Aging-accelerated differential production and aggregation of STAT3 protein in neuronal cells and neural stem cells in the male mouse spinal cord.

Aging-affected cellular compositions of the spinal cord are diverse and region specific. Age leads to the accumulation of abnormal protein aggregates and dysregulation of proteostasis. Dysregulated proteostasis and protein aggregates result from dysfunction of the ubiquitin-proteasome system (UPS) and autophagy. Understanding the molecular mechanisms of spinal cord aging is essential and important for scientists to discover new therapies for rejuvenation. We found age-related increases in STAT3 and decreases in Tuj1 in aging mouse spinal cords, which was characterized by increased expression of P16. Coaggregation of lysine-48 and lysine-63 ubiquitin with STAT3 was revealed in aging mouse spinal cords. STAT3-ubiquitin aggregates formed via lysine-48 and lysine-63 linkages were increased significantly in the aging spinal cords but not in central canal ependymal cells or neural stem cells in the spinal cord. These results highlight the increase in STAT3 and its region-specific aggregation and ubiquitin-conjugation during spinal cord aging.

N-rich hypercrosslinked porous polymers for highly efficient preconcentration and sensitive detection of chlorophenols.

Three novel N-rich hypercrosslinked porous polymers (NHCP1, NHCP2, and NHCP3) were facilely developed using Friedel-Crafts alkylation. NHCP1 with a remarkably large surface area (2066 m2 g-1) showed the best adsorption performance for chlorophenol pollutants. A sensitive and simple method was developed by using NHCP1 as a sorbent for solid-phase extraction to preconcentrate several chlorophenols in honey, water, and peach beverage samples followed by determination using a high-performance liquid chromatography-ultraviolet detector. The detection wavelength was 280 nm. Under the optimized conditions, the linear ranges were 1.67-1000 ng g-1 for honey, 0.170-100 ng mL-1 for water, and 0.330-100 ng mL-1 for peach beverage samples. The detection limits (S/N = 3) were 0.500-2.00 ng g-1, 0.0500-0.100 ng mL-1, and 0.100-0.200 ng mL-1, respectively. Recovery values were 89.3-111% with relative standard deviations <9.4%. The proposed extraction/preconcentration and quantitative analysis method provides an affordable and effective alternative for the preconcentration and determination of low levels of chlorophenols in real samples.

Ultralow Doppler frequency extraction for the self-mixing dual-frequency laser velocimetry.

In self-mixing dual-frequency laser Doppler velocimetry, the self-mixing Doppler frequency shift of the optical frequency difference is a linear function of the velocity of an external dynamic object; however, it is always ultralow for signal processing. Therefore, an ultralow frequency extraction method based on artificial neural networks (NNs) is presented because NNs can accurately create a fitting function for a Doppler signal and extend the signal to the DC value, increasing the signal length and sampling points without yielding unnecessary influences on the Doppler frequency. We precisely measured Doppler frequencies in the frequency domain with a low sampling rate and calculated the velocities for a target with longitudinal movements. Compared to time-domain extraction, frequency-domain extraction can reflect the complete information of the original Doppler signal. This feature potentially contributes to the signal processing of velocimetry in practical engineering applications.

Ionic Signal Enhancement by the Space Charge Effect through the DNA Rolling Circle Amplification on the Outer Surface of Nanochannels.

DNA species are recognized as a powerful probe for nanochannel analyses to address the issues of specific target recognition and highly efficient signal conversion due to their programmable and predictable Watson-Crick bases. However, in the conventional view, abundant sophisticated DNA structures synthesized by DNA amplification strategies are unsuitable for use in nanochannel analyses owing to their low probability to enter a nanochannel restricted by the smaller opening of the nanochannel, as well as the faint ion signal produced by the steric effect. Here, we present an integrated strategy of nanochannel analyses that combines the target recognitions by encoded rolling circle amplification (RCA) in solution and the ionic signal enhancement by the space charge effect through the immobilization of highly negative-charged RCA amplicons on the outer surface of the nanochannels. Owing to the highly negative-charged RCA amplicons with 100 nm sizes, a sharp increase of ionic current up to 7454% has been achieved. The RCA amplicon triggered by mRNA-21 on the outer surface of the poly(ethylene terephthalate) membrane with a single nanochannel realized the single-base mismatch detection of mRNA-21 with a sensitivity of 6 fM. The DNA amplicon endows the nanochannel with high sensitivity and selectivity that could extend to other applications, such as DNA sequencing, desalination, sieving, and water-energy nexus.

Exposure-time-dependent subcellular staging of gold nanoparticles deposition and vesicle destruction in mice livers.

Several advances in nanomedicine have been accompanied by rising concerns about the bioaccumulation and toxicity of gold nanoparticles (AuNPs). Here, we assessed the in vivo fate of diversely sized AuNPs that were injected into mice as a computed tomography contrast agent and examined with multi-scale analyses across the organ, tissue, cell, and subcellular levels. After focusing on the strong detected accumulation in livers, our data revealed a set of three clear, exposure-time-dependent patterns based on i) AuNPs deposit morphology and ii) readily identifiable phenotypes for AuNP-impacted subcellular vesicles. Importantly, we detected no obvious differences in liver function, liver cell apoptosis, or autophagy upon exposure to AuNPs. Thus, our study illustrates an accessible experimental and high-resolution data interpretation framework for quickly obtaining and contextualizing informative trends about any AuNP-triggered patterns of subcellular damage in nanomedicine studies; these can help guide cytotoxity and safety testing of diagnostic nanomedical technologies.

[An integrative metabolomics and network pharmacology method for exploring bioactive components and preliminary pharmacodynamics in medicinal parts of Harrisonia perforata].

In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.

[Efficacy and safety of lactase additive in preterm infants with lactose intolerance: a prospective randomized controlled trial].

OBJECTIVE: To study the efficacy and safety of lactase additive in improving lactose intolerance in preterm infants. METHODS: A total of 60 preterm infants with lactose intolerance who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 were randomly divided into a lactase treatment group and a control group, with 30 infants in each group. The infants in the lactase treatment group were given 4 drops of lactase additive (180 mg) added into preterm formula or breast milk, and those in the control group were given placebo, oral administration of probiotics (live combined Bifidobacterium, Lactobacillus and Enterococcus powder) at half an hour after feeding (1 g each time, twice a day), and clockwise abdominal massage around the belly button at 1 hour after feeding for 15 minutes each time, 3 times a day. Fecal pH, fecal reducing sugar, growth indicators, symptoms of lactose intolerance, and laboratory markers were measured at the end of the first and second weeks after intervention. RESULTS: Finally 29 infants in the lactase treatment group and 26 infants in the control group completed the trial. At the end of the first week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and gastric retention amount (P < 0.05) and a significantly higher proportion of infants with fecal pH > 5.0 (P < 0.05). At the end of the second week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and 24-hour abdominal circumference difference (P < 0.05) and a significantly higher proportion of infants with the absence of gastric retention, fecal pH > 5.0, or negative reducing sugar in feces (P < 0.05). No adverse reactions associated with the lactase additive or probiotics were observed during the trial. CONCLUSIONS: Lactase additive can safely and effectively improve the clinical symptoms caused by lactose intolerance in preterm infants.

Pirfenidone and nintedanib attenuate pulmonary fibrosis in mice by inhibiting the expression of JAK2.

Background: Pirfenidone and nintedanib were approved by the Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF). These two drugs can slow the progression of the disease, but the specific mechanisms are not fully understood. In the current study, bleomycin (BLM) induced pulmonary fibrosis in mice was accompanied by high p-JAK2 expression in lung tissue, mainly in the nucleus. The expression of p-JAK2 significantly decreased after intragastric administration of pirfenidone and nintedanib. p-JAK2 is reportedly expressed mainly in the cytoplasm and exerts its effect by activating downstream p-STAT3 in the nucleus. Methods: In vivo experiments, pulmonary fibrosis was induced in mice with BLM and then treated with pirfenidone and nintedanib. The levels of transforming growth factor-ß (TGF-ß1), SP-A, SP-D and KL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Pathological staining was performed to assess lung fibrosis in mice, Western blot was performed to detect the expression levels of relevant proteins, and immunofluorescence was performed to observe the fluorescence expression of p-JAK2. In cellular experiments, MLE12 was stimulated with TGF-ß1 and intervened with TGF-ß1 receptor inhibitor and si-JAK2, pirfenidone and nintedanib, respectively, and the related protein expression levels were detected by Western blot. Results: In both in vivo and in vitro experiments, pirfenidone and nintedanib were found to attenuate the expression of lung fibrosis markers by inhibiting the expression of JAK2, which may reduce the entry of p-JAK2 into the nucleus by downregulating JAK2 phosphorylation through inhibition of the TGF-ß receptor. In contrast, inhibition of JAK2 expression greatly reduced the expression of TGF-ß receptor and α-smooth muscles actin (a myofibroblast activation marker). Conclusions: In both in vivo and in vitro experiments, the present study demonstrated that TGF-ß1 promotes JAK2 phosphorylation through a non-classical pathway, and conversely, inhibition of JAK2 expression affects the TGF-ß1 signalling pathway. Therefore, we speculate that TGF-ß1 and JAK2 signaling pathways interact with each other and participate in fibrosis.

Testing the applicability of the Modelling-Ongrowing Fish farms-Monitoring B (MOM-B) investigation system for assessing benthic habitat quality in the manila clam Ruditapes philippinarum aquaculture areas.

The coastal aquaculture areas have been subject to a variety of anthropogenic pressures in recent studies, and reasonable environmental quality assessment is essential for both ecological conservation and production practices. However, there are significant differences between the results produced from various environmental quality assessment regarding the focus of the evaluation and the fundamental methodology. Furthermore, many of these methods are very specific and difficult to adapt to general applications. Here, we utilized the Modelling-Ongrowing fish farms-Monitoring B investigation system (MOM-B), we assessed the benthic habitat quality of benthic bivalve aquaculture areas in the Xiaoqing River estuary located in Laizhou Bay, China. The aim was to validate the accuracy and practicality of this system. The biological, chemical, and sensory parameters of the MOM-B system, temperature, chlorophyll a (Chl-a), food availability, and planktonic larvae were evaluated throughout the investigation area during the summer of 2021. The MOM-B results indicated that the benthic habitat quality in the survey area was good and lightly disturbed, but the quality in the middle tide area began to deteriorate in August, the hottest month of the summer. Environmental factors indicated that the combined effects of high temperatures and fine sedimentation had led to increased environmental stress in the middle tide area. Food availability and population recruitment also suggested that the benthic habitat quality was better in the high tide and low tide areas than in the middle tide area, and more favorable for the survival of Manila clams. The accuracy, sensitivity, and discriminatory ability of the MOM-B system were demonstrated by environmental and biological indicators. This work showed that the MOM-B system is a practical, simple, and sensitive environmental assessment tool that is easy to implement in estuarine and benthic bivalve aquaculture areas. It can be used for long-term continuous monitoring and as an early warning tool for benthic habitat quality.

Association of left atrial wall thickness with recurrence after cryoballoon ablation of paroxysmal atrial fibrillation.

BACKGROUND: Transmural injury plays a role in successful atrial fibrillation ablation. The effect of left atrial wall thickness (LAWT) on the efficacy of radiofrequency ablation has been identified, but data on the relationship between LAWT and cryoballoon for paroxysmal atrial fibrillation (PAF) are lacking. We aim to explore the relationship between LAWT and recurrence after cryoballoon ablation (CBA). METHODS: We studied 364 patients (mean age 62 years) with PAF who underwent a second-generation CBA and pre-procedure cardiac CTA. LAWT and left atrial volume index (LAVI) were obtained based on pre-procedure cardiac CTA measurements. Follow-up was at least 12 months and predictors of atrial tachyarrhythmia recurrence during follow-up were assessed. RESULTS: Patients were followed up for a median of 19 (12-28) months, with an atrial tachyarrhythmia-free rate of 77.5% after cryoablation. Greater LAVI (50.0 ± 19.6 mL/m2 vs. 44.3 ± 15.4 mL/m2, P = 0.018) and greater LAWT (1.67 ± 0.24 vs. 1.46 ± 0.25 mm, P < 0.001) were associated with atrial tachyarrhythmia recurrence. The mean LAWT of PV antrum correlated with TTI (R = 0.252, P < 0.001). Adding LAWT to the established risk model improved both the discrimination and reclassification effects (IDI: 0.099, 95% CI: 0.065-0.134, P < 0.001; NRI: 0.685, 95% CI: 0.455-0.915, P < 0.001). In a multivariable Cox proportional hazard model, the mean LAWT of PV antrum (hazard ratio [HR]:3.657, 95%CI: 2.319-5.765, P < 0.001) was an independent predictor of atrial tachyarrhythmia recurrence after cryoablation. CONCLUSIONS: The mean LAWT of PV antrum, obtained from preoperative measurements on CT, was associated with atrial tachyarrhythmia recurrence after cryoablation.

Effectiveness of APG and Honey Gauze in Pressure Injury of Elderly: A Randomized Control Trial.

This study was designed to evaluate the efficiency of the combination of autologous platelet-rich plasma gel (APG) and Manuka honey gauze in the treatment of Stages 3-4 pressure injury of older adults. Patients were divided into four groups: Manuka honey gauze and APG (M + A), Manuka honey gauze (M), APG (A), and a control group (C). Different treatments were given, then wound bed coverage with granulation tissue, wound size reduction, and Pressure Ulcer Scale for Healing (PUSH) score were examined. Paraffin-embedded sections of wound tissues were analyzed and wound swab cultures were assessed. Kruskal-Wallis test and Mann-Whitney U test were performed in statistical analysis at a 5% significance level. A total of 42 patients were accepted. Significant increase of wound bed coverage with granulation tissue (51.24%, P = .004, Kruskal-Wallis test) and decrease of PUSH score (-5) were observed in the M + A group at the end of the observation (P = .032, Mann-Whitney U test). The hematoxylin-eosin staining of wound tissues showed that typical squamous epithelium was seen in wound bed of patient in M + A group. Manuka honey gauze and APG were proved to be superior treatments for pressure injury of old patient. Increase of granulation tissue coverage, reduction of PUSH score, and improved growth of epithelium were observed in M + A group. There was no side-effect, and the treatment would not cause infection.

Swellable microneedle-coupled light-addressable photoelectrochemical sensor for in-situ tracking of multiple pesticides pollution in vivo.

In vivo monitoring of multiple pesticide contamination is of great significance for evaluating the health risks of different pesticides, agricultural production safety, and ecological and environmental assessment. Here, we report a hydrogel microneedle array coupled light-addressable photoelectrochemical sensor for tracking multiple pesticide uptake and elimination in living animals and plants, holding three prominent merits: i) enables in-situ detection of in vivo pesticides, avoiding cumbersome and complex sample transportation and handling processes; ii) allows repeated in vivo sampling of the same organism, improving tracking test controllability and accuracy; iii) avoids lethal sampling, providing a better understanding of the pesticides fate in living organisms. The coupled sensor is mechanically robust for withstanding more than 0.35 N per needle and highly swellable (800 %) for timely extraction of sufficient in vivo solution for analysis. For proof-of-concept, it achieves in-situ detection of atrazine, acetamiprid, and carbendazim efficiently and quantitatively in artificial agarose skin models, mouse skin interstitial fluids, and plant leaves with little inflammatory reaction. This simple, highly integrated, minimally invasive, and high-throughput in vivo monitoring method is ideal for future field environmental monitoring and plant and animal disease diagnosis.

Morphine timing-dependent modulation of TRPV1 phosphorylation correlates with differential morphine effects on myocardial ischemia/reperfusion injury.

Opioids are used for pain relief in patients suffering from acute myocardial ischemia or infarction. Clinical and laboratory studies demonstrate that morphine treated patients or the experimental animal model suffering acute myocardial ischemia and reperfusion, may worsen myocardial viability. As transient receptor potential vanilloid 1 (TRPV1) plays important roles in pain sensation and cardio-protection, we query whether opioids may exacerbate myocardial viability via interaction with TRPV1 activity in the pain relief. We found the co-expressions of TRPV1 and opioid µ, δ and κ receptors in adult rat cardiomyocytes. Intravenous injection of morphine (0.3 mg/kg) at 20 min after induction of myocardial ischemia, in the rat model of acute myocardial ischemia and reperfusion, induced significant reduction of phosphorylated TRPV1 (p-TRPV1) in the ventricular myocardium and increase in serum cardiac troponin I (cTnI), compared with the ischemia/reperfusion controls (all P < 0.05). The effects of morphine were completely reversed by selective opioid µ, δ and κ receptor antagonists. While significant upregulation of p-TRPV1 (P < 0.05) and improvement of ±dP/dt max (all P < 0.05) were detected in the animals giving the same dose of morphine before induction of myocardial ischemia. The changes in p-TRPV1 correlate with the alterations of cTnI (r = -0.5840, P = 0.0283) and ±dP/dt max (r = 0.8084, P = 0.0005 and r = -0.8133, P = 0.0004, respectively). The findings of this study may indicate that potentiation and attenuation of TRPV1 sensitivity correlate with the improvement of the cardiac performance and the aggravation of myocardial viability, respectively, by giving morphine before and during myocardial ischemia and reperfusion.

Stimuli-Responsive Ion Transport Regulation in Nanochannels by Adhesion-Induced Functionalization of Macroscopic Outer Surface.

Responsive regulation of ion transport through nanochannels is crucial in the design of smart nanofluidic devices for sequencing, sensing, and water-energy nexus. Functionalization of the inner wall of the nanochannel enhances interaction with ions and fluid but restricts versatile chemical approaches and accurate characterizations of fluidic interfaces. Herein, we reveal a responsive regulating mechanism of ion transport through nanochannels by polydopamine (PDA)-induced functionalization on the macroscopic outer surface of nanochannels. Responsive molecules were codeposited with PDA on the outer surface of nanochannels and formed a valve of nanometer thickness to manually manipulate ion transport by changing its gap spacing, surface charge, and wettability under external stimulus. The response ratio can be up to 100-fold by maximizing the proportion of responsive molecules on the outer surface. Laminating the codepositions of different responsive molecules with PDA on the channel's outer surface produces multiple responses. A nearly universal adhesion of PDA with responsive molecules on the open outer surface induces nanochannels responsive to different external stimuli with variable response ratios and arbitrary combinations. The results challenge the primary role of functionalization on the nanoconfined interface of nanofluidics and open opportunities for developing new-style nanofluidic devices through the functionalization of macroscopic interface.

Involvement of long non-coding RNA LOXL1-AS1 in the tumourigenesis and development of malignant tumours: a narrative review.

Background and Objective: Long noncoding RNAs (lncRNAs) are involved in a wide variety of physiological and pathological processes in organisms. LncRNAs play a significant role as oncogenic or tumour-suppressing factors in various biological processes associated with malignant tumours and are closely linked to the occurrence and development of malignancies. Lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) is a recently discovered lncRNA. It is upregulated in various malignant tumours and is associated with pathological characteristics such as tumour size, tumour node metastasis (TNM) staging, lymph node metastasis, and tumour prognosis. LOXL1-AS1 exerts its oncogenic role by competitively binding with multiple microRNAs (miRs), thereby regulating the expression of downstream target genes and controlling relevant signalling pathways. This article aims to explore the structure and the function of LOXL1-AS1, and the relationship between LOXL1-AS1 and the occurrence and development of human malignant tumours to provide a reference for further clinical research. Methods: English literature on LOXL1-AS1 in the occurrence and development of various malignant tumours was searched in PubMed. The main search terms were "LOXL1-AS1", "tumour". Key Content and Findings: This article mainly summarizes the biological processes in which LOXL1-AS1 is involved in various human malignant tumours and the ways in which this lncRNA affects malignant biological behaviours such as proliferation, metastasis, invasion, and apoptosis of tumour cells through different molecular regulatory mechanisms. This article also explores the potential clinical significance and application prospects of LOXL1-AS1, aiming to provide a theoretical basis and reference for the clinical diagnosis, treatment, and screening of prognostic markers for malignant tumours. Conclusions: LOXL1-AS1 acts as a competing endogenous RNA (ceRNA), binding to miRs to regulate downstream target genes and exert its oncogenic effects. LOXL1-AS1 may become a novel molecular biomarker for cancer diagnosis and treatment in humans, and it may also serve as an independent prognostic indicator.

A Gender-, Age-, and Weight Status-Specific Analysis of the High Prevalence of Hyperuricemia Among Chinese Children and Adolescents with Obesity.

Objective: To explore the gender-, age-, and weight status-specific prevalence of hyperuricemia (HUA) and its associated risk factors among Chinese children and adolescents with obesity. Methods: A total of 1329 children aged 2-17 years, who were diagnosed with obesity and hospitalized in our center from January 2016 to December 2022 were recruited. They were divided into mild obesity, moderate obesity, and severe obesity groups. HUA was defined as fasting serum uric acid level >420 µmol/L for boys and >360 µmol/L for girls. Multivariate logistic regression analyses were performed to identify risk factors for HUA. Results: The highest proportion of hospitalized obese children was aged 10-13 years comprising 677 (50.9%) followed by those aged 6-9 years comprising 348 (26.2%) whereas the least proportion was aged 2-5 years comprising 76 (5.7%). The above differences in age distribution were still present in subgroup analyses according to weight status. Most hospitalized obese children were boys (64.7%), especially in the severe obesity group (75.0%). The overall estimated prevalence of HUA in obese children was 54.8%. It presented a gradual increase trend over the last 7 years, with more rapidly in boys than in girls. Subgroup analysis by weight status showed that the prevalence of HUA was higher in children with moderate obesity (64.3%) and severe obesity (64.2%) when compared with mild obesity (48.2%) (P all<0.01). Boys reached a relatively high HUA incidence level (≥60%) at age 12, which occurred about 2 years later than in girls (age 10). With 12 years as the cut-off point, a high prevalence of HUA (≥60%) was observed in both genders. Multivariable logistic regression analyses showed that boy (OR=2.844, 95% CI 2.024-3.998), age (OR=1.253, 95% CI 1.155-1.360), BMI-Z score (OR=2.132, 95% CI 1.438-3.162), fasting blood glucose (OR=0.907, 95% CI 0.860-0.956), phosphorus (OR=4.123, 95% CI 2.349-7.239), alkaline phosphatase (OR=1.002, 95% CI 1.001-1.004), creatinine (OR=1.067, 95% CI 1.037-1.098), urea nitrogen (OR=1.193, 95% CI 1.032-1.378), aspartate aminotransferase (OR=1.016, 95% CI 1.002-1.030), triglycerides (OR=1.339, 95% CI 1.075-1.667), and high-density lipoprotein cholesterol (OR=0.381, 95% CI 0.160-0.910) were independently associated with odds of HUA (P all<0.05). Conclusion: The prevalence of HUA in Chinese obese children and adolescents is unexpectedly high. Childhood HUA was significantly associated with obesity. Gender and age differences were observed in the association between childhood obesity and HUA. Obese children aged ≥12 years should be focused on screening the risk of HUA.

What condition leads to an unreasonable pharmaceutical price? Impact research on the effect of medical service provision on pharmaceutical price regulation based on fuss-set QCA.

Given that the pharmaceutical market has experienced severe market failures, it is necessary that we regulate pharmaceutical prices for many countries. Toward ensuring that pharmaceutical price regulation is efficient, this study investigated the antecedents that lead to an unreasonable pharmaceutical price. Based on 33 case-study countries, this study utilized QCA to analyze the conditional configuration of unreasonable pharmaceutical prices from the perspective of medical service provision. The results showed that the causes of unreasonable pharmaceutical prices are configured by medical service provision, especially cost compensation systems and payment mechanism. This study's conclusions contribute to the research on pharmaceutical price regulation and the institution of medical service provision.

GIS-based spatial suitability assessment for pacific oyster Crassostrea gigas reef restoration: A case study of Laizhou Bay, China.

The oyster reef restoration has raised concerns worldwide due to the advantage of alleviating eutrophication and other ecosystem services. The necessary prerequisite for oyster restoration is identifying suitable sites. A restoration suitability index model for C. gigas reefs was built by combining the Monte Carlo simulation, analytic hierarchy process, hydrodynamic modelling and geographic information systems and applied in Laizhou Bay (LZB), China. The model outputs and sensitivity analysis showed that the east coastal area, the southern part, and the western part of LZB were restoration sites with the maximum suitability, accounting for 15.3 % of LZB. The middle and northern parts of LZB were unsuitable sites restricted by water depth and flow velocity. Ship waterways and marine industries were the major factors causing degradation of the historically recorded oyster reefs. This model can support oyster restoration planning, and can be applied to other oyster species with adjusted indicator system.

Environmental influence on summer survival of Manila Clam Ruditapes philippinarum: A case study in an aquaculture bay.

The aquaculture of Manila clam (Ruditapes philippinarum) is under threat due to its high mortality in summer. To investigate the environmental influence on mortality of the species, we have conducted field surveys in the aquaculture area in Laizhou Bay, during the summers of 2019 and 2020. Environmental and biological data were collected. The results of data analysis have shown that in 2020, large-scale mortality events were not recorded and spatial variations of environmental variables were no significant within the survey area. However, in August 2019, significant variations of environmental variables were detected in the middle tidal area. This area was charactered with relatively high-water temperature (with maximum temperature of 31.49 °C and mean value of 26.17 ± 1.62 °C), elevated hydrogen sulfide concentrations (with a maximum concentration of 24.72 µmol/L and a mean concentration of 7.89 ± 4.14 µmol/L), and low dissolved oxygen concentrations (with a minimum concentration of 3.35 mg/L and a mean concentration of 6.27 ± 0.42 mg/L). Correspondingly, high mortality of the clam was recorded in the area, the abundance of live Manila clams has decreased by 80%. No significant abnormalities of environmental variables and clam growth were observed in other regions in 2019. Glycogen content and condition index of the clam were analyzed to investigate the relationship between environmental stress and the health of the clam. Compared to the condition index, glycogen content is a more sensitive indicator of the health status of the clam because changes in glycogen content appeared earlier than changes in condition index and mortality. A principal component analysis further indicated that the high mortality of the clam corresponds with a few environmental variables, including elevated temperature, hypoxia and the concentration of hydrogen sulfide. The simultaneous presence of these multiple environmental stressors could have triggered alterations in the physiological responses of the clam.

Defense System of the Manila Clam Ruditapes philippinarum under High-Temperature and Hydrogen Sulfide Conditions.

Hydrogen sulfide (H2S) acts as an environmental toxin. Despite its toxicity, little is known about the defense strategies of marine bivalves against it. Thus, the tolerance, behavioral characteristics, and physiological response strategies against H2S treatment in the sentinel organism Manila clam Ruditapes philippinarum were examined. We monitored the survival and behavioral status of Manila clams exposed to different combinations of temperature and H2S. The physiological response strategies were examined by measuring the enzymatic activity of cytochrome C oxidase (CCO), fumarate reductase (FRD), superoxide dismutase (SOD), and catalase enzymes (CAT). Moreover, adverse effects of H2S on the tissue and cell structure of Manila clams were also examined under a transmission electron microscope. Manila clams responded to H2S stress through behavioral and chemical defenses. With exposure to H2S alone, Manila clams primarily enhanced aerobic respiratory metabolic pathways in the beginning stages by opening the shell and increasing the CCO activity to obtain more oxygen; with increasing exposure time, when aerobic respiration was inhibited, the shell was closed, and FRD, CAT, and SOD were activated. At this point, Manila clams responded to H2S stress through the anaerobic metabolism and antioxidant defense systems. However, high temperatures (≥28 °C) altered the defense strategy of Manila clams. With co-exposure to high temperatures and high H2S concentrations (≥20 µmol/L), the Manila clams immediately closed their shells and changed from aerobic respiration to anaerobic metabolism while immediately activating antioxidant defense systems. Nevertheless, this defense strategy was short lived. In addition to this, apparent damage to tissue and cell structures, including mitochondrial ridge dissolution and many vacuoles, was observed in Manila clams exposed to high temperatures and high H2S concentrations. Thus, prolonged exposure to high temperature and H2S damages the tissue structure of Manila clams, affecting their behavioral capacity and future survival. In summary, profiling Manila clams' physiological response strategies to H2S exposure provided ecological behavioral support for our current understanding of H2S detrimental toxicity on marine bivalves.