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Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multi‐omics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. The non‐targeted omics and targeting studies of diagnostic markers for ASD were also reviewed. Moreover, we summarized the progress and methods of behavioral and educational interventions, intervention methods related to technological devices, and research on medical interventions and potential drug targets. This review highlighted the application of high‐throughput omics methods in ASD research and emphasized the importance of seeking homogeneity from heterogeneity and exploring the convergence of disease mechanisms, biomarkers, and intervention approaches, and proposes that taking into account individuality and commonality may be the key to achieve accurate diagnosis and treatment of ASD. [ABSTRACT FROM AUTHOR]

Machine learning has been applied to neuroimaging data for estimating brain age and capturing early cognitive impairment in neurodegenerative diseases. Blood parameters like neurofilament light chain are associated with aging. In order to improve brain age predictive accuracy, we constructed a model based on both brain structural magnetic resonance imaging (sMRI) and blood parameters. Healthy subjects (n = 93; 37 males; aged 50–85 years) were recruited. A deep learning network was firstly pretrained on a large set of MRI scans (n = 1,481; 659 males; aged 50–85 years) downloaded from multiple open‐source datasets, to provide weights on our recruited dataset. Evaluating the network on the recruited dataset resulted in mean absolute error (MAE) of 4.91 years and a high correlation (r =.67, p <.001) against chronological age. The sMRI data were then combined with five blood biochemical indicators including GLU, TG, TC, ApoA1 and ApoB, and 9 dementia‐associated biomarkers including ApoE genotype, HCY, NFL, TREM2, Aβ40, Aβ42, T‐tau, TIMP1, and VLDLR to construct a bilinear fusion model, which achieved a more accurate prediction of brain age (MAE, 3.96 years; r =.76, p <.001). Notably, the fusion model achieved better improvement in the group of older subjects (70–85 years). Extracted attention maps of the network showed that amygdala, pallidum, and olfactory were effective for age estimation. Mediation analysis further showed that brain structural features and blood parameters provided independent and significant impact. The constructed age prediction model may have promising potential in evaluation of brain health based on MRI and blood parameters. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. Existing data suggest that early diagnosis and intervention can improve ASD outcomes. However, the causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. More mechanisms and biomarkers of autism have been found with the development of advanced technology such as mass spectrometry. Many recent studies have found a link between ASD and elevated oxidative stress, which may play a role in its development. ASD is caused by oxidative stress in several ways, including protein post-translational changes (e.g., carbonylation), abnormal metabolism (e.g., lipid peroxidation), and toxic buildup [e.g., reactive oxygen species (ROS)]. To detect elevated oxidative stress in ASD, various biomarkers have been developed and employed. This article summarizes recent studies about the mechanisms and biomarkers of oxidative stress. Potential biomarkers identified in this study could be used for early diagnosis and evaluation of ASD intervention, as well as to inform and target ASD pharmacological or nutritional treatment interventions. [ABSTRACT FROM AUTHOR]

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is one of the more common complications in the middle and late stages of pregnancy, which requires early detection and intervention. Objective: The aim of the study is to investigate the changes in the metabolic profile of bile acids (BAs) in plasma of pregnant women with ICP and to look biomarkers for the diagnosis and grading of ICP, and to explore the disease mechanism. Methods: The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze plasma BAs. Results: Twenty-seven BAs can be quantified in all participants. Among them, 22 BAs were identified as differential BAs between ICP and control groups. Five BAs include 3β-CA, 3β-DCA, CDCA-3Gln, NCA, and Tβ-MCA, were found to be associated with ICP for the first time. Nine BAs include NCA, GCA, GCDCA, GHCA, GUDCA, HCA, TCA, TCDCA and THCA, can be used as possible ICP diagnostic biomarkers. Four BAs, i.e., GLCA, THCA, GHCA and TLCA-3S may be used as potential biomarkers for ICP grading. Conclusion: There were significant differences in plasma BA profiles between ICP patients and the control. The BA profiles of mild ICP group and severe ICP group partially overlapped. Potential diagnostic and grading BA markers were identified. A significant characteristic of ICP group was the increase of conjugated BAs. A mechanism to sustain the equilibrium of BA metabolism and adaptive response has been developed in ICP patients to accelerate excretion and detoxification. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects millions of people worldwide. However, there are currently no reliable biomarkers for ASD diagnosis. Materials and Methods: The strategy of computational prediction combined with experimental verification was used to identify blood protein biomarkers for ASD. First, brain tissue–based transcriptome data of ASD were collected from Gene Expression Omnibus database and analyzed to find ASD-related genes by bioinformatics method of significance analysis of microarrays. Then, a prediction program of blood-secretory proteins was applied on these genes to predict ASD-related proteins in blood. Furthermore, ELISA was used to verify these proteins in plasma samples of ASD patients. Results: A total of 364 genes were identified differentially expressed in brain tissue of ASD, among which 59 genes were predicted to encode ASD-related blood-secretory proteins. After functional analysis and literature survey, six proteins were chosen for experimental verification and five were successfully validated. Receiver operating characteristic curve analyses showed that the area under the curve of SLC25A12, LIMK1, and RARS was larger than 0.85, indicating that they are more powerful in discriminating ASD cases from controls. Conclusion: SLC25A12, LIMK1, and RARS might serve as new potential blood protein biomarkers for ASD. Our findings provide new insights into the pathogenesis and diagnosis of ASD. [ABSTRACT FROM AUTHOR]

Inductive pulsed power supplies have become a promising option for the power supplies of electromagnetic launchers, because they can reach a good balance between the energy storage density and the power density. This article presents a status for our research work, namely an integrated pulsed power module. The length, width, height, and volume of this module are 0.48 m, 0.3 m, 0.24 m, and 0.034 m3, respectively. In the so-far conducted highest energy-level experiment, this module reached 4.91-kA inductor charging current, 77.6-kJ inductor charging energy, and 2.36-MJ/m3 module energy density. The output current pulse reached 15.0-kA first peak value, 15.4-kA second peak value, and 14.1-ms half-peak value pulsewidth. The performance of this module has been confirmed to be stable and consistent within the range of 0–80 kJ. [ABSTRACT FROM AUTHOR]

The electromagnetic railguns possess the characteristics of active and accurate control of the muzzle velocity. As to our understanding, the muzzle velocity control has two levels. One is to design the triggering strategy of the pulsed power supplies before the launching process, while the other is to adjust the triggering strategy during the launching process. The objective of the first one is to realize the desired muzzle velocity with ideal system parameters, and the target of the second one is to design a closed-loop adjusting system for the precalculated triggering strategy, so as to keep the actual muzzle velocity equal or closed to the desired value when the launching process has some kind of turbulences, e.g., nonideal charging voltage and errors of the armature mass. This paper proposes a closed-loop velocity control system and four different methods to adjust the actual muzzle velocity in real launching time. The core idea of this system is to detect the armature velocities at key points along the rails and adjust the following triggering pulsed forming unit (PFU) number of the pulsed power supplies. In simulations, the desired muzzle velocity is 2000 m/s, the capacitance of the energy storage capacitors $C_{\mathrm {PFU}}$ is 2 mF, the precharged voltage $U_{0}$ is 5 kV, and the armature mass ${m}$ is 0.15 kg. Without the closed-loop adjusting, if $U_{0}$ , $C_{\mathrm {PFU}}$ , and ${m}$ simultaneously and randomly change within [−2%, 2%] in actual operations, the muzzle velocity relative errors are within [0%, 2.1346%]. However, after using this closed-loop system, the results show that the muzzle velocity errors can be less than 1%, even when there is ±0.5% detection error. [ABSTRACT FROM AUTHOR]

This paper at first proposes a method to calculate a trigger strategy before launching in order to control the muzzle velocity of railguns. Five triggering points are set equidistantly and six pulsed forming unit (PFU) groups are triggered in total. First, given a desired muzzle velocity, the expected uniformly accelerated rectilinear motion of the armature is calculated. Second, the module number of each PFU group is obtained according to the principle of minimizing the absolute relative error between the actual and the expected velocity at each triggering point. The results show that, when the desired muzzle velocity is within [1500, 2000] m/s, the absolute muzzle velocity relative error $\delta $ is less than 0.5%. In order to achieve a better control performance, the places of the five triggering points are then optimized by a genetic algorithm (GA). The objective function is the sum of absolute $\delta $ , when the desired muzzle velocities are 1500, 1600, $\ldots $ , 2000 m/s. After the optimization, $\delta $ is reduced to less than 0.05%. At last, based on this velocity control method, the railgun system is optimized to pursue the highest system efficiency $\eta $ by GA. The independent variables are the armature mass, the precharged voltage, and the places of the five triggering points. The constraints are that the desired muzzle velocity is 1800 m/s and the absolute $\delta $ is within 1%. The results show that $\eta $ increases from 6.57% to 25.37%. [ABSTRACT FROM AUTHOR]

A novel circuit with the better performance for the inductive pulsed power supplies in the electromagnetic launch system is proposed in this paper, namely, the meat grinder with capacitive pulse forming unit (CPFU). Its working process is qualitatively analyzed stage by stage. Its practical feasibility is verified through a 7.5-kJ experiment. From the perspectives of circuit structure and working principle, this circuit can be regarded as the combination of a meat grinder and a CPFU. Compared with its preceding circuits, this circuit possesses following advantages: 1) the self-recovery of the capacitor precharged voltage can easily be achieved, which is conducive to continuous operations of the whole circuit and 2) the waveforms of the inductor currents contain no capacitive components, which can promote the energy storage density of the inductors. [ABSTRACT FROM PUBLISHER]

Because it possesses higher current turn-off capability, the inverse current commutation with semiconductor devices (ICCOS) is a better option for the opening switch of an inductive pulsed power supply than the integrated gate commutated thyristor. This paper investigates the counter-current capacitor, which is the key component that determines the turn-off result and the volume of the counter-current branch. The major contributions of this paper include the following: 1) deriving an analytical expression for the minimum precharged capacitor voltage that can reliably turn off the main switch; 2) verifying this expression through a series of experiments within a current range of 0 to 4000 A and an energy range of 0 to 50 kJ; 3) giving an approximate expression for the optimal capacitance that minimizes the precharged energy; and 4) investigating the variation trends of the optimal capacitance and the corresponding optimal precharged energy with varying inductor current. [ABSTRACT FROM PUBLISHER]

The major strengths of inductors in energy density and power density make an inductive pulsed power supply (IPPS) a promising option for pulsed power supplies in an electromagnetic launch system. Among the circuits for an IPPS, the capacitor-aided meat grinder circuits constitute an important branch. An analytical method for the working processes of these circuits is proposed in this paper. The core of this method is the decoupling of a high-order circuit into the superposition of a resistor–inductor first-order equivalent subcircuit and a resistor–inductor–capacitor second-order equivalent subcircuit. The validity and accuracy of this method have been verified through comparison with a numerical simulation. The results show that this method possesses both satisfactory accuracy and excellent computational speed. With the same circuit parameters and time step, the time cost of this method is three orders of magnitudes lower than the time cost of a numerical simulation. Moreover, this method contributes to more intuitive understanding and more essential insight into the working principles of the capacitor-aided meat grinder circuits. [ABSTRACT FROM PUBLISHER]

The meat grinder with SElf-charged Capacitor and Thyristors circuit is a novel circuit for inductive pulsed power supplies. The energy transfer capacitor is one of the key components in this circuit. And its capacitance C and the precharged voltage UC are key parameters worth investigating. The circuit working process and corresponding numerical calculation method are briefly introduced. And the method validity is verified through experiments. Then, the influences of $C$ and UC on circuit performance indices, i.e., the maximum voltage across the main switch $V_{{\mathrm{sopm}}} , the secondary current multiplication factor m2 , the ratio of the maximum capacitor energy over the inductor charging energy \eta C , and the self-recovery rate of the precharged capacitor voltage k\mathrm{UC} , are quantitatively analyzed through parameter sweep. Generally speaking, large C is conducive to lower $V_{{\mathrm{sopm}}} ; small m2 ; small C and low UC are conducive to lower \eta C and higher $k_{{\mathrm{UC}}}$ . Moreover, the analytical expression of $k_{{\mathrm{UC}}}$ is given. With C and UC elaborately selected, $k_{{\mathrm{UC}}}$ can achieve 100%. In addition, the balance relationship between two contradictory indices $V_{{\mathrm{sopm}}}$ and $k_{{\mathrm{UC}}}$ is obtained by solving a biobjective optimization problem and using the genetic algorithm. [ABSTRACT FROM AUTHOR]

With inherent strengths in energy density and power density, the inductive pulsed power supplies (IPPS) have become an attractive option for the power supplies in electromagnetic launch systems. The meat grinder circuits, including the slow transfer of energy through capacitive hybrid (STRETCH) meat grinder circuit, the STRETCH meat grinder with inverse current commutation with semiconductor devices circuit, and the meat grinder with self-charged capacitor and thyristors circuit, constitute one major branch among the IPPS circuits. This paper summarizes the fundamental research work and contributions of the meat grinder circuits from the perspectives of circuit improvements, performance analysis, inductor design, module collaboration, and efficiency promotion. The future directions of single IPPS module are higher energy level, larger energy density, and higher efficiency. [ABSTRACT FROM PUBLISHER]

The meat grinder is a basic circuit for inductive pulsed-power supply (IPPS). Based on meat grinder, the Institute of Advanced Technology proposed a circuit called the slow transfer of energy through capacitive hybrid (STRETCH) meat grinder, in which an Integrated Gate Commutated Thyristors (IGCT) is selected as the main switch. Tsinghua University proposed the STRETCH meat grinder with inverse current commutation with semiconductor devices (ICCOS) in which the main switch is replaced by a thyristor and the ICCOS subcircuit is introduced to turn off the main switch. To reduce the opening switch voltage and increase the current turning-off capacity for IPPS, this paper presents a novel circuit topology named the meat grinder with self-charged capacitor and thyristors (SECTs). The key idea of the SECT topology is to turn off the primary current by the energy transfer capacitor, which is precharged. The meat grinder with SECT has larger capacity than the STRETCH meat grinder because it replaces the IGCT with a thyristor and is simpler than the STRETCH meat grinder with ICCOS because it only needs one capacitor. The suggested circuit is more suitable for IPPS module with high energy density. Simulation and experiment have been carried out to validate the circuit. [ABSTRACT FROM PUBLISHER]

The air-core flat spirals of strip coil structure is a typical type of the tightly coupled energy storage inductors used in inductive pulsed power supplies. This paper improves the speed and the parameter scope of the inductance calculation method for these inductors. Specifically, the analytical expressions using the structural parameters to represent the performance parameters, e.g., the inductance, the resistance, and the current conducting capability of the primary inductor and the secondary inductor L1 , L2 , R1 , R2 , I\mathrm{ 1limit} , I\mathrm{ 2limit} , the total volume V\mathrm{ tot} , and the energy density \omega , are given. The validity of this method is confirmed by practical measurements of a set of constructed inductors with 2.67-mH total inductance. The absolute error is within 0.02 mH. On the basis of this method, parameter optimization on energy density is conducted for the 70-kJ energy level module. Results show that the energy density can reach 11.2 MJ/ \text{m}^{3} when the total inductance is 5.07 mH and the total volume is 6.3\times 10^{-3}~\text{m}^{3}$ . [ABSTRACT FROM AUTHOR]

Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin–Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS byN-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells. [ABSTRACT FROM PUBLISHER]

A fast solving method for the launching process of the electromagnetic railgun and an automatic assignment method for the trigger strategy of the capacitive pulsed power supply (CPPS) are proposed. The accuracy of the solving method and the feasibility of the assignment method are verified through an illustrative example with a 1.8-MJ initially stored energy. On the basis of these methods, parameter optimization in design phase and performance analysis in operation phase are conducted around the projectile muzzle kinetic energy Ek and the system energy transfer efficiency $\eta $ . To be specific, the single-objective optimal solutions of Ek and $\eta $ and the biobjective Pareto front of Ek – $\eta $ are acquired by evolutionary computation. And the influence relations of certain system parameters on Ek and $\eta $ are acquired by parameter sweep. The research methods and results in this paper have both theoretical and pragmatic values in improving the performance of the CPPS-based electromagnetic railgun system. [ABSTRACT FROM AUTHOR]

Arsenic (As) is one of the most important toxic elements in the natural environment. Currently, although the assessment of the potential health risks of chronic arsenic poisoning has received great attention, the research on the effects of arsenic on the brain is still limited. It has been reported that dictyophora polysaccharide (DIP), a common bioactive natural compound found in dietary plants, could reduce arsenic toxicity. Following behavioral research, comparative proteomics was performed to explore the molecular mechanism of arsenic toxicity to the hippocampi of SD (Sprague Dawley) rats and the protective effect of DIP. The results showed that exposure to arsenic impaired the spatial learning and memory ability of SD rats, while DIP treatment improved both the arsenic-exposed rats. Proteomic analysis showed that arsenic exposure dysregulated the expression of energy metabolism, apoptosis, synapse, neuron, and mitochondria related proteins in the hippocampi of arsenic-exposed rats. However, DIP treatment reversed or restored the expression levels of these proteins, thereby improving the spatial learning and memory ability of arsenic-exposed rats. This study is the first to use high-throughput proteomics to reveal the mechanism of arsenic neurotoxicity in rats as well as the protective mechanism of DIP against arsenic neurotoxicity. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neurological developmental disorder in children, and is associated with social isolation and restricted interests. The etiology of this disorder is still unknown. There is neither any confirmed laboratory test nor any effective therapeutic strategy to diagnose or cure it. We performed data independent acquisition (DIA) and multiple reaction monitoring (MRM) analysis of plasma from children with ASD and controls. The result showed that 45 differentially expressed proteins (DEPs) were identified between autistic subjects and controls. Among these, only one DEP was down-regulated in ASD; other DEPs were up-regulated in ASD children's plasma. These proteins are found associated with complement and coagulation cascades, vitamin digestion and absorption, cholesterol metabolism, platelet degranulation, selenium micronutrient network, extracellular matrix organization and inflammatory pathway, which have been reported to be related to ASD. After MRM verification, five key proteins in complement pathway (PLG, SERPINC1, and A2M) and inflammatory pathway (CD5L, ATRN, SERPINC1, and A2M) were confirmed to be significantly up-regulated in ASD group. Through the screening of machine learning model and MRM verification, we found that two proteins (biotinidase and carbonic anhydrase 1) can be used as early diagnostic markers of ASD (AUC = 0.8, p = 0.0001). ASD is the fastest growing neurodevelopmental disorder in the world and has become a major public health problem worldwide. Its prevalence has been steadily increasing, with a global prevalence rate of 1%. Early diagnosis and intervention can achieve better prognosis. In this study, data independent acquisition (DIA) and multiple reaction monitoring (MRM) analysis was applied to analyze the plasma proteome of ASD patients (31 (±5) months old), and 378 proteins were quantified. 45 differentially expressed proteins (DEPs) were identified between the ASD group and the control group. They mainly were associated with platelet degranulation, ECM proteoglycar, complement and coagulation cascades, selenium micronutrient network, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), cholesterol metabolism, vitamin metabolism, and inflammatory pathway. Through the integrated machine learning methods and the MRM verification of independent samples, it is considered that biotinidase and carbon anhydrase 1 have the potential to become biomarkers for the early diagnosis of ASD. These results complement proteomics database of the ASD patients, broaden our understanding of ASD, and provide a panel of biomarkers for the early diagnosis of ASD. [Display omitted] • MS analysis of plasma low abundance proteins in patients with early ASD • The integrated machine learning model seeks for early biomarkers of ASD • The reliability of the biomarkers (biotinidase and carbonic anhydrase 1) were verified by MS in independent samples. • It was found that the complement coagulation cascade and inflammatory pathway may be activated in early ASD patients. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social and communication difficulties. Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD. However, the mechanisms involved have not yet been determined. In this study, we used iTRAQ (isobaric tags for relative and absolute quantification) proteomics analysis of the cerebral cortex of a VPA rat model (VPA group) and controls (CON group). The results showed that 79 differentially expressed proteins (DEPs) were identified between the VPA group and the CON group. Based on bioinformatics analysis, the DEPs were mainly enriched at synapses, especially glutamatergic synapses and GABAergic synapses. Some DEPs were involved in energy metabolism, thyroid hormone synthesis pathway, and Na + -K + -ATPase. Cytoskeleton and endoplasmic reticulum (ER) stress-related proteins were also involved. Some DEPs matched either the ASD gene database or previous reports on cerebral cortical transcriptome studies in VPA rat models. Dysregulation of these DEPs in the cerebral cortex of VPA rats may be responsible for autism-like behavior in rats. We also found that some DEPs were associated with neuropsychiatric disorders, implying that these diseases share common signaling pathways and mechanisms. Moreover, increased expression of DEPs was associated with energy metabolism in the cerebral cortex of VPA rats, implying that ASD may be a distinct type of mitochondrial dysfunction that requires further investigation.

Exosomes are often a promising source of biomarkers for cancer diagnosis in the early stages. Therefore, it is important to develop a sensitive and low-cost detection method. Here, we introduce a new substrate using gold nanorods (GNRs) on a silver-island film that produces a 360-fold AF647 molecule fluorescence enhancement compared to glass. The amplified fluorescence was proven theoretically by using finite difference time-domain simulation (FDTD). Utilizing the enhanced fluorescence from the substrate, GNRs attached with the biomolecules and created a sandwich immunoassay that can significantly detect human CD63 antigen on the exosome. By applying the method, the detection limit of mouse IgG goes down to 0.3 ng/mL, which is considerably better than the existing methods. Moreover, the sensitivity and accuracy for clinical plasma from six patients confirm its diagnostic feasibility. The proposed substrate can be uniformly extended to the identification of other biomarkers by modifying the antibodies on the surfaces of the GNRs.

Se-methylselenocysteine (SMC) is a major selenocompound in selenium (Se) enriched plants and has been found to ameliorate neuropathology and cognitive deficits in triple-transgenic mice model of Alzheimer's disease (3 × Tg-AD mice). To explore the underlying molecular mechanisms, the present study is designed to elucidate the protein changes in the cortex of SMC-treated 3 × Tg-AD mice. After SMC supplementation, proteomic analysis revealed that 181, 271, and 41 proteins were identified as differentially expressed proteins (DEPs) between 3 × Tg-AD mice vs wild type (AD/WT group), SMC-treated AD mice vs AD (AD + SMC/AD), and AD + SMC/WT group, respectively. Among these, 138 proteins in the diseased group were reversed by SMC treatment. The DEPs in AD/WT group and AD + SMC/AD group were mainly related to metabolism, synapses, and antioxidant proteins, while their levels were decreased in AD mice but up-regulated after treating with SMC. In addition, we found reduced ATP levels and destroyed synaptic structures in the AD mice brains, which were significantly ameliorated upon SMC treatment. Our study suggests that energy metabolism disorders, abnormal amino acid metabolism, synaptic dysfunction, and oxidative stress may be the key pathogenic phenomena of AD. SMC reversed the expression of proteins associated with them, which might be the main mechanism of its intervention in AD.

BACKGROUND Prostatic calculi are common in urological treatments. Our major purpose in the present study was to explore the occurrence and composition of prostatic calculi, and investigate the effect of calcium oxalate (CaOx) on clusterin expression and lower urinary tract symptom (LUTS) in prostatitis and benign prostatic hyperplasia (BPH) patients with calculi. MATERIAL AND METHODS From December 2016 to January 2017, a total of 79 prostatitis patients aged more than 50 years were enrolled. The patients were divided into 3 groups: group A had small calculi (discrete, small echoes); group B had large calculi (large masses of multiple echoes, much coarser), and group C had no calculi. Immunohistochemical analysis was performed to evaluate the tissue scores. The clusterin expression was detected by quantitative real-time CR (qRT-PCR), Western blot, and immunofluorescence. RESULTS According to multifactor analysis, age was significantly associated with prostatic calculus. The composition of prostatic calculus was an independent factor of LUTS. The clusterin expression was elevated in group B. The mRNA and protein levels of clusterin in prostatitis and BPH patients with stones were obviously higher than those in prostatitis and BPH patients without stones. CaOx enhanced clusterin expression in a dose-dependent manner. CONCLUSIONS Large prostatic calculi were associated with LUST. Furthermore, CaOx enhanced clusterin expression, leading to large prostatic calculi. These results may provide a therapeutic strategy for prostatitis and BPH.