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Qi-ping Zeng,* Zhi-hong Liu,* Ai-wen Huang, Jing Zhang, Hong-tao Song Department of Pharmacy, Fuzhou General Hospital of Nanjing Command PLA, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The pharmacological activity of herbal medicine is an overall action of each component in accordance with their original proportion. An efficient, sustained, and controlled-release drug delivery system of herbal medicine should ensure the synchronized drug release of each active component during the entire release procedure. In this study, silymarin (SM), a poorly soluble herbal medicine, was selected as a model drug to develop a synchronized-release drug delivery system: an SM microporous osmotic pump (MPOP) tablet. The SM was conjugated with phospholipid (SM phytosome complex, SM-PC) to improve the solubility, and the difference in the apparent octanol–water partition coefficient between the two components was significantly reduced. The dissolution rate of SM-PC was significantly higher than SM active pharmaceutical ingredients and was the same as that of the commercial SM capsule. The SM-PC was used to generate the MPOP tablet. SM was mixed with poly(ethylene) oxide and sodium chloride (an osmotic agent) to form the MPOP core, followed by coating with cellulose acetate and poly(ethylene) oxide to generate the SM MPOP. The results demonstrated that SM MPOP could synchronically and sustainably release the five active components within 12 hours (the similar coefficient f2 between two components was >65), and the average cumulative release rate was 85%. Fitting of the drug-release curve showed a zero-order release profile for SM MPOP. Our study showed that the phytosome complex technique combined with the MPOP system will achieve synchronized release of the various active components of herbal medicine and have potential applications in developing sustained release preparations in herbal medicine. Keywords: silymarin, synchronized release, sustained release, phytosome complex, microporous osmotic pump tablets, dissolution test

In this article a L1 adaptive state feedback controller is presented for the three-dimensional integrated guidance and control of interceptor. The model of three-dimensional integrated guidance and control is first built by using engagement kinematics and interceptor dynamics. The objective is to control the fin deflection angles to make the line-of-sight rates converge to zero. The L1 adaptive control is then applied to design the three-dimensional integrated guidance and control controller. The L1 adaptive controller guarantees uniformly asymptotic and bound transient tracking for the system inputs and outputs, which are important for interceptions with strong robustness and high timeliness. The design issues of L1 adaptive controller are also discussed. In the interception simulation, the L1 adaptive state feedback controller demonstrates the robustness to different kinds of uncertainties, while guaranteeing the transient performance of dynamic interception process. [ABSTRACT FROM PUBLISHER]

Calcination of MgCO 3 is an important industrial reaction, but it causes significant and unfavorable CO 2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO 2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO 3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO 3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO 2 *→ COOH* trans → COOH* cis → CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO 3 . For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO 3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O-CH 2 → sur-O-CH 3 → sur-O + CH 4 *).

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Chrysochroinae Laporte de Castelnau, 1835 is the very colourful subfamily of Buprestidae. There are 127 species and subspecies of the subfamily which have been recorded in China., New Information: In this paper, we reported three genera, two subgenera and five species of the subfamily Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) which are all newly recorded from China. These reported taxa belong to two tribes and four genera: Chrysochroa (Chroodema) corbetti (Kerremans, 1893), Chrysochroa (Pyranthe) fulgens ephippigera White, 1843, Demochroa (Demoxantha) gratiosa indica Csiki, 1900, Xanthocatabonvouloirii (Deyrolle, 1861) (all the above four being Chrysochroini) and Cardiaspismouhotii E. Saunders, 1866 (Dicercini). The five newly-recorded species are briefly described, illustrated and supplemented with relevant biological information., (Hong-Mu Ai, Zhi-Hao Qi, Rong-Xiang Su, Zhi-Yu Liao, Hai-Tian Song.)

In this paper, two new species of Buprestis subgenus Akiyamaia Kurosawa, 1988 are described: B. (A.) gengmini Qi & Song, new species from Yunnan Province, China and B. (A.) wenii Qi & Song, new species from Yen Bai Province, Vietnam. The descriptions and illustrations of two new species are provided, and the diagnostic characters are provided to distinguish the two new species from other related species. A key is given for identification of all Akiyamaia species.The holotype of B. (A.) costipennis (Fairmaire, 1891) and pictures of living individuals are illustrated for the first time.

The conversion of CO 2 into valuable fuels and multi-carbon chemical substances by electrical energy is an effective strategy to solve environmental problems by using renewable energy sources. In this work, the density functional theory (DFT) method is used to reveal the electrocatalytic mechanism of CO 2 reduction reaction (CO 2 RR) over the surface of CuAl-Cl-layered double hydroxides (LDHs) with Cu monoatoms (Cu@CuAl-Cl-LDH), Cu 2 diatoms (Cu 2 @CuAl-Cl-LDH), orthotetrahedral Cu 4 clusters (Td-Cu 4 @CuAl-Cl-LDH) and planar Cu 4 clusters (Pl-Cu 4 @CuAl-Cl-LDH). The active sites, density of states, adsorption energy, charge density difference and free energy are calculated. The results show that CO 2 RR over all the above five catalysts can generate C 2 products. Pl-Cu 4 @CuAl-Cl-LDH tends to generate C 2 H 5 OH, while the remaining four structures all tend to produce C 2 H 4 . Cu δ+ favors CO 2 RR, and Td-Cu 4 @CuAl-Cl-LDH with a larger positively charged area at the active site has the better electrocatalytic performance among the calculated systems with a maximum step height of 0.78 eV. The selectivity of the products C 2 H 4 and C 2 H 5 OH depends on the dehydration of the intermediate *C 2 H 2 O to *C 2 H 3 O or *CCH; if the dehydration produces *CCH intermediate, the final product is C 2 H 4 , and if no dehydration occurs, C 2 H 5 OH is produced. This work provides theoretical information and guidance for further rational design of efficient CO 2 RR catalysts for energy saving and emission reduction.

In this prospective, multi-reader, multi-vendor study, we evaluated the performance of a commercially available deep neural network (DNN)-based MR image reconstruction in enabling accelerated 2D fast spin-echo (FSE) knee imaging. Forty-five subjects were prospectively enrolled and randomly divided into three 3T MRIs. Conventional 2D FSE and accelerated 2D FSE sequences were acquired for each subject, and the accelerated FSE images were reconstructed and enhanced with DNN-based reconstruction software (FSE-DNN). Quantitative assessments and diagnostic performances were independently evaluated by three musculoskeletal radiologists. For statistical analyses, paired t-tests, and Pearson's correlation were used for image quality comparison and inter-reader agreements. Accelerated FSE-DNN reduced scan times by 41.0% on average. FSE-DNN showed better SNR and CNR (p < 0.001). Overall image quality of FSE-DNN was comparable (p > 0.05), and diagnostic performances of FSE-DNN showed comparable lesion detection. Two of cartilage lesions were under-graded or over-graded (n = 2) while there was no significant difference in other image sets (n = 43). Overall inter-reader agreement between FSE-conventional and FSE-DNN showed good agreement (R 2  = 0.76; p < 0.001). In conclusion, DNN-based reconstruction can be applied to accelerated knee imaging in multi-vendor MRI scanners, with reduced scan time and comparable image quality. This study suggests the potential for DNN-accelerated knee MRI in clinical practice., (© 2023. Springer Nature Limited.)

Purpose: Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer's disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1- 13 C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism., Materials and Methods: ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1- 13 C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells., Results: As a perfusion marker, the total 13 C signals in the brain of T2DM mice ( p =0.07) and agmatine-treated mice ( p <0.05) were reduced. The conversion constant (K pl ) from [1- 13 C]pyruvate to [1- 13 C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ratio and lactate generation., Conclusion: Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1- 13 C]pyruvate to HP [1- 13 C]lactate., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Purpose: This study aimed to evaluate whether quantitative water fraction parameters could predict fracture age in patients with benign vertebral compression fractures (VCFs)., Methods: A total of 38 thoracolumbar VCFs in 27 patients imaged using modified Dixon sequences for water fraction quantification on 3-T MRI were retrospectively reviewed. To calculate quantitative parameters, a radiologist independently measured the regions of interest in the bone marrow edema (BME) of the fractures. Furthermore, five features (BME, trabecular fracture line, condensation band, cortical or end plate fracture line, and paravertebral soft-tissue change) were analyzed. The fracture age was evaluated based on clear-onset symptoms and previously available images. A correlation analysis between the fracture age and water fraction was evaluated using a linear regression model, and a multivariable analysis of the dichotomized fracture age model was performed., Results: The water fraction ratio was the only significant factor and was negatively correlated with the fracture age of VCFs in multiple linear regression (p = 0.047), whereas the water fraction was not significantly correlated (p = 0.052). Water fraction and water fraction ratio were significant factors in differentiating the fracture age of 1 year in multiple logistic regression (odds ratio 0.894, p = 0.003 and odds ratio 0.986, p = 0.019, respectively). Using a cutoff of 0.524 for the water fraction, the area under the curve, sensitivity, and specificity were 0.857, 85.7%, and 87.1%, respectively., Conclusions: Water fraction is a good imaging biomarker for the fracture healing process. The water fraction ratio of the compression fractures can be used to predict the fracture age of benign VCFs., (© 2023. Italian Society of Medical Radiology.)

A new species Coomaniella sunfengyii Liao, Su, Qi & Song, sp. nov. from Fujian Province, China, is described and placed in the Coomaniella macropus species-group. The description, illustrations, host plant information and diagnostic characters of the new species are provided.

BACKGROUND The COVID-19 pandemic has caused varying degrees of psychological stress among medical students. This research explored the post-traumatic stress symptoms (PTSS) of medical students in China and their relationship with positive coping and social support. MATERIAL AND METHODS In the form of cross-sectional online survey, 2280 medical students locked down at home were selected by random cluster method to investigate social support, coping style, and PTSS using the Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire (SCSQ), and Post-traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), respectively. RESULTS This research found that the PTSS detection rate in medical students was 10.42% during the COVID-19 pandemic. The PTSS scores of females were significantly higher than that of the males. However, the PTSS detection rate in females (9.71%) was not significantly different from that in males (11.24%). Compared with those of the non-PTSS group, the total score and its all-factor score of social support, the total score of coping style and the positive coping score of the PTSS group were much lower, while the negative coping score of the PTSS group was much higher (P<0.01). Positive coping was positively correlated with social support, while positive coping and social support were negatively correlated with PTSS. The total effect of positive coping on PTSS was -0.310 (P<0.001), the direct effect was -0.128 (P<0.01), and the indirect effect was -0.182 (P<0.001). Social support played a mediating role between positive coping and PTSS, with the mediating effect accounting for 58.81% of the total effect. CONCLUSIONS Social support plays a mediating role between positive coping and post-traumatic stress symptoms. Objective support and positive coping are the 2 main protective factors of PTSS.

A new stag beetle is described from Yunnan Province, China: Lucanus jiaozishanus Qi, He, Su & Song, new species. It is the third species of the L. boileaui group which are distributed only in Southwestern China and Northeastern Myanmar. The differences of the new species with the more related taxa (L. boileaui Planet, 1897, L. ludivinae Boucher, 1998 and L. takeoi Adachi, 2020) are discussed. A new synonymy, L. bidentis Schenk, 2013 = L. boileaui, is proposed. Keys to males and females of the L. boileaui group are provided. The variation of males, the female and the host plant of L. takeoi (L. maculifemoratus group) are illustrated for the first time.

Background: The genus Cantonius Théry, 1929 is a small group with two subgenera and 12 species. However, the biology of this genus is still unknown., New Information: In this paper, three species of the genus Cantonius Théry, 1929 were found on bamboo leaves, revealing for the first time that Cantonius species are also leaf-miners. Two new species were recorded from Jiangxi Province and are described here: Cantonius (Cantonius) anjiensis sp. n. (host plant: Pleioblastusamarus ) and Cantonius (Procantonius) qiyunensis sp. n. (host plant: Bambusablumeana ) followed by C. (P.) austrisinicus Kalashian, 2021 (host plant: Oligostachyumpaniculatum ) recorded from Guangxi Province. Including habitats, photos of three species together with C. (P.) qiyunensis sp. n. pupa, host plants, and leaf mines of the three species are presented. Moreover, the bionomics and habits of the genus are discussed for the first time, and a hypothesis for the distribution of Cantonius is provided., (Xiao-Di Shi, Zhi-Ming Wu, Xiao-Hua Dai, Jia-Sheng Xu, Hai-Tian Song.)

Objective: To investigate the prognosis impact of adjuvant trastuzumab treatment on human epidermal growth factor receptor 2 (HER-2) positive early breast cancer patients. Methods: A retrospective study was conducted, HER-2-positive T1N0M0 stage breast cancer patients who underwent surgery in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2010 to December 2019 were divided into treatment group and control group according to whether they were treated with trastuzumab or not. Propensity score matching (PSM) was used to balance the confounding bias caused by differences in baseline characteristics between the two groups. Cox proportional hazards model was used to analyze the risk factors affecting disease-free survival (DFS). The Kaplan-Meier method was used to estimate the 3- and 5-year DFS and overall survival (OS) rates of the two groups before and after PSM. Results: There were 291 patients with HER-2 positive T1N0M0 stage breast cancer, including 21 cases in T1a (7.2%), 61 cases in T1b (21.0%), and 209 cases in T1c (71.8%). Before PSM, there were 132 cases in the treatment group and 159 cases in the control group, the 5-year DFS rate was 88.5%, and the 5-year OS rate was 91.5%. After PSM, there were 103 cases in the treatment group and 103 cases in the control group, the 5-year DFS rate was 86.0%, and the 5-year OS rate was 88.5%. Before PSM, there were significant differences in tumor size, histological grade, vascular invasion, Ki-67 index, postoperative chemotherapy or not and radiotherapy between the treatment group and the control group ( P <0.05). After PSM, there were no significant difference in clinicopathological features between the treatment group and the control group ( P >0.05). Multivariate analysis showed that histological grade ( HR =2.927, 95 CI: 1.476, 5.805; P =0.002), vascular invasion ( HR =3.410, 95 CI: 1.170, 9.940; P =0.025), menstrual status ( HR =3.692, 95 CI: 1.021, 13.344, P =0.046), and chemotherapy ( HR =0.238, 95 CI: 0.079, 0.720; P =0.011) were independent factors affecting DFS. After PSM, the 5-year DFS rate of the treatment group was 89.2%, while that of the control group was 83.5%( P =0.237). The 5-year OS rate of the treatment group was 96.1%, while that of the control group was 84.7%( P =0.036). Conclusion: Postoperative targeted therapy with trastuzumab can reduce the risk of recurrence and metastasis in patients with HER-2-positive T1N0M0 stage breast cancer.

Objectives: To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens. Methods: The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively. Results: A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations. Conclusion: We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations., 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 © 2022 Fu, Tian, Zhang, Song and Zhang.)

Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis with characteristic involvement of the spine and sacroiliac joints. MRI may be the only indicator of disease activity or response. This study aimed to use a novel water fraction measurement technique on MRI as a biomarker to predict disease activity in patients with AS. Methods: We enrolled 39 patients (18 men [mean age, 38.6 years; range, 18−59 years] and 21 women [mean age, 39.3 years; range, 23−61 years]) who were clinically diagnosed with AS and underwent MRI, including mDixon sequences. Water fraction values of sacroiliac joint subchondral bone marrow were derived from the mDixon sequences. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was recorded using clinical information and laboratory values from medical records. Multiple linear regression, Firth logistic regression, and intraclass correlation coefficients were used for the statistical analysis. Results: In multiple linear regression, water fraction, subchondral bone marrow edema, subchondral bone erosion, and subchondral bone marrow enhancements were significantly associated with ASDAS with C-reactive protein (ASDAS-CRP). The water fraction parameters showed a good linear correlation with ASDAS-CRP and ASDAS with erythrocyte sedimentation rate (ASDAS-ESR) (beta coefficient = 1.98, p < 0.001 and beta coefficient = 1.60, p = 0.003). Firth logistic regression showed that water fraction was a significant predictor of ASDAS-CRP but not ASDAS-ESR. The intraclass correlation coefficient showed excellent repeatability for the three repeated measures of the water fraction. Conclusion: Water fraction parameter could be a good imaging biomarker of disease activity status. The sacroiliac joint evaluated by mDixon MRI may be a promising biomarker of disease progression in patients with spondyloarthritis.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF., 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 © 2022 Liu, Xie, Liu, Wang, Mu, Zhang, Zhao, Yuan, Guo, Wang, Xiang, Song, Jiang, Xiang and Cui.)

Background: Curcumin exerts a protective effect on diabetic encephalopathy (DN), It is known for its potent neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. However, the underlying mechanisms of curcumin's neuroprotective effects resulting from high glucose (HG)-induced injuries remain unknown. The purpose of this study is to identify the protective mechanism of Curcumin in the DN., Methods: In this study, pheochromocytoma cells (PC12 cells) were pretreated with different concentrations of Curcumin and then co-treated with Curcumin and glucose for 48 hours, and the cell viability was evaluated by CCK-8, the expression of the inflammatory mediators were detected by ELISA, the miR-218-5p and toll-like receptors (TLR4) level were examined by both quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, the potential target genes of miR-218-5p were identified using luciferase reporter assay., Results: The viability of PC12 cells treated with HG was significantly reduced in a dose- and time-dependent manner. Cotreatment of curcumin with HG significantly increased cell viability. Curcumin inhibited the expression of the inflammatory mediators, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and induced the expression of the anti-inflammatory mediator interleukin-10 (IL-10). Curcumin upregulated the levels of miR-218-5p and downregulated the expression of TLR4 in HG-treated PC12 cells. The curcumin-induced anti-inflammatory effect was abrogated by a miR-218-5p inhibitor and overexpression of TLR4. The results suggest that curcumin ameliorates the inflammatory response by upregulating miR-218-5p levels in PC12 cells., Conclusions: Our results indicate a protective role for curcumin in PC12 cells and suggest that it should be considered for the prophylactic treatment of DN in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study is designed to investigate the mental health status of college students under the current coronavirus disease-2019 (COVID-19) pandemic and explore potential influential factors. We surveyed 1128 people including 435 medical students and 693 nonmedical students by a self-designed questionnaire containing general demographic characteristics, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Chinese Perceived Stress Scale. SPSS 23.0 software was used for statistical analysis. The incidence of anxiety, depression, and perceived stress were 8.4, 22.7, and 42.9% among college students during the COVID-19, respectively. Pearson correlation analysis showed that sex, specialty, and Family conflict were all positively associated with SAS, SDS, and CPSS ( p< 0.05). Stepwise linear retrospective analysis showed that family conflicts and specialty were the influencing factors of SAS, SDS, and CPSS. There were significantly differences between medical students and nonmedical students in the frequency of SDS abnormality score ( Z =-4.125, p< 0.001) and the frequency of CPSS abnormality (χ 2 =7.836, p= 0.005). According to the results, we can come to the conclusion that college students have different degrees of psychological problems during the COVID-19. Family conflicts and specialty were the influencing factors of anxiety, depression, and perceived stress.

In this study, while aiming at the prevention of fire accidents in underground commercial streets, an underground commercial street is selected as a research object, and the building fire is numerically simulated using the PyroSim software. Fire simulation scenarios are divided according to different fire zones by analyzing the temperature, carbon monoxide (CO) concentration, and visibility in the smoke layer inside a building. The available safe evacuation time is calculated according to the critical fire hazard judgment conditions. We found that the time when the flue gas temperature and CO concentration reached the critical value in the fire site was longer than the time when the visibility reached the critical value reducing or even avoiding the spread of smoke from the fire area to the evacuation stairs can provide effective help for crowd evacuation. Finally, the safety of the building is evaluated, and fire prevention countermeasures are defined based on the actual situation and fire numerical simulation results to reduce fire incidence, casualties, and economic losses., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Hao-Wei Yao et al.)

Exothermic reaction systems of non-class A geometries are very common, with an endless rectangular rod typical. As a strong nonlinear source word is included in the governing equation, which is sensitive to the frank-kamenetskii parameter, there is no analytical solution. Many methods were previously suggested. However, with them are often non-physical solutions obtained. In this paper, the lattice Boltzmann process provides us with complete physical and precise solutions. We also analysed the sensitivity of the strong nonlinear source term and suggested advice for similar numerical calculations and experiments with thermal explosion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A new stag beetle fossil is described from the Yixian Formation in northeastern China. A new genus is established based on this well-preserved specimen. Prolucanus beipiaoensis gen. et sp. nov. is firmly placed in the extant lucanid subfamily Lucaninae based on its broad prosternal process and geniculate antennae. Our discovery represents the first fossil record of Lucaninae from the Late Mesozoic of China and the oldest reliable record belonging to the subfamily. We also summarize the fossil species of stag beetles found in China and the described fossil species of the subfamily Lucaninae found in the world. A key to all fossil genera of Lucanidae from China is provided.

The genus Chrysodema currently recorded from China contains 6 species/subspecies: C. (Chrysodema) aurostriata Saunders, 1866 from Yunnan, C. (C.) lewisii nakatai Frank Sekerka, 2020, C. (C.) eximia berliozi Descarpentries, 1948, C. (Pseudochrysodema) dalmanni dalmanni (Mannerheim, 1837), C. (P.) dalmanni penghuensis Hattori Ong, 2020 and C. (P.) yasumatsui Kurosawa, 1954 all from Taiwan. In this study, one new species, Chrysodema (Chrysodema) hainanensis sp. nov. from Hainan Island, China is described, illustrated, and the variation is given. The host plant Toona ciliata is new for the genus Chrysodema. The differences of the new species to its related species and subspecies are discussed and keyed. C. (C.) aurostriata from Yunnan probably belonged toC. (C.)vrabeci and still need verification. C. (C.) tonkinea Kerremans, 1909 was recorded from Guangxi (new country record). All Chrysodema species and subspecies recorded from China except C. (P.) dalmanni penghuensis and the unverified C. (C.) aurostriata were examined, and a key is given for identification.

Backgrounds: Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches., Methods: Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively., Results: The results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway., Conclusions: The present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG., (Copyright © 2021. Published by Elsevier GmbH.)

An increase in hyperpolarized (HP) [1- 13 C]lactate production has been suggested as a biomarker for cancer occurrence as well as for response monitoring of cancer treatment. Recently, the use of metformin has been suggested as an anticancer or adjuvant treatment. By regulating the cytosolic NAD + /NADH redox state, metformin stimulates lactate production and increases the HP [1- 13 C]lactate conversion rate in the kidney, liver, and heart. In general, increased HP [1- 13 C]lactate is regarded as a sign of cancer occurrence or tumor growth. Thus, the relationship between the tumor suppression effect of metformin and the change in metabolism monitored by HP [1- 13 C]pyruvate MRS in cancer treatment needs to be investigated. The present study was performed using a brain metastasis animal model with MDA-MB-231(BR)-Luc breast cancer cells. HP [1- 13 C]pyruvate MRS, T 2 -weighted MRI, and bioluminescence imaging were performed in groups treated with metformin or adjuvant metformin and radiation therapy. Metformin treatment alone did not display a tumor suppression effect, and the HP [1- 13 C]lactate conversion rate increased. In radiation therapy, the HP [1- 13 C]lactate conversion rate decreased with tumor suppression, with a p-value of 0.028. In the adjuvant metformin and radiation treatment, the tumor suppression effect increased, with a p-value of 0.001. However, the apparent HP [1- 13 C]lactate conversion rate (K pl ) was observed to be offset by two opposite effects: a decrease on radiation therapy and an increase caused by metformin treatment. Although HP [1- 13 C]pyruvate MRS could not evaluate the tumor suppression effect of adjuvant metformin and radiation therapy due to the offset phenomenon, metabolic changes following only metformin pre-treatment could be monitored. Therefore, our results indicate that the interpretation of HP [1- 13 C]pyruvate MRS for response monitoring of cancer treatment should be carried out with caution when metformin is used as an adjuvant cancer therapy., (© 2021 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

A new genus and species, Termitocnemis huangi gen. et sp. nov., of the tenebrionine tribe Amarygmini Gistel, 1848 is described from Fujian Province, southeastern China. All specimens were collected from a healthy nest of the termite genus Nasutitermes Dudley, 1890, implying that this species is truly termitophilous. Transitional habitus characters of the new species shed further light on the evolution of amarygmine beetles from free-living to termitophily. Given the discovery of this new genus a revised key is provided to the Oriental genera of termitophilous Amarygmini.

Background: Recent evidences suggested that IL-37 may participate in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, its exact biological role was unknown. The objective of this study was to determine the associations of serum IL-37 with the severity and prognosis in CAP patients based on a retrospective cohort study., Methods: The whole of 120 healthy subjects and 240 CAP patients were summoned. Peripheral blood was collected and IL-37 was detected using ELISA., Results: Serum IL-37 was obviously decreased in CAP patients on admission. In addition, serum IL-37 was gradually decreased in parallel with CAP severity scores. Correlative analysis revealed that serum IL-37 was negatively associated with CAP severity scores and inflammatory cytokines. Further logistical regression found that reduction of serum IL-37 augmented the severity of CAP patients. Moreover, the follow-up research was performed in CAP patients. Serum lower IL-37 on admission prolonged the hospital stay in CAP patients. Serum IL-37 combination with PSI and CURB-65 had a stronger predictive capacity for death than IL-37 and CAP severity score alone in CAP patients., Conclusion: There are remarkably negative correlations between serum IL-37 with the severity and prognosis in CAP patients. Serum IL-37 on admission prolongs the hospital stay, demonstrating that IL-37 may involve in the process of CAP. Serum IL-37 may be regarded as a biomarker for diagnosis and prognosis for CAP patients., 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 © 2021 Wang, Chen, Xu, Chen, Wang, Liu, Song, Fei, Zhao and Fu.)

A new species, T. yaolihuoi Huang, Jiang Song sp. nov. of the genus Teratozephyrus Sibatani, 1946 is described from southeastern China. Among the other representatives of the genus, the new species resembles only T. hinomaru Fujioka, 1994 from southwestern China, from which the new species can be separated easily by examining details in both wing pattern and the male genitalia. Wing patterns and genitalia of the new species and T. hinomaru are illustrated and compared.

Rationale and Objectives: To compare the diagnostic ability of modified Dixon (mDixon) turbo spin echo (TSE) T1-weighted (T1W) shoulder magnetic resonance arthrography (MRA) with that of conventional shoulder MRA, and evaluate the feasibility of mDixon TSE in-phase (IP) images in measuring the fat fraction and size of rotator cuff muscles., Materials and Methods: This retrospective study included 57 patients who underwent 3T shoulder MRA examinations with conventional and mDixon TSE T1W images (mean age: 56.7 years; range: 20-78 years). Two musculoskeletal radiologists independently evaluated the rotator cuff tendons with fat saturated T1W images and mDixon TSE T1W water images. Occupation ratios measured on T1W and mDixon TSE T1W IP images were compared. The fat fraction of the supraspinatus from the mDixon TSE T1W images was calculated and correlated with fatty infiltration of the supraspinatus on T1W images., Results: For tendon pathology, the kappa value for inter-sequence and inter-reader agreement was 0.957 (95% confidence interval [CI]: 0.923-0.990) and 0.839 (95% CI: 0.778-0.899), respectively. For retear, the kappa value for inter-sequence and inter-reader agreement was 0.913 (95% CI: 0.796-1.000) and 0.779 (95% CI: 0.594-0.963), respectively. The intraclass correlation coefficient for both occupation ratios was 0.986 (95% CI: 0.973-0.993). Comparison of mDixon TSE T1W fat fraction with Goutallier grade showed a strong positive linear correlation (r = 0.929)., Conclusions: The mDixon TSE T1W sequence is a good alternative to conventional sequences in shoulder MRA for evaluating rotator cuff pathology. Furthermore, this sequence provides information on the size and fat infiltration of rotator cuff muscles., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

A new species Coomaniella (Coomaniella) dentata sp. nov. from Guangxi Province, China, is described and placed in the C. (C.) chinensis species-group. The variability is discussed, and a new adult host plant is recorded. New distributional records are given for C. biformissima Jendek & Kalashian, 1999 and C. lingafelteri Jendek & Pham, 2013., (Hai-Tian Song.)

Background: Cardiovascular diseases are associated with proliferation and phenotypic switch. Platelet-derived growth factor-BB (PDGF-BB) is a major initiating factor for proliferative vascular diseases, such as neointimal lesion formation, restenosis after angioplasty, and atherosclerosis. Ruxolitinib, a potent Janus kinase (JAK) 1 and 2 inhibitor, has been reported to significantly block the proliferation-related signaling pathway of JAK2/signal transducers and activators of transcription 3 (STAT3) and harbor a broad spectrum of anti-cancer activities, including proliferation inhibition, apoptosis induction, and anti-inflammation. However, the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation remains to be elucidated. Thus, this study investigates the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation and its underlying mechanisms., Methods: In vivo, the medial thickness of the carotid artery was evaluated using a mouse carotid ligation model, ruxolitinib was administered orally to the mice every other day, and the mice were euthanized on day 28 to evaluate the therapeutic effects of ruxolitinib. Cell proliferation markers were measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. In vitro, VSMCs were treated with ruxolitinib with or without PDGF-BB at an indicated time and concentration. Cell proliferation and apoptosis were measured using Cell Counting Kit-8 assay, MTS assays and flow cytometry. The JAK2/STAT3 signaling pathway involved in the effects of ruxolitinib on VSMCs was detected by western blotting with the specific pathway inhibitor AG490., Results: In vivo, ruxolitinib significantly decreased the ratio-of-intima ratio (I/M ratio) by inhibiting the expression of PCNA and cyclinD1 (p <0.05). In vitro, ruxolitinib inhibited PDGF-BB-induced VSMC proliferation compared with the PDGF-BB treatment group (p <0.05). In addition, ruxolitinib inhibited the PDGF-BB-induced activation of the JAK2/STAT3 signaling pathway and decreased the expression of proliferation related-proteins cyclinD1 and PCNA in VSMCs (p <0.05)., Conclusion: Our findings suggest that ruxolitinib inhibits VSMC proliferation in vivo and in vitro by suppressing the activation of the JAK2/STAT3 signaling pathway. Therefore, ruxolitinib has a therapeutic potential for proliferative vascular diseases., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Previous studies of the dynamics of sulfate-reducing bacteria (SRB) and sulfur-oxidizing bacteria (SOB) have focused on deep stratified lakes. The objective of this study is to present an in-depth investigation of the structure and dynamics of sulfur bacteria (including SRB and SOB) in the water column of shallow freshwater lakes. A cyanobacterial bloom biomass (CBB)-amended mesocosm experiment was conducted in this study, in which water was taken from a shallow eutrophic lake with sulfate levels near 40 mg L -1 . Illumina sequencing was used to investigate SRB and SOB species involved in CBB decomposition and the effects of the increases in sulfate input on the water column microbial community structure. The accumulation of dissolved sulfide (∑H 2 S) produced by SRB during CBB decomposition stimulated the growth of SOB, and ∑H 2 S was then oxidized back to sulfate by SOB in the water column. Chlorobaculum sequences (the main SOB species in the study) were significantly influenced by increases in sulfate input, with relative abundance increasing approximately four-fold in treatments amended with 40 mg L -1 sulfate (referred to as 40S) when compared to the treatment without additional sulfate addition (referred to as CU). Additionally, an increase in SOB number was observed from day 26-37, concurrent with the decrease in SRB number, indicating the succession of sulfur bacteria. These findings suggest that biological sulfur oxidation and succession of sulfur bacteria occur in the water column during CBB decomposition in shallow freshwater ecosystems, and the increases in sulfate input stimulate microbial sulfur oxidation., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To assess the clinical utility of a prototype sequence for metal artifact reduction, the multiacquisition variable-resonance image combination selective (MAVRIC-SL) at 3 T. This sequence allows a surgical prosthesis-dependent reduction in the number of spectral bins. We compared the prototype MAVRIC SL to the conventional two-dimensional fast spin-echo (FSE) sequences and MAVRIC SL images acquired with all spectral bins to those acquired with the optimized number of spectral bins., Methods: MAVRIC SL images were acquired in 25 image sets from August 2017 to April 2018. For each subject, the optimized number of spectral bins was determined using a short spectral calibration scan. The image sets obtained with magnetic resonance imaging that were used for the analysis consisted of MAVRIC-SL proton density (PD)-weighted or short inversion time inversion recovery (STIR) images acquired with all 24 spectral bins, the corresponding images with the optimized number of spectral bins, and the conventional two-dimensional FSE or STIR PD-weighted images. A musculoskeletal radiologist reviewed and scored the images using a five-point scale for artifact reduction around the prosthesis and visualization of the prosthesis and peri-prosthetic tissues. Quantitative evaluation of the peri-prosthetic tissues was also performed. The Wilcoxon rank-sum test was used to test for significance., Results: The MAVRIC SL images enabled a significantly improved reduction in metallic artifacts compared to the conventional two-dimensional FSE sequences. The optimized number of spectral bins ranged from 6 to 20, depending on the prosthesis susceptibility difference, size, and orientation to the B 0 field. The scan times significantly decreased with a reduced number of spectral bins (354.0 ± 139.1 versus 283.0 ± 89.6 s; 20% reduced scan time; p < .05). Compared to the MAVRIC SL images acquired with all 24 bins, the artifact reduction and visualization of the prosthesis and peri-prosthetic tissues on the MAVRIC SL images acquired with calibrated bins were not significantly different., Conclusions: Compared to the MAVRIC SL images acquired with all 24 spectral bins, those acquired with an optimized number of spectral bins can reduce metallic artifacts with no significant image quality degradation while providing reduced scan time., Competing Interests: Declaration of Competing Interest Dr. S.S. Kaushik works for GE Healthcare. MAVRIC SL is a GE Healthcare product., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Oomyzus spiraculus Song, Fei & Cao sp. nov. (Hymenoptera, Eulophidae) is described and illustrated as a gregarious larval-pupal endoparasitoid of Coccinella septempunctata L. (Coleoptera, Coccinellidae). Differentiation between O. spiraculus and its similar species is discussed and a key to differentiate the female and male of these species is provided. DNA barcodes of O. spiraculus and O. scaposus are analyzed and compared., (Hai-Tian Song, Ming-Hui Fei, Bao-Ping Li, Chao-Dong Zhu, Huan-Xi Cao.)

Dengue fever is a re-emergent mosquito-borne disease, which prevails in tropical and subtropical regions, mainly in urban and peri-urban areas. Its incidence has increased fourfold since 1970, and dengue fever has become the most prevalent mosquito-borne disease in humans now. In order to study the effect of temperature on the dengue virus transmission, we formulate a dengue virus transmission model with maturation delay for mosquito production and seasonality. The basic reproduction number $\mathbb{R}&#95;0$ of the model is computed, and results suggest that the dengue fever will die out if $\mathbb{R}&#95;0$ < 1, and there exists at least one positive periodic solution and the disease will persist if $\mathbb{R}&#95;0$ > 1. Theoretical results are applied to the outbreak of dengue fever in Guangdong province, China. Simulations reveal that the temperature change causes the periodic oscillations of dengue fever cases, which is good accordance with the reported cases of dengue fever in Guangdong province. Our study contributes to a better understanding of dengue virus transmission dynamics and proves beneficial in preventing and controlling of dengue fever.

This study aims to investigate the feasibility of dynamic hyperpolarized 13 C MR spectroscopic imaging (MRSI) using the SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE) technique and an estimation of the spatially resolved conversion constant rate (k pl ). An acquisition scheme comprising a single training dataset and several imaging datasets was proposed considering hyperpolarized 13 C circumstances. The feasibility and advantage of the scheme were investigated in two parts: (a) consistency of spectral basis over time and (b) accuracy of the estimated k pl . The simulations and in vivo experiments support accurate k pl estimation with consistent spectral bases. The proposed method was implemented in an enzyme phantom and via in vivo experiments. In the enzyme phantom experiments, spatially resolved homogeneous k pl maps were observed. In the in vivo experiments, normal diet (ND) mice and high-fat diet (HFD) mice had k pl (s -1 ) values of medullar (ND: 0.0119 ± 0.0022, HFD: 0.0195 ± 0.0005) and cortical (ND: 0.0148 ±0.0023, HFD: 0.0224 ±0.0054) regions which were higher than vascular (ND: 0.0087 ±0.0013, HFD: 0.0132 ±0.0050) regions. In particular, the k pl value in the medullar region exhibited a significant difference between the two diet groups. In summary, the feasibility of using modified SPICE for dynamic hyperpolarized 13 C MRSI was demonstrated via simulations and in vivo experiments. The consistency of spectral bases over time and the accuracy of the estimated k pl values validate the proposed acquisition scheme, which comprises only a single training dataset. The proposed method improved the spatial resolution of dynamic hyperpolarized 13 C MRSI, which could be used for k pl estimation using high signal-to-noise ratio spectral bases., (© 2019 John Wiley & Sons, Ltd.)

Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal system defects because of its higher soft-tissue contrast and spatial resolution. With the recent development of MRI-related technology, faster imaging and various image plane reconstructions are possible, enabling better assessment of three-dimensional musculoskeletal anatomy and lesions. Furthermore, the image quality, diagnostic accuracy, and acquisition time depend on the MRI protocol used. Moreover, the protocol affects the efficiency of the MRI scanner. Therefore, it is important for a radiologist to optimize the MRI protocol. In this review, we will provide guidance on patient positioning; selection of the radiofrequency coil, pulse sequences, and imaging planes; and control of MRI parameters to help optimize the MRI protocol for the six major joints of the musculoskeletal system., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2020 The Korean Society of Radiology.)

Increasing evidence suggests there is a relationship between cognitive impairment and metabolic dysfunction. Diabetes is a chronic disease, and metabolic factors affecting brain metabolisms, such as serum glucose, insulin, and glucagon, are altered according to disease progression. In our previous study, we applied hyperpolarized [1- 13 C] pyruvate magnetic resonance spectroscopy in prediabetic mice after feeding them a 60% high-fat diet (HFD) for 6 months. Ultimately, we detected significantly increased [1- 13 C]lactate conversion in the whole brain and an almost five-fold increased [1- 13 C]lactate/pyruvate ratio in the hippocampal region. In the present study, we induced diabetes in mice by injecting streptozotocin and feeding them an HFD for 6 months. Unlike in prediabetic mice, [1- 13 C]lactate conversion in the diabetic mice did not differ from that in the control group, but [1- 13 C]lactate/total 13 C ratio showed an almost 1.4-fold increase in the hippocampal region. We measured the amount of the lactate and mRNA levels of glucose transporters from isolated hippocampus and cortex samples. In the hippocampus, significantly decreased GLUT1 mRNA levels and increased lactate were detected, suggesting an inconsistency between glucose and pyruvate metabolism. Pyruvate can be produced from oxaloacetate as well as glucose. We investigated ATP citrate lyase (ACLY) because it cleaves citrate into oxaloacetate and acetyl CoA. Phosphorylated ACLY (Ser455), the active form, was increased in both hippocampus and cortex samples of mice injected with streptozotocin and fed an HFD. Also, phosphorylated ACLY/total ACLY showed a positive correlation with lactate amount in the hippocampus. Our results suggest that the brain has different responses to diabetic progression, but, in the hippocampus, maintains metabolic alteration toward increasing lactate production from the prediabetic to the diabetic stage. We suggest that ACLY-mediated pyruvate be used to support lactate levels in the hippocampus in cases of limited glucose availability.

Objectives: To investigate the agreement between double-inversion recovery (DIR) with synthetic magnetic resonance imaging (MRI) and T1-weighted contrast-enhanced (CE)-MRI for the assessment of knee synovitis., Methods: T1-weighted CE-MRI and synthetic MRI of 30 patients were compared. Synthetic DIR image reconstruction was performed with two inversion times (280-330 ms and 2800-2900 ms). Subjective image quality, visibility of synovium, detection of synovitis, and total synovitis score in the knee joint were evaluated on both MR images. The relative signal intensity (SI) and relative contrast of synovium, joint effusion, and bone marrow for two imaging were assessed. Differences in data between two imaging were assessed by using Wilcoxon's signed-rank test and chi-square test/Fisher's exact test. Interobserver agreement was expressed as weighted kappa value. Accuracy of synthetic DIR image was calculated by using CE-MRI as reference standard., Results: T1-weighted CE-MRI yielded better image quality than synthetic DIR imaging (p < 0.001). Interobserver agreements for detecting synovitis diagnosis/sum of the synovitis score were moderate to almost perfect (κ = 0.58/0.44, synthetic DIR; κ = 0.83/0.65, T1-weighted CE-MRI). There were no statistical differences in visibility of synovium (p = 0.058-0.190), detection of synovitis (p < 0.001), and relative SI of structures between two imaging (p = 0.086-0.360). Synovium-to-effusion contrast was higher in synthetic DIR (p = 0.003) and synovium-to-bone marrow contrast was higher in CE-MRI (p < 0.001)., Conclusion: Synthetic DIR imaging showed a moderate degree of interobserver agreement and good accuracy for detecting synovitis. Though it has limitations, it may play a role in imaging of degenerative joint disease or larger cohort scientific studies where gadolinium application is not feasible., Key Points: • Synthetic double-inversion recovery (DIR) imaging avoids the use of contrast agent. • There was no significant difference between T1-weighted CE-MRI and synthetic DIR imaging in evaluating presence of synovitis in knee joint. • Synthetic DIR imaging showed moderate degree of interobserver agreement and good accuracy for detecting synovitis compared to CE-MRI, and it may facilitate evaluation of some regions of peripatellar synovitis.

Objectives: To investigate the feasibility of three-dimensional fast spin echo (3D-FSE) imaging with compressed sensing (CS) and parallel imaging (PI) compared to 3D-FSE imaging with only PI in evaluating ankle joint pathologies., Materials and Methods: Twenty consecutive patients underwent ankle magnetic resonance imaging (MRI), including acquisition of image sets of 2D-FSE sequences, and 3D-FSE sequences without and with CS, between June 2016 and November 2017. Three MR image sets were independently rated by two radiologists for the presence/absence of ankle pathology. Quantitative image similarity and subjective image quality were evaluated using 3D-FSE images without CS and those with CS-PI. Inter-sequence agreement between 3D-FSE sequences without CS and with CS-PI in both readers was evaluated., Results: Interobserver agreements were nearly perfect for sprain of the anterior talofibular ligament (ATFL, κ=0.77), osteochondral lesion of the talus (OLT, κ=0.76-0.88), osteochondral lesion of the distal tibia (OLTi, κ=0.74) and os subfibulare (OSF, κ=0.62-0.64). The structural similarity index (mean, 0.996; range, 0.990-0.997) between the 3D-FSE sequences without CS and with CS-PI was acceptable. There was no significant difference in subjective image quality between the two imaging sequences (ATFL, p = 0.317; bone marrow, p = 0.083; cartilage, p = 1.000, tendon, p = 1.000). Intersequence agreement between the 3D-FSE sequences with and without CS was nearly perfect (ATFL and OLTi, κ=1.00; OLT, κ=0.87-0.96; OSF, κ=0.62-0.64) in both readers., Conclusions: Isotropic 3D-FSE ankle MRI with CS provides acceptable diagnostic performance with reduced scan time. Compressed sensing-related artifacts could be minimized with CS reconstruction enhancement, allowing for better image quality for evaluating ankle joint pathologies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 ( 13 C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed decreased perfusion (p < 0.01) and increased conversion from pyruvate to lactate (p < 0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p < 0.01) and striatum (p < 0.05), while PDH activity was decreased in the cortex (p < 0.01) and striatum (p < 0.001) and the phosphorylated PDH was increased in the striatum (p < 0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p < 0.05). To determine whether hyperpolarized 13 C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3 months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1- 13 C] pyruvate MR spectroscopy showed increased lactate conversion (P < .001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1- 13 C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1- 13 C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.

Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption., (Copyright © 2018 Elsevier Inc. All rights reserved.)