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Urinary hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and catecholamines (CAs) are important biomarkers of PAHs exposure. In this study, a novel magnetic boronic acid hypercrosslinked composite (Fe 3 O 4 @HCP-BA) is synthesized using a facile one-pot strategy and applied as a sorbent for the simultaneous extraction of OH-PAHs and CAs in urine samples. The synthesized Fe 3 O 4 @HCP-BA composites are characterized by rich pore structure, highly specific surface area, good magnetic response, and excellent selectivity and adsorption efficiency (range: 65.26-496.71 and 1227.3-1581.8 µmol g -1 for CAs and OH-PAHs, respectively). The mechanisms governing the adsorption of the OH-PAHs and CAs to the Fe 3 O 4 @HCP-BA composites were systematically studied via adsorption kinetics, isotherm models, XPS characterization, and molecular simulation. The resultant Fe 3 O 4 @HCP-BA composite-based MSPE/HPLC-FLD method exhibited good linearity (R 2 > 0.9916), low limits of detection (0.2-0.3 pg mL -1 and 0.2-0.3 ng mL -1 for OH-PAHs and CAs, respectively), and good precision (intra-day and inter-day RSDs < 11.1%). The analysis of CAs and OH-PAHs in the urine samples from 14 smokers and 14 non-smokers revealed a positive correlation between the concentrations of CAs and OH-PAHs. Our findings not only establish the proposed method as a green, environmentally friendly, and simple strategy for preparing magnetic adsorbents, but also confirm it as a promising alternative method for accurate determination of OH-PAHs and CAs in biological samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: In this study, the diagnostic value of C-reactive protein (CRP), interleukin-6 (IL)-6, and specific markers for type I hypersensitivity were evaluated in pediatric patients with severe acute appendicitis., Methods: A total of 140 pediatric patients with "acute appendicitis" who underwent surgery at the Department of General Surgery of the Anhui Provincial Pediatric Patients' Hospital between December 2022 and April 2023 were studied retrospectively. The data collected included the gender, age, onset time, white blood cell count (WBC), CRP, procalcitonin (PCT), serum IgE, serum IL-4, serum IL-5, serum IL-6, serum IL-9, and serum IL-13 levels. The pediatric patients were divided into two groups based on the intraoperative situation and postoperative pathology: the non-complicated acute appendicitis group (NCAA) and the complicated acute appendicitis group (CAA). We analyzed the data from both groups using univariate and multivariate logistic regression models and constructed an ROC curve., Results: The CAA group outperformed the NCAA group in terms of onset time, WBC, CRP, PCT, IgE, IL-6, IL-9, and IL-13 levels (P < 0.05), but there was no statistically significant difference between the two groups in terms of gender, IL-4, or IL-5 levels (P > 0.05). Then, significant independent variables were incorporated into multivariate logistic regression. According to the results, CRP, IgE, IL-6, and IL-13 are all independent risk factors for CAA. The OR and 95% CI for each factor are as follows: CRP (OR = 1.073, 95%CI: 1.010-1.140, P = 0.022), IgE (OR = 0.975, 95%CI: 0.952-0.999, P = 0.038), IL-6 (OR = 1.494, 95%CI: 1.052-2.121, P = 0.025), and IL-13 (OR = 1.310, 95%CI: 1.036-1.657, P = 0.024). The receiving operator characteristics analysis yielded area under the curve (AUC) values of 0.8187, 0.9083, 0.8947, and 0.8394, respectively, for CRP, IgE, IL-6, and IL-13, confirming their significance in the diagnosis of CAA (P < 0.05)., Conclusion: Risk factors for CAA include CRP, IgE, IL-6, and IL-13. The combination of these serological markers can be used to diagnose CAA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is an age-related neurodegenerative disease that progressively impairs cognitive function and memory. The occurrence and development of Alzheimer's disease involves many processes. In response to the complex pathogenesis of AD, the Traditional Chinese medicine formula Liuwei Dihuang Pill (LWD) has been shown to improve the cognitive function of AD animal models. However, the active ingredients and mechanism of action of LWD have not been fully elucidated. In this study, network pharmacological analysis predicted 40 candidate compounds in LWD, acting on 227 potential targets, of which 185 were associated with AD. Through network pharmacological analysis, the mechanism of action of LWD therapy AD is related to the inhibition of inflammatory response, regulation of neuronal state, and autophagy. In this experiment, LWD was detected in the APP/PS1 transgenic mouse model. The objective was to observe the effects of LWD on hippocampal learning and memory ability, Aβ clearance, autophagy and inflammatory response in APP/PS1 mice. The results showed that LWD improved long-term memory and working memory in APP/PS1 mice compared with the WT group. At the same time, LWD can increase the expression of hippocampal autophagy biomarkers, reduce the precipitation of Aβ, and the activation of microglia and astrocytes. Its mechanism may be related to the regulation of the PI3K/Akt signaling pathway. Thus, we demonstrate for the first time that LWD has a neuroprotective effect on APP/PS1 mice and provide theoretical foundation for the development of a new clinical treatment for AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Liu, Hao, Ma, Shao, Yu, Shi, Zhang and Zhang.)

Parkinson's disease (PD) is a complex syndrome with many elements, such as chronic inflammation, oxidative stress, mitochondrial dysfunction, loss of dopaminergic neurons, build-up of alpha-synuclein ( α -syn) in cells, and energy depletion in neurons, that drive the disease. We and others have shown that treatment with mimetics of the growth factor glucagon-like peptide 1 (GLP-1) can normalize energy utilization, neuronal survival, and dopamine levels and reduce inflammation. Liraglutide is a GLP-1 analogue that recently showed protective effects in phase 2 clinical trials in PD patients and in Alzheimer disease patients. We have developed a novel dual GLP-1/GIP receptor agonist that can cross the blood-brain barrier and showed good protective effects in animal models of PD. Here, we test liraglutide against the dual GLP-1/GIP agonist DA5-CH (KP405) in the A53T tg mouse model of PD which expresses a human-mutated gene of α -synuclein. Drug treatment reduced impairments in three different motor tests, reduced levels of α -syn in the substantia nigra, reduced the inflammation response and proinflammatory cytokine levels in the substantia nigra and striatum, and normalized biomarker levels of autophagy and mitochondrial activities in A53T mice. DA5-CH was superior in almost all parameters measured and therefore may be a better drug treatment for PD than liraglutide., Competing Interests: CH is a named inventor on patents that cover the use of GLP-1/GIP receptor agonists in treating neurodegenerative disorders. He is the CSO of the company Kariya Pharmaceuticals. The other authors declare that they have no conflicts of interest., (Copyright © 2023 Zijuan Zhang et al.)

Synaptic impairment and loss are an important pathological feature of Alzheimer's disease (AD). Memory is stored in neural networks through changes in synaptic activity, and synaptic dysfunction can cause cognitive dysfunction and memory loss. Cholecystokinin (CCK) is one of the major neuropeptides in the brain, and plays a role as a neurotransmitter and growth factor. The level of CCK in the cerebrospinal fluid is decreased in AD patients. In this study, a novel CCK analogue was synthesized on the basis of preserving the minimum bioactive fragment of endogenous CCK to investigate whether the novel CCK analogue could improve synaptic plasticity in the hippocampus of the APP/PS1 transgenic mouse model of AD and its possible molecular biological mechanism. Our study found that the CCK analogue could effectively improve spatial learning and memory, enhance synaptic plasticity in the hippocampus, normalize synapse numbers and morphology and the levels of key synaptic proteins, up-regulate the PI3K/Akt signaling pathway and normalize PKA, CREB, BDNF and TrkB receptor levels in APP/PS1 mice. The amyloid plaque load in the brain was reduced by CCK, too. The use of a CCKB receptor antagonist and targeted knockdown of the CCKB receptor (CCKBR) attenuated the neuroprotective effect of the CCK analogue. These results demonstrate that the neuroprotective effect of CCK analogue is achieved by activating the PI3K/Akt as well as the PKA/CREB-BDNF/TrkB signaling pathway that leads to protection of synapses and cognition., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Integrating bioinformatics and experimental validation to explore the mechanisms of inflammaging in the Brain., Method: After dividing the GSE11882 dataset into aged and young groups, we identified co-expressed differentially expressed genes (DEGs) in different brain regions. Enrichment analysis revealed that the co-expressed DEGs were mainly associated with inflammatory responses. Subsequently, we identified 12 DEGs that were related to the inflammatory response and used the DGIdb website for drug prediction. By using both the least absolute shrinkage and selection operator (LASSO) and random forest (RF), four biomarkers were screened and an artificial neural network (ANN) was developed for diagnosis. Subsequently, the biomarkers were validated through animal studies. Then we utilized AgeAnno to investigate the roles of biomarkers at the single cell level. Next, a consensus clustering approach was used to classify the aging samples and perform differential analysis to identify inflammatory response-related genes. After conducting a weighted gene co-expression network analysis (WGCNA), we identified the genes that are correlated with both four brain regions and aging. Wayne diagrams were used to identify seven inflammaging-related genes in different brain regions. Finally, we performed immuno-infiltration analysis and identified macrophage module genes., Key Findings: Inflammaging may be a major mechanism of brain aging, and the regulation of macrophages by CX3CL1 may play a role in the development of inflammaging., Significance: In summary, targeting CX3CL1 can potentially delay inflammaging and immunosenescence in the brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Wang, Yang, Zhang, Jiang and Zhang.)

In this study, a borate hyper-crosslinked polymer was synthesized by crosslinking 1-naphthalene boric acid and dimethoxymethane via the Friedel-Crafts reaction. The prepared polymer exhibits excellent adsorption performance toward alkaloids and polyphenols with maximum adsorption capacities ranging from 25.07 to 39.60 mg/g. Adsorption kinetics and isotherms model results indicated the adsorption was a monolayer and chemical process. Under the optimal extraction conditions, a sensitive method was established for the simultaneous quantification of alkaloids and polyphenols in green tea and Coptis chinensis by coupling with the proposed sorbent and ultra-high performance liquid chromatography detection. The proposed method exhibited a wide linear range of 5.0-5000.0 ng/ml with R 2 ≥ 0.99, a low limit of detection (0.66-11.25 ng/ml), and satisfactory recoveries (81.2%-117.4%). This work provides a simple and convenient candidate for the sensitive determination of alkaloids and polyphenols in green tea and complex herbal products., (© 2023 Wiley-VCH GmbH.)

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, generates a serious threat to the health of the elderly. The AD brain is microscopically characterized by amyloid plaques and neurofibrillary tangles. There are still no effective therapeutic drugs to restrain the progression of AD though much attention has been paid to exploit AD treatments. Ferroptosis, a type of programmed cell death, has been reported to promote the pathological occurrence and development of AD, and inhibition of neuronal ferroptosis can effectively improve the cognitive impairment of AD. Studies have shown that calcium (Ca 2+ ) dyshomeostasis is closely related to the pathology of AD, and can drive the occurrence of ferroptosis through several pathways, such as interacting with iron, and regulating the crosstalk between endoplasmic reticulum (ER) and mitochondria. This paper mainly reviews the roles of ferroptosis and Ca 2+ in the pathology of AD, and highlights that restraining ferroptosis through maintaining the homeostasis of Ca 2+ may be an innovative target for the treatment of AD., Competing Interests: Declaration of Competing Interest The authors have declared that no conflicts of interest exist., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation., Aim of the Study: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1., Materials and Methods: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells., Results: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment., Conclusions: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1., Competing Interests: Declaration of conpeting interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Histone lysine specific demethylase 1 (LSD1) is responsible for the demethylation of mono-/dimethylated lysine residue on histone proteins. LSD1 plays an extensive and essential role in the pathogenesis and progression of many human diseases such as cancers, and thus is becoming an attractive therapeutic target for cancer treatment. Tranylcypromine (TCP) is an important chemical template for developing irreversible LSD1 inhibitors, representing a major chemotype of clinical candidates. Here we report a novel pool of TCP derivatives with triazolopyrimidine as a privileged heterocylic motif. Starting from ticagrelor, a clinically available antiplatelet agent, as a hit compound, our medicinal efforts have led to the identification of compound 9j with nanomolar inhibitory potency against LSD1 as well as broad-spectrum antiproliferative activities against tumor cells. Enzyme studies show that compound 9j is selective over MAO-A/B enzymes, and also cellular active to elevate the expression of H3K4me2 by inhibiting LSD1 in cells. Furthermore, in a H1650 xenograft mouse model, oral administration of compound 9j at low 10 and 20 mg/kg dosages could enable a significant reduction in tumor size and a remarkable extension of survival. The current work is expected to provide an additional strategy to achieve new TCP-based LSD1 inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The Zhurong rover of the Tianwen-1 mission landed in southern Utopia Planitia, providing a unique window into the evolutionary history of the Martian lowlands. During its first 110 sols, Zhurong investigated and categorized surface targets into igneous rocks, lithified duricrusts, cemented duricrusts, soils and sands. The lithified duricrusts, analysed by using laser-induced breakdown spectroscopy onboard Zhurong, show elevated water contents and distinct compositions from those of igneous rocks. The cemented duricrusts are likely formed via water vapor-frost cycling at the atmosphere-soil interface, as supported by the local meteorological conditions. Soils and sands contain elevated magnesium and water, attributed to both hydrated magnesium salts and adsorbed water. The compositional and meteorological evidence indicates potential Amazonian brine activities and present-day water vapor cycling at the soil-atmosphere interface. Searching for further clues to water-related activities and determining the water source by Zhurong are critical to constrain the volatile evolution history at the landing site., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

In this work, Friedel-Crafts alkylation was successfully applied to prepare a magnetic ionic liquid hypercrosslinked polymer composite (Fe 3 O 4 @IL-HCP), which was subsequently employed as magnetic solid-phase extraction (MSPE) adsorbent for the isolation and enrichment of trace non-steroidal anti-inflammatory drugs (NSAIDs). The developed composite was comprehensively characterized using various techniques, with the results indicating that it possessed high saturation magnetization (39.44 em g  -   1 ), large specific surface area (175 m 2 g  -   1 ), and high adsorption capacity for NSAIDs. The adsorption behavior and mechanisms were also investigated in detail. NSAIDs were adsorbed onto the Fe 3 O 4 @IL-HCP sorbent via a heterogeneous multilayer process consisting of hydrogen bonding and π-π and electrostatic interactions. Additionally, the composite's large surface area and multiple active sites enabled extraction equilibrium within 6 min. By coupling with high performance liquid chromatography (HPLC), the developed MSPE/HPLC method was applied for the determination of selected NSAIDs in water and urine samples. The developed method displayed wide linear ranges, low limits of detection (0.12-0.30 ng mL -1 and 0.15-1.5 ng mL -1 in water and urine samples, respectively), sufficient recoveries (92.8-109%), and good precision (relative standard deviations ≤ 4.6%). Thus, the findings of this work provide an appealing alternative for the extraction and determination of trace NSAIDs in environmental water and biological samples., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, covalent organic framework@MXene (COF@Ti 3 C 2 T x ) composites were synthesized and employed as solid phase microextraction coatings for isolation of polycyclic aromatic hydrocarbons (PAHs) from honey samples. The developed composites possessed unique structural characteristics and multiple interactions (π-π and hydrophobic interaction, etc.), which provided them with excellent extraction capacity towards the targeted PAHs. Under optimized conditions, the resultant COF@Ti 3 C 2 T x -coating fiber-based HS-SPME/GC-FID method exhibited a wide linear range (2.0-2000 ng g -1 ), good linearities (r > 0.9964), and low limits of detection (0.20-0.60 ng g -1 ). The recoveries of PAHs in the honey samples were in the range of 73.2-112%, with RSDs less than 9.4%. In addition, the findings showed that the composite-based fiber offers a long lifetime, high enhancement factors (483-598), and excellent fiber-to-fiber reproducibility (RSDs <10.5%, n = 3). This work not only details the development of a multi-functional composite, but it also presents an effective strategy for the determination of trace PAHs in complex food matrix., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Celastrol is a promising antitumor drug candidate, but the poor water solubility and cytotoxicity limit its clinical application. Herein, we synthesized a Celastrol (Cel)-chitosan oligosaccharide (CSO) conjugate (Cel-CSO) for drug delivery. Celastrol was conjugated to a CSO backbone via amide bond formation, which was verified by infrared spectrum (IR) analyses. The Cel-CSO contained ∼10 wt% of Celastrol showed excellent aqueous solubility (18.6 mg/mL) in comparation with the parent Celastrol. Cel-CSO significantly inhibited tumor growth, induced apoptosis, and effectively suppressed tumor metastasis in human pancreatic cancer cells (BxPC-3). While the cytotoxicity of Cel-CSO in hepatic cells (HL7702) was lower than that of the free Celastrol. Cel-CSO enhanced the anticancer efficacy, promoted the circulation time of Celastrol, and reduced the subacute toxicity, which indicated that CSO can be a promising Celastrol delivery system for pancreatic cancer therapy.

Ethnopharmacological Relevance: LiuweiDihuang (LW) pills was mainly used to treatment of children's fontanelle incomplete closure, enuresis and nervous system development delays and other diseases.Following the deepening of pharmacological research, LW has a good effect on neurological diseases include senile dementia. However, the neuroprotection mechanism of LW on Alzheimer's disease (AD) through regulation of inflammation remains unclear., Aim of the Study: Here, we aimed to explore the effects and mechanism of LW on learning and memory deficits in SAMP8 mice., Materials and Methods: Mice aged 6 months were treated with LW for 2 months and BV2, C6 and HT22 cells were treated with LW pharmaceutic serum and Lipopolysaccharide (LPS) continuously. Then, cognitive tests were performed, including the Morris water maze and Y maze tests. The mRNA level of cyclooxygenase 2 (COX-2) and pro-inflammatory factors (IL-1β, IL-6 and TNF-α) were examined in cells and the cortex and hippocampus by quantitative RT-PCR. The expression of postsynaptic density protein 95, synaptophysin and various inflammatory factors were detected in the cortex and hippocampus by Western blot. Furthermore, Ionized calcium binding adapter molecule 1, glial fibrillary acidic protein and Aβ were examined in the brain of AD mice by immunofluorescence staining and immunohistochemistry. And synaptic loss and neuronal ultrastructure were observed by transmission electron microscope., Results: We found that LW suppressed LPS-induced COX-2 expression in vitro. Importantly, LW dramatically improved spatial learning and memory in SAMP8 mice through inhibiting Aβ accumulation and restoring structural synaptic integrity. Furthermore, LW inhibited the glial activation and neuroinflammation (COX-2, IL-1β, IL-6 and TNF-α) in the cortex and hippocampus of SAMP8 mice., Conclusion: Taken together, the present data not only indicated that LW is an effective agent on improving the learning and memory deficits through mitigating neuroinflammation but highlighted the LW can be a potential therapeutic drug for AD therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Calcium transportation and homeostasis are essential for marine bivalves to maintain basic metabolism and build their shells. Calmodulin-like proteins (CaLPs) are important calcium sensors and buffers and can respond to ocean acidification (OA) in marine calcifiers. However, no further study of their physiological function in calcium metabolism under elevated CO 2 has been performed. Here, we identified a novel CaLP (designated CgCaLP) in the Pacific oyster Crassostrea gigas and demonstrated its participation in the calcification process: the mRNA expression level of CgCaLP peaked at the trochophore larval stage and remained high at stages when shells were shaped; the mRNA and protein of CgCaLP were more highly expressed in mantle tissue than in other tissues. Under elevated CO 2 levels, the protein expression level of CgCaLP in hemocytes increased, while in contrast, significantly decreased protein levels were detected in gill and mantle tissues. Shell dissolution caused the imbalance of calcium in hemocytes and decreased calcium absorption and transportation demand in gill and mantle tissues, inducing the molecular function allocation of CgCaLP under CO 2 exposure. Despite the decreased protein level in mantle tissue, CgCaLP was found to translocate to outer mantle epithelium (OME) cells where condensed calcium-rich deposits (CRDs) were detected. We further demonstrated that CgCaLP mRNA and protein expression levels could respond to seawater Ca 2+ availability, suggesting that the calcium deposition capacity of oysters might be enhanced to fight against shell dissolution problems and that CgCaLP might serve as an essential participator of the process. In summary, CgCaLP might enhance calcium deposition under CO 2 exposure and thus play a significant and flexible molecular function involved in a compensation strategy of oysters to fight against the acidified ocean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The main characteristic of Alzheimer's disease (AD) is the progressive decline of learning and memory ability. Electroacupuncture (EA) may improve AD-related learning and memory ability. However, the underlying molecular mechanism of action remains unclear. The objective of the present study was to assess the effects and the molecular mechanism of EA on learning and memory in an amyloid β 25-35 (A β 25-35 ) induced AD mouse model. The AD model was established by intracerebroventricular (ICV) administration of A β 25-35 oligomers. AD mice were electroacupunctured with wisdom three-needle combined with Baihui (GV20) five times per week for three consecutive weeks. The Morris water maze (MWM) and Y maze tests were applied to evaluate spatial learning and memory ability. A transmission electron microscope (TEM) was used to measure mitochondria and autophagy of hippocampal neurons, and western blot was applied to observe molecular changes in the mice hippocampus. The results suggested that EA treatment significantly alleviated learning and memory impairment related to AD, reduced mitochondria damage, improved autophagy, increased mitochondrial protein 2 (Mfn2), Beclin 1, and LC3B, and decreased the expressions of fission protein 1 (Fis1) level. Furthermore, EA further upregulated the protein expression of phosphatidylinositol 3-kinase (PI3K) and the ratio of p-Akt/Akt in the hippocampus of AD mice. This study demonstrates that EA treatment attenuates cognitive deficits, modulates mitochondrial fusion and fission, and enhances autophagy via the PI3K/Akt pathway in a mouse AD model., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Si-Mai Shao et al.)

In this study, a new Ti 3 C 2 T x -coated fiber was synthesized and utilized as coatings for solid-phase microextraction of seven polychlorinated biphenyls. The as-produced multilayered Ti 3 C 2 T x MXene was characterized by X-ray diffractometer, thermos-gravimetric analysis, scanning electron microscopy, and energy dispersive spectroscopy. It is noteworthy that the Ti 3 C 2 T x showed some attractive features including unique 2D layered structures, large surface area, good hydrophilicity, and rich active recognition sites, endowing it has a high affinity towards the target polychlorinated biphenyls. Subsequently, the affecting parameters on the extraction efficiency of polychlorinated biphenyls were optimized. Under the optimal conditions, a novel method for the analysis of polychlorinated biphenyls in water samples was proposed. The Ti 3 C 2 T x -coated fiber-based solid-phase microextraction method showed good linearity (r 2  > 0.9928), high enrichment factors (268-442), low limits of detection (0.06-0.15 ng/L), and satisfactory repeatability (RSDs < 7.5%) for the polychlorinated biphenyls. The excellent method recoveries were in the range of 90.0-98.4, 92.0-98.2, and 92.0-98.0% for river water, lake water, and tap water samples, respectively. These results suggested that the proposed Ti 3 C 2 T x -coated fiber-based method represents a promising alternative for the analysis of polychlorinated biphenyls., (© 2021 Wiley-VCH GmbH.)

The accumulation of iron-dependent lipid peroxides is one of the important causes of NAFLD. The purpose of this study is to explore the effect of dehydroabietic acid (DA) on ferroptosis in nonalcoholic fatty liver disease (NAFLD) mice and its possible mechanisms. DA improved NAFLD and reduced triglycerides (TG), total cholesterol (TC), and lipid peroxidation level and inhibited ferroptosis in the liver of HFD-induced mice. DA binds with Keap1 to form 3 stable hydrogen bonds at VAL512 and LEU557 and increased nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elemen (ARE) luciferase activity. DA promoted the expression downstream of Nrf2 such as heme oxygenase-1 (HO-1), glutathione (GSH) and its peroxidase 4 (GPX4), so as to eliminate the accumulation of reactive oxygen species (ROS) and reduce lipid peroxides malondialdehyde (MDA) in the liver. DA inhibited ferroptosis and increased the expression of key genes such as ferroptosis suppressor protein 1 (FSP1) in vitro and vivo. In all, DA may bind with Keap1, activate Nrf2-ARE, induce its target gene expression, inhibit ROS accumulation and lipid peroxidation, and reduce HFD-induced NAFLD.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells derived from immature myeloid cells (IMCs). MDSCs are known to play important roles in tumor immune evasion. While we know that there are a large number of circulating and tumor-infiltrating MDSCs existing in gastric cancer (GC) patients, the phenotypic characteristics and arginase 1 (ARG1) expression levels of these MDSCs remain very unclear. In our study, flow cytometric analysis of circulating MDSCs from 20 gastric adenocarcinoma (GAC) patients found that ≥80% ARG1-expressing MDSCs were mainly early-stage MDSCs (HLA-DR - CD33 + CD14 - CD15 - MDSCs). In addition, our investigation showed that tumor-infiltrating MDSCs from 6 GAC patients consisted of >35% ARG1-expressing naïve MDSCs (HLA-DR - CD33 - CD11b - CD14 - CD15 - MDSCs), >15% early-stage MDSCs and >40% monocytic MDSCs (HLA-DR - CD14 + MDSCs). This preliminary study describes the phenotypic characteristics and ARG1 expression levels of MDSCs from GAC patients and shows that circulating and tumor-infiltrating ARG1-expressing cells were mainly immature and monocytic MDSCs, which provides information to better understand the mechanisms that allow gastric cancer cells to evade the immune system.

Aim: Blockage of the urinary tract is often connected with renal function impediment, including reductions in glomerular filtration rate (GFR) and the power to control sodium as well as water elimination through urination. Melatonin, known to be the primary product of the pineal gland, prevents renal damage caused by ischemic reperfusion. However, the effects of melatonin on urinary obstruction, as well as release of obstruction induced kidney injury are still largely unknown. The aim of present study was to investigate the effect of melatonin on mediating protection against renal injury triggered from either bilateral ureteral obstruction (BUO) or BUO release (BUO-R)., Main Methods: Adult male Sprague-Dawley rats (n = 60) were clustered into six treatment groups: sham treated-1; BUO-non-treated (24 h BUO only); BUO + melatonin; sham treated-2; BUO-48hR (24 h of BUO and then release for 2 days); and BUO-48hR + melatonin. Kidney tissues, blood and urine samples were obtained for further assessment., Key Findings: It was found that melatonin treatment remarkably promoted the recovery of the handling capacity of urinary excretion of water as well as sodium in BUO and BUO-48hR models. Melatonin treatment partially inhibited inflammatory cytokine expression and the downregulation of aquaporin (AQPs, AQP-1, -2 and -3) expression in these two models. Moreover, the cytoarchitecture of BUO rats exposed to melatonin was well preserved., Significance: Melatonin treatment potently prevents BUO or BUO-R induced renal injury, which may be partially attributed to restoring the expression of AQPs and inhibition of inflammatory response, as well as preserving renal ultrastructural integrity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetes-related infections have become challenging and important public health problems in China and around the world. P. aeruginosa plays an important role in diabetic foot infections. As a gram-negative opportunistic pathogen, P. aeruginosa causes recurrent and refractory infections that are characterized by biofilm formation. Previous studies have demonstrated that biofilm-challenged wounds typically take longer to heal than non-biofilm-challenged normal wounds in diabetic mouse models. In the present study, we sought to explore the mechanism via which insulin treatment affects cyclic di-GMP signaling in P. aeruginosa -infected chronic wounds in db/db diabetic mice. We found that the wounds of diabetic mice healed more slowly than those of nondiabetic mice. Moreover, wound healing in diabetic mice treated with insulin exhibited a considerable delay. Peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) was used to detect biofilms on P. aeruginosa -infected wound tissues. Increased intracellular c-di-GMP levels promoted biofilm formation in wound tissues from nondiabetic mice. Greater biofilm formation was observed in the wounds of insulin-treated diabetic mice than in the wounds of untreated diabetic mice or nondiabetic mice, in both the PAO1/p lac - yhjH - and PAO1-infected groups. Quantitative RT-PCR indicated that upon infection with PAO1/P lac - yhjH (the low c-di-GMP expression strain), the expression of IL-4 RNA was significantly higher in diabetic mice treated with insulin than in untreated diabetic mice or nondiabetic mice at each observation time point. Peak expression of IFN-γ occurred earlier in diabetic mice treated with insulin than in untreated diabetic mice with each of the experimental strains. Finally, P. aeruginosa harboring the plasmid pCdrA: gfp s was used as a reporter strain to monitor c-di-GMP levels. We found that insulin could promote biofilm formation by increasing intracellular c-di-GMP levels in vitro. Taken together, these data demonstrate that insulin treatment increases intracellular c-di-GMP levels, promotes biofilm formation and prolongs the inflammation period during the healing of infected wounds, resulting in delayed wound healing., Competing Interests: None.

Objective: To clone and analyze variable region gene sequences of mouse monoclonal antibody against human S100A9( anti-human S100A9 mAb)., Methods: Total RNA was extracted from the hybridoma cell line( Ⅱ D4B10)secreting mouse anti-human S100A9 mAb. Furthermore,the heavy chain variable region( VH) and light chain variable region( VL) genes were amplified using reverse transcription-polymerase chain reaction( RT-PCR). After the cloning and sequencing of the VHand VLgenes,the sequence analyses were performed by BLAST program., Results: The VLgene,a member of the mouse IGKV14-111* 01 family,had an open reading frame( ORF) of 291 bp with 97 amino acids,and the VHgene,a member of the mouse IGHV1-80* 01 family,had an ORF of 324 bp with 108 amino acids. In addition,the sequences of VH and VLgenes presented the characteristics of antibody variable region with individual frameworks and complementarity determining regions., Conclusion: The variable region gene sequences of mouse anti-human S100A9 mAb have been successfully obtained,which are helpful to construct genetically engineered antibody in the future.

Objective: To evaluate the short-term therapeutic effect of the three-part massotherapy on insomnia due to deficiency of both the heart and spleen., Methods: Two hundred cases were randomly divided into a treatment group and a control group, each consisting of 100 cases. Patients in the treatment group were treated with the three-part massotherapy, while those in the control group with oral administration of Guipi Wan (Pill for Invigorating the Spleen and Nourishing the Heart). The total clinical therapeutic effects, the total scores of Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) of the treatment group were compared with those of the control group., Results: After the treatment, the total therapeutic effects, PSQI, SAS, and SDS of the two groups all showed significant improvement (P<0.01), and the scores of the treatment group were superior to those of the control group (P<0.01)., Conclusion: The three-part massotherapy has definite therapeutic effects on insomnia due to deficiency of both the heart and the spleen, which is safe and easy to operate, and worthy of popularization.