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BackgroundLong-distance running can be a form of stress to the heart. Technological improvements combined with the public’s gradual turn toward mobile health (mHealth), self-health, and exercise effectiveness have resulted in the widespread use of wearable exercise products. The monitoring of dynamic cardiac function changes during running and running performance should be further studied. ObjectiveWe investigated the relationship between dynamic cardiac function changes and finish time for 3000-meter runs. Using a wearable device based on a novel cardiac force index (CFI), we explored potential correlations among 3000-meter runners with stronger and weaker cardiac functions during running. MethodsThis study used the American product BioHarness 3.0 (Zephyr Technology Corporation), which can measure basic physiological parameters including heart rate, respiratory rate, temperature, maximum oxygen consumption, and activity. We investigated the correlations among new physiological parameters, including CFI = weight * activity / heart rate, cardiac force ratio (CFR) = CFI of running / CFI of walking, and finish times for 3000-meter runs. ResultsThe results showed that waist circumference, smoking, and CFI were the significant factors for qualifying in the 3000-meter run. The prediction model was as follows: ln (3000 meters running performance pass probability / fail results probability) = –2.702 – 0.096 × [waist circumference] – 1.827 × [smoke] + 0.020 × [ACi7]. If smoking and the ACi7 were controlled, contestants with a larger waist circumference tended to fail the qualification based on the formula above. If waist circumference and ACi7 were controlled, smokers tended to fail more often than nonsmokers. Finally, we investigated a new calculation method for monitoring cardiac status during exercise that uses the CFI of walking for the runner as a reference to obtain the ratio between the cardiac force of exercise and that of walking (CFR) to provide a standard for determining if the heart is capable of exercise. A relationship is documented between the CFR and the performance of 3000-meter runs in a healthy 22-year-old person. During the running period, data are obtained while participant slowly runs 3000 meters, and the relationship between the CFR and time is plotted. The runner’s CFR varies with changes in activity. Since the runner’s acceleration increases, the CFR quickly increases to an explosive peak, indicating the runner’s explosive power. At this period, the CFI revealed a 3-fold increase (CFR=3) in a strong heart. After a time lapse, the CFR is approximately 2.5 during an endurance period until finishing the 3000-meter run. Similar correlation is found in a runner with a weak heart, with the CFR at the beginning period being 4 and approximately 2.5 thereafter. ConclusionsIn conclusion, the study results suggested that measuring the real-time CFR changes could be used in a prediction model for 3000-meter running performance.

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.

Abstract Background Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. Methods Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. Results After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. Conclusions Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.

Abstract Previous studies have proved circFN1 is highly expressed in acute myeloid leukemia (AML) patients and AML cell lines. This study aims to investigate the impact of circFN1 on AML and its mechanism. Via real‐time quantitative PCR to detect circFN1, miR‐1294, ARHGEF10L expressions in clinical plasma samples and AML cell lines, AML cells were cultured in vitro and transfected with si‐circFN1, pcDNA3.1‐circFN1, and si‐ARHGEF10L, respectively, or co‐transfected pcDNA3.1‐circFN1 + miR‐1294 mimic and pcDNA3.1‐circFN1 + si‐ARHGEF10L. Using dual luciferase reporter experiment to detect the relationship between circFN1 and miR‐1294, as well as miR‐1294 and ARHGEF10L. CCK‐8 was used to detect cell proliferation, Transwell to cell invasion, TUNEL staining and flow cytometry to detect cell apoptosis, RT‐qPCR to circFN1 RNA, miR‐1294, and ARHGEF10L expression levels in HL‐60 cells, and western blot to ARHGEF10L protein expression level in HL‐60 cells. We found highly expressed circFN1 and ARHGEF10L, as well as low‐expressed miR‐1294 in AML patients and AML cell lines. In contrast to si‐NC group, si‐circFN1 group could signally inhibit HL‐60 cell proliferation and migration, but promote cell apoptosis; compared with mimic NC group, miR‐1294 mimic group could visually inhibit HL‐60 cell proliferation and migration, but promote cell apoptosis. miR‐1294 was the target of circFN1, and ARHGEF10L was the target of miR‐1294. Over‐expressing miR‐1294 or silencing ARHGEF10L could signally inhibit circFN1 promoting HL‐60 cell proliferation and migration and repressing cell apoptosis. circFN1 promotes proliferation and invasion of AML cell and represses cell apoptosis via regulating miR‐1294/ARHGEF10L axis, which provides new insight for molecular targeted‐treatment for AML.

Abstract The “Eight Scenic Views Paintings” represent crucial visual materials for investigating the history of cultural landscapes. However, traditional methods of interpreting materials struggle to discern the inherent connections between different landscape elements. This study proposes an approach for deconstructing historical images, taking the example of the Forty Scenic Views in the Late Ming Dynasty in Nanjing, China. To explore the co-occurrence structure, hierarchical clustering, and correlation features among various elements, various digital humanities quantification methods were applied, including spatial analysis of ArcGIS, co-occurrence and clustering of KH Coder, and correlation analysis of SPSS. This study reveals the characteristics of the landscape construction of Nanjing in the Late Ming: natural landscape as the foundation, artificial landscape as the core, and advocating tradition as the fashion. It also uncovers the landscape order: mountains, waters, and scenic views interweaved and coexisted, as well as nature and culture intertwined and clustered. In addition, multiple information graphs of the subordinate and co-occurrence relationships of 20 landscape elements were constructed, 5 landscape paradigms were extracted, and 36 pairs of related relationships were discovered, deepening the historical understanding of the urban landscape construction of Nanjing in the Late Ming. This paper puts forward the idea of analyzing historical images by digital method, which provides some essential and detailed historical basis for explaining the value of cultural landscape heritage and shaping contemporary urban landscape.

Abstract Background Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. Methods Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. Results Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. Conclusion Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression. Graphical Abstract

Utilizing a bespoke CO2 phase transition pulse pressure experimental system, we conducted pulse pressure characterization tests across various activator masses, CO2 filling pressures, and energy discharge plate thicknesses. This approach enabled us to ascertain the pulse pressure's response characteristics and variation patterns under diverse conditions. The formula for calculating the peak supercritical CO2 pulse pressure was deduced by modeling the ultimate load calculation of the clamped circular plate, and then the time-course expression of the supercritical CO2 phase transition pulse pressure and energy was carried out by introducing the time factor and taking into account the parameters of the activator mass and the thickness of the energy discharging plate. Our findings reveal a four-stage pressure evolution in the cracking tube during initiation: a gradual increase, a rapid spike, swift attenuation, and eventual negative pressure formation. The activator mass and discharge plate thickness critically influence the peak pressure's timing and magnitude. Specifically, increased activator mass hastens peak pressure onset, while a thicker discharge plate amplifies it. The errors between calculated and experimental values for peak supercritical CO2 phase transition pressure fall within −5%–5%. Furthermore, the pressure peak and arrival time model demonstrates less than 10% error compared to experimental data, affirming its strong applicability. These insights offer theoretical guidance for controlling phase transition pressure and optimizing energy in supercritical CO2 systems.

IntroductionThe ratio of lysine (Lys) to methionine (Met) with 3.0: 1 is confirmed as the “ideal” profile for milk protein synthesis, but whether this ratio is suitable for milk protein synthesis under HS needs to be further studied.MethodsTo evaluate the molecular mechanism by which HS and Lys to Met ratios affect mammary cell functional capacity, an immortalized bovine mammary epithelial cell line (MAC-T) is incubated with 5 doses of Met while maintaining a constant concentration of Lys. The MAC-T cells was treated for 6 h as follow: Lys: Met 3.0: 1 (control 37°C and IPAA 42°C) or treatments under HS (42°C) with different ratios of Lys: Met at 2.0: 1 (LM20), 2.5: 1 (LM25), 3.5: 1 (LM35) and 4.0: 1 (LM40). RNA sequencing was used to assess transcriptome-wide alterations in mRNA abundance.ResultsThe significant difference between control and other groups was observed base on PCA analysis. A total of 2048 differentially expressed genes (DEGs) were identified in the IPAA group relative to the control group. Similarly, 226, 306, 148, 157 DEGs were detected in the LM20, LM25, LM35 and LM40 groups, respectively, relative to the IPAA group. The relative mRNA abundance of HSPA1A was upregulated and anti-apoptotic genes (BCL2L1 and BCL2) was down-regulated in the IPAA group, compared to the control group (p < 0.05). Compared with the IPAA group, the relative mRNA abundance of anti-apoptotic genes and casein genes (CSN1S2 and CSN2) was up-regulated in the LM25 group (p < 0.05). The DEGs between LM25 and IPAA groups were associated with the negative regulation of transcription RNA polymerase II promoter in response to stress (GO: 0051085, DEGs of BAG3, DNAJB1, HSPA1A) as well as the mTOR signaling pathway (ko04150, DEGs of ATP6V1C2, WNT11, WNT3A, and WNT9A). Several DEGs involved in amino acids metabolism (AFMID, HYKK, NOS3, RIMKLB) and glycolysis/gluconeogenesis (AFMID and MGAT5B) were up-regulated while DEGs involved in lipolysis and beta-oxidation catabolic processes (ALOX12 and ALOX12B) were down-regulated.ConclusionThese results suggested that increasing Met supply (Lys: Met at 2.5: 1) may help mammary gland cells resist HS-induced cell damage, while possibly maintaining lactation capacity through regulation of gene expression.

Background and purposeThe efficacy of intravenous thrombolysis (IVT) in patients with acute minor ischaemic stroke (AMIS) remains unclear. We performed a meta-analysis to compare the efficacy and safety of IVT and dual antiplatelet therapy (DAPT) in patients with AMIS.MethodsThe Embase, Cochrane Library, PubMed, and Web of Science databases were searched up to 10 October, 2023. Prospective and retrospective studies comparing the clinical outcomes of IVT and DAPT were included. Odds ratios (ORs) and 95% confidence intervals (CIs) for early neurological deterioration (END), excellent and favourable functional outcomes, recurrent ischaemic stroke at 3 months, mortality at 3 months, and symptomatic intracranial haemorrhage (ICH) were pooled using a random-effects model.ResultsOf the five included studies, 6,340 patients were included. In patients with AMIS, IVT was not significantly associated with excellent and favourable functional outcomes, recurrent ischaemic stroke, or all-cause mortality at 3 months compared to early DAPT. However, a higher risk of symptomatic ICH (OR, 9.31; 95% CI, 3.39–25.57) and END (OR, 2.75; 95% CI, 1.76–4.30) were observed with IVT.ConclusionThis meta-analysis indicated that IVT was not superior to DAPT in patients with AMIS, especially in those with nondisabling AIS. However, these findings should be interpreted with caution and have some limitations. Further, well-designed randomised controlled trials are warranted.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.MethodsA multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as “confirmed,” “probable,” or “possible” TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome—assessed using the modified Barthel disability index—were recorded and compared.FindingsA total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 “not TBM.” Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298–11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372–10.761), age > 60 years (OR = 3.566; 95%CI: 1.022–12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027–5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score 60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Ginger, as a rich herb resource in China, has played an important role in food and medicine since ancient times. It is also known as a medicinal and edible homologous plant that possesses unique medical and nutritional values. Ginger polysaccharide is considered one of the most important bio-active components in ginger, which have attracted many attentions for various of bioactivities. In this review, the methods of extraction and purification of polysaccharide, as well as structural characteristics are discussed, what’s more, functional properties including antioxidant, immunity regulatory, anti-tumor and their influencing factors are reviewed. It is expected to provide valuable reference for further research and industrial application of ginger polysaccharide.

Abstract Background The aim of this study was to investigate the imaging features, lymph node metastasis, and genetic mutations in micropapillary lung adenocarcinoma (imaging with mixed ground‐glass nodules) ≤2 cm, to provide a more precise and refined basis for the selection of lung segment resection. Methods A retrospective analysis of 162 patients with surgically resected pathologically confirmed cancers ≤2.0 cm in diameter (50 cases of micropapillary mixed ground‐glass nodules [mGGNs], 50 cases of nonmicropapillary mGGNs, and 62 cases of micropapillary SNs [solid nodules]) was performed. mGGNs were classified into five categories according to imaging features. The distribution of these five morphologies in micropapillary with mGGN and nonmicropapillary with mGGN was analyzed. The postoperative pathology and prognosis of lymph node metastasis were also compared between micropapillary mGGNs and micropapillary with SNs. After searching the TCGA database, we demonstrated heterogeneity, high malignancy and high risk of microcapillary lung cancer cancers. Results Different pathological subtypes of mGGN differed in morphological features (p

Crowd evacuation simulation using virtual reality (VR) is significant for digital emergency response construction. However, existing evacuation simulation studies suffer from poor adaptation to complex environments, inefficient evacuations, and poor simulation effects and do not fully consider the impacts of specific disaster environments on crowd evacuation. To more realistically express the crowd evacuation results obtained under the influence of fire environments and the subjective consciousness of pedestrians in subway stations, we designed a dynamic pedestrian evacuation path planning method under multiple constraints, analysed the influences of an ‘environmental role’ and a ‘subjective initiative’ on crowd evacuation, established an improved social force model (ISFM)-based crowd evacuation simulation method in VR, developed a prototype system and conducted experimental analyses. The experimental results show that the crowd evacuation time of the ISFM is affected by the disaster severity. In simulation experiments without disaster scenarios, the improved model's crowd evacuation efficiency improved by averages of 12.53% and 15.37% over the commercial Pathfinder software and the original social force model, respectively. The method described herein can effectively support real-time VR crowd evacuation simulation under multiexit and multifloor conditions and can provide technical support for emergency evacuation learning and management decision analyses involving subway fires.

Efficient and intuitive representation of floods can improve people’s perception, which is useful for flood emergency management and decision making. However, the current methods of visualizing flood disaster scenes have the shortcomings of data redundancy and low-efficiency. The interference of the complex background can be avoided through region of interest (ROI) extraction, because the attention will be quickly attracted by a few salient visual objects. First, the characteristics of the flood disaster scene object are analysed, and the method for scene division and data organization is established. Second, the region of interest is extracted according to the time series data of the flood evolution process simulated using cellular automata, and the dynamic identification model of the objects of interest is established. Then, a dynamic scheduling queue model with service interruption is designed to optimize the rendering efficiency of flood scenes and improve the perception efficiency. Finally, a prototype visualization system was developed and the experimental results show that approximately 30% of the redundant data are reduced, and the scene rendering efficiency is increased by approximately 15%. The non-ROI visualization is weakened by using the rules of human visual cognition, which improves the perception efficiency of flood scenes.

Holographic projection technology can provide a more intuitive and efficient visualization effect for a digital twin bridge construction scene. However, pre-rendering methods in the existing research work are usually used to implement holographic visualization, which is static display. The above-mentioned methods for static display have many shortcomings, such as poor adaptability, low rendering efficiency and lack of real-time. A dynamic holographic modelling approach is proposed for the augmented visualization of digital twin scenes for bridge construction. Firstly, a dynamic segmentation algorithm with adaptive screen size was designed to high-efficiently generate holographic scenes. Secondly, a motion blur control method was designed to improve the rendering efficiency of holographic scenes according to human visual characteristics. Finally, a prototype system was developed, and the corresponding experimental analysis was completed. The experimental results show that the method proposed in this article can support adaptive screen size image segmentation and real-time generation of holographic scenes for bridge construction. The amount of scene data can be reduced to more than 30%, which significantly improves rendering efficiency and reduces glare.

Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment.

Promoting green investment is the inevitable choice for sustainable economics against climate change. We examine how the COVID-19 pandemic affected corporate green investment. Using a sample of publicly listed firms in China, we document the negative and significant effect of the COVID-19 pandemic on corporate green investment. Further analyses suggest that the COVID-19 pandemic impeded corporate green investment by exacerbating firms’ financial constraints. We also find that the COVID-19 pandemic had no significant effect on total investment, suggesting that the pandemic shock only changed investment structure. In summary, our findings reveal the real effects of the COVID-19 pandemic on green development at the firm level.

Primary vesicoureteral reflux (VUR) is the prevailing congenital anomaly of the kidneys and urinary tract, posing a significant risk for pyelonephritis scarring and chronic renal insufficiency in pediatric patients. Nevertheless, the precise genetic etiology of VUR remains enigmatic. In this current investigation, we conducted whole-exome sequencing on a child exhibiting single kidney, devoid of any familial VUR background, along with both biological parents. Two missense variants (NM_019105.8: exon11: c.4111G>A and NM_019105.8: exon2: c.31A>T) in the TNXB gene were identified through whole-exome sequencing of the child. These variants were found to be inherited from the child’s parents, with each parent carrying one of the variants. Molecular dynamics simulations were conducted to assess the impact of these variants on the tenascin XB proteins encoded by them, revealing varying degrees of impairment. Based on our findings, it is suggested that the TNXB compound heterozygous variant, consisting of c.4111G>A and c.31A>T, may be the underlying cause of right renal agenesis and left hydronephrosis in afflicted child. This discovery broadens the genetic range of the TNXB gene and establishes a genetic foundation for disease-specific preimplantation genetic diagnosis (PGD) in prospective pregnancies involving the parents of this afflicted child.

AbstractThe total chromatic number, [Formula: see text] is the minimum number of colors which need to be assigned to obtain a total coloring of the graph G. The Total Coloring Conjecture (TCC) made independently by Behzad and Vizing that for any graph, [Formula: see text] where [Formula: see text] represents the maximum degree of G. In this paper we obtained the total chromatic number for some classes of four regular circulant graphs.