Microplastics induced endoplasmic reticulum stress to format an inflammation and cell death in hepatocytes of carp (Cyprinus carpio).

Microplastics (MPs) are a serious threat to the living environment of aquatic organisms. However, there are fewer studies on the toxicity of microplastics to freshwater organisms. This study aimed to establish a polystyrene microplastics (PS-MPs) model by feeding carp (Cyprinus carpio) PS-MP (1000 ng/L) particles 8 µm in size. HE staining revealed a mass of inflammatory cells infiltrated in the carp hepatopancreas. The activities of alkaline phosphatase (AKP), aspartate transaminase (AST), lactate dehydrogenase (LDH), and alanine transaminase (ALT) were strengthened considerably, suggesting that PS-MPs cause injury to the hepatopancreas of carp. Real-Time polymerase chain reaction and western blotting results indicated increased levels of glucose-regulated protein 78 (GRP78), (PKR)-like ER kinase (PERK), eukaryotic translation initiation Factor 2α (EIF2α) and activating transcription Factor 4 (ATF4) genes and increased levels of inflammatory factors downstream of endoplasmic reticulum stress (ERs) thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), interleukin-18 (IL-18), interleukin-1ß (IL-1ß), and caspase 1. Increased expression of microtubule-associated protein-2 (LC3II), autophagy-related 5 (ATG5) and autophagy-related 12 (ATG12) genes revealed that PS-MPs promoted autophagy in carp hepatocytes. The enhanced expression of the Caspase 12, Caspase 3, and Bax genes suggested that PS-MPs led to the apoptosis of carp hepatocytes. These results suggest that PS-MPs result in serious injury to the hepatopancreas of carp. The present study of PS-MPs in freshwater fish from the aspect of endoplasmic reticulum stress was conducted to provide references and suggestions for toxicological studies of PS-MPs in freshwater environments.

Polyethylene microplastics cause apoptosis via the MiR-132/CAPN axis and inflammation in carp ovarian.

Microplastics (MPs) are widely distributed pollutants in the environment and accumulate in the aquatic environment due to human activities. Carp, a common edible aquatic organism, has been found to accumulate MPs in body. MicroRNA (miRNAs) is a non-coding short RNA that regulates protein expression by binding to target genes in various physiological processes such as proliferation, differentiation and apoptosis. The ovary is a crucial role in carp reproduction. In this study, we established a model of carp exposed to polyethylene microplastics (PE-MPs) in the aquatic environment to investigate the specific mechanism of PE-MPs causing ovarian injury and the involvement of miR-132/calpain (CAPN) axis. H&E stained sections revealed that PE-PMs induced inflammation in ovarian tissues and impaired oocyte development. TUNEL analysis showed an increased rate of apoptosis in ovarian cells treated with PE-PMs. RT-PCR and Western Blot assays confirmed that exposure to PE-MPs significantly decreased miR-132 expression while increasing CAPN expression at both mRNA and protein levels. The concentration of calcium ions was significantly increased in tissues, leading to CAPN enzyme activity increase. The expression of mitochondrial damage-related genes (bax, AIF, cyt-c, caspase-7, caspase-9, and caspase-3) was higher while the expression of anti-apoptotic genes (bcl-2 and bcl-xl) was lower. Protein levels of bax, AIF, caspase-3, bcl-2 and bcl-xl changed accordingly with the genetic alterations. Additionally, we discovered that PE-MPs can activate the p65 factor through the TRAF6/NF-kB pathway resulting in elevated production of pro-inflammatory factors IL-6, IL-1ß and TNF-a which contribute to ovarian inflammation development. This study investigates the impact of PE-MPs on carp ovarian function and provides insights into miRNAs' role and their target genes.

Selenium deficiency induced inflammation and apoptosis via NF-κB and MAPKs pathways in muscle of common carp (Cyprinus carpio L.).

Selenium (Se), one of the essential trace elements of fish, regulates immune system function and maintains immune homeostasis. Muscle is the important tissue that generate movement and maintain posture. At present, there are few studies on the effects of Se deficiency on carp muscle. In this experiment, carps were fed with dietary with different Se content to successfully establish a Se deficiency model. Low-Se dietary led to the decrease of Se content in muscle. Histological analysis showed that Se deficiency resulted in muscle fiber fragmentation, dissolution, disarrangement and increased myocyte apoptosis. Transcriptome revealed a total of 367 differentially expressed genes (DEGs) were screened, including 213 up-regulated DEGs and 154 down-regulated DEGs. Bioinformatics analysis showed that DEGs were concentrated in oxidation-reduction process, inflammation and apoptosis, and were related to NF-κB and MAPKs pathways. Further exploration of the mechanism showed that Se deficiency led to excessive accumulation of ROS, decreased the activity of antioxidant enzymes, and also resulted in increased expression of the NF-κB and MAPKs pathways. In addition, Se deficiency significantly increased the expressions of TNF-α, IL-1ß and IL-6, and the pro-apoptotic factors BAX, p53, caspase-7 and caspase-3, while decreased the expressions of anti-apoptotic factors Bcl-2 and Bcl-xl. In conclusion, Se deficiency reduced the activities of antioxidant enzymes and led to excessive accumulation of ROS, which caused oxidative stress and affected the immune function of carp, leading to muscle inflammation and apoptosis.

Differences in nutritional risk assessment between NRS2002, RFH-NPT and LDUST in cirrhotic patients.

Nutritional status is an independent predictor of outcome in cirrhosis patients. Nutritional Risk Screening 2002 (NRS2002), Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT), and Liver Disease Undernutrition Screening Tool (LDUST) were employed to detect cirrhosis with malnutrition risk in this work. Meanwhile, their diagnostic performances were compared to find the best screening method. This work aimed to establish the sarcopenia cut-off value of the transversal psoas thickness index (TPTI), and identify the risk factors for malnutrition. Cirrhosis patients who were admitted to Heibei Gerneral hospital from April 2021 to October 2021 and underwent abdominal CT examination were enrolled. 78 patients were assessed by NRS2002, RFH-NPT, and LDUST. The Global Leadership Initiative for Malnutrition (GLIM) criteria were selected as the gold standard for the diagnosis of malnutrition. Meanwhile the cut-off value of sarcopenia was established based on the TPTI of malnourished patients. Logistic regression analysis was adopted to assess the influencing factors of malnutrition risk and malnutrition. The prevalence of malnutrition was 42.31%. The prevalence of malnutrition risk was 32.1%, 61.5%, and 62.8% with NRS2002, RFH-NPT, and LDUST, respectively. NRS2002 presented the best specificity compared with the other methods, while RFH-NPT showed the highest sensitivity. The optimal gender-specific TPTI cut-off value for diagnosing sarcopenia was determined as TPTI < 14.56 mm/m (male) and TPTI < 8.34 mm/m (female). In the multivariate analysis, ascites was associated with malnutrition risk, while sarcopenia showed a significant risk for malnutrition. NRS2002 and RFH-NPT were superior to LDUST at detecting the malnutrition in cirrhosis patients diagnosed according to GLIM criteria. The gender-specific TPTI cut-off value was TPTI < 14.56 mm/m (male) and TPTI < 8.34 mm/m (female). Malnutrition risk should be screened for patients with ascites as soon as possible. In addition, it was important to evaluate malnutrition in sarcopenia patients in time.

How financial development scale and R&D influence regional innovation efficiency: empirical evidence from the financial industry.

Financial elements and R&D elements are significant drivers for enhancing regional innovation efficiency. This paper measures financial elements by financial development scale and the marketization level of the financial industry and R&D elements by the inputs and flow of R&D personnel and R&D capital and specifically considers R&D element flow to quantify the consequential spatial spillover effects. Based on provincial panel data from 2008 to 2018, the paper firstly estimates the regional innovation efficiency of China's 30 provincial-level administrative regions using super-efficiency DEA and then conducts an empirical analysis of the influence of financial elements and R&D elements on regional innovation efficiency by the use of the Tobit model and three spatial econometric models. It is found that, by and large, the financial development scale, the marketization level of the financial industry, the inputs of R&D personnel and R&D capital, and R&D capital flow all have significant effects on regional innovation efficiency. Nonetheless, by region, R&D personnel flow in central China can significantly boost regional innovation efficiency while fails in eastern and western China. From the spatial perspective, both financial elements and R&D elements have significant positive spatial spillover effects. Therefore, in order to bolster regional innovation efficiency, it is crucial to improve the allocation of financial elements and R&D elements and build a tight regional collaborative innovation network.

Polyethylene microplastics trigger cell apoptosis and inflammation via inducing oxidative stress and activation of the NLRP3 inflammasome in carp gills.

Microplastics cause varying degrees of damage to aquatic organisms. Exposure to microplastics contaminated water, the gills are among the first tissues, after the skin, to be affected by microplastics. As an essential immune organ, prolonged stimulation by microplastics disrupts immune function not only in the gills but throughout the body, yet the underlying mechanisms remain elusive. A model of gill injury from exposure to polyethylene (PE) microplastics was developed in this study. H&E staining revealed that polyethylene microplastics caused gill inflammation, vascular remodeling, and mucous cell proliferation. An increase in collagen indicates severe tissue damage. Additional analysis showed that polyethylene microplastics profoundly exacerbated oxidative stress in the gills. TUNEL assay demonstrated cell apoptosis induced by polyethylene microplastic. The mRNA levels were subsequently quantified using RT-PCR. The results showed that polyethylene microplastics increased the expression of the nuclear factor-κB (NF-κB) pathway (NF-κB p65, IKKα, IKKß) and apoptosis biomarkers (p53, caspase-3, caspase-9, and Bax). Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes, which is an influential component of innate immunity, were overactive. What's more, the pro-inflammatory factors (TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-1ß) that induce immune disorder also increased significantly, while the anti-inflammatory factors (IL-4, IL-10) decreased significantly. These results suggested that oxidative stress acted as an activation signal of apoptosis triggered by the NF-κB pathway and activating the NLRP3 inflammasome to promote inflammatory immune responses. The present study provided a different target for the prevention of toxin-induced gill injury under polyethylene microplastics.

Tea Polyphenols Protect the Mammary Gland of Dairy Cows by Enhancing Antioxidant Capacity and Regulating the TGF-ß1/p38/JNK Pathway.

Tea polyphenols (TPs) are the main active substances in tea and they have many beneficial effects, such as anti-inflammation, antioxidant, anti-cancer and metabolic regulation effects. The quality of milk is affected by mammary gland diseases and there are substantial economic losses resulting from reduced milk production as a consequence of inflammatory injury of the mammary gland. In this study, transcriptome analysis and molecular biology techniques were used to study the effects of TPs on inflammatory injury of the mammary gland. After intervention with TPs, a total of 2085 differentially expressed genes were identified, including 1189 up-regulated genes and 896 down-regulated genes. GO analysis showed that differentially expressed genes played an important role in proton transmembrane transport, oxidation-reduction reactions and inflammatory response. KEGG enrichment suggested that differential genes were concentrated in the TGF-ß pathway and active oxygen metabolism process. Experiments were performed to confirm that TPs increased SOD, CAT, T-AOC and GSH-Px content along with a reduction in MDA. Meanwhile, TPs inhibited the expression of TGF-ß1 and reduced the phosphorylation of p38 and JNK. The expression of inflammatory cytokines IL-1ß, IL-6 and TNF-α were significantly decreased after intervention with TPs. In summary, all the data indicated that TPs protected the mammary gland by enhancing the antioxidant capacity and down-regulating the TGF-ß1/p38/JNK pathway.

The contribution of pore size and porosity of 3D printed porous titanium scaffolds to osteogenesis.

Porous titanium implants were popularly fabricated to promote bone formation. A desirable porous scaffold was recommended to be with porosity of >60% or/and pore size of >300 µm for better osteointegration. However, whether the pore size and porosity could be randomly selected within the recommended values? And what is the correlation between pore size and porosity for accelerating osteointegration? In this study, porous titanium with cubic cell structure was produced by selective laser melting. The designed porosities of scaffolds with 700-µm pore size were 40%, 70% and 90%; and the pore sizes of scaffolds with 70% porosity were 400, 700 and 900 µm. The in vitro osteogenic potential and in vivo bone formation were investigated. Results showed that porosity and pore size could be tuned by altering strut size, which was further directly responsible for mechanical properties. Besides, pore size and porosity synergistically contributed to osteogenic activity in vitro and new bone formation in vivo. In regard to pore sizes herein, the optimized one for better osteogenic response and bone forming ability was ~600-700 µm (p70). Too smaller or too larger pore size might more or less hinder cellular behaviors and bone regeneration, even if both pore size (300-900 µm) and porosity (70%) were within the recommended value range. At a constant pore size (~600-700 µm), p70 and p90 with higher porosity was more conductive to biological effects, compared with p40. As a result, pore-size variation revealed more significant influence on osteogenesis, compared with variation of porosity within recommended values. However, the applicable porosity within recommended values should be designed with the consideration of specific load-bearing conditions. This study helps to provide guidance for designing porous scaffolds with appropriate mechanical strengths and effective bone-forming ability, so as to develop better custom-made bone substitutes.

Changes of psychotic-like experiences and their association with anxiety/depression among young adolescents before COVID-19 and after the lockdown in China.

OBJECTIVE: Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study. METHODS: In total, 1825 adolescents were surveyed before COVID-19 and after the lockdown in China (T0, October 20th, 2019 and T1, May 18th, 2020). PLEs, anxiety, and depression were measured with paranoia, anxiety and depression subscales of the Mental Health Inventory of Middle school students (MMHI-60). Within-subjects Wilcoxon test, Spearman correlation test, and Kruskal-Wallis test were adopted. RESULTS: Significant increase in adolescent PLEs scores was observed after the lockdown (Wilcoxon's w = 9.302, p < 0.001). We also found positive correlation between changes of PLEs and changes of anxiety/depression (Spearman's rho = 0.59/0.53, both p < 0.001). Furthermore, four PLEs trajectories were identified based on the report of PLEs at two timepoints: 60.4% with no PLEs, 9.3% remitted PLEs, 16.7% new PLEs, and 13.6% persistent PLEs. Significant difference was found in changes of anxiety/depression among four groups (p < 0.001); notably, the group with new-onset PLEs had the greatest exacerbation in anxiety/depression symptoms (both p Bonferroni <0.001). CONCLUSIONS: This work is the first to identify increases in adolescent PLEs across the COVID-19 pandemic and suggested a close longitudinal association between PLEs and anxiety/depression. Our findings have implications for adolescent mental health crisis interventions during the pandemic.

Family functioning as a moderator in the relation between perceived stress and psychotic-like experiences among adolescents during COVID-19.

BACKGROUND: The COVID-19 pandemic has increased psychological stress among adolescents, and the relation between perceived stress (PS) and psychotic-like experiences (PLEs) has been well-established. However, little is known about the role of family functioning (FF) in this relation, especially when adolescents experienced the extended lockdown period with family members. METHODS: A total of 4807 adolescents completed this retrospective paper-and-pencil survey after school reopening between May 14th and June 6th, 2020 in Hunan Province, China. We measured PS with the Perceived stress scale (PSS-10), PLEs with the eight positive items from Community Assessment of Psychic Experiences (CAPE-8), and FF with the Family APGAR scale. We conducted subgroup analysis based on three FF levels (good, moderate, and poor) determined by previous studies. Finally, correlation and moderation analysis were performed to detect the effect of FF in the relation between PS and PLEs after adjusting for demographic variables. RESULTS: Adolescents with poor FF had higher levels of PS and higher prevalence of PLEs compared to those with good FF (both p < 0.001). FF was negatively associated with both PS (r = -0.34, p < 0.001) and PLEs (r = -0.29, p < 0.001). Higher FF significantly attenuated the effect of PS on PLEs after adjusting for sex and age (effect = -0.011, bootstrap 95% CI -0.018, -0.005). CONCLUSION: Our findings indicate that well-functioned family could protect against stress-induced PLEs among adolescents during this crisis. Thus family system could be an early interventional target for distressing psychotic-like experiences in youngsters.

Drug-naïve first-episode schizophrenia spectrum disorders: Pharmacological treatment practices in inpatient units in Hunan Province, China.

AIM: This study describes antipsychotic prescription patterns for drug-naïve inpatients diagnosed with first-episode schizophrenia-spectrum (FES) disorders and factors associated with practices deviating from China's current guidelines. METHODS: All inpatients aged 7 to 45 years experiencing a first episode of schizophrenia-spectrum disorder with a duration of untreated illness of less than 18 months and admitted between 1 August 2016 and 1 August 2017 to one of eight psychiatric hospitals in Hunan were included. Demographics, clinical characteristics and prescriptions at discharge were collected from electronic medical records. Logistic regression and random forest methods were used to model relationships between demographic and clinical factors and deviations from China's guidelines. RESULTS: Of the 602 inpatients included in the study, 598 (99.3%) were prescribed antipsychotics, and no patients were discharged on long-acting injectable antipsychotics. Polypharmacy (more than one antipsychotic prescribed) was present in 121 (20.2%) participants. Clozapine was prescribed to 45 (7.5%) patients. Adults receiving polypharmacy were more likely to be prescribed high-dose antipsychotics than those receiving a single antipsychotic. Minors under 13 years of age were more likely to receive polypharmacy and unapproved antipsychotics than those older than 13 years. CONCLUSIONS: Our findings suggest that most of the inpatients were prescribed a single antipsychotic at discharge, consistent with China's guidelines. Minors with FES and patients discharged on polypharmacy and clozapine may require more intense monitoring and management. With the current implementation of China's National Mental Health Working Plan, these results will assist decision-makers in allocating resources and conducting reforms to facilitate best practice treatment for FES.