Treating waste with waste: adsorption behavior and mechanism of phosphate in water by modified phosphogypsum biochar.

The use of green methods to treat industrial waste and waste reuse has become a key environmental issue. In order to achieve this goal, this study treated waste phosphogypsum (PG) and produced modified PG biochar to adsorb and remove phosphorus from PG leachate, so that the PG pollution problem was controlled. In this study, PG was modified with sodium carbonate (Na2CO3) to prepare a modified PG biochar that was used for the removal of phosphorus-containing wastewater. An X-ray diffraction (XRD) analysis of the modified PG revealed that the main component was calcium carbonate (CaCO3), and a suitable amount of modified PG could load calcium oxide (CaO) onto the biochar and improve its physical properties. The experimental results showed that the modified PG biochar had a maximum phosphorus adsorption capacity of 132 mg/g. A further investigation of the mechanism of adsorption revealed the importance of electrostatic attraction and chemical precipitation, and it was found that the CaO in the modified PG biochar could effectively facilitate the conversion of phosphate to hydroxylapatite (Ca5(PO4)3OH) in water. The phosphorus removal rate from leachate obtained from a landfill containing PG was 99.38% for a specific dose of the modified PG biochar. In this study, a PG pollution control technology was developed to realize the goal of replacing waste with waste.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Decoupling of the onset of anharmonicity between a protein and its surface water around 200 K.

The protein dynamical transition at ~200 K, where the biomolecule transforms from a harmonic, non-functional form to an anharmonic, functional state, has been thought to be slaved to the thermal activation of dynamics in its surface hydration water. Here, by selectively probing the dynamics of protein and hydration water using elastic neutron scattering and isotopic labeling, we found that the onset of anharmonicity in the two components around 200 K is decoupled. The one in protein is an intrinsic transition, whose characteristic temperature is independent of the instrumental resolution time, but varies with the biomolecular structure and the amount of hydration, while the one of water is merely a resolution effect.

Efficacy and safety of insulin glargine 300 U/mL in people with type 2 diabetes in China: The INITIATION study.

AIM: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) in people with suboptimally controlled type 2 diabetes (T2D) in China. METHODS: INITIATION (NCT05002933) was a prospective, interventional, multicentre, single-arm, phase IV study conducted in China. Individuals with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin (insulin experienced) were included. The primary endpoint was the change in HbA1c from baseline to week 24. Safety assessments included hypoglycaemia and adverse events (AEs). RESULTS: In total, 568 participants were enrolled and 562 initiated Gla-300 treatment (189 in the insulin-naïve subgroup; 373 in the insulin-experienced subgroup). At week 24, the mean ± standard error (SE) change in HbA1c from baseline was -0.91% ± 0.05% (-9.9 ± 0.5 mmol/mol; P < .0001). Significant HbA1c reductions were also observed in the insulin-naïve (mean ± SE change: -1.38% ± 0.09% [-15.1 ± 1.0 mmol/mol]) and insulin-experienced (-0.68% ± 0.05% [-7.4 ± 0.5 mmol/mol]) subgroups (both P < .0001). During the 24-week treatment period, the incidence of confirmed hypoglycaemia (plasma glucose ≤ 3.9 mmol/L) was 39.7% for all hypoglycaemia and 13.3% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.5%). Overall, treatment-emergent AEs (TEAEs) were reported in 126 participants (22.4%), with no serious treatment-related TEAEs. CONCLUSIONS: Gla-300 was effective in improving glycaemic control and had a relatively low risk of hypoglycaemia in people with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin in China.

Role of ginsenoside Rb1 in attenuating depression-like symptoms through astrocytic and microglial complement C3 pathway.

Ginsenoside Rb1, known as gypenoside III, exerts antidepressant-like effects in previous studies. It has also been indicated that ginsenoside Rb1 regulated neuroinflammation via inhibiting NF-κB signaling. According to the evidence that astrocytes can regulate microglia and neuroinflammation by secreting complement C3, the present study aimed to demonstrate the molecular mechanisms underlying ginsenoside Rb1-induced antidepressant-like effects from the astrocytic and microglial complement C3 pathway. The complement C3 mediated mechanism of ginsenoside Rb1 was investigated in mice exposed to chronic restraint stress (CRS). The results showed that ginsenoside Rb1 reversed the depressive-like behaviors in CRS. Treatment with ginsenoside Rb1 reduced both the number of astrocytes and microglia. In addition, ginsenoside Rb1 suppressed TLR4/NF-κB/C3 signaling in the astrocytes of the hippocampus. Furthermore, ginsenoside Rb1 attenuated the contents of synaptic protein including synaptophysin and PSD95 in microglia, suggesting the inhibition of microglia-mediated synaptic elimination caused by CRS. Importantly, ginsenoside Rb1 also maintained the dendritic spines in mice. In conclusion, our results demonstrate that ginsenoside Rb1 produces the antidepressant-like effects by inhibiting astrocyte TLR4/NF-κB/C3 signaling to covert microglia from a pro-inflammatory phenotype (amoeboid) towards an anti-inflammatory phenotype (ramified), which inhibit the synaptic pruning in the hippocampus.

Predictive analytics for early detection of hospital-acquired complications: An artificial intelligence approach.

BACKGROUND: Hospital-acquired complications (HACs) have an adverse impact on patient recovery by impeding their path to full recovery and increasing healthcare costs. OBJECTIVE: The aim of this study was to create a HAC risk prediction machine learning (ML) framework using hospital administrative data collections within North Metropolitan Health Service (NMHS), Western Australia. METHOD: A retrospective cohort study was performed among 64,315 patients between July 2020 to June 2022 to develop an automated ML framework by inputting HAC and the healthcare site to obtain site-specific predictive algorithms for patients admitted to the hospital in NMHS. Univariate analysis was used for initial feature screening for 270 variables. Of these, 77 variables had significant relationship with any HAC. After excluding non-contemporaneous data, 37 variables were included in developing the ML framework based on logistic regression (LR), decision tree (DT) and random forest (RF) models to predict occurrence of four specific HACs: delirium, aspiration pneumonia, pneumonia and urinary tract infection. RESULTS: All models exhibited similar performance with area under the curve scores around 0.90 for both training and testing datasets. For sensitivity, DT and RF exceeded LR performance while on average, false positives were lowest for LR-based models. Patient's length of stay, Charlson Index, operation length and intensive care unit stay were common predictors. CONCLUSION: Integrating ML-based risk detection systems into clinical workflows can potentially enhance patient safety and optimise resource allocation. LR-based models exhibited best performance. IMPLICATIONS: We have successfully developed a "real-time" risk prediction model, where patient risk scores are calculated and reviewed daily.

[Exploring the mechanism of IgA vasculitis pathogenesis through the interaction of thrombin and inflammatory factors using urinary proteomics]. / è¿ç”¨å°¿è›‹ç™½ç»„å­¦æŠ€æœ¯æŽ¢ç´¢å‡è¡€é ¶ä¸Žç‚Žç—‡å› å­ç›¸äº’ä½œç”¨å‚ä¸ŽIgAè¡€ç®¡ç‚Žå‘ç— çš„æœºåˆ¶.

OBJECTIVES: To explore the evidence, urinary biomarkers, and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis (IgAV). METHODS: Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry, followed by Reactome pathway analysis. Protein-protein interaction (PPI) network analysis was conducted using STRING and Cytoscape software. In the validation cohort, 15 healthy children and 25 children with IgAV were included, and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay. RESULTS: A total of 772 differential proteins were identified between the IgAV group and the control group, with 768 upregulated and 4 downregulated. Reactome pathway enrichment results showed that neutrophil degranulation, platelet activation, and hemostasis pathways were involved in the pathogenesis of IgAV. Among the differential proteins, macrophage migration inhibitory factor (MIF) played a significant role in neutrophil degranulation and hemostasis, while thrombin was a key protein in platelet activation and hemostasis pathways. PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses, and these interactions involved MIF. Validation results showed that compared to healthy children, children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels (P<0.05). CONCLUSIONS: Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors. Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

METTL14-mediated methylation of SLC25A3 mitigates mitochondrial damage in osteoblasts, leading to the improvement of osteoporosis.

PURPOSE: Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood. METHODS AND RESULTS: This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice. CONCLUSIONS: Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis.

Association between negative life events through mental health and non-suicidal self-injury with young adults: evidence for sex moderate correlation.

BACKGROUND: Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). METHODS: We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. RESULTS: Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047-0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. CONCLUSION: Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives.

[Short-term nitrogen addition reduces soil microbial nitrogen fixation rate in subtropical Pinus taiwanensis and Castanopsis faberi forests]. / çŸ­æœŸæ°®æ·»åŠ é™ä½Žäºšçƒ­å¸¦é»„å±±æ¾æž—å’Œç½—æµ®æ ²æž—åœŸå£¤å¾®ç”Ÿç‰©å›ºæ°®é€ŸçŽ‡.

Biological nitrogen (N) fixation is an important source of N in terrestrial ecosystems, but the response of soil microbial N fixation rate to N deposition in different forest ecosystems still remains uncertain. We conducted a field N addition experiment to simulate atmosphere N deposition in subtropical Pinus taiwanensis and Castanopsis faberi forests. We set up three levels of nitrogen addition using urea as the N source: 0 (control), 40 (low N), and 80 g N·hm-2·a-1(high N) to examine the chemical properties, microbial biomass C, enzyme activities, and nifH gene copies of top soils (0-10 cm). We also measured the microbial N fixation rate using the 15N labeling method. Results showed that N addition significantly reduced the soil microbial N fixation rate in the P. taiwanensis and C. faberi forests by 29%-33% and 10%-18%, respectively. Nitrogen addition significantly reduced N-acquiring enzyme (i.e., ß-1, 4-N-acetylglucosaminidase) activity and nifH gene copies in both forest soils. There was a significant positive correlation between the microbial N fixation rate and soil dissolved organic C content in the P. taiwanensis forest, but a significant negative relationship between the rate of soil microbial nitrogen fixation and NH4+-N content in the C. faberi forest. Overall, soil microbial N fixation function in the P. taiwanensis forest was more sensitive to N addition than that in the C. faberi forest, and the factors affecting microbial N fixation varied between the two forest soils. The study could provide insights into the effects of N addition on biological N fixation in forest ecosystems, and a theoretical basis for forest management.

Nail salon dust reveals alarmingly high photoinitiator levels: Assessing occupational risks.

Photoinitiators (PIs) are chemical additives that generate active substances, such as free radicals to initiate photopolymerization. Traditionally, polymerization has been considered a green technique that seldomly generates contaminants. However, many researches have confirmed toxicity effects of PIs, such as carcinogenicity, cytotoxicity, endocrine disrupting effects. Surprisingly, we found high levels of PIs in indoor dust. Our analysis revealed comparable levels of PIs in dust from printing shops (geometric mean, GM: 1.33 ×103 ng/g) and control environments (GM: 874 ng/g), underscoring the widespread presence of PIs across various settings. Alarmingly, in dust samples from nail salons, PIs were detected at total concentrations ranging from 610 to 1.04 × 107 ng/g (GM: 1.87 ×105 ng/g), significantly exceeding those in the control environments (GM: 1.43 ×103 ng/g). Nail salon workers' occupational exposure to PIs through dust ingestion was estimated at 4.86 ng/kg body weight/day. Additionally, an in vitro simulated digestion test suggested that between 10 % and 42 % of PIs present in ingested dust could become bioaccessible to humans. This is the first study to report on PIs in the specific environments of nail salons and printing shops. This study highlights the urgent need for public awareness regarding the potential health risks posed by PIs to occupational workers, marking an important step towards our understanding of environmental pollution caused by PIs.

A systematic review of transcranial magnetic stimulation treatment for autism spectrum disorder.

Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Morphological and molecular data reveal Cerrenacaulinicystidiata sp. nov. and Polyporusminutissimus sp. nov. in Polyporales from Asia.

Two new species of Polyporales, Cerrenacaulinicystidiata and Polyporusminutissimus, are illustrated and described on the basis of morphological studies and phylogenetic analyses from southern China and Vietnam. C.caulinicystidiata is characterized by annual, resupinate, sometimes effused-reflexed basidiocarps, greyish orange to brownish orange pore surface, irregular pores (3-8 per mm), a trimitic hyphal system, pyriform to ventricose cystidia, and subglobose basidiospores 3.2-4.5 × 2.8-3.5 µm in size. P.minutissimus is characterized by annual, solitary, fan-shaped with a depressed center or infundibuliform basidiocarps, obvious black stipe, cream to buff yellow pileal surface with glabrous, occasionally zonate and radially aligned stripes, angular pores (6-9 per mm), a dimitic hyphal system, and cylindrical basidiospores, 5-9.2 × 2.2-4 µm. Detailed descriptions and illustrations of the two new species are provided. The differences between the two new species and their morphologically similar and phylogenetically related species are discussed.

Multi-omics analysis of five species of milk and specific composition links within each species.

The gold standard of milk is human milk, not cow milk. The present study expects to explored the comprehensive nutritional value of different kinds of milk and the differences between them through multi-omics analysis and found functional components that are more similar to human milk. This study employed untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D label-free proteomics analysis techniques. The findings revealed substantial disparities in metabolites, lipids, and proteins among the five types of milk. Notably, pig milk exhibited a remarkable abundance of N-acetylneuraminic acid (Neu5Ac) and specific polar lipids. Yak milk stood out with significantly elevated levels of creatine and lipoprotein lipase (LPL) compared to other species. Buffalo milk boasted the highest concentrations of L-isoleucine, echinocystic acid, and alkaline phosphatase, tissue-nonspecific isozyme (ALPL). The concentrations of iminostilbene and osteopontin (OPN) were higher in cow milk.

Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration.

Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.

Association of combined healthy lifestyle factors with incident osteoporosis in patients with and without type 2 diabetes.

PURPOSE: The association between type 2 diabetes mellitus (T2DM), lifestyle factors, and the risk of osteoporosis (OP) is well-established. However, the impact of a healthy lifestyle on diabetes-related osteoporosis needs further investigation. Our objective was to explore if a combination of healthy lifestyle factors could mitigate the risk of OP in individuals with type 2 diabetes. METHODS: This longitudinal analysis included 237,725 middle-aged and older participants. An overall lifestyle score, ranging from 0 to 7, was calculated by assigning a point for each of the seven healthy lifestyle factors, including no current smoking, non-excessive alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and adequate sunshine exposure. RESULTS: During a median follow-up 12.21 years, 5760 OP cases were documented. Participants with T2DM showed a higher risk of OP than those without diabetes. Compared with participants without diabetes who had a lifestyle score of 6-7, the hazard ratios (HRs) for OP were 1.58 (95% CI 1.23-2.03), 1.62 (95% CI 1.16-2.25), and 2.58 (95% CI 1.64-4.05) for participants with T2DM who had a lifestyle score of 4, 3, and 0-2, respectively. There was a graded association between higher lifestyle scores and lower risks of incident OP among participants without diabetes as well as among those with T2DM. We estimated that the population attributable fraction for not adhering to 6-7 lifestyle behaviors was 15.7%. CONCLUSIONS: Participants with T2DM who adhered to a variety of healthy lifestyle factors demonstrated a substantially reduced risk of developing OP.

Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

PVDF-HFP@Nafion-based quasisolid polymer electrolyte for high migration number in working rechargeable Na-O2 batteries.

Rechargeable sodium-oxygen (Na-O2) battery is deemed as a promising high-energy storage device due to the abundant sodium resources and high theoretical energy density (1,108 Wh kg-1). A series of quasisolid electrolytes are constantly being designed to restrain the dendrites growth, the volatile and leaking risks of liquid electrolytes due to the open system of Na-O2 batteries. However, the ticklish problem about low operating current density for quasisolid electrolytes still hasn't been conquered. Herein, we report a rechargeable Na-O2 battery with polyvinylidene fluoride-hexafluoropropylene recombination Nafion (PVDF-HFP@Nafion) based quasisolid polymer electrolyte (QPE) and MXene-based Na anode with gradient sodiophilic structure (M-GSS/Na). QPE displays good flame resistance, locking liquid and hydrophobic properties. The introduction of Nafion can lead to a high Na+ migration number (tNa+ = 0.68) by blocking the motion of anion and promote the formation of NaF-rich solid electrolyte interphase, resulting in excellent cycling stability at relatively high current density under quasisolid environment. In the meantime, the M-GSS/Na anode exhibits excellent dendrite inhibition ability and cycling stability. Therefore, with the synergistic effect of QPE and M-GSS/Na, constructed Na-O2 batteries run more stably and exhibit a low potential gap (0.166 V) after an initial 80 cycles at 1,000 mA g-1 and 1,000 mAh g-1. This work provides the reference basis for building quasisolid state Na-O2 batteries with long-term cycling stability.