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Background: Virtual reality (VR) offers significant potential for hands-on learning environments by providing immersive and visually stimulating experiences. Interacting with such environments can bring numerous benefits to learning, including enhanced engagement, knowledge construction, and higher-order thinking. However, many current VR studies in hands-on learning tend to utilise one-way learning materials, limiting participants' ability to interact with and reflect on their actions and learning experiences. Moreover, these studies often neglect to assess learners' capacity to transfer their skills from VR learning to real-world scenarios. Therefore, this study aims to investigate participants' engagement, learning outcomes, higher-order thinking, and their ability to apply acquired skills in real-world contexts. Method and Objective: Participants were immersed in a hands-on learning environment in VR, where they received feedback and engaged in reflection during the learning process. This study recruited 68 university students to participate in the experiment, employing a quasi-experimental design. Participants experienced learning units both with and without reflection on the feedback. The theme of these learning units was related to embedded systems, encompassing topics such as the assembly of embedded components and Python programming. The investigation aimed to assess whether reflection in VR could enhance cognitive levels, engagement, real-world hands-on tasks abilities, and higher-order thinking. Results: The research results indicate that in the VR hands-on learning environment, participants engage in reflection through the provided feedback, effectively enhancing their engagement, cognitive levels, and hands-on task abilities. Simultaneously, it also successfully assists participants in developing problem-solving skills and critical thinking in higher-order thinking. Conclusions: Participants actively engaged in reflection on their own learning tasks and actions within the hands-on learning environment, enabling them to develop a deeper understanding of the learning material and enhance their real-world hands-on tasks abilities, we encourage the integration of reflection strategies in VR learning environments for hands-on learning, as they can yield positive benefits for learners.

Financial education for children has drawn considerable attention and has recently been advocated in schools; however, its impact still needs to be examined with a more comprehensive evaluation framework. This study carries out a paired-design experiment to evaluate the effectiveness of the Aflatoun Child Social & Financial Education program, which is initiated by the International Children's Savings Foundation and covers more than 100 countries and millions of children and adolescents. The participants are students in grades 4-5 of primary schools in China. By using difference-in-differences estimation, this study finds that the Aflatoun curriculum can significantly improve children's behaviors in regular saving, rational consumption, and social participation. At the same time, unintended adverse negative effects are spotted in terms of children's attitudes and personality development. The estimation of its heterogeneous effects shows that financial education for children can achieve greater success in improving boys' financial behaviors and in underdeveloped areas.

Science, Technology, Engineering, and Mathematics (STEM) education is essential for developing future-ready learners in both secondary and higher education levels. However, as students transition to higher education, many encounter challenges with independent learning and research. This can negatively impact their Higher-Order Thinking Skills (HOTS), engagement, and practical expertise. This study introduces a solution: Computational Thinking Scaffolding (CTS) in the Jupyter Notebook environment, designed to enhance STEM education at the tertiary level. CTS incorporates five phases: Decomposition, Pattern Recognition, Abstraction, Algorithm Design, and Evaluation. Utilizing a quasi-experimental method, we assessed the impact of CTS on the HOTS, engagement, and practical skills of undergraduate and postgraduate students. Our findings hold substantial relevance for university educators, academic advisors, and curriculum designers aiming to enhance students' HOTS and hands-on capabilities in STEM disciplines. The results validate the effectiveness of CTS in elevating tertiary STEM learning outcomes, and they spotlight the adaptability of the Jupyter Notebook as a valuable tool in higher education. In conclusion, our research underscores the merits of CTS for improving outcomes in higher STEM education and sets a benchmark for future endeavors in this domain.

In the evolving landscape of higher education, challenges such as the COVID-19 pandemic have underscored the necessity for innovative teaching methodologies. These challenges have catalyzed the integration of technology into education, particularly in blended learning environments, to bolster self-regulated learning (SRL) and higher-order thinking skills (HOTS). However, increased autonomy in blended learning can lead to learning disruptions if issues are not promptly addressed. In this context, OpenAI's ChatGPT, known for its extensive knowledge base and immediate feedback capability, emerges as a significant educational resource. Nonetheless, there are concerns that students might become excessively dependent on such tools, potentially hindering their development of HOTS. To address these concerns, this study introduces the Guidance-based ChatGPT-assisted Learning Aid (GCLA). This approach modifies the use of ChatGPT in educational settings by encouraging students to attempt problem-solving independently before seeking ChatGPT assistance. When engaged, the GCLA provides guidance through hints rather than direct answers, fostering an environment conducive to the development of SRL and HOTS. A randomized controlled trial (RCT) was employed to examine the impact of the GCLA compared to traditional ChatGPT use in a foundational chemistry course within a blended learning setting. This study involved 61 undergraduate students from a university in Taiwan. The findings reveal that the GCLA enhances SRL, HOTS, and knowledge construction compared to traditional ChatGPT use. These results directly align with the research objective to improve learning outcomes through providing guidance rather than answers by ChatGPT. In conclusion, the introduction of the GCLA has not only facilitated more effective learning experiences in blended learning environments but also ensured that students engage more actively in their educational journey. The implications of this study highlight the potential of ChatGPT-based tools in enhancing the quality of higher education, particularly in fostering essential skills such as self-regulation and HOTS. Furthermore, this research offers insights regarding the more effective use of ChatGPT in education.

Abstract For breast cancer patients with physical exam node negative but radiological finding node abnormal (cN0/rNa), the NCCN and ASCO guidelines recommend sentinel lymph node biopsy (SLNB) as the first-line axillary staging. However, patients who undergo surgery firstly may be upstaged to pathological II–III status, and these patients happen to be the adaptive population of neoadjuvant therapy (NAT). There is no consensus on the optimal management of cN0/rNa patients. The aim is to explore the optimal management strategy of these patients. We performed a retrospective real-world study of 1414 cN0/rNa patients from June 2014 to October 2022. There were 1003 patients underwent surgery first and 411 patients underwent surgery after NAT. We analyzed the real-world conditions of these patients, compared axilla tumor burden between these two groups. In addition, we compared benefit ratio of axillary surgery and regional nodal irradiation (RNI) de-escalation under the two strategies. Among 1003 patients underwent surgery first, the positive and negative rates of fine needle aspiration (FNA) were 18.5% and 81.5%, respectively. There were 66.1% had ≤ 2 lymph nodes+. There were 40.8% of FNA+ patients could be exempted from ALND underwent surgery first. In 411 patients underwent surgery after NAT, the FNA positive and negative rates were 60.8% and 49.2%, respectively. There were 54.4% of FNA+ patients achieved axilla pathologic complete response (apCR) and could omit ALND after NAT. The apCR was 67.3% in HER2+/TNBC subtypes. According to the NSABP-B51 trial, there were 0 and 54.4% of FNA+ patients could omit RNI among surgery first and after NAT, respectively. Among 1–2 sentinel lymph node (SLN)-positive patients underwent surgery first, with a median follow-up 49 months, there was no difference of survival benefit between SLNB-only and SLNB-ALND. Compared with 1–2 SLN+ patients without RNI, RNI could bring better invasive disease-free survival (97.38% vs. 89.36%, P = 0.046) and breast cancer special survival (100% vs. 94.68%, P = 0.020). It is safe to perform SLNB omitting ALND when detected 1–2 positive SLNs in cN0/rNa patients. Patients with HER2+/TNBC subtypes underwent surgery after NAT had more chance to benefit from dual de-escalation, including axillary surgery and RNI de-escalation.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract Background Laser acupuncture is a proven non-invasive treatment with effects comparable to traditional acupuncture in different types of headaches, but there is still insufficient evidence for chronic migraine (CM) in adults. We aim to investigate the efficacy and safety of laser acupuncture (LA) as an add-on preventive therapy on CM. Methods A single-blind randomized controlled trial was conducted from January 2022 to November 2023. CM patients with unsatisfactory pharmacological effects were randomly assigned in a 1:1 ratio to receive either LA or sham treatment over a course of 8 sessions spanning 4 weeks. The co-primary outcomes were changes in monthly migraine days (MMD) and acute headache medications usage days per month from baseline. Evaluations were taken at baseline (12 weeks before randomization), at 4th week (treatment completed), 8th week and 12th week from baseline. Results A total of 60 patients (30 in each group) were included in the intention-to-treat analyses. Baseline headache characteristics between trial groups were similar. Compared with the sham group, the LA group had a significant reduction in MMD (5.2 vs. 1.5 days at 8th week, p = 0.015; 7.3 vs. 1.8 days at 12th week, p = 0.001), and acute headache medications usage days per month (3.1 vs. 0.4 days at 4th week, p = 0.007; 3.2 vs. 0.0 days at 8th week, p = 0.005; 3.9 vs. 0.0 days at 12th week, p

Abstract The kidney is vulnerable to ischemia and reperfusion (I/R) injury that can be fatal after major surgery. Currently, there are no effective treatments for I/R-induced kidney injury. Trimethylamine N-oxide (TMAO) is a gut-derived metabolite linked to many diseases, but its role in I/R-induced kidney injury remains unclear. Here, our clinical data reveals an association between preoperative systemic TMAO levels and postoperative kidney injury in patients after post-cardiopulmonary bypass surgery. By genetic deletion of TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) and dietary supplementation of choline to modulate TMAO levels, we found that TMAO aggravated acute kidney injury through the triggering of endoplasmic reticulum (ER) stress and worsened subsequent renal fibrosis through TGFβ/Smad signaling activation. Together, our study underscores the negative role of TMAO in I/R-induced kidney injury and highlights the therapeutic potential through the modulation of TMAO levels by targeting FMO3, thereby mitigating acute kidney injury and preventing subsequent renal fibrosis.

Abstract Triplostegia glandulifera Wall (T. glandulifera) is an ethnomedicine commonly used by ethnic minorities in Yunnan, China, to treat kidney disease. However, there are few reports on the renoprotective effects of this substance, and the active ingredients remain unclear. In this study, we extracted the polysaccharide fractions TGB and TGC using the water extraction-alcohol precipitation method and determined their molecular weight (Mw) and monosaccharide composition. The study investigated the protective effects of TGB and TGC fractions against diabetic nephropathy (DN) using an in vitro high glucose-induced HRMCs model and an in vivo STZ-induced diabetic mouse model. HPLC analysis revealed that TGB contained D-galacturonic acid, D-glucose, D-galactose, and D-arabinose, and had a lower Mw than TGC. In vitro, TGB showed concentration-dependent antioxidant activity and effectively reduced abnormal proliferation and while attenuating oxidative stress in HRMCs. In mice with diabetes, TGB corrected the dysregulation of glucose-lipid metabolism and alleviated oxidative stress in the kidneys. Additionally, it improved renal function and reduced renal tissue damage. The study suggests that the low Mw polysaccharides (TGB) have better activity against DN through the antioxidative stress mechanism. Graphical Abstract

Abstract Background and Aims Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. Methods In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. Results As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. Conclusions TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Abstract The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

Abstract Background Sleeping late has been a common phenomenon and brought harmful effects to our health. The purpose of this study was to investigate the association between sleep timing and major adverse cardiovascular events (MACEs) in patients with percutaneous coronary intervention (PCI). Methods Sleep onset time which was acquired by the way of sleep factors questionnaire in 426 inpatients was divided into before 22:00, 22:00 to 22:59, 23:00 to 23:59 and 24:00 and after. The median follow-up time was 35 months. The endpoints included angina pectoris (AP), new myocardial infarction (MI) or unplanned repeat revascularization, hospitalization for heart failure, cardiac death, nonfatal stroke, all-cause death and the composite endpoint of all events mentioned above. Cox proportional hazards regression was applied to analyze the relationship between sleep timing and endpoint events. Results A total of 64 composite endpoint events (CEEs) were reported, including 36 AP, 15 new MI or unplanned repeat revascularization, 6 hospitalization for heart failure, 2 nonfatal stroke and 5 all-cause death. Compared with sleeping time at 22:00–22:59, there was a higher incidence of AP in the bedtime ≥ 24:00 group (adjusted HR: 5.089; 95% CI: 1.278–20.260; P = 0.021). In addition, bedtime ≥ 24:00 was also associated with an increased risk of CEEs in univariate Cox regression (unadjusted HR: 2.893; 95% CI: 1.452–5.767; P = 0.003). After multivariable adjustments, bedtime ≥ 24:00 increased the risk of CEEs (adjusted HR: 3.156; 95% CI: 1.164–8.557; P = 0.024). Conclusion Late sleeping increased the risk of MACEs and indicated a poor prognosis. It is imperative to instruct patients with PCI to form early bedtime habits.

Abstract Background The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. Results We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. Conclusions Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.

Abstract To investigate the distribution characteristics of selenium (Se) in mountainous soil-crop systems and examine the threshold value of Se-rich soil, 275 soil samples and 153 associated crop samples (rice, maize, tea, nuts, konjac, mushrooms, buckwheat, and coffee) were collected in Ximeng County, a typical mountainous area in southwest China. The total Se, available Se, organic matter, pH, sampling point elevation, and crop Se content were analyzed to examine the distribution characteristics of soil Se and the ability of primary crops to enrich Se in Ximeng County. Random forest and multiple regression models were established to identify the factors influencing the available soil Se and the crop Se enrichment coefficient. Finally, the Se-rich soil threshold was examined based on the total Se, available Se, and Se content in primary crops (rice, maize, and tea). The results showed soil Se resource abundance in the study region, with high Se soil accounting for 64.72% of the entire area. The soil Se content displayed significant spatial autocorrelation. The average Se enrichment coefficient of the main cultivated crops included mushrooms > nuts > rice > coffee > tea > maize > buckwheat > konjac. The total Se content in the soil had the highest impact on the available Se content in the soil and the Se enrichment coefficient of crops. A Se-rich soil threshold of 0.3 mg·kg−1 was used for rice and maize, while that of tea was 0.4 mg·kg−1. This result provided a theoretical basis for developing and utilizing Se resources in mountainous soil in southwestern China and dividing the Se-rich soil threshold.

Abstract Lipid metabolism reprogramming involves in epithelial-mesenchymal transition (EMT), cancer stemness and immune checkpoints (ICs), which influence the metastasis of cancer. This study aimed to generate lipid metabolism-based signatures to predict prognosis, immunotherapy and chemotherapy response for colorectal adenocarcinoma (COAD). Transcriptome data and clinical information of COAD patients were collected from the cancer genome atlas (TCGA) database. The expression of EMT-, stem cell-, and IC-related genes were assessed between COAD and control samples. Modules and genes correlated EMT, ICs and stemness signatures were identified through weighted gene co-expression network analysis (WGCNA). Prognostic signatures were generated and then the distribution of risk genes was evaluated using single-cell RNA sequencing (scRNA-seq) data from GSE132465 dataset. COAD patients exhibited increased EMT score and stemness along with decreased ICs. Next, 12 hub genes (PIK3CG, ALOX5AP, PIK3R5, TNFAIP8L2, DPEP2, PIK3CD, PIK3R6, GGT5, ELOVL4, PTGIS, CYP7B1 and PRKD1) were found within green and yellow modules correlated with EMT, stemness and ICs. Lipid metabolism-based prognostic signatures were generated based on PIK3CG, GGT5 and PTGIS. Patients with high-risk group had poor prognosis, elevated ESTIMATEScore and StromalScore, 100% mutation rate and higher TIDE score. Samples in low-risk group had more immunogenicity on ICIs. Notably, PIK3CG was expressed in B cells, while GGT5 and PTGIS were expressed in stromal cells. This study generates lipid metabolism-based signatures correlated with EMT, stemness and ICs for predicting prognosis of COAD, and provides potential therapeutic targets for immunotherapy in COAD.

Abstract Cu catalyses electrochemical CO2 reduction to valuable multicarbon products but understanding the structure-function relationship has remained elusive due to the active Cu sites being heterogenized and under dynamic re-construction during electrolysis. We herein coordinate Cu with six phenyl-1H-1,2,3-triazole derivatives to form stable coordination polymer catalysts with homogenized, single-site Cu active sites. Electronic structure modelling, X-ray absorption spectroscopy, and ultraviolet–visible spectroscopy show a widely tuneable Cu electronics by modulating the highest occupied molecular orbital energy of ligands. Using CO diffuse reflectance Fourier transform infrared spectroscopy, in-situ Raman spectroscopy, and density functional theory calculations, we find that the binding strength of *CO intermediate is positively correlated to highest occupied molecular orbital energies of the ligands. As a result, we enable a tuning of C–C coupling efficiency—a parameter we define to evaluate the efficiency of C2 production—in a broad range of 0.26 to 0.86. This work establishes a molecular platform that allows for studying structure-function relationships in CO2 electrolysis and devises new catalyst design strategies appliable to other electrocatalysis.

Abstract Fluid movability in tight sands may not be accurately characterized by pore size-based classification methods solely because of the complex pore structure and heterogeneity in pore size. In this study, on the basis of casting thin slices and scanning electron microscope observation, pore structure was analyzed using mercury injection, NMR, and micron CT to classify and evaluate the tight oil reservoir. The experiment suggest that the quality of tight reservoir is determined by its pore structure, particularly the throat radius, with the microthroat being an essential factor in permeability. Uniquely, we divide the reservoir by Q-cluster with throat radius, displacement pressure, permeability and other parameters. Based on reservoir classification, this study proposed a method for studying the pore size classification of samples on the T2 spectrum by combining CT scanning with mercury intrusion and a NMR experiment. Pore fluids are generally classified into movable fluid and irreducible fluid by one or two NMR T2 cut-offs. The pore size distributions and capillarity boundaries are converted from T2 and mercury injection capillary pressure (MICP). We categorized pores into micropores (T2 10, with T2 > 300 as fractures), and medium pores (the rest). The saturation of movable fluid and the percentage of micro-fractures can characterize the seepage characteristics of tight reservoirs, which is of great significance for the later periods of oilfield development.

Abstract Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, tankyrasel binding protein 1 (TNKS1BP1) was found to interact with tripartite motif containing 21 (TRIM21) and mediated the ubiquitination of CCR4-NOT transcription complex subunit 4 (CNOT4) at the K239 residue via K48 and K6 linkage, which was essential for its tumorigenesis function. Autophagy and lipid reprogramming were identified as two possible mechanisms underlying the pro-tumor effect of TNKS1BP1. Upregulated TNKS1BP1 inhibited autophagy while induced lipid accumulation by inhibiting the JAK2/STAT3 pathway upon the degradation of CNOT4 in HCC. Importantly, knocking down TNKS1BP1 synergized with anti-PD-L1 treatment by upregulating PD-L1 expression on tumor cells via the JAK2/STAT3 pathway, and remodeling the tumor microenvironment by increasing infiltration of tumor-infiltrating lymphocytes as well as augmenting the effect of cytotoxic T lymphocytes. In conclusion, this study identified TNKS1BP1 as a predictive biomarker for patient prognosis and a promising therapeutic target to overcome anti-PD-L1 resistance in HCC.

Sapphire exhibits typical anisotropy due to its unique crystal structure, and there are significant property differences in different processing areas during the machining of curved sapphire component, making it essential to investigate the anisotropy in the removal process of sapphire materials for efficient curved surface machining. In this study, the force and acoustic emission (AE) signals were monitored at different scratch stages and orientations, and the anisotropic characteristics of ductile-brittle transition (DBT) depths, material removal morphology, and subsurface crack propagation direction were analyzed. The results indicate that the anisotropy of force signals and DBT depths is mainly reflected in the differences between crystal planes. In addition, the removal morphology of materials with different crystal orientations showed smooth scratch grooves with unclear anisotropic characteristics during the ductile removal (DR) stage, while the crack propagation direction with different scratch orientations during the DBT stage showed significant anisotropic characteristics. The brittle removal (BR) stage is characterized by brittle spalling in the form of shell-like, blocky, and fishbone spalling, and there is a significant anisotropic difference in the spalling shapes on both sides of the scratch. The original AE signals, Fast Fourier Transform (FFT), and Short Time Fourier Transform (STFT) results show that the AE frequencies of different crystal planes are different, and the differences in different scratch orientations on the same crystal plane are reflected in the peak amplitude. Finally, the propagation directions of subsurface cracks with different directions are anisotropic due to different scratching crystal planes, and propagate mainly along directions of 15°, 29°, 32°, 58°, and 105°.

Abstract Traditional catalytic techniques often encounter obstacles in the search for sustainable solutions for converting CO2 into value-added products because of their high energy consumption and expensive catalysts. Here, we introduce a contact-electro-catalysis approach for CO2 reduction reaction, achieving a CO Faradaic efficiency of 96.24%. The contact-electro-catalysis is driven by a triboelectric nanogenerator consisting of electrospun polyvinylidene fluoride loaded with single Cu atoms-anchored polymeric carbon nitride (Cu-PCN) catalysts and quaternized cellulose nanofibers (CNF). Mechanistic investigation reveals that the single Cu atoms on Cu-PCN can effectively enrich electrons during contact electrification, facilitating electron transfer upon their contact with CO2 adsorbed on quaternized CNF. Furthermore, the strong adsorption of CO2 on quaternized CNF allows efficient CO2 capture at low concentrations, thus enabling the CO2 reduction reaction in the ambient air. Compared to the state-of-the-art air-based CO2 reduction technologies, contact-electro-catalysis achieves a superior CO yield of 33 μmol g−1 h−1. This technique provides a solution for reducing airborne CO2 emissions while advancing chemical sustainability strategy.

Abstract The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Highlights MIL-88C (Fe) with varying aspect ratios as a precursor was synthesized by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. High-efficiency microwave absorption properties were achieved with RL min value of -67.4 dB (2.13 mm) and wide effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm) under the low filler loading. A symmetric gradient honeycomb structure was constructed utilizing the high-frequency structure simulator, achieving an EAB of 14.6 GHz and a RL min of -59.0 dB.

The blue carbon reservoir plays a unique role in addressing climate change and holds significant importance for China’s advancement in the “dual carbon” initiative. The mechanisms, carbon reduction potential, and potential economic value of blue carbon align with the goals of the Green Silk Road initiative. China’s conceptual frameworks, strategies and practices provide strong impetus for enhancing international cooperation and supporting the high-quality development of the Belt and Road Initiative. Looking ahead, integrating blue carbon into the focal points of international cooperation will contribute China’s wisdom and solutions to global sustainable development.

Abstract Objective Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. Methods A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. Results POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). Conclusion For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.

Typhoon disaster factors show multiplicity, so the risk assessment of typhoon-related disasters is more difficult than other hazards. Using the typhoon precipitation and maximum wind speed data of 81 national meteorological stations and 1 035 regional automatic meteorological stations in Anhui Province, a comprehensive typhoon wind and rain intensity index is first constructed. Then the typhoon wind and rain intensity index and disaster pregnant environment impact coefficient are used to assess the risk of typhoon disasters. According to the theory of natural disaster risk assessment, the risk assessment of housing damage by typhoon disaster in Anhui Province is conducted by integrating disaster-causing hazards, exposure level and vulnerability of disaster-bearing bodies. The results show that Anhui Province is affected by about 1.9 typhoons per year on average, with a duration of 2-4 days. The results are as follows. The southern part and mountainous areas usually have more typhoon precipitation than the northern part and plain areas. The high-hazard region caused by typhoon disasters is mainly located in the southern mountainous and Dabie Mountains in Anhui Province, with the relatively high-hazard region in the east of Jianghuai region, and the low-hazard area in most of the regions to the north of the Huaihe River and in the northwest of Jianghuai region. The high and relatively high-risk area of housing damage caused by typhoon disasters is located in the Dabie Mountains, the eastern part of the Jianghuai region, and the southern mountainous area in Anhui Province. These areas are generally high in elevation, and easily suffer from geological disasters and mountain floods during typhoon transit. In addition, the vulnerability of houses is high, which further causes a high risk of house collapse and damage. The medium-risk region is scattered in the Huaihe River region and Jiangnan region. Lower and low-risk areas are located in the central and western parts to the north of the Huaihe River, regions along the Yangtze River, and main urban areas. Using reports on house damage caused by typhoons from different counties in Anhui Province, the zoning results are verified through spatial consistency and scatter correlation. A high degree of spatial consistency between the risk zoning results and the actual damage, with scatter correlation between them passing a significance test of 0.01, indicating that the risk zoning results of housing damage by typhoon disaster in Anhui Province are basically consistent with the actual situation.

Abstract Translationally controlled tumor protein (TCTP), also known as histamine-releasing factor (HRF) or fortilin, is a highly conserved protein found in various species. To date, multiple studies have demonstrated the crucial role of TCTP in a wide range of cellular pathophysiological processes, including cell proliferation and survival, cell cycle regulation, cell death, as well as cell migration and movement, all of which are major pathogenic mechanisms of tumorigenesis and development. This review aims to provide an in-depth analysis of the functional role of TCTP in tumor initiation and progression, with a particular focus on cell proliferation, cell death, and cell migration. It will highlight the expression and pathological implications of TCTP in various tumor types, summarizing the current prevailing therapeutic strategies that target TCTP.

AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Strong-textural Mg-RE alloy exhibits creep asymmetry at 200°C, with a much higher creep resistance in compression than in tension, albeit a higher yield strength in tension than in compression. Creep asymmetry is ascribed to the non-Schmid effects of pyramidal slip, which enables a higher friction in compression and thus induces a lower mobility of pyramidal slip in compression than in tension. Additionally, the dissociation of dislocations into sessile structures in compression is more frequent than in tension, which contributes to the hardening response and thus lowers the compressive creep rate.

Verticillium dahliae is a broad host-range pathogen that causes vascular wilt in plants. The Verticillium wilt disease severity assay on plants caused by V. dahliae mainly includes two methods, one is a plant disease grade classification based on disease severity statistics [namely the disease index (DI)], and the other is the V. dahliae biomass quantification in plants (namely the fungal biomass). In this study, the relationships of pathogenicity with the DI, pathogenicity with the biomass, and the correlation analysis of the DI and relative fungal biomass were analysed. The results showed that pathogenicity assessment of V. dahliae strains using the DI method was able to give an intuitive reflection of the pathogenic ability for defoliating and non-defoliating strains; moreover, the method of quantitative PCR for fungal biomass also had high repeatability and stability. As a whole, the correlation coefficient between the DI and fungal biomass values of 28 strains was 0.728, indicating that the two data sets were highly correlated; however, the correlation coefficients of the defoliating strains and non-defoliating strains were only 0.5384 and 0.4547, respectively. In conclusion, the correlation coefficient between the DI and the fungal biomass presented high consistency, which could provide some meaningful exploration for the more accurate pathogenicity identification of V. dahliae.

Abstract Background Cotton is globally important crop. Verticillium wilt (VW), caused by Verticillium dahliae, is the most destructive disease in cotton, reducing yield and fiber quality by over 50% of cotton acreage. Breeding resistant cotton cultivars has proven to be an efficient strategy for improving the resistance of cotton to V. dahliae. However, the lack of understanding of the genetic basis of VW resistance may hinder the progress in deploying elite cultivars with proven resistance. Results We planted the VW-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2) in an artificial greenhouse and disease nursery. ZZM2 cotton was subsequently subjected to transcriptome sequencing after Vd991 inoculation (6, 12, 24, 48, and 72 h post-inoculation). Several differentially expressed genes (DEGs) were identified in response to V. dahliae infection, mainly involved in resistance processes, such as flavonoid and terpenoid quinone biosynthesis, plant hormone signaling, MAPK signaling, phenylpropanoid biosynthesis, and pyruvate metabolism. Compared to the susceptible cultivar Junmian No.1 (J1), oxidoreductase activity and reactive oxygen species (ROS) production were significantly increased in ZZM2. Furthermore, gene silencing of cytochrome c oxidase subunit 1 (COX1), which is involved in the oxidation-reduction process in ZZM2, compromised its resistance to V. dahliae, suggesting that COX1 contributes to VW resistance in ZZM2. Conclusions Our data demonstrate that the G. hirsutum cultivar ZZM2 responds to V. dahliae inoculation through resistance-related processes, especially the oxidation-reduction process. This enhances our understanding of the mechanisms regulating the ZZM2 defense against VW.

Abstract Ferroptosis is a novel form of programmed cell death which can exacerbate lung injury in septic acute respiratory distress syndrome (ARDS). Alveolar macrophages, crucial innate immune cells, play a pivotal role in the pathogenesis of ARDS. Ferritinophagy is a process of ferritin degradation mediated by nuclear receptor coactivator 4 (NCOA4) which releases large amounts of iron ions thus promoting ferroptosis. Recent evidence revealed that inhibiting macrophage ferroptosis can effectively attenuate pulmonary inflammatory injury. Melatonin (MT), an endogenous neurohormone, has antioxidant and anti-inflammatory effects and can reduce septic ARDS. However, it is not clear whether MT’s pulmonary protective effect is related to the inhibition of macrophage ferritinophagy. Our in vitro experiments demonstrated that MT decreased intracellular malondialdehyde (MDA), Fe2+, and lipid peroxidation levels, increased glutathione (GSH) levels and cell proliferation, and upregulated glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) protein levels in LPS-treated macrophages. Mechanistically, the antiferroptotic effect of MT on LPS-treated macrophages was significantly compromised by the overexpression of NCOA4. Our in vivo experiments revealed that MT alleviated the protein expression of NCOA4 and FTH1 in the alveolar macrophages of septic mice. Furthermore, MT improved lipid peroxidation and mitigated damage in alveolar macrophages and lung tissue, ultimately increasing the survival rates of septic mice. These findings indicate that MT can inhibit ferroptosis in an NCOA4-mediated ferritinophagy manner, thereby ameliorating septic ARDS.

Abstract Background The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. Methods We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). Results Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = − 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = − 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p

Abstract Background Low grade intraepithelial neoplasia (LGIN) and high grade intraepithelial neoplasia (HGIN) are potential precancerous lesion of gastric neoplasms. Endoscopic submucosal dissection (ESD) is the first option for the treatment of precancerous lesion and early gastric cancer (EGC). Traction is an effective method to improve efficiency, and reduce complications during ESD. In this study, we shared a useful traction method using the clip-and-snare method with a pre-looping technique (CSM-PLT) for precancerous lesion and EGC. Methods We retrospectively analyzed patients received ESD combined with CSM-PLT or conventional ESD from June 2018 to December 2021 in Shenzhen People’s hospital. The primary outcome was resection speed. Results Forty-two patients were enrolled in ESD combined with CSM-PLT group and sixty-five patients in conventional ESD group respectively. Baseline characteristics were comparable among two groups (P>0.05). There were no significant differences in terms of R0 resection rate, en bloc resection rate (97.6% vs. 98.5%, P = 1.000 and 97.6% vs. 96.9%, P = 1.000, respectively), operation costs (933.7 (644.1-1102.4) dollars vs. 814.7 (614.6-988.3) dollars, P = 0.107), and hospital stays (8.0 ± 3.1 days vs. 7.3 ± 3.2 days, P = 0.236). In addition, no significant difference was observed with respect to complications (P>0.05). However, the resection speed of ESD combined with CSM-PLT was faster than that of conventional ESD (11.3 (9.4–14.9) mm2/min vs. 8.0 (5.8–10.9) mm2/min, P

Abstract Bats serve as reservoirs for numerous zoonotic viruses, yet they typically remain asymptomatic owing to their unique immune system. Of particular significance is the MHC-I in bats, which plays crucial role in anti-viral response and exhibits polymorphic amino acid (AA) insertions. This study demonstrated that both 5AA and 3AA insertions enhance the thermal stability of the bat MHC-I complex and enrich the diversity of bound peptides in terms of quantity and length distribution, by stabilizing the 310 helix, a region prone to conformational changes during peptide loading. However, the mismatched insertion could diminish the stability of bat pMHC-I. We proposed that a suitable insertion may help bat MHC-I adapt to high body temperatures during flight while enhancing antiviral responses. Moreover, this site-specific insertions may represent a strategy of evolutionary adaptation of MHC-I molecules to fluctuations in body temperature, as similar insertions have been found in other lower vertebrates.

Abstract The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

Abstract The Changjinghuang Railway Xinjiang Xizhi Bridge is a (90 + 180 + 90) m continuous beam arch bridge, and the arch rib steel pipe installation adopts “short bracket assembly and overall lifting method”. In order to ensure the accuracy of closure, the stress and deformation of the arch rib and bracket must be strictly controlled. Midas Civil is used to establish the finite element model to simulate the overall lifting construction process of the arch rib. Based on the model, the stress and deformation of the arch rib and the supports are analyzed, and the determination method of the horizontal cable force under temperature variations is proposed. The results show that the stress and deformation of the arch rib and bracket meet the requirements. Considering the variation of temperature, the tension force of the horizontal cables is taken as 200 t. The construction plan proposed under the guidance of numerical calculation results has been proven by practical engineering to meet the requirement of closure accuracy, which can be used as a reference for similar projects.