedonia” to other IA clusters. Internet addiction was common among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic. Core and bridge symptoms identified in this study could be prioritized as targets for the prevention and treatment of IA in this population.

BackgroundIn context of COVID-19 as a collective trauma and the intense involvement of healthcare workers (HCWs) in the pandemic, perceived stress continues to have a tremendous impact on their psychological well-being. However, few studies have attempted to delineate the underlying mechanisms. This study examined whether COVID-19-related traumatic stress symptoms and mentalization act as mediators.MethodsA sample of HCWs (N = 2610) from 22 hospitals in Beijing, China participated in this cross-sectional investigation. Data on their perceived stress, psychological well-being, the impact of event, and reflective function during the COVID-19 pandemic were collected using self-report questionnaires. Different mediating models were tested.ResultsCOVID-19-related stress symptoms and mentalization independently mediate the association between perceived stress and psychological well-being. These two mediators also compose a serial mediation model. In particular, higher perceived stress inhibits the psychological well-being of HCWs through increased severity of traumatic stress symptoms, which in turn is associated with hypomentalizing.ConclusionThese findings shed light on the mechanisms underlying the relationship between perceived stress and psychological well-being in HCWs. We strongly recommend incorporating a mentalization framework with trauma-informed practice in prevention and intervention work with this population during this and future healthcare crisis.

BackgroundHaemoglobin H (HbH) disease is caused by a disorder of α-globin synthesis, and it results in a wide range of clinical symptoms. M6A methylation modification may be one of the mechanisms of heterogeneity. Therefore, this article explored the role of methyltransferase like 16 (METTL16) in HbH disease.MethodThe results of epigenetic transcriptome microarray were analysed and verified through bioinformatic methods and qRT-PCR, respectively. The overexpression or knock down of METTL16 in K562 cells was examined to determine its role in reactive oxygen species (ROS), cell cycle processes or iron overload. YTH domain family protein 3 (YTHDF3) was knocked down in K562 cells and K562 cells overexpressing METTL16 via siRNA to investigate its function. In addition, haemoglobin expression was detected through benzidine staining. qRT-PCR, WB, methylated RNA Immunoprecipitation (MeRIP) and (RNA Immunoprecipitation) RIP experiments were conducted to explore the mechanism of intermolecular interaction.ResultsMETTL16, YTHDF3 and solute carrier family 5 member 3 (SLC5A3) mRNA and the methylation level of SLC5A3 mRNA were downregulated in HbH patients. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA expression was negatively correlated with HGB content among patients with HbH-CS disease. Overexpression of METTL16 increased ROS and intracellular iron contents in K562 cells, changed the K562 cell cycle, reduced hemin-induced haemoglobin synthesis, increased the expressions of SLC5A3 and HBG and increased SLC5A3 mRNA methylation levels. Knockdown of METTL16 reduced ROS and intracellular iron contents in K562 cells. Hemin treatment of K562 cells for more than 14 days reduced the protein expressions of METTL16 and SLC5A3 and SLC5A3 mRNA methylation levels. Knockdown of YTHDF3 rescued the intracellular iron content changes induced by the overexpression of METTL16. The RIP experiment revealed that SLC5A3 mRNA can be enriched by METTL16 antibody.ConclusionMETTL16 may affect the expression of SLC5A3 by changing its m6A modification level and regulating ROS synthesis, intracellular iron and cycle of red blood cells. Moreover, METTL16 possibly affects the expression of haemoglobin through IGF2BP3, which regulates the clinical phenotype of HbH disease.

The Dongbao River Xin’an Bridge is the first hybrid continuous girder bridge with corrugated steel webs in China. To assess its service conditions and guarantee its safe operation, a continuous structural health monitoring (SHM) system is designed in this paper. The SHM system consists of a sensor system, a data acquisition and transmission system, and a data processing and control system. The measurement parameters, including vehicle loads, temperature, deformation, strain, and acceleration, are determined, and a detailed sensor layout is given based on the mechanical characteristics of the bridge. The SHM system adopts a bus gateway and an IP modem to collect and transmit sensor data. Monitoring data from October 9, 2022, to March 16, 2023, were analyzed. The probability distributions of the daily maximum temperature differences and vehicle loads are reconstructed. The correlation of girder deflection and strain with ambient temperature has been demonstrated. The identification and tracking of modal parameters are implemented. The results show that the maximum deflection is within the threshold range and that the modal parameters are basically stable. All the results demonstrate the healthy structural condition of the bridge and the excellent working performance of the SHM system. The collected data provide scientific guidance for the performance evaluation of the Dongbao River Xin’an Bridge and the optimized design of similar bridges.

IntroductionLeaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5).MethodsWe created MRL/lpr mice with global Tlr5 deletion through CRISPR/Cas9 and investigated lupus-like disease in these mice.ResultContrary to our hypothesis that the deletion of Tlr5 would attenuate lupus, our results showed exacerbation of lupus with Tlr5 deficiency in female MRL/lpr mice. Remarkably higher levels of proteinuria were observed in Tlr5-/- MRL/lpr mice suggesting aggravated glomerulonephritis. Histopathological analysis confirmed this result, and Tlr5 deletion significantly increased the deposition of IgG and complement C3 in the glomeruli. In addition, Tlr5 deficiency significantly increased renal infiltration of Th17 and activated cDC1 cells. Splenomegaly and lymphadenopathy were also aggravated in Tlr5-/- MRL/lpr mice suggesting impact on lymphoproliferation. In the spleen, significant decreased frequencies of regulatory lymphocytes and increased germinal centers were observed with Tlr5 deletion. Notably, Tlr5 deficiency did not change host metabolism or the existing leaky gut; however, it significantly reshaped the fecal microbiota.ConclusionGlobal deletion of Tlr5 exacerbates lupus-like disease in MRL/lpr mice. Future studies will elucidate the underlying mechanisms by which Tlr5 deficiency modulates host-microbiota interactions to exacerbate lupus.

Objective: The three-dimensional morphological structures of periodontal ligaments (PDLs) are important data for periodontal, orthodontic, prosthodontic, and implant interventions. This study aimed to employ a deep learning (DL) algorithm to segment the PDL automatically in cone-beam computed tomography (CBCT). Method: This was a retrospective study. We randomly selected 389 patients and 1734 axial CBCT images from the CBCT database, and designed a fully automatic PDL segmentation computer-aided model based on instance segmentation Mask R-CNN network. The labels of the model training were ‘teeth’ and ‘alveolar bone’, and the ‘PDL’ is defined as the region where the ‘teeth’ and ‘alveolar bone’ overlap. The model’s segmentation performance was evaluated using CBCT data from eight patients outside the database. Results: Qualitative evaluation indicates that the PDL segmentation accuracy of incisors, canines, premolars, wisdom teeth, and implants reached 100%. The segmentation accuracy of molars was 96.4%. Quantitative evaluation indicates that the mIoU and mDSC of PDL segmentation were 0.667 ± 0.015 (>0.6) and 0.799 ± 0.015 (>0.7) respectively. Conclusion: This study analysed a unique approach to AI-driven automatic segmentation of PDLs on CBCT imaging, possibly enabling chair-side measurements of PDLs to facilitate periodontists, orthodontists, prosthodontists, and implantologists in more efficient and accurate diagnosis and treatment planning.

Abstract Introduction Neonatal hypoxic–ischemic brain damage (HIBD) is a serious inflammatory injury. At present, the standard treatment for this disease is hypothermia therapy, and the effect of drug intervention is still limited. L‐F001 is a compound of fasudil and lipoic acid. Previous in vitro experiments have confirmed that L‐F001 has anti‐inflammatory neuroprotective functions. However, its therapeutic effect on neonates with HIBD remains unknown. This study was aimed at exploring the therapeutic effect of L‐F001 on HIBD rats. Methods The newborn rats were divided into three groups: Sham operation group, HIBD group, and HIBD + L‐F001 group. HE staining, Nissil staining, the immunofluorescence of iNOS and COX‐2, ELISA (IL‐1β, IL‐6, TNF‐α, and IL‐10), and western blotting analyses were performed to determine the therapeutic effect of L‐F001. Finally, we evaluated the growth and development of each group by measuring body weight. Results The hippocampal structure of HIBD rats was disordered, and the Nissil body was small and shallow. The expressions of iNOS and COX‐2 in HIBD rats were increased, whereas the expressions of IL‐1β, IL‐6, and TNF‐α in plasma were upregulated, and the expression of IL‐10 was decreased. L‐F001 could improve the tissue structure and reduce the expression of iNOS and COX‐2 in HIBD rats. Meanwhile, L‐F001 could also reduce the expression of pro‐inflammatory cytokines and restore the content of anti‐inflammatory cytokines in plasma. We further found that the TLR4 pathway was activated after hypoxic‐ischemia in neonatal rats. L‐F001 could inhibit the activation of TLR4 pathway. Finally, we found that after L‐F001 treatment, the body weight of HIBD rats increased significantly compared with the untreated group. Conclusions L‐F001 antagonizes the inflammatory response after hypoxic‐ischemia by inhibiting the activation of the TLR4 signaling pathway, thus playing a neuroprotective role. L‐F001 may be a potential therapeutic agent for neonatal HIBD.