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Abstract Background Sustainable Development Goals (SDGs) are universally recognised targets designed to combat poverty, inequality, and climate change. However, there exists limited awareness and understanding of these goals among nursing and midwifery students. To address this knowledge gap, a co-designed audio podcast was introduced as an educational tool to enhance students’ comprehension of SDGs and their relevance to the healthcare profession. Methods A prospective study was conducted at Queen’s University Belfast, involving 566 first-year nursing and midwifery students. A 60-minute SDG podcast, co-designed with students and stakeholders, was made accessible within the university’s learning management system. Pre- and post-test questionnaires were administered to assess changes in students’ knowledge levels and attitudes toward SDGs. Additionally, 37 participants engaged in focus group interviews six months after listening to the podcast to explore their experiences and reflections. Quantitative data was analysed using paired t-tests and descriptive statistics, while qualitative data was analysed thematically. Results The podcast significantly increased students’ awareness of SDGs and their understanding of the goals’ relevance to their profession and personal lives. Post-test scores showed substantial improvements across all three sub-scales: knowledge, professional relevance, and personal relevance. Moreover, participants rated the podcast as a valuable learning resource with high acceptability, although some expressed uncertainty about replay intentions. Focus group interviews revealed three themes, including 1) More than you know’, which described how participants developed new knowledge and understanding about SDGs, 2) ‘Nurse-Midwife Nudges’, which illuminated how participants made minor changes to their behaviour and 3) ‘Fitting Format’, which highlighted how participants favoured the use of an audio podcast to learn about SDGs. Discussion This study demonstrates the potential of audio podcasts as an effective and engaging tool for increasing awareness and understanding of SDGs among nursing and midwifery students. The results suggest that such interventions can positively impact students’ knowledge, attitudes, and behavioural intentions regarding the SDGs. The findings also emphasise the importance of co-design in developing educational resources tailored to the specific needs and preferences of students.

Abstract This study aims to investigate whether growing geopolitical competition has affected international collaboration in sustainable development research, with a particular focus on structural changes in bilateral research collaboration between China and the United States. Three datasets have been created and compared using bibliographic information provided by the Web of Science core collection: before the Trump administration, during the Trump administration, and during the Biden administration. The results indicate that countries worldwide have conducted extensive research in sustainable development, and the United States, China, and the United Kingdom have produced the most publications, demonstrating a high level of scientific research productivity. Concerning the collaborative patterns of sustainable development research, China and the United States are each other’s largest collaborative partners. The intensity of scientific research collaboration between the two countries has not declined due to geopolitical tensions. Conversely, the intensity of scientific research between the two countries is still increasing. The keyword thematic explorations reveal that research on China–US collaboration has focused differently across the three time periods and that despite differences in research bias, efforts to contribute to advancing the achievement of the SDGs have been consistent. It is possible that geopolitical considerations have heightened the urgency of policy research and led to its incorporation into research centers.

Abstract Background Obesity is a well-known risk factor for developing malignant tumors and promoting tumor cell growth and spread. However, recent studies have shown that obese cancer patients, who typically have a worse prognosis than nonobese cancer patients, show a significant improvement in survival after receiving immune checkpoint inhibitor (ICI) therapy. This phenomenon is known as the “obesity paradox”. However, this phenomenon is influenced by tumor type and sex. Therefore, this study aimed to explore the impact of obesity on immunotherapy efficacy from multiple perspectives, aiming to verify this paradox and provide new scientific evidence on the effect of obesity on ICI efficacy. Methods This retrospective study evaluated the data of patients who received ICI therapy between June 2019 and August 2023. Automatic segmentation of skeletal muscle, subcutaneous fat, and visceral fat was performed using Slice-O-Matic software, and the corresponding skeletal muscle index (SMI), subcutaneous fat index (SFI) and visceral fat index (VFI) were calculated. The neutrophil-to-lymphocyte ratio (NLR) was determined by dividing the neutrophil count by the lymphocyte count. Univariate and multivariate Cox regression analyses were used to evaluate the correlation between body mass index (BMI), body composition parameters, and the NLR with overall survival (OS) and progression-free survival (PFS) in obese patients receiving ICI therapy. Results We analyzed 219 patients with a median age of 60 years (IQR 53–69 years; 155 men and 64 women). Obese patients, particularly those with visceral fat accumulation, exhibited extended OS after ICI therapy (log­rank P = 0.027). Cox multivariate analysis revealed that the NLR (HR = 1.036; 95% CI: 0.996 to 1.078; P = 0.002) was independently associated with OS. Patients with a high NLR had worse OS than those with a low NLR. Conclusions This study corroborates the veracity of the "obesity paradox" under specific conditions and identifies NLR as an independent prognostic factor, with elevated NLR indicative of a poor prognosis.

Abstract Background The association between smoking cessation and decreased mortality existed among former smokers has been well documented. However, evidence is limited for smokers with long-term exposure. This study aims to quantify the association between smoking cessation and mortality by years since quitting in older adults with long-term smoking history. Methods Data from Beijing Healthy Aging Cohort Study (BHACS), conducted among communities aged over 55 years old at recruitment, were collected via questionnaire between July 2009 and September 2015 and followed up for all-cause and cancer mortality until March 2021. Self-reported smoking status and years since quitting were collected at baseline. Cox proportional hazards models were used to examine the association between smoking cessation and all-cause and cancer mortality. Results A total of 11 235 participants (43.9% male) were included, with a mean age of 70.35 (SD 7.71) years. Former smokers comprised 31.7% of the cohort, with a median smoking duration of 43 (IQR: 34–50) years. During 71 573 person-years of follow-up, there were 1 617 deaths (14.4% of the total cohort), of which 872 (17.7%) occurred among male participants. Compared with never smokers, HR (95%CI) for participants who current smoked was 2.898 (2.092–4.013); quit smoking less than 10 years (medians [quartiles] 4 [1, 7] years) before recruitment was 2.738(1.972–3.802); 10 to 20 years (16 [13, 20] years), 1.807(1.286–2.540); and 20 years or more (30 [25, 37] years), 1.293(0.981–1.705). The risk of all-cause and cancer mortality decreased gradually over years since quitting. Quitting less than 10 years, 10 to 20 years and 20 years or more, former smokers avoided an estimated 8.4%, 57.5% and 84.6% of excess all-cause mortality associated with current smoking, respectively. The association between smoking cessation and decreased mortality was observed among former smokers regardless of smoking history. Conclusions In this study, current smoking was associated with nearly triple the mortality risk compared to never smoking. Smoking cessation, even after a long-term smoking history, was associated with significant decreases in the relative excess mortality linked to continuing smoking. The association were more pronounced in men.

Abstract This study examines the impact of geopolitical risk on energy transition, focusing on the moderating roles of environmental regulations and green innovation within OECD countries. By employing a multivariate linear and nonlinear regression model, we identify a substantial positive effect of geopolitical risk on energy transition. Our analysis indicates that stronger environmental regulations and advancements in green innovation significantly amplify this effect. Through threshold effect bootstrap sampling tests, we detect a nonlinear relationship between geopolitical risk and energy transition at varying levels of environmental regulation and green innovation. We also explore lag effects, revealing that the influence of geopolitical risk on energy transition grows stronger over time. The inclusion of interaction terms in our analysis further clarifies the moderating influences of environmental regulation and green innovation. Utilizing a range of geopolitical risk indicators and regression methods, our findings are robust, consistently highlighting the proactive role of geopolitical risk in fostering energy transition. These insights highlight the importance of integrated strategies that harness environmental regulations and technological innovation to facilitate a resilient and efficient energy transition in the face of challenges posed by geopolitical uncertainties.

Abstract Background As a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD. Case presentation Herein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient. Conclusions This rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

Abstract The intersection of geopolitics and energy security is a critical area of study that has garnered increasing interest from scholars around the globe. This paper employs bibliometric theory and methodologies to explore the research trajectory concerning the influence of geopolitical dynamics on energy security. Our findings, derived from both quantitative and qualitative analysis of relevant literature, reveal several key insights. Firstly, there is a notable upward trend in publications on this topic, reflecting a widespread recognition of the intricate link between geopolitics and energy security. This growing body of research aligns with the exponential growth law observed in scientific literature, showcasing a novel pattern of geographical distribution centered around energy issues. Secondly, an examination of collaboration networks at the national, institutional, and individual levels identifies China as the leading country in terms of research partnerships, positioning Chinese institutions and scholars at the forefront of this field. Lastly, our analysis delineates the research evolution within this domain through three distinct phases—pre-, mid-, and post-development stages. It highlights the shifting focus of global researchers towards the energy transition process, energy policy formulation, the stability of energy markets, and the environmental impacts of energy production and consumption. This study not only maps the current landscape of research on geopolitics and energy security but also signals the critical areas of interest and collaboration that shape this vital field of inquiry.

Abstract This study examines the multifaceted impact of artificial intelligence (AI) on environmental sustainability, specifically targeting ecological footprints, carbon emissions, and energy transitions. Utilizing panel data from 67 countries, we employ System Generalized Method of Moments (SYS-GMM) and Dynamic Panel Threshold Models (DPTM) to analyze the complex interactions between AI development and key environmental metrics. The estimated coefficients of the benchmark model show that AI significantly reduces ecological footprints and carbon emissions while promoting energy transitions, with the most substantial impact observed in energy transitions, followed by ecological footprint reduction and carbon emissions reduction. Nonlinear analysis indicates several key insights: (i) a higher proportion of the industrial sector diminishes the inhibitory effect of AI on ecological footprints and carbon emissions but enhances its positive impact on energy transitions; (ii) increased trade openness significantly amplifies AI’s ability to reduce carbon emissions and promote energy transitions; (iii) the environmental benefits of AI are more pronounced at higher levels of AI development, enhancing its ability to reduce ecological footprints and carbon emissions and promote energy transitions; (iv) as the energy transition process deepens, AI’s effectiveness in reducing ecological footprints and carbon emissions increases, while its role in promoting further energy transitions decreases. This study enriches the existing literature by providing a nuanced understanding of AI’s environmental impact and offers a robust scientific foundation for global policymakers to develop sustainable AI management frameworks.

Abstract Effective management of natural resources is crucial for diminishing carbon emissions. This research explores how economic, financial, and political risks influence the relationship between natural resources rents and carbon emissions. Analyzing data from 66 countries, this study utilizes methods such as quantile regression and dynamic threshold regression to thoroughly assess the data. The findings reveal: (i) Natural resources rents tend to increase carbon emissions consistently across different quantiles (0.1 to 0.9). The fact is confirmed by robustness checks, illustrating that increased natural resources rents lead to higher emissions. (ii) Economic, financial, and political risks affect how natural resources rents impact carbon emissions. Notably, reduced economic and financial risks lessen the propensity of natural resources rents to boost emissions at higher quantiles, while a decline in political risk decreases the exacerbating effect of natural resources rents on emissions from the 0.1 to 0.9 quantiles. (iii) This analysis uncovers threshold effects where economic, financial, and political risks act as threshold factors. Specifically, when economic and political risks are low, a rise in natural resources rents actually leads to a decline in carbon emissions. The findings underscore the importance of considering these risks in the formulation of policies aimed at reducing carbon emissions from natural resource exploitation.

Abstract This study investigates the impact of corporate scale on manufacturing corporate carbon efficiency (MCEE) using empirical analyses and diverse modeling techniques. The research begins with rigorous unit root and cointegration tests, confirming the stationary nature of the data and establishing long-term equilibrium relationships among the variables. Subsequently, benchmark regression analyses employing various models, including system GMM, reveal a robust and significantly positive association between corporate scale and MCEE. The findings emphasize that as corporate scale increases, there is a substantial enhancement in MCEE, attributed to expanded resources, technological advancements, and improved management systems. Robustness tests employing alternative approaches consistently reaffirm this positive correlation, further validating the pivotal role of corporate scale in augmenting MCEE. Furthermore, nonlinear analyses demonstrate varying impacts across different quantile levels of MCEE, highlighting the consistent positive correlation between corporate scale and MCEE. Additionally, the panel threshold model underscores the influence of environmental regulations, R&D investments, and trade openness on this relationship. Notably, stricter environmental regulations intensify the impact of corporate scale on MCEE, emphasizing the importance of corporate expansion in minimizing environmental costs and enhancing resource efficiency. These findings underscore the significance of corporate scale in driving corporate carbon efficiency. They advocate for corporations to not only expand their production capacities but also focus on optimizing management strategies and resource allocation, particularly in contexts influenced by environmental regulations, R&D investments, and trade openness. Overall, this research contributes comprehensive insights into understanding the dynamics governing corporate environmental efficiency and emphasizes the critical role of corporate scale in fostering environmental sustainability.

The ZCuPb15Sn5/1045 bimetallic composites were prepared by the melt-casting composite method. The mechanical and tribological properties of the copper-steel bimetallic composites under different cooling process conditions were studied. The results showed that with the acceleration of the cooling rate, the copper layer of the copper-steel bimetallic composite became harder, the grain became finer, and the distribution of the anti-friction element Pb became more uniform. Underwater cooling conditions, the shear strength increased, and the shear fracture gradually showed the tendency of tough and brittle fracture. The cooling process had a more significant influence on the tribological properties of the material. When the cooling rate was slow, the copper layer of the bimetallic composites had a high friction coefficient and relatively serious adhesive wear and oxidation wear. For the water cooling sample with a very fast cooling rate, the friction coefficient of the copper layer was low and the wear degree was relatively light.

Abstract Background Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). Methods In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III–IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy. Results After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. Conclusions This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. Trial registration www.ClinicalTrials.gov . NCT02923258 (date of registration: October 4, 2016)

Highlights A new type of metallacage was successfully fabricated and used as containers for hypocrellin-type photosensitizers, which prevented the self-aggregation of photosensitizers in aqueous solution. The metallacage was also employed as an energy donor to promote the singlet oxygen generation ability via fluorescence resonance energy transfer, thereby achieving highly efficient photodynamic therapy.

ABSTRACT Chinese serow (Capricornis milneedwardsii) is mainly distributed in the south of Yellow River in China, which has been listed as vulnerable by the International Union for Conservation of Nature (IUCN). However, the reference genome of serow has not been reported and its taxonomic status is still unclear. Here, we first constructed a high‐quality chromosome‐level reference genome of C. milneedwardsii using PacBio long HiFi reads combined with Hi‐C technology. The assembled genome was ~2.83 Gb in size, with a contig N50 of 100.96 Mb and scaffold N50 of 112.75 Mb, which were anchored onto 24 chromosomes. Furthermore, we found that the Chinese serow was more closely related to muskox, which diverged from ~4.85 million years ago (Mya). Compared to the karyotype of goat (2n = 60), we found the Chinese serow (2n = 48) experienced six chromosome fusions, which resulted in the formation of six central centromere chromosomes. We also identified two positively selected genes (MYH6 and DCSTAMP) specific to Chinese serow, which were involved in ‘viral myocarditis’ and ‘Cardiac muscle contraction’. Interestingly, compared to other Caprinae animals, the MYH6 protein of Chinese serow occurred two mutations (E1520S and G1521S), which might be related to hypoxia tolerance. The high‐quality reference genome of C. milneedwardsii provides a valuable information for protection of serows and insights into its evolution.

Background and purpose: The composite score for insulin resistance (IR), known as the Metabolic Score of Insulin Resistance (METS-IR), serves as an assessment tool for IR and has been previously linked to symptomatic intracranial hemorrhage and poor functional outcomes in patients with acute ischemic stroke (AIS). Despite these associations, the impact of METS-IR on early neurological deterioration (END) in patients with minor AIS who underwent intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) remains inadequately established. This investigation explored the link between METS-IR and END in patients with minor AIS receiving IV-rtPA treatment. Methods: In this study, a cohort comprising 425 consecutive patients with National Institutes of Health Stroke Scale Score (NIHSS)≤5 who underwent IV-rtPA treatment was included. The METS-IR was computed using the formula ln METS-IR=ln (2 × FBG + TG) × BMI/ln (HDL). END was defined as a NIHSS ≥2 within 24 h post IV-rtPA administration, while poor functional outcome was defined as a modified Rankin Scale (mRS) of 2–6. Multivariate logistical regression was performed to investigate the association between METS-IR and both poor functional outcomes and END. Results: Among the 425 enrolled patients, 64 (15.1 %) patients experienced END, while 80 (18.8 %) had poor functional outcomes three months post-discharge. Upon adjusting for confounding factors, a higher METS-IR emerged as an independent predictor for both END and poor functional outcomes. Similarly, noteworthy findings were observed when METS-IR was defined as a categorical group. The restricted cubic spline (RCS) analysis indicated a linear relationship between METS-IR and END (P = 0.593 for non-linearity, P = 0.034 for overall). The incorporation of METS-IR into the conventional model resulted in a significant enhancement of predictive accuracy for both END and poor functional outcomes. Conclusion: METS-IR emerges as an independent predictor for END and poor functional outcome at three months post-discharge in patients with minor AIS subjected to IV-rtPA. Considering its simplicity and clinical accessibility as an indicator of IR, METS-IR may hold guiding significance in clinical practice.

Airway stenosis, a significant cause of dyspnea, is commonly managed with airway stents. However, conventional stents frequently lead to restenosis. Excessive proliferation of fibroblasts and smooth muscle cells during abnormal repair processes is a key factor in airway restenosis. To address this challenge, a novel drug-loaded airway stent has been designed with personalized tailoring for the patient. This stent features a three-layered structure: an outer layer made from a blend of thermoplastic polyurethane (TPU) and Poloxamer 407 (P407), a drug-loading intermediate layer, and an inner layer made of TPU. This design aims to minimize airway irritation and enable adjustable drug release rates by adjusting the drug carrier and/or the content of P407 in the stent’s outer layer. Drug release profile conforms to the Improved First-Order model. Notably, P407 is released from the stent, serving a dual purpose: it creates micropores to regulate the drug release rate and synergizes with PTX to inhibit the proliferation of fibroblasts. This combination significantly enhances the inhibitory effect on the proliferation of fibroblasts and smooth muscle cells, without adversely affecting airway epithelial cells. This may represent a novel approach to reducing restenosis by addressing a critical complication associated with the use of airway stents.

Recent research has shown that deep learning (DL) faces physical realism challenges in predicting runoff responses under climate change, mainly due to DL’s data dependence and lack of process understanding. In this study, a physics-encoded neural network model (dNN) was developed to adress this. dNN enables a fully process-based way to training and prediction by encoding process-based modeling knowledge into the DL architecture, including the water balance principle and causal linkages of catchment hydrological processes. To examine whether dNN can produce reliable runoff responses under warming scenarios, we first conducted regional training for dNN on daily runoff in 29 catchment in California. Two process-based models, EXP-HYDRO and HBV, were then developed as benchmarks. Both dNN and a pure data-driven LSTM were forced under warming scenarios, and the monthly hydrographs and total runoff ratios metrics were evaluated relative to the benchmarks. The results demonstrated: (1) For monthly hydrographs, dNN exhibited advantages in capturing cold-season runoff increase and warm-season recession than LSTM, effectively predicting the changes and trends in monthly runoff under warming scenarios; (2) For total runoff ratios, dNN predicted fewer catchments with increased runoff, indicating it can better maintain the total water budget under warming scenarios; (3) Through the synergy with physics, dNN was able to reasonably infer unobserved snowpack dynamics under warming scenarios. These results highlight the credibility and necessity of considering physics for DL in predicting runoff responses under climate change. Overall, this study provides a promising solution for considering physics in DL to further improve the process understanding in changing environments.

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (Fe3O4 NCs), – CUR layer, – and MnO2 (CUR-Fe@MnO2 NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO2 NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO2 NFs to release Mn2+ and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO2 NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO2 NFs were effective T1/T2 contrast agents for molecular magnetic resonance imaging due to the release of Mn2+ and Fe3O4 NCs.

Abstract Zinc bromine flow batteries (ZBFBs) are well suited for stationary energy storage due to their attractive features of high energy density and low cost. Nevertheless, the ZBFBs suffer from low power density and limited efficiency owing to the relatively severe polarization of the Br2/Br− redox couple. Herein, a three‐dimensional (3D) hierarchical composite electrode based on core‐shell Ni/NiO heterostructures anchored on graphite felt (Ni/NiO@GF) is designed to promote the kinetics of the Br2/Br− couple, so as to improve the power density and efficiency of the ZBFB. In this design, the highly conductive carbon felt and Ni cores provide a composite electrode with a 3D electron transporting framework to guarantee excellent electronic conductivity, while the NiO shells possess great absorption ability to Br2 and brilliant catalytic activity for the Br2/Br− redox reaction to reduce the electrochemical polarization. As a result, an enhanced ZBFB with Ni/NiO@GF electrode shows an outstanding energy efficiency of 86% at 20 mA cm−2 and can be operated at a current density of up to 160 mA cm−2 with a respectable energy efficiency of 67%. These results exhibit a promising strategy to fabricate catalytic electrodes for high‐performance ZBFBs.

Abstract Population aging is discreetly reshaping the dynamics of social demand and labor supply, introducing potential turbulence to global carbon emissions. Understanding the impact of aging on carbon emissions is imperative for steering the next phase of sustainable development. This study, focusing on China, the world’s largest carbon emitter, delved into the intricacies of how population aging influences carbon emissions using a dynamic panel threshold model and a mediated effects model. Geographic heterogeneity within China was also considered. On the one hand, this study incorporated three consumer-side intermediation mechanisms: energy consumption, residential consumption and medical consumption. It was found that the positive driving effect of consumption-side variables on carbon emissions was characterized by an inverted “U”-shaped change in China’s highly aging regions, while an asymptotic upward trend of 7.65% was observed in regions with moderate and low aging. On the other hand, this study scrutinized three supply-side mediating mechanisms: industrial structure, R&D innovation and labor supply. The mechanism of supply-side variables on carbon emissions exhibited a shift from robustly positive driving to more nuanced weak positive driving or even negative inhibiting in highly aging regions, while inhibiting effects dominated in regions with moderate and low aging. This study offers a dual perspective encompassing both the production and consumption sides, which lays a foundation for exploring the internal mechanism of aging on carbon emission.

Purpose: This study aims to investigate patient characteristics with lens zonular ligament abnormalities in Acute Primary Angle Closure (APAC), identifying related risk factors, and evaluating the efficacy of Pilocarpine, a miotic agent. Design: Retrospective case-control study. Methods: Conducted as a retrospective case-control study at Hebei Provincial Eye Hospital from January 1, 2019, to December 31, 2021, the study included APAC cases undergoing ultrasound phacoemulsification with or without glaucoma surgery. Zonular ligament status was determined by intraoperative indicators such as lens equator visibility post-mydriasis and anterior capsule wrinkling during capsulorhexis. Patients were categorized into APAC and APAC with Lens Subluxation (APACLS) groups. Demographic details, Central Anterior Chamber Depth (ACD), Axial Length (AL), ACD difference between eyes (ACDD), Lens Thickness (LT), Lens Position (LP), and Relative Lens Position (RLP) were recorded and compared. Pilocarpine's impact on intraocular pressure reduction was assessed. Statistical analysis involved bilateral t-tests (for normally distributed data comparing both eyes in each group), non-parametric tests (for comparing two groups with non-normally distributed data), binary logistic regression, and Receiver Operating Characteristic (ROC) curve analysis for cutoff value determination related to zonular abnormalities. Results: The APAC and APACLS groups showed no significant difference in age of onset (70.11 ± 8.67 years vs. 70.11 ± 8.67 years, P = 0.159) or axial length of the eye (22.35 ± 0.64 mm vs. 22.36 ± 0.78 mm, P = 0.929). In the APACLS group, LT was greater (5.24 ± 0.37 mm vs. 5.01 ± 0.36 mm, P = 0.011), ACD was shallower (1.42 ± 0.24 mm vs. 1.69 ± 0.24 mm, P = 0.000), and ACDD was larger (0.38 ± 0.22 mm vs. 0.18 ± 0.18 mm, P = 0.000). The LP was lower (4.04 ± 0.32 vs. 4.20 ± 0.22, P = 0.013), and RLP was also lower (0.18 ± 0.02 vs. 0.19 ± 0.01, P = 0.015) in the APACLS group. A shallow ACD and a large ACDD were identified as risk factors associated with lens zonular abnormalities in the affected eyes (ACD OR value 63.97, P = 0.027; ACDD OR value 0.029, P = 0.027). Using ROC curve analysis, the cutoff value for ACDD was determined to be 0.375 mm, and for ACD, it was 1.6 mm. After pupil constriction with Pilocarpine eye drops, the proportion of patients whose intraocular pressure normalized was 75.36 % (52/69) in the APAC group and 71.43 % (25/35) in the APACLS group. Conclusion: ACD and ACDD in the affected eye are indicative of increased risk for APACLS. An ACD 0.375 mm should prompt consideration of zonular ligament abnormalities. Pilocarpine as a miotic treatment is safe and effective for such patients.

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Given the increased incidence of pluvial floods due to climate change and urbanization, the demand for highly efficient and accurate modeling within urban drainage systems has intensified, making machine learning and deep learning techniques increasingly popular. Nonetheless, these data-driven approaches face challenges in adequately capturing and interpreting dynamic process-evolving features, especially the spatiotemporal effects emanating from manholes during urban waterlogging events. To address these issues, this study proposes a general framework that extracts the spatiotemporal effects using the dynamic spatial Durbin model, integrates such effects with four machine learning models (i.e., artificial neural network, Bayesian neural network (BNN), light gradient boosting machine, and long short-term memory network), and clarifies decision-making processes of the best model by employing the Shapley Additive Explanations (SHAP) method. The results indicate that (1) the BNN with spatiotemporal effects (BNNST) not only outperforms other benchmark models but also provides accurate forecasts with quantifiable uncertainties; (2) compared to the original model, spatiotemporal effects enhance the models’ understanding of urban flooding dynamics, thereby improving predictive precision; (3) spatiotemporal effects comprise roughly 14 % of the contributions to the BNNST’s output, as interpreted by SHAP-based explanations; (4) incorporating interpretability into the BNN technique underscores the trustworthiness of the explanations at varying confidence levels, thereby deepening the understanding of decision-making processes.

Abstract Research over the past three decades has provided rich empirical evidence for the inverted U-shaped EKC theory, but current problems facing advancing climate mitigation actions require us to re-examine the shape of global EKC rigorously. This paper examined the N-shaped EKC in a panel of 214 countries with 12 traditional and emerging variables, including institutions and risks, information and communication technology (ICT), artificial intelligence(AI), resource and energy use, and selected social factors. The two-dimensional Tapio decoupling model based on N-shaped EKC to group homogeneous countries is developed to explore the inter-group heterogeneous carbon emission effects of each variable. Global research results show that the linear and cubic terms of GDP per capita are significantly positive, while the quadratic term is significantly negative, regardless of whether additional variables are added. This means the robust existence of an N-shaped EKC. Geopolitical risk, ICT, and food security are confirmed to positively impact per capita carbon emissions, while the impact of composite risk, institutional quality, digital economy, energy transition, and population aging are significantly negative. The impact of AI, natural resource rents, trade openness, and income inequality are insignificant. The inflection points of the N-shaped EKC considering all additional variables are 45.08 and 73.44 thousand US dollars, respectively. Combining the turning points and the calculated decoupling coefficients, all countries are categorized into six groups based on the two-dimensional decoupling model. The subsequent group regression results show heterogeneity in the direction and magnitude of the carbon emission impacts of most variables. Finally, differentiated carbon emission reduction strategies for countries in six two-dimensional decoupling stages are proposed.

Introduction: Metastasis is an important cause of high mortality and lethality of oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects of Fn-derived extracellular vesicles on oral cancer metastasis and the underlying mechanisms are unclear. Objectives: We aimed to determine whether and how Fn OMVs mediate oral cancer metastasis. Methods: OMVs were isolated from brain heart infusion (BHI) broth supernatant of Fn by ultracentrifugation. Tumour-bearing mice were treated with Fn OMVs to evaluate the effect of OMVs on cancer metastasis. Transwell assays were performed to determine how Fn OMVs affect cancer cell migration and invasion. The differentially expressed genes in Fn OMV-treated/untreated cancer cells were identified by RNA-seq. Transmission electron microscopy, laser confocal microscopy, and lentiviral transduction were used to detect changes in autophagic flux in cancer cells stimulated with Fn OMVs. Western blotting assay was performed to determine changes in EMT-related marker protein levels in cancer cells. Fn OMVs’ effects on migration after blocking autophagic flux by autophagy inhibitors were determined by in vitro and in vivo experiments. Results: Fn OMVs were structurally similar to vesicles. In the in vivo experiment, Fn OMVs promoted lung metastasis in tumour-bearing mice, while chloroquine (CHQ, an autophagy inhibitor) treatment reduced the number of pulmonary metastases resulting from the intratumoral Fn OMV injection. Fn OMVs promoted the migration and invasion of cancer cells in vivo, leading to altered expression levels of EMT-related proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that Fn OMVs activate intracellular autophagy pathways. Blocking autophagic flux with CHQ reduced in vitro and in vivo migration of cancer cells induced by Fn OMVs as well as reversed changes in EMT-related protein expression. Conclusion: Fn OMVs not only induced cancer metastasis but also activated autophagic flux. Blocking autophagic flux weakened Fn OMV-stimulated cancer metastasis.

Abstract Environmental degradation has profoundly impacted both human society and ecosystems. The environmental Kuznets curve (EKC) illuminates the intricate relationship between economic growth and environmental decline. However, the recent surge in trade protectionism has heightened global economic uncertainties, posing a severe threat to global environmental sustainability. This research aims to investigate the intricate pathways through which trade protection, assessed by available trade openness data, influences the nexus between economic growth and environmental degradation. Leveraging comprehensive global panel data spanning 147 countries from 1995 to 2018, this study meticulously examines the non-linear dynamics among trade, economy, and the environment, with a particular emphasis on validating the EKC hypothesis. This study encompasses exhaustive global and panel data regressions categorized across four income groups. The research substantiates the validity of the EKC hypothesis within the confines of this investigation. As income levels rise, the impact of economic growth on environmental degradation initially intensifies before displaying a diminishing trend. Additionally, trade protection manifests as a detriment to improving global environmental quality. The ramifications of trade protectionism display nuanced variations across income strata. In high-income nations, trade protection appears to contribute to mitigating environmental degradation. Conversely, within other income brackets, the stimulating effect of trade protection on environmental pressure is more conspicuous. In other words, trade protectionism exacerbates environmental degradation, particularly affecting lower-income countries, aligning with the concept of pollution havens. The study’s results illuminate nuanced thresholds in the relationship between trade, economic growth, and environmental degradation across income groups, emphasizing the heterogeneous impact and underlying mechanisms. These findings provide valuable insights for policymakers, urging collaborative efforts among nations to achieve a harmonious balance between economic advancement and environmental preservation on a global scale.

Abstract Seed germination is a complex process regulated by internal and external factors. Melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous signaling molecule, playing an important role in regulating seed germination under normal and stressful conditions. In this review, we aim to provide a comprehensive overview on melatonin's effects on seed germination on the basis of existing literature. Under normal conditions, exogenous high levels of melatonin can suppress or delay seed germination, suggesting that melatonin may play a role in maintaining seed dormancy and preventing premature germination. Conversely, under stressful conditions (e.g., high salinity, drought, and extreme temperatures), melatonin has been found to accelerate seed germination. Melatonin can modulate the expression of genes involved in ABA and GA metabolism, thereby influencing the balance of these hormones and affecting the ABA/GA ratio. Melatonin has been shown to modulate ROS accumulation and nutrient mobilization, which can impact the germination process. In conclusion, melatonin can inhibit germination under normal conditions while promoting germination under stressful conditions via regulating the ABA/GA ratios, ROS levels, and metabolic enzyme activity. Further research in this area will deepen our understanding of melatonin's intricate role in seed germination and may contribute to the development of improved seed treatments and agricultural practices.

Abstract Objective This study, based on the China Hainan Centenarians Cohort Study (CHCCS), aims to comprehensively describe the characteristic of daytime, night and total sleep duration, sleep quality and different sleep mode of Hainan centenarians and their associations with activity of daily living (ADL) functions. Method The baseline data of CHCCS was used. ADL function was evaluated the Bathel index, sleep quality was evaluated by Pittsburgh sleep quality index (PSQI), sleep status including daytime, night and total sleep duration as well as sleep quality and sleep mode. Multivariate logistic regression model was used to explore the association between sleep status and ADL disability and ADL moderate & severe disability. Results A total of 994 centenarians were included in this study with the age range 100–116 years old. Compared with the centenarians who sleep 6–9 h at night and 9 h at night and sleep ≥ 2 h in the daytime and ADL disability was 2.93 (95% CI: 1.02–8.44), and adjusted OR of ADL moderate & severe disability was 2.75 (95% CI: 1.56–4.83). Compared with centenarians who sleep for 7–9 h and have good sleep quality, centenarians who sleep for > 9 h and have poor sleep quality have an increased risk of ADL moderate & severe disability (OR = 3.72, 95% CI: 1.54–9.00). Conclusion Relation between sleep duration and ADL disability was more significant compared with sleep quality in Hainan centenarians. Poor sleep quality can aggravate the relationship between sleep duration and ADL moderate & severe disability.

The Middle Permian Qixia Formation in the Shuangyushi area, northwestern Sichuan Basin, develops shoal-facies dolomite reservoirs. To pinpoint promising reservoirs in the Qixia Formation, deep thin shoal-facies dolomite reservoirs were predicted using the techniques of pre-stack Kirchhoff-Q compensation for absorption, inverse Q filtering, low-to high-frequency compensation, forward modeling, and facies-controlled seismic meme inversion. The results are obtained in six aspects. First, the dolomite reservoirs mainly exist in the middle and lower parts of the second member of Qixia Formation (Qi2 Member), which coincide with the zones shoal cores are developed. Second, the forward modeling shows that the trough energy at the top and bottom of shoal core increases with increasing shoal-core thickness, and weak peak reflections are associated in the middle of shoal core. Third, five types of seismic waveform are identified through waveform analysis of seismic facies. Type-I and Type-II waveforms correspond to promising facies (shoal core microfacies). Fourth, vertically, two packages of thin dolomite reservoirs turn up in the sedimentary cycle of intraplatform shoal in the Qi2 Member, and the lower package is superior to the upper package in dolomite thickness, scale and lateral connectivity. Fifth, in plane, significantly controlled by sedimentary facies, dolomite reservoirs laterally distribute with consistent thickness in shoal cores at topographical highs and extend toward the break. Sixth, the promising prospects are the zones with thick dolomite reservoirs and superimposition of horst–graben structural traps.

The CuMgAl-x catalysts derived from hydrotalcite precursors with different Mg/Al molar ratios were synthesized and applied to CO2 hydrogenation to methanol reaction. In this study, the effects of Mg/Al molar ratio on the structure and surface properties of CuMgAl-x catalysts were investigated by XRD, N2 adsorption-desorption, SEM, TEM, H2-TPR, CO2-TPD, XPS, and in situ DRIFTS characterization methods. The results showed that an appropriate Mg/Al molar ratio can enhance the Cu-MgO interaction, increasing the basic sites and obtaining suitable acid sites. The dispersion of active Cu on the CuMgAl-x catalysts can be improved by strong Cu-MgO interaction, which enhances the adsorption capacity of CO2 and makes H2 activation easier, accelerates the conversion of intermediate species CO3* and HCO3*to HCOO*, and facilitates further conversion to CH3O* and CH3OH. The strong interaction between Cu and MgO was conducive to the formation of Cu+, which can inhibit the desorption of CO in the reverse water gas shift reaction. The CuMgAl-3 catalyst showed the highest CO2 Conversion rate (14.3%), methanol selectivity (94.5%), and STY of methanol (419.3 g⋅kgcat.−1⋅h−1) at 240°C and 2.5 MPa. The results obtained in this paper can provide a new idea for the design of high-performance catalysts for CO2 hydrogenation to methanol.

Abstract Background Although hypoalbuminemia was associated with high risk of mortality in community-dwelling older adults, as well as in the hospitalized older adults, little is known among centenarians. And there are limited data on whether having cardiometabolic diseases (CMDs) is associated with additive effects. Methods Baseline examinations including a determination of albumin levels were performed in 1002 Chinese centenarians from January 2014 through to December 2016, and the survival status was subsequently ascertained until 31 May 2021. Cox proportional risk model was performed to assess the risk of all-cause mortality associated with albumin levels and hypoalbuminemia combined with CMDs. Results Of 1002 participants included in the analysis, the mean level of albumin was 38.5 g/L (± standard deviation, 4.0 g/L), and 174 (17.4%) had hypoalbuminemia (albumin

Xylem-associated fungus can secrete many secondary metabolites to help Aquilaria trees resist various stresses and play a crucial role in facilitating agarwood formation. However, the dynamics of endophytic fungi in Aquilaria sinensis xylem after artificial induction have not been fully elaborated. Endophytic fungi communities and xylem physio-biochemical properties were examined before and after induction with an inorganic salt solution, including four different times (pre-induction (0M), the third (3M), sixth (6M) and ninth (9M) month after induction treatment). The relationships between fungal diversity and physio-biochemical indices were evaluated. The results showed that superoxide dismutase (SOD) and peroxidase (POD) activities, malondialdehyde (MDA) and soluble sugar content first increased and then decreased with induction time, while starch was heavily consumed after induction treatment. Endophytic fungal diversity was significantly lower after induction treatment than before, but the species richness was promoted. Fungal β-diversity was also clustered into four groups according to different times. Core species shifted from rare to dominant taxa with induction time, and growing species interactions in the network indicate a gradual complication of fungal community structure. Endophytic fungi diversity and potential functions were closely related to physicochemical indices that had less effect on the relative abundance of the dominant species. These findings help assess the regulatory mechanisms of microorganisms that expedite agarwood formation after artificial induction.

Abstract Research on the impact of foreign direct investment (FDI) on environmental quality has not reached consensus. This paper examines the potential structural break in the relationship between FDI and the environment from the perspective of economic scale. The results of the panel threshold estimation for 67 countries of different income groups show that the impact of FDI on carbon emissions shifts from positive to negative at different income level stages, using GDP as the threshold. This conclusion is further verified by the group regression results of the robustness test. When the GDP per capita is below $541.87, FDI shows a significant positive impact on carbon emissions, and this interval corresponds to a wide range of low-income economies today, however, when the GDP per capita exceeds $541.87, this positive impact almost disappears. The negative impact of FDI on carbon emissions manifests itself once the GDP per capita reaches $46515, and the sample countries corresponding to this interval since 2014 are mainly Switzerland, Iceland, Denmark, Sweden, the United States, Singapore, and Australia. Therefore, we call on countries to raise their income levels so that they can cross the lower threshold and thus take advantage of the emission reduction effect provided by FDI.

Abstract Background Cardiovascular disease has become the leading cause of death worldwide, but there is a lack of data on whether cardiovascular health (CVH) is associated with elderly mortality in China. We investigated the relationship between the ideal CVH score of Chinese elderly and the all-cause mortality. Methods The Beijing Elderly Comprehensive Health Cohort Study included a total of 4,499 participants aged 60 years and above. The CVH metric was calculated at baseline and had a score ranging from 0 to 12. The relationship of CVH metrics with all-cause mortality was investigated using Cox proportional hazard regression analysis. The robustness of results was tested using subgroup and sensitivity analysis. Results The median CVH score among participants was 8.00 (2.00), with only 8.0% scoring 11–12 points. 667 deaths were observed during an average follow-up time of 8.2 years. Participants with a CVH score of 11–12 had a decreased risk of all-cause mortality when compared to those with a CVH score of 0–4(HR = 0.584, 95% CI: 0.373–0.913). Participants had a 7.5% lower risk of all-cause death with each unit higher CVH score (HR = 0.925, 95%CI: 0.885–0.967) with a linearly decreasing trend (P nonlinear = 0.575). The relationships were greater in younger elderly people and stroke patients (P interaction = 0.011 and 0.037. respectively). The consistency of significant trends in sensitivity analysis shows the robustness of association (P trend

Impoverished sub-Saharan Africa (SSA) is under increasing environmental pressure from global environmental changes. It is now generally accepted in academic circles that economic development in SSA countries can cause environmental pressure in other countries. However, there is research gap on the impact of economic assistance on environmental pressure in SSA countries and whether economic assistance causes spatial spillovers of environmental pressure between SSA countries. To better understand the impact of economic assistance on environmental pressures in SSA, a dynamic spatial Dubin panel model was developed. It helped us explore the spatial spillover effects of economic assistance on environmental pressures in recipient countries based on the panel data from 34 SSA countries. The results show that economic assistance had a positive stimulating effect on environmental pressures of recipient countries, which means that the degree of human disturbance to the environment has deepened. Due to the regional correlation effect, neighboring countries were saddled with environmental pressures from the target country. Moreover, environmental pressures have time inertia, which can easily produce a snowball effect. The decomposition of effects shows that the impact of economic assistance on environmental pressures is relatively minor. Environmental pressures have spillover effects, so to deal with diffuse risks, joint regional prevention and control policies should be developed.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR-associated (Cas) proteins serve as an adaptive immune system that safeguards prokaryotes and some of the viruses that infect prokaryotes from foreign nucleic acids (such as viruses and plasmids). The genomes of the majority of archaea and about half of all bacteria contain various CRISPR-Cas systems. CRISPR-Cas systems depend on CRISPR RNAs (crRNAs). They act as a navigation system to specifically cut and destroy foreign nucleic acids by recognizing invading foreign nucleic acids and binding Cas proteins. In this review, we provide a brief overview of the evolution and classification of the CRISPR-Cas system, focusing on the functions and applications of the CRISPR-Cas13a system. We describe the CRISPR-Cas13a system and discuss its RNA-directed ribonuclease function. Meanwhile, we briefly introduce the mechanism of action of the CRISPR-Cas13a system and summarize the applications of the CRISPR-Cas13a system in pathogen detection, eukaryotes, agriculture, biosensors, and human gene therapy. We are right understanding of CRISPR-Cas13a has been broadened, and the CRISPR-Cas13a system will be useful for developing new RNA targeting tools. Therefore, understanding the basic details of the structure, function, and biological characterization of CRISPR-Cas13a effector proteins is critical for optimizing RNA targeting tools.

The treatment of bone or cartilage damage and inflammation-related diseases has been a long-standing research hotspot. Traditional treatments such as surgery and cell therapy have only displayed limited efficacy because they can’t avoid potential deterioration and ensure cell activity. Recently, exosomes have become a favorable tool for various tissue reconstruction due to their abundant content of proteins, lipids, DNA, RNA and other substances, which can promote bone regeneration through osteogenesis, angiogenesis and inflammation modulation. Besides, exosomes are also promising delivery systems because of stability in the bloodstream, immune stealth capacity, intrinsic cell-targeting property and outstanding intracellular communication. Despite having great potential in therapeutic delivery, exosomes still show some limitations in clinical studies, such as inefficient targeting ability, low yield and unsatisfactory therapeutic effects. In order to overcome the shortcomings, increasing studies have prepared genetically or chemically engineered exosomes to improve their properties. This review focuses on different methods of preparing genetically or chemically engineered exosomes and the therapeutic effects of engineering exosomes in bone regeneration and anti-inflammation, thereby providing some references for future applications of engineering exosomes.

To identify candidate pathogenic genes of early-stage Crohn's disease (CD) and predict potential roles of genetic factors in CD, we performed whole exome sequencing on a child with early-stage Crohn's disease (CD) and her parents (core family), found that the patient carried heterozygous variants of 4 genes: NOD2 c. 2257 C > T, IL10RA c. 301 C > T, PLA2G6 c. 2029 C > T, COL7A1 c. 3190 G > A. Heterozygous variants of NOD2, IL10RA, PLA2G6 and COL7A1, intestinal inflammatory response is triggered, normal intestinal wall tissue damage, leading to CD phenotype.

Abstract Background Treatment options are limited for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all‐trans retinoic acid (ATRA) combined with low‐dose apatinib in patients with R/M ACCHN according to a secondary analysis of a phase II study. Methods Patients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment‐related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25 mg/m2/day) and apatinib (250 mg/day) between March 2019 and October 2021 until progression of disease (PD). Results A total of 16 patients were included with nine (56.3%) males and aged 35–69 years old. All recruited patients previously received anti‐angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow‐up of 23.9 months (range:17.8–31.7 months), 11 (68.8%) patients developed PD and one of them died in 20.9 months. The median of progression‐free survival (PFS) was 16.3 months (95% CI: 7.2–25.4 months), and the 6‐month, 12‐month, and 24‐month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (n = 2, 12.5%) and hand‐foot syndrome (n = 1, 6.25%). Conclusion All‐trans retinoic acid combined with low‐dose apatinib might be a potential efficacy therapeutic option for patients with R/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT 04433169).

Power system with large scale Inverter-based Resources (IBR) penetration is challenged with insufficient voltage and frequency support capacity. This paper restructures the control blocks of virtual synchronous generator (VSG) from the perspective of traditional synchronous generators’ control, the control path of the system over its active and reactive power output is clarified and simplified, which has facilitated the tuning of virtual inertia and damping parameters. Firstly, the small signal model of VSG control IBR is established, including instantaneous power calculation module, LC filter and power loop, voltage and current loops. In the meantime, the improved VSG voltage and frequency regulation control strategy is proposed based on the stability analysis of the small signal model. The stable operation range of the VSG control grid-connected inverter system is studied with the objective to improve the stability and robustness of the VSG-controlled grid-connected inverter system. Finally, MATLAB/Simulink simulation verifies the correctness of the proposed VSG’s dynamic model of power grid voltage and frequency regulation. The effectiveness of the restructures of VSG is verified as well. The results show that the control strategy not only improves the inertia of the system, but also enables the IBR to support the frequency and voltage of the system.

Stellate ganglion blocks (SGBs) has been applied in clinics to alleviate pain-related syndromes for almost a century. In recent years, it has been reported that SGB can attenuate acute lung injury (ALI) in animals. However, the details of these molecular mechanisms remain complex and unclear. In this study, rats were randomly divided into four groups: group C (receiving no treatment), group NS (receiving the intratracheal instillation of normal saline), group L (receiving the intratracheal instillation of LPS) and group LS (receiving SGB after the intratracheal instillation of LPS). The pathological damage of lung tissue, arterial blood gases, the differentiation of alveolar macrophages (AMs) and inflammatory cytokines (IL-1β, IL-6, IL-10) were detected. Furthermore, the oxidative stress indexes (ROS, CYP-D, T-SOD, Mn-SOD and CAT) in serum and the levels of Sirt3 signaling-associated proteins (JAK2/STAT3, NF-κb p65, CIRP and NLRP3) in the lungs were measured. The results revealed that SGB could attenuate lung tissue damage, improve pulmonary oxygenation, promote the differentiation of AMs to the M2 phenotype, decrease the secretion of IL-1β and IL-6, and increase the secretion of IL-10. Meanwhile, SGB was found to inhibit the production of ROS and CYP-D, and enhance the activities of T-SOD, Mn-SOD and CAT. Furthermore, SGB upregulated Sirt3 and downregulated JAK2/STAT3 and NF-κb p65 phosphorylation, CIRP and NLRP3. Our work revealed that SGB could attenuate LPS-induced ALI by activating the Sirt3-mediated regulation of oxidative stress and pulmonary inflammation; this may shed new light upon the protection of SGB and provide a novel prophylactic strategy for LPS-induced ALI.

To investigate the difference between rumen-protected niacin (RPN) and rumen-protected nicotinamide (RPM) in the transcriptome of genes relating to the lipid metabolism of the liver of periparturient dairy cows, 10 healthy Chinese Holstein cows were randomly divided into two groups and fed diets supplemented with 18.4 g/d RPN or 18.7 g/d RPM, respectively. The experiment lasted from 14 days before to 21 days after parturition. Liver biopsies were taken 21 days postpartum for transcriptomic sequencing. In addition, human LO2 cells were cultured in a medium containing 1.6 mmol/L of non-esterified fatty acids and 1 mmol/L niacin (NA) or 2 mmol/L nicotinamide (NAM) to verify the expression of the 10 genes selected from the transcriptomic analysis of the liver biopsies. The expression of a total of 9837 genes was detected in the liver biopsies, among which 1210 differentially expressed genes (DEGs) were identified, with 579 upregulated and 631 downregulated genes. These DEGs were associated mainly with lipid metabolism, oxidative stress, and some inflammatory pathways. Gene ontology (GO) enrichment analysis showed that 355 DEGs were enriched in 38 GO terms. The differences in the expression of these DEGs between RPN and RPM were predominantly related to the processes of steroid catabolism, steroid hydroxylase, monooxygenase activity, oxidoreductase activity, hemoglobin binding, and ferric iron binding, which are involved mainly in lipid anabolism and redox processes. The expressions of FADS2, SLC27A6, ARHGAP24, and THRSP in LO2 cells were significantly higher (p < 0.05) while the expressions of BCO2, MARS1, GARS1, S100A12, AGMO, and OSBPL11 were significantly lower (p < 0.05) on the NA treatment compared to the NAM treatment, indicating that NA played a role in liver metabolism by directly regulating fatty acid anabolism and transport, inflammatory factor expression, and oxidative stress; and NAM functioned more as a precursor of nicotinamide adenine dinucleotide (NAD, coenzyme I) and nicotinamide adenine dinucleotide phosphate (NADP, coenzyme II) to participate indirectly in biological processes such as ether lipid metabolism, cholesterol metabolism, energy metabolism, and other processes.

Although there are many studies on the social welfare of renewable energy, the systematic study of the impact of renewable energy on life expectancy is relatively rare. Aiming at filling the research gap, we incorporate renewable energy consumption, economic growth, and life expectancy into a framework to study the relationship between them using the linear fixed-effect model and non-linear panel threshold model. Both the fixed-effect model and the threshold model results show a positive relationship between renewable energy consumption and life expectancy. Renewable energy consumption has a double threshold effect of per capita GDP on life expectancy. As per capita GDP crosses these two thresholds in turn, the correlation coefficient between renewable energy consumption and life expectancy increases. In addition, the relationship between renewable energy and life expectancy varies across income groups. The correlation between renewable energy consumption and life expectancy in the high-income group is the highest among all income groups, implying that renewable energy consumption is more helpful in increasing life expectancy in high-income countries. We call for the integration of health policy and renewable energy policy so that renewable energy generates greater health benefits.

This study explores whether increasing renewable energy consumption can alleviate environmental pressures (per capita carbon emissions and per capita ecological footprint) and the heterogeneity of the effects of increasing renewable energy consumption on the environmental pressures of countries in different income groups. We analyze 130 countries and three income groups from 1992 to 2019 based on a panel threshold regression estimation approach. The results show that (i) There is a negative relationship between renewable energy consumption and per capita ecological footprint and per capita carbon emissions, indicating that renewable energy consumption alleviates environmental pressure. (ii) When renewable energy consumption increases, the negative effects of renewable energy on per capita ecological footprint and per capita carbon emissions become more significant. This means that the more renewable energy is developed, the more it helps to alleviate environmental pressure. (iii) The inhibitory effect of renewable energy consumption on per capita ecological footprint is more significant in low-income countries than in middle-income countries. This indicates that renewable energy is more effective in reducing environmental pressures in poor countries than in rich countries.

Abstract Non-traumatic osteonecrosis of the femoral head (ONFH) relies on multiple pathogenic factors, including intravascular coagulation, osteoporosis and lipid metabolism disorders. Despite extensively explored from various aspects, genetic mechanism underlying non-traumatic ONFH has not been fully elucidated. We randomly collected blood and necrotic tissue samples from 32 patients with non-traumatic ONFH as well as blood samples from 30 healthy individuals for whole exome sequencing (WES). Germline mutation and somatic mutation were analyzed to identify new potential pathogenic genes responsible for non-traumatic ONFH. Three genes might correlate with non-traumatic ONFH: VWF, MPRIP (germline mutations) and FGA (somatic mutations). Germline or somatic mutations in VWF, MPRIP and FGA correlate with intravascular coagulation, thrombosis, and consequently, ischemic necrosis of the femoral head.

A fast multidither coherent optical adaptive technology (fCOAT) focuses light through scattering tissue for optogenetic stimulation with subcellular resolution.

Abstract Aims The aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances. Research design and methods We recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed. Results We found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a “U-shaped” trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p

Prompt and accurate traffic flow forecasting is a key foundation of urban traffic management. However, the flows in different areas and feature channels (inflow/outflow) may correspond to different degrees of importance in forecasting flows. Many forecasting models inadequately consider this heterogeneity, resulting in decreased predictive accuracy. To overcome this problem, an attention-based hybrid spatiotemporal residual model assisted by spatial and channel information is proposed in this study. By assigning different weights (attention levels) to different regions, the spatial attention module selects relatively important locations from all inputs in the modeling process. Similarly, the channel attention module selects relatively important channels from the multichannel feature map in the modeling process by assigning different weights. The proposed model provides effective selection and attention results for key areas and channels, respectively, during the forecasting process, thereby decreasing the computational overhead and increasing the accuracy. In the case involving Beijing, the proposed model exhibits a 3.7% lower prediction error, and its runtime is 60.9% less the model without attention, indicating that the spatial and channel attention modules are instrumental in increasing the forecasting efficiency. Moreover, in the case involving Shanghai, the proposed model outperforms other models in terms of generalizability and practicality.

Context A novobiocin derivative, XN4, has been shown to promote cell apoptosis in chronic myeloid leukaemia.Objective This study explores the mechanism by which XN4 promotes ferroptosis of gastric cancer (GC) cells.Materials and methods Human GC SGC-7901 and BGC-823 cells were treated with different XN4 concentrations (0, 0.1, 0.5, 1.0, 5.0, and 10.0 μmol/L) to evaluate effects of XN4. Additionally, cells were pre-treated for 24 h with si-NOX4, for 1 h with the iron chelator deferoxamine mesylate (DFO) or for 1 h with the lipid peroxidation inhibitor liproxstatin-1 before being treated with XN4 to analyse the mechanism of XN4.Results XN4 increased cell death (IC50 values of XN4 on SGC-7901 and BGC-823 cells: 1.592 ± 0.14 μmol/L and 2.022 ± 0.19 μmol/L) and Fe2+ levels in SGC-7901 and BGC-823 cells. These effects of 2.0 μmol/L XN4 were abolished by 100 μmol/L DFO treatment. XN4 enhanced transferrin and transferrin receptor expression to induce Fe2+ accumulation. XN4 decreased mitochondrial membrane potentials in GC cells, similar to erastin. Additionally, XN4 increased MDA, hydrogen peroxide, and ROS levels, but diminished total glutathione levels. Liproxstatin-1 (200 nmol/L) nullified the effects of XN4 (2.0 μmol/L) on MDA levels and cell death. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown.Discussion and conclusions The pro-ferroptotic role of XN4 in GC might enable it to become a promising drug for GC treatment in the future despite the need for extensive research.

A new series of 5-trifluoromethylpyrimidine derivatives were designed and synthesised as EGFR inhibitors. Three tumour cells A549, MCF-7, PC-3 and EGFR kinase were employed to evaluate their biological activities. The results were shown that most of the target compounds existed excellent antitumor activities. In particular, the IC50 values of compound 9u (E)-3-((2-((4-(3-(3-fluorophenyl)acrylamido)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylthiophene-2-carboxamide against A549, MCF-7, PC-3 cells and EGFR kinase reached to 0.35 μM, 3.24 μM, 5.12 μM, and 0.091 μM, respectively. Additionally, further researches revealed that compound 9u could induce early apoptosis of A549 cells and arrest the cells in G2/M phase. Taken together, these findings indicated that compound 9u was potential for developing as antitumor reagent.