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This study was conducted to investigate the effects and mechanisms of glutamine (Gln) on the repair of acid-induced injury in dairy cow ruminal epithelial cells (RECs) in vitro. Dairy cow RECs were cultured in a medium with pH of 5.5 for 3 h and subsequently treated with various concentrations of Gln (4, 8, 12, 32 mmol/l) for 12 h. The messenger ribonucleic acid (mRNA) expression levels of occludin (OCLN), claudin 1 (CLDN1), toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and genes for inflammatory factors were measured using reverse transcription-quantitative real-time PCR (RT-qPCR). The results showed that cellular activity and OCLN expression were significantly highest at 8 mmol/l Gln (P < 0.05). CLDN1 expression was significantly higher at 4 mmol/l Gln compared to the other groups (P < 0.05). The relative expression levels of tumour necrosis factor (TNF), interleukin 1B (IL1B), C-X-C motif chemokine ligand 8 (CXCL8), TLR2 and TLR4 in the acid treatment group were significantly higher than those in the control group (P < 0.05), but they were lower in the Gln-treated groups than in the acid treatment group (P < 0.05). These findings demonstrate that Gln promotes the proliferation of RECs, enhances the expression of epithelial cell junction proteins, and inhibits the expression of inflammatory factors and surface receptors. In conclusion, Gln shows a potential for repairing acid-induced injury in RECs.

Abstract Poultry meat, an essential source of animal protein, requires stringent safety and quality measures to address public health concerns and growing international attention. This review examines both direct and indirect factors that compromise poultry meat quality in intensive farming systems. It highlights the integration of rapid and micro-testing with traditional methods to assess meat safety. The paper advocates for adopting probiotics, prebiotics, and plant extracts to improve poultry meat quality.

In this study, we investigated the effects of supplemental Glycyrrhiza polysaccharide (GCP) on growth performance and intestinal health of weaned piglets. Ninety piglets weaned at 28 days of age were randomly allocated to three groups with five replicates per treatment. Piglets were fed the following diets for 28 days: (1) CON (control group), basal diet; (2) G500, CON + 500 mg/kg GCP; (3) G1000, CON + 1000 mg/kg GCP. The results showed that supplementation with 1000 mg/kg GCP increased the average daily gain (ADG) and decreased the feed-to-gain ratio (F/G) (P

ObjectiveAccording to Bronfenbrenner’s bioecological model of human development, focus on exploring the mechanism of person characteristics (achievement motivation) in their own development (improvement of educational practice ability).MethodA survey was conducted on 1,225 pre-service teachers in Anhui Province, China, using the Achievement Motivation Scale, Professional Identity Scale, Learning Engagement Scale, and Educational Practice Ability Scale.Results(1) Achievement motivation can significantly and positively predict pre-service teachers’ educational practice ability; (2) Achievement motivation can indirectly affect pre-service teachers’ educational practice ability through the mediating effects of professional identity and learning engagement; (3) Professional identity and learning engagement play a chain mediated role in the impact of achievement motivation on pre-service teachers’ educational practice ability.

Abstract Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children’s brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3–10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.

ABSTRACT: During the perinatal period, dairy cows undergo negative energy balance, resulting in elevated circulating levels of nonesterified fatty acids (NEFA). Although increased blood NEFA concentrations are a physiological adaptation of early lactation, excessive NEFA in dairy cows is a major cause of fatty liver. Aberrant lipid metabolism leads to hepatic lipid accumulation and subsequently the development of fatty liver. Both inositol-requiring enzyme 1α (IRE1α) and c-Jun N-terminal kinase (JNK) have been validated for their association with hepatic lipid accumulation, including their regulatory functions in calf hepatocyte insulin resistance, oxidative stress, and apoptosis. Meanwhile, both IRE1α and JNK are involved in lipid metabolism in nonruminants. Therefore, the aim of this study was to investigate how IRE1α and JNK regulate lipid metabolism in bovine hepatocytes. An experiment was conducted on randomly selected 10 healthy cows (hepatic triglyceride [TG] content 5%). Liver tissue and blood samples were collected from experimental cows. Serum concentrations of NEFA and β-hydroxybutyrate (BHB) were greater, whereas serum concentrations of glucose and milk production were lower in cows with fatty liver. The western blot results revealed that dairy cows with fatty liver had higher phosphorylation levels of JNK, c-Jun, and IRE1α in the liver tissue. Three in vitro experiments were conducted using primary calf hepatocytes isolated from 5 healthy calves (body weight: 30–40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h, which showed that the phosphorylated levels of JNK, c-Jun, and IRE1α increased in both linear and quadratic effects. In the second experiment, hepatocytes were treated with high concentrations of NEFA (1.2 mM) for 12 h with or without SP600125, a canonical inhibitor of JNK. Western blot results showed that SP600125 treatment could decrease the expression of lipogenesis-associated proteins (PPARγ and SREBP-1c) and increase the expression of fatty acid oxidation (FAO)-associated proteins (CPT1A and PPARα) in NEFA-treated hepatocytes. The perturbed expression of lipogenesis-associated genes (FASN, ACACA, and CD36) and FAO-associated gene ACOX1 were also recovered by JNK inhibition, indicating that JNK reduced excessive NEFA-induced lipogenesis and FAO dysregulation in calf hepatocytes. Third, short hairpin RNA targeting IRE1α (sh-IRE1α) was transfected into calf hepatocytes to silence IRE1α, and KIRA6 was used to inhibit the kinase activity of IRE1α. The blockage of IRE1α could at least partially suppressed NEFA-induced JNK activation. Moreover, the blockage of IRE1α downregulated the expression of lipogenesis genes and upregulated the expression of FAO genes in NEFA-treated hepatocytes. In conclusion, these findings indicate that targeting the IRE1α-JNK axis can reduce NEFA-induced lipid accumulation in bovine hepatocytes by modulating lipogenesis and FAO. This may offer a prospective therapeutic target for fatty liver in dairy cows.

Tumor-associated macrophage (TAM) play a crucial role in the immune microenvironment of lung cancer. Through changes in their phenotype and phagocytic functions, TAM contribute to the initiation and progression of lung cancer. By promoting the formation of an immune-suppressive microenvironment and accelerating the growth of abnormal tumor vasculature, TAM facilitate the invasion and metastasis of lung cancer. Macrophages can polarize into different subtypes with distinct functions and characteristics in response to various stimuli, categorized as anti-tumor M1 and pro-tumor M2 types. In tumor tissues, TAM typically polarize into the alternatively activated M2 phenotype, exhibiting inhibitory effects on tumor immunity. This article reviews the role of anti-angiogenic drugs in modulating TAM phenotypes, highlighting their potential to reprogram M2-type TAM into an anti-tumor M1 phenotype. Additionally, the functional alterations of TAM play a significant role in anti-angiogenic therapy and immunotherapy strategies. In summary, the regulation of TAM polarization and function opens up new avenues for lung cancer treatment and may serve as a novel target for modulating the immune microenvironment of tumors.

Abstract Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions.

Objective The purpose of this systematic review and meta-analysis was to assess the clinical efficacy and safety of ultrasound (US)-guided high intensity focused ultrasound (HIFU) in the treatment of breast fibroadenoma in different studies.Methods Studies evaluating the efficacy and safety of US-guided HIFU in the treatment of histologically-proven FA with follow-up outcomes of more than 3 months were searched through MEDLINE/PubMed databases. Volume reduction rate (VRR) and side effects were extracted and compared for further analysis.Results Of 29 identified articles, 10 studies involving 385 women and more than 545 FAs met the inclusion criteria. The mean VRR at 6 months and 12 months after HIFU was 52.00% and 72.00%. In terms of intraoperative safety, nine studies reported mild to moderate pain, with an average visual analogue scale (VAS) score ranging from 1.60 to 7.10. The most common postoperative side effect associated with HIFU was subcutaneous ecchymosis and less frequent were pain, erythema, and skin pigmentation, most of which disappeared within weeks. No serious side effects were observed.Conclusion S-guided HIFU is an effective and safe noninvasive treatment for breast FA that does not cause serious side effects. Further studies are needed to explore crucial influencing factors of VRR.

In this study, we conducted a thorough investigation into the mechanisms by which miR-29 influences lipid metabolism. Thirty-two cows were selected and categorized into distinct groups based on their liver triglyceride (TG) content: healthy, mild fatty liver, and moderate fatty liver groups. Dairy cows with moderate fatty liver showed higher levels of hepatic lipid accumulation, MDA content and serum AST, ALT and ALP contents and lower hepatic catalase CAT and SOD activities. Subsequently, hepatocytes isolated from healthy calves were exposed to sodium oleate (SO) in the presence or absence of pre-incubation with miR-29 inhibitor or inhibitor NC. Pre-transfection with miR-29 inhibitor resulted in reduced hepatocyte lipid accumulation and MDA levels, as well as decreased levels of AST, ALT, and ALP in the supernatant. In the miR-29 inhibitor + SO group, there was an increase in the expression of SREBP-1, FAS, SCD1, and Sirt1. Meanwhile, the expression of PPARα, CPT1, CPT2, PGC-1α, NRF-1, UCP2, and miR-29 were observed to be decreased. In comparison to the miR-29 inhibitor + SO group, some of the measured indicators showed partial reversal in the miR-29 inhibitor + siSirt1 + SO group. Collectively, these findings provide evidence that miR-29 may play a crucial role in the pathogenesis of fatty liver in dairy cows.

Short-form video apps, such as TikTok, have become popular worldwide. Compared to traditional social media, they have powerful push algorithms and are more entertaining, which might lead to some negative effects. Research has attempted to identify the relationship between short-form video use and depression, but the processes mechanism underly the relationship was few in number. The present study explored the association between short-form video use and depression among Chinese adolescents and analyzed the mediating roles of need gratification and short-form video addiction. The participants included 1302 senior high school students (Mage = 16.03, SD = 0.76, 42.6 % boys). And a structure equation model with chain mediating was established using Mplus. The results showed (1) a direct association between short-form video use and adolescent depression, (2) that entertainment need gratification, social-related need gratification, and short-form video addiction acted as chain mediating factors, and (3) no gender difference in the model. The present study's findings revealed the important mediating role of addictive behavior between normal use behavior and depression and suggested that preventative and interventional plans based on need gratification should be developed to reduce short-form video addiction and improve mental health.

Abstract Irinotecan (Ir) is commonly employed as a first-line chemotherapeutic treatment for colorectal cancer (CRC). However, tremendous impediments remain to be addressed to surmount drug resistance and ameliorate adverse events. Poly-ADP-Ribose Polymerase (PARP) participates in the maintenance of genome stability and the repair of DNA damage, thus playing a critical role in chemotherapy resistance. In this work, we introduce a novel curative strategy that utilizes nanoparticles (NPs) prepared by dynamic supramolecular co-assembly of Ir and a PARP inhibitor (PARPi) niraparib (Nir) through π-π stacking and hydrogen bond interactions. The Ir and Nir self-assembled Nano-Twin-Drug of (Nir-Ir NPs) could enhance the therapeutic effect on CRC by synergistically inhibiting the DNA damage repair pathway and activating the tumor cell apoptosis process without obvious toxicity. In addition, the Nir-Ir NPs could effectively reverse irinotecan-resistance by inhibiting the expression of multiple resistance protein-1 (MRP-1). Overall, our study underscores the distinctive advantages and potential of Nir-Ir NPs as a complementary strategy to chemotherapy by simultaneously overcoming the Ir resistance and improving the anti-tumor efficacy against CRC.

The prevalence of excessive drinking-related alcoholic liver disease (ALD) is rising, yet therapeutic options remain limited. High alcohol consumption and consequent oxidative metabolism by cytochrome P450 (CYP) can lead to extremely high levels of reactive oxygen species, which overwhelm cellular defenses and harm hepatocytes. Our previous investigations showed that inhibiting Cyp2e1 using RNA interference reduced the incidence of ALD. However, compensatory mechanisms other than CYP2E1 contribute to oxidative stress in the liver. Therefore, we coupled triple siRNA lipid nanoparticles (LNPs) targeting Cyp2e1 with two isoenzymes Cyp4a10 and Cyp4a14 to treat ALD mouse models fed with Lieber–Decarli ethanol liquid diet for 12 weeks at the early (1st week), middle (5th week), and late (9th week) stages. The administration of triple siRNA LNPs significantly ameliorated chronic alcoholic liver injury in mice, and early treatment achieved the most profound effects. These effects can be attributed to a reduction in oxidative stress and increased expression of antioxidant genes, including Gsh-Px, Gsh-Rd, and Sod1. Moreover, we observed the alleviation of inflammation, evidenced by the downregulation of Il-1β, Il-6, Tnf-α, and Tgf-β, and the prevention of excessive lipid synthesis, evidenced by the restoration of the expression of Srebp1c, Acc, and Fas. Finally, triple siRNA treatment maintained normal metabolism in lipid oxidation. In brief, our research examined the possible targets for clinical intervention in ALD by examining the therapeutic effects of triple siRNA LNPs targeting Cyp2e1, Cyp4a10, and Cyp4a14. The in vivo knockdown of the three genes in this study is suggested as a promising siRNA therapeutic approach for ALD.

Abstract Background Anlotinib has demonstrated encouraging clinical outcomes in the treatment of lung cancer, soft tissue sarcoma and thyroid carcinoma. Several clinical studies have shown a relationship between anlotinib treatment and the occurrence of hyperlipidemia. The fundamental mechanisms, however, are still largely unclear. Here, the effect of anlotinib on lipid metabolism in an animal model and human cancer cells was evaluated and the role of lipid metabolism in the antitumor efficacy of anlotinib was investigated. Methods The C57BL/6 J mouse model as well as A549 and H460 human lung cancer cell lines were used to examine the impact of anlotinib on lipid metabolism both in vivo and in vitro. Levels of triglycerides, high-density lipoprotein, low-density lipoprotein (LDL), and total cholesterol in serum or cell samples were determined using assay kits. The expression levels of crucial genes and proteins involved in lipid metabolism were measured by quantitative RT-PCR and Western blotting. Furthermore, exogenous LDL and knockdown of low-density lipoprotein receptor (LDLR) were used in H460 cells to investigate the relevance of lipid metabolism in the anticancer efficacy of anlotinib. Results Anlotinib caused hyperlipidemia in C57BL/6 J mice, possibly by downregulating hepatic LDLR-mediated uptake of LDL cholesterol. AMP-activated protein kinase and mammalian target of rapamycin inhibition may also be involved. Additionally, anlotinib enhanced sterol response element binding protein 1/2 nuclear accumulation as well as upregulated LDLR expression in A549 and H460 cells, which may be attributable to intracellular lipid accumulation. Knockdown of LDLR reduced intracellular cholesterol content, but interestingly, anlotinib significantly improved intracellular cholesterol accumulation in LDLR-knockdown cells. Both exogenous LDL and LDLR knockdown decreased the sensitivity of cells to anlotinib. Conclusions Anlotinib modulates host lipid metabolism through multiple pathways. Anlotinib also exerts a significant impact on lipid metabolism in cancer cells by regulating key transcription factors and metabolic enzymes. In addition, these findings suggest lipid metabolism is implicated in anlotinib sensitivity.

AbstractObjective To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer.Materials and methods Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared.Results The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer.Conclusions The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor.

AbstractObjective This nonrandomized prospective clinical trial aimed to assess the efficacy, safety and follow-up outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) surgery in patients with breast fibroadenoma.Methods With the approval of the institutional ethics committee and written informed consent, a total of 113 patients diagnosed with breast fibroadenoma by core-needle biopsy in our hospital were recruited. USgHIFU surgery was performed under local anesthesia. Contrast-enhanced ultrasound (CEUS) or contrast-enhanced MRI (CEMRI) was performed to evaluate the nonperfused volume (NPV). The patients were followed up with physical examination and ultrasound imaging.Results The clinical outcome of 85 patients with 147 fibroadenomas with a follow-up time of more than 3 months was analyzed in this study. Fifty-two patients had one lesion, twenty-one patients had two lesions and twelve patients had more than two lesions. During USgHIFU, the median localization time for all fibroadenomas was 3 (interquartile range: 1, 5) min, and the median treatment time was 9 (interquartile range: 5, 15) min. Under local anesthesia, all the patients tolerated the treatment well. No serious epidermal burns were observed in any of the patients. Based on CEUS or CEMRI imaging evaluation, the median NPV ratio was 100% (interquartile range: 79.2%, 116.8%). The VRR were 26.77 ± 50.05%, 50.22 ± 42.01% and 72.74 ± 35.39% at 3–6 months, 6–12 months and >12 months, respectively, which showed significant statistical difference (p

AbstractObjective To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA).Methods A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment.Results All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %.Conclusion Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis.Key pointsThis study was the first study of detailed histopathological analysis for FAs after FUAS treatment.FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells.FUAS ablation of multiple fibroadenomas is safe and effective.

ABSTRACT: Fatty liver (i.e., hepatic lipidosis) is a prevalent metabolic disorder in dairy cows during the transition period, characterized by excess hepatic accumulation of triglyceride (TG), tissue dysfunction, and cell death. Detailed pathological changes, particularly hepatic fibrosis, during fatty liver remain to be determined. Liver fibrosis occurs as a consequence of liver damage, resulting from the excessive accumulation of extracellular matrix, which distorts the architecture of the normal liver, compromising its normal synthetic and metabolic functions. Thus, we aimed to investigate liver fibrosis status and its potential causal factors including oxidative stress, hepatocyte apoptosis, and production of inflammatory cytokines in the liver of cows with fatty liver. Forty-five dairy cows (parity, 3–5) were selected, and liver biopsy and blood were collected on the second week postpartum (days in milk, 10–14 d). On the basis of the degree of lipid accumulation in liver, selected cows were categorized into normal (n = 25; TG

Family income is an important factor that affects depression in children and can indirectly be associated with children’s development through family and individual factors. However, few studies have examined the mechanism of multiple risk factors. Therefore, this study focused on the relationship between family income and child depression, as well as the chain mediating the roles of parental involvement and children’s self-esteem both in single-parent families and intact families. A total of 1355 primary school students completed questionnaires that assessed family income, parental involvement, children’s self-esteem, and depression. The results showed that family income influenced child depression through both the mediating roles of parental involvement and children’s self-esteem and the chain mediating role of parental involvement and children’s self-esteem. Meanwhile, family income only influenced child depression through chain mediation in single-parent families. The group differences in the mechanism of depression provide a reference for empirical research on depression intervention in children from different family structures.

The potential hepatotoxicity of Herba Epimedii is a focal point in traditional Chinese medicine security applications. As determined in our previous study, the flavonoid constituents of Herba Epimedii, sagittatoside A, icariside I, baohuoside I and icaritin, are related to the hepatotoxicity of this herb. However, the hepatotoxic mechanism of these components needs to be clarified further, and whether these components can maintain their injury action following liver metabolism needs to be confirmed. Herein, the effects of sagittatoside A, icariside I, baohuoside I and icaritin on the apoptosis of HepG2 cells and the expression of key proteins, including Bax, Bcl-2, Caspase-3 and Caspase-9, were evaluated. Moreover, with liver microsome incubation, the influences of metabolism on the apoptotic activities of these components were investigated. Then, by HPLC–MS/MS analyses, the in vitro metabolic stability of these components was determined after incubation with different kinds of liver microsomes to explain the reason for the influence. The results suggested that sagittatoside A, baohuoside I and icaritin could induce apoptosis, which is likely to be closely related to the induction of the intrinsic apoptosis pathway. After metabolic incubation, the sagittatoside A and icaritin metabolism mixture could still induce apoptosis due to less metabolic elimination, while the icariside I and baohuoside I metabolism mixtures respectively got and lost the ability to induce apoptosis, probably due to quick metabolism and metabolic transformation. The findings of this study may provide important references to explore the material basis and mechanism of the hepatotoxicity of Herba Epimedii.

IntroductionMacrophages or T-lymphocytes triggered inflammation and, consequently, activated glial cells may contribute to neuroinflammation and neurotransmitter dysfunction in schizophrenia (SZ), while omega(n)-3 polyunsaturated fatty acids (PUFAs) can attenuate some SZ symptoms through anti-inflammatory effects. However, the correlations between macrophage/T-lymphocyte-produced cytokines and glia phenotypes, between inflammatory status and PUFAs composition, between cytokines and neurotransmitter function, and between n-3 PUFAs and neurotransmitter abnormality in SZ are unclear.MethodsChanges in T-helper (h) patterns, peripheral macrophage/glial markers, PUFAs profile, membrane fluidity, and neurotransmitter functions were evaluated in SZ patients (n = 50) and healthy controls (n = 30) using ELISA, gas chromatography, fluorescence anisotropy techniques, and HPLC, respectively.ResultsCompared to the control, blood lymphocyte proliferation, the concentration of macrophage/microglia phenotype M1 markers, including cytokines IL-1β, TNF-α (Th1) and IL-6 (Th2), and astrocyte phenotype A1 marker S100β was significantly increased, while IL-17 and n-3 PUFAs contents, n-3/n-6 ratio, and membrane fluidity (FLU) were significantly decreased in SZ. Moreover, increased DA and HVA, decreased 5-HT and NE, and their metabolites appeared in SZ. Moreover, negative correlations between IL-6 and A2 marker Brain-Derived Neurotrophic Factor (BDNF) or n-3 PUFAs EPA and between IL-1β and FLU or 5HIAA, while positive correlations between EPA and 5-HIAA and between FLU and DHA were found in SZ.DiscussionThese findings showed (1) no clear Th pattern, but pro-inflammatory-dominant immunity occurred; (2) the pro-inflammatory pattern may result in the activated microglia M1 and astrocyte A1 phenotype; and (3) increased pro-inflammatory cytokines were related to decreased n-3 PUFA and decreased membrane fluidity and dysfunctional neurotransmitter systems in SZ.

BackgroundPeer victimization used to be considered as a crucial risk factor for children addicted to the internet. Whereas some victimized ones are function better than would be expected. Variability across individuals indicates that it is necessary to understand how children cope with being bullied and why they do not exhibit maladaptive outcomes.ObjectiveWe explored the underlying mechanisms by testing whether subjective well-being was a mediator between peer victimization and Internet addiction and whether the mediation effects conditioned on the levels of parent–child relationship (PCR).MethodsData were collected from 65, 868 elementary school students in China (Mage = 9.56 years, SD = 0.62, 54.0% male) using four questionnaires.ResultsWe found that: (1) subjective well-being can partially mediate the relationship of the two variables; and (2) PCR can moderate direct path and second half of the intermediary process. These moderating effects were stronger for children with higher PCR vs. lower PCR, as a strong PCR can help children to deal with intense emotions and to access effective resources to obtain support.ConclusionThis study deepens our understanding of how peer victimization leads to internet addiction, identifies a supportive PCR as a crucial factor that strengthens the resilience of child victims, and highlights the value of focusing on improving the relationship between parents and children in intervening internet addiction related to peer victimization.

Abstract Locoregional delivery of chimeric antigen receptor (CAR)-modified T (CAR-T) cells has emerged as a promising strategy for brain tumors. However, the complicated ex vivo cell manufacturing procedures and the rapid progression of the disease have limited its broader applications. Macrophages (MΦs) exhibit unique effector functions and a high degree of infiltration within the solid tumor microenvironment (TME), especially in the brain, where MΦs function as structural support, and the main immune effector cells of the CNS represent 5–12% of brain cells. Here, we report a synthetic universal DNA nanocarrier for in situ genetic editing of intratumoral MΦs with an ErbB2-specific CAR to direct their phagocytic activity towards tumors and subsequently initiate a locoregional antitumor immune response. Specifically, we demonstrated that when delivered locoregionally, the RP-182 peptide, located in the shell of a nanoparticle, targeted MΦs and reprogrammed M2-like tumor-associated macrophages (TAMs) to an antitumor M1-like phenotype. Subsequently, the CAR gene-laden DNA nanocomplex can be used to introduce ErbB2-targeted CAR, and the generated CAR-MΦs then act as “living” cures, thereby serially clearing the invasive tumor cells. Our work demonstrates a practical antitumor immunotherapy for brainstem gliomas (BSGs) that may be broadly applicable for patients suffering from other ErbB2-positive solid malignancies.

Background & Aims: Gamma delta (γδ) T cells are heterogeneous and functionally committed to producing interferon (IFN)-γ and interleukin (IL)-17. γδT cells are defined as tissue-resident lymphocytes in barrier tissues. Among them, IL-17–producing γδT cells are relatively abundant in the liver. However, a systematic and comprehensive understanding of the residency characteristics and function of hepatic IL-17A+ γδT cells is lacking. Methods: We undertook a single-cell analysis of γδT17 cells derived from murine livers. A parabiosis model was used to assess tissue residency. Fluorescence-activated cell sorting and adoptive transfer experiments were used to investigate the response and protective role of liver-resident CD44hiCD27− γδT cells in Listeria monocytogenes infection. Transwell assay was used to assess the role of macrophages in the chemotaxis of liver-resident CD44hiCD27− γδT cells. Results: We identified hepatic IL-17A–producing γδT cells as CD44hiCD27− γδT cells. They had tissue-resident characteristics and resided principally within the liver. Vγ6+ T cells also exhibited liver-resident features. Liver-resident CD44hiCD27− γδT cells had significantly increased proliferation capacity, and their proportion rapidly increased after infection. Some CD44hiCD27− γδT cells could produce IL-17A and IFN-γ simultaneously in response to Lm infection. Adoptive transfer of hepatic CD44hiCD27− γδT cells into Lm-infected TCRδ−/− mice led to markedly lower bacterial numbers in the liver. Hepatic macrophages promoted the migration and accumulation of liver-resident CD44hiCD27− γδT cells into infection sites. Conclusions: Liver-resident CD44hiCD27− γδT cells protect against Lm infection. Hepatic macrophages coordinate with liver-resident CD44hiCD27− γδT cells and contribute to the clearance of Lm at the early stage of infection corporately.

Abstract Tibial dyschondroplasia (TD) with multiple incentives is a metabolic skeletal disease that occurs in fast-growing broilers. Perturbations in the gut microbiota (GM) have been shown to affect bone homoeostasis, but the mechanisms by which GM modulates bone metabolism in TD broilers remain unknown. Here, using a broiler model of TD, we noted elevated blood glucose (GLU) levels in TD broilers, accompanied by alterations in the pancreatic structure and secretory function and damaged intestinal barrier function. Importantly, faecal microbiota transplantation (FMT) of gut microbes from normal donors rehabilitated the GM and decreased the elevated GLU levels in TD broilers. A high GLU level is a predisposing factor to bone disease, suggesting that GM dysbiosis-mediated hyperglycaemia might be involved in bone regulation. 16S rRNA gene sequencing and short-chain fatty acid analysis revealed that the significantly increased level of the metabolite butyric acid derived from the genera Blautia and Coprococcus regulated GLU levels in TD broilers by binding to GPR109A in the pancreas. Tibial studies showed reduced expression of vascular regulatory factors (including PI3K, AKT and VEFGA) based on transcriptomics analysis and reduced vascular distribution, contributing to nonvascularization of cartilage in the proximal tibial growth plate of TD broilers with elevated GLU levels. Additionally, treatment with the total flavonoids from Rhizoma drynariae further validated the improvement in bone homoeostasis in TD broilers by regulating GLU levels through the regulation of GM to subsequently improve intestinal and pancreatic function. These findings clarify the critical role of GM-mediated changes in GLU levels via the gut–pancreas axis in bone homoeostasis in TD chickens.

Abstract Background Newcastle disease virus (NDV) strain ZM10, a typical enterotropic avirulent vaccine strain, has been widely used in China for chickens against Newcastle disease. To elucidate its enterotropic mechanism and develop recombiant multivalent vaccines based on it, the reverse genetics system for NDV ZM10 is an indispensable platform. Results A full-length cDNA clone of NDV ZM10 and three supporting plasmids were constructed using the ligation-independent cloning method. Recombinant NDV rZM10 was successfully rescued after these plasmids were co-transfected into BHK-21 cells. Besides, the recombinant virus rZM10-RFP encoding the red fluorescent protein was generated by inserting the RFP gene into the full-length clone of NDV between the P and M genes. These rescued viruses were genetically and biologically identical to the parental strain and showed similar growth kinetics. Conclusion The recovery system of NDV ZM10 strain was established, and can be used as a foundation for research on the enterotropic mechanism and development of multivalent vaccines against viral diseases of livestock and poultry.

Objective To explore the learning curve of high intensity focus ultrasound (HIFU) treatment for breast fibroadenoma.Methods A database of 110 patients with 255 breast fibroadenomas who underwent HIFU treatment at two different clinical centers (Center 1 and 2) were retrospectively analyzed. The learning curves of HIFU treatment for breast fibroadenoma were drawn by CUSUM analysis in two centers, respectively. According to the inflection point of the learning curves, the treatment was divided into two groups: initial phase and consolidation phase. HIFU treatment parameters were compared between two groups. The effectiveness and safety results were also evaluated.Results The inflection points of the learning curves were the 60th treatment in Center 1 and the 65th treatment in Center 2. The screening time, treatment time, sonication time and hyperechoic scale change time were significantly shorter in consolidation phase than those in initial phase of the two centers (p

Objective To explore a new high-intensity focused ultrasound (HIFU) sonication strategy for cesarean scar pregnancy (CSP) and to compare the clinical effectiveness and safety of this new HIFU sonication strategy with the conventional HIFU sonication strategy followed by ultrasound-guided dilation and curettage (USg-D&C) for CSP. Materials and methods 91 patients with CSP treated by HIFU and USg-D&C in People’s Hospital of Deyang City between January 2017 and December 2019 were retrospectively reviewed in this study. Based on the HIFU sonication strategy, patients were divided to two groups: 44 patients were exposed to ‘C-shape’ sonication layer by layer around the implantation location of the pregnancy sac (control group), while the other 47 patients were exposed to ‘I-shape’ sonication layer by layer only on the deep part which close to the bladder of the implantation location of the pregnancy sac (experimental group). The differences in clinical efficacy between the two groups were analyzed. Baseline characteristics, technical parameters of HIFU treatment and USg-D&C data were recorded. Adverse events were also recorded. Results No statistically significant difference was observed between the two groups in baseline characteristics including age, body mass index (BMI), menopause time, largest diameter of gestational sac, pretreatment serum β-hCG, thickness of gestational sac, embedding myometrium, previous cesarean sections and interval from last cesarean section (CS). The average treatment intensity in the experimental group was significantly lower than that in the control group (p < .05). The median sonication time, total energy used for HIFU ablation, and energy efficiency factor (EEF) in the experimental group were significantly lower than the control group (p < .05). No statistically significant difference was observed between the two groups in treatment power and treatment time (p > .05). Sciatic/buttock pain and postoperative lower abdominal pain in the control group were significantly stronger than that in the experimental group (p < .05). There were no statistically significant differences in post-HIFU vaginal bleeding and discharging, urinary tract irritation, the operation time of USg-D&C, the amount of vaginal bleeding during USg-D&C, and the time for serum β-hCG back to a normal level between the two groups (p > .05). Conclusions The ‘I-shape’ strategy of HIFU treatment for CSP was effective and safe, with shorter sonication time, less energy input and lower incidence of sonication-related pain occurred in postoperative lower abdominal and sciatic nerve/buttock.

Objective To investigate the factors influencing the sonication dosage and efficiency of ultrasound-guided high intensity focused ultrasound (USgHIFU) for breast fibroadenomas.Materials and Methods Forty-nine patients with 78 breast fibroadenomas who underwent USgHIFU were retrospectively analyzed. The energy efficiency factor (EEF) was set as dependent variable, and the factors possibly influencing the sonication dosage, including age, body mass index (BMI), fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin, distance from the deep margin of the fibroadenoma to pectoralis major, types of near field acoustic pathway, and Adler blood flow classification of ultrasound, were set as independent variables. The correlation between EEF and these independent variables were analyzed, and an optimal scaling regression model was established.Results Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway had significant correlation with EEF (p

ABSTRACT: Sustained lipolysis and insulin resistance increase the risk of metabolic dysfunction in dairy cows during the transition period. Proinflammatory cytokines are key regulators of adipose tissue metabolism in nonruminants, but biological functions of these molecules in ruminants are not well known. Thus, the objective of this study was to investigate whether tumor necrosis factor-α (TNF-α) could affect insulin sensitivity and lipolysis in bovine adipocytes as well as the underlying mechanisms. Bovine adipocytes (obtained from the omental and mesenteric adipose depots) isolated from 5 Holstein female calves (1 d old) with similar body weight (median: 36.9 kg, range: 35.5–41.2 kg) were differentiated and used for (1) treatment with different concentrations of TNF-α (0, 0.1, 1, or 10 ng/mL) for 12 h; (2) pretreatment with 10 μM lipolytic agonist isoproterenol (ISO) for 3 h, followed by treatment with or without 10 ng/mL TNF-α for 12 h; and (3) pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM for 2 h) and nuclear factor kappa B (NF-κB) inhibitor BAY 11–7082 (10 μM for 1 h) followed by treatment with or without 10 ng/mL TNF-α for 12 h. The TNF-α increased glycerol content in supernatant, decreased triglyceride content and insulin-stimulated phosphorylation of protein kinase B suggesting activation of lipolysis and impairment of insulin sensitivity. The TNF-α reduced cell viability, upregulated mRNA abundance of Caspase 3 (CASP3), an apoptosis marker, and increased activity of Caspase 3. In addition, increased phosphorylation of NF-κB and JNK, upregulation of mRNA abundance of interleukin-6 (IL-6), TNFA, and suppressor of cytokine signaling 3 (SOCS3) suggested that TNF-α activated NF-κB and JNK signaling pathways. Furthermore, ISO plus TNF-α-activated NF-κB and JNK signaling pathway to a greater extent than TNF-α alone. Combining TNF-α and ISO aggravated TNF-α-induced apoptosis, insulin insensitivity and lipolysis. In the absence of TNF-α, inhibition of NF-κB and JNK did not alter glycerol content in supernatant, triglyceride content or insulin-stimulated phosphorylation of protein kinase B. In the presence of TNF-α, inhibition of NF-κB and JNK alleviated TNF-α-induced apoptosis, insulin insensitivity and lipolysis. Overall, TNF-α impairs insulin sensitivity and induces lipolysis and apoptosis in bovine adipocytes, which may be partly mediated by activation of NF-κB and JNK. Thus, the data suggested that NF-κB and JNK are potential therapeutic targets for alleviating lipolysis dysregulation and insulin resistance in adipocytes.

ABSTRACT: The search for effective in-feed antibiotic alternative is growing due to the global trend to reduce or ban the utilization of antibiotics as growth promotors in poultry diets. This study was processed to assess the effect of dietary refined functional carbohydrates (RFCs) replacing antibiotic growth promoters (AGP) on growth performance, intestinal morphologic structure and microbiota, as well as intestinal immune function and barrier function of broilers reared on a commercial broilers farm. Trials contained 3 treatments with 4 replicate broiler houses, with about 25,000 birds each room. The treatments were control group (CON), RFCs group (CON + 100 mg/kg RFCs), and AGP group (CON + 50 mg/kg bacitracin methylene disalicylate (BMD), respectively. Results showed that RFCs and AGP group significantly increased (P < 0.05) average daily gain (ADG) during d 22 to 45 in contrast to control. Compared with the control and AGP-treated groups, feeding RFCs increased (P < 0.05) jejunal villus height to crypt depth ratio. AGP addition reduced (P < 0.05) the jejunal villi surface area compared to broilers fed control and RFC supplemented diets. Supplementation of RFCs promoted (P < 0.05) the growth of Lactobacillus but inhibited Escherichia coli and Salmonella proliferation compared with the control group. Inclusion of RFCs and BMD enhanced (P < 0.05) antibody titers against avian influenza virus H9 compared with control. RFCs and AGP both down-regulated (P < 0.05) intestinal TLR4 mRNA levels, whereas RFCs tended to up-regulate (P = 0.05) IFN-γ gene expression compared to control. Expression of intestinal tight junction genes was not affected by either AGP or RFCs supplementation. Based on above observation, we suggested that RFCs could replace in-feed antibiotic BMD in broiler diets for reducing intestinal pathogenic bacteria and modulating immunity of broilers.

ABSTRACT: Activated autophagy-lysosomal pathway (ALP) can degrade virtually all kinds of cellular components, including intracellular lipid droplets, especially during catabolic conditions. Sustained lipolysis and increased plasma fatty acids concentrations are characteristic of dairy cows with hyperketonemia. However, the status of ALP in adipose tissue during this physiological condition is not well known. The present study aimed to ascertain whether lipolysis is associated with activation of ALP in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes. In vivo, blood and subcutaneous adipose tissue (SAT) biopsies were collected from nonhyperketonemic (nonHYK) cows [blood β-hydroxybutyrate (BHB) concentration

C-terminal truncation of a-syn results in a more extended and exposed conformation, providing further insight into the pathological role of this truncation event in the progression of Parkinson’s disease.

Pulmonary hypertension due to left heart disease (PH-LHD) represents approximately 65%–80% of all patients with PH. The progression, prognosis, and mortality of individuals with left heart failure (LHF) are significantly influenced by PH and right ventricular (RV) dysfunction. Consequently, cardiologists should devote ample attention to the interplay between HF and PH. Patients with PH and HF may not receive optimal benefits from the therapeutic effects of prostaglandins, endothelin receptor antagonists, or phosphodiesterase inhibitors, which are specific drugs for pulmonary arterial hypertension (PAH). Sacubitril/valsartan, the angiotensin receptor II blocker-neprilysin inhibitor (ARNI), was recommended as the first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF) by the 2021 European Society of Cardiology Guidelines. Although ARNI is effective in treating left ventricular (LV) enlargement and lower ejection fraction, its efficacy in treating individuals with PH and HF remains underexplored. Considering its vasodilatory effect at the pre-capillary level and a natriuretic drainage role at the post-capillary level, ARNI is believed to have a broad range of potential applications in treating PH-LHD. This review discusses the fundamental pathophysiological connections between PH and HF, emphasizing the latest research and potential benefits of ARNI in PH with various types of LHF and RV dysfunction.

Aims: The purpose of this research was to assess the effect of chlorogenic acid (CGA) in the diet on ileac structure, barrier function, immunological state, and microbial profile of broiler chickens in a high stocking density (HD) environment.Methods: Four hundred and seventy-six male AA broiler chickens were randomly split into four groups, two with a normal stocking density (ND) of fourteen birds per m2 and two with a high stocking density of twenty-two birds per m2. Each of the treatments consisted of five replicates. One of the two ND and HD groups received the usual feed, while the other two were given at 1.5 g/kg CGA as part of their dietary regimen.Results: The ND CGA group showed a greater increase in villus height and villus height/crypt depth compared to the ND group at 35 and 42 days. The HD group experienced a greater elevation in villus height due to CGA supplementation than the HD group across days 28, 35, and 42. At day 42, the HD group saw a decline in OCLN and ZO-1 mRNA expression in the ileum, but CGA was able to restore them. The HD group experienced a greater rise in OCLN mRNA than the control HD group when supplemented with CGA. The expression of TNF-α, IL-1β, and IL-6 in the ileum was higher in the HD group, and CGA supplementation enhanced this effect. The HD group experienced a greater rise in IL-10 mRNA expression than the control group following the administration of CGA. The HD group showed reduced alpha diversity and an increase in detrimental microbes such as Turicibacter and Shigella in the gut compared to the ND group, while the HD CGA group saw a reduction in Turicibacter, Shigella, and other harmful microbes. These findings reveal that HD stress suppressed the growth of ileac villi, decreased the expression of tight-junction genes, amplified the expression of inflammatory genes, and disturbed the gut microbiota, ultimately leading to increased intestinal permeability.Conclusion: We conclude that when chickens are given dietary CGA, the disruption of the ileac barrier and increased oxidative damage and inflammation due to HD stress are reduced, which increases ileac integrity and the presence of beneficial intestinal bacteria.

Examining iron (Fe) speciation in marine sediments is critical to understand Fe and carbon biogeochemical cycling in polar regions. In this study, we investigated the speciation of Fe in sediments from Prydz Bay and the adjacent Southern Ocean, and examined the factors controlling Fe speciation and its relationship with total organic carbon (TOC). Our results reveal that unreactive silicate Fe (FeU) is the dominant pool of total Fe (FeT), followed by poorly reactive sheet silicate Fe (FePRS), reducible crystalline Fe oxides (Feox2), easily reducible amorphous/poorly crystalline Fe oxides (Feox1), and magnetite (Femag), with carbonate-associated ferrous Fe (Fecarb) being the smallest pool. The highly reactive Fe (FeHR)/FeT ratios (0.13 ± 0.06) in our study area are among the lowest end-member globally, primarily due to weak bedrock weathering and slow glacier melting. The Feox1/FeT ratios are similar to those in continental shelf and marginal seas containing highly weathered materials, while the Feox2/FeT ratios are significantly lower. This result implicates that low temperature inhibits the aging of iceberg melting-sourced Feox1 potentially, and accordingly the regulation of weathering on the FeHR/FeT ratio is mainly reflected in Feox2/FeT ratio. There are no significant correlations between TOC and FeHR, Fecarb, Feox1 or Feox2 in the research region. Four distinct patterns of TOC/FeHR ratio can be discerned by summarizing the global data set: (a) high TOC/FeHR ratios (> 2.5) are likely the result of high marine primary productivity and low chemically weathered source materials; (b) low TOC/FeHR ratios (< 0.6) are caused by high rates of FeHR inputs and OC remineralization; (c) mid-range TOC/FeHR ratios (0.6 – 2.5) typical of most river particulates and marginal sea sediments indicate the same FeHR and OC sources and/or interactions between each other; (d) both low TOC and FeHR content is the result of low marine primary productivity and weak chemical weathering. Our findings provide new insights into the relationship between FeHR and TOC in polar sediments.

IntroductionThe impairment of blood-brain barrier (BBB) is one of the key contributors to maternal inflammation induced brain damage in offspring. Our previous studies showed Fibrinogen-like protein 2 (FGL2) deficiency alleviated maternal inflammation induced perinatal brain damage. However, its role in BBB remains undefined.MethodsLipopolysaccharide (LPS) was intraperitoneally injected to dams at Embryonic day 17 to establish maternal inflammation model. FGL2 knockout mice and primary brain microvascular endothelial cells (BMECs) were used for the in-vivo and in-vitro experiments. BBB integrity was assessed by sodium fluorescein extravasation and tight junction (TJ) protein expression. Oxidative stress and the activation of PI3K/NF-κB pathway were evaluated to explore the mechanisms underlying.ResultsUpon maternal inflammation, BBB integrity was remarkedly reduced in neonatal mice. Meanwhile, FGL2 expression was consistently increased in BBB-impaired brain as well as in LPS-treated BMECs. Moreover, FGL2 deficiency attenuated the hyperpermeability of BBB, prevented the decline of TJ proteins, and reduced the cytokine expressions in LPS-exposed pups. Mechanistically, the indicators of oxidative stress, as well as the activation of PI3K/NF-κB pathway, were upregulated after LPS exposure in vivo and in vitro. FGL2 deletion decreased the generation of ROS and NO, reduced the endothelial iNOS and NOX2 expressions, and suppressed the PI3K/NF-κB pathway activation. Besides, inhibition of PI3K by LY294002 decreased the oxidative stress in LPS-treated wild-type BMECs. While, overexpression of PI3K by lentivirus reemerged the induction of NOX2 and iNOS as well as NF-κB activation in FGL2-deleted BMECs.ConclusionOur findings indicate that FGL2 deficiency alleviates the maternal inflammation-induced BBB disruption by inhibiting PI3K/NF-κB mediated oxidative stress in BMECs. Targeting FGL2 may provide a new therapy for prenatal brain damage of offspring.

ABSTRACT: Subclinical ketosis (SCK) in dairy cows, a common metabolic disorder during the peripartal period, is accompanied by systemic inflammation. Excessive release of azurophil granule (AG) contents during degranulation of polymorphonuclear neutrophils (PMN) could contribute to systemic inflammation in SCK cows. Although the increase in blood free fatty acids (FFA) in SCK cows may promote AG degranulation from PMN, the underlying mechanisms are unclear. Thirty multiparous cows (within 3 wk postpartum) with similar lactation numbers (median = 3, range = 2–4) and days in milk (median = 6, range = 3–15) were classified based on serum β-hydroxybutyrate (BHB) level as control (n = 15, BHB < 0.6 mM) or SCK (n = 15, 1.2 mM < BHB < 3.0 mM). Cows with SCK had greater levels of serum haptoglobin, serum amyloid A, IL-1β, IL-6, IL-8 and tumor necrosis factor-α. These proinflammatory factors had strong positive correlations with myeloperoxidase (MPO), a marker protein of PMN AG, whose content was greater in the serum of SCK cows. Both the number of AG and the protein abundance of MPO were lower in PMN isolated from SCK cows. Additionally, we found a greater ratio of blood CH138A+/CD63high cells and greater mean fluorescence intensity of CD63 on the PMN membrane, further confirming the greater degree of AG degranulation in cows with SCK. In vitro FFA dose response (0, 0.3, 0.6, 1.2, and 2.4 mM for 4 h) and time course (0, 0.5, 1, 2, and 4 h with 0.6 mM) experiments were performed on PMN isolated from control cows. The increase in MPO content in extracellular supernatant resulting from those experiments led to the selection of 0.6 mM FFA for 1 h duration as conditions for subsequent studies. After FFA treatment, release of intracellular MPO was increased along with increased levels of CD63 mean fluorescence intensity on the PMN membrane, confirming that FFA promoted degranulation of AG. In addition, FFA treatment increased reactive oxygen species (ROS) production by PMN, an effect that was attenuated by incubation with diphenyleneiodonium chloride (DPI), a NADPH oxidase-derived ROS inhibitor. The mitochondrial-derived ROS inhibitor carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) did not affect ROS in response to FFA treatment. Treatment with FFA increased p47 phosphorylation and mRNA abundance of NCF1, NCF2, and CYBB in PMN. Furthermore, DPI, but not FCCP, dampened the degranulation of PMN AG induced by FFA in vitro. These data suggested that the degranulation of AG in PMN induced by FFA was mediated by NADPH oxidase-derived ROS. As verified ex vivo, PMN from SCK cows had greater levels of ROS, phosphorylation of p47, and mRNA abundance of NCF1, NCF2, and CYBB. Overall, the present study revealed that high blood concentrations of FFA in SCK cows induce the production of NADPH oxidase-derived ROS, thereby promoting degranulation of AG in PMN. The stimulatory effect of FFA on the release of AG content during degranulation, especially MPO, provides a new insight into the systemic inflammation experienced by peripartal cows with SCK.

With its unique geographical location, the coastal zone has concentrated great advantages in resources, population and economy. However, with the deepening of marine resources development activities, a series of problems have emerged in the coastal zone, such as the gradual shortage of resources, the decline of environmental quality and the increase of ecological risks. The coastal zone ecosystem has shown a certain degradation trend. Maintaining the health of the coastal zone ecosystem has become the primary task of the sustainable development of the marine economy. Monitoring the coastal ecosystem carrying capacity, diagnosing the health status of the coastal ecosystem, effectively planning and managing the development and utilization of natural resources in the coastal zone, and controlling human activities related to the sea within the ecological carrying capacity and health limits of the coastal zone are of great significance to the sustainable development of society and economy in the coastal zone. In this study, the ecosystem health model, state space model and ecological health early warning principle were comprehensively applied to construct the coastal ecosystem health diagnosis framework of “Carrying type →Early warning degree →Health level;” The evaluation index system of coastal ecosystem carrying capacity was established; Taking Shandong Province as the empirical research object, the health status of the coastal ecosystem in Shandong Province was diagnosed by using the relevant data from 2007 to 2019. The empirical results show that: (1) From 2007 to 2013, the carrying capacity of the coastal ecosystem in Shandong Province was relatively good, in the state of “loadable” or “critical overload,” while from 2014 to 2019, the carrying capacity was poor, in the state of “overload;” (2) From 2007 to 2013, the early warning degree of coastal ecosystem health in Shandong Province was in the state of “no alarm,” “light alarm,” and “medium alarm,” and the health level was in the state of “very healthy,” “healthy,” and “sub-health;” from 2014 to 2019, the health warning level of the coastal ecosystem in Shandong Province was in the state of “serious alarm” and “extremely serious alarm,” and the health level was in the state of “unhealthy” and “Morbid,” and the health status was worrying; (3) The key influencing factors affecting the carrying capacity of the coastal ecosystem mainly included the output of marine mining, marine GDP, per capita marine production, total amount of main pollutants directly discharged into the sea, domestic tourist arrivals in coastal cities, area of marine nature reserves, proportion of class IV and inferior class IV seawater, average density of beach garbage in the monitoring area, number of medical and health institutions; Finally, some policy suggestions were put forward to improve the health of coastal ecosystem in Shandong Province. In the “discussion” part of this study, the consistency between the research results of this paper and the actual situation of the marine ecosystem in Shandong Province and the existing research results of the same kind is compared, and the applicability and limitations of the research methods in this paper are put forward, indicating that the research methods in this paper are more applicable to the comparative analysis under the same ideal value determination criteria.

Maternal obesity has a significant impact on the metabolism of offspring both in childhood and adulthood. The metabolic regulation of offspring is influenced by the intrauterine metabolic programming induced by maternal obesity. Nevertheless, the precise mechanisms remain unclear. The hypothalamus is the primary target of metabolic programming and the principal regulatory center of energy metabolism. Accumulating evidence has indicated the crucial role of hypothalamic regulation in the metabolism of offspring exposed to maternal obesity. This article reviews the development of hypothalamus, the role of the hypothalamic regulations in energy homeostasis, possible mechanisms underlying the developmental programming of energy metabolism in offspring, and the potential therapeutic approaches for preventing metabolic diseases later in life. Lastly, we discuss the challenges and future directions of hypothalamic regulation in the metabolism of children born to obese mothers.

BackgroundClinical prevalence of major depression is higher in women than men, while the psychoneuroimmunological mechanisms underlying the differences between the two sexes are not fully understood.MethodsThe present study explored sex differences in the behaviors and depressive pathological mechanisms induced by chronic unpredictable mild stress (CUMS). Depression- and anxiety-like behaviors were assessed by the sucrose preference test (SPT), force swimming test (FST), open field test (OFT), and elevated plus-maze (EPM). The enzyme-linked immunosorbent assay (ELISA) was used to measure cytokine concentrations, high-performance liquid chromatography (HPLC) was used to measure monoamine neurotransmitters and metabolite contents, and real-time quantitative PCR (qPCR) and western blotting (WB) were used to measure glial parameters in the hippocampus.ResultsUnder control conditions, female rats exhibited shorter immobility times in the FST, lower interferon (IFN)-γ, and interleukin (IL)-4 levels in the hippocampus, lower norepinephrine (NE) and homovanillic acid (HVA), and higher p75 and glial-derived neurotrophic factor (GDNF) expression than male rats. CUMS markedly reduced rat body weight gain, sucrose preference, locomotor activity, number of entries into the central zone and rearing in the OFT, as well as the number of entries into and time spent in open arms of the EPM; however, CUMS increased the immobility times of the rats of both sexes in the FST. Interestingly, more pronounced changes in sucrose preference and locomotor activity were observed in female rats than in males. Consistently, CUMS-increased glucocorticoid concentration, M1 microglial marker CD11b, and peripheral IL-1β and IL-4, while decreased hippocampal IL-10, serotonin (5-HT), dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were more significant in females than in males.ConclusionThese data revealed possible mechanisms by which females suffer more depression than males at least in a stressful environment.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate and presents a major challenge for human health. Activation of multiple oncogenes has been reported to be strongly associated with the progression of HCC. Moreover, the immunosuppressive tumor microenvironment (TME) and the host immune system are also implicated in the development of malignant HCC tumors. Glypican-3 (GPC-3), a proteoglycan involved in the regulation of cell proliferation and apoptosis, is aberrantly expressed in HCC. We synthesized a short 5ʹ-triphosphate (3p) RNA targeting GPC-3, 3p-GPC-3 siRNA, and found that it effectively inhibited subcutaneous HCC growth by raising type I IFN levels in tumor cells and serum and promoting tumor cell apoptosis. Moreover, 3p-GPC-3 siRNA was able to enhance the activation of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells while reducing the proportion of regulatory T cells (Tregs) in the TME. Most intriguingly, a blocking anti-PD-1 antibody improved the anti-tumor effect of 3p-GPC-3 siRNA, predominantly by activating the immune response, reversing immune exhaustion, and improving immune memory. Our study suggests that the combination of 3p-GPC-3 siRNA administration and PD-1 blockade may represent a promising therapeutic strategy for HCC.

Activation of the stimulator of interferon gene (STING)-mediated innate immune response has been suggested as a promising therapeutic strategy for cancers. However, the effects of STING agonist on natural killer (NK) cell-mediated anti-tumor responses in pancreatic cancer remains unknown. Herein, we evaluated the effects of a classical STING agonist cyclic GMP-AMP (cGAMP) on NK cells in pancreatic cancer. We found that cGAMP could directly activate NK cells and enhance the sensitivity of pancreatic cancer cells to NK cell cytotoxicity, suggesting that cGAMP may become a potential adjuvant for NK cell therapy. In addition, combination of CAR-NK-92 cells targeting mesothelin and cGAMP displayed greater antitumor efficacy by inhibiting tumor growth and prolonging survival of the mouse model of pancreatic cancer. These results suggest that the combination of a STING agonist and NK cells may become a novel immunotherapy strategy for pancreatic cancer.

Abstract Background Moyamoya disease (MMD) is an uncommon cerebrovascular disease which leads to progressive stenosis and occlusion of the bilateral internal carotid artery and main intracerebral arteries. Concerns are always on how the hemisphere with infarction affects cognitive function, while little attention is paid to the role that the non-infarcted hemisphere plays. Therefore, we aimed to detect cortical indexes, especially cortical complexity in the left or right hemisphere separately in patients with MMD after stroke. Methods 28 patients with MMD (14 males, 14 females) and 14 healthy controls were included in this study. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scan. The preprocessing of three-dimensional T1 weighted images were performed by standard surface-based morphometry. Surface-based morphometry statistical analysis was carried out with a threshold of False Discovery Rate (FDR) P

Abstract In this paper, a standard (3, 5)-threshold quantum secret sharing scheme is presented, in which any three of five participants can resume cooperatively the classical secret from the dealer, but one or two shares contain absolutely no information about the secret. Our scheme can be fulfilled by using the singular properties of maximally entangled 6-qubit states found by Borras. We analyze the scheme’s security by several ways, for example, intercept-and-resend attack, entangle-and-measure attack, and so on. Compared with the other standard threshold quantum secret sharing schemes, our scheme needs neither to use d-level multipartite entangled states, nor to produce shares by classical secret splitting techniques, so it is feasible to be realized.

Abstract Background Asymptomatic carotid artery stenosis (aCAS) impairs haemodynamic and cognitive functions; however, the relationship between these changes and brain network connectivity remains largely unknown. This study aimed to determine the relationship between functional connectivity and neurocognition in patients with aCAS. Methods We compared functional status in 14 patients with aCAS and 15 healthy controls using resting state functional magnetic resonance imaging sequences. The subjects underwent a full range of neuropsychological tests and a graphical theoretical analysis of their brain networks. Results Compared with controls, patients with aCAS showed significant decline in neuropsychological functions, particularly short-term memory (word-memory, p = .046 and picture-memory, p = .014). Brain network connectivity was lower in patients with aCAS than in the controls, and the decline of functional connectivity in aCAS patients was mainly concentrated in the left and right inferior frontal gyri, temporal lobe, left cingulate gyrus, and hippocampus. Decreased connectivity between various brain regions was significantly correlated with impaired short-term memory. Patients with aCAS showed cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. The cognitive defects were mainly manifested in the short-term memory of words and pictures. Conclusions This study is the first of its kind to identify an association between disruption of functional connections in left carotid stenosis and impairment of short-term memory. The findings suggest that alterations in network connectivity may be an essential mechanism underlying cognitive decline in aCAS patients. Clinical trial registration-URL Unique identifier: 04/06/2019, ChiCTR1900023610 .

Purpose: To investigate the correlation between pre-ablation ultrasound radiomics features and the sonication energy for focused ultrasound surgery (FUS) of benign breast tumors.Method: 53 benign breast tumors of 28 patients treated by ultrasound-guided focused ultrasound surgery (USgFUS) were included in this study. The sonication energy per unit volume of each tumor was calculated. Three-quarter point was chosen as the cut-off to divide the 53 included tumors into high sonication energy (HSE, n = 14) and low sonication energy (LSE, n = 39) groups. For each tumor, the region of interest (ROI) of both the tumor itself (tROI) and the near field tissue (nfROI) were delineated and analyzed separately using ImageJ software. Pearson correlation coefficient and multiple linear regression analysis were used for radiomics feature selection. To explore the diagnostic performance of different ultrasound radiomics features, a receiver operating characteristic (ROC) curve analysis was performed.Results: In total of 68 radiomics features were extracted from pre-ablation ultrasound images of each tumor. Of all radiomics features, BX in tROI (p < 0.001), BX (p = 0.001) and Circ (p = 0.019) in nfROI were independently predictive features of sonication energy per unit volume. The ROC curves showed that the area under the curve (AUC) values of BX in tROI, BX, and Circ in nfROI were 0.797, 0.787 and 0.822, respectively.Conclusion: This study provided three radiomics features of pre-ablation ultrasound image as predictors of sonication dose for FUS in benign breast tumors. Further clinical trials are needed to confirm the predictive effect of these radiomics features.

Neuroinflammation induced by microglial and astrocyte polarizations may contribute to neurodegeneration and cognitive impairment. Omega (n)-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory and neuroprotective effects, but conflicting results were reported after different n-3 PUFA treatments. This study examined both the change in glial polarizations in ageing rats and the differential effects of two omega-3 PUFAs. The results showed that both PUFAs improved spatial memory in ageing rats, with docosahexaenoic acid (DHA) being more effective than eicosapentaenoic acid (EPA). The imbalance between microglial M1/M2 polarizations, such as up-regulating ionized calcium binding adaptor molecule 1 (IBA1) and down-regulating CD206 and arginase-1 (ARG-1) was reversed in the hippocampus by both n-3 PUFAs, while the DHA effect on CD206 was stronger. Astrocyte A1 polarization presented increasing S100B and C3 but decreasing A2 parameter S100A10 in the ageing brain, which were restored by both PUFAs, while DHA was more effective on S100A10 than EPA. Consistent with microglial M1 activation, the concentration of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were significantly increased, which were attenuated by DHA, while EPA only suppressed IL-6. In correlation with astrocyte changes, brain-derived neurotrophic factor precursor was increased in ageing rats, which was more powerfully down-regulated by DHA than EPA. In summary, enhanced microglial M1 and astrocytic A1 polarizations may contribute to increased brain pro-inflammatory cytokines, while DHA was more powerful than EPA to alleviate ageing-associated neuroimmunological changes, thereby better-improving memory impairment.

As a main oxidizer in solid composite propellants, ammonium perchlorate (AP) plays an important role because its thermal decomposition behavior has a direct influence on the characteristic of solid composite propellants. To improve the performance of solid composite propellant, it is necessary to take measures to modify the thermal decomposition behavior of AP. In recent years, transition metal oxides and carbon-supported transition metal oxides have drawn considerable attention due to their extraordinary catalytic activity. In this review, we highlight strategies to enhance the thermal decomposition of AP by tuning morphology, varying the types of metal ion, and coupling with carbon analogue. The enhanced catalytic performance can be ascribed to synergistic effect, increased surface area, more exposed active sites, and accelerated electron transportation and so on. The mechanism of AP decomposition mixed with catalyst has also been briefly summarized. Finally, a conclusive outlook and possible research directions are suggested to address challenges such as lacking practical application in actual formulation of solid composite propellant and batch manufacturing.

CircRNAs are a large class of endogenous single-stranded RNA that is different from other linear RNA, which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops. CircRNAs are found in almost all living organisms and have emerged as potentially important players effecting on all life activities. It was characterized by stable structure, resistant to RNA degradation, highly abundance and conservation and tissue-specific expression. Early circRNAs were ignored as a by-product of meaningless abnormally cut RNA and had little biological function. Currently, circRNAs have become a research hotspot due to its special characteristics. CircRNAs could function as miRNA sponges, interfere with splicing and bind to protein to regulate the expression of parental genes and so on. In recent years, an increasing number of studies have revealed that circRNAs are closely related to a series of physiological and pathological processes. Additionally, circRNAs play an important role in the occurrence and development of a variety of diseases, suggesting circRNAs may be as novel indicators or biomarkers for cancer and other diseases with which they are associated. In this article, we review the biogenesis, biological functions of circRNAs and recent advances in circRNAs research in human diseases. Results will provide new insights on the roles and new ideas of circRNAs for the diagnosis and treatment of diseases and possible directions and approach for future circRNA applications.