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Abstract Adolescence is a time when important changes occur in behavioral development, and previous studies have confirmed the relationship between excessive Internet use and decreased oral health behavior. Our purpose is to identify the indirect effects and behavioral factors of smartphone screen time on the caries symptom experience of adolescents. Using data from the 16–17th Korea youth risk behavior web based survey (2020–2021), we investigated the smartphone screen time of 109,796 students in middle school 1st to high school 3rd. Adolescents who used smartphones more than 6 h per week were 28% more likely to experience caries symptoms than those who used smartphones less than 2 h (odds ratio = 1.28; 95% confidence interval, 1.22–1.35). Those who consumed cariogenic drinks more than once a day were 25% more likely to experience caries symptoms, and those who brushed their teeth less than once a day were 26% more likely to experience caries symptoms (odds ratio = 1.25, 1.26; 95% confidence interval, 1.07–1.46, 1.06–1.51). Excessive smartphone screen time is associated with addictive eating habits and reduced physical activity that increase cariogenic dietary behaviors, and decrease oral health behaviors. It suggests that excessive smartphone use indirectly related to the experience of caries symptoms.

Abstract The significance of health literacy for elderly individuals with chronic illnesses lies in managing and delaying disease development, which is affected by personal and environmental factors. Family communication can provide an emotional support environment; self-efficacy is an important factor of subjective initiative and personality. A relatively persistent thinking and behavior pattern can affect the environment, subjective initiative, and individual health outcomes. This study aims to explore the effects of the Big Five personality traits on the health literacy of elderly individuals with chronic illnesses and to hypothesize that family communication and self-efficacy mediate the Big Five personalities and health literacy. A cross-sectional study of 2251 elderly individuals with chronic diseases was conducted through nationwide random quota sampling. The structural equation model was used to explore the mediating role of family communication and self-efficacy between the Big Five personality and health literacy. Family communication played a simple mediating role in the influence of extraversion, agreeableness, conscientiousness, and neuroticism on health literacy. Self-efficacy played a simple mediating role in the influence of the Big Five personalities on health literacy. Self-efficacy and family communication played a chain mediating role between extraversion, agreeableness, conscientiousness, neuroticism, and health literacy. Nurses can enhance the health literacy of elderly individuals with chronic illnesses with extraversion, agreeableness, conscientiousness, and neuroticism through family communication and self-efficacy while promoting the health literacy of those with openness through self-efficacy.

Abstract Background Previous studies have suggested a significant association between mobile phone addiction (MPA) and non-suicidal self-injury (NSSI) in general adolescents. However, limited research has analyzed this relationship in clinical populations, such as those with major depressive disorder (MDD), and the potential mediation mechanisms remain unclear. Methods This cross-sectional observational study analyzed data from 2343 adolescents with MDD (77.9% females; mean age = 14.99 years, SD = 1.65). Using mediation models, we explored the roles of self-esteem and depression severity (measured by Patient Health Questionnaire-9) in the relationship between MPA and NSSI. Additionally, we evaluated the associations between existing school-implemented mobile phone usage policies and levels of MPA, self-esteem, depression symptoms, and NSSI. Results MPA was significantly associated with NSSI, with low self-esteem and increased depression severity almost entirely mediating this effect (log-odds = 0.016, 95%CI = 0.02–0.013). Subdomains of MPA, including inability to control craving, feelings of anxiety, and productivity loss, followed similar mediation models, while the subdomain of withdrawal/escape had a partial effect mediated by depression severity. Additionally, enforced restrictions on mobile phone usage in schools did not show positive effects on related variables and even exacerbated MPA by increasing cravings and reducing productivity. Conclusion Our study suggests that MPA in adolescents with MDD may be an important risk factor for NSSI occurrence, and that reducing the negative impact of mobile phone usage on self-esteem and depressive symptoms, rather than simply restricting usage, may be crucial for effective intervention.

Abstract Background The aim of this study is to assess the feasibility and safety of monitored anesthesia care (MAC) versus intubated general anesthesia (IGA) for patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). Methods This prospective observational study included patients scheduled for cardiac surgery involving CPB at our institution between April 2012 and February 2017. The enrolled patients were categorized into MAC and IGA groups. MAC involved local anesthesia at the sternotomy site, sedation with dexmedetomidine, analgesia with remifentanil/sufentanil, and electroacupuncture (EA). Eleven patients underwent MAC, and 13 patients received IGA. There were no instances of conversion from MAC to IGA, and both groups exhibited no major complications. The demographic characteristics, baseline parameters, and operative variables were comparable between the two groups. Results Intraoperative opioid consumption was significantly lower in the MAC group compared to the IGA group (P

Abstract Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the expression of KLF2 and CEBPA, both of which further synergistically drive the differentiation program of AT1 cells and benefit regeneration and anti-fibrosis. Our findings elucidate the modulation function of the TRβ-KLF2/CEBPA axis on AT2 cell fate and provide a potential treatment strategy to facilitate lung regeneration and anti-fibrosis.

Abstract The need for equitable access to primary healthcare services in the current global context has attracted widespread attention, prompting nations to continuously enhance their grassroots medical service levels. In response, China launched the "Healthy China" initiative, which prioritizes the enhancement of national health as a core goal of the healthcare system and uses this opportunity to deepen reforms aimed at strengthening primary care. However, in remote and rural areas, the optimization of medical resource allocation and the achievement of balanced service development remain critical challenges owing to limited resources. This study selected Liannan Yao Autonomous County, which is situated in the northwestern corner of Guangdong Province, as a case study due to its remote mountainous location, underdeveloped economy, and minority region characteristics. Through field research and interviews, this study thoroughly explored the needs of both supply and demand, factoring in elements such as the service capability of healthcare facilities and residents' travel thresholds to enhance the two-step floating catchment area model, thus making it more applicable to remote villages. By integrating electric bikes and cars, which are the primary means of transportation in rural areas, this study conducted a thorough analysis and comparison of the accessibility of medical services in Liannan Yao Autonomous County (Liannan County) . The results reveal significant disparities in healthcare accessibility, an uneven distribution of medical resources, and varying impacts of transportation conditions and facility service capabilities on accessibility. Notably, the study revealed that improving transportation conditions alone has limited effects in rural areas; the key lies in balancing medical service capabilities and the rationality of overall layouts. From the perspectives of equity and efficiency, this study employs the equitable coverage model and the efficiency-driven model to construct two scenarios, comparing accessibility changes in Liannan County under both conditions and proposing strategies to improve the spatial layout of local healthcare facilities. This research not only deepens the understanding of healthcare service accessibility in rural areas but also provides a scientific basis for optimizing resource allocation and enhancing primary medical services, offering valuable guidance and reference for Liannan County and other similar rural regions.

Abstract Objective This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. Methods A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups’ progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. Results The surgical staging group started radiotherapy 10.2 days (range 9–12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). Conclusion Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs. Graphical Abstract

Abstract Background Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children’s quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. Methods This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. Discussion This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. Trial registration This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Abstract Aims The purpose of this study was to analyze the dynamic trends of ischemic heart disease (IHD) mortality attributable to high low-density lipoprotein cholesterol (LDL-C). Methods Data on IHD mortality attributable to high LDL-C from 1990 to 2021 were extracted from the global disease burden database. Joinpoint software was used to estimate the average annual percentage change (AAPC) in the age-standardized mortality rate (ASMR). An age‒period‒cohort model was used to analyze the impacts of age, period, and cohort on these changes. The Bayesian framework was used to predict IHD mortality attributable to high LDL-C from 2022 to 2040. Results The overall ASMR of IHD attributable to high LDL-C decreased from 50. 479 per 100,000 people in 1990 to 32.286 per 100,000 people in 2021, and ASMR of IHD attributable to high LDL-C was higher in males than in females. The longitudinal age curves of the overall IHD mortality attributable to high LDL-C showed a monotonic upward trend, especially after 65 years of age. The period and cohort effect relative risk (RR) values of overall IHD mortality attributable to high LDL-C showed a downward trend. The overall ASMR of IHD attributable to high LDL-C is predicted to show a downward trend, and male IHD mortality attributable to high LDL-C is expected to be higher than that of females. Conclusion This study revealed a sustained decrease in IHD mortality attributable to high LDL-C over three decades, with a continued decline expected. Despite this, gender disparities persist, with males experiencing higher mortality rates and elderly individuals remaining a vulnerable group.

Abstract High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM’s gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.

Abstract Targeted alpha (α) therapy (TAT) is an emerging therapeutic strategy for cancer treatment. To evaluate the safety and efficacy of targeted α‐therapy, the biodistribution and internal radiation dose of α‐emitting radionuclides should be determined. In vivo imaging of these radionuclides often involves the detection of gamma rays, X‐rays, and positrons generated during their complex decay processes. This review aims to classify the α‐emitting radionuclides (astatine‐211, actinium‐225, radium‐223, bismuth‐212, bismuth‐213, thorium‐227, and terbium‐149) according to their imageable signals. Additionally, this study summarizes various imaging modalities, including gamma camera imaging, single‐photon emission computed tomography, positron emission tomography, Compton imaging, bremsstrahlung imaging, and Cerenkov luminescence imaging, which hold potential for imaging α‐emitting radionuclides, to explore their biomedical applications in qualitative nuclide tracing and diagnosis, quantifying pharmacokinetics, and assessing prognosis and response to therapy.

Abstract Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. “Organs-on-chips: Intestine” is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

Abstract Optically addressable spin defects hosted in two-dimensional van der Waals materials represent a new frontier for quantum technologies, promising to lead to a new class of ultrathin quantum sensors and simulators. Recently, hexagonal boron nitride (hBN) has been shown to host several types of optically addressable spin defects, thus offering a unique opportunity to simultaneously address and utilise various spin species in a single material. Here we demonstrate an interplay between two separate spin species within a single hBN crystal, namely S = 1 boron vacancy defects and carbon-related electron spins. We reveal the S = 1/2 character of the carbon-related defect and further demonstrate room temperature coherent control and optical readout of both S = 1 and S = 1/2 spin species. By tuning the two spin ensembles into resonance with each other, we observe cross-relaxation indicating strong inter-species dipolar coupling. We then demonstrate magnetic imaging using the S = 1/2 defects and leverage their lack of intrinsic quantization axis to probe the magnetic anisotropy of a test sample. Our results establish hBN as a versatile platform for quantum technologies in a van der Waals host at room temperature.

Abstract Background Recent studies have reported the inhomogeneity in the light emitted by dental light-curing units (LCUs). It is essential to understand how this uneven light distribution affects the physical properties of resin-based composites (RBCs) at various points across their surfaces. This study aimed to evaluate the effect of LCU beam’s inhomogeneity on the microhardness of RBCs with different shades and thicknesses. Methods Four body (A1B, A2B, A3B, and A4B), one dentin (A3D), and one enamel shade (A3E) of RBC (Filtek Z350 XT) were examined. The specimens were fabricated in four thicknesses (1, 2, 3, and 4 mm) and subjected to a 40-second light-curing. Vickers microhardness testing was performed at the center point, and 3 mm left and right from the center at the bottom surface of each sample. The LCU beam profile was characterized using a beam profiler, while irradiance after specimen passage was measured using a spectrometer. One-way analysis of variance (ANOVA) and Tukey’s post-hoc tests were used to analyze the effects of shades and thicknesses on irradiance and microhardness, respectively. One-way repeated-measures ANOVA was used to compare the microhardness across different points. Pearson’s correlation analysis examined the relationship between irradiance and microhardness. Results The beam profile of LCU revealed inhomogeneous light distribution. Light irradiance was decreased with both the increase in thickness and darker shade of the specimens (p

Abstract The anticancer drug of tyrosine kinase-inhibitors (TKIs) has significantly improved the prognosis of patients with specific leukemia but has also increased the risk of organ adverse reactions. Herein, we present a case of a patient diagnosed with myeloproliferative neoplasms who experienced recurrent chest pain after receiving treatment with Olverembatinib. Electrocardiography and coronary angiography confirmed the diagnosis of myocardial infarction with non-obstructive coronary arteries. This case serves as a reminder for clinicians to pay more attention and actively prevent the cardiac adverse reactions of TKIs when using such medications.

Abstract Background Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co‐differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Methods Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real‐time polymerase chain reaction, Cell Counting Kit‐8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. Results PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA‐432‐5p (miR‐432‐5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR‐433‐3p in PMECs, and upregulate zinc finger AN1‐type containing 5 (ZFAND5) expression by targeting miR‐3613‐5p in PCs. Conclusions Our results suggest that circPMS1 promotes cell proliferation through the miR‐432‐5p/DEPDC1 or miR‐432‐5p/POL2D axis in PASMCs, through the miR‐433‐3p/MXI1 axis in PMECs, and through the miR‐3613‐5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

Abstract Background Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy. Methods From December 2022 to December 2023, a large-scale screening study was conducted in Fujian, China. Based on traditional Chinese medicine theory, we simultaneously collected tongue images and inquiry information from 1034 participants, considering the potential of these data for PLGC screening. Then, we introduced inquiry information for the first time, forming a multimodality artificial intelligence model to integrate tongue images and inquiry information for pre-endoscopic screening. Moreover, we validated this approach in another independent external validation cohort, comprising 143 participants from the China-Japan Friendship Hospital. Results A multimodality artificial intelligence-assisted pre-endoscopic screening model based on tongue images and inquiry information (AITonguequiry) was constructed, adopting a hierarchical prediction strategy, achieving tailored endoscopic recommendations. Validation analysis revealed that the area under the curve (AUC) values of AITonguequiry were 0.74 for overall PLGC (95% confidence interval (CI) 0.71–0.76, p

Esophageal cancer is predominantly diagnosed at a locally advanced or distant metastasis stage in patients. Once the disease progresses to the advanced stage, its prognosis is poor, and the median overall survival time of patients receiving traditional chemotherapy is less than one year. Treatment with immune checkpoint inhibitors has provided new opportunities to patients with esophageal cancer and changed the previous treatment pattern. Chemotherapy combined with immunotherapy (PD-1 inhibitor) has become the standard first-line treatment for advanced esophageal cancer. However, chemotherapy combined with immunotherapy have been reported a median overall survival time of only 12.4-17.2 months for patients. Such a survival time remains insufficient to meet clinical needs. Combining systemic treatment with local treatment and seeking new comprehensive treatment models are important research directions for improving efficacy. This article reviews the research progress and prospects of radiotherapy in the treatment of advanced esophageal cancer.

Abstract In the last few years, with the fast growing of neural network field such as those for virtual reception and enhanced nature, the practice and theory of conventional landscape are impacted and challenged by virtual landscape based on these sorts of neural network technologies. On the one hand, the virtual landscape changes the carrier of landscape design from material real world to the networked virtual world, which breaks the traditional way of generating landscape and the way of expression of results. On the other hand, the virtualized and networked morphological characteristics of the virtual landscape itself and its capacity that can offer users a sense of immertion, interplay and enjoyment of the experience provide a way of extending and deepening the realm of scenery. It is also a new type of landscape that conforms to the trend of the times created in the background of the fast evolution of scientific and technical development. Virtual landscape brings new construction thinking and practical means for the application of digital city, the construction of urban context, and the development and utilization of relics. It provides an important research source for thinking about the relationship between current humanities and science, material and virtual, history and contemporary. After the research and experiment on the urban environment landscape design of PSO-BP neural network, the experimental data showed that before using the neural network method to improve Yanta East Garden, 57% of the crowd were satisfied with the overall impression of Yanta East Garden, and 17% were dissatisfied. After the improvement, 67% were satisfied with the landscape of Yanta East Garden, only 5% were dissatisfied, and the landscape satisfaction increased by 10%. The survey group believed that the landscape color of Yanta East Garden was full of historical flavor, especially the small sculptures convey the unique Qin Opera culture. The above data show that the method based on neural network is very suitable for the improvement and development of urban landscape design.

Abstract Background Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades. Aims To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats. Methods Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined. Results The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application. Conclusions ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. Methods and design The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. Conclusions As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. Registration Number in ClinicalTrials.gov NCT05311072.

Abstract Objective To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). Methods Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. Results (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4–5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. Conclusions The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

Abstract Background Traditional fixed thresholds for oral glucose tolerance test (OGTT) results may inadequately prevent adverse pregnancy outcomes in twin pregnancies. This study explores latent OGTT patterns and their association with adverse outcomes. Methods This study retrospectively analyzed 2644 twin pregnancies using latent mixture models to identify glucose level patterns (high, HG; medium, MG; and low, LG) and their relationship with maternal/neonatal characteristics, gestational age at delivery, and adverse outcomes. Results Three distinct glucose patterns, HG, MG, and LG patterns were identified. Among the participants, 16.3% were categorized in the HG pattern. After adjustment, compared with the LG pattern, the HG pattern was associated with a 1.79‐fold, 1.66‐fold, and 1.32‐fold increased risk of stillbirth, neonatal respiratory distress, and neonatal hyperbilirubinemia, respectively. The risk of neonatal ICU admission for MG and HG patterns increased by 1.22 times and 1.32 times, respectively, compared with the LG pattern. As gestational weeks increase, although there is an overlap in the confidence intervals between the HG pattern and other patterns in the restricted cubic splines analysis, the trend suggests that pregnant women with the HG pattern are more likely to face risks of their newborns requiring neonatal intensive care unit admission, and adverse comprehensive outcomes, compared with other patterns. In addition, with age and body mass index increasing in HG mode, gestation weeks at delivery tend to be later than in other modes. Conclusion Distinct OGTT glucose patterns in twin pregnancies correlate with different risks of adverse perinatal outcomes. The HG pattern warrants closer glucose monitoring and targeted intervention.

Fibrosis is the process whereby cells at a damaged site are transformed into fibrotic tissue, comprising fibroblasts and an extracellular matrix rich in collagen and fibronectin, following damage to organs or tissues that exceeds their repair capacity. Depending on the affected organs or tissues, fibrosis can be classified into types such as pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and cardiac fibrosis. The primary pathological features of fibrotic diseases include recurrent damage to normal cells and the abnormal activation of fibroblasts, leading to excessive deposition of extracellular matrix and collagen in the intercellular spaces. However, the etiology of certain specific fibrotic diseases remains unclear. Recent research increasingly suggests that the cytoskeleton plays a significant role in fibrotic diseases, with structural changes in the cytoskeleton potentially influencing the progression of organ fibrosis. This review examines cytoskeletal remodeling and its impact on the transformation or activation of normal tissue cells during fibrosis, potentially offering important insights into the etiology and therapeutic strategies for fibrotic diseases.

ObjectiveTo investigate the effects of multiple stress events in different stages of life on the incidence of metabolic syndrome (MetS).MethodsMiners from Tangshan, China, were recruited for this study. Workers of the Kailuan Mining Group were evaluated to investigate whether exposure to Tangshan earthquakes during the fetal period in 1976. Adult life events and childhood trauma were assessed separately via the Life Event Scale and Childhood Trauma Questionnaire. The subjects were physically examined and general demographic data such as waist circumference were collected. Blood samples were collected for measurement of metabolic parameters. Corticotropin releasing hormone(CRH) levels was measured by enzyme-linked immunosorbent assay (ELISA). The subjects were divided into four groups according to their exposure to traumatic events in different stages of life: no exposure group, 1-exposure group, 2-exposures group, and 3-exposures group. The incidence of MetS, metabolic parameters and CRH levels in each of the four groups was compared.ResultsIn all, 626 people were enrolled; of these, 183, 262, 150, and 31 were in the no exposure, 1-exposure, 2-exposures, and 3-exposure groups, respectively. A remarkable variation in the incidence of MetS was observed among the four groups (x2 = 16.462, P

Background: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions. Methods: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales. Results: Throughout a median follow-up of 37.60 (interquartile: 24.77–50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend

Industrial parks are the important carriers to promote regional innovation and economic development. The policy preferences of the government, the support orientation of the industrial park and the innovation willingness of the enterprises in the park play a significant role in promoting the high-quality development of the industrial parks. In order to clarify the decision-making process of each subject, this paper constructs a triple evolutionary game model between the government, industrial park and enterprises in the park, Matlab software is used to conduct simulation research, and the strategy selection of each subject in the process of promoting high-quality development of the park is analyzed, as well as the influence of variables on the evolutionary game. Through numerical simulation, this study finds that the strategy choice of the government and the industrial park is influenced by the cost of innovation management for enterprises. In addition, the innovation willingness of enterprises is affected by the policy preference of the government and the support orientation of the industrial park, the excessive tax preference of the government will lead to negative innovation behaviors of the enterprises, the “inward incentives” support orientation of the industrial park can stimulate the enterprises’ innovation willingness on “active innovation”, the enterprises behavior of “active innovation” will strengthen the “inward incentives” support orientation of the industrial park in turn. The difference of the benefits and the costs between the two support orientations by the industrial park will lead to the equilibrium points stabilized at different strategy combinations. Based on these findings, countermeasures and suggestions are proposed in this study.

Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT‒qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.

Effective exploration of the pattern dynamic behaviors of reaction–diffusion models is a popular but difficult topic. The Schnakenberg model is a famous reaction–diffusion system that has been widely used in many fields, such as physics, chemistry, and biology. Herein, we explore the stability, Turing instability, and weakly non-linear analysis of the Schnakenberg model; further, the pattern dynamics of the fractional-in-space Schnakenberg model was simulated numerically based on the Fourier spectral method. The patterns under different parameters, initial conditions, and perturbations are shown, including the target, bar, and dot patterns. It was found that the pattern not only splits and spreads from the bar to spot pattern but also forms a bar pattern from the broken connections of the dot pattern. The effects of the fractional Laplacian operator on the pattern are also shown. In most cases, the diffusion rate of the fractional model was higher than that of the integer model. By comparing with different methods in literature, it was found that the simulated patterns were consistent with the results obtained with other numerical methods in literature, indicating that the Fourier spectral method can be used to effectively explore the dynamic behaviors of the fractional Schnakenberg model. Some novel pattern dynamics behaviors of the fractional-in-space Schnakenberg model are also demonstrated.

BackgroundIdiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acids play a crucial role in IPF, but the role of D-amino acids is not yet clear. The aim of this study was to identify novel mediators in order to test the hypothesis that D-amino acid oxidase (DAO) plays a significant role in the pathogenesis of IPF.MethodsWe analyzed DAO gene expression in patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis. We performed in vitro and in vivo assays to determine the effect of DAO on primary type II alveolar epithelial cells from mice and A549 cells.ResultsDAO expression was downregulated in the lungs of IPF patients and BLM-induced fibrotic mice. Treatment with D-serine (D-Ser) or drug inhibition of DAO promoted cell senescence through the p53/p21 pathway. Dao−/− mice showed an intensified fibrotic response, and the anti-fibrotic role of T3 was abolished.ConclusionWe concluded that the DAO-p53/p21 axis might be a key anti-fibrotic pathway regulating the progress of fibrosis and facilitating the therapeutic role of T3.

IntroductionThe selection of an optimal scale or granularity in landscape analysis is pivotal for uncovering inherent patterns and changes driven by processes. Variations in spatial resolution can significantly alter the proportions and distributions of various landscape types, thereby impacting the assessment of landscape patterns. Despite its importance, the scale factor is frequently neglected in studies focusing on long-term landscape dynamics.MethodsBridging this gap, we utilized remote sensing imagery data from 1986 to 2020 for Lushui City, integrating remote sensing (RS) and geographic information system (GIS) technologies to generate land cover maps. Our focus centered on investigating the sensitivity of landscape pattern indices within the 30–1000m scale. Combining the first scale domain with an information loss assessment model, we identified the optimal granularity for the analysis, conducting a detailed spatiotemporal examination of landscape pattern from 1986 to 2020 using the index analysis method.Results and discussionThe results show that: (1) The dominance of forests in Lushui City, yet reveal a significant increase in construction land area over the study period, primarily driven by the conversion of forest and grassland. (2) Among the 10 examined indices, four (PD, ED, TE, and LSI) demonstrated predictable responses to changes in granularity, while three (PAFEAC, COHESION, AI) exhibited unpredictable stepwise reactions. Three indices (LPI, SHDI, PLAND) displayed minimal regularity to granularity changes. (3) The optimal long-term landscape analysis granularity for Lushui was identified as 100 m. (4) Before 1996, the city’s landscape exhibited characteristics of aggregation, good connectivity, and minimal anthropogenic disturbance. However, post-1996, the landscape experienced disruptions, leading to an overall increase in fragmentation. The expansion of cultivated land and construction land due to urbanization has intensified landscape fragmentation. However, policies such as converting cropland to forest and planned ecological civilization initiatives have restored forest coverage and improved landscape cohesion and connectivity in Lushui City. This research offers vital insights for ecological planning and resource management in alpine valley watershed cities, deepening our grasp of landscape pattern evolution.

The two-mass nonlinear vocal cord vibration system (VCVS) serves as a mechanical representation of the fundamental vocalization process. Traditional models of the VCVS, which are based on integer-order dynamics, often overlook the impact of memory effects. To address this limitation and enhance the accuracy of simulations, this study incorporates the memory effects of vocal cord vibrations by integrating the Grunwald–Letnikov fractional derivative into the two-mass nonlinear VCVS framework. Initially, a high-precision computational scheme is formulated for the two-mass nonlinear fractional-order VCVS. Subsequently, the model undergoes a comprehensive series of numerical simulations to investigate its dynamic characteristics. The findings reveal that the dynamics of the fractional-order VCVS exhibit a significantly higher complexity compared to the conventional integer-order models, with the emergence of novel chaotic behaviors that were previously unobserved.

Canopy layer urban heat island (CLUHI) is closely related to about 4.7 billion urban residents’ well-being. Compared with sparse observation stations, remote sensing can obtain spatially continuous temperature, which is conducive to intra-annual variation and associated factors of CLUHI over large regions. Such research is scarce, especially from apparent temperature perspective. Thus, the intra-annual spatio-temporal variations and twelve determinants of CLUHI intensities (CLUHIIs) were investigated for 917 urban region agglomerations in China’s five ecological regions, using remotely sensed near-surface air temperature, apparent temperature and other multi-source data, and several spatial analysis and mathematical statistic methods. The findings revealed that annual CLUHIIs by mean temperatures were most between 0.5 and 1.0 ℃, higher in the summer and spring, and larger in North China than South China in the summer. The annual CLUHIIs by maximum temperatures were negative in several cities, especially in rainless West China. North China generally had stronger CLUHIIs by minimum temperatures in all seasons compared to South China. The CLUHIIs by mean apparent temperatures were larger in the summer (most between 0.5 and 2.0 ℃) and varied across ecological regions. Significant positive correlations generally existed among CLUHIIs by various air temperature and land surface temperature indices (p

Summary: Extracellular vesicles (EVs) are secreted, cell-derived, membrane-bound compartments implicated in various diseases for their ability to influence distant targets and as carriers of biomarkers. Here, we present a protocol for separating EVs from mammalian pancreatic cancer cells and their characterization using western blot and electron microscopy. We then demonstrate how they are utilized to affect tumor development in a murine model of metastatic pancreatic cancer including a method to quantify hepatic tumor burden in histologic samples.For complete details on the use and execution of this protocol, please refer to Dudgeon et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In order to improve the biological effect of proton therapy, the authors first propose a new method of boron-based proton-enhanced radiotherapy in a " ternary " radiotherapy mode, based on the existing sensitizing effect of proton radiotherapy: i.e, Boron-based mediators (11B and 10B) induce the proton-hydrogen-boron fusion reaction of the low-energy protons arriving at the Bragg peak region of the tumor target area (p+11B→3α) and thermal neutron capture (10B+n→7Li3+(0.84 MeV)+4He2+(1.47 MeV)+\begin{document}$ {\text{γ}} $\end{document}(0.477 MeV)), which release low-energy α-particles with high LETs to enhance the biological effect of proton dose in the target area, thus improve the clinical effect of proton therapy. Then, the advantages and disadvantages of the "ternary" model were analyzed from the theoretical basis and current research status, and finally, the "ternary" model is summarized and prospected.

Abstract Sound event detection involves identifying sound categories in audio and determining when they start and end. However, in real-life situations, sound events are usually not isolated. When one sound event occurs, there are often other related sound events that take place as co-occurrences or successive occurrences. The timing relationship of sound events can reflect their characteristics. Therefore, this paper proposes a sound event detection method for traffic scenes based on a graph convolutional network, which considers this timing relationship as a form of multimodal information. The proposed method involves using the acoustic event window method to obtain co-occurrences or successive occurrences of relationship information in the sound signal while filtering out possible noise relationship information. This information is then represented as a graphical structure. Next, the graph convolutional neural network is improved to balance relationship weights between neighbors and itself and to avoid excessive smoothing. It is used to learn the relationship information in the graph structure. Finally, the convolutional recurrent neural network is used to learn the acoustic feature information of sound events, and the relationship information of sound events is obtained by multi-modal fusion to enhance the performance of sound event detection. The experimental results show that using multi-modal information with the proposed method can effectively improve the performance of the model and enhance the perception ability of smart cars in their surrounding environment while driving.

Abstract We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

Abstract Aglaonema commutatum is a famous species in the Aglaonema genus, which has important ornamental and economic value. However, its chloroplast genome information and phylogenetic relationships among popular green cultivars of Aglaonema in southern China have not been reported. Herein, chloroplast genomes of one variety of A. commutatum and seven green cultivars of Aglaonema, namely, A. commutatum ‘San Remo’, ‘Kai Sa’, ‘Pattaya Beauty’, ‘Sapphire’, ‘Silver Queen’, ‘Snow White’, ‘White Gem’, and ‘White Horse Prince’, were sequenced and assembled for comparative analysis and phylogeny. These eight genomes possessed a typical quadripartite structure that consisted of a LSC region (90,799–91,486 bp), an SSC region (20,508–21,137 bp) and a pair of IR regions (26,661–26,750 bp). Each genome contained 112 different genes, comprising 79 protein-coding genes, 29 tRNA genes and 4 rRNA genes. The gene orders, GC contents, codon usage frequency, and IR/SC boundaries were highly conserved among these eight genomes. Long repeats, SSRs, SNPs and indels were analyzed among these eight genomes. Comparative analysis of 15 Aglaonema chloroplast genomes identified 7 highly variable regions, including trnH-GUG-exon1-psbA, trnS-GCU-trnG-UCC-exon1, trnY-GUA-trnE-UUC, psbC-trnS-UGA, trnF-GAA-ndhJ, ccsA-ndhD, and rps15-ycf1-D2. Reconstruction of the phylogenetic trees based on chloroplast genomes, strongly supported that Aglaonema was a sister to Anchomanes, and that the Aglaonema genus was classified into two sister clades including clade I and clade II, which corresponded to two sections, Aglaonema and Chamaecaulon, respectively. One variety and five cultivars, including A. commutatum ‘San Remo’, ‘Kai Sa’, ‘Pattaya Beauty’, ‘Silver Queen’, ‘Snow White’, and ‘White Horse Prince’, were classified into clade I; and the rest of the two cultivars, including ‘Sapphire’ and ‘White Gem’, were classified into clade II. Positive selection was observed in 34 protein-coding genes at the level of the amino acid sites among 77 chloroplast genomes of the Araceae family. Based on the highly variable regions and SSRs, 4 DNA markers were developed to differentiate the clade I and clade II in Aglaonema. In conclusion, this study provided chloroplast genomic resources for Aglaonema, which were useful for its classification and phylogeny.

Abstract Stretchable phosphorescence materials potentially enable applications in diverse advanced fields in wearable electronics. However, achieving room-temperature phosphorescence materials simultaneously featuring long-lived emission and good stretchability is challenging because it is hard to balance the rigidity and flexibility in the same polymer. Here we present a multiphase engineering for obtaining stretchable phosphorescent materials by combining stiffness and softness simultaneously in well-designed block copolymers. Due to the microphase separation, copolymers demonstrate an intrinsic stretchability of 712%, maintaining an ultralong phosphorescence lifetime of up to 981.11 ms. This multiphase engineering is generally applicable to a series of binary and ternary initiator systems with color-tunable phosphorescence in the visible range. Moreover, these copolymers enable multi-level volumetric data encryption and stretchable afterglow display. This work provides a fundamental understanding of the nanostructures and material properties for designing stretchable materials and extends the potential of phosphorescence polymers.

Abstract Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization.

0Cr16Ni5Mo1 super martensitic stainless steel has excellent weldability and is an economical material with a high life cycle and low cost, but there are few researches and applications of this material in additive manufacturing. In order to realize the application of 0Cr16Ni5Mo1 large-area laser cladding technology, the multi-track lap cladding of the material was studied. In this work, a multi-physical finite element model of multi-layer multi-track laser cladding was established, taking into account thermodynamic processes such as phase transition, Marangoni convection, and buoyancy. The flow and heat transfer behavior of 0Cr16Ni5Mo1 in multi-layer multi-track laser cladding process and the characteristics of the molten pool are studied. The research focused on the flow heat transfer behavior and molten pool characteristics of 0Cr16Ni5Mo1 during multi-layer multi-track laser cladding. The discussed aspects include the evolution history of the temperature field within the molten pool, flow field characteristics, molten pool dimensions, and dilution ratio under various laser powers and overlap rates. The results show that with the increase of overlap rate, the morphology of molten pools in different clad tracks will also change, and the flow rate, dilution ratio, and length of molten pools in the second track are negatively correlated, while the temperature and height of molten pools are positively correlated. As the laser power increases, all the characteristic quantities are positively correlated with it.

Abstract RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B’s involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.