Search

Abstract Aims/Introduction We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease’s degree. Materials and Methods We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)‐194 and thrombospondin‐1 (TSP‐1) messenger ribonucleic acid (mRNA) in the participants’ circulation were measured using a quantitative real‐time polymerase chain reaction. Results Circulating TSP‐1 mRNA (P = 0.024) and miR‐194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP‐1 mRNA (P = 0.040) and miR‐194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP‐1 mRNA expression increased with urinary microalbumin. However, miR‐194 declined in group B and increased in group C. Circulating TSP‐1 mRNA was positively correlated with cystatin‐c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR‐194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin‐c (β = 0.578; P = 0.021) and UmALB/Cr (β = 0.001; P = 0.009) as independent factors for TSP‐1 mRNA; UmALB/Cr (β = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP‐1 mRNA and miR194 were 0.756 (95% confidence interval 0.620–0.893; sensitivity 0.69 and specificity 0.71, P

In this research, we report fabrication of AZ91 (Mg–Al–Mn–Zn) matrix composites reinforced with a hybrid of hexagonal boron nitride nanoplatelets (BNNP) and nanotubes (BNNT) using spark plasma sintering (SPS) and hot isostatic pressing (HIP). The resultant composites present dense microstructure featured by the refined α-Mg grains decorated with eutectic along the α-Mg grain boundaries, and trace amounts of in-situ interfacial-reaction products such as Mg3N2 and MgB2 are observed to serve as chemical anchors for stronger interface. More importantly, the AZ91 composites reinforced with a hybrid of 0.4 wt% BNNPs-0.1 wt% BNNTs displays ∼209 MPa of compressive yield strength, ∼329 MPa of ultimate compressive strength and ∼19.4% of elongation, achieving satisfactory balance of strength and ductility when compared to the AZ91 composite reinforced with sole BNNPs. This improvement can be attributed to the unique three-dimensional hybrid structure, where BNNPs maintain their high specific surface area, and the de-bundled BNNTs extend like tentacles, further contributing to their interfacial adhesion with the matrix. This research is expected to pave the way for the development of Mg-based composites with an optimal balance of strength and ductility.

Abstract Background Lung cancer (LC) is currently the number one malignancy death rate disease in China, and its disease burden is serious. The study aimed to analyze trends of LC and its risk factor attributable disease in China from 1990 to 2019 and predict the next 41 years. Methods The average annual percentage change (AAPC) was used to analyze the trend of LC and its risk factor attributable incidence, deaths, and disability‐adjusted life years (DALYs) rate in China from 1990 to 2019, collected in the Global Burden of Disease 2019. Cochran–Armitage trends examine trends in lung cancer disease burden by sex, age, and attributable risk factor groups in China from 1990 to 2019. In addition, based on data on death and DALYs rate due to LC and its risk factors between 1990 and 2019, an autoregressive integrated moving average (ARIMA) model was developed to predict the change in the trend of burden of disease due to LC and its risk factors over the next 41 years, and the model was evaluated using the model parameters root mean square error, mean absolute error, and mean absolute percentage error. Results From 1990 to 2019, the incidence, mortality and DALYs of LC were all increased. Among the eight risk factors associated with lung cancer, the DALYs rate and mortality rate of lung cancer risk factors for Chinese residents increased from 1990 to 2019, except for household air pollution from solid fuels and diet low in fruit, which showed a decrease; among them, the DALYs rate and mortality rate due to ambient particulate matter pollution showed the greatest increase with AAPC values of 2.880 and 3.310, respectively, while DALYs and mortality rates due to household air pollution from solid fuels showed the largest decreases, with AAPC values of −4.755 and −4.348, respectively. The results of the ARIMA model predictions show that both the mortality rate and the rate of DALYs for lung cancer are increasing yearly, and it is predicted that the rate of DALYs for lung cancer by 2060 will reach 740.095/100 000 and the mortality rate will reach 35.151/100 000. It is expected that by 2060, the top four risk factors for lung cancer in China will be, in order of DALYs rate and mortality rate, smoking, ambient particulate matter pollution, high fasting plasma glucose (HFPG), and secondhand smoke, with HFPG showing the greatest increase. Conclusions The LC burden increased from 1990 to 2019 in China, the LC burden that could be attributed to HFPG will continue to increase in the next 40 years, and will be the third most factor by 2060. Targeted interventions are warranted to facilitate the prevention of LC and improvement of health‐related quality of life patients with LC.

Abstract Objective The objective of this retrospective cohort study is to investigate the impact of monitoring serum estradiol (E2) levels before progesterone administration within hormone replacement therapy (HRT) on pregnancy outcomes in women undergoing frozen-thawed embryo transfer (FET). Methods Analyzed HRT-FET cycles conducted at a reproductive center from 2017 to 2022. Serum E2 levels were measured prior to progesterone administration. Multivariate stratified and logistic regression analyses were performed on 26,194 patients grouped according to terciles of serum E2 levels before progesterone administration. Results The clinical pregnancy rate (CPR) and live birth rate (LBR) exhibited a gradual decline with increasing serum E2 levels across the three E2 groups. Even after controlling for potential confounders, including female age, body mass index, infertility diagnosis, cycle category, number of embryos transferred, fertilization method, indication for infertility, and endometrial thickness, both CPR and LBR persistently showed a gradual decrease as serum E2 levels increased within the three E2 groups. The same results were obtained by multivariate logistic regression analysis. Conclusions This large retrospective study indicates that elevated serum E2 levels before progesterone administration during HRT-FET cycles are associated with reduced CPR and LBR post-embryo transfer. Therefore, it is advisable to monitor serum E2 levels and adjust treatment strategies accordingly to maximize patient outcomes.

Abstract Natural killer (NK) cell-based therapies have made great progress in treating both hematological and solid tumors. Their unique mechanism of action does not rely on antigen presentation to recognize and eliminate tumor cells, making them a promising approach for cancer immunotherapy. In this review, we present a comprehensive summary of the latest clinical data of the novel NK cell-based therapies from the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the potential of these advancements to revolutionize the treatment of hematologic malignancies and solid tumors.

Abstract Objectives Ants are ecologically dominant insects in most terrestrial ecosystems, with more than 14,000 extant species in about 340 genera recorded to date. However, genomic resources are still scarce for most species, especially for species endemic in East or Southeast Asia, limiting the study of phylogeny, speciation and adaptation of this evolutionarily successful animal lineage. Here, we assemble and annotate the genomes of Odontoponera transversa and Camponotus friedae, two ant species with a natural distribution in China, to facilitate future study of ant evolution. Data description We obtained a total of 16 Gb and 51 Gb PacBio HiFi data for O. transversa and C. friedae, respectively, which were assembled into the draft genomes of 339 Mb for O. transversa and 233 Mb for C. friedae. Genome assessments by multiple metrics showed good completeness and high accuracy of the two assemblies. Gene annotations assisted by RNA-seq data yielded a comparable number of protein-coding genes in the two genomes (10,892 for O. transversa and 11,296 for C. friedae), while repeat annotations revealed a remarkable difference of repeat content between these two ant species (149.4 Mb for O. transversa versus 49.7 Mb for C. friedae). Besides, complete mitochondrial genomes for the two species were assembled and annotated.

Abstract Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

In this paper, the remelting process is applied to Laser Directed Energy Deposition (L-DED) to repair single crystal superalloys. The main formation modes of stray grains in single crystal epitaxial growth were analyzed, and the inhibitory effect of remelting process on stray grains in single crystal epitaxial growth using L-DED was studied. Comparative experiments between remelting and non-remelting processes have been conducted. Three process parameters in the remelting process: power, z-axis lift and cladding-remelting interval time were studied. The impact of different remelting process parameters on single crystal epitaxial growth and the formation of stray grains has been studied. Remelting has been shown to effectively prevent the formation of stray grains during the solidification of the melt pool, which are otherwise caused by the presence of unmelted powder during the powder feeding phase of the L-DED process. A cladding layer without stray grains on both sides is obtained. After remelting, the epitaxial growth structure can achieve larger cellular and columnar dendritic zones and smaller primary dendrite arms. A favorable epitaxial growth structure was obtained in this paper, under the optimized remelting process window.

Abstract Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Abstract Chemotherapy is an important therapuetic strategy for colorectal cancer (CRC), but chemoresistance severely affects its efficacy, and the underlying mechanism has not been fully elucidated. Increasing evidence suggests that lipid peroxidation imbalance-mediated ferroptosis is closely associated with chemoresistance. Hence, targeting ferroptosis pathways or modulating the tolerance to oxidative stress might be an effective strategy to reverse tumor chemoresistance. HtrA serine protease 1 (HTRA1) was screened out as a CRC progression- and chemoresistance-related gene. It is highly expressed in CRC cells and negatively correlated with the prognosis of CRC patients. Gain- and loss-of-function analyses demonstrated a stimulatory role of HTRA1 on the proliferation of CRC cells. The enrichment analysis of HTRA1-interacting proteins indicated the involvement of ferroptosis in the HTRA1-mediated chemoresistance. Moreover, electron microscope analysis, as well as the ROS and MDA levels in CRC cells also confirmed the effect of HTRA1 on ferroptosis. We also verified that HTRA1 could interact with SLC7A11 through its Kazal structural domain and up-regulate the expression of SLC7A11, which in turn inhibited the ferroptosis and leaded to the chemoresistance of CRC cells to 5-FU/L-OHP. Hence, we propose that HTRA1 may be a potential therapeutic target and a prognostic indicator in CRC.

Abstract Coal is a non-renewable fossil energy source on which humanity relies heavily, and producing one ton of raw coal requires the discharge of 2–7 tons of mine water from the ground. The huge drainage task increases the cost of coal mining in coal mines significantly, so saving the drainage cost while guaranteeing the safe production of coal mines is a problem that needs to be solved urgently. Most of the fuzzy controllers used in the traditional dynamic planning methods applied to mine drainage are two-dimensional fuzzy controllers with limited control effect, so the traditional two-dimensional fuzzy controllers are improved by introducing the rate of change of gushing water to form a three-dimensional fuzzy controller with three-dimensional control of instantaneous section—water level—rate of change of gushing water, and at the same time, the optimized dynamic planning method is designed by combining the Avoiding Peak Filling Valley strategy and the optimal dy-namic planning method is used in conjunction with the un-optimized dynamic planning method. The optimized dynamic planning method is applied to the same coal mine water silo gushing water experiments; experimental comparison found that the pumping station system before the optimi-zation of the electricity consumed is 52,586 yuan/day, while after the optimization of the electricity consumed is reduced to 41,692 yuan/day, the cost per day consumed compared with the previous reduction of 20.69%, a year can be saved 3,969,730 yuan. Therefore, the mine water bin drainage method based on fuzzy control and Avoiding Peak Filling Valley strategy proposed in this paper can be used as an improvement method of the existing mine drainage method, which can further ex-pand the economic benefits of coal mines and realize safe production while realizing cost savings.

Abstract Background Immunotherapy based on the application of immune checkpoint inhibitors (ICIs) is one of the standard treatments for advanced non-small cell lung cancer (NSCLC). Non-alcoholic fatty liver Disease (NAFLD) has demonstrated predictive value for response to immunotherapy in non-lung cancer types. Our study investigated the effect of NAFLD on the efficacy of real-life use of ICIs for patients with stage III / IV NSCLC. Methods The clinical and imaging data of patients with stage III / IV NSCLC who were first admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to July 2022 were retrospectively collected to ensure that they underwent at least one CT scan before treatment. A total of 479 patients were divided into the NAFLD group (Liver/Spleen density ratio ≤ 1) and the non-NAFLD group (Liver/Spleen density ratio > 1) by measuring the baseline liver and spleen CT value. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the patients were obtained. Results A total of 118 patients with NAFLD and 361 patients without NAFLD were included in the study. Patients with NAFLD tended to have higher BMI and higher total bilirubin compared to patients without NAFLD. The median duration of follow-up in the study was 22 m (IQR, 17–29 m). Both of 2 groups had a higher DCR (94% vs. 92%, p = 0.199) and ORR (38.1% vs. 44.9%, p = 0.452) respectively. There was no difference in efficacy between the two groups. In univariate analysis, NAFLD had no significant effect on PFS (p = 0.785) and OS (p = 0.851). Surprisingly, the presence of hypertension was observed to be associated with a higher OS (HR 1.471 95%CI 1.018–2.127, p = 0.040). Besides, based on multivariate analysis, lactic dehydrogenase was associated with PFS (HR 1.001 95%CI 1.000,1.002, p = 0.037) and OS (HR 1.002, 95%CI 1.001–1.003, p

Abstract Background Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear. Methods In the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC. Results The data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis. Conclusion Taken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis.

Abstract Background The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Methods Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. Results ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. Conclusions The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors.

Background Gestational diabetes mellitus (GDM) can increase the risk of adverse outcomes for both mothers and infants. Preventive interventions can effectively assist pregnant women suffering from GDM. At present, pregnant women are unaware of the importance of preventing GDM, and they possess a low level of self-management ability. Recently, mHealth technology has been used worldwide. Therefore, developing a mobile health app for GDM prevention could potentially help pregnant women reduce the risk of GDM. Objective To design and develop a mobile application, evaluate its acceptance, and understand the users’using experience and suggestions, thus providing a valid tool to assist pregnant women at risk of GDM in enhancing their self-management ability and preventing GDM. Methods An evidence-based GDM prevent app ( Better pregnancy ) was developed using user-centered design methods, following the health belief model, and incorporating GDM risk prediction. A convenient sampling method was employed from June to August 2022 to select 102 pregnant women at risk of GDM for the pilot study. After a week, the app's acceptability was evaluated using an application acceptance questionnaire, and we updated the app based on the feedback from the women. We used SPSS 26.0 for data analysis. Results The application offers various functionalities, including GDM risk prediction, health management plan, behavior management, health information, personalized guidance and consultation, peer support, family support, and other functions. In total, 102 pregnant women consented to participate in the study, achieving a retention rate of 98%; however, 2% ( n = 2) withdrew. The Better pregnancy app's average acceptability score is 4.07 out of 5. Additionally, participants offered several suggestions aimed at enhancing the application. Conclusions The Better pregnancy app developed in this study can serve as an auxiliary management tool for the prevention of GDM, providing a foundation for subsequent randomized controlled trials.

Abstract Modulation of light underpins a central part of modern optoelectronics. Conventional optical modulators based on refractive‐index and absorption variation in the presence of an electric field serve as the workhorse for diverse photonic technologies. However, these approaches based on electro‐refraction or electro‐absorption effect impose limitations on frequency converting and signal amplification. Lanthanide‐activated phosphors offer a promising platform for nonlinear frequency conversion with an abundant spectrum. Here, we propose a novel approach to achieve frequency conversion and digital modulation of light signal by coupling lanthanide luminescence with an electrically responsive ferroelectric host. The technological benefits of such paradigm‐shifting solution are highlighted by demonstrating a quasi‐continuous and enhancement of the lanthanide luminescence. The ability to locally manipulate light emission can convert digital information signals into visible waveforms, and visualize electrical logic and arithmetic operations. The proof‐of‐concept device exhibits perspectives for developing light‐compatible logic functions. These results pave the way to design more controllable lanthanide photonics with desired opto‐electronic coupling.

Summary: Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

Melon (Cucumis melo L.) is one of the most extensively grown horticulture crops of the world. Based on the morphological characters, melon was formerly divided into two subspecies, Cucumis melo ssp. melo and C. melo ssp. agrestis. However, the present methods are still inadequate to distinguish between them. The phylogenetic analysis based on chloroplast genome sequences could provide essential evidence for the classification of melon varieties. We sequenced the chloroplast genomes of nine different melon varieties by the Illumina Hiseq and performed bioinformatic analyses including repeat element analysis, genome comparison and phylogenetic analysis. The results showed that the melon chloroplast genome has a typical quadripartite structure that was conserved across the analyzed sequences. Its length ranges between 155, 558 and 156, 569 bp, with a total GC content varying from 36.7% to 37%. We found 127–132 genes in melon chloroplast genomes, including 85–87 protein-coding regions, 34–37 tRNA and 6-8 rRNA genes. The molecular structure, gene order, content, codon usage, long repeats, and simple sequence repeats (SSRs) were mostly conserved among the nine sequenced genomes. Phylogenetic analysis showed that the chloroplast genome could clearly distinguish between C. melo ssp. melo and C. melo ssp. agrestis. This study not only provides valuable knowledge on melon chloroplasts, but also offers a theoretical basis and technical support for the genetic breeding of melons.

Abstract Soft magnetic materials with stable permeability up to hundreds of megahertz (MHz) are urgently needed for integrated transformers and inductors, which are crucial in the more-than-Moore era. However, traditional frequency-stable soft magnetic ferrites suffer from low saturation magnetization and temperature instability, making them unsuitable for integrated circuits. Herein, we fabricate a frequency-stable soft magnetic composite featuring a magnetic vortex structure via cold-sintering, where ultrafine FeSiAl particles are magnetically isolated and covalently bonded by Al2SiO5/SiO2/Fe2(MoO4)3 multilayered heterostructure. This construction results in an ultrastable permeability of 13 up to 1 gigahertz (GHz), relatively large saturation magnetization of 105 Am2/kg and low coercivity of 48 A/m, which we ascribe to the elimination of domain walls associated with almost uniform single-vortex structures, as observed by Lorentz transmission electron microscopy and reconstructed by micromagnetic simulation. Moreover, the ultimate compressive strength has been simultaneously increased up to 337.1 MPa attributed to the epitaxially grown interfaces between particles. This study deepens our understanding on the characteristics of magnetic vortices and provides alternative concept for designing integrated magnetic devices.

Abstract Background Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis. Timely diagnosis and precise treatment of TNBC are substantially challenging. Abnormal tumor vessels play a crucial role in TNBC progression and treatment. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis, while effective NO delivery can normalize the tumor vasculature. Accordingly, we have proposed here a tumor vascular microenvironment remodeling strategy based on NO-induced vessel normalization and extracellular matrix collagen degradation with multimodality imaging-guided nanoparticles against TNBC called DNMF/PLGA. Results Nanoparticles were synthesized using a chemotherapeutic agent doxorubicin (DOX), a NO donor L-arginine (L-Arg), ultrasmall spinel ferrites (MnFe2O4), and a poly (lactic-co-glycolic acid) (PLGA) shell. Nanoparticle distribution in the tumor was accurately monitored in real-time through highly enhanced magnetic resonance imaging and photoacoustic imaging. Near-infrared irradiation of tumor cells revealed that MnFe2O4 catalyzes the production of a large amount of reactive oxygen species (ROS) from H2O2, resulting in a cascade catalysis of L-Arg to trigger NO production in the presence of ROS. In addition, DOX activates niacinamide adenine dinucleotide phosphate oxidase to generate and supply H2O2. The generated NO improves the vascular endothelial cell integrity and pericellular contractility to promote vessel normalization and induces the activation of endogenous matrix metalloproteinases (mainly MMP-1 and MMP-2) so as to promote extravascular collagen degradation, thereby providing an auxiliary mechanism for efficient nanoparticle delivery and DOX penetration. Moreover, the chemotherapeutic effect of DOX and the photothermal effect of MnFe2O4 served as a chemo-hyperthermia synergistic therapy against TNBC. Conclusion The two therapeutic mechanisms, along with an auxiliary mechanism, were perfectly combined to enhance the therapeutic effects. Briefly, multimodality image-guided nanoparticles provide a reliable strategy for the potential application in the fight against TNBC. Graphical Abstract

Abstract Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based therapies specifically tailored for those with R/R AML remains scarce. Here, we provide a comprehensive overview of the latest data presented at the 65th American Society of Hematology Annual Meeting, shedding light on the progress and efficacy of VEN-based therapies for R/R AML.

Abstract Background Fatty liver hemorrhage syndrome (FLHS) becomes one of the most major factors resulting in the laying hen death for caged egg production. This study aimed to investigate the therapeutic effects of Lactiplantibacillus plantarum (Lp. plantarum) FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism, and gut microbiota. Results The FLHS model of laying hens was established by feeding a high-energy low-protein (HELP) diet, and the treatment groups were fed a HELP diet supplemented with differential proportions of Lp. plantarum FRT4. The results indicated that Lp. plantarum FRT4 increased laying rate, and reduced the liver lipid accumulation by regulating lipid metabolism (lipid synthesis and transport) and improving the gut microbiota composition. Moreover, Lp. plantarum FRT4 regulated the liver glycerophospholipid metabolism. Meanwhile, “gut-liver” axis analysis showed that there was a correlation between gut microbiota and lipid metabolites. Conclusions The results indicated that Lp. plantarum FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating “gut-liver” axis. Our findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of Lp. plantarum FRT4 and for future use of Lp. plantarum FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.

Micro holes with high aspect ratios are essential for the cooling performance of aero-engines. Challenges persist in deep hole drilling due to the escalating stringent requirements in terms of hole diameters, aspect ratios, and 3D profiles. In this study, we propose a two-step femtosecond laser drilling method to produce cylindrical micro holes with diameters of ∼100 μm, aspect ratios >20, and near-zero taper angle in Inconel 718 plates. In the first drilling period, the laser polarization trepanning method is used, yielding through-holes with aspect ratios >20 but undesired tapers and irregular shapes at the hole exit. A new method called laser spinning is then introduced in the second drilling period, proficiently decreasing taper angles to be

Background Renal fibrosis contributes to chronic renal failure and a decline in the quality of life. Bushen Huoxue (BSHX) formula is a Traditional Chinese Medicine used to treat chronic renal failure. However, its mechanisms of action remain unclear.Methods and results In this study, a rat model of renal fibrosis was constructed by 5/6 nephrectomy in vivo, and histopathological changes were analyzed using hematoxylin-eosin and Masson’s trichrome staining. Angiotensin II (Ang II) was used to establish an in vitro renal fibrosis cell model in vitro. Pyroptosis was measured using flow cytometry. Related markers of fibrosis and NOD-like receptor protein 3 (NLRP3) inflammasome activation were measured using western blotting and enzyme-linked immunosorbent assay. Treatment with BSHX (0.25, 0.5, and 1 g/kg) significantly inhibited renal fibrosis and damage in 5/6 nephrectomized rats and simultaneously reduced oxidative stress and NLRP3 inflammasome activation. Similarly, BSHX treatment reduced the levels of hydroxyproline, transforming growth factor-β, matrix metalloproteinase 2, and matrix metalloproteinase 9 and inactivated the Smad2/3 signaling pathway in Ang II-treated HK-2 cells. Our data also showed that treatment with BSHX reduced NLRP3 inflammasome activation and pyroptosis in Ang II-treated HK-2 cells. Moreover, fibrosis and pyroptosis in HK-2 cells induced by NLRP3 overexpression were reduced by treatment with BSHX.Conclusions BSHX significantly reduced renal fibrosis and pyroptosis, and its mechanism was mainly associated with the inhibition of reactive oxygen species (ROS)/NLRP3-mediated inflammasome activation.

Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered type of programmed cell death, is involved in the pathological process of Th2-high asthma; however, the underlying mechanisms remain incompletely understood. In this study, we demonstrated that the serum level of malondialdehyde (MDA), an index of lipid peroxidation, positively correlated with IL-13 level and negatively correlated with the predicted forced expiratory volume in 1 s (FEV1%) in asthmatics. Furthermore, we showed that IL-13 facilitates ferroptosis by upregulating of suppressor of cytokine signaling 1 (SOCS1) through analyzing immortalized airway epithelial cells, human airway organoids, and the ovalbumin (OVA)-challenged asthma model. We identified that signal transducer and activator of transcription 6 (STAT6) promotes the transcription of SOCS1 upon IL-13 stimulation. Moreover, SOCS1, an E3 ubiquitin ligase, was found to bind to solute carrier family 7 member 11 (SLC7A11) and catalyze its ubiquitinated degradation, thereby promoting ferroptosis in airway epithelial cells. Last, we found that inhibiting SOCS1 can decrease ferroptosis in airway epithelial cells and alleviate airway hyperresponsiveness (AHR) in OVA-challenged wide-type mice, while SOCS1 overexpression exacerbated the above in OVA-challenged IL-13-knockout mice. Our findings reveal that the IL-13/STAT6/SOCS1/SLC7A11 pathway is a novel molecular mechanism for ferroptosis in Th2-high asthma, confirming that targeting ferroptosis in airway epithelial cells is a potential therapeutic strategy for Th2-high asthma.

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and β-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

BackgroundImmune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs.MethodsThis study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves.ResultsA total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008).ConclusionLower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

Background: Virtual simulation systems are being increasingly used in the field of nursing education. However, these systems are mostly designed based on the perspective of developers, and the needs of the end users are often neglected. The purpose of this study was to explore the perceptions and needs of Chinese undergraduate nursing students for the development of a community nursing virtual simulation system. Methods: This was a descriptive qualitative study enrolling 12 undergraduate nursing students at a University in China. Data were collected through semi-structured interviews. The content analysis method was used for data analysis. Result: Three themes and 15 sub-themes were extracted from this study: (1) Positive perceptions regarding virtual systems: a) Provides space for trials and errors, b) Not limited by time and space, c) Provides auxiliary tools; (2) Design and use requirements: a) Performance needs, b) Contents design needs, c) Appearance design needs, d) Support Needs; (3) Competency enhancement needs: a) Community nursing practice ability, b) Critical thinking ability, c) Independent thinking ability, d) Ability to deal with emergencies, e)Teamwork skills, f) Self-efficacy, g) Resilience, h)Interpersonal communication skills. Conclusion: Designers and engineers should consider students' needs, aim to improve students' abilities, improve the diversity, the scientific and rigor of content, and enhance user immersion and interest. The system should be programmed to provide real-time feedback, timely technical and professional support, in order to optimize use experience of nursing students.

Abstract Background Cancer-related psychological and physical disorders can mean stressful and painful experiences for patients. Art therapy, a form of complementary and alternative medicine, is an increasingly popular way to decrease emotional stress, alleviate somatic symptoms, and improve quality of life in patients with cancer. However, current systematic reviews have not explored the beneficial effects of art therapy. Moreover, there have been inconsistent findings on the effect of this therapy, and there is insufficient evidence to confirm the effects in adults with cancer. The objective of this study was to determine the efficacy of art therapy in improving quality of life and psychosomatic symptoms in adults with cancer. Methods This systematic review and meta-analysis included adults with all kinds of cancer. Six English-language and three large Chinese-language databases were comprehensively searched for relevant studies. Gray literature and references were also checked. The quality of the included studies was evaluated using the Cochrane risk-of-bias assessment tool. Results Eight eligible randomized controlled trials conducted in four countries were included. Art therapy improved overall quality of life, but had no significant effect on psychological health or physical health sub-dimensions in women with cancer. Moreover, art therapy alleviated anxiety and depression, but had only a tendency toward an effect on somatic symptoms. Conclusions Moderate-quality evidence shows that art therapy is beneficial for women with cancer in terms of improving the overall quality of life and alleviating emotional symptoms (anxiety and depression). However, more high-quality randomized controlled trials are needed to determine the efficacy of this therapy on somatic symptoms.

ABSTRACTSilibinin is a natural flavonoid with anti-diabetic activity. Glucagon-like peptide−1 (GLP−1), an intestinal hormone mainly secreted from L cells, which regulates insulin production and sensitivity, appears to be a potential therapeutic strategy for T2DM. The current study aims to determine the protective effect of silibinin against palmitic acid (PA)-induced damage in GLUTag cells. The results revealed that PA triggered endoplasmic reticulum (ER) stress and apoptosis in GLUTag cells, while silibinin attenuated PA-induced lipotoxicity. Based on the estrogen-like effects of silibinin and the role of estrogen receptors in regulating glycolipid metabolism, the involvement of estrogen receptors in the protective effects of silibinin in GLUTag cells was further investigated. The results showed that estrogen receptor α- and β-specific inhibitors reversed the inhibitory impact of silibinin on ER stress. Our study demonstrated that silibinin protects GLUTag cells from PA-induced injury by decreasing ER stress under the regulation of estrogen receptors α and β.

Abstract Background The genotype-phenotype relationships between TUBB8 variants and female infertility are difficult to clearly define due to the complex inheritance patterns and the highly heterogeneous phenotypes. This study aims to identify novel TUBB8 variants and relevant phenotypes in more infertile females. Methods A total of 35 females with primary infertility were recruited from two reproductive centers and investigated for identifying variants in TUBB8. Pedigree analysis, in-silico analysis and molecular remodeling were performed to assess their clinical significance. The effects of the variants on human oocytes and embryos as well as HeLa cells were analyzed by morphological observations, immunostaining and Western blot. Results We totally identified five novel variants (p.G13R, p.Y50C, p.T136I, p.F265V and p.T366A) and five previously reported variants (p.I4L, p.L42V, p.Q134*, p.V255M and p.V349I) in TUBB8 from 9 unrelated females with primary infertility. These variants were rare and highly conserved among different species, and were inherited in autosomal dominant/recessive patterns, or occurred de novo. In vitro functional assays in HeLa cells revealed that exogenous expression of mutant TUBB8 proteins caused different degrees of microtubule structural disruption. The existence of these pathogenic TUBB8 variants finally induced oocyte maturation arrest or morphological abnormalities, fertilization failure, cleavage failure, embryonic development defects and implantation failure in the affected females. Conclusion These findings enriched the variant spectrum of TUBB8 gene and could contribute to optimize genetic counselling and clinical management of females with primary infertility.

Abstract HCC is one of the most common malignant tumors worldwide. Although traditional treatment methods have been improved in recent years, the survival rate of HCC patients has not been significantly improved. Immunotherapy has shown extremely high clinical value in a variety of tumors. In this study, we found that TUG1 could regulate the expression of PD-L1 through JAK2/STAT3 to mediate immunosuppression. Here, The expression of TUG1 and PD-L1 in HCC tissues was evaluated through analysis of databases and verified in HCC tissue and HCC cancer cells by qRT-PCR. The effect of TUG1 on tumor immune escape was detected by coculture, and cell viability was detected with a CCK8 assay. The results demonstrated that TUG1 was closely associated with anticancer immunity. TUG1 and PD-L1 were highly expressed in HCC tissues and HCC cancer cells, and high expression of TUG1 and PD-L1 was related to the poor prognosis of HCC patients. In addition, knocking down TUG1 expression could reduce PD-L1 expression and enhance the cancer cell-killing capability of T cells. Downregulating TUG1 expression could also decrease the mRNA and protein expression of JAK2 and STAT3. To sum up, TUG1 and PD-L1 are overexpressed in patients with liver cancer and are related to the poor prognosis of these patients. Silencing TUG1 expression reduced the mRNA and protein expression of PD-L1 by affecting the JAK2/STAT3 pathway.

Aboveground biomass (AGB) serves as a crucial indicator of the carbon sequestration capacity of coastal wetland ecosystems. Conducting extensive field surveys in coastal wetlands is both time-consuming and labor-intensive. Unmanned aerial vehicles (UAVs) and satellite remote sensing have been widely utilized to estimate regional AGB. However, the mixed pixel effects in satellite remote sensing hinder the precise estimation of AGB, while high-spatial resolution UAVs face challenges in estimating large-scale AGB. To fill this gap, this study proposed an integrated approach for estimating AGB using field sampling, a UAV, and Sentinel-2 satellite data. Firstly, based on multispectral data from the UAV, vegetation indices were computed and matched with field sampling data to develop the Field–UAV AGB estimation model, yielding AGB results at the UAV scale (1 m). Subsequently, these results were upscaled to the Sentinel-2 satellite scale (10 m). Vegetation indices from Sentinel-2 data were calculated and matched to establish the UAV–Satellite AGB model, enabling the estimation of AGB over large regional areas. Our findings revealed the AGB estimation model achieved an R2 value of 0.58 at the UAV scale and 0.74 at the satellite scale, significantly outperforming direct modeling from field data to satellite (R2 = −0.04). The AGB densities of the wetlands in Xieqian Bay, Meishan Bay, and Hangzhou Bay, Zhejiang Province, were 1440.27 g/m2, 1508.65 g/m2, and 1545.11 g/m2, respectively. The total AGB quantities were estimated to be 30,526.08 t, 34,219.97 t, and 296,382.91 t, respectively. This study underscores the potential of integrating UAV and satellite remote sensing for accurately assessing AGB in large coastal wetland regions, providing valuable support for the conservation and management of coastal wetland ecosystems.

Guanidinoacetic acid (GAA) can effectively improve the metabolism of energy and proteins by stimulating creatine biosynthesis. We present a study exploring the impact of GAA on production performance, serum biochemistry, meat quality and rumen fermentation in Hu sheep. A total of 144 weaned male Hu sheep (body weight 16.91 ± 3.1 kg) were randomly assigned to four groups with three replicates of twelve sheep in each group. The diets were supplemented with 0 (CON), 500 (GAA−1), 750 (GAA−2) and 1000 mg/kg (GAA−3) of GAA (weight of feed), respectively. After a comprehensive 90-day experimental period, we discovered that the supplementation of GAA had a remarkable impact on various muscle parameters. Specifically, it significantly enhanced the average daily growth (ADG) of the animals and improved the shear force and fiber diameter of the muscle, while also reducing the drip loss and muscle fiber density. Furthermore, the addition of GAA to the feed notably elevated the serum concentrations of high-density lipoprotein cholesterol (HDL−C), total protein (TP) and globulin (GLB), as well as the enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH−Px). Concurrently, there was a decrease in the levels of triglycerides (TG) and malondialdehyde (MDA) in the serum. In addition, GAA decreased the pH and the acetate-to-propionate ratio and increased the total volatile fatty acids (TVFA) and ammoniacal nitrogen (NH3−N) levels of rumen fluid. Additionally, GAA upregulated acetyl-CoA carboxylase (ACC) gene expression in the Hu sheep’s muscles. In conclusion, our findings suggest that GAA supplementation not only enhances muscle quality but also positively affects serum biochemistry and ruminal metabolism, making it a potential candidate for improving the overall health and performance of Hu sheep.

Background: Myoprotein degradation accelerates in obese individuals, resulting in a decline in muscular mass. Atg7 plays a crucial role in regulating protein stability and function through both autophagy-dependent and independent pathways. As obesity progresses, the expression of Atg7 gradually rises in muscle tissue. Nonetheless, the precise impact and mechanism of Atg7 in promoting muscle mass decline in obesity remain uncertain. The study aimed to elucidate the role and underly mechanism of Atg7 action in the context of obesity-induced muscle mass decline. Methods: In this study, we established a murine model of high-fat diet-induced obesity (DIO) and introduced adeno-associated virus delivery of short hairpin RNA to knock down Atg7 (shAtg7) into the gastrocnemius muscle. We then examined the expressions of Atg7 and myoprotein degradation markers in the gastrocnemius tissues of obese patients and mice using immunofluorescence and western blotting techniques. To further investigate the effects of Atg7, we assessed skeletal muscle cell diameter and the myoprotein degradation pathway in C2C12 and HSkMC cells in the presence or absence of Atg7. Immunofluorescence staining for MyHC and western blotting were utilized for this purpose. To understand the transcriptional regulation of Atg7 in response to myoprotein degradation, we conducted luciferase reporter assays and chromatin immunoprecipitation experiments to examine whether FoxO3a enhances the transcription of Atg7. Moreover, we explored the role of Akt in Atg7-mediated regulation and its relevance to obesity-induced muscle mass decline. This was accomplished by Akt knockdown, treatment with MK2206, and GST pulldown assays to assess the interaction between Atg7 and Akt. Results: After 20 weeks of being on a high-fat diet, obesity was induced, leading to a significant decrease in the gastrocnemius muscle area and a decline in muscle performance. This was accompanied by a notable increase in Atg7 protein expression (p

Abstract Background and Aims The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Methods Thrombomodulin (TM), thrombin‐antithrombin complex (TAT), α2‐plasmininhibitor‐plasmin complex (PIC), and tissue plasminogen activator‐inhibitor complex (t‐PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d‐dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan–Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single‐factor and multifactor cox regression analysis model. Results The following indicators (TM, TAT, PIC, t‐PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination “TAT + PIC + DD + FDP + Fbg” can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. Conclusion The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

Summary: Newcastle disease is a global problem that causes huge economic losses and threatens the health and welfare of poultry. Despite the knowledge gained on the metabolic impact of NDV on cells, the extent to which infection modifies the plasma metabolic network in chickens remains unknown. Herein, we performed targeted metabolomic and lipidomic to create a plasma metabolic network map during NDV infection. Meanwhile, we used single-cell RNA sequencing to explore the heterogeneity of lung tissue cells in response to NDV infection in vivo. The results showed that NDV remodeled the plasma phospholipid metabolism network. NDV preferentially targets infected blood endothelial cells, antigen-presenting cells, fibroblasts, and neutrophils in lung tissue. Importantly, NDV may directly regulate ribosome protein transcription to facilitate efficient viral protein translation. In conclusion, NDV infection remodels the plasma phospholipid metabolism network in chickens. This work provides valuable insights to further understand the pathogenesis of NDV.

Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.

BackgroundImmunotherapy, represented by immune checkpoint inhibitors (ICIs), is a major breakthrough in cancer treatment. Studies have reported that the use of ICIs is associated with an increase in the pulmonary artery to ascending aorta diameter (PAD/AoD) ratio. However, the impact of PAD/AoD ratio progression on the prognosis of patients is unclear.MethodsThis retrospective cohort study included patients with stage III or IV non-small cell lung cancer (NSCLC) treated with ICIs at the Wuhan Union Hospital between March 1, 2020, and September 1, 2022. The baseline and post-treatment PAD/AoD ratios of patients were evaluated through chest CT scans. The primary outcome of this study was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR).ResultsThe PAD/AoD ratio increased after the initiation of ICIs (from 0.75 to 0.78; P < 0.001). A total of 441 patients were divided into severe group (n=221) and non-severe group (n=220) according to the median increase of PAD/AoD ratio (1.06). Compared with the non-severe group, the severe group had a lower DCR (87.8% vs. 96.0%, P = 0.005) and ORR (87.5% vs. 96.0%, P = 0.063). Over the entire duration of follow-up (median 22.0 months), 85 (38.5%) patients in the severe group and 30 (7.3%) patients in the non-severe group died. An increased PAD/AoD ratio was associated with shorter PFS (Hazard ratio (HR): 1.48 [95% CI, 1.14 to 1.93]; P = 0.003) and OS (HR: 3.50 [95% CI, 2.30 to 5.30]; P < 0.001). Similar results were obtained across subgroups.ConclusionsICI treatment exacerbates an increase in the PAD/AoD ratio in patients with cancer, and greater increase in the PAD/AoD ratio was associated with a worse prognosis. PAD/AoD ratio could be a biomarker to stratify prognosis of NSCLC patients treated with ICIs.

Wetlands, as a special ecological environment, are not only important biodiversity conservation areas but also one of the important agricultural resources. Agriculture plays an irreplaceable role in human society. It is directly related to human survival and development, and is also a part of people's environmental awareness and cultural inheritance. Based on the principles of sustainable development and strengthening environmental protection, people should pay more attention to the development and improvement of agriculture. However, with the advancement of urbanization, the area of wetlands continues to decrease, causing damage to ecosystems and posing a threat to some agricultural production. This article combined the transfer matrix of agricultural wetland utilization, landscape change rate, and landscape pattern index, used RS (Remote Sensing) and GIS (Geographic Information System) technologies to analyze the dynamic changes in agricultural wetland utilization and landscape of Honghu Lake in the Four Lakes region, and explored its changing factors. The results indicated that the construction land area showed an increasing trend in 2016, 2019, and 2022, while the wetland area of rice fields showed a first decreasing and then increasing trend. HIGHLIGHTS The correlation between agricultural wetland and its change factors was analyzed.; To forecast the future development trend of the Honghu agricultural wetland.; Help the planning department to adopt corresponding measures and strategies according to the law of change.; Effective protection of the Honghu agricultural wetland.; To achieve its sustainable use.;

Abstract Objective To examine the impact of sacroiliac screw position and length on the biomechanical properties of triangular osteosynthesis in treating unilateral vertical sacral fractures and provide a clinical reference. Methods Unilateral Denis type II sacral fractures were modelled using finite elements to represent Tile C pelvic ring injuries. Six sacroiliac screws were used with iliolumbar fixation patterns to fix the sacral fractures, and the sacral stability, maximum pressure, and stress distribution were compared among the internal fixation modalities. Results The best vertical stability of the internal fixation model was achieved when the S1 segment was fixed with lengthened sacroiliac screws, followed by when the S1 segment was fixed using normal sacroiliac screws. There was no significant difference in vertical stability between the S1 + S2 dual-segment fixation model and the S1-segment fixation model. The maximum pressure under a vertical force of 600 N showed a trend of L5LS1

Abstract Background Porcine fetal fibroblasts (PFFs) are important donor cells for generating genetically modified pigs, but the transfection efficiencies of PFFs are often unsatisfactory especially when large-size vectors are to be delivered. In this study, we aimed to optimize the transfection conditions for delivery of a large-size vector in PFFs using Lonza 4D-Nucleofector™ vessels and strips. Methods We firstly delivered a 13 kb Cas9-EGFP and a 3.5 kb pMAX-GFP vector into PFFs via 7 programs recommended by the Lonza basic protocol. We then tested 6 customized dual-electroporation programs for delivering the 13 kb plasmid into PFFs. In addition, we screened potential alternative electroporation buffers to the Nucleofector™ P3 solution. Finally, three CRISPR/Cas9-sgRNAs targeting Rosa26, H11, and Cep112 loci were delivered into PFFs with different single and dual-electroporation programs. Results Notably lower transfection efficiencies were observed when delivering the 13 kb vector than delivering the 3.5 kb vector in PFFs via the single-electroporation programs. The customized dual-electroporation program FF-113 + CA-137 exhibited higher transfection efficiencies than any of the single-electroporation programs using vessels (98.1%) or strips (89.1%) with acceptable survival rates for the 13 kb vector. Entranster-E buffer generated similar transfection efficiencies and 24-hour survival rates to those from the P3 solution, thus can be used as an alternative electroporation buffer. In the genome-editing experiments, the FF-113 + CA-137 and CA-137 + CA-137 programs showed significantly superior (P

Abstract Variations in the pathogenicity of Newcastle disease virus (NDV), the agent causing Newcastle disease, are associated with variants of different virulence. A few studies have characterized the expression of microRNAs (miRNAs) in NDV-infected avian cells. Here, the expression of miRNAs in chicken embryo fibroblasts (CEFs) infected with Herts/33 and LaSota NDV strains (highly virulent and nonvirulent, respectively) was determined using RNA sequencing. miRNAs involved in NDV infection included 562 previously documented and 184 novel miRNAs. miRNA target genes involved transcription factors, cell apoptosis, ubiquitin-mediated proteolysis, and protein processing in the endoplasmic reticulum. Potential target genes associated with autophagy were verified by qRT-PCR. No studies have documented the miRNA profiles of CEFs infected with NDVs variants. This study adds to our knowledge of the cellular miRNAs involved in NDV infection and the complex molecular mechanisms mediating virus-host interactions. The results of this study will aid the development of strategies against the chicken virus.

Abstract Introduction/objectives Systemic lupus erythematosus (SLE) is a classic prototype of the multisystem autoimmune disease and follows a relapsing and remitting course. Triptolide is a diterpene triepoxide extracted from Chinese medicine Tripterygium wilfordii Hook F, with potent immunosuppressive and anti-inflammatory properties. Our previous work observed that triptolide alleviated lupus in MRL/lpr lupus mice with the upregulation of regulatory T cells (Treg) proportion in previous study. In this study, we explored the proportion of follicular T regulatory (Tfr), follicular T helper (Tfh) and germinal center (GC) B cells in lupus mice and evaluated the efficacy of triptolide for lupus treatment in vivo. Methods 20 female MRL/lpr mice were randomly divided into 2 treatment groups and treated orally with vehicle or triptolide. C3H mice were all housed as controlled group and treated orally with vehicle. The percentage of Tfr cells, Tfh cells and GC B cells in spleen of mice were detected by Flow cytometric analysis and immunohistochemistry after 13 weeks of treatment. Results We found that the percentage of Tfr cells decreased in MRL/lpr mice compared with controlled mice. The percentage of Tfh cells in MRL/lpr mice was significantly higher compared with that in controlled mice. The ratio of Tfr/Tfh is also decreased in lupus mice. After treated with triptolide in MRL/Lpr mice in vivo, the percentage of Tfr cells and ratio of Tfr/Tfh increased. The proportion of GC B cells also decreased in mice treated with triptolide by FACS and immunohistochemistry. Conclusions Our results demonstrate that the effect of triptolide in alleviating lupus is partly by reversing immune imbalance with increased percentage of Tfr cells and ratio of Tfr/Tfh. Triptolide might also has effect on immune response through inhibiting proliferating GC B cells.

Abstract Aim To explore the factors affecting the quality of accelerated rehabilitation for patients with cervical spinal cord injury, therefore, to propose targeted improvement strategies and provide reference for promoting the quality of nursing care for accelerated rehabilitation. Design This descriptive qualitative inquiry followed the COREQ guidelines. Methods From December 2020 to April 2021, 16 subjects including orthopaedic nurses, nursing management experts, orthopaedic surgeons, anaesthesiologists and physical therapists experienced in accelerated rehabilitation were selected by objective sampling method to conduct semi‐structured interviews. Thematic analysis was used to analyse the interview content. Results Through analysis and summary of the interview data, the following two themes and nine sub‐themes were finally extracted. Factors related to the quality of accelerated rehabilitation structure include: construction of multidisciplinary teams, thorough system guarantee and adequate staffing. Factors related to the quality of accelerated rehabilitation process include: inadequate training and assessment, lack of medical staff's awareness, incapability of the accelerated rehabilitation team members, poor multidisciplinary communication and collaboration, lack of patient's awareness, and ineffective health education. Conclusion Quality of implementation of accelerated rehabilitation can be improved by maximizing the role of multidisciplinary team, establishing a flawless accelerated rehabilitation system, increasing allocation of nursing resources, enhancing knowledge of medical staff, improving their awareness of accelerated rehabilitation, establishing personalized clinical pathways of accelerated rehabilitation, increasing communication and collaboration among multidisciplinary disciplines, and improving health education of patients.

Skeletal muscle myogenesis hinges on gene regulation, meticulously orchestrated by molecular mechanisms. While the roles of transcription factors and non-coding RNAs in myogenesis are widely known, the contribution of RNA-binding proteins (RBPs) has remained unclear until now. Therefore, to investigate the functions of post-transcriptional regulators in myogenesis and uncover new functional RBPs regulating myogenesis, we employed CRISPR high-throughput RBP-KO (RBP-wide knockout) library screening. Through this approach, we successfully identified Eef1a1 as a novel regulatory factor in myogenesis. Using CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) technologies, we successfully established cellular models for both CRISPRko and CRISPRi. Our findings demonstrated that Eef1a1 plays a crucial role in promoting proliferation in C2C12 myoblasts. Through siRNA inhibition and overexpression methods, we further elucidated the involvement of Eef1a1 in promoting proliferation and suppressing differentiation processes. RIP (RNA immunoprecipitation), miRNA pull-down, and Dual-luciferase reporter assays confirmed that miR-133a-3p targets Eef1a1. Co-transfection experiments indicated that miR-133a-3p can rescue the effect of Eef1a1 on C2C12 myoblasts. In summary, our study utilized CRISPR library high-throughput screening to unveil a novel RBP, Eef1a1, involved in regulating myogenesis. Eef1a1 promotes the proliferation of myoblasts while inhibiting the differentiation process. Additionally, it acts as an antagonist to miR-133a-3p, thus modulating the process of myogenesis.

Abstract Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

Abstract We propose a robust fuzzy design model for a sustainable closed-loop supply chain network. The model is based on a risk dynamic regulation mechanism. In this way, we can solve the problem of sudden disruptions and uncertain demand in the supply chain of Chinese herbal medicines. We also develop a hybrid algorithm solution to solve the model and design a resilient supply chain network. The specific steps are as follows: (1) The risk dynamic regulation mechanism is created with strong risk resistance by considering the information sharing platform, facility defense, drying station scheduling, safety stock, and shared inventory. (2) Based on the dynamic risk regulation mechanism, we establish a sustainable Chinese herbal medicine supply chain network design model. Then, we use the robust fuzzy method and the epsilon constraint to deal with the uncertainty and integrate the model. (3) We introduce opposition-based learning, cosine convergence factor, and levy flight to the original Whale and Grey wolf algorithms to obtain the Hybrid algorithm, which is used to solve the processed model. The results show the model and algorithm proposed in this paper have strong applicability and advantages in designing closed-loop supply chain networks for Chinese herbal medicine and provide references for relevant decision-makers.

Abstract Mesenchymal stem/Stromal cells (MSCs) have great therapeutic potentials, and they have been isolated from various tissues and organs including definitive endoderm (DE) organs, such as the lung, liver and intestine. MSCs have been induced from human pluripotent stem cells (hPSCs) through multiple embryonic lineages, including the mesoderm, neural crest, and extraembryonic cells. However, it remains unclear whether hPSCs could give rise to MSCs in vitro through the endodermal lineage. Here, we report that hPSC-derived, SOX17+ definitive endoderm progenitors can further differentiate to cells expressing classic MSC markers, which we name definitive endoderm-derived MSCs (DE-MSCs). Single cell RNA sequencing demonstrates the stepwise emergence of DE-MSCs, while endoderm-specific gene expression can be elevated by signaling modulation. DE-MSCs display multipotency and immunomodulatory activity in vitro and possess therapeutic effects in a mouse ulcerative colitis model. This study reveals that, in addition to the other germ layers, the definitive endoderm can also contribute to MSCs and DE-MSCs could be a cell source for regenerative medicine.