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Abstract Background Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). Methods All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. Results Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. Conclusion Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.

Abstract Methanogenic hydrocarbon degradation can be carried out by archaea that couple alkane oxidation directly to methanogenesis, or by syntrophic associations of bacteria with methanogenic archaea. However, metagenomic analyses of methanogenic environments have revealed other archaea with potential for alkane degradation but apparent inability to form methane, suggesting the existence of other modes of syntrophic hydrocarbon degradation. Here, we provide experimental evidence supporting the existence of a third mode of methanogenic degradation of hydrocarbons, mediated by syntrophic cooperation between archaeal partners. We collected sediment samples from a hot spring sediment in Tengchong, China, and enriched Hadarchaeota under methanogenic conditions at 60 °C, using hexadecane as substrate. We named the enriched archaeon Candidatus Melinoarchaeum fermentans DL9YTT1. We used 13C-substrate incubations, metagenomic, metatranscriptomic and metabolomic analyses to show that Ca. Melinoarchaeum uses alkyl-coenzyme M reductases (ACRs) to activate hexadecane via alkyl-CoM formation. Ca. Melinoarchaeum likely degrades alkanes to carbon dioxide, hydrogen and acetate, which can be used as substrates by hydrogenotrophic and acetoclastic methanogens such as Methanothermobacter and Methanothrix.

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 The challenge of feeding an additional 2 billion people by 2050 is one of the most pressing issues of our generation. The required changes in the current food system must be achieved while reducing the negative environmental impacts of current farming practices on our climate and biodiversity and avoiding deforestation. This formidable challenge must be overcome in a projected climate that is more variable and where extreme weather events are increasingly common. While the green revolution, agricultural land expansion and agrotechnological innovations have significantly increased crop productivity over the last 50 years, the gains in the yields of most major crops have reached a plateau. Moreover, global hunger remains at a record high. Climate change‐associated changes in weather patterns have decreased the yields of major crops. Further land expansion is impossible without severe trade‐offs with biodiversity and climate change mitigation. Wars and pandemics are currently severely disrupting the global agri‐food system, increasing prices and exacerbating food insecurity, with the world's poorest suffering the most. The climate change–social instability nexus will continue to cause additional stress to the agri‐food system. Here, we consider the inequities in the current food system, highlighting the weak interconnection among research, policy and societal action that is hindering mitigation and adaptation efforts. We argue that improved interconnections among research, policy, governance and societal action will unlock the potential to achieve food security while supporting climate change mitigation targets. Our analysis includes specific strategies such as strengthening small‐scale farmers, promoting fair trade practices and reducing food waste to achieve these goals.

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.

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 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

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.

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.

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.

Background: Influenza vaccination is essential for type 2 diabetes mellitus (T2DM) patients due to their higher risks of severe complications and mortality from influenza. This study investigated the willingness of T2DM patients in Chongqing, China, to receive the influenza vaccination during the 2023/2024 season, using behavioral and social drivers (BeSD) tools to improve vaccination uptake in this high-risk group. Methods: A multi-stage sampling method was used to select participants, and face-to-face surveys were conducted in community health centers between March 1 and May 1, 2023. Binary logistic regression was used to analyze the factors influencing vaccination willingness, and standardized scores identified barriers and drivers. Results: Among 1672 T2DM patients, 11.7% had been vaccinated during the 2022/2023 season, and 59.6% were willing to receive the vaccination in the 2023/2024 season. Higher willingness was associated with ethnic minorities (odds ratio [OR], 3.18, 95% confidence interval [CI]: 1.58–6.39), being unemployed individuals (OR 2.69, 95% CI: 1.60–4.52), higher monthly household income per capita (OR 2.72, 95% CI: 1.65–4.50), having diabetes complications (OR 1.76, 95% CI: 1.23–2.51), sufficient vaccine knowledge (OR 1.87, 95% CI: 1.48–2.37), and previous vaccination (OR 7.75, 95% CI: 4.83–12.44). Concerning BeSDs, fear of infecting friends or family members and trust in vaccine efficacy were the predominant drivers, while high vaccine costs were the greatest barrier. Conclusions: Future strategies should focus on improving vaccine knowledge, supporting healthcare workers and peer recommendations, and enhancing vaccination policies. Key interventions such as health education among high-risk groups, such as unemployed individuals, advocacy campaigns, pay-it-forward strategies, and policies for free vaccination could improve coverage in Chongqing.

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.

Objectives To understand the sleep quality and its influencing factors in patients with type 2 diabetes mellitus (T2DM) who suffered diabetic peripheral neuropathy (DPN), and provide evidence for clinicians to carry out comprehensive intervention measures to improve the sleep quality of patients. Methods Patients who were admitted to the Endocrinology Department of Affiliated Hospital of Zunyi Medical University were recruited from May to December 2022, and the investigation were conducted by face-to-face interview. The questionnaires included PSQI questionnaire and influencing factors, such as lifestyle and health status. Results Among the 193 patients, 40.4% of the patients never took physical examination, 56.5% of the patients had duration of illness greater than 5 years, 61.7% of the patients had had an operation, 10.4% of the patients had bad dietary status, and 55.4% of the patients had physical pain. In addition, the PSQI general score was 8.34 ± 3.98, the occurrence rate of poor sleep quality (PSQI ≥ 8) was 54.4%, and the results showed that sleep quality of the physical pain group was worse than the no pain group. Moreover, the results of multivariate analysis revealed that the factors affecting sleep quality were lower frequency of exercise, bad dietary status, lower frequency of physical examination, longer duration of illness, and smoking, and the OR and 95% CI were [1.40, 1.04∼1.89], [3.42, 1.86∼6.29], [1.49, 1.01∼2.20], [1.78, 1.09∼2.92], [2.38, 1.17∼4.88], respectively. Conclusion Patients with DPN have higher risk of poor sleep quality. Moreover, there were many risk factors associated with poor sleep quality, clinicians and health policymakers should timely detect and effectively intervene in these factors to improve the sleep quality, which is important to enhance the quality of life of T2DM patients complicated with DPN.

Elderly tourism constitutes an important sector within the sustainable development of the tourism industry, attracting an increasing body of research focused on market development. This study aims to outline the progression of elderly tourism research within the past five years (2019–2023) and determine prospective research trajectories and opportunities in the subject. Employing CiteSpace visual analysis technology, this investigation constructs knowledge graphs of authors, institutions, and countries from 332 English-language academic articles from the Web of Science and culminates a keyword co-occurrence knowledge graph. Next, cluster and burst analyses revealed the prevailing trends and focal points in elderly tourism research. The results underscore that while many researchers have been drawn to elderly tourism, the collaborative relationships between these scholars remain tenuous, resulting in the relatively disparate study and the absence of a lead author group. China dominates the field, producing a far greater quantity of studies than other nations. Hence, this study encourages different countries, higher education institutions and disciplines to strengthen cooperation in the management and development of elderly tourism, especially paying attention to the importance of elderly tourism services, quality management and technology integration for the sustainable development of elderly tourism.

Abstract At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan–Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2’-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.

Abstract Development of effective recycling strategies for cathode materials in spent lithium-ion batteries are highly desirable but remain significant challenges, among which facile separation of Al foil and active material layer of cathode makes up the first important step. Here, we propose a reaction-passivation driven mechanism for facile separation of Al foil and active material layer. Experimentally, >99.9% separation efficiency for Al foil and LiNi0.55Co0.15Mn0.3O2 layer is realized for a 102 Ah spent cell within 5 mins, and ultrathin, dense aluminum-phytic acid complex layer is in-situ formed on Al foil immediately after its contact with phytic acid, which suppresses continuous Al corrosion. Besides, the dissolution of transitional metal from LiNi0.55Co0.15Mn0.3O2 is negligible and good structural integrity of LiNi0.55Co0.15Mn0.3O2 is well-maintained during the processing. This work demonstrates a feasible approach for Al foil-active material layer separation of cathode and can promote the green and energy-saving battery recycling towards practical applications.

A field experiment with double cropping rice was carried out to study the foliar application effects of dicarboxylicdimethylammonium chloride (DDAC) on cadmium (Cd) and arsenic (As) accumulation in rice grains. The results showed that the spraying of DDAC could significantly reduce the accumulation of Cd and As in rice grains. The highest reductions in Cd and As content were observed when 1.5 mmol L−1 DDAC was sprayed, with 49.1% and 27.4% reductions in Cd and As content in early rice grains and 56.5% and 28.1% reductions in Cd and As content in late rice grains, respectively. In addition, the content of calcium (Ca) in rice grains increased significantly after DDAC foliar application, which was also conducive to the synthesis of amino acids such as glutamate (Glu), glycine (Gly) and cysteine (Cys) in rice grains. The results indicated that the foliar spraying of DDAC can inhibit the absorption, transport, accumulation and toxicity of Cd and As in rice grains by increasing amino acid synthesis and regulating the absorption and transport of essential elements.

Background: Unhealthy lifestyles among adolescents are reaching alarming levels and have become a major public health problem. This study aimed to assess the relationship between sleep time, physical activity (PA) time, screen time (ST), and nutritional literacy (NL). Methods: This cross-sectional online study involving adolescents aged 10–18 years was conducted in September 2020 in 239 schools in Chongqing, China. NL was measured using the “Nutrition Literacy Scale for middle school students in Chongqing (CM-NLS)”. According to the recommended by the Chinese dietary guidelines (2022), we divided the sleep time of junior high school students into Results: A total of 18,660 adolescents (50.2% males) were included. The proportion of participants that were junior high school students and attended boarding schools was 57.2% and 65.3%, respectively. Compared with senior high school students, junior high school students had a higher level of NL. Whether on workdays or weekends, participants with sleep time ≥ 8/9 h, PA time ≥ 1 h, and ST < 2 h per day had higher levels of NL. On weekdays, participants who met the sleep time ≥ 8 h/9 h (OR = 1.48, 95% CI: 1.36, 1.62) and PA time ≥ 1 h (OR = 1.69, 95% CI: 1.59, 1.81) had higher reporting of NL levels. Conclusions: Sleep time, PA time, and ST were positively correlated with NL among adolescents, especially junior high school students.

Abstract Transportation stress is one of the most serious issues in the management of yak. Previous studies have demonstrated that transport stress is caused by a pro-oxidant state in the animal resulting from an imbalance between pro-oxidant and antioxidant status. In this context, vitamin C has the ability to regulate reactive oxygen species (ROS) synthesis and alleviate oxidative stress. Although this effect of vitamin C is useful in pigs, goats and cattle, the effect of vitamin C on the mitigation of transport stress in yaks is still unclear. The purpose of this study was to better assess the metabolic changes induced by the action of vitamin C in yaks under transportation stress, and whether these changes can influence antioxidant status. After the yaks arrived at the farm, control or baseline blood samples were collected immediately through the jugular vein (VC_CON). Then, 100 mg/kg VC was injected intramuscularly, and blood samples were collected on the 10th day before feeding in the morning (VC). Relative to the control group, the VC injection group had higher levels of VC. Compared with VC_CON, VC injection significantly (P 0.05) in GGT, ALP, TBA, TP, ALBII, GLO, A/G, TC, TG, HDL-C, LDL-C, GLU and l-lactate between VC_CON and VC. The injection of VC led to greater (P 0.05) the serum concentrations of LPO and ROS. The injection of VC led to greater (P 0.05) in GSH, GSH-ST and GR was observed between VC_CON and VC. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 156 differential metabolites with P 1.5 in the VC injection group. The injection of VC resulted in significant changes to the intracellular amino acid metabolism of glutathione, glutamate, cysteine, methionine, glycine, phenylalanine, tyrosine, tryptophan, alanine and aspartate. Overall, our study indicated that VC injections were able to modulate antioxidant levels by affecting metabolism to resist oxidative stress generated during transport.

Highlights The first construct of a multi-field-coupled synergistic ion transport system (MSITS) in Li+ extraction is proposed. Effectively suppress the ion concentration polarization effect of the ion-enrichment zone at the membrane interface. The MSITS equipped with heterogeneous membrane exhibited outstanding separation performance with Li+ flux of 367.4 mmol m−2 h−1 and Li+/Co2+ selectivity of 216,412, outperforming previous reports.

Ardisia kteniophylla A. DC, widely known as folk medicinal herb and ornamental plant, has been extensively investigated due to its unique leaf color, anti-cancer and other pharmacological activities. The quantitative real-time PCR (qRT-PCR) was an excellent tool for the analysis of gene expression with its high sensitivity and quantitative properties. Normalizing gene expression with stable reference genes was essential for qRT-PCR accuracy. In addition, no studies have yet been performed on the selection, verification and stability of internal reference genes suitable for A. kteniophylla, which has greatly hindered the biomolecular researches of this species. In this study, 29 candidate genes were successfully screened according to stable expression patterns of large-scale RNA seq data that from a variety of tissues and the roots of different growth stages in A. kteniophylla. The candidates were then further determined via qRT-PCR in various experimental samples, including MeJA, ABA, SA, NaCl, CuSO4, AgNO3, MnSO4, CoCl2, drought, low temperature, heat, waterlogging, wounding and oxidative stress. To assess the stability of the candidates, five commonly used strategies were employed: delta-CT, geNorm, BestKeeper, NormFinder, and the comprehensive tool RefFinder. In summary, UBC2 and UBA1 were found to be effective in accurately normalizing target gene expression in A. kteniophella regardless of experimental conditions, while PP2A-2 had the lowest stability. Additionally, to verify the reliability of the recommended reference genes under different colored leaf samples, we examined the expression patterns of six genes associated with anthocyanin synthesis and regulation. Our findings suggested that PAP1 and ANS3 may be involved in leaf color change in A. kteniphella. This study successfully identified the ideal reference gene for qRT-PCR analysis in A. kteniphella, providing a foundation for future research on gene function, particularly in the biosynthesis of anthocyanins.

Objective This study aimed to investigate the current status and influencing factors of healthy diet knowledge, attitude, and practice (KAP) among middle-aged and older adults aged 45–75 in Southwest China. Methods A questionnaire survey was conducted among 1822 middle-aged and older adults in Southwest China (including Guizhou, Sichuan, Yunnan, and Chongqing) from February to May 2021. Results The average score of healthy diet knowledge was (4.82 ± 2.98), with a passing rate of 7.6%. The mean score of healthy diet attitude was (21.26 ± 4.18), with a passing rate of 69.5%. The average score of healthy diet practice was (13.76 ± 2.84), with a passing rate of 55.5%. The score for healthy diet KAP was (39.85 ± 7.21), with a passing rate of 41.2%. Univariate analysis showed that the scores of healthy diet KAP were significantly different among participants of different ages, genders, ethnicities, residences, education levels, monthly household incomes, and regions, as well as varying according to whether several generations have lived in the same area (p < 0.05). The results of multiple linear regression showed that the healthy diet KAP of participants was influenced by age, gender, residence, education level, monthly household income, and region (p < 0.05). Conclusion The healthy diet KAP of middle-aged and older adults aged 45–75 in Southwest China shows room for improvement. The knowledge regarding healthy diet was relatively low, and certain specific healthy diet practices were not up to the standard. However, there was a positive trend in the attitude towards a healthy diet. Healthy diet education should be promoted for middle-aged and older adults.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

Oxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury. Previous research established that yeast extract (YE) has antioxidant, immune-boosting or microbiota-regulating properties. However, there is currently lack of information regarding the efficacy of YE on alcoholic liver injury. This study seeks to obtain data that will help to address this research gap using a Wistar male rat experimental model. Histologic and biochemical analysis results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of Peptococcus and Ruminococcus reduced in the low-dose yeast extract (YEL) group, while that of Peptococcus, Romboutsia, Parasutterella, and Faecalibaculum reduced in the high-dose (YEH) group. Furthermore, Spearman analysis showed that the gut microbes were significantly associated with several liver-related indicators. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5′ -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder. Besides, high-dose YE has been found to be more effective than low-dose YE in metabolic regulation, as well as in dealing with oxidative stress and inflammatory responses.

This work compares the threshold applied to the swirling strength as well as the vortex orientation statistics in the total and fluctuating velocity fields using direct numerical simulations of compressible and incompressible turbulent channel flows. It is concluded that the difference in the swirling strength for vortex identification is minimal in the logarithmic region such that these two situations share the same threshold. Regarding the vortex orientation, the inclination angle remains similar. However, as the wall-normal distance increases, a more and more obvious distinction is noticed for its orientation with respect to the spanwise (z) direction. It is mainly due to their intrinsic differences and attendant contrasting preference for the vortex identification, i.e., vortices rotating in the −z direction for the total velocity field and in the z direction for the fluctuating one. These observations function as a reasonable explanation for various remarks in previous studies.

As an important technology of digital construction, real 3D models can improve the immersion and realism of virtual reality (VR) scenes. The large amount of data for real 3D scenes requires more effective rendering methods, but the current rendering optimization methods have some defects and cannot render real 3D scenes in virtual reality. In this study, the location of the viewing frustum is predicted by a Kalman filter, and eye-tracking equipment is used to recognize the region of interest (ROI) in the scene. Finally, the real 3D model of interest in the predicted frustum is rendered first. The experimental results show that the method of this study can predict the frustrum location approximately 200 ms in advance, the prediction accuracy is approximately 87%, the scene rendering efficiency is improved by 8.3%, and the motion sickness is reduced by approximately 54.5%. These studies help promote the use of real 3D models in virtual reality and ROI recognition methods. In future work, we will further improve the prediction accuracy of viewing frustums in virtual reality and the application of eye tracking in virtual geographic scenes.

The objective of disaster scenes is to share location-based risk information to a large audience in an effective and intuitive way. However, current studies on three-dimensional (3D) representation for dam-break floods have the following limitations: (1) they are lacking a reasonable logic to organize the whole process of dam-break floods, (2) they present information in a way that cannot be easily understood by laypersons. Geospatial storytelling helps to create exciting experiences and to explain complex relationships of geospatial phenomena. This article proposes a three-dimensional virtual representation method for the whole process of dam-break floods from a geospatial storytelling perspective. The creation of a storyline and a storytelling-oriented representation of dam-break floods are discussed in detail. Finally, a prototype system based on WebGL is developed to conduct an experiment analysis. The results of the experiment show that the proposed method can effectively support 3D representation of the spatiotemporal process of dam-break floods. Furthermore, the statistical results indicate that the storytelling is useful for assisting participants in understanding the occurrence and development of dam-break floods, and is applicable to the popularization of disaster science for the general public.

Decarbonisation is a complex systemic issue that involves multiple market failures. Thus, the integrated application of multiple policy instruments is required. This study used the fuzzy-set qualitative comparative analysis (fsQCA) method to explore the causality relationship between decarbonisation policies with reference to the Intergovernmental Panel on Climate Change (IPCC) and the decoupling elasticity of Tapio from a configuration perspective. We found that taxation and regulation are the critical drivers of decoupling, while information and public goods and services are ancillary. Three decoupled policy mixes were tabled, each focusing on a) taxation, b) taxation and economic instruments, and c) trading system and regulations. In contrast, the execution of information and voluntary instruments, as well as the non-implementation of the tax, are essential to non-decoupling. Three combinations that are negative for decoupling were also introduced: a) trade and economic incentives, b) trade, information and voluntary instruments, and c) information, public goods and services, and voluntary instruments. The most valuable policy mix for China is the implementation of taxes, trade, economic and regulations with the provision of auxiliary decarbonised information and public goods and services. The following processes are involved: a) integrate regulations with economic policies for more flexibility; b) introduce the carbon tax and a tax rebate policy to complement the carbon market policy based on research into the feasibility and cost-effectiveness; c) provide information and public services mainly on the consumption side; and d) recommend voluntary policies for innovative practices. On the basis of more cases and a configuration perspective, this study offers various policy mixes that are conducive or not to decoupling and suggestions for optimising China’s decarbonisation policy. We also offered a way to measure the intensity of the decarbonisation policy with respect to the carbon emission structure of sectors.

Abstract Background Prostate cancer is a major health issue affecting the male population worldwide, and its etiology remains relatively unknown. As presented on the Gene Expression Profiling Interactive Analysis database, acetyl-CoA acetyltransferase 1 (ACAT1) acts as a prostate cancer-promoting factor. ACAT1 expression in prostate cancer tissues is considerably higher than that in normal tissues, leading to a poor prognosis in patients with prostate cancer. Here, we aimed to study the role of the ACAT1-fused in sarcoma (FUS) complex in prostate cancer and identify new targets for the diagnosis and treatment of the disease. Methods We conducted immunohistochemical analysis of 57 clinical samples and in vitro and in vivo experiments using a mouse model and plasmid constructs to determine the expression of ACAT1 in prostate cancer. Results The relationship between the expression of ACAT1 and the Gleason score was significant. The expression of ACAT1 was higher in tissues with a Gleason score of > 7 than in tissues with a Gleason score of ≤7 (P = 0.0011). In addition, we revealed that ACAT1 can interact with the FUS protein. Conclusions In prostate cancer, ACAT1 promotes the expression of P62 and Nrf2 through FUS and affects reactive oxygen species scavenging. These effects are due to the inhibition of autophagy by ACAT1. That is, ACAT1 promotes prostate cancer by inhibiting autophagy and eliminating active oxygen species. The expression of ACAT1 is related to prostate cancer. Studying the underlying mechanism may provide a new perspective on the treatment of prostate cancer.

Abstract Deep learning (DL) has shown unprecedented performance for many image analysis and image enhancement tasks. Yet, solving large-scale inverse problems like tomographic reconstruction remains challenging for DL. These problems involve non-local and space-variant integral transforms between the input and output domains, for which no efficient neural network models are readily available. A prior attempt to solve tomographic reconstruction problems with supervised learning relied on a brute-force fully connected network and only allowed reconstruction with a 1284 system matrix size. This cannot practically scale to realistic data sizes such as 5124 and 5126 for three-dimensional datasets. Here we present a novel framework to solve such problems with DL by casting the original problem as a continuum of intermediate representations between the input and output domains. The original problem is broken down into a sequence of simpler transformations that can be well mapped onto an efficient hierarchical network architecture, with exponentially fewer parameters than a fully connected network would need. We applied the approach to computed tomography (CT) image reconstruction for a 5124 system matrix size. This work introduces a new kind of data-driven DL solver for full-size CT reconstruction without relying on the structure of direct (analytical) or iterative (numerical) inversion techniques. This work presents a feasibility demonstration of full-scale learnt reconstruction, whereas more developments will be needed to demonstrate superiority relative to traditional reconstruction approaches. The proposed approach is also extendable to other imaging problems such as emission and magnetic resonance reconstruction. More broadly, hierarchical DL opens the door to a new class of solvers for general inverse problems, which could potentially lead to improved signal-to-noise ratio, spatial resolution and computational efficiency in various areas.

Obesity is a major global health issue that contributes to the occurrence of metabolic disorders. Based on this fact, understanding the underlying mechanisms and to uncover promising therapeutic approaches for obesity have attracted intense investigation. Brown adipose tissue (BAT) can help burns excess calories. Therefore, promoting White adipose tissue (WAT) browning and BAT activation is an attractive strategy for obesity treatment. MicroRNAs (miRNAs) are small, non-coding RNAs, which are involved in regulation of adipogenic processes and metabolic functions. Evidence is accumulating that miRNAs are important regulators for both brown adipocyte differentiation and white adipocyte browning. Here we report that the expression of miR-669a-5p increases during the adipogenic differentiation of 3T3-L1 and C3H10T1/2 adipocytes. miR-669a-5p supplementation promotes adipogenic differentiation and causes browning of 3T3-L1 and C3H10T1/2 cells. Moreover, the expression of miR-669a-5p is upregulated in iWAT of mice exposed to cold. These data demonstrate that miR-669a-5p plays a role in regulating adipocyte differentiation and fat browning. Abbreviations: Acadl: long-chain acyl-Coenzyme A dehydrogenase; Acadm: medium-chain acyl-Coenzyme A dehydrogenase; Acadvl: very long-chain acyl-Coenzyme A dehydrogenase, very long chain; Aco2: mitochondrial aconitase 2; BAT: brown adipose tissue; Bmper: BMP-binding endothelial regulator; Cpt1-b:carnitine palmitoyltransferase 1b; Cpt2: carnitine palmitoyltransferase 2; Crat: carnitine acetyltransferase; Cs: citrate synthase; C2MC: Chromosome 2 miRNA cluster; DMEM: Dulbecco’s modified Eagle medium; eWAT: epididymal white adipose tissue; ETC: electron transport chain; FAO: fatty acid oxidation; Fabp4:fatty acid binding protein 4; FBS: fetal bovine serum; Hadha: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; Hadhb: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta; HFD: high fat diet; Idh3a: isocitrate dehydrogenase 3 alpha; iWAT: inguinal subcutaneous white adipose tissue; Lpl: lipoprotein lipase; Mdh2: malate dehydrogenase 2; NBCS: NewBorn Calf Serum; mt-Nd1: mitochondrial NADH dehydrogenase 1; Ndufb8:ubiquinone oxidoreductase subunit B8; Nrf1: nuclear respiratory factor 1; Pgc1α: peroxisome proliferative activated receptor gamma coactivator 1 alpha; Pgc1b: peroxisome proliferative activated receptor, gamma, coactivator 1 beta; Pparγ: peroxisome proliferator activated receptor gamma; Prdm16: PR domain containing 16; Rgs4: regulator of G-protein signaling 4; Sdhb: succinate dehydrogenase complex, subunit B; Sdhc: succinate dehydrogenase complex, subunit C; Sdhd: succinate dehydrogenase complex, subunit D; Sh3d21: SH3 domain containing 21; Sfmbt2: Scm-like with four mbt domains 2; TG: triglyceride; TCA: tricarboxylic acid cycle; Tfam: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine, methyl ester; Ucp1: uncoupling protein 1; Uqcrc2: ubiquinol cytochrome c reductase core protein 2; WAT: White adipose tissue

Internet gaming disorder (IGD) has a great negative impact on teenagers’ study and life. It has been included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders in 2013. However, the neural mechanism of its effect is yet to be unveiled. In this study, we used resting-state functional magnetic resonance imaging (resting-state fMRI) to explore the differences of rich club structures in the functional brain networks of 30 IGD subjects and 30 age/sex-matched healthy controls. The rich club was found in both IGD subjects and healthy controls, involving important brain regions in default mode, executive control, salience, sensorimotor, auditory and visual networks. IGD subjects had significantly higher rich club connection and higher degree in the right pars orbitalis of inferior frontal gyrus than healthy controls. These findings might suggest that IGD might be more correlated with damage to the rich club connection.

Abstract Elevated extrachromosomal circular DNA (eccDNA) has been reported to accelerate tumor pathogenesis. Although the eccDNA profiles of other tumors have been established, the landscape of the eccDNA of acute myeloid leukemia (AML) has not been revealed. Our study first depicted the eccDNA profile of normal hematopoiesis and AML evolution by exploiting the ATAC-seq and RNA-seq data from nine healthy donors and 12 AML patients, which contained a total of 137 cell samples and 96 RNA-seq samples (including 16 blood cell types of the normal hematopoietic and AML hierarchies). We found the number of eccDNAs generally increased with the evolution of normal hematopoiesis and AML. The ecDNAs and ring chromosomes were found to reappear both in normal hematopoiesis and AML cells. Furthermore, we compared the eccDNAs of AML with normal cells. There were almost 300 AML-specific genes, including the known oncogenes NRAS, MCL1, EVI1, GATA2, WT1, and PAK1. And the ecDNA (chr11: 58668376-58826008) occurred in five out of 17 AML evolution-related cells, which was associated with the high expression of the GLYATL1 gene and the high expressed GLYATL1 was a poor prognostic factor. In conclusion, the eccDNA profiles of normal hematopoiesis and AML evolution were depicted and the recurrent eccDNAs we revealed might be utilized in the treatment of AML as biomarkers.

Increasing evidence have demonstrated that early-life exposure to environmental toxicants elevates risk of allergic asthma. Cadmium (Cd) is widely present in the environment. The purposes of this study were to evaluate the impact of early-life Cd exposure on susceptibility to ovalbumin (OVA)-evoked allergic asthma. Newly weaned mice were subjected to a low concentration of CdCl2 (1 mg/L) by drinking water for 5 consecutive weeks. Penh value, an index of airway obstruction, was increased in OVA-stimulated and challenged pups. Abundant inflammatory cells were observed in the lung of OVA-exposed pups. Goblet cell hyperplasia and mucus secretion were shown in the airway of OVA-stimulated and challenged pups. Early-life Cd exposure exacerbated OVA-evoked airway hyperreactivity, Goblet cell hyperplasia and mucus secretion. The in vitro experiments showed that mucoprotein gene MUC5AC mRNA was upregulated in Cd-exposed bronchial epithelial cells. Mechanistically, endoplasmic reticulum (ER) stress-related molecules GRP78, p-eIF2α, CHOP, p-IRE1α and spliced XBP-1 (sXBP-1) were elevated in Cd-subjected bronchial epithelial cells. The blockade of ER stress, using chemical inhibitor 4-PBA or sXBP-1 siRNA interference, attenuated Cd-induced MUC5AC upregulation in bronchial epithelial cells. These results indicate that early-life Cd exposure aggravates OVA-induced allergic asthma partially through inducing ER stress in bronchial epithelial cells.

In this study, we aimed to compare the mechanical properties and tribological properties of specimens after different thermal treatments. We treated specimens in oxidation and nitriding with argon in the chamber with 900 °C and 950 °C respectively. The results of the microhardness showed that the oxidized specimens were observed the highest value of 788VHN (0.05). We found that comparing to oxidized specimens (CoF=0.6 ± 0.09), the nitrided specimens showed lower coefficient of friction (CoF=0.52±0.06). There was around two times improvement of microhardness comparing to untreated specimens. And oxidized specimens (1.61±0.29 μm3/Nmm) showed five times lower value of wear rate than nitrided specimens (4.12±0.79 μm3/Nmm), and around ten times lower value of wear rate than nitrided with mechanic pump (9.54±0.68 μm3/Nmm). We concluded that oxidation could help to achieve the enhancement of hardness and wear properties, but with thinner layer on the surface. Nitriding with diffusion pump increased the efficiency of Ar+ and N+ diffusion than only with mechanic pump.

The goal of the current study was to explore the potential benefits of Tretinoin (Tre) fatty acid vesicles (Tre-FAV) as a prospective antipsoriatic topical delivery system. This promising system can counteract the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Tre-loaded fatty acid vesicles were successfully developed and entirely characterised. The selected formulation was investigated for in vitro release, ex vivo skin retention and psoriasis efficacy studies. The characterisation results of Tre-FAV showed it has a globular shape with a particle size of 126.37 ± 1.290 nm (0.188 ± 0.019 PDI). The entrapment efficiency and zeta potential were discovered to be 84.26 ± 0.816% and −28.9 ± 1.92 mV, respectively. Encapsulation of the drug in the fatty acid vesicles was also strengthened by differential scanning calorimetric and powder FTIR diffraction studies. In vitro release results showed that Tre-FAV significantly increased skin absorption and retention in comparison to the Tre solution. The topical application of Tre-FAV to a mouse model confirmed that it has superior in vivo antipsoriatic properties in terms of well-demarcated papules, erythema and reduced epidermal thickness in comparison to other treatments. The weight of the spleen and the levels of the cytokines IL-17 and IL-6 decreased after treatment. In conclusion, FAV dramatically increased the water solubility and skin permeability of Tre and its anti-psoriasis activity.

Depression is one of the most common psychological problems in adolescence. Familial and school-related factors are closely related to adolescents’ depression, but their combined effects need further examination. The purpose of this study was to explore the combined effects of risk/protective factors of depression in family and school domains using a sample of Chinese adolescents differing in gender, age group and left-behind status. A total of 2455 Chinese students in primary and secondary school participated in the cross-sectional survey and reported multiple risk/protective factors in family and school environments and depressive symptoms. Association rule mining, a machine learning method, was used in the data analyses to identify the correlation between risk/protective factor combinations and depression. We found that (1) Family cohesion, family conflict, peer support, and teacher support emerged as the strongest factors associated with adolescent depression; (2) The combination of these aforementioned factors further strengthened their association with depression; (3) Female gender, middle school students, and family socioeconomic disadvantages attenuated the protective effects of positive relational factors while exacerbating the deleterious effects of negative relational factors; (4) For individuals at risk, lack of mental health education resources at school intensified the negative impact; (5) The risk and protective factors of depression varied according to gender, age stage and left-behind status. In conclusion, the findings shed light on the identification of high-risk adolescents for depression and underscore the importance of tailored programs targeting specific subgroups based on gender, age, or left-behind status.

Abstract Background Extracellular vesicles (EVs) play a key role in constructing a microenvironment that favors the differentiation of stem cells. The present work aimed to determine the molecular mechanisms by which EV derived from inflammatory dental pulp stem cell (iDPSC-EV) influence periodontal ligament stem cells (PDLSCs) and provide a potential strategy for bone and dental pulp regeneration. Methods The osteogenic and odontogenic differentiation was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, alkaline phosphatase (ALP) activity assay, ALP staining, alizarin red S (ARS) staining, and immunofluorescence staining. To detect proliferation, the Cell Counting Kit-8 (CCK-8) assay, and flow cytometry analysis were used. EVs were isolated by the Exoperfect kit and ultrafiltration and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. The expression profile of miRNAs in EVs was studied using miRNA sequence and bioinformatics, and one of the upregulated miRNAs was evaluated on PDLSCs. Results The inflammatory microenvironment stimulated osteogenic and odontogenic differentiation of DPSCs and iDPSC-EV behaved alike on PDLSCs. MiR-758-5p was upregulated in iDPSC-EV and was demonstrated to play a significant role in the osteogenic and odontogenic commitment of PDLSCs. A dual-luciferase reporter assay confirmed the binding site between miR-758-5p and limb development membrane protein 1 (LMBR1). The knockdown of LMBR1 also enhanced the above potential. Mechanically, bone morphogenetic protein (BMP) signaling was activated. Conclusions EVs from the inflammatory microenvironment enhanced the osteogenic and odontogenic differentiation of PDLSCs partly by shuttering LMBR1-targeting miR-758-5p via BMP signaling.

Abstract Iron deposits are neuropathological hallmark of Parkinson’s disease (PD). Iron regulatory protein 2 (IRP2) is a key factor in regulating brain iron homeostasis. Although two ubiquitin ligases that promote IRP2 degradation have been identified, the deubiquitylase for stabilization of IRP2 in PD remains undefined. Here, we report OTUD3 (OTU domain-containing protein 3) functions as a deubiquitylase for IRP2, interacts with IRP2 in the cytoplasm, de-polyubiquitylates, and stabilizes IRP2 protein in an iron-independent manner. Depletion of OTUD3 results in a disorder of iron metabolism. OTUD3 knockout mice display nigral iron accumulation, motor deficits, and nigrostriatal dopaminergic neurodegeneration, which resembles the pathology of PD. Consistently, decreased levels of OTUD3 are detected in transgenic PD mice expressing A53T mutant of human α-synuclein. Five single nucleotide polymorphism mutations of OTUD3 are present in cases of sporadic PD or controls, although no significant associations of OTUD3 SNPs with sporadic PD are detected. Taken together, these findings demonstrate that OTUD3 is a bona fide deubiquitylase for IRP2 and plays a critical role in the nigral iron deposits in PD.

Objectives: This present study aimed to infer the association between aspirin exposure prior to ICU admission and the clinical outcomes of patients with Sepsis-associated acute respiratory failure (S-ARF).Methods: We obtained data from the Medical Information Mart for Intensive Care IV 2.0. Patients were divided into pre-ICU aspirin exposure group and Non-aspirin exposure group based on whether they took aspirin before ICU admission. The primary outcome is 28-day mortality. Augmented inverse propensity weighted was used to explore the average treatment effect (ATE) of the pre-ICU aspirin exposure. A generalized additive mixed model was used to analyze the longitudinal data of neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), oxygenation index (P/F), dynamic lung compliance (Cdyn), mechanical power (MP), and mechanical power normalized to predicted body weight (WMP) in the two groups. A multiple mediation model was constructed to explore the possible mediators between pre-ICU aspirin exposure and outcomes of patients with S-ARF.Results: A total of 2090 S-ARF patients were included in this study. Pre-ICU aspirin exposure decreased 28-day mortality (ATE, −0.1945, 95% confidence interval [CI], −0.2786 to −0.1103, p < 0.001), 60-day mortality (ATE, −0.1781, 95% Cl, −0.2647 to −0.0915, p < 0.001), and hospital mortality (ATE, −0.1502, 95%CI, −0.2340 to −0.0664, p < 0.001). In subgroup analysis, the ATE for 28-day mortality, 60-day mortality, and hospital mortality were not statistically significant in the coronary care unit group, high-dose group (over 100 mg/d), and no invasive mechanical ventilation (IMV) group. After excluding these non-beneficiaries, Cdyn and P/F ratio of the pre-ICU aspirin exposure group increased by 0.31mL/cmH2O (SE, 0.21, p = 0.016), and 0.43 mmHg (SE, 0.24, p = 0.041) every hour compared to that of non-aspirin exposure group after initialing IMV. The time-weighted average of NLR, Cdyn, WMP played a mediating role of 8.6%, 24.7%, and 13% of the total effects of pre-ICU aspirin exposure and 28-day mortality, respectively.Conclusion: Pre-ICU aspirin exposure was associated with decreased 28-day mortality, 60-day mortality, and hospital mortality in S-ARF patients except those admitted to CCU, and those took a high-dose aspirin or did not receive IMV. The protective effect of aspirin may be mediated by a low dynamic level of NLR and a high dynamic level of Cdyn and WMP. The findings should be interpreted cautiously, given the sample size and potential for residual confounding.

BackgroundThe worldwide prevalence of eczema has continued to rise over the past decades. This has led to the emphasis on the association between air pollution and eczema. This study investigated the relationship between daily exposure to air pollution and the number of eczema outpatient visits in Guangzhou with the overarching goal of providing novel insights on the interventions for eczema aggravation and prevention.MethodsDaily air pollution data, meteorological data, and the number of eczema outpatients were obtained from 18 January 2013 to 31 December 2018 in Guangzhou. A generalized additive model with Poisson distribution was used to assess the association between the number of eczema outpatient visits and short-term exposure to PM2.5 and PM10. In addition, the association of PM2.5 and PM10 by age (

This study evaluated the effects of inoculation with adult goat ruminal fluid on growth, health, gut microbiota and serum metabolism in lambs during the first 15 days of life. Twenty four Youzhou dark newborn lambs were selected and randomly distributed across 3 treatments (n = 8/group): autoclaved goat milk inoculated with 20 mL sterilized normal saline (CON), autoclaved goat milk inoculated with 20 mL fresh ruminal fluid (RF) and autoclaved goat milk inoculated with 20 mL autoclaved ruminal fluid (ARF). Results showed that RF inoculation was more effective at promoting recovery of body weight. Compared with CON, greater serum concentrations of ALP, CHOL, HDL and LAC in the RF group suggested a better health status in lambs. The relative abundance of Akkermansia and Escherichia-Shigella in gut was lower in the RF group, whereas the relative abundance of Rikenellaceae_RC9_gut_group tended to increase. Metabolomics analysis shown that RF stimulated the metabolism of bile acids, small peptides, fatty acids and Trimethylamine-N-Oxide, which were found the correlation relationship with gut microorganisms. Overall, our study demonstrated that ruminal fluid inoculation with active microorganisms had a beneficial impact on growth, health and overall metabolism partly through modulating the gut microbial community.