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Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2–3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC. Methods In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo. Results Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967–0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033–6.605, P

Abstract Background Third-generation sequencing (TGS) based on long-read technology has been gradually used in identifying thalassemia and hemoglobin (Hb) variants. The aim of the present study was to explore genotype varieties of thalassemia and Hb variants in Quanzhou region of Southeast China by TGS. Methods Included in this study were 6,174 subjects with thalassemia traits from Quanzhou region of Southeast China. All of them underwent common thalassemia gene testing using the DNA reverse dot-blot hybridization technology. Subjects who were suspected as rare thalassemia carriers were further subjected to TGS to identify rare or novel α- and β-globin gene variants, and the results were verified by Sanger sequencing and/or gap PCR. Results Of the 6,174 included subjects, 2,390 (38.71%) were identified as α- and β-globin gene mutation carriers, including 40 carrying rare or novel α- and β-thalassemia mutations. The αCD30(−GAG)α and Hb Lepore-Boston-Washington were first reported in Fujian province Southeast China. Moreover, the βCD15(TGG> TAG), βIVS−II−761, β0-Filipino(~ 45 kb deletion), and Hb Lepore-Quanzhou were first identified in the Chinese population. In addition, 35 cases of Hb variants were detected, the rare Hb variants of Hb Jilin and Hb Beijing were first reported in Fujian province of China. Among them, one case with compound αααanti3.7 and Hb G-Honolulu variants was identified in this study. Conclusion Our findings may provide valuable data for enriching the spectrum of thalassemia and highlight the clinical application value of TGS-based α- and β-globin genetic testing.

Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)3 molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)3 endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.

Highlights By introducing fluorine modulation into MXene, a new MXene-derived material TiOF/Ti3C2 was successfully synthesized with a distinctive three-dimensional structure and a tailored F distribution. In situ characterizations and electrochemical analyses demonstrate that TiOF/Ti3C2 catalysts effectively coupled the multiphase sulfur species conversion processes. The investigations reveal that the theoretical basis of the fluorine catalysis in Li–S batteries originated from Lewis acid–base mechanisms and charge compensation mechanisms.

Abstract Feeding behavior, the most fundamental physiological activity, is controlled by two opposing groups of factors, orexigenic and anorexigenic factors. The sulfakinin family, an insect analogue of the mammalian satiety factor cholecystokinin (CCK), has been shown to suppress food intake in various insects. Nevertheless, the mechanisms through which sulfakinin regulates feeding behavior remain a biological question. This study aimed to elucidate the signaling pathway mediated by the anorexigenic peptide sulfakinin in Bombyx mori. We identified the Bombyx mori neuropeptide G protein-coupled receptor A9 (BNGR-A9) as the receptor for sulfakinin through functional assays. Stimulation with sulfakinin triggered a swift increase in intracellular IP3, Ca2+, and a notable enhancement of ERK1/2 phosphorylation, in a manner sensitive to a Gαq-specific inhibitor. Treatment with synthetic sulfakinin resulted in decreased food consumption and average body weight. Additionally, administering synthetic sulfakinin to silkworms significantly elevated hemolymph trehalose levels, an effect markedly reduced by pre-treatment with BNGR-A9 dsRNA. Consequently, our findings establish the sulfakinin/BNGR-A9 signaling pathway as a critical regulator of feeding behavior and hemolymph trehalose homeostasis in Bombyx mori, highlighting its roles in the negative control of food intake and the positive regulation of energy balance.

Abstract Background Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. Methods RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. Results COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. Conclusions The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE–COVID-19 comorbidity.

Abstract The porcine epidemic diarrhea virus (PEDV) infection inflicted substantial economic losses upon the global pig-breeding industry. This pathogen can infect all pigs and poses a particularly high fatality risk for suckling piglets. The S1 subunit of spike protein is a crucial target protein for inducing the particularly neutralizing antibodies that can intercept the virus-host interaction and neutralize virus infectivity. In the present study, the HEK293F eukaryotic expression system was successfully utilized to express and produce recombinant S1 protein. Through quantitative analysis, five monoclonal antibodies (mAbs) specifically targeting the recombinant S1 protein of PEDV were developed and subsequently evaluated using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and flow cytometry assay (FCA). The results indicate that all five mAbs belong to the IgG1 isotype, and their half-maximal effective concentration (EC50) values measured at 84.77, 7.42, 0.89, 14.64, and 7.86 pM. All these five mAbs can be utilized in ELISA, FCA, and IFA for the detection of PEDV infection. MAb 5-F9 exhibits the highest sensitivity to detect as low as 0.3125 ng/mL of recombinant PEDV-S1 protein in ELISA, while only 0.096 ng/mL of mAb 5-F9 is required to detect PEDV in FCA. The results from antigen epitope analysis indicated that mAb 8-G2 is the sole antibody capable of recognizing linear epitopes. In conclusion, this study has yielded a highly immunogenic S1 protein and five high-affinity mAbs specifically targeting the S1 protein. These findings have significant implications for early detection of PEDV infection and provide a solid foundation for further investigation into studying virus-host interactions.

Background: The carrying rate of thalassemia is high in Quanzhou city. However, there are few large-scale studies on the correlation analysis between genotype and phenotype of thalassemia in Quanzhou. In this study, the genotype and phenotype data of 1076 individuals with thalassemia in Quanzhou city were analyzed to provide reference data for screening and diagnosis of thalassemia in this region. Material and methods: Reverse dot blot hybridization (RDB-PCR), Gap-PCR and nested PCR were used to detect the thalassemia genotype. Clinical and hematological parameters of 1076 individuals of thalassemia were collected to analyze the correlation between genotype and phenotype. Results: Among 2997 subjects, 1076 cases diagnosed as thalassemia gene carrier or patients, with detection rate 35.9 %, among which Southeast Asian deletion (--SEA)/αα was the most common α-thalassemia genotype (48.4 %) and one rare genotype was detected: HKαα/--SEA (0.1 %). Subjects with thalassemia alone showed the least severe symptoms of anemia with higher red blood cell count (RBC) and hemoglobin (Hb), lower red blood cell distribution width (RDW) than those with iron deficiency (ID) or iron overload (IO) (p

Background: The incidence of a disease can help health professionals to identify risk factors and health-care policymakers to develop corresponding policies. The realization of both purposes depends on comprehensive studies, especially studies done on a large scale. However, comprehensive studies on the incidence of anaphylaxis among inpatients in China are still notably scarce. Hence we aim to explore the incidence and clinical characteristics of anaphylaxis among inpatients over a span of 21 years in Wuhan, China. Methods: We retrieved data on anaphylaxis cases from the Data Platform Application Portal (DPAP) across 3 medical centers of Tongji Hospital, Wuhan, China from January 1, 2003, to December 31, 2023. Results: The data encompassed a total of 362 anaphylaxis patients from 2,139,272 inpatients. Among them 204 (56.4%) were male, and the median age was 45 years old. Over the past 2 decades, the incidence rate of anaphylaxis at Tongji Hospital was 16.92 per 100,000 individuals. After adjusting for gender and age, the annual standardized incidence rate was 234.53 per 100,000 individuals. The incidence rate of anaphylaxis among the inpatients revealed a relatively stable but slowly rising trend over the 21-year observation period. As for the triggers of anaphylaxis, drugs were responsible for 73.6% of triggers, with antibiotics representing the highest proportion of these cases (38.4%). Drug triggers also showed age-specific features: chemotherapy (17.9%) had the highest proportions among children aged 0–3 years; blood products were more prevalent in school-age children. 13.5% of the cases had an unknown cause. In anaphylaxis cases, despite that only 36.0% received epinephrine treatment, the application of epinephrine still showed an ascending trend. Moreover, the mortality rate for anaphylaxis was relatively low (1.6%), displaying a consistent downward trend. Conclusion: Our study provides insights into the incidence of anaphylaxis among inpatients in Wuhan over a 21-year period. Drugs are the most common triggers for anaphylaxis, and the use of epinephrine in anaphylaxis management is far from optimal.

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Significantly activated uridine nucleotide and fatty acid metabolism in HCC cells promote malignant proliferation and immune evasion. Herein, it is demonstrated that the tripartite motif 65 (TRIM65) E3 ubiquitin‐protein ligase, O‐GlcNAcylated via O‐GlcNAcylation transferase, is highly expressed in HCC and facilitated metabolic remodeling to promote the accumulation of products related to uracil metabolism and palmitic acid, driving the progression of HCC. Mechanistically, it is showed that TRIM65 mediates ubiquitylation at the K44 residue of neurofibromatosis type 2 (NF2), the key protein upstream of classical Hippo signaling. Accelerated NF2 degradation inhibits yes‐associated protein 1 phosphorylation, inducing aberrant activation of related metabolic enzyme transcription, and orchestrating metabolic and immune advantages. In conclusion, these results reveal a critical role for the TRIM family molecule TRIM65 in supporting HCC cell survival and highlight the therapeutic potential of targeting its E3 ligase activity to alter the regulation of proteasomal degradation.

ABSTRACT The vaginal microbiome (VM) is associated with human papillomavirus (HPV) infection and progression, but a thorough understanding of the relation between HPV infection, and VM needs to be elucidated. From August to December 2022, women who underwent routine gynecological examinations were screened for HPV infection. The distribution of HPV variants and clinical characteristics were collected. Then, a total of 185 participants were enrolled and divided into HPV-negative (HC), high-risk HPV (H), low-risk HPV (L), multiple high-risk HPV (HH), and mixed high-low risk HPV (HL) groups. Samples were collected from the mid-vagina of these 185 participants and sent for 16S rDNA sequencing (V3–V4 region). Among 712 HPV-positive women, the top 3 most frequently detected genotypes were HPV52, HPV58, and HPV16. Among 185 participants in the microbiology study, the β diversity of the HC group was significantly different from HPV-positive groups (P < 0.001). LEfSe analysis showed that Lactobacillus iners was a potential biomarker for H group, while Lactobacillus crispatus was for L group. Regarding HPV-positive patients, the α diversity of cervical lesion patients was remarkably lower than those with normal cervix (P < 0.05). Differential abundance analysis showed that Lactobacillus jensenii significantly reduced in cervical lesion patients (P < 0.001). Further community state type (CST) clustering displayed that CST IV was more common than other types in HC group (P < 0.05), while CST I was higher than CST IV in H group (P < 0.05). Different HPV infections had distinct vaginal microbiome features. HPV infection might lead to the imbalance of Lactobacillus spp. and cause cervical lesions.IMPORTANCEIn this study, we first investigated the prevalence of different HPV genotypes in south China, which could provide more information for HPV vaccinations. Then, a total of 185 subjects were selected from HPV-negative, high-risk, low-risk, multiple hr-hr HPV infection, and mixed hr-lr HPV infection populations to explore the vaginal microbiome changes. This study displayed that HPV52, HPV58, and HPV16 were the most prevalent high-risk variants in south China. In addition, high-risk HPV infection was featured by Lactobacillus iners, while low-risk HPV infection was by Lactobacillus crispatus. Further sub-group analysis showed that Lactobacillus jensenii was significantly reduced in patients with cervical lesions. Finally, CST clustering showed that CST IV was the most common type in HC group, while CST I accounted the most in H group. In a word, this study for the first time systemically profiled vaginal microbiome of different HPV infections, which may add bricks to current knowledge on HPV infection and lay the foundation for novel treatment/prevention development.

Background: The incidence of muscle atrophy or sports injuries is increasing with time and population aging, thereby attracting considerable attention to muscle generation research. Muscle satellite cells, which play an important role in this process, lack comprehensive literature regarding their use for muscle regeneration. Hence, this study aimed to analyze the hotspots and trends in satellite cell research from 2010 to 2023, providing a reference for muscle regeneration research. Methods: Studies on satellite cells’ role in muscle regeneration from 2010 to 2023 were retrieved from the Web of Science Core Collection. Using CiteSpace and VOSviewer, we analyzed annual publications, authors and co-citing authors, countries and institutions, journals and co-citing journals, co-citing references, and keywords. Results: From 2010 to 2023, 1468 papers were retrieved, indicating an overall increasing trend in the number of annual publications related to satellite cells in muscle regeneration. The United States had the highest number of publications, while the Institut National de la Santé et de la Recherche Médicale was the institution with the most publications. Among journals, '' PloS One'' had the highest number of published papers, and ''Cell'' emerged as the most co-cited journal. A total of 7425 authors were involved, with Michael A. Rudnicki being the author with the highest number of publications and the most co-cited author. The most cited reference was ''Satellite cells and the muscle stem cell niche.'' Among keywords, “satellite cells” was the most common, with ''heterogeneity'' having the highest centrality. Frontier themes included ''Duchenne muscular dystrophy,” ''skeletal muscle,” ''in-vivo,” ''muscle regeneration,” ''mice,'' ''muscle atrophy,” ''muscle fibers,” ''inflammation,” '' mesenchymal stem cells,” and ''satellite cell.'' Conclusion: This study presents the current status and trends in satellite cell research on muscle regeneration from 2010 to 2023 using bibliometric analyses, providing valuable insights into numerous future research directions.

Background Adverse left ventricular remodeling is a significant cardiovascular predictor for patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF). However, the remodeling indexes reflecting left ventricular spherization by myocardial perfusion imaging are underexplored. Methods and Results 727 patients (mean age 59.8±13.5 years, 329 women) diagnosed or suspected coronary artery disease with preserved LVEF who underwent resting myocardial perfusion imaging were retrospectively enrolled. The myocardial perfusion imaging findings including the total perfusion deficit and sphericity indexes (shape index (SI) and eccentricity index (EI) obtained from gated (QGS) and non‐gated (QPS) images) were collected. Major adverse cardiovascular events (MACE) were followed up for 45.1±22.0 months. All patients were divided into 4 subgroups based on total perfusion deficit at 10% and LVEF at 65%. Univariable comparative analyses were performed in 5 cohorts (all patients and 4 subgroups). Patients who experienced MACE displayed higher SI and/or lower EI (all P

Summary: Universal coatings with versatile surface adhesion, good mechanochemical robustness, and the capacity for secondary modification are of great scientific interest. However, incorporating these advantages into a system is still a great challenge. Here, we report a series of catechol-decorated polyallylamines (CPAs), denoted as pseudo-Mytilus edulis foot protein 5 (pseudo-Mefp-5), that mimic not only the catechol and amine groups but also the backbone of Mefp-5. CPAs can fabricate highly adhesive, robust, multifunctional polyCPA (PCPA) coatings based on synergetic catechol-polyamine chemistry as universal building blocks. Due to the interpenetrating entangled network architectures, these coatings exhibit high chemical robustness against harsh conditions (HCl, pH 1; NaOH, pH 14; H2O2, 30%), good mechanical robustness, and wear resistance. In addition, PCPA coatings provide abundant grafting sites, enabling the fabrication of various functional surfaces through secondary modification. Furthermore, the versatility, multifaceted robustness, and scalability of PCPA coatings indicate their great potential for surface engineering, especially for withstanding harsh conditions in multipurpose biomedical applications.

Heparin-induced thrombocytopenia thrombosis (HITT) is a rare and potentially life-threatening complication after abdominal surgery, and it always occurs after the prophylactic or therapeutic use of heparin. HITT after pancreaticoduodenectomy (PD) has not been reported before. Herein, we reported a case of HITT after PD without prophylactic or therapeutic use of heparin. A 74-year-old female patient who suffered resectable pancreatic head cancer was transferred to our center for surgery. An open PD procedure was performed, and the operation was smooth. No heparin was used after surgery. Nine days after surgery, the platelet sharply declined to 48 × 109/L (100–350), and the D-dimer soared up to 33.56 mg/L (0–0.55). Ultrasound examination showed vein thrombosis in both the lower limb and the right upper limb. HIT-antibody was 6.3 U/mL (0–0.6). The diagnosis of HITT was confirmed. Fondaparinux was used. On postoperative day (POD) 23, the platelet recovered to the normal range. On POD 27, she was discharged without thromboembolism or active bleeding, and oral rivaroxaban was prescribed. One month after discharge, the platelet remained normal, and she did not complain of discomfort.

Thrombus formation and tissue embedding significantly impair the clinical efficacy and retrievability of temporary interventional medical devices. Herein, we report an insect sclerotization-inspired antifouling armor for tailoring temporary interventional devices with durable resistance to protein adsorption and the following protein-mediated complications. By mimicking the phenol-polyamine chemistry assisted by phenol oxidases during sclerotization, we develop a facile one-step method to crosslink bovine serum albumin (BSA) with oxidized hydrocaffeic acid (HCA), resulting in a stable and universal BSA@HCA armor. Furthermore, the surface of the BSA@HCA armor, enriched with carboxyl groups, supports the secondary grafting of polyethylene glycol (PEG), further enhancing both its antifouling performance and durability. The synergy of robustly immobilized BSA and covalently grafted PEG provide potent resistance to the adhesion of proteins, platelets, and vascular cells in vitro. In ex vivo blood circulation experiment, the armored surface reduces thrombus formation by 95 %. Moreover, the antifouling armor retained over 60 % of its fouling resistance after 28 days of immersion in PBS. Overall, our armor engineering strategy presents a promising solution for enhancing the antifouling properties and clinical performance of temporary interventional medical devices.

Aqueous multivalent ion batteries have attracted increasing attention due to their high capacity, long cycle life, and impressive output energy. Considering that intercalation electrodes are more suitable for long cycle battery compared to the conversion ones, Cu2+ with appropriate ion radii has been chosen as intercalation carriers and bismuth sulfide with the matched lattice spacing as cathode to achieve long cycle life aqueous battery. We have synthesized the micrometer-scale flower-like Bi2S3 by regulating temperature and it is proved to be a perennial phase during Cu2+ intercalation/deintercalation of the Bi2S3 host when charge/discharge with a capacity of 104.5 mAh g–1 retention at 0.5 A g–1 after 1000 cycles. Lastly, build a hybrid ion battery with Zn and ZnSO4 electrolyte, the Bi2S3 cathode for Cu2+ intercalation can reach a maximum energy of 427.5 Wh Kg–1. The study provides a new intercalation cathode for aqueous multivalent ion batteries and will broaden the energy storage system.

Abstract Epidemiological investigations indicate that parental drug abuse experiences significantly influenced the addiction vulnerability of offspring. Studies using animal models have shown that paternal cocaine use and highly motivated drug-seeking behavior are important determinants of offspring addiction susceptibility. However, the key molecules contributing to offspring addiction susceptibility are currently unclear. The motivation for cocaine-seeking behavior in offspring of male rats was compared between those whose fathers self-administered cocaine (SA) and those who were yoked with them and received non-contingent cocaine administrations (Yoke). We found that paternal experience with cocaine-seeking behavior, but not direct cocaine exposure, could lead to increased lever-pressing behavior in male F1 offspring. This effect was observed without significant changes to the dose-response relationship. The transcriptomes of ventral tegmental area (VTA) in offspring were analyzed under both naive state and after self-administration training. Specific transcriptomic changes in response to paternal cocaine-seeking experiences were found, which mainly affected biological processes such as synaptic connections and receptor signaling pathways. Through joint analysis of these candidate genes and parental drug-seeking motivation scores, we found that gamma-aminobutyric acid receptor subunit gamma-3 (Gabrg3) was in the hub position of the drug-seeking motivation-related module network and highly correlated with parental drug-seeking motivation scores. The downregulation of Gabrg3 expression, caused by paternal motivational cocaine-seeking, mainly occurred in GABAergic neurons in the VTA. Furthermore, down-regulating GABAergic Gabrg3 in VTA resulted in an increase in cocaine-seeking behavior in the Yoke F1 group. This down-regulation also reduced transcriptome differences between the Yoke and SA groups, affecting processes related to synaptic formation and neurotransmitter transmission. Taken together, we propose that paternal cocaine-seeking behavior, rather than direct drug exposure, significantly influences offspring addiction susceptibility through the downregulation of Gabrg3 in GABAergic neurons of the VTA, highlighting the importance of understanding specific molecular pathways in the intergenerational inheritance of addiction vulnerability.

Abstract It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.

Objective: Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression. How neutrophils promote lung cancer progression, however, has not been established. Methods: Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer patients. The effect of neutrophils on lung cancer was determined using the Transwell migration assay, a proliferation assay, and a murine tumor model. Gene knockdown was used to determine poly ADP-ribose polymerase (PARP)-1 function in lung cancer-educated neutrophils. Western blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9 (MMP-9). Immunoprecipitation coupled to mass spectrometry (IP/MS) was used to identify the proteins interacting with PARP-1. Co-immunoprecipitation (Co-IP) was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase (ALOX5). Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer progression. Results: An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients (P < 0.001). Neutrophil activation promoted lung cancer cell invasion, migration, and proliferation in vitro, and murine lung cancer growth in vivo. Mechanistically, PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification (PARylation). Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production, and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor growth. Conclusion: We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression, which exacerbates lung cancer progression.

Proteins, cells and bacteria adhering to the surface of medical devices can lead to thrombosis and infection, resulting in significant clinical mortality. Here, we report a zwitterionic polymers-armored amyloid-like protein surface engineering strategy we called as “armored-tank” strategy for dual functionalization of medical devices. The “armored-tank” strategy is realized by decoration of partially conformational transformed LZM (PCTL) assembly through oxidant-mediated process, followed by armoring with super-hydrophilic poly-2-methacryloyloxyethyl phosphorylcholine (pMPC). The outer armor of the “armored-tank” shows potent and durable zone defense against fibrinogen, platelet and bacteria adhesion, leading to long-term antithrombogenic properties over 14 days in vivo without anticoagulation. Additionally, the “fired” PCTL from “armored-tank” actively and effectively kills both Gram-positive and Gram-negative bacterial over 30 days as a supplement to the lacking bactericidal functions of passive outer armor. Overall, this “armored-tank” surface engineering strategy serves as a promising solution for preventing biofouling and thrombotic occlusion of medical devices.

Abstract Background Colorectal cancer (CRC) is one of the most common malignancies and is characterized by reprogrammed metabolism. Ferroptosis, a programmed cell death dependent on iron, has emerged as a promising strategy for CRC treatment. Although small nucleolar RNAs are extensively involved in carcinogenesis, it is unclear if they regulate ferroptosis during CRC pathogenesis. Methods The dysregulated snoRNAs were identified using published sequencing data of CRC tissues. The expression of the candidate snoRNAs, host gene and target gene were assessed by real-time quantitative PCR (RT-qPCR), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and western blots. The biological function of critical molecules was investigated using in vitro and in vivo strategies including Cell Counting Kit-8 (CCK8), colony formation assay, flow cytometry, Fe2+/Fe3+, GSH/GSSG and the xenograft mice models. The ribosomal activities were determined by polysome profiling and O-propargyl-puromycin (OP-Puro) assay. The proteomics was conducted to clarify the downstream targets and the underlying mechanisms were validated by IHC, Pearson correlation analysis, protein stability and rescue assays. The clinical significance of the snoRNA was explored using the Cox proportional hazard model, receiver operating characteristic (ROC) and survival analysis. Results Here, we investigated the SNORA56, which was elevated in CRC tissues and plasma, and correlated with CRC prognosis. SNORA56 deficiency in CRC impaired proliferation and triggered ferroptosis, resulting in reduced tumorigenesis. Mechanistically, SNORA56 mediated the pseudouridylation of 28 S rRNA at the U1664 site and promoted the translation of the catalytic subunit of glutamate cysteine ligase (GCLC), an indispensable rate-limiting enzyme in the biosynthesis of glutathione, which can inhibit ferroptosis by suppressing lipid peroxidation. Conclusions Therefore, the SNORA56/28S rRNA/GCLC axis stimulates CRC progression by inhibiting the accumulation of cellular peroxides, and it may provide biomarker and therapeutic applications in CRC.

Despite the interaction between polyphenols and polysaccharides in food products, their specific non-covalent interactions and effects on macrophage functions are not well understood. Therefore, the interaction and mechanism of purified lotus root polysaccharide (PLRP) with polyphenols, and the regulatory mechanisms of the PLRP-polyphenol complex on the macrophage functionals were studied. By combining ferulic acid (FA) and chlorogenic acid (CHA) with PLRP, the complexes PLRP-FA, PLRP-CHA and the physical mixtures PLRP&FA and PLRP&CHA were prepared, where their mass ratios of polyphenols to PLRP were 143.97 and 601.67 mg g−1. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Ultraviolet (UV), and Transmission electron microscopy (TEM) analyses confirmed that PLRP and polyphenols may engage in non-covalent interactions via hydrogen bonds and hydrophobic interactions. We confirmed that non-covalent interactions led to high molecular weight, dense complexes. Both PLRP and its polyphenol complexes stimulated NO production by macrophages to varying degrees without exacerbating lipopolysaccharide-induced inflammatory responses. PLRP and PLRP-polyphenol complexes repaired cells with impaired antioxidant capacity, depending on doses. Those results indicated that after the combination of lotus root polysaccharide and polyphenol, the molecular weight and conformation changed significantly, which influenced the biological activity. RNA-seq analysis suggested that the regulatory mechanism of PLRP-polyphenol complex in macrophages may mainly involve oxidative phosphorylation, FoxO, TNF, IL-17, MAPK, NF-kappa B, and other signaling pathways. This study investigated the effects of polyphenol binding on the physicochemical characteristics and functional activities of polysaccharides, which provided references for the development of polysaccharide functional products and the control of nutritional quality.

The giant magnetoresistance effect in two-dimensional (2D) magnetic materials has sparked substantial interest in various fields; including sensing; data storage; electronics; and spintronics. Their unique 2D layered structures allow for the manifestation of distinctive physical properties and precise performance regulation under different conditions. In this review, we present an overview of this rapidly developing research area. Firstly, these 2D magnetic materials are catalogued according to magnetic coupling types. Then, several vital effects in 2D magnets are highlighted together with theoretical investigation, such as magnetic circular dichroism, magneto-optical Kerr effect, and anomalous Hall effect. After that, we forecast the potential applications of 2D magnetic materials for spintronic devices. Lastly, research advances in the attracting magnons, skyrmions and other spin textures in 2D magnets are discussed.

ObjectiveThis study aimed to systematically evaluate the efficacy and safety of the double-guidewire technique along with other methods (persistent standard cannulation techniques, transpancreatic sphincterotomy, and pancreatic stent-assisted technique) for difficult biliary cannulation.MethodsTwo researchers searched for literature on the efficacy and safety of the double-guidewire technique and other techniques in difficult biliary cannulation in databases, including PubMed, Embase, Cochrane, China National Knowledge Infrastructure, and Wanfang Data, based on the inclusion and exclusion criteria. The success rate of cannulation, duration of cannulation, post-ERCP pancreatitis, and overall postoperative complications were also analyzed using RevMan 5.4 software.ResultsIn total, 20 randomized controlled trial (RCT) studies involving 2008 participants were identified. The success rate of cannulation in the double-guidewire technique was much higher than that in persistent standard cannulation techniques [RR = 1.37, 95%CI (1.05, 1.79), p = 0.02]. However, it was lower than the success rate observed with transpancreatic sphincterotomy [RR = 0.89, 95%CI (0.81, 0.97), p = 0.01]. There was no significance in post-ERCP pancreatitis [RR = 1.09, 95% CI (0.85, 1.40), p = 0.49], overall postoperative complications [RR = 0.90, 95% CI (0.56, 1.45), p = 0.66], and duration of cannulation [SMD = -0.14, 95%C I (−1.43, 1.15), p = 0.83] between the double-guidewire technique and other techniques.ConclusionThis study demonstrated that the success rate of cannulation ranged from transpancreatic sphincterotomy to the double-guidewire technique and then to persistent standard cannulation techniques.

Objectives: We explored the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of atopic dermatitis (AD).Methods: We downloaded RNA-seq data (GSE121212) from 10 healthy control skin samples (healthy, Ctrl), 10 non-lesional skin samples with AD damage (non-lesional, NL), and 10 lesional skin samples with AD damage (lesional, LS). We performed the analysis of differentially expressed genes (DEGs), differentially expressed RBPs (DE-RBPs), alternative splicing (AS), functional enrichment, the co-expression of RBPs and RASEs, and quantitative polymerase chain reaction (qPCR).Results: We identified 60 DE-RBP genes by intersecting 2141 RBP genes from existing reports with overall 2697 DEGs. Most of the DE-RBP genes were found to be upregulated in the AD LS group and related to immune and apoptosis pathways. We observed different ASEs and RASEs among the healthy, AD NL, and AD LS groups. In particular, alt3p and alt5p were the main ASEs and RASEs in AD NL and AD LS groups, compared to the healthy group. Furthermore, we constructed co-expression networks of DE-RBPs and RAS, with particular enrichment in biological pathways including cytoskeleton organization, inflammation, and immunity. Subsequently, we selected seven genes that are commonly present in these three pathways to assess their expression levels in the peripheral blood mononuclear cells (PBMCs) from both healthy individuals and AD patients. The results demonstrated the upregulation of four genes (IFI16, S100A9, PKM, and ENO1) in the PBMCs of AD patients, which is highly consistent with DE-RBP genes analysis. Finally, we selected four RAS genes regulated by RBPs that were related to immune pathways and examined their RASEs in PBMCs from both AD patients and healthy controls. The results revealed an increased percentage of RASEs in the DDX60 gene in AD, which is highly consistent with AS analysis.Conclusion: Dysregulated RBPs and their associated RASEs may have a significant regulatory role in the development of AD and could be potential therapeutic targets in the future.

Background: The prevalence of food allergy (FA) has risen in recent decades, yet there is limited data on the cognition and beliefs of FA among the parents of FA children. Objective: To investigate the prevalence of FA and assess the knowledge and perception of FA among parents of FA children in Wuhan, China. Methods: Online questionnaires were conducted for the parents of 3- to 16-year-old children. They reported symptoms of suspected FA in the screening questionnaire were interviewed for further diagnostic evaluation. All the parents of the suspected FA children completed the subsequent assessments of the knowledge and perception on FA as well as their attitude towards the current online platforms. Results: A total of 1963 children were recruited. The prevalence of self-reported FA was 10.2% (95% CI: 8.1–12.4%) and the physician-diagnosed FA was 6.2% (95% CI: 5.1–7.2%) in 3- to 16-year-olds in Wuhan. And the children with family history (57.9%) were predisposed to developing FA (P＜0.001). The total Brief Illness Perception Questionnaire (B-IPQ) score was 41.3 ± 10.0 among the parents. The B-IPQ scores correlated with symptom onset, but not with family history or other atopic comorbidities. The parents who never sought treatments obtained lower B-IPQ scores on most items compared to those who received treatments. The accuracy rate of the FA knowledge questionnaire was 56.7%. 11.6% of participants reported that children's FA had an impact on their lives. 67.2% of participants had searched information of FA online, among whom 80% expected to obtain professional suggestions on management and prevention strategies of FA from online platform. Conclusion: In 3- to 16-year-old children in Wuhan, the prevalence of self-reported and physician-diagnosed FA was 10.2% and 6.2% respectively. Parents’ knowledge of FA was insufficient and only a small proportion of parents perceived that their lives and careers have been affected considerably by FA of their children. Patient education and current online platforms should be improved among parents of FA children.

Abstract To determine the risk factors for dilated cardiomyopathy (DCM) and construct a risk model for predicting HF in patients with DCM, We enrolled a total of 2122 patients, excluding those who did not meet the requirements. A total of 913 patients were included in the analysis (611 males and 302 females) from October 2012 to May 2020, and data on demographic characteristics, blood biochemical markers, and cardiac ultrasound results were collected. Patients were strictly screened for DCM based on the diagnostic criteria. First, these patients were evaluated using propensity score matching (PSM). Next, unconditional logistic regression was used to assess HF risk. Furthermore, receiver operating characteristic (ROC) curve analysis was conducted to determine diagnostic efficiency, and a nomogram was developed to predict HF. Finally, the Kaplan‒Meier survival curve was plotted. Of the initial 2122 patients, the ejection fraction (EF) in males was worse. We included 913 patients after the final DCM diagnosis. The results showed that the levels of NT-proBNP, WBC, PLT, neutrophils, lymphocytes, eosinophils, and IL-6, C-reactive protein (CRP) and the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CRP/lymphocyte ratio (CLR) were higher in males than in females (P

Abstract Pig producers have faced considerable economic losses due to porcine epidemic diarrhea virus (PEDV) infection, emphasizing the need for PEDV antibody development. The S1/S2 junction (S1S2J) cleavage site of the S protein of PEDV is one of the major determinants of coronavirus infection success. In this study, we specifically selected the S1S2J protein of PEDV-AJ1102 (a representative strain of the G2 type) as a target protein to immunize mice and generated monoclonal antibodies (mAbs) using hybridoma technology. Three mAbs with high-binding activities to the S1S2J protein and were obtained and further analyzed. To reveal the characterization of these mAbs, variable region genes of antibodies were studied by using DNA sequencing, thereby revealing differences in their CDR3 amino acid sequences. We then developed a new method to identify the isotypes of these three mAbs. Results showed that these three antibodies were of the IgM type. As for the functions of these three mAbs, indirect immunofluorescence assay confirmed their good binding ability to Vero E6 cells infected with the PEDV-SP-C strain (G1 type). Epitope analysis showed linear epitopes for all three mAbs. These antibodies were also used to detect infected cells via flow cytometry analysis. In summary, we prepared and examined three mAbs against PEDV-S1S2J. These mAbs can be employed as detection antibodies for diagnostic reagents and further developed for other applications. We also designed a novel technique for easy and cost-saving identification of isotypes of mouse mAbs. Our results lay a good foundation for the development of research on PEDV.

Control of premature corrosion of magnesium (Mg) alloy bioresorbable stents (BRS) is frequently achieved by the addition of rare earth elements. However, limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after. Herein, we report a “built-up” composite film consisting of a bottom layer of MgF2 conversion coating, a sandwich layer of a poly (1, 3-trimethylene carbonate) (PTMC) and 3-aminopropyl triethoxysilane (APTES) co-spray coating (PA) and on top a layer of poly (lactic-co-glycolic acid) (PLGA) ultrasonic spray coating to decorate the rare earth element-free Mg–2Zn–1Mn (ZM21) BRS for tailoring both corrosion resistance and biological functions. The developed “built-up” composite film shows synergistic functionalities, allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling. Of special importance is that the synergistic corrosion control effects of the “built-up” composite film allow for maintaining the mechanical integrity of stents for up to 3 months, where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries. Moreover, the functionalized ZM21 BRS accomplished re-endothelialization within one month.

Clarifying the driving mechanisms of spatial and temporal changes in the regulating ecosystem service value (RESV) is an important part of realizing the goal of sustainable development. Existing studies have focused on specific factors, ignoring the complex interactions between factors and their regional differences. In this regard, the spatial and temporal changes of RESV and its driving mechanisms in the different zones (core area, fringe area, and peripheral area) were explored in the Poyang Lake Area, China. The results showed that RESV spatially showed the distribution characteristics of fringe area > core area > peripheral area, while the lakes influenced the provision of regulating ecosystem services, showing that RESV per unit area was higher in the core area, and gradually declined with the increase of distance from the lakes, presenting the decreasing trend of fringe area > peripheral area. From 2000 to 2020, the study area lost 70.5988 billion CNY for RESV, in which the core area was the most affected. Further analysis of the driving mechanism of RESV in different areas found that there are regional differences in the paths of the driving factors: Population density mainly affects the core area, precipitation mainly affects the fringe area, and GDP per land mainly affects the peripheral area.

Thrombosis and infection are 2 major complications associated with central venous catheters (CVCs), resulting in substantial mortality and morbidity. The concurrent long-term administration of antibiotics and anticoagulants to address these complications have been demonstrated to cause severe side effects such as antibiotic resistance and bleeding. To mitigate these complications with minimal or no drug utilization, we developed a bioinspired zwitterionic block polymer-armored nitric oxide (NO)-generating functional coating for surface modification of CVCs. This armor was fabricated by precoating with a Cu-dopamine (DA)/selenocysteamine (SeCA) (Cu-DA/SeCA) network film capable of catalytically generating NO on the CVCs surface, followed by grafting of a zwitterionic p(DMA-b-MPC-b-DMA) polymer brush. The synergistic effects of active attack by NO and copper ions provided by Cu-DA/SeCA network and passive defense by zwitterionic polymer brush imparted the CVCs surface with durable antimicrobial properties and marked inhibition of platelets and fibrinogen. The in vivo studies confirmed that the surface-armored CVCs could effectively reduce inflammation and inhibit thrombosis, indicating a promising potential for clinical applications.

The engineering of porous boron-doped diamond (BDD) film has sparked significant interest in improving electric double-layer (EDL) capacitance. However, the presence of disordered and tortuous pores in the BDD film hinders the accessibility of the bottom pore surface area, leading to a decrease in specific EDL capacitance. Herein, a novel porous BDD film with vertically open pore channels is constructed through the overcoating of diamond nanoplatelet template with a BDD layer using chemical vapor deposition. Electrochemical investigations manifest that the specific areal EDL capacitance of the porous BDD is ∼428 times greater than that of the planar BDD film. More impressively, the porous BDD film demonstrates a higher specific volumetric EDL capacitance (39.30 F/cm3) and superior long-term stability (100% capacitance retention after 12,000 cycles), surpassing the performance of most developed porous BDD electrodes. The exceptional performance of the porous BDD film was attributed to the abundant vertically open pore channels, good hydrophilic property, maximized electrochemical available area, and good chemical/mechanical stability. This work benefits the development of the BDD film as an EDL micro-capacitor electrode, and the methodology proposed here shows great potentials to fabricate an ordered porous BDD nanostructure with large specific area for more electrochemical applications.

As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.

Incorporating two-dimensional (2D) diamond nanosheets with fluorescent color centers exhibits great potential in the application of quantum sensing. However, color centers always show poor optical emission in chemical-vapor-deposited (CVD) diamond nanomaterials. To address this issue, Si doped diamond/graphite hybrid films were successfully fabricated in microwave-plasma CVD device. The films consist of diamond-core/graphite-shell nanosheets with high amount of diamond nanocrystalline particles. Two post treatments of acid oxidation and annealing in air were used to tailor photoluminescence (PL) of silicon-vacancy (SiV) centers. The SiV centers in the oxidized samples exhibit small PL increase compared with the as-deposited samples with SiV PL quenching. It is found that the graphite phase is selectively etched away with the presence of nanocrystalline diamond particles during the treatment of acid oxidation while the nanocrystalline diamond particles are efficiently removed with the presence of graphite using the air annealing method. Based on this result, a two-step approach of acid oxidation followed by air annealing was conducted to etch the non-diamond phase, forming diamond nanosheets. The SiV centers exhibit significant PL enhancement with a maximum value of 28 folds, compared with the single-step oxidized samples. The Raman and XPS results reveal that such PL increase originates from direct bonding of oxygen on the sp3 carbon. Therefore, our work provides a feasible approach to prepare 2D diamond nanosheets with high-brightness color centers.

Abstract Artificial molecular machines have captured the imagination of researchers, given their clear potential to mimic and influence human life. Key to behavior simulation is to reproduce the specific properties of physical or abstract systems. Dice throwing, as a stochastic model, is commonly used for result judgment or plan decision in real life. In this perspective we utilize DNA cube framework for the design of a dice device at the nanoscale to reproduce probabilistic events in different situations: equal probability, high probability, and low probability. We first discuss the randomness of DNA cube, or dice, adsorbing on graphene oxide, or table, and then explore a series of events that change the probability through the way in which the energy released from entropy-driven strand displacement reactions or changes in intermolecular forces. As such, the DNA nano-dice system provides guideline and possibilities for the design, engineering, and quantification of behavioral probability simulation, a currently emerging area of molecular simulation research.

Objective: Objective To analyze the differential expression and prognosis of Solute Carrier Family 47 Member 1 (SLC47A1) in human pan-cancer using bioinformatic methods to explore the prognostic value of SLC47A1 for human pan-cancer and to determine its immune regulatory role. Methods: The Cancer Genome Atlas (TCGA) pan-cancer database was used to analyze the diagnostic and prognostic value of SLC47A1, as well as its expression patterns. Pearson correlation analysis was used to evaluate the relationship between SLC47A1 and stromal scores, immune scores, tumor mutation burden (TMB), and microsatellite instability (MSI). The correlation between SLC47A1 and specific tumor immune subtypes was analyzed using the Tumor-Immune System Interactions Database (TISIDB). Analysis of differential methylation of SLC47A1 and prognostic analyses were performed using the Disease Meth and TCGA Pan-Cancer databases. Results: SLC47A1 was abnormally expressed in 17 tumors and shows low expression levels in 11 tumor tissues. Low expression of SLC47A1 was associated with poor prognosis and diagnosis. Moreover, SLC47A1 was also involved in tumor microenvironment regulation. SLC47A1 methylation was disordered in 15 tumors, and disordered methylation was associated with survival. Conclusion: Overall, these results indicate that SLC47A1 may serve as an important prognostic biomarker and may correlate with tumor immunity in human pan-cancer.

AIM: To detect the concentrations of reactive oxygen species (ROS), transient receptor potential mucin-1 (TRPML1), and autophagy-related (Atg) proteins (LC3-I, LC3-II, and Beclin1) in vitreous humor of patients with simple rhegmatogenous retinal detachment (RRD). METHODS: RRD patients enrolled as the RRD group, and patients with idiopathic macular hole (IMH) and idiopathic macular epiretinal membrane (IMEM) were enrolled as control group. The levels of ROS, TRPML1, LC3-I, LC3-II, and Beclin1 in vitreous humor of patients in the RRD and control groups were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The RRD group included 28 eyes 28 patients and had a higher concentration of ROS in vitreous humor (631.86±18.05 vs 436.34±108.22 IU/mL, P

Exploring the impact of economic modernization on carbon balance is an essential endeavor to achieve carbon neutrality and combat climate change. However, the spatial impact of economic modernization on carbon balance remains ambiguous. Therefore, this study aims to explore the spatial spillover effects of agricultural modernization, industrialization, and urbanization on carbon balance during the economic modernization process in China, taking 30 provinces and cities in China as examples from 2010 to 2021. This study utilizes the spatial Durbin model to derive the following results: In the past decade, the carbon balance ratio has shown a fluctuating and decreasing dynamic evolution trend. There is an increase in regions with serious carbon deficits. Further investigation into the spatial spillover effect of carbon balance unveils that for every 1% increase in the carbon balance ratio of a province, neighboring provinces experience a decrease of 0.833%. Additionally, the spatial spillover effects of the three modernizations in China on the carbon balance ratio behave differently. Agricultural modernization and urbanization demonstrate negative spatial spillover effects on the carbon balance in neighboring regions, while industrialization exerts a significant positive spatial spillover effect on the carbon balance of neighboring regions. Regarding control variables, the level of innovation solely contributes to local carbon balance realization without generating a trickle-down effect, whereas infrastructure development operates inversely. At the same time, there are differences in the spatial effects of agricultural modernization and industrialization on the carbon balance between the eastern region and the central and western regions. The study underscores the importance of economic modernization and development processes focusing on fostering synergistic growth between economic and environmental benefits within both local and neighboring areas.

Chips-based platforms intended for single-cell manipulation are considered powerful tools to analyze intercellular interactions and cellular functions. Although the conventional cell co-culture models could investigate cell communication to some extent, the role of a single cell requires further analysis. In this study, a precise intercellular interaction model was built using a microelectrode array [microelectrode array (MEA)]-based and dielectrophoresis-driven single-cell manipulation chip. The integrated platform enabled precise manipulation of single cells, which were either trapped on or transferred between electrodes. Each electrode was controlled independently to record the corresponding cellular electrophysiology. Multiple parameters were explored to investigate their effects on cell manipulation including the diameter and depth of microwells, the geometry of cells, and the voltage amplitude of the control signal. Under the optimized microenvironment, the chip was further evaluated using 293T and neural cells to investigate the influence of electric field on cells. An examination of the inappropriate use of electric fields on cells revealed the occurrence of oncosis. In the end of the study, electrophysiology of single neurons and network of neurons, both differentiated from human induced pluripotent stem cells (iPSC), was recorded and compared to demonstrate the functionality of the chip. The obtained preliminary results extended the nature growing model to the controllable level, satisfying the expectation of introducing more elaborated intercellular interaction models.

Diatoms are ecologically important phytoplankton as they contribute 40% of the marine primary production and play an essential role in the biogeochemical cycles of many elements. Ocean warming, as a pressing environmental stressor, can profoundly affect the population structure and ecological services of diatoms. However, the molecular mechanisms underpinning cellular and physiological changes of diatoms under heat wave and heat selection conditions remain underexplored. This study revealed the transcriptomic and physiological responses of a model diatom species P. tricornutum to ocean warming at an elevated temperature (25 °C in comparison with 20 °C) under scenarios of heat shock (∼7 days; ∼7 generations) and heat selection (∼175 days; ∼165 generations). While unchanged cell growth and reduced Fv/Fm were recorded in the heat shock treatment, significant reductions in the cell growth rate and Fv/Fm were evident in the heat selection treatment. Contents of Chl-a, carotenoid, total soluble protein, carbon (C), and nitrogen (N) increased significantly in both treatments. Transcriptomics analysis showed that elevated temperature suppressed signaling pathways related to photosynthesis but activated signaling pathways involving in fatty acid metabolism and nitrogen metabolism following the heat selection, associated with elevated substance storage and enlarged cell size. As a result, the increase of both C and N suggest that more energy was likely allocated to growth than division under ocean warming. Notably, P. tricornutum showed a higher resistance to nitrogen limitation condition after acclimating to ocean warming possibly by activation of nitrogen metabolism and uptake. P. tricornutum responded to the projected ocean warming through readjusting energy metabolism.

Abstract In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.

Background & Aims: Hepatoblastoma (HB) is a common pediatric malignant liver tumor that is characterized by a low level of genetic mutations. Alternative splicing (AS) has been shown to be closely associated with cancer progression, especially in tumors with a low mutational burden. However, the role of AS in HB remains unknown. Methods: Transcriptome sequencing was performed on 5 pairs of HB tissues and matched non-tumor tissues to delineate the AS landscape in HB. AS events were validated in 92 samples from 46 patients. RNA pull-down and RNA immunoprecipitation assays were carried out to identify splicing factors that regulate the AS of small nucleolar RNA host genes (SNHG). Patient-derived organoids (PDOs) were established to investigate the role of the splicing factor polyadenylate-binding nuclear protein 1 (PABPN1). Results: This study uncovered aberrant alternative splicing in HB, including lncRNAs from SNHG family that undergo intron retention in HB. Further investigations revealed that PABPN1, a significantly upregulated RNA binding protein, interacts with splicing machinery in HB, inducing the intron retention of these SNHG RNAs and the downregulation of intronic small nucleolar RNAs (snoRNAs). Functionally, PABPN1 acts as an oncofetal splicing regulator in HB by promoting cell proliferation and DNA damage repair via inducing the intron retention of SNHG19. Knock-down of PABPN1 increases the cisplatin sensitivity of HB PDOs. Conclusions: Our findings revealed the role of intron retention in regulating snoRNA expression in hepatoblastoma, explained detailed regulatory mechanism between PABPN1 and the intron retention of SNHG RNAs, and provided insight into the development of new HB treatment options.

Textureless building surfaces composed of homogenized pixels could lead to failure of photometric consistency. However, textureless regions widely present in artificial scenes usually exhibit strong planarity enabling depth estimation of textureless regions with planar priors. However, existing methods for generating planar priors suffer from oversegmentation of large planes with textureless regions, which indicates that planarity is not fully exploited. In this study, we propose a novel generation method of planar prior by combining mean-shift clustering and superpixel segmentation. The planarity is fully utilized given preferential generation of planar priors for large planes with textureless regions in artificial scenes. Finally, a probabilistic graphical model is used to adopt the planar priors and smoothing constraints into depth estimation process. The image gradient is used as a criterion of the degree of texture to adaptively adjust the weights of different constraints. Experimental results on the benchmark dataset ETH3D, UDD5, and SenseFly demonstrate that the proposed method can effectively recover the depth information of textureless regions in high-resolution images to obtain highly complete three-dimensional (3-D) models of artificial scenes.

With the expansion of the semiconductor industry, determining the huge associated water and energy consumption and accomplishing sustainable development can be key issues for this industry. This study surveyed the sustainability reports of 28 semiconductor corporations and summarized their environmental stewardship information. Overall, the total water withdrawal in 2021 was 7.89 ​× ​108 ​m3, total energy consumption was 1.49 ​× ​1011 ​kWh, and total greenhouse gas (GHG) emissions were 7.15 ​× ​107 tons CO2 equivalent. The total Scope 1 and Scope 2 GHG emissions were 2.74 and 4.41 ​× ​107 ​t CO2 equivalent, respectively. Surface water intake, municipal water supply, groundwater withdrawal, third party supply, and external reclaimed water intake accounted for 47.0%, 35.3%, 8.5%, 5.8%, and 3.2% of total water use, respectively. Electricity, fossil fuel, renewable energy, and others accounted for 83.7%, 12.0%, 2.7%, and 1.7% of the total energy use. In 2021, average water use, energy consumption, and GHG emissions were calculated to be 8.22 ​L/cm2, 1.15 ​kWh/cm2, and 0.84 ​kg CO2 equivalent/cm2, respectively, based on announced data. Ultrapure water consumption was predicted to be 5.51 and 0.95 ​× ​108 ​m3 worldwide and for China, respectively. Effective sustainability strategies are supposed to be implemented to meet the considerable growth in water and energy consumption and GHG emissions for the semiconductor industry worldwide and in China.

Semiconductor manufacturing is a rapidly growing industry and water-intensive industry. Water strategy formulation and decisions can be crucial factors in realizing the sustainable development of the semiconductor industry. This study surveyed the sustainability reports of 24 semiconductor corporations and investigated their water strategies and practices. Water targets proposed in the early stage of the 21st century are summarized. Water recycling, reuse, and restoration were the main strategies. Reverse osmosis played a dominant role in water treatment and reclamation. Classified wastewater collection and separate treatment systems have contributed greatly to improvement of water recycling rate in industrial parks. Finally, a future water cycle system for semiconductor manufacturing parks is proposed, which comprises water source, water use and recycling, and water discharge. This study is of theoretical and practical significance for the formulation and implementation of water strategies in the semiconductor industry to help accomplish its sustainable development with rapid growth.

Transforming growth factor-β (TGF-β) plays a critical role in regulating cell growth and differentiation. Epithelial to mesenchymal transition (EMT) induced by TGF-β promotes cancer cell migration, invasion, and proliferation. Pirfenidone (5-methyl-1-phenyl-2(1 H)-pyridone, PFD), an approved drug for treating pulmonary and renal fibrosis, is a potent TGF-β inhibitor and found reduced incidence of lung cancer and alleviated renal function decline. However, whether PFD plays a role in controlling renal cancer progression is largely unknown. In the present study, we demonstrated that high TGF-β1 expression was negatively associated with ten-year overall survival of patients with renal cancer. Functionally, blockade of TGF-β signaling with PFD significantly suppressed the progression of renal cancer in a murine model. Mechanistically, we revealed that PFD significantly decreased the expression and secretion of TGF-β both in vitro and in vivo tumor mouse model, which further prevented TGF-β-induced EMT and thus cell proliferation, migration, and invasion. Importantly, the downregulation of TGF-β upon PFD treatment shaped the immunosuppressive tumor microenvironment by limiting the recruitment of tumor-infiltrating MDSCs. Therefore, our study demonstrated that PFD prevents renal cancer progression by inhibiting TGF-β production of cancer cells and downstream signaling pathway, which might be presented as a therapeutic adjuvant for renal cancer.

In this paper, a new thermal energy storage (TES) scheme of basalt fiber bundles is proposed. This basalt fiber bundle TES tank adopts two-stage runner arrangement to increase the specific surface area and improve the heat exchange effect. Based on this, a variable flow rate and preheating control scheme is proposed to enhance the discharging stability. The results when the air initial flow rate is 1m/sshow that the two methods of automatically controlling the flow rate change and using two tanks in series to make full use of the waste heat can significantly increase the stable discharging time of the TES tank. The increase in the stable discharging time reached 115% with variable flow rate scheme. And the simultaneous use of variable flow and preheating control schemes can extend the stable discharging time to 166% of the constant flow scheme. This TES tank can provide a wide heating power range and the maximum discharging power per unit area reaches 1.005MW±1% when the initial flow rate is 1m/s. However, it is difficult for honeycomb and packed bed to achieve such output under the same flow rate. In short, this new scheme can realize the coexistence of high thermal energy storage density, strong stable discharging, small volume and high discharging power, and can be used in mobile thermal energy storage system to meet user groups with significant differences in heating demand.

Abstract An incomplete understanding of the cellular functions and underlying mechanisms of zinc ions released from zinc‐based stents in atherosclerosis (AS) therapy is one of the major obstacles to their clinical translation. The existing evaluation methodology using cell monolayers has limitations on accurate results due to the lack of vascular architectures and pathological features. Herein, the authors propose a 3D biomimetic AS model based on a multi‐layer vascular structure comprising endothelial cells and smooth muscle cells with hyperlipidemic surroundings and inflammatory stimulations as AS‐prone biochemical conditions to explore the biological functions of zinc ions in AS therapy. Concentration‐dependent biphasic effects of zinc ions on cell growth are observed both in cell monolayers and 3D AS models. Nevertheless, the cells within 3D AS model exhibit more accurate biological assessments of the zinc ions, as evidenced by augmented pathological features and significantly higher half‐maximal inhibitory concentration values against zinc ions. Based on such a developed 3D biomimetic AS model, the inhibitory effects on the deoxyribonucleic acid (DNA) synthesis, significantly influenced biological processes like cell motility, proliferation, and adhesion, and several potential bio‐targets of zinc ions of cells are revealed.