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High-entropy alloys (HEAs) present unique advantages in surface modification due to their stable mixed-state structures and resistance to intermetallic compound formation. This study investigates the surface modification behavior of equiatomic TiNbHfZnZr HEA components in Ti6Al4V alloy using friction stir processing (FSP). The aim is to enhance the mechanical properties and structural stability of Ti6Al4V by incorporating HEA elements. It was found that the introduction of high-entropy alloys forms shear bands with distinctive micro and nano gradient structures on the surface of the Ti6Al4V alloy. These shear bands not only significantly refine the grains but also promote β phase and β twin formation. The HEA-induced shear bands enhance the strength and stability of the alloy by creating bcc twins and dislocation networks that suppress martensitic transformation and maintain superelasticity. Concurrently, the introduction of HEA components leads to the formation of stable dual-phase (α + bcc) microstructures within the α matrix, significantly improving hardness and modulus.

Objective To investigate the serological characteristics and gene mutation mechanism of RhD variant blood donors in Zhengzhou. Methods From January 2023 to December 2023, 1 619 RhD-negative blood donors sent to our laboratory were selected for the study, and RhD negative confirmation test and RhCE phenotype detection were applied by tube method and microcolumn gel indirect antiglobulin test method. RHD gene amplification and Sanger sequencing were used to detect RhD variant sample genotypes. Results A total of 69 cases of RhD variants were detected in the RhD negative confirmation test, with a proportion of 4.26%(69/1 619).The RhCE phenotypes were ccEe, Ccee, CcEe and CCee.There were 17 genotypes and 15 phenotypes of the D variant.The RHD*weak partial 15 allele was the most frequent(33 cases), with a frequency of 47.83%(33/69), and the main phenotype was the ccEe. This was followed by the RHD*DVI.3 allele in 20 cases with a frequency of 28.99%(20/69) and the predominant phenotype was Ccee. The RHD*weak partial 15/RHD*01EL.01 heterozygote was found in 3 cases with a frequency of 4.35%(3/69), all with the CcEe phenotype. Other rare genotypes were present in 13 cases with a frequency of 18.84%(13/69). Antibody screening was positive in 3 cases with a frequency of 4.35%(3/69). Two cases of female blood donors, both with history of pregnancy and childbirth, were identified as anti-D; one case of male donor was anti-M. Conclusion The RHD*weak partial 15 genotype was the most common among the RhD variants in blood donors in Zhengzhou, followed by the RHD*DVI.3 genotype. It plays an important role in guaranteeing the safety of blood supply and guiding precision transfusion.

Abstract Background The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES. Methods In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 μg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile. Results In total, 2 of the 30 (6.7%, 95% CI: 0.82–22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28–45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0–5 years and the 13–18 years groups, and 2 patients experienced FN in the 6–12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0–5 years, 6–12 years, and 13–18 years groups, respectively. Conclusion Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted. Trial registration This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.

Abstract With its annually increasing prevalence, non‐alcoholic fatty liver disease (NAFLD) has become a serious threat to people's life and health. After a preliminary research, we found that Lactucopicrin has pharmacological effects, such as lowering blood lipids and protecting the liver. Further research showed its significant activation for fatty acid β‐oxidase hydroxyacyl‐coenzyme A (CoA) dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), so we hypothesized that Lactucopicrin could ameliorate lipid accumulation in hepatocytes by promoting fatty acid β‐oxidation. In this study, free fatty acid (FFA)‐induced human hepatoblastoma cancer cells (HepG2) were used to establish an in vitro NAFLD model to investigate the molecular basis of Lactucopicrin in regulating lipid metabolism. Staining with Oil red O and measurements of triglyceride (TG) content, fatty acid β‐oxidase (FaβO) activity, reactive oxygen species (ROS) content, mitochondrial membrane potential, and adenosine triphosphate (ATP) content were used to assess the extent to which Lactucopicrin ameliorates lipid accumulation and promotes fatty acid β‐oxidation. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot methods were used to explore the regulatory effects of Lactucopicrin on factors related to fatty acid β‐oxidation. Results showed that Lactucopicrin downregulated phosphorylated mammalian target of rapamycin (P‐mTOR) by activating the adenosine monophosphate‐activated protein kinase (AMPK) pathway and upregulated the messenger RNA (mRNA) and protein expression levels of coactivators (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α)), transcription factors (peroxisome proliferator‐activated receptor α (PPARα) and peroxisome proliferator‐activated receptor γ (PPARγ)), and oxidative factors (carnitine palmitoyltransferase 1A (CPT1A) and HADHA). This phenomenon resulted in a significant increase in FaβO activity, ATP content, and JC‐1 and a significant decrease in ROS level, TG content, and intracellular lipid droplets. With the addition of Dorsomorphin, all the effects of Lactucopicrin intervention were suppressed. In summary, Lactucopicrin promotes fatty acid β‐oxidation by activating the AMPK pathway, thereby ameliorating FFA‐induced intracellular lipid accumulation in HepG2 cells.

Abstract Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/− HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Objective To analyze the application of serological test results in the diagnosis and treatment of anti-M-induced hemolytic disease of the fetus and newborn(HDFN), and to explore HDFN prevention strategies. Methods The serological test results of 12 cases of HDFN caused by anti-M diagnosed in our laboratory from January 2017 to December 2023 were retrospectively analyzed, including blood group identification of mothers and children, serum total bilirubin/hemoglobin/antibody titer test, and three hemolysis tests in newborns. Clinical data of the children and mothers were collected, including pregnancy history, blood transfusion history, prenatal antibody testing, history of intrauterine blood transfusion and gestational week of delivery, and the prognosis of the children was followed up. Results All 12 cases of fetal neonatal hemolytic disease due to anti-M were RhD+ MN phenotype newborn born to RhD+ NN mother, with maternal- fetal incompatiblility in MN blood groups. In the ABO blood group system, ABO incompatibility between mother and child accounted for 41.7%(5/12).None of the mothers had a history of blood transfusion, and the median titer of the test at 4℃ was 32, and the median titer at 37℃ was 4. The mothers of 3 cases had a history of multiple intrauterine blood transfusions, with an incidence of 25%(3/12). One case had an abnormal first pregnancy, with an incidence of 8.3%(1/12), and seven cases had an abnormal pregnancy with a miscarriage, with an incidence of abnormal pregnancy and birth history of 58.3%(7/12). There were 6 cases of premature labor, with an incidence of 50%(6/12). The mothers in three cases underwent regular obstetric examination and the specificity of the antibodies was determined, accounting for 25%(3/12). Twelve children had free antibodies with a median titer of 6 at 4℃ and 2 at 37℃. Two children had anti-M antibodies that were not reactive at 37℃, with a negative rate of 16.7%(2/12). The positive rate of DAT and elution test was respectively 8.3%(1/12) and 16.7%(2/12) in the children. The median minimum hemoglobin value was 75 g/L, and all 12 children received blood transfusions. The median peak total bilirubin value was 157.5 μmol/L, and none of them reached the threshold for blood exchange. The rate of delayed anemia was 16.7%(2/12), the postnatal mortality rate was 8.3%(1/12), and 11 children was free of growth and neurodevelopmental delay in prognosis. Conclusion Anti-M can cause severe HDFN, which can also occur in primigravida. The intensity of antibody titer does not correlate with the severity of the disease, and it is prone to cause delayed anemia, which should be monitored regularly according to the serological characteristics of anti-M and clinical symptoms, and should be treated timely.

Abstract Abnormalities in the extracellular matrix (ECM) play important roles in the regulation and progression of clear cell renal cell carcinoma (ccRCC). The cysteine cathepsin is one of the major proteases involved in ECM remodeling and has been shown to be aberrantly expressed in multiple cancer types. However, the clinical significance and biological function of distinct cysteine cathepsins in ccRCC remain poorly understood. In this study, several bioinformatics databases, including UALCAN, TIMER, GEPIA and the Human Protein Atlas datasets, were used to analyze the expression and prognostic value of different cysteine cathepsin family members in ccRCC. We found that the expression level of CTSF was downregulated in tumor tissues and closely related to the poor survival of ccRCC patients. Further in vitro experiments suggested that CTSF overexpression suppressed the proliferation and migration of ccRCC cells. Moreover, the expression of CTSF was shown to be associated with several immune-infiltrating cells and immunomodulators in ccRCC. These results indicated that CTSF might be a promising diagnostic and prognostic marker in ccRCC.

PurposeTo explore the clinical, muscle pathological, and pathogenic gene mutation characteristics of Andersen-Tawil Syndrome (ATS) and enhance the understanding of ATS among clinical practitioners.MethodsRetrospective analysis of clinical data and muscle pathology of two ATS families, along with genetic testing for probands and some family members.ResultsIn Family 1, spanning four generations, four individuals were affected, while Family 2 had two affected individuals across four generations. All six patients in both families experienced onset in childhood, presenting with periodic paralysis, arrhythmias, and craniofacial skeletal abnormalities. In Family 1, the proband’s periodic paralysis was more triggered by low temperature and exercise, occurring several times a year, lasting 4–7 days. All three adult patients in Family 1 had a history of hypokalemia, and the frequency and severity of attacks were reduced after regular oral potassium supplement therapy. Two adult females in Family 1 experienced limb weakness triggered by stress, exertion, and premenstrual period, with milder symptoms than the proband. In Family 2, the proband’s periodic paralysis typically occurred the day after excessive exertion, with a frequency of approximately 2–3 months. Two years prior, the proband developed arrhythmias without palpitations or chest tightness. The proband’s brother experienced intermittent limb weakness during adolescence, remained untreated, and had sudden death at age 40. Physical examination revealed characteristic features in Family 1 and both probands: small mandible, wide eye spacing, and fifth-digit clinodactyly. Four adult patients were shorter in stature, while the growth status of a pediatric patient was indeterminate. Supplementary tests showed a history of hypokalemia during muscle weakness episodes in Family 1, while Family 2 patients had normal potassium levels during episodes. The long exercise tests were positive in both probands. Muscle MRI showed no significant abnormalities, but muscle pathology revealed rimmed vacuoles and tubular aggregates. Genetic testing identified KCNJ2 gene mutations in two probands and some of their family members, with c.407C > T (p.S136F) heterozygous mutation in Family 1 and c.652C > T (p.R218W) heterozygous mutation in Family 2.ConclusionAmong the clinical symptoms of the patients with Andersen-Tawil Syndrome in this study, not everyone exhibits the full triad of signs: periodic paralysis is the most common initial symptom, craniofacial and digit skeletal abnormalities are characteristic signs, and ventricular arrhythmias pose the most serious potential risk. Given that these typical symptoms were observed in 5 out of 6 patients, clinicians should pay special attention to these typical symptoms, and patients with these symptoms should be followed up over time. Muscle biopsy May reveal pathological changes such as tubular aggregates, but genetic testing for KCNJ gene mutations remains a crucial diagnostic criterion for this syndrome.

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies.

Abstract Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

Abstract Aims In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. Methods Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. Results In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. Conclusion E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.

Abstract Background The aim of this study was to review clinical features of adolescent malignant germ cell tumors (MGCTs) in Beijing and analyze the peculiar characteristics of this age group. Methods Clinical characteristics, pathological presentations, and survival outcomes of 34 patients were analyzed retrospectively. Results Of 34 patients, 12 girls and 22 boys, 18 (52.9%) had an extra‐cranial tumor, including one testicular tumor, five ovarian tumors, one sacrococcygeal tumor, and 11 mediastinal tumors. Histologically, we found immature teratomas (n = 6), yolk sac tumors (n = 5), mixed malignant tumors (n = 5), an embryonic carcinoma (n = 1), and seminoma (n = 1). Three‐year event‐free survival (EFS) and overall survival (OS) were 48.8% and 62.9%, respectively. Another 16 (47.1%) patients had an intracranial tumor, including nine in the pineal region, five in the suprasellar region, one in basal ganglia, and one in cerebellopontine. All patients had localized disease and an excellent outcome with 3‐year EFS and OS of 93.7% and 100%, respectively. Conclusions Adolescent MGCTs are rare with a strong dependence on gender, and the mediastina and pineal region are the most common tumor locations. The prognosis is promising compared with that of other adolescent tumors and MGCTs in other age groups. MGCTs in mediastina have a tendency to companion with other hematological malignancies, and the prognosis is extremely poor in these patients.

Abstract We report two children with hepatoblastoma (HB) with a history of neonatal necrotizing enterocolitis (NEC). Case 1 was diagnosed with HB at 5 months of age. Liver enlargement was found during the NEC operation at 3 months of age and then was clinically diagnosed by imaging. After six chemotherapy courses, a partial hepatectomy was performed. Three months after ceasing the chemotherapy, a chest computed tomography scan suggested that distant metastasis of the tumor should be considered, and the lesion was removed. However, 9 months after the operation, alpha‐fetoprotein concentrations were increased, and abdominal imaging showed a recurrence of the tumor in situ, resulting in a hepatectomy. Case 2 was diagnosed with NEC shortly after birth and underwent an intestinal resection and anastomosis 1 month later. He was diagnosed with HB at 3 years of age. Hepatectomy was performed after five courses of chemotherapy. Chemotherapy was stopped after 10 courses, and alpha‐fetoprotein concentrations were normal. At present, both children have survived and are in a healthy condition. Physicians should be aware of the possibility of HB and a history of NEC in children. Premature birth and low birth weight are common factors leading to the pathogenesis of HB and NEC. The association between these two diseases requires further study.

Abstract This study aims to investigate the effects of Chorum glandulosum Boiss. et Huet (CG) on the intestinal microbiota and serum bile acid (BA) in db/db mice. A total of 12 db/db mice were randomly divided into model (MOD), high‐dose CG (CGH), and control (CON) groups. The CON and MOD groups received distilled water by gavage for 8 weeks. Whereas, the CGH group received an alcohol extract of CG at a dose of 200 mg/kg/day. Results showed that CG can reduce blood lipid levels. It change the composition of the intestinal microbiota, and increase the relative abundances of Muribaculaceae, Prevotellaceae, Bifidobacterium_pseudolongum, Bacteroidaceae in db/db mice as well. LC–MS metabolomics results showed that CG adjusted the serum BA levels. The results reduced the levels of primary BAs, such as cholic acid (CA) and chenodeoxycholic acid (CDCA). The results decreased the primary BA/secondary BA (PSA/SBA) ratio in db/db mice. Correlation analysis showed that the abundances of Bifidobacterium_pseudolongum and Bacteroidaceae were positively correlated with acetic acid level and negatively correlated with ursocholic acid (UCA), α‐muricholic acid (αMCA), triglyceride (TG), and total cholesterol levels (TC), indicating an interaction between the intestinal microbiota and serum BAs. CG may play a positive role in the interaction between the intestinal microbiota and BAs in lipid metabolism.

Abstract The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have been found in plants, namely (+)-CPP, ent-CPP and syn-CPP. Here, we used X-ray crystallography and cryo-EM methods to describe different oligomeric structures of a syn-copalyl diphosphate synthase from Oryza sativa (OsCyc1), and provided a cryo-EM structure of OsCyc1D367A mutant in complex with the substrate GGPP. Further analysis showed that tetramers are the dominant form of OsCyc1 in solution and are not necessary for enzyme activity in vitro. Through rational design, we identified an OsCyc1 mutant that can generate ent-CPP in addition to syn-CPP. Our work provides a structural and mechanistic basis for comparing different CPSs and paves the way for further enzyme design to obtain diterpene derivatives with specific chirality.

Antimicrobial peptides (AMPs) constitute a group of small molecular peptides that exhibit a wide range of antimicrobial activity. These peptides are abundantly present in the innate immune system of various organisms. Given the rise of multidrug-resistant bacteria, microbiological studies have identified AMPs as potential natural antibiotics. In the context of antimicrobial resistance across various human pathogens, AMPs hold considerable promise for clinical applications. However, numerous challenges exist in the detection of AMPs, particularly by immunological and molecular biological methods, especially when studying of newly discovered AMPs in proteomics. This review outlines the current status of AMPs research and the strategies employed in their development, considering resent discoveries and methodologies. Subsequently, we focus on the advanced techniques of mass spectrometry for the quantification of AMPs in diverse samples, and analyzes their application, advantages, and limitations. Additionally, we propose suggestions for the future development of tandem mass spectrometry for the detection of AMPs.

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA

Background: Emerging evidence has demonstrated the impact of psychological stress on intestinal microbiota, however, the precise mechanisms are not fully understood. Enteric glia, a unique type of peripheral glia found within the enteric nervous system (ENS), play an active role in enteric neural circuits and have profound effects on gut functions. In the present study, we tested the hypothesis that enteric glia are involved in the alterations in the intestinal microflora and barrier induced by chronic water-avoidance stress (WAS) in the gut. Methods and results: Western blotting and immunohistochemical (IHC) staining were used to examine the expression of glial fibrillary acidic protein (GFAP), nitric oxide synthetase (NOS) and choline acety1transferase (ChAT) in colon tissues. 16S rDNA sequencing was performed to analyse the composition of the intestinal microbiota in rats. Changes in the tight junction proteins Occludin, Claudin1 and proliferating cell nuclear antigen (PCNA) in the colon tissues were detected after WAS. The abundance of Firmicutes, Proteobacteria, Lactobacillus and Lachnospiraceae_NK4A136 decreased significantly, whereas the abundance of Actinobacteria, Ruminococcaceae_UCG−005 and Christensenellaceae-R-7 increased significantly in stressed rats. Meanwhile, the expression of Occludin, Claudin1 and PCNA significantly decreased after WAS. Treatment with L-A-aminohexanedioic acid (L-AA), a gliotoxin that blunts astrocytic function, obviously decreased the abundance of Actinobacteria, Ruminococcaceae_UCG−005 and Christensenel-laceae_R-7 in stressed rats and significantly increased the abundance of Proteobacteria, Lactobacillus and Lachnospiraceae_NK4A136. In addition, the protein expression of colon Occludin, Claudin1, and PCNA increased after intraperitoneal injection of L-AA. Furthermore, the expression level of NOS in colon tissues was significantly decreased, whereas that of ChAT was significantly increased following L-AA treatment. Conclusions: Our results showed that enteric glial cells may contribute to WAS-induced changes in the intestinal microbiota and barrier function by modulating the activity of NOS and cholinergic neurones in the ENS.

Objective To carry out serological and molecular biological identification of B (A) subtype, and discuss the rational blood transfusion strategy. Methods Serological and direct sequencing methods were used to detect serotype and genotype of 7 cases of B (A) subtype, and cross matching was performed by saline medium and anti human globulin card to analyze the red blood cells(RBCs) transfusion strategy. Results The serology results of blood type of 7 samples were similar, with B(A)04/O01 in 3 cases, B(A)04/O02 in 2 cases and B(A)02/O01 in 2 cases. 7 cases of B (A) subtypes were matched with randomly selected blood donors of type O and B on the major side. Conclusion B(A) subtypes should be identified by genotyping techniques. Washed RBCs of type B and O can be used for B(A) blood type transfusion.

Two new polyketide derivatives, penirubenones A and B (1 and 2), and two naturally rare amino-bis-tetrahydrofuran derivatives, penirubenamides A and B (3 and 4), together with nine known compounds (5–13) were isolated from the marine-derived fungus Penicillium rubens BTBU20213035. The structures were identified by HRESIMS and 1D and 2D NMR analyses, and their absolute configurations were determined by a comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy and 13C NMR data. We found that 6 exhibited antibacterial activity against Staphylococcus aureus, with an MIC value of 3.125 μg/mL, and 1 and 2 showed synergistic antifungal activity against Candida albicans at 12.5 and 50 μg/mL with 0.0625 μg/mL rapamycin.

In order to better understand pore–throat structure characteristics, the coupling relationship between micropore–throat structure and macro reservoir quality and influencing factors caused by authigenic minerals were studied. Petrographic analyses, scanning electron microscopy (SEM), pressure-controlled mercury injection (PMI), nuclear magnetic resonance (NMR), and X-ray diffraction (XRD) were performed on a suite of tight reservoir samples from the Chang 8 Member of the Upper Triassic Yanchang Formation in the southwestern Ordos Basin, China. The results show that the pore–throat sizes obtained with the combination of PMI and NMR methods varied from nano- to microscale, revealing pore–throat sizes ranging from 0.001 μm to 70 μm, and showing that pore–throats with a radius larger than 1.0 μm are rare. Larger pore–throats with good connectivity (>rapex) account for a smaller part of the total pore volume, ranging from approximately 7.58% to 38.90% with an average of 22.77%, but account for more than 80% of contributions to permeability. The effective movable fluid porosity (φemp) measured by NMR, ranging from approximately 0.10% to 7.07% with an average of 2.56%, had a positive contribution to permeability. The contents of chlorite occurrence state, other than illite, are beneficial to pore–throat preservation. A new reservoir evaluation scheme of the Chang 8 reservoir is established. These research results provide a theoretical basis for the evaluation and development of tight sandstone oil and gas exploration.

Abstract Rhabdomyosarcomas (RMSs) are highly malignant soft‐tissue sarcomas. Head and neck RMSs often pose unique challenges to treatment because of their closeness to important structures. We here report a rare case of a 1‐year‐old boy with a 1‐month history of right eye swelling and an eye mass. Biopsy of deep tumors in the maxillofacial region supports embryonal RMS. Postoperative positron emission computed tomography showed a 5.0 cm × 4.8 cm × 4.2 cm malignant tumor in the right maxillary region. In accordance with the international RMS study group guideline, the child was diagnosed with IIIa and TNM stage T2bN1M1 embryonal RMS. The child was treated with a combination of chemotherapy and 125I seed implantation radiotherapy and eventually achieved partial remission. This case report shows that 125I seed implantation is a safe and effective means of delivering radiotherapy to young children with head and neck RMSs. It may be an option for children with RMSs for whom surgery or external radiotherapy is unsuitable.

Starting from the traditional receiver loop multipath suppression method, the delay effect of multipath effect on receiver tracking and capture is mitrgated in parallel by correcting the code loop correlation curve distortion and adaptive carrier signal update mechanism to track the weak dynamic carrier signal at two levels. First, an adaptive threshold carrier tracking signal state model is designed to solve the problem of limited signal tracking under high occlusion and low CNR conditions, with the aid of the Random Hough Transform slope detection method in the field of machine learning to reduce the error of narrow correlator. Comparson was made with existing methods from different perspectives. The results show that the localization modeling property of applying the RHT method assisted by adaptive enhanced carrier signal tracking is significantly improved compared with both the conventional HRC and Kalman filter carrier tracking methods, with the method proposed in this paper being able to recover the carrier signal out of lock in time for a signal delay of around 1.8 s. In addition, the final localization results show that the root mean square error is reduced by 6.3 m in the D region of the experimental scenario where the MP effect is strong.

Titanium and its alloys are promising materials for engine production, special pump manufacturing, and bone implants. However, the abrasion resistance and fracture toughness of Ti alloys are insufficient to withstand extreme high loading conditions and harsh environments. Surface modification is an effective way to improve the performance of Ti alloys. In this study, Ag and Cu were added to Ti6Al4V alloy through friction stir processing to modify its surface. The different ratios of the Ag/Cu powder mixture were designed to optimize the surface modification of Ti6Al4V, and the relationship between intermetallic compounds and martensitic transformation was analyzed. The martensitic transformation was induced by AgCuTi phases. The submicron-size martensite was distributed outside the AgCuTi particle, while the nano-laminar martensitic band was generated inside the AgCuTi particle. Under the co-modification of Ti alloy using Ag and Cu, the surface of Ti6Al4V alloy exhibited higher hardness (4.3 GPa) values and lower modulus (100.6 GPa), which gave the credit to the formation of AgCuTi and martensitic transformation. The alloy specimen was subjected to short heat treatment at 600 °C for 30 min to further modify the gradient structure. After the short heat treatment of the Ag/Cu co-modified specimen, a lower modulus (88.8 GPa) and a high level of hardness (4.1 GPa) were achieved. In addition, superelastic strain recovery was also enhanced, showing the further induced martensitic transformation. This work provides new insight into the surface modification of titanium alloys using the FSP method to achieve the ideal hardness and elastic modulus balance.

Abstract Background Regular sleep is very important for human health; however, the short-term and long-term effects of nightshift with sleep deprivation and disturbance on human metabolism, such as oxidative stress, have not been effectively evaluated based on a realistic cohort. We conducted the first long-term follow-up cohort study to evaluate the effect of nightshift work on DNA damage. Methods We recruited 16 healthy volunteers (aged 33 ± 5 years) working night shifts at the Department of Laboratory Medicine at a local hospital. Their matched serum and urine samples were collected at four time points: before, during (twice), and after the nightshift period. The levels of 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), two important nucleic-acid damage markers, were accurately determined based on a robust self-established LC‒MS/MS method. The Mann–Whitney U or Kruskal–Wallis test was used for comparisons, and Pearson’s or Spearman’s correlation analysis was used to calculate the correlation coefficients. Results The levels of serum 8-oxodG, estimated glomerular filtration rate-corrected serum 8-oxodG, and the serum-to-urine 8-oxodG ratio significantly increased during the nightshift period. These levels were significantly higher than pre-nightshift work level even after 1 month of discontinuation, but no such significant change was found for 8-oxoG. Moreover, 8-oxoG and 8-oxodG levels were significantly positively associated with many routine biomarkers, such as total bilirubin and urea levels, and significantly negatively associated with serum lipids, such as total cholesterol levels. Conclusion The results of our cohort study suggested that working night shifts may increase oxidative DNA damage even after a month of discontinuing nightshift work. Further studies with large-scale cohorts, different nightshift modes, and longer follow-up times are needed to clarify the short- and long-term effects of night shifts on DNA damage and find effective solutions to combat the negative effects.

Abstract Background Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. Methods The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. Results Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. Conclusions A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It’s also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.

Abstract Background To summarize the characteristics and treatment, and analyze the prognosis of large number of infants with retinoblastoma (RB) in China through a multicenter, 10-year retrospective analysis. Methods The data of RB infants were collected from multiple centers. The characteristics and survival prognosis were analyzed. The overall survival (OS) rate was estimated by the Kaplan–Meier method. Multivariate Cox survival analysis was to evaluate the independent risk factors affecting the prognosis of RB infants. Results A total of 373 RB infants (202 boys and 171 girls) were included, the median age was 6.22 months (10 days to 11.93 months). The median follow-up time of RB infants was 18.4 (1.02–122.81 months). After excluding the lost to follow-up cases, the OS rate was 97.7% (345/353). Kaplan–Meier survival analysis indicated that 9 cases died and the median survival time was not reached. Univariate analysis of prognostic factors revealed eye affected, presenting signs, left eye stage and recurrence to be poor prognostic factors for OS rate in RB infants (all P

Out-of-face gradient sandwich structures have been widely studied for their excellent impact resistance. One uniform and two out-of-plane gradient cores are proposed based on the bionic structure of Royal Water Lily, and the midspan deflection of the back panel and the energy absorption of the out-of-plane gradient sandwich structures under various blast loads are studied. Two frequently adopted methods of explosive loading are applied to the sandwich panels, and the responses are contrasted for the loads applied as a time-dependent pressure history versus imposition of the initial velocity. The effect of the fluid–structure interaction is considered in the blast impulsion, and the dynamic responses of the sandwich structures with different out-of-plane density arrangements are analyzed under two loading approaches. Results show that the energy absorption of the core layer under the prescribed velocity approach is approximately 3–5 times that of the applied pressure approach, while the back panel deflections of different out-of-plane gradient sandwiches are similar. There are significant differences in the deformation mechanisms of structures under these two types of impact loads. Under the same type of impact load, the core compression process of the out-of-plane positive gradient sandwich panel is decoupled from the whole tensile bending deformation process of the structure, whereas the core compression process of the out-of-plane negative gradient sandwich panel is strongly coupled with the whole tensile bending deformation process of the structure. The related research will lay the foundation for an in-depth understanding of the theoretical study of the impact of out-of-face gradient sandwich structures.

ABSTRACT: Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which often reduces the prevention and control effects of various vaccines, including infectious bursal disease virus (IBDV) vaccine, and brings enormous economic losses to the poultry industry. However, the molecular mechanisms of SIIS inhibiting immune response to IBDV vaccine remain unclear. In this study, suppressor of cytokine signaling 3 (SOCS3) gene was selected and stress-induced immunosuppressed chickens were simulated using dexamethasone (Dex). Quantitative real-time PCR (qRT-PCR) was conducted to analyze its expression characteristics and game relationships between SOCS3 gene and miR-27b-3p (it could target SOCS3 gene) in the process of SIIS inhibiting immune response to IBDV vaccine in chicken, and the potential application value of circulating miR-27b-3p as a biomarker was also identified. The results showed that SOCS3 gene and miR-27b-3p were significantly differentially expressed in the candidate tissues during SIIS inhibiting the immune response to IBDV (P < 0.05), respectively, which were key factors involved in the process. Moreover, miR-27b-3p and SOCS3 gene showed game regulation relationships in several tissues during the process, so the miR-27b-3p/SOCS3 regulatory network was one of the key mechanisms of SOCS3 gene participating in the process. Circulating miR-27b-3p was differentially expressed in serum at 10 time points (1, 2, 3, 4, 5, 7, 14, 21, 28, and 35 days postimmunization (dpi)) in the process (P < 0.05), showing that circulating miR-27b-3p was a valid candidate target as a molecular marker for detecting SIIS inhibiting the IBDV immune response. This study can provide references for further studying molecular mechanisms of stress affecting immune response.

ABSTRACTAccumulating evidence suggests that the bile acid regulates type 2 diabetes mellitus (T2DM) through gut microbiota-host interactions. However, the mechanisms underlying such interactions have been unclear. Here, we found that glycoursodeoxycholic acid (GUDCA) positively regulates gut microbiota by altering bile acid metabolism. GUDCA in mice resulted in higher taurolithocholic acid (TLCA) level and Bacteroides vulgatus abundance. Together, these changes resulted in the activation of the adipose G-protein-coupled bile acid receptor, GPBAR1 (TGR5) and upregulated expression of uncoupling protein UCP-1, resulting in elevation of white adipose tissue thermogenesis. The anti-T2DM effects of GUDCA are linked with the regulation of the bile acid and gut microbiota composition. This study suggests that altering bile acid metabolism, modifying the gut microbiota may be of value for the treatment of T2DM.

The purification of 1,3-butadiene from C4 hydrocarbon mixtures currently relies on energy-intensive extractive distillation. In this study, we employed ZIF membranes for this challenging separation for the first time, unveiling their superior capability in isolating 1,3-butadiene from other C4 hydrocarbons with similar sizes, including 1-butene, isobutene, and n-butane. This strong sieving effect was evident from two types of ZIF-8 membranes: one with low crystallinity fabricated via the all-vapor-phase ligand-induced permselectivation (LIPS) method and another with high crystallinity synthesized through the seeded growth method. The gas permeances decreased with increasing kinetic diameters, following the order of 1,3-butadiene (4.31 Å) > 1-butene (4.46 Å) > n-butane (4.687 Å) > isobutene (4.84 Å). The LIPS-ZIF-8 membrane exhibited a high 1,3-butadiene permeance of approximately 1.43 × 10−7 mol/m2 s Pa (∼430 GPU) and ideal separation factors of 18, 56, and 134 for 1,3-butadiene over 1-butene, n-butane, and isobutene, respectively. In separating four-component C4 mixtures, these membranes could enrich 1,3-butadiene content from 50% in the feed to 96–98% in the permeate through a single separation step. This unprecedented performance is attributed to differences in C4 diffusivities that span several orders of magnitude.

Polar organic chemical integrative sampler (POCIS) represents a promising passive sampling approach for the monitoring of per- and polyfluoroalkyl substances (PFAS) in water. However, the use of polymer membranes has limited the long-term application of conventional POCIS in the field. This work aimed to develop ceramic membranes with controllable PFAS diffusion and mass transfer suitable for PFAS passive sampling applications. Our results showed that PFAS diffusion through ceramic membranes was strongly dependent on membrane structures and properties, particularly membrane porosity. Through controlling membrane fabrication conditions, including particle size and morphology of the membrane material and sintering temperature, ceramic membranes with a range of PFAS diffusivities and mass transfer rates were obtained that varied by over two orders of magnitude, which substantially expanded the limits of polyethersulfone (PES) membranes. Further, modification of ceramic membranes with a thin TiO2 layer did not influence the PFAS mass transfer. Integrative passive samplers consisting of ceramic membranes and a sorbent receiving phase were then developed and assessed through calibration studies. The passive samplers showed linear uptake of PFAS over an extended period of time up to 25 days, and the PFAS sampling rates were affected by both the type of ceramic membranes and the PFAS structures. Results of this study demonstrated the proof-of-concept of the use of ceramic membranes in PFAS passive sampling applications.

Abstract Background Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. Methods The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. Results GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746–179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo–YAP1 pathway in both in vitro and in vivo models. Conclusions Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.

Currently, little is known about the characteristics of polyphenol oxidase from wheat bran, which is closely linked to the browning of wheat product. The wheat PPO was purified by ammonium sulfate precipitation, DEAE-Sepharose ion-exchange column, and Superdex G-75 chromatography column. Purified wheat PPO activity was 11.05-fold higher, its specific activity was 1365.12 U/mg, and its yield was 8.46%. SDS-PAGE showed that the molecular weight of wheat PPO was approximately 21 kDa. Its optimal pH and temperature were 6.5 and 35 °C for catechol as substrate, respectively. Twelve phenolic substrates from wheat and green tea were used for analyzing the substrate specificity. Wheat PPO showed the highest affinity to catechol due to its maximum Vmax (517.55 U·mL−1·min−1) and low Km (6.36 mM) values. Docking analysis revealed strong affinities between catechol, gallic acid, EGCG, and EC with binding energies of −5.28 kcal/mol, −4.65 kcal/mol, −4.21 kcal/mol, and −5.62 kcal/mol, respectively, for PPO. Sodium sulfite, ascorbic acid, and sodium bisulfite dramatically inhibited wheat PPO activity. Cu2+ and Ca2+ at 10 mM were considered potent activators and inhibitors for wheat PPO, respectively. This report provides a theoretical basis for controlling the enzymatic browning of wheat products fortified with green tea.

ObjectiveOur aim was to analyze the trends and hotspots on glial fibrillary acidic protein (GFAP) within the area of Alzheimer’s disease (AD) by using a bibliometric method, which is currently missing.MethodsAll articles and reviews on GFAP within the area of AD from inception to December 31, 2022, were searched from the Web of Science Core Collection. Full records were derived, imported into Microsoft Excel, and analyzed by BIBLIOMETRC, VOSviewer, and CiteSpace.ResultsIn total, 2,269 publications, including 2,166 articles, were ultimately included. The number of publications from 81 countries/regions and 527 academic journals increased annually. The top three prolific countries and institutions were the USA, China, and England, the University of Gothenburg (Sweden), Federal University of Rio Grande do Sul (Brazil), and UCL Queen Square Institute of Neurology (England). Henrik Zetterberg from the University of Gothenburg, Kaj Blennow from the University of Gothenburg, and Alexei Verkhratsky from the University of Manchester were the top three prolific and cited authors; Journal of Alzheimer’s Disease, Brain Research, and Neuroscience contributed the most publications. The top key areas of research included “molecular, biology, and genetics” and “molecular, biology, and immunology,” and the top published and linked meaningful keywords included oxidative stress, inflammation/neuroinflammation, microglia, hippocampus, amyloid, cognitive impairment, tau, and dysfunction.ConclusionBased on the bibliometric analysis, the number of publications on GFAP within the area of AD has been rapidly increasing, especially in the past several years. Oxidative stress and inflammation are research hotspots, and GFAP in body fluids, especially blood, could be used for large-scale screening for AD.

Objective To analyze and master the serological and genetic characteristics of the samples with CisAB subtype and their genetic background. Methods From January 2018 to January 2022, blood samples with discrepant ABO blood typing results, from Zhengzhou voluntary blood donors and hospital patients, were subjected to phenotypic classification using micro column gel card and tube method, as well as amplification of exons 6 and 7 in ABO gene using PCR. The pedigrees of individuals with the same CisAB subtype but different serological typing results in the same family were analyzed. Results 11 The forward typing of 12 samples was AB type, and unexpected antibodies against weaker antigens were found in 11 serum samples, including 9 cases with strong antigen A, 2 cases with strong antigen B, and 1 case with consistent forward and reverse typing results. Gene sequencing confirmed that 11 cases were CisAB01 subtype and 1 case was CisAB05 subtype.Among them, 7 cases had the genotype of CisAB01/O and serological phenotype of A2B3; 2 cases had the genotype of CisAB01/B and phenotype of A2B; 2 cases had the genotype of CisAB01/A and serological phenotype of A1Bx and A1B3; 1 case had the phenotype of AxB. In the CisAB01 family, 1 case of CisAB01/O with A2B3 phenotype and 1 case of CisAB01/B with A2B phenotype were detected. In the CisAB05 family, 2 CisAB05/O01 and 1 CisAB05/O02 were detected. Conclusion The serological phenotypes of different individuals in the same CisAB01 family can be different when paired with different ABO alleles. It is advisable to accurately identify the CisAB subtype genes with molecular biological methods to ensure blood transfusion safety.

Abstract Background Currently, the direct method is the main approach for establishment of reference interval (RI). However, only a handful of studies have described the effects of sample size on establishment of RI and estimation of sample size. We describe a novel approach for estimation of the sample size when establishing RIs using the transformed parametric and non-parametric methods. Methods A total of 3,697 healthy participants were enrolled in this study. We adopted a two-layer nested loop sample size estimation method to determine the effects of sample size on RI, using thyroid-related hormone as an example. The sample size was selected as the calculation result when the width of the confidence interval (CI) of the upper and lower limit of the RI were both stably

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and there are no effective drugs available so far. Lactucin and Lactucopicrin belong to sesquiterpene lactones and are extracted from Cichorium glandulosum Boiss. et Huet (CG) possesses multiple biopharmacological activities. However, the therapeutic effects of both Lactucin and Lactucopicrin on many diseases and their underlying mechanisms remain largely unknown. Here, we analyzed the both natural compounds hypolipidemic effects on FFA-induced HepG2 cells and their potential mechanisms based on transcriptomics and experimental tests. Our results indicated that Lactucin (10 μM) and Lactucopicrin (20 μM) remarkably reduced TG accumulation. Transcriptomics analysis identified 1960, 1645, and 1791 differentially expressed genes (DEGs) and obtained 611 and 635 specific genes in different comparisons, respectively. The enrichment analysis and experimental validations (RT-qPCR and Western Blot) showed that their hypolipidemic activities were most probably exerted via regulating numerous key DEGs involved in lipid metabolism. Taken together, both Lactucin and Lactucopicrin may represent potent hepatoprotective agents. Both of them exhibited therapeutic effects against liver diseases such as NAFLD by regulating multi-gene and proteins like HADHA, ADAM17, SQSTM1, and GBA and modulating multi-pathways like fatty acid oxidation metabolic signaling.

The develop of organic functional materials requires the exploration of the pressure dependent emissive mechanisms of molecular structures, conformations and stacking modes. Here, Tong et al propose a strategy for monitoring the pressure-induced fluorescence under multiple excitation channels.

Abstract Background Immunotherapy has proven to be an emerging treatment for non-small-cell lung cancer in recent years. Notably, smokers show higher programmed cell death ligand-1 (PD-L1) expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Genome-wide association studies show that the CHRNΑ5 encoding α5-nicotinic acetylcholine receptor (α5-nAChR) is especially relevant to lung cancer and nicotine dependence. Jab1 is a key regulatory factor and promotes the stabilization of PD-L1. Our previous study reported that α5-nAChR mediates lung adenocarcinoma (LUAD) epithelial-mesenchymal transition (EMT) and metastasis via STAT3/Jab1. However, the link between α5-nAChR and PD-L1 is unclear in LUAD. Methods We used various bioinformatics databases to analyze the expression of related genes and their correlations. Expression and clinicopathologic significance of α5-nAChR and PD-L1 were detected by immunohistochemistry in a tissue microarray. α5-nAChR regulated LUAD cell immune escape by targeting the STAT3/Jab1-PD-L1 signalling by Western-blotting and ChIP in vitro. We used T cell coculture, flow cytometry, ELISA, CCK8 assay and crystal violet staining to detect the expression of regulatory T cell (Tregs), IFN-γ, IL-2 and the ability of T cell-mediated tumour cell killing respectively. IF assays were performed in both cancer cells and tumour xenograft paraffin sections to analyze the protein expression. The in vivo experiments in mouse model were performed to show the α5-nAChR-mediated immune escape via PD-L1 pathway. Results The expression of α5-nAChR was correlated with PD-L1 expression, smoking status and lower survival of LUAD in vivo. In vitro, the expression of α5-nAChR mediated phosphorylated STAT3 (pSTAT3), Jab1 and PD-L1 expression. STAT3 bound to the Jab1 or PD-L1 promoter and mediated PD-L1 expression. Jab1 stabilized PD-L1 expression in LUAD cells. Furthermore, in primary T cell cocultured system, downregulation of α5-nAChR suppressed the function of CD4+CD25+FOXP3+ Tregs, enhanced IFN-γ secretion, and increased T cell-mediated killing of LUAD cells. In the Jurkat T cells and LUAD cells coculture assay, inhibition of α5-nAChR increased IL-2 secretion. In tumour xenograft tissues, α5-nAChR expression was related to PD-L1, Jab1, pSTAT3, CD4 and granzyme B expression (GB). Conclusions Our results suggest that the novel α5-nAChR/STAT3-Jab1-PD-L1 axis is involved in LUAD immune escape, which could lead to potential therapeutic strategies for cancer immunotherapy. Video abstract

ABSTRACT: Adipose tissue (AT) is considered as a regional immune organ and plays an important role in the anti-infection immune response. However, the function and mechanism of chicken AT in response to secondary immune response remain poorly understood. Here, we used mRNA and microRNA (miRNA) sequencing technology to survey the transcriptomic landscape of chicken abdominal adipose tissue (AAT) during the first and second immunization with Newcastle disease virus (NDV) vaccine, and carried out bioinformatics analysis, such as Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, protein–protein interaction (PPI) analysis, and miRNA–mRNA integrated analysis. The results indicated that chicken AAT actively responded to the secondary immune response. DNA replication and cytoskeleton regulation as the regulatory functions of immune activation changed significantly, and weakened lipid metabolism was an effective strategy for the secondary immunity. Mechanically, the regulatory network between the differentially expressed miRNAs (DEMs) and their targeted differentially expressed genes (DEGs), such as miR-206/miR-499-5p-nuclear receptor subfamily 4 group A member 3 (NR4A3)/methylsterol monooxygenase 1 (MSMO1) pathway, was one of the potential key mechanisms by which AAT responded to the secondary immune response. In conclusion, regional immunity of chicken AT responds to secondary immunity by promoting immune activation and weakening lipid metabolism, and this study can instruct future research on antiviral strategy.

The search for alternative salt formulations similar to sodium chloride and their effect on marinated meat products is of great significance to the low-sodium meat processing industry. The main purpose of this study was to investigate the effect of partially replacing sodium chloride with potassium lactate, calcium ascorbate, and magnesium chloride on the sodium content, water activity and distribution, protein solubility, microstructure, sensory characteristics and volatile flavor compounds in low-sodium marinated beef. The sodium content in the test group decreased up to 28% compared to 100% in the sodium chloride group C1. The formulation including 60% sodium chloride and a total of 40% compound alternative salts in groups F1 and F2 increased their myofibril fragmentation index and promoted the disruption of the myogenic fiber structure. Group F1 (the ratio of potassium lactate, calcium ascorbate and magnesium chloride was 2:1:1) performed higher solubility of myofibrillar proteins and lower transverse relaxation value than group F2 detected by low-field nuclear magnetic resonance, which indicated that F1 formulation was beneficial to promote the solubility of myofibrillar proteins and attenuate the water mobility of marinated beef. Moreover, group F1 had a more similar microstructure and more similar overall sensory attributes to group C1 according to the scanning electron microscopy. The sensory evaluation showed higher peak intensity and response values of volatile flavor compounds than group C1 and C2 (only 60% sodium chloride) when detected using gas chromatography–ion mobility spectrometry technology, which indicated that the compound alternative salts of group F1 can improve the lower quality of low-sodium marinated beef and perform similar attributes to the C1 sample regarding moisture distribution and microstructure and even performs better than it with regards to flavor. Therefore, the F1 formula possessed greater potential for application in low-sodium marinated meat products.

Lipid metabolism plays an important role in maintaining lipid homeostasis and regulating immune functions. However, the regulations and mechanisms of lipid metabolism on the regional immune function of avian adipose tissue (AT) have not been reported. In this study, qRT-PCR was used to investigate the changes and relationships of different lipid metabolism pathways in chicken AT during stress-induced immunosuppression (SIIS) inhibiting immune response to Newcastle disease virus vaccine, then the miRNA regulation patterns of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene and its potential applications were further identified. The results showed that AT actively responded to SIIS, and ATGL, CPT1A and HMGCR were all the key genes involved in the processes of SIIS inhibiting the immune responses. SIIS significantly inhibited the natural and specific immune phases of the primary immune response and the initiation phase of the secondary immune response in AT by suppressing T cells by up-regulating steroid anabolism. Moreover, steroid metabolism could play dual roles in regulating the regional immune functions of AT. The miR-29a/c-3p-HMGCR network was a potential regulation mechanism of steroid metabolism in AT, and serum circulating miR-29a/c-3p had the potential as molecular markers. The study can provide valuable references for an in-depth investigation of the regional immune functions regulated by lipid metabolism in AT.