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The coarse columnar grains that typically occur during additive manufacturing introduce mechanical anisotropy. Both to achieve a columnar-to-equiaxed transition (CET) and to investigate the effects of high growth restriction factor elements on the hardness distribution, this study introduced Ni and Cu into TA15 via laser directed energy deposition (LDED). The resulting as-built structures exhibited both equiaxed grains and uniform hardness. The CET, greater variety of grain orientations, differences in α′-phase variants and alterations in slip system and residual stress contributed to this uniformity. This research provides insights into designing isotropic LDED titanium alloys.

Abstract The deep continental crust represents a vast potential habitat for microbial life where its activity remains poorly constrained. Organic acids like acetate are common in these ecosystems, but their role in the subsurface carbon cycle - including the mechanism and rate of their turnover - is still unclear. Here, we develop an isotope-exchange ‘clock’ based on the abiotic equilibration of H-isotopes between acetate and water, which can be used to define the maximum in situ acetate residence time. We apply this technique to the fracture fluids in Birchtree and Kidd Creek mines within the Canadian Precambrian crust. At both sites, we find that acetate residence times are

Abstract Background Effective medication management is crucial for ensuring timely pain and symptom control at the end of life. Dying in pain is a major concern for patients, yet some find less effective pain control at home. Family caregivers (FCGs) play a vital role in managing pain and symptom control for dying patients. However, the experience of administering medications at home for terminal-stage patients has not been widely recognized or understood. Our study aimed to explore the experiences of FCGs in administering medications to adult dying patients. Methods We conducted a directed content analysis of data from 73 semi-structured interviews with FCGs across 19 Chinese provinces from 2021 to 2023. FCGs were recruited through the Voluntary Cooperative Network Research. We asked, “Could you recall the end-of-life care process for the patients?” We aligned the themes with the five issues identified by Wilson et al. (2018): administration, organizational skills, empowerment, relationships, and support. Results FCGs in China exhibit concerns about over-engagement and empowerment in medication administration, concealing medication information from the patient, and medication accessibility. FCGs faced significant challenges in accurately identifying and addressing pain and symptoms, determining appropriate dosages, accessing effective medications, and managing the emotional stress associated with potential medication errors. Financial burden, medication regulatory restrictions, geographical inequality, and travel restrictions during COVID impeded patients and FCGs from accessing medication. A culturally specific finding is the use of alternative medicine at the end of life. Conclusion Our findings build upon Wilson et al.‘s framework and extend their insights on empowerment, highlighting the need for policies to support home-based palliative care professionals in training FCGs for effective medication administration.

The present study systematically investigated the influence of forging strategies on the microstructures and deformation behaviors of a Ti–5Al–5Mo–5V–1Cr–1Fe (Ti-55511) near β-titanium alloy. Microstructure analysis revealed that the as-cast alloy exhibited a basket-weave structure predominantly comprised of lamellar α phase. Three different forging methods were used to adjust the morphology of the primary α phase during the final two forging steps: 1) dual-phase (825 °C) + dual-phase forging (DD sample), 2) dual-phase + β single-phase (900 °C) forging (DS sample), and 3) β single-phase + dual-phase forging (SD sample). After standard heat treatment, the DD samples exhibited equiaxed αp due to sufficient deformation in dual-phase region, while DS samples transformed into lamellar shape due to αp reforming during the cooling process of the final β single-phase forging. In contrast, the SD samples displayed short-rod αp due to reforming in the single-phase region and insufficient deformation in the dual-phase region. All these αp and βt phases can hinder dislocation motion to enhance the strength. The DS sample exhibited the best combination of strength, ductility, and impact toughness. During tensile deformation, planar dislocation slip and {101‾1} twinning were dominant in the αp, while wave slip occurred in the βt phase. The fracture behavior transitioned from brittle to ductile after forging and heat treatment. Overall, this study offers a practical and effective method for optimizing the mechanical properties of the Ti-55511 alloy.

Highlights Fundamental principles for designing synergistic composite catalysts are reviewed. The synergistic effect between various active sites, promoting electrocatalytic performance in different reactions are highlighted. The challenges and perspectives for multiple active sites catalysts are discussed.

CoCrMoW alloys with different nitrogen (N) additions (0, 0.05, 0.1, and 0.2 ​wt%) were prepared via laser powder bed fusion (LPBF). The effects of N content on the microstructure and mechanical properties were investigated. The results indicate that the LPBFed CoCrMoW alloy with 0.1 ​wt% N addition (0.1 ​N alloy) shows the best combination of mechanical properties with a yield strength of ∼983 ​MPa and an elongation of ∼19 ​%. Both the LPBF process and the N addition impose great effects on suppressing the γ to ε martensitic transformation, resulting in a decrease in the width and amount of ε laths/stacking faults. Besides, the N addition promotes the segregation of elements Mo, W, and Si along the cellular sub-grain boundaries (CBs), forming fine and discontinuous precipitates rich in Mo, W and Si along the CBs in the 0.1 ​N alloy, but dense and continuous (Mo,W)5Si3 precipitates along the CBs in the 0.2 ​N alloy. The (Mo,W)5Si3 precipitates with a tetragonal structure were observed and characterized for the first time in the Co–Cr based alloys. The negative mixing enthalpy between the non-metallic elements N, Si and the metallic elements Mo, W, Cr, and the rapid solidification induced segregation of high melting point elements such as Mo and W along CBs during LPBF process, synergistically contribute to the chemical heterogeneity in the alloys. The pure FCC matrix, the slightly increased segregation of Mo, W, Si elements and fine precipitates along the CBs contribute to the good combination of strength and elongation of the 0.1 ​N alloy. However, though pure FCC phase was present in the 0.2 ​N alloy, the dense and continuous (Mo,W)5Si3 precipitates along CBs acted as nucleation sites for cracks, deteriorating the elongation of the alloy. Overall, it is possible to tune the mechanical properties of the LPBFed CoCrMoW alloy by adjusting the local chemical heterogeneity.

The elusive factors determining peroxymonosulfate (PMS) activation lead to the “trial-and-error” method when developing efficient catalysts. Herein, we demonstrate that the suitable bonding pattern between PMS and exposed facets of CuO is the key parameter in catalysis. The kobs of ibuprofen removal by CuO with (110) facet (p-CuO) was 1.67 times higher than that of CuO with (001) facet (c-CuO). Simultaneously, Cu(III) was confirmed to be the primary intermediate oxidant among multiple reactive species (Cu(III), •OH, and 1O2 in both CuO/PMS systems, whereas O2•− only in c-CuO/PMS system). Furthermore, density functional theory calculations unveiled that compared to chaise longue connection between p-CuO and PMS, the higher adsorption energy (Eads) of bridge-like connection between c-CuO and PMS leads to a more stable intermediate (−5.56 eV vs −3.76 eV), thus hindering the formation of Cu(III). This work provides new opportunities for fabricating diverse metal oxides with new interfaces as PMS catalysts.

Abstract Stem cells are pivotal players in the intricate dance of embryonic development, tissue maintenance, and regeneration. Their behavior is delicately balanced between maintaining their pluripotency and differentiating as needed. Disruptions in this balance can lead to a spectrum of diseases, underscoring the importance of unraveling the complex molecular mechanisms that govern stem cell fate. Forkhead box O (FOXO) proteins, a family of transcription factors, are at the heart of this intricate regulation, influencing a myriad of cellular processes such as survival, metabolism, and DNA repair. Their multifaceted role in steering the destiny of stem cells is evident, as they wield influence over self-renewal, quiescence, and lineage-specific differentiation in both embryonic and adult stem cells. This review delves into the structural and regulatory intricacies of FOXO transcription factors, shedding light on their pivotal roles in shaping the fate of stem cells. By providing insights into the specific functions of FOXO in determining stem cell fate, this review aims to pave the way for targeted interventions that could modulate stem cell behavior and potentially revolutionize the treatment and prevention of diseases.

Intermediate temperature embrittlement (ITE) is very common in Ni and Ni–Co based superalloys, which seriously restricts the application of these alloys. In this work, we developed a new Ni–Co based superalloy by increasing the content of Cr to eliminate ITE. The superalloy has a yield strength of ∼950 MPa in the intermediate temperature range (600–780 °C), while also maintain a tensile elongation of ∼15 %. Microstructural investigations showed that in the temperature range of 600–780 °C, the microstructure of the alloy consists of nano-sized L12 phase (γ′) distributing inside the γ matrix, and the deformation is dominated by anti-phase boundary (APB) shearing γ′ precipitates, which makes the yield strength of the alloy decrease only slightly at 600–780 °C (compared to that tested at room temperature). More importantly, the element Cr is enriched along the grain boundaries (GBs) to form a protective layer without the formation of brittle topologically close-packed (TCP) phases due to the inverse two-stage aging design. In addition, the formation of a discontinuous precipitation (DP) zone at the GBs can act as a stress buffer and introduce GB serrations to withstand intergranular cracking.

Objective This study aimed to identify significantly differentially expressed genes (DEGs) related to cervical cancer by exploring extensive gene expression datasets to unveil new therapeutic targets. Methods Gene expression profiles were extracted from the Gene Expression Omnibus, The Cancer Genome Atlas, and the Genotype-Tissue Expression platforms. A differential expression analysis identified DEGs in cervical cancer cases. Weighted gene co-expression network analysis (WGCNA) was implemented to locate genes closely linked to the clinical traits of diseases. Machine learning algorithms, including LASSO regression and the random forest algorithm, were applied to pinpoint key genes. Results The investigation successfully isolated DEGs pertinent to cervical cancer. Interleukin-24 was recognized as a pivotal gene via WGCNA and machine learning techniques. Experimental validations demonstrated that human interleukin (hIL)-24 inhibited proliferation, migration, and invasion, while promoting apoptosis, in SiHa and HeLa cervical cancer cells, affirming its role as a therapeutic target. Conclusion The multi-database analysis strategy employed herein emphasized hIL-24 as a principal gene in cervical cancer pathogenesis. The findings suggest hIL-24 as a promising candidate for targeted therapy, offering a potential avenue for innovative treatment modalities. This study enhances the understanding of molecular mechanisms of cervical cancer and aids in the pursuit of novel oncological therapies.

ObjectiveTo address the research gap in the epidemiology of pediatric respiratory tract infections (RTIs) in Luzhou, Southern Sichuan, China, by analyzing respiratory pathogens in a large pediatric cohort from 2018 to 2021, covering the pre- and during-COVID-19 periods.MethodsThis study conducted a retrospective analysis of children with RTIs in Luzhou from July 2018 to January 2021. Strict exclusion criteria were applied to ensure an accurate representation of the pediatric population. Pathogen detection included viruses, bacteria, and atypical agents.ResultsPathogens were identified in 52.8% of 12,546 cases. Viruses accounted for 32.2% of infections, bacteria for 29.8%, and atypical agents for 29.7%, with significant findings of Staphylococcus aureus, Moraxella catarrhalis, and Mycoplasma pneumoniae. Age-related analysis indicated a higher incidence of bacterial infections in infants and viral infections in preschool-aged children, with atypical pathogens being most prevalent in 3–5-year-olds. Gender-based analysis, adjusted for age, revealed similar overall pathogen presence; however, females were more susceptible to viral infections, while males were more prone to Streptococcus pneumoniae. Notably, there was an unusual increase in pathogen cases during spring, potentially influenced by behavioral changes and public health measures related to COVID-19. Co-infections were identified as a significant risk factor for the development of pneumonia.ConclusionThe study provides essential insights into the epidemiology of respiratory pathogens in pediatric populations, emphasizing the need for healthcare strategies tailored to age, gender, and seasonality. The findings highlight the impact of environmental and public health factors, including COVID-19 measures, on respiratory pathogen prevalence, underscoring the importance of targeted diagnostic and treatment protocols in pediatric respiratory infections.

Mitochondrial diseases are disorders caused primarily by mutations in mitochondrial DNA, with the mitochondrial 3243A > G (m.3243A > G) mutation being one of the most common pathogenic mutations. Here, a pluripotent stem cell line with high m.3243A > G mutation load was generated by reprogramming the skin fibroblasts from a patient with mitochondrial disease. This cell line exhibited pluripotency, multilineage differentiation potential and normal karyotype, representing a valuable cell resource for studying the pathogenesis of mitochondrial diseases and screening drugs.

The formability and mechanical properties of magnesium (Mg) alloys are strongly related to the crystallographic basal texture. Twins play critical roles in adjusting crystallographic orientation of grains during both deformation and annealing treatment via deformation twinning and twinning-assisted recrystallization. In this study, cold rolling and subsequent annealing were conducted on a Mg-5.9Gd-3.3Y-0.5Zr alloy to investigate the recrystallization behavior and texture evolution. Electron backscatter diffraction and transmission electron microscopy techniques were applied to characterize the nucleation of recrystallized grains, especially the twinning-assisted recrystallization, at multi-scales. The results indicated that a large number of {101‾2}, {101‾1} twins and {101‾1}‐{101‾2} double twins were introduced after cold rolling. The {101‾1}‐{101‾2} double twins, double twin - grain boundary intersections and dense twin-twin intersections acted as the preferential nucleation sites for recrystallization during annealing treatment, while the coarse and parallel {101‾2} twins were unfavorable for the nucleation of recrystallized grains. Although {101‾2} tension twins are the most common twins in Mg alloys, the interface of this type of twin has strong mobility and is easy to expand. Therefore, it is generally difficult for a single {101‾2} twin to recrystallize. However, the {101‾1} compression twins and {101‾1}‐{101‾2} double twins are generally difficult to expand and can store high deformation energy, so they are conducive to becoming nucleation sites for recrystallization. During the recrystallization process, the texture type (basal texture) of the cold rolled sample remained unchanged, but the overall texture intensity was significantly reduced due to the dispersion of grain orientations brought by new grains generated by twinning recrystallization.

Introduction Cigarette smoking may impact the progression of idiopathic pulmonary fibrosis (IPF), and the intensity of smoking presents a dose-response association with IPF. Methods We retrospectively analyzed IPF patients diagnosed in our hospital from 2014 to 2018 and performed follow-up to confirm survival status and duration, and determine the effect of smoking on the prognosis of IPF. We retrieved information on IPF from a bioinformatics database to identify the differential expression of lncRNAs and proteins in smokers. Therefore, we explored and verified the mechanism by which cigarette smoke exposure (CSE) regulates LINC00665/XBP-1 involvement in pulmonary fibrosis through cell experiments. We clarified the mechanism between LINC00665 and XBP-1 through cellular and molecular experiments, and verified the inhibitory effect of silencing LINC00665 on pulmonary fibrosis by using a bleomycin (BLM)-induced pulmonary fibrosis model. Results We found that smokers with IPF had a poor prognosis compared with non-smokers. Both the expression of LINC00665 and XBP-1 in IPF lung tissue and smoker lung tissue were significantly upregulated, moreover, LINC00665 was higher in smoker IPF lung tissue than in smoker healthy people. Exposure to CSE could upregulate LINC00665/XBP-1 in lung fibroblast-to-myofibroblast transition. Cellular and molecular experiments showed that LINC00665 regulates the expression of XBP-1 by targeting miR-214-3p. LINC00665 expression, was significantly upregulated in BLM-induced mouse lung fibrosis tissues, and LINC00665 knockdown inhibited fibrogenesis in BLM-induced lung fibrosis. Conclusions Our study found that the high expression of LINC00665 is involved in the pathogenesis of smoker IPF and that CSE may positively regulate LINC00665/ XBP-1 to participate in lung fibroblast-to-myofibroblast transition. These findings help elucidate the pathogenesis of smoker IPF and may contribute to the development of new targeted drugs for IPF therapy.

AbstractContext Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine’s active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD’s major components remains unclear.Objective This study evaluates the herb–drug interaction between DBD’s major components and gemcitabine and validates the underlying pharmacokinetic mechanism.Materials and methods The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis.Results The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD’s major components in rats. The Cmax and AUC of calycosin-7-O-β-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression.Discussion and conclusions Gemcitabine could modulate the pharmacokinetics of DBD’s major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.

Approximately one-third of the entire world’s food resources are deemed to be wasted. Palm kernel meal (PKM), a product that is extensively generated by the palm oil industry, exhibits a unique nutrient-rich composition. However, its recycling is seldom prioritized due to numerous factors. To evaluate the impact of enzymatic pretreatment and Lactobacillus plantarum and Lactobacillus reuteri fermentation upon the antioxidant activity of PKM, we implemented integrated metagenomics and metabolomics approaches. The substantially enhanced (p < 0.05) property of free radicals scavenging, as well as total flavonoids and polyphenols, demonstrated that the biotreated PKM exhibited superior antioxidant capacity. Non-targeted metabolomics disclosed that the Lactobacillus fermentation resulted in substantial (p < 0.05) biosynthesis of 25 unique antioxidant biopeptides, along with the increased (p < 0.05) enrichment ratio of the isoflavonoids and secondary metabolites biosynthesis pathways. The 16sRNA sequencing and correlation analysis revealed that Limosilactobacillus reuteri, Pediococcus acidilactici, Lacticaseibacillus paracasei, Pediococcus pentosaceus, Lactiplantibacillus plantarum, Limosilactobacillus fermentum, and polysaccharide lyases had significantly dominated (p < 0.05) proportions in PMEL, and these bacterial species were strongly (p < 0.05) positively interrelated with antioxidants peptides. Fermented PKM improves nutritional value by enhancing beneficial probiotics, enzymes, and antioxidants and minimizing anti-nutritional factors, rendering it an invaluable feed ingredient and gut health promoter for animals, multifunctional food elements, or as an ingredient in sustainable plant-based diets for human utilization, and functioning as a culture substrate in the food sector.

This study was conducted to investigate the effects of supplementing fermented mulberry leaves (FML) on intestinal morphology, antioxidant capacity, and immune function in the gut of finishing pigs. Eighteen 132-day-old healthy crossbred (Duroc × Landrace × Yorkshire) male castrated pigs were randomly divided into two treatment groups with nine replicates per group. The control (CON) group was fed the basal diet, and the FML group was fed the basal diet supplemented with 10% FML. The experiment lasted 69 days. The results showed that 10% FML improved gut health. The apparent total tract digestibility in dry matter, crude protein, crude fiber, neutral detergent fiber, acidic detergent fiber, ether extract, and crude ash increased in the 10% FML group of finishing pigs compared to the CON group (p < 0.05). Duodenal, jejunal, and ileal intestinal morphology, such as villus height and villus-height-to-crypt-depth ratio, increased in the 10% FML group compared to the CON group, whereas crypt depth decreased in the duodenum, jejunum, and ileum (p < 0.05). Total antioxidant capacity increased in the ileum of the 10% FML group compared with the CON group (p < 0.05). The FML supplementation improved the contents of duodenal immunoglobulin A, jejunal interleukin-1β, interleukin-8, ileal interleukin-1β, interleukin-6, interferon-γ, and immunoglobulins A and M compared to the control group (p < 0.05). Moreover, FML downregulated the mRNA expression levels of tumor necrosis factor-α in the duodenum, Toll-like receptor 4, nuclear factor-κ B-P65, and myeloid differentiation factor 88 in the jejunum, and Toll-like receptor 4 and nuclear factor-κ B-P65 in the ileum (p < 0.05). The FML also upregulated Montrose uniting church 1 in the duodenum and claudin 2 in the ileum (p < 0.05). In conclusion, dietary supplementation with 10% FML improved the gut health of finishing pigs and FML is a potential feed ingredient for pig breeding.

Colon cancer ranks among the most prevalent malignancies worldwide, trailing only lung and breast cancer in incidence. Despite the availability of numerous therapeutic strategies, the burden of new cases and fatalities remains high in countries undergoing socioeconomic transitions. Natural products offer promising avenues for developing more effective and less toxic anticancer agents, expanding the clinical arsenal. In this investigation, we isolated a triterpenoid, (21 S,23 R,24 R)-21,23-epoxy-24-hydroxy-21-methoxytirucalla-7,25-dien-3-one (EHMT), from the fruits of Melia azedarach L., which exhibited significant inhibitory activity against colon cancer cells while sparing normal cells. EHMT effectively curtailed colony formation and induced apoptosis and cell cycle arrest in the HCT116 cell line. Furthermore, EHMT prompted the generation of reactive oxygen species (ROS) and the depolarization of mitochondrial membrane potential. Notably, EHMT treatment triggered ROS-mediated cell apoptosis via activation of the JNK signaling pathway in HCT116 cells. Additionally, our findings extended to Caenorhabditis elegans, where EHMT induced ROS accumulation and apoptosis. Collectively, these findings position EHMT as a promising candidate for the development of anticancer agents in the treatment of colon cancer, offering new hope in the battle against this formidable disease.

Mitochondrial diseases are a heterogeneous group of inherited disorders characterized by mitochondrial dysfunction, and these diseases are often severe or even fatal. Mitochondrial diseases are often caused by mitochondrial DNA mutations. Currently, there is no curative treatment for patients with pathogenic mitochondrial DNA mutations. With the rapid development of traditional gene editing technologies, such as zinc finger nucleases and transcription activator-like effector nucleases methods, there has been a search for a mitochondrial gene editing technology that can edit mutated mitochondrial DNA; however, there are still some problems hindering the application of these methods. The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing. In this paper, we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

Abstract Detection of vector magnetic fields at nanoscale dimensions is critical in applications ranging from basic material science and fundamental physics to information storage and medical diagnostics. So far, nanoscale vector magnetic field sensing is achieved solely by exploiting a single nitrogen‐vacancy (NV) center in a diamond, by evaluating the Zeeman splitting of NV spin qubits by using the technique of an optically‐detected magnetic resonance. This protocol requires a complex optical setup and expensive detection systems to detect the photoluminescence light, which may limit miniaturization and scalability. Here, a simple approach with all‐electric operation to sensing a vector magnetic field at 200 × 200 nm2 dimensions is experimentally demonstrated, by monitoring a stochastic nanomagnet's transition probability from a metastable state, excited by a driving current due to spin‐orbit torque, to a settled state.

Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China. The concentrations of total PCBs, PBDEs and eBFRs were in the range of 0.321–4.24 ng/g dry weight (dw), 0.255–25.5 ng/g dw and 3.00 × 10−3-47.2 ng/g dw in kelp, respectively. The pollutant pattern was dominated by decabromodiphenyl ethane (DBDPE, 13.0 ± 11.7 ng/g dw) followed in decreasing order by BDE-209 (2.74 ± 4.09 ng/g dw), CB-11 (1.32 ± 1.06 ng/g dw). The tested results showed that kelp could reflect the pollution status of PCBs, PBDEs and eBFRs, indicating the suitability of kelp as a biomonitor of these harmful substances. Finally, the data obtained was used to evaluate human non-cancer and cancer risks of PCBs and PBDEs via kelp consumption for Chinese. Though the calculated risk indices were considered acceptable according to the international standards even in the worst scenarios, the POPs levels in kelp should be monitored continuously as a good environmental indicator.

AbstractRanunculus ternatus Thunb. 1784 is a plant with important medicinal values. Here we report its chloroplast genome. This chloroplast genome was 156,003 bp in length with a GC content of 37.86%. It is composed of a large single copy (LSC) of 85,397 bp and a small single copy (SSC) of 19,856 bp, which are separated by a pair of inverted repeats (IR) of 25,375 bp each. The chloroplast genome contained 110 unique genes, including 77 protein-coding genes, 4 rRNA genes, and 29 tRNA genes. Phylogenetic analysis indicated that R. ternatus was closely related to R. cassubicifolius. This chloroplast genome not only enriches the genome information of Ranunculus but also will be useful for the evolution study of the family Ranunculaceae.

By using state-of-the-art characterisation techniques including atom probe tomography and atomic resolved elemental mapping, we successfully probed the site occupation evolution associated with composition change in γ′, during 1100°C creep of a fourth generation Ru-bearing Ni-based superalloy. It is quantified that, W and Ru maintain unchanged site preference after creep rupture, while interestingly, the rest elements especially Co, Ta and Re show a weakened preference at both α- and β-sites in the γ′ lattice. This indicates the overall reduced γ′ ordering degree and thus the possible decrease in planar fault energies, which further facilitates dislocation shearing in γ′.

Abstract Inflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in many contexts such as cardiovascular diseases and cancer. One potential reason for the unsuccessful outcome is the mutual dependent role between inflammation and angiogenesis. Inflammation-based therapies primarily target inflammatory cytokines such as interleukin-6 (IL-6) in T cells, macrophages, cancer cells, and muscle cells, and there is a limited understanding of how these cytokines act on endothelial cells. Thus, we focus on one of the major inflammatory cytokines, IL-6, mediated intracellular signaling in endothelial cells by developing a detailed computational model. Our model quantitatively characterized the effects of IL-6 classic and trans-signaling in activating the signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) signaling to phosphorylate STAT3, extracellular regulated kinase (ERK) and Akt, respectively. We applied the trained and validated experiment-based computational model to characterize the dynamics of phosphorylated STAT3 (pSTAT3), Akt (pAkt), and ERK (pERK) in response to IL-6 classic and/or trans-signaling. The model predicts that IL-6 classic and trans-signaling induced responses are IL-6 and soluble IL-6 receptor (sIL-6R) dose-dependent. Also, IL-6 classic and trans-signaling showed similar potency in inducing downstream signaling; however, trans-signaling induces stronger downstream responses and plays a dominant role in the overall effects from IL-6 due to the in vitro experimental setting of abundant sIL-6R. In addition, both IL-6 and sIL-6R levels regulate signaling strength. Moreover, our model identifies the influential species and kinetic parameters that specifically modulate the downstream inflammatory and/or angiogenic signals, pSTAT3, pAkt, and pERK responses. Overall, the model predicts the effects of IL-6 classic and/or trans-signaling stimulation quantitatively and provides a framework for analyzing and integrating experimental data. More broadly, this model can be utilized to identify potential targets that influence IL-6 mediated signaling in endothelial cells and to study their effects quantitatively in modulating STAT3, Akt, and ERK activation.

In this study, hot rolling treatment followed by water quenching was conducted on a TC18 titanium alloy in β single-phase region with varying reductions. Experimental evidences from X-ray diffraction and transmission electron microscopy indicate the formation of α phase, induced by sufficient stress and assisted by ω phase. In addition, the existence of α'' phase and diffuse streaks were also observed during the hot working processing. Furthermore, dynamic recrystallization (DRX) including continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX) was proved to exist in the hot rolling process. During the whole DRX process, with increasing the deformation degree, recrystallized grains nucleated preferentially at high-energy areas such as grain boundaries and shear bands, then accumulated and grew until achieving a complete recrystallization state. It should be noted that DDRX mainly occurred at the grain boundaries, while CDRX grains nucleated within the shear bands. The elongation gradually decreased and tensile strength gradually increased with the increment of the deformation degree.

TiAl alloys possess excellent properties, such as low density, high specific strength, high elastic modulus, and high-temperature creep resistance, which allows their use to replace Ni-based superalloys in some high-temperature applications. In this work, the traditional TiAl alloy Ti-48Al-2Nb-2Cr (Ti4822) was alloyed with additional Nb and fabricated using laser metal deposition (LMD), and the impacts of this additional Nb on the microstructure and mechanical and tribological properties of the as-fabricated alloys were investigated. The resulting alloys mainly consisted of the γ phase, trace β0 and α2 phases. Nb was well distributed throughout the alloys, while Cr segregation resulted in the residual β0 phase. Increasing the amount of Nb content increased the amount of the γ phase and reduced the amount of the β0 phase. The alloy Ti4822-2Nb exhibited a room-temperature (RT) fracture strength under a tensile of 568 ± 7.8 MPa, which was nearly 100 MPa higher than that of the Ti4822-1Nb alloy. A further increase in Nb to an additional 4 at.% Nb had little effect on the fracture strength. Both the friction coefficient and the wear rate increased with the increasing Nb content. The wear mechanisms for all samples were abrasive wear with local plastic deformation and oxidative wear, resulting in the formation of metal oxide particles.

About one-third of the global food supply is wasted. Brewers’ spent grain (BSG), being produced in enormous amounts by the brewery industry, possesses an eminence nutritional profile, yet its recycling is often neglected for multiple reasons. We employed integrated metagenomics and metabolomics techniques to assess the effects of enzyme treatments and Lactobacillus fermentation on the antioxidant capacity of BSG. The biotreated BSG revealed improved antioxidant capability, as evidenced by significantly increased (p < 0.05) radical scavenging activity and flavonoid and polyphenol content. Untargeted metabolomics revealed that Lactobacillus fermentation led to the prominent synthesis (p < 0.05) of 15 novel antioxidant peptides, as well as significantly higher (p < 0.05) enrichment of isoflavonoid and phenylpropanoid biosynthesis pathways. The correlation analysis demonstrated that Lactiplantibacillus plantarum exhibited strong correlation (p < 0.05) with aucubin and carbohydrate-active enzymes, namely, glycoside hydrolases 25, glycosyl transferases 5, and carbohydrate esterases 9. The fermented BSG has potential applications in the food industry as a culture medium, a functional food component for human consumption, and a bioactive feed ingredient for animals.

Selective Laser Melting (SLM) prepared 316L stainless steel has been widely deployed in academia and industry today. This paper studied the influence of laser power (50–450 W) and scanning speed (1000–2800 mm/s) on formability, hardness, microstructure, internal and external quality, and porosity of the built, and further analyzed the internal relationship between input energy density and them. The results revealed that high laser power needs to match high scanning speed to obtain better formability; that is, appropriate energy density was the fundamental guarantee of formability. Besides, high energy density will lead to a smaller ratio of width and height (W/H) and a larger area of the molten pool. And the cellular grain's size increased significantly from 181 to 1615 nm, with the energy density increasing from 26.8 to 750.0 J/mm3. In addition, the sample's quality was also related to the energy density. And the porosity variation trend was similar to that of surface roughness, indicating a strong correlation between internal quality and surface quality.

Abstract Background With the increasing aging population, dementia has become a significant socioeconomic burden. However, the effects of albumin on delayed recall (DR) impairment remain unclear, and there are limited reports on sex and race differences in this relationship. This study aimed to investigate the association between albumin levels and DR impairment in older adults. Methods A total of 1507 normal cognitive function and 553 DR impairment from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were included in this cross‐sectional analysis. Participants aged 60 years and above were assessed using the Consortium to Establish a Registry for Alzheimer's Disease DR (CERAD‐DR) test to evaluate cognitive function. Participants were categorized into DR impairment and normal cognitive function groups according to their CERAD‐DR scores. Logistic regression analyses, generalized additive models, and fitted smoothing curves were utilized for data analysis. Results After adjusting for potential confounders, a negative association was found between albumin levels and cognitive function (odds ratio [OR] = 0.60, 95% confidence interval [CI] 0.41–0.87). Subgroup analysis stratified by sex, race/ethnicity, and age revealed that the negative association remained significant in men (OR = 0.53, 95%CI 032–0.87), Blacks (OR = 0.35, 95%CI 0.17–0.74), and the age group of 60–70 years (OR = 0.48, 95%CI 0.28–0.81). However, no significant association was observed in women (OR = 0.72, 95%CI 0.41–1.28), whites (OR = 0.58, 95%CI 0.31–1.07), or Mexican Americans (OR = 1.11, 95%CI 0.35–3.46), as well as the age group of 71–80 years (OR = 0.62, 95%CI 0.37–1.03). Conclusions Our study suggests that elevated albumin levels are associated with a decreased incidence of cognitive function impairment, particularly in older men and Blacks. This finding indicates that maintaining high levels of albumin may be beneficial for cognitive function in older adults.

The blood–brain barrier (BBB) is pivotal in maintaining neuronal physiology within the brain. This review delves into the alterations of the BBB specifically in the context of geriatric epilepsy. We examine how age-related changes in the BBB contribute to the pathogenesis of epilepsy in the elderly and present significant challenges in pharmacotherapy. Subsequently, we evaluate recent advancements in drug delivery methods targeting the BBB, as well as alternative approaches that could bypass the BBB’s restrictive nature. We particularly highlight the use of neurotropic viruses and various synthetic nanoparticles that have been investigated for delivering a range of antiepileptic drugs. Additionally, the advantage and limitation of these diverse delivery methods are discussed. Finally, we analyze the potential efficacy of different drug delivery approaches in the treatment of geriatric epilepsy, aiming to provide insights into more effective management of this condition in the elderly population.

The SM4 block cipher is standardized in ISO/IEC, and it is also the national standard of commercial cryptography in China. In this paper, we propose two new techniques called “split-and-join” and “off-peak and stagger” to make SM4 more applicable to resource-constrained environments. The area optimization method uses a 1-bit data path while reducing the number of registers from 64 to 8 and the number of XOR gates from 194 to 8. As a result, we report a 1-bit-serial SM4 encryption circuit that occupies 1771 GE with a latency of 2,336 cycles. Additionally, the “off-peak and stagger” technique compresses all the operations within the state update and key schedule into 32 clock cycles to reduce the latency. In other words, it takes 32 clock cycles to complete one round encryption. The new circuit occupies 1861 GE with a latency of 1,344 cycles. Moreover, we also discuss how to further reduce the latency by increasing the data path with a small area overhead to provide wider area-latency tradeoffs for SM4. Our designs make SM4 competitive with many ciphers specifically designed for lightweight cryptography.

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-α antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe.

In the process of grading and dynamically optimizing the design and construction parameters of the surrounding rock mass of a rock tunnel face, efficiently and accurately acquiring the geometrical parameters of the rock discontinuities is an important basic task. To address the problems of time consuming, low accuracy, and high danger associated with traditional methods of obtaining the structural information of rock mass, this paper proposes a method for three-dimensional reconstruction and intelligent information extraction of tunnel face based on binocular stereo vision (BSV). First, the parallel binocular device with a single camera was improved, calibrated using the checkerboard calibration method. By integrating with the semi-global matching algorithm, the BSV based method for the three-dimensional reconstruction of the rock mass of the tunnel face was optimized. Furthermore, based on the results from on-site engineering applications, this study leveraged two parameters, point cloud density and algorithm runtime, to determine the optimal values for the disparity range and window size parameters within the semi-global stereo matching algorithm. This enhancement improved the performance of the 3D reconstruction method based on binocular stereo vision. Finally, efficient and refined intelligent methods for extracting structural parameters of the rock mass were proposed based on k-nearest neighbor search and kernel density estimation. The research results can provide reliable technical support for the intelligent and efficient acquisition of rock mass structural information in rock tunnel engineering faces.

BackgroundEpilepsy is associated with a significant global burden of disease, affecting over 50 million people worldwide. The specific aim of this study is to compare the burden of epilepsy in the People’s Republic of China (PRC) with the global burden, and to analyze the epidemiological trends of epilepsy, the relationship between the burden of epilepsy and social demographic index (SDI), and the relative contributions of epidemiological factors.MethodsThis is a retrospective population-based study, data were obtained from the Global Burden of Disease (GBD) study in 2019. We employed Joinpoint software and the age-period-cohort (APC) model to analyze epilepsy’s epidemiological trends. Health inequality analysis was conducted to investigate the impact of SDI on epilepsy burden. Decomposition analysis was performed to examine the relative contributions of age, population, and epidemiological changes to epilepsy.ResultsBetween 1990 and 2019, the incidence rate in the PRC increased by 45%, significantly surpassing the global incidence of epilepsy. However, Disability-Adjusted Life Years (DALY) decreased notably, and the proportion of Years of Life Lost (YLL) decreased from 62.73 to 39.03%. Concerning incidence, the period Rate Ratio (RR) in the PRC initially increased and then decreased, while the cohort RR in the PRC and globally exhibited a consistent upward trend. In terms of mortality, period RR and cohort RR in the PRC displayed a gradual decrease, with mortality starting higher but eventually falling below the global mortality. The net drifts of incidence were greater than 0, whereas the net drifts of mortality were less than 0, both were lower in the PRC than at the global level. Decomposition analysis indicated that the changes of incidence and mortality in the PRC were mainly attributed to epidemiological changes. Additionally, global disparities in epilepsy decreased, with the burden concentrating in low SDI countries.ConclusionThe incidence of epilepsy in the PRC rose during the 30-year study period, while epilepsy mortality decreased. The improved survival rate in the PRC is predominantly attributable to epidemiological changes. The burden of epilepsy in the PRC predominantly affects males, children, and the elderly, Chinese government should focus on specific populations.

Concrete in cold environments may suffer from frost damage, which effects the hydration reaction and early strength development of cement. This study aims to test the early strength development of recycled coarse aggregate concrete in cold region using an assisted heating method. Based on Nurse-Saul and Hansen-Pedersen maturity calculation methods, the early strength of recycled and natural coarse aggregate concrete is fitted and predicted using exponential and logarithmic type functions. The results showed that active heating and thermal insulation can ensure early concrete hydration. The temperature of recycled coarse aggregate concrete was slightly higher than that of natural concrete, while its strength was slightly lower. The early strength development of natural and recycled coarse aggregate concrete correlated more with the logarithmic type function. The prediction error of natural and recycled coarse aggregate concrete is basically within 10% for the first 14 days of compressive strength.

ABSTRACTThe precipitation hardening is widely applied to strengthen Al alloys. Here, we report an alternative way to achieve high-strength Al alloys via forming the dislocation gradient through pre-torsion. Remarkably, the gradient Al alloys exhibit a sharp increase in ultimate tensile strength up to 605 MPa yet nearly without reducing the uniform elongation, thereby outperforming their counterparts. The superior strength–ductility combination is ascribed to the excellent strengthening and strain hardening effects stemming from the substantial hetero-deformation-induced hardening in the coarse-grained gradient Al alloys. Our study thus paves a new way to improve the mechanical properties of Al alloys.

Abstract Nitrous acid (HONO) is the major precursor of hydroxyl (OH) radicals to initiate tropospheric chemistry leading to formation of secondary pollutants. The sources of atmospheric HONO, however, are not fully understood. Here we show two additional HONO sources that stem from atmospheric oxidation of nitrogen oxide (NOx = NO + NO2). Nitric acid (HNO3) formed from photooxidation of NO2 can be converted into HONO with a yield of ~53%, and dark NO oxidation by NO3 radicals in the presence of H2O produces HONO with a yield of 2%. The diurnal variations of HONO levels from field observations in the urban (Beijing) and rural (Wangdu) areas of the North China Plain can be well reproduced by the WRF-Chem model when the two new HONO sources are taken into account. The findings imply that atmospheric NOx oxidation pathways are the major sources for HONO, which can significantly accelerate ozone formation in polluted regions as well.

Highlights Fundamental principles for designing highly efficient two-electron oxygen reduction reaction catalysts are briefly reviewed. Strategies to integrate the components into an efficient device for hydrogen peroxide production are discussed. The challenges and perspectives for catalyst and cell design are discussed.

ABSTRACTIn this work, by using multi-scale characterizations from electron channeling contrast imaging (ECCI) to atom probe tomography (APT), we directly evidenced that the massive cracking events in the selective-laser-melted (SLMed) Haynes 230 superalloy are due to the continuous decoration of an M23C6-type thin film at grain boundaries. The high-melting-point nature of the carbide rules out the possibility of liquidation cracking, while the long and straight film surface facilitates stress-induced solid-state cracking. Impurities, Si, Mn and Fe, greatly enhance the cracking susceptibility despite the interesting fact that they are strongly depleted from the carbide.

Abstract Background Open-wedge high tibial osteotomy (OWHTO) is commonly performed for the treatment of medial compartment knee osteoarthritis (KOA), and is classified into proximal tibial tubercle osteotomy (PTO) and distal tibial tubercle osteotomy (DTO). The PTO osteotomy point is generally located about 3–4 cm below the joint of the proximal tibia, and the osteotomy line points to the upper part of the proximal tibiofibular joint. The DTO osteotomy point is generally located about 0.5–1.0 cm below the tibial tubercle, and the osteotomy line points to the contralateral cortex. However, there is currently no consensus on which surgical technique is superior. The purpose of our study was to investigate which among the two is superior for medial KOA, with respect to knee joint parameters, clinical function, and complications. Methods This study was conducted as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Cochrane Central Library, MEDLINE, Embase, PubMed, CNKI, and WanFang databases were systematically searched for trials comparing PTO and DTO in patients with medial compartment KOA, from inception until March 2022. The meta-analysis was conducted using RevMan 5.2 software. The Cochrane risk-of-bias tool was used to assess methodological quality. Statistical analysis was performed with Stata 12.0. Outcomes of interest included the Insall-Salvati index (ISI), Caton-Deschamps index (CDI), Blackburne-Peel index (BPI), posterior tibial slope (PTS), and the Hospital for Special Surgery (HSS) knee-rating scale. Results A total of 15 retrospective studies (910 knees) were included. There were no significant differences in the age or sex of included patients. There was a significant difference in the ISI, CDI, BPI, and PTS between the two groups (all p ≤ 0.05). Further, DTO was associated with a significantly greater number of postoperative complications (p 0.05). Conclusions Compared with DTO, PTO is associated with a greater incidence of postoperative patella baja and increased PTS, whereas DTO is associated with more postoperative complications. Nevertheless, both can significantly correct knee varus deformity and improve knee function; their early knee function scores are also similar. Trial Registration. Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42021284443.

Abstract This cohort study aimed to identify the characteristics and risk factors of adult idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) and further explore the prognostic factors of IIM-ILD. We extracted data regarding 539 patients with laboratory-confirmed idiopathic inflammatory myopathy (IIM) with or without interstitial lung disease (ILD) from the Second Xiangya Hospital of Central South University between January 2016 and December 2021. The regression analysis was conducted to identify the possible risk factors for ILD as well as mortality. Of 539 IIM patients, 343 (64.6%) were diagnosed with IIM-ILD. The median (IQR) baseline neutrophil-to-lymphocyte ratio (NLR), C-reactive protein to albumin ratio (CAR) and ferritin were 4.1371 (2.6994–6.8143), 0.1685 (0.0641–0.5456) and 393.6 (210.6–532.2), respectively. Risk factors associated with IIM-ILD were older age (p = 0.002), arthralgia (p = 0.014), lung infection (p = 0.027), hemoglobin (p = 0.022), high CAR (p = 0.014), anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive (p

To explore and compare the failure modes, deformation behaviors, and load-bearing capacities of single-edge notched (SEN) beams strengthened with carbon fiber-reinforced polymer (CFRP) and steel bars, static and dynamic three-point bending tests on both types of concrete beams have been carried out in this study. During the static tests, the electro-hydraulic servo machine served as a loading device to apply pressure to CFRP beams and reinforced concrete (RC) beams. During the impact experiments, different impact velocities were imparted by adjusting the drop hammer’s height. Thus, information regarding crack propagation, energy absorption, and deformation was obtained. The results from the static tests showed that the RC beams predominantly experienced shear failure. In contrast, the CFRP beams primarily exhibited bending–shear failure, attributed to the relatively weaker bond strength between the bars and the concrete. Impact tests were conducted at three different velocities in this study. As the impact velocity increased, both types of concrete beams transitioned from bending failure to bending–shear failure. At the lowest velocity, the difference in energy absorption between beams reinforced with different materials was insignificant during the bending process. However, at the highest velocity, CFRP beams absorbed less energy than RC beams. The study of structures’ impact failure modes and their mechanical characteristics offers valuable references for the anti-collision design and protection of structures.

Mulberry leaves are rich in nutrients but contain anti-nutrient factors that hinder their digestion and absorption. Feeding animals with mulberry leaves directly could harm their health. The microbial fermentation of mulberry leaves could reduce their anti-nutritional factors’ content and improve their nutritional value. Sequencing and analyzing mulberry leaves before and after fermentation showed that fermentation increased the relative abundance of Pediococcus, Bradyrhizobium, Hydrotalea, and Rhodanobacteria, and decreased that of Enterobacter. Fermentation improved the quality of mulberry leaves by rebuilding the bacterial community. Finishing pigs were raised on fermented mulberry leaves (FML), and their carcass performance, meat quality, economic benefits, and gut microbiome were evaluated. FML had no negative impact on pig carcass performance, meat quality, and antioxidant capacity, and could somewhat improve the economic benefits. FML decreased the relative abundance of Proteobacteria in the colon and Streptococcus in the feces, and increased that of Actinobacteria (cecum, colon, feces) and Prevotella (colon). The gut core microorganisms in the FML group were mainly enriched with Actinobacteria, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, and other beneficial microorganisms. Dietary FML reduced ammonia, indole, and skatole contents in the feces. In conclusion, FML reshaped the gut microbiota without negatively affecting pig product performance, produced cleaner waste, and improved environmental protection and sustainability, making it an attractive prospective feed for pigs.

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3β-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3β-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7–17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3β-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 μM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).

Existing vehicle-to-grid (V2G) applications are aimed at the power grid and the government. It is difficult for charging stations (CSs) to execute the schedules in real time. To figure out the multiple-layer energy management from the perspective of CS, the dispatch potential assessment model is constructed based on the EV users’ charging demand and Minkowski summation. And the optimal energy management schedule model of CS with ESS is proposed considering peak shaving and valley filling under the time-in-use tariff. Besides, the real-time charging control model of EVs in CS is designed under the premise of meeting the charging needs. The simulation results show that the proposed strategy can promote CS operation revenues and track the scheduling plan of CS. The arbitrage of tariffs and peak shaving ancillary services are realized while the charging loads of CSs are smoothed by the charging/discharging of ESS. The proposed strategy is applicable for the CS aggregators and can help the grid operators for dispatch schedules.

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anti-colorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited pre-clinical evidence and safety concerns. This study aimed to determine the pre-clinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration.Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS.Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p < 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 μg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 μg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair.Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration.

BackgroundWe have previously reported that human cytomegalovirus (HCMV) infection could promote the progression of glioma. Here we discovered a stress-induced nuclear protein ZC3H11A (ZC3) through high-throughput sequencing after HCMV infection, which has been reported recently by our research group in regulating mRNA export under stress conditions. And also, a thorough analysis of ZC3 in pan-cancer and the omics data of ZC3 are yet to be conducted.MethodsThe transcriptomes of glioma cells after HCMV infection were assessed by RNA sequencing. ZC3 mRNA and protein level following HCMV infection were validated and measured by qRT-PCR and Western-blot. The RNA sequencing and protein expression information of ZC3 across pan-cancer were analyzed and visualized by R packages. The localization of ZC3 protein was assessed by IHC images from HPA. The ZC3 proteomics and transcriptomics data in different cancers were extracted through the CPTAC data portal, and comparisons were conducted with a Python script. The genetic alteration, survival prognosis, immune infiltration analysis of ZC3 in pan-cancer were analyzed by cBioPortal, TCGA, and TIMER2 databases. The protein interaction networks were revealed by STRING, GEPIA2 and TCGA.ResultsGenes in mRNA processing pathways were upregulated after HCMV infection and ZC3 expression in mRNA and protein level was validated. We also discovered that the status of ZC3 were generally at high levels in cancers, although varied among different cancer types. ZC3 protein in tumor cells localized to the nuclear whereas in normal cells it was mainly found in cytoplasmic/membranous. However, from ZC3 proteomics and transcriptomics data in some cancer types, the increase in ZC3 protein was not accompanied by a significant elevation in mRNA level. Additionally, our analysis indicated that elevated ZC3 expression was primarily linked to a negative prognosis in majority cancers but still varied depending on the cancer types. Our annotation analysis suggested that ZC3-related proteins are mainly involved in mRNA processing clusters.ConclusionWe demonstrated that ZC3 significantly impacted by HCMV infection in gliomas. Furthermore, we identified a set of genes exhibiting analogous expression patterns to ZC3H11A in TCGA pan-cancer cohorts, implying a potential functional role for ZC3H11A in mRNA processing. Our study provided valuable insights into the role of a new mRNA export protein ZC3 in HCMV infection and pan-cancer progression. These results lay the foundation for our next research on the regulatory mechanism of ZC3 in virus-infected tumors.

Machine learning (ML) includes a broad class of computer programs that improve with experience and shows unique strengths in performing tasks such as clustering, classification and regression. Over the past decade, microbial communities have been implicated in influencing the onset, progression, metastasis, and therapeutic response of multiple cancers. Host-microbe interaction may be a physiological pathway contributing to cancer development. With the accumulation of a large number of high-throughput data, ML has been successfully applied to the study of human cancer microbiomics in an attempt to reveal the complex mechanism behind cancer. In this review, we begin with a brief overview of the data sources included in cancer microbiomics studies. Then, the characteristics of the ML algorithm are briefly introduced. Secondly, the application progress of ML in cancer microbiomics is also reviewed. Finally, we highlight the challenges and future prospects facing ML in cancer microbiomics. On this basis, we conclude that the development of cancer microbiomics can not be achieved without ML, and that ML can be used to develop tumor-targeting microbial therapies, ultimately contributing to personalized and precision medicine.