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Alzheimer's disease (AD) is rapidly becoming one of the most expensive, burdening, and deadly diseases of this century. Up to now, there is still a lack of pharmacotherapy with substantial efficacy, and physical exercise is a promising and low‐cost way to aid in delaying the process of AD. The aim of this review is to summarise the efficacy of different physical exercise approaches and doses in the management of AD, including aerobic exercise, resistance exercise and multicomponent exercise. A literature search using MeSH terms for each topic is undertaken using PubMed and the Web of Science Core Collection database, supplemented by hand searching for additional references. Retrieved articles were reviewed, synthesised, and summarised. This review shows that aerobic exercise has been almost unanimously recognised for the improvement of cognition, neuropsychiatric symptoms and activities of daily living. Resistance exercise also shows a good prospect in the above aspects and has a unique advantage in enhancing muscle strength, while multicomponent physical activity does not seen to significantly improve cognitive function. Each type of exercise has a dose effect, but for individuals with AD, the most appropriate exercise dose is still controversial. [ABSTRACT FROM AUTHOR]

This paper takes the risk preference of modern listed companies as the research object, uses the financial data of Chinese listed companies combined with the literary inquisition file in Qing Dynasty to conduct an empirical study, and examines the influence of literary inquisition on the risk preference of modern corporate CEOs in Qing Dynasty. The study found that the literary inquisition incident in Qing Dynasty significantly affected and reduced the risk preference of modern enterprises. The competitive hypothesis of the influence of Confucian culture and China City Commercial Credit Environment Index (CEI) on CEOs' risk preference is excluded. In addition, through the study of heterogeneity, this paper also verifies that the influence of literary inquisition is more significant in areas with a higher degree of marketization, indicating that the influence of informal institutions depends on the establishment of formal institutions. Finally, in the mechanism study, this paper points out that the rulers' suppression of ideas will change long-term social capital and lead to the decrease of general trust in society, which will make the enterprise managers born in the region tend to be conservative in their risk preference. [ABSTRACT FROM AUTHOR]

Recently, the World Health Organization noted the increasing signs of pandemic fatigue around the world and repeatedly warned the public to continue to stay cautious. The current study explores whether social media use plays a role in the formation and development of pandemic fatigue. Drawing on a survey of 849 social media users in China, the findings indicated that different social media behaviors play different roles in affecting pandemic fatigue. Specifically, social interaction use is negatively associated with pandemic fatigue, mediated by more social support and reduced hopelessness. Active content use contributes to pandemic fatigue development, an association explained by information overload and desensitization. Notably, passive content use is found to trigger reactance but is negatively associated with pandemic fatigue, which is fully mediated by reduced information overload. This study seeks to understand how pandemic fatigue is associated with social media use and to explicate the underlying mechanism. The implications of the findings and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

In the study, silicon doped carbon quantum dots (Si-CQDs) was prepared by one-pot hydrothermal method with (3-aminopropyl) triethoxysilane (APTES) and o-phenylenediamine (OPD) as raw materials. Then a new ratiometric fluorescent probe (RF-probe) was successfully established for sensitively and selectively monitoring proanthocyanidins (PAs) with a linear range of 10–500 nM and limit of detection (LOD) of 5.6 nM. that is, the fluorescence (FL) intensity of Si-CQDs at 570 nm was used as the built-in reference, while dopamine (DA) reacting with 4-hexylresorcinol (4-HR) could produce a new fluorescent substance (named as azamonardine, AZMON), and its FL intensity at 480 nm was reduced because Cr(VI) could oxidize DA to generate quinone without fluorescence. In the presence of PAs, Cr(VI) was reduced to Cr(III), which caused that the amount of DA reacting with 4-HR was increased, thus the FL intensity of AZMON was recovered. Furthermore, the RF-probe was successfully used for the determination of PAs in black goji berry from two different areas and PAs capsule with satisfactory results compared to the standard HPLC method. [ABSTRACT FROM AUTHOR]

Background. Ginsenoside Rg1 (Rg1) is one of the key bioactive components of the precious Traditional Chinese Medicine that has been used to treat diabetes in China. Ginsenosides have been reported to protect diabetics from tissue damage, inflammation, and insulin resistance. Type 1 diabetes (T1D) is an organ-specific autoimmune disease that occurred frequently among adolescents over the world, its development was related to inflammation and β-cells immunodeficiency. The aim of this study is to explore the biological mechanism of Rg1 on inflammation and autophagy of β-cells in T1D and its therapeutic potential. Methods. The model of T1D mice was established by injecting Streptozotocin (STZ) (55 mg/kg) or citric acids once a day for 5 days and from the fourth day of injection, mice were administered with Rg1 (20 mg/kg) or saline by gavage once a day for 12 days. Hematoxylin-eosin staining, immunofluorescence, ELISA, quantitative real-time PCR, and Western blot were used to observe the histopathological changes, inflammatory factor levels, and autophagy markers after administration of ginsenoside Rg1. Results. Compared to the T1D mice, Rg1 improved the weight (p < 0.05) and blood glucose (p < 0.01) of mice, advanced the injury and apoptosis of β-cells in islets (p < 0.01), and markedly inhibited the protein expression degrees of CD45, CXCL16, ox-LDL, and TF in the pancreas and spleens (p < 0.01), also activated the degrees of insulin in serum (p < 0.01). Besides, in T1D mice' pancreas and spleen, Rg1 markedly repressed the IL-1β, TNF-α, and NOS2 mRNA levels (p < 0.05 or p < 0.01), inhibited the CXCL16, NF-κB, and TF proteins (p < 0.05 or p < 0.01), while elevating the ratio of LC3 II/I (p < 0.01) and P62 (p < 0.05) protein level. Conclusions. This study proved that Rg1 protected mice against T1D possibly by improving islet injury and tissue inflammation, raising serum insulin, and tissue autophagy marker. [ABSTRACT FROM AUTHOR]

The excess accumulation of nonessential Al3+ in the human body can cause serious health problems, thus there is significant interest in the detection of Al3+. A new ratio fluorescent probe (RF‐probe) based on the mixing of red‐emitting D‐penicillamine (DPA) stabilized copper nanoclusters (DPA‐CuNCs) with pyridoxal 5'‐phosphate (PLP) was designed for sensitive and selective determination of Al3+. The −CHO group of PLP is expected to form an imine linkage with the free −NH2 group available of the DPA on the surface of DPA‐CuNCs. The content of Al3+ could be mensurated by the as‐prepared RF‐probe with a linear response in the range of 1.33–46.67 μmol ⋅ L−1, and corresponding limit of detection (LOD) was calculated to be 0.33 μmol ⋅ L−1. Moreover, the RF‐probe was successfully extended to the assay of Al3+ in aluminum carbonate chewing tablets, baking powder, pond water and drink water with satisfactory results compared to the standard atomic absorption spectroscopy (AAS). [ABSTRACT FROM AUTHOR]

This paper presents a novel substrateless packaging solution for the D-band active e mixer MMIC module, using a waveguide line with a glide-symmetric periodic electromagnetic bandgap (EBG) hole configuration. The proposed packaging concept has the benefit of being able to control signal propagation behavior by using a cost-effective EBG hole configuration for millimeter-wave- and terahertz (THz)-frequency-band applications. Moreover, the mixer MMIC is connected to the proposed hollow rectangular waveguide line via a novel wire-bond wideband transition without using any intermediate substrate. A simple periodical nail structure is utilized to suppress the unwanted modes in the transition. Additionally, the presented solution does not impose any limitations on the chip's dimensions or shape. The packaged mixer module shows a return loss lower than 10 dB for LO (70–85 GHz) and RF (150–170 GHz) ports, achieving a better performance than that of traditional waveguide transitions. The module could be used as a transmitter or receiver, and the conversion loss shows good agreement in multiple samples. The proposed packaging solution has the advantages of satisfactory frequency performance, broadband adaptability, low production costs, and excellent repeatability for millimeter-wave- and THz-band systems, which would facilitate the commercialization of millimeter-wave and THz products. [ABSTRACT FROM AUTHOR]

Non-contact vital sign detection technology has brought a more comfortable experience to the detection process of human respiratory and heartbeat signals. Ensemble empirical mode decomposition (EEMD) is a noise-assisted adaptive data analysis method which can be used to decompose the echo data of frequency modulated continuous wave (FMCW) radar and extract the heartbeat and respiratory signals. The key of EEMD is to add Gaussian white noise into the signal to overcome the mode aliasing problem caused by original empirical mode decomposition (EMD). Based on the characteristics of clutter and noise distribution in public places, this paper proposed a static clutter filtering method for eliminating ambient clutter and an improved EEMD method based on stable alpha noise distribution. The symmetrical alpha stable distribution is used to replace Gaussian distribution, and the improved EEMD is used for the separation of respiratory and heartbeat signals. The experimental results show that the static clutter filtering technology can effectively filter the surrounding static clutter and highlight the periodic moving targets. Within the detection range of 0.5 m~2.5 m, the improved EEMD method can better distinguish the heartbeat, respiration, and their harmonics, and accurately estimate the heart rate. [ABSTRACT FROM AUTHOR]

A compact fully metallic antenna with high endfire gain and vertical polarization is presented for applications that require the antenna to be mounted on large metallic platforms. The proposed structure includes one driven element on a ground plane, in addition to several parasitic directors and reflectors. The antenna behaves like a Yagi array, but with vertical polarization, where multiple directors and reflectors are used to enhance the endfire gain in the plane that contains the ground surface. The driven element is an upside-down U-shaped metallic strip with short vertical sides connected to the ground plane. The radiation is predominantly emitted from these vertical sides giving the antenna its vertical polarization radiation. Directors and reflectors are designed based on the driven element, with directors having the center of the U-shaped strip connected to the ground plane and reflectors without shorting pins in the middle. A prototype is fabricated with a volume of 104 $\times 55\times $ 6 mm3. The measured bandwidth is 18% (5.32–6.38 GHz). The variation of endfire gain is 2 dB around the nominal gain of 10.3 dBi across the bandwidth. [ABSTRACT FROM AUTHOR]

The path of crack propagation in a graphene sheet is significant for graphene patterning via the tearing approach. In this study, we evaluate the fracture properties of pre-cracked graphene during the tearing process, with consideration of the effects of the aspect ratio, loading speed, loading direction, and ambient temperatures on the crack propagation in the monolayer sheet. Some remarkable conclusions are drawn based on the molecular dynamic simulation results, i.e., a higher loading speed may result in a complicated path of crack propagation, and the propagation of an armchair crack may be accompanied by sp carbon links at high temperatures. The reason for this is that the stronger thermal vibration reduces the load stress difference near the crack tip and, therefore, the crack tip can pass through the sp link. A crack propagates more easily along the zigzag direction than along the armchair direction. The out-of-plane tearing is more suitable than the in-plane tearing for graphene patterning. The path of crack propagation can be adjusted by changing the loading direction, e.g., a rectangular graphene ribbon can be produced by oblique tearing. This new understanding will benefit the application of graphene patterning via the tearing approach. [ABSTRACT FROM AUTHOR]

Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients' survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies. [ABSTRACT FROM AUTHOR]

• CHIT1 regulates brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment. • CHIT1 skews polarization from a pro-inflammatory environment toward an anti-inflammatory one. • CHIT1 has a potential therapeutic value in AD via modulation of inflammation. Chitotriosidase (CHIT1, chitinase 1) is increased in the cerebrospinal fluid and peripheral blood of Alzheimer's disease (AD) patients. Our previous study has shown that CHIT1 provides potential protection through microglial polarization and reduction of β-amyloid (Aβ) oligomers on rat models of AD. Histone deacetylase 3 (HDAC3) plays a significant role in the expression and regulation of proteins related to the pathophysiology of AD. In addition, nuclear factor-kappa B (NF-κB) signaling pathway activation in neurons is associated with the progression of AD. NF-κB activation is regulated by HDAC3 deacetylation. In the present study, we researched the role of CHIT1 in HDAC3/NF-κB signaling in D-galactose (D-gal) and aluminum-exposed rat model with cognitive impairments. Following CHIT1 treatment, we found that the protein and mRNA levels of HDAC3 and NF-κB were reduced, the expression level of IκBα increased, anti-inflammatory factors (Arg-1, IL-10, and CD206) were elevated while pro-inflammatory factors (TNF-a, iNOS, and IL-1β) were decreased in D-gal/aluminum-induced AD rats. These results indicate that CHIT1 can regulate brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment. [ABSTRACT FROM AUTHOR]

A water‐soluble and polyethyleneimine protected copper nanoclusters (CuNCs@PEI) was prepared by one‐step ultraviolet radiation (UVI) combined with microwave heating (MWH) method, and the influence of different energy suppliers on the CuNCs@PEI luminescence performance was investigated in detail. The as‐prepared CuNCs@PEI could be used as a viable fluorescent probe for sensitive and selective mensurating TCH (tetracycline hydrochloride)/VB12 (vitamin B12) with a linear response in the range of 0.33–66.67/0.33‐53.33 μmol L−1, and corresponding limit of detection (LOD) and limit of quantification (LOQ) were calculated to be 55.50/56.34 and 184.82/187.61 nmol L−1. The fluorescence (FL) quenching of CuNCs@PEI by TCH/VB12 came from the combination of FRET (Förster resonance energy transfer) and IFE (inner filter effect). Moreover, the probe was successfully extended to the assays of TCH in veterinary powder or TCH tablets and VB12 in oral liquid or VB12 tablets with satisfactory results compared to the standard HPLC method. Besides, the CuNCs@PEI probe exhibited a good temperature sensing. [ABSTRACT FROM AUTHOR]

Doping Ag-enhanced and glutathione-stabilized Au nanoclusters (GSH–Ag/AuNCs) were prepared by the one-step ultraviolet radiation combined with microwave heating method. The effects of the molar ratio of Au–Ag and different types of energy suppliers on the fluorescent performance of GSH–Ag/AuNCs were studied in detail. After that, a new ratio fluorescent probe (RF-probe) based on the mixing of GSH–Ag/AuNCs with carbon dots (CDs) was designed for sensitive and selective determination of copper gluconate (CG) and cupric sulfate (CS). For the CDs–GSH–Ag/AuNCs RF-probe, the fluorescence (FL) of CDs (at 440 nm) and that of alloy nanoclusters (NCs) (at 605 nm) were, respectively, unaffected and strongly quenched in the presence of CG/CS at λ ex = 3 7 0 nm coming from the dynamic quenching process. Corresponding linear ranges and limit of detection (LOD) of the RF-probe for the CG/CS assay were estimated to be 0.17–6.20/0.17–5.62 μ mol/L and 16.80/15.95 nmol/L, respectively. Furthermore, the proposed RF-probe was successfully used for the assays of CG in CG tablets and CG additive, and CS in infant formula and CS additive, respectively. Fluorescent-enhanced GSH–Ag/AuNCs were synthesized by simply doping Ag ions and the method of UV irradiation combined with microwave heating. Subsequently, a new and simple RF-probe was developed based on the mixing CDs and GSH–Ag/AuNCs. The concentration of CG/CS could be monitored indirectly by the RF-probe (CDs–GSH–Ag/AuNCs system) with remarkable selectivity and high sensitivity. Moreover, the proposed RF-probe was successfully used for the assays of CG in CG tablets and CG additive, and CS in infant formula and CS additive, respectively. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to elucidate whether malnutrition is associated with cognitive impairment in an older Chinese population. Methods: A cross‐sectional study was conducted in 2365 participants aged 60 years or older from January 2013 to September 2019. Nutritional status was measured by using the Mini Nutritional Assessment Short Form (MNA‐SF). Cognitive function was assessed with the Mini‐Mental State Examination (MMSE). The relationship between malnutrition or each Mini Nutritional Assessment Short Form domain and cognitive impairment was examined with univariate and multivariate logistic regression analysis. Results: The prevalence of malnutrition, risk of malnutrition, and cognitive impairment was 5.54%, 33.45%, and 36.74%, respectively. The prevalence was higher in those 80 years and older: 7.88%, 40.75%, and 53.65%, respectively. The Mini‐Mental State Examination score was positively correlated with the Mini Nutritional Assessment Short Form score (r = 0.364, P < 0.001). After adjustment for age, gender, education, marital status, and living alone, malnutrition (odds ratio (OR) = 3.927, 95% confidence interval (CI): 2.650–5.819), anorexia (OR = 1.454, 95%CI: 1.192–1.774), weight loss (OR = 1.697, 95%CI: 1.406–2.047), impaired mobility (OR = 4.156, 95%CI: 3.311–5.218), and psychological stress (OR = 1.414, 95%CI: 1.070–1.869) were significantly associated with an increased risk of cognitive impairment. Conclusions: Our results suggest that the prevalence of malnutrition and cognitive impairment is relatively high and increases with age. Malnutrition, anorexia, weight loss, impaired mobility, and psychological stress are significantly associated with an increased risk of cognitive impairment. Therefore, clinicians should assess the nutritional and cognitive status of the elderly regularly to improve early detection and timely intervention. [ABSTRACT FROM AUTHOR]

Background: To investigate the use and adherence of antidementia drugs in elderly patients with dementia from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University. Methods: Patients were recruited from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University from December 2010 to December 2018. Medical charts were reviewed, including diagnosis, dosage of antidementia medicines, neuropsychological testing scores, and the further questionnaires were conducted via face‐to‐face or telephone, included duration of treatment, types of antidementia drugs, and reasons for treatment discontinuation. Results: The data from 422 patients were analysed retrospectively for this study. Three hundred and fifteen were diagnosed with Alzheimer's disease (AD), 67 with mild cognitive impairment (MCI), and 40 with other types of dementia. From the 422 patients, 26.8% were treated with original donepezil (n = 113), 11.6% with generic donepezil (n = 49), 24.6% with memantine (n = 104), 13.3% with huperzine A (n = 56), and 23.7% with a combination of drugs (n = 100). However, 73% of patients discontinued treatment within 1 year of initiation. Patients treated for more than 36 months (37.8%) were more likely to choose combined medication, as compared with patients treated for less than 36 months. Patients with less than 9 years of education (odds ratio (OR): 2.394; 95% CI: 1.508–3.801) were more likely to discontinue treatment than patients with more than 9 years of education. Patients with elevated physical self‐maintenance scale (PSMS) scores (OR: 1.195; 95% CI: 1.086–1.316) had a high risk of discontinuation. Conclusions: Overall treatment compliance is relatively poor in memory clinics in Chongqing. Our study demonstrates that higher education may lead to better treatment adherence in dementia care. Combination therapy may increase treatment time. However, poorer PSMS scores are a significant risk factor for treatment discontinuation. [ABSTRACT FROM AUTHOR]

Clinically, superimposed systemic inflammation generally has significant deleterious effects on the Alzheimer's disease (AD) progression. However, the related molecular mechanisms remain poorly understood. Microglial toll-like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells 2 (TREM2) are two key regulators of inflammation that may play an essential role in this complex pathophysiological process. In this study, intraperitoneal injection of lipopolysaccharide (LPS) into APP/PS1 transgenic AD model was used to mimic systemic inflammation in the development of AD. Initial results from the cortex showed that compared with wild-type mice, APP/PS1 mice exhibited elevated gene and protein expression levels of both TLR4 and TREM2 with different degree. Interestingly, after LPS treatment, TLR4 expression was persistently up-regulated, while TREM2 expression was significantly down-regulated in APP/PS1 mice, suggesting that the negative regulatory effect of TREM2 on inflammation might be suppressed by LPS-induced hyperactive TLR4. This imbalance of TLR4/TREM2 contributed to microglial over-activation, followed by increased neuronal apoptosis in the cortex of APP/PS1 mice; these changes did not alter the expression level of Aβ1−42. Similar alterations were observed in our in vitro experiment with β-amyloid1–42 (Aβ1–42)-treated N9 microglia. Further, Morris water maze (MWM) testing data indicated that LPS administration acutely aggravated cognitive impairment in APP/PS1 mice, suggesting that the addition of systemic inflammation can potentially accelerate the progression of AD. Collectively, we conclude that an imbalance of TLR4/TREM2 may be a potential link between AD and systemic inflammation. TREM2 can serve as a potential therapeutic target for treating systemic inflammation in AD progression. [ABSTRACT FROM AUTHOR]

Phosgene is widely used as an industrial chemical, and phosgene inhalation causes acute lung injury (ALI), which may further progress into pulmonary edema. Currently, an antidote for phosgene poisoning is not known. Alpha-1 antitrypsin (α1-AT) is a protease inhibitor used to treat patients with emphysema who are deficient in α1-AT. Recent studies have revealed that α1-AT has both anti-inflammatory and anti-SARS-CoV-2 effects. Herein, we aimed to investigate the role of α1-AT in phosgene-induced ALI. We observed a time-dependent increase in α1-AT expression and secretion in the lungs of rats exposed to phosgene. Notably, α1-AT was derived from neutrophils but not from macrophages or alveolar type II cells. Moreover, α1-AT knockdown aggravated phosgene- and lipopolysaccharide (LPS)-induced inflammation and cell death in human bronchial epithelial cells (BEAS-2B). Conversely, α1-AT administration suppressed the inflammatory response and prevented death in LPS- and phosgene-exposed BEAS-2B cells. Furthermore, α1-AT treatment increased the inhibitor of DNA binding 1 (ID1) gene expression, which suppressed NF-κB pathway activation, reduced inflammation, and inhibited cell death. These data demonstrate that neutrophil-derived α1-AT acts as a self-protective mechanism, which protects against phosgene-induced ALI by activating the ID1-dependent anti-inflammatory response. This study may provide novel strategies for the treatment of patients with phosgene-induced ALI. Phosgene inhalation leads to the recruitment of neutrophils into the lungs. The recruited neutrophils express and release α1-AT, which enters bronchial epithelial cells and increases ID1 expression, thereby inhibiting NF-κB activation. The inactivation of NF-κB reduces the release of inflammatory cytokines and death of bronchial epithelial cells. Endogenous and exogenous α1-AT alleviate phosgene-induced inflammation and acute lung injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • Chitotriosidase (CHIT1) treatment alone had no impact on TGFβ-Smad signaling and uptake of β-amyloid (Aβ) in N9 microglia. • CHIT1 enhanced TGFβ1-induced expression of TβRI and activation of Smad signaling in N9 microglia. • CHIT1 enhanced TGFβ1-induced phagocytosis of Aβ in N9 microglia, which was blocked by pretreatment with a TβRI inhibitor. Abstract TGFβ-Smad signaling is involved in the modulation of β-amyloid (Aβ) clearance in microglia. This signaling is impaired in the brain of Alzheimer's disease (AD). Chitotriosidase (CHIT1) is elevated in the cerebrospinal fluid and peripheral blood of AD patients, and has been reported to augment TGFβ signaling in fibroblast and T cells. In this study, we investigated the role of CHIT1 in TGFβ-Smad signaling and Aβ phagocytosis in N9 microglia. We found that CHIT1 significantly enhanced TGFβ1-induced expression of TβRI (TGFβ receptor I) and activation of Smad signaling. CHIT1 did not affect Aβ uptake in microglia by itself, but did enhance TGFβ1-induced phagocytosis of Aβ, which was blocked by pretreatment with SB431542 (TβRI inhibitor). These results indicate that CHIT1 may play a protective role in Aβ clearance by enhancing TGFβ signaling in microglia. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate the effects of ADP dependent glucokinase antisense RNA 1 (ADPGK-AS1)/ miR-205-5p/ zinc finger E-box binding homeobox 1 (ZEB1) on PC cells. Methods: Differentially expressed lncRNAs and miRNAs in pancreatic cancer (PC) were identified by microarray analysis. In silico ceRNA analysis was conducted to find out the interactions among lncRNAs, miRNAs and mRNAs. Quantitative real-time PCR (qRT-PCR) was utilized to examine the expression of miR-205-5p and lncRNA ADPGK-AS1 in PC and non-cancerous cells. The association between miR-205-5p and ADPGK-AS1 as well as miR-205-5p and ZEB1 was determined by dual-luciferase reporter gene assay. After manipulating the expression of ADPGK-AS1, mir-205-5p and ZEB1 in PANC-1 and SW-1990 cells, cell proliferation, migration, invasion and apoptosis were respectively confirmed by cell counting kit-8 (CCK-8) assay, transwell assay and TUNEL. Western blot was applied to examine the expression of Epithelial-mesenchymal Transition-related proteins. In vivo experiment was conducted to further determine the effect of miR-205-5p/ZEB1 on tumorigenic ability of PC cells. Results: MiR-205-5p was low-expressed while ZEB1 and ADPGK-AS1 were high-expressed in PC tissues and cells compared with the normal. Dual-luciferase reporter gene assay proved that ADPGK-AS1 could directly target miR-205-5p and miR-205-5p could directly target ZEB1 3′UTR. The expression of MiR-205-5p was negatively correlated with proliferation, migration and invasion, and positively correlated with apoptosis rate of PC cells, while ZEB1 and ADPGK-AS1 had an inversed effect. Further in vitro and in vivo investigation indicated that epithelial-mesenchymal transition (EMT) could be restrained by miR-205-5p through targeting ZEB1. ADPGK-AS1 strongly promoted the tumorigenesis via downregulating miR-205-5p expression and induced the EMT process in vivo. Conclusion: ADPGK-AS1 inhibited miR-205-5p and therefore promoted PC progression through activating ZEB1-induced EMT. [ABSTRACT FROM AUTHOR]

Background: Rapidly growing healthcare demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To develop a fully automated Mini-Mental State Examination (MMSE) assessment model and validate the model's rating consistency. Methods: The Automated Assessment Model for MMSE (AAM-MMSE) was an about 10-min computerized cognitive screening tool containing the same questions as the traditional paper-based Chinese MMSE. The validity of the AAM-MMSE was assessed in term of the consistency between the AAM-MMSE rating and physician rating. Results: A total of 427 participants were recruited for this study. The average age of these participants was 60.6 years old (ranging from 19 to 104 years old). According to the intraclass correlation coefficient (ICC), the interrater reliability between physicians and the AAM-MMSE for the full MMSE scale AAM-MMSE was high [ICC (2,1)=0.952; with its 95% CI of (0.883,0.974)]. According to the weighted kappa coefficients results the interrater agreement level for audio-related items showed high, but for items "Reading and obey", "Three-stage command", and "Writing complete sentence" were slight to fair. The AAM-MMSE rating accuracy was 87%. A Bland-Altman plot showed that the bias between the two total scores was 1.48 points with the upper and lower limits of agreement equal to 6.23 points and −3.26 points. Conclusions: Our work offers a promising fully automated MMSE assessment system for cognitive screening with pretty good accuracy. [ABSTRACT FROM AUTHOR]

Chitinase activity is increased in Alzheimer’s disease (AD). However, the role of chitinase1 in AD is unknown. We investigated the effects of chitinase1 on Alzheimer’s pathology and microglia function. Artificial chitinase1 and chitinase inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on inflammatory factors and β-amyloid (Aβ) oligomers deposition in D-galactose/AlCl 3 -induced rat model with cognitive impairments. Aβ-treated N9 microglia cells were analyzed to further verify whether the changes in inflammatory factors following chitinase1 treatment were associated with microglia alternative activation. Our data displayed that the activity of chitinase1 was both improved in D-galactose/AlCl 3 -injected rats and Aβ-pretreated microglia. Moreover, there was an improvement in cognitive function in chitinase1-treated AD rats. Furthermore, anti-inflammation factors (Arginase 1, Arg-1, mannose receptor type C 1, MRC1/CD206) were increased and pro-inflammation factors (tumor necrosis factor alpha, TNFα, interleukin 1 beta, IL-1β) were decreased in D-galactose/AlCl 3 -induced AD rats with chitinase1 treatment. A higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1 markers (TNFa, IL-1β) were obtained in Aβ-pretreated N9 cells with chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2 phenotype. We also detected that chitnase1 could weaken the deposition of Aβ oligomers in the brain of D-galactose/ AlCl 3 - induced AD rats. In conclusion, Chitinase1 might exert protective effects against AD by polarizing microglia to an M2 phenotype and resisting Aβ oligomer deposition. [ABSTRACT FROM AUTHOR]

Purpose Smad anchor for receptor activation (SARA) is an important regulator of transforming growth factor β (TGF-β) signaling by recruiting Smad2/3 to TGF-β receptors. Although TGF-β signaling is critically involved in epileptogenesis, whether SARA activation is sufficient to facilitate TGF-β pathway to regulate epilepsy remains unknown. Methods The expression of SARA and downstream Phospho-Smad3 (p-Smad3) was examined in rats with pilocarpine induced epilepsy. Additionally, knockdown of SARA was performed via recombinant lentiviral vector in the pilocarpine-induced rats. Results Here we show that expressions of SARA and p-Smad3 are increased in the hippocampus as rats subjected to pilocarpine-induced status epilepticus (SE). Both SARA and p-Smad3 are also upregulated in the temporal cortex of epileptic rats. Furthermore, SARA mRNA levels reach peak as early as 6 hr following SE onset and remain elevated in the chronic phase. Transfection of recombinant lentiviral shRNA targeting SARA knocks down SARA expression, attenuates TGF-β/p-Smad3 signaling in the hippocampus, and postpones the SE onset. Conclusion Our results demonstrate that SARA/Smad3 pathway contributes to mechanism of seizure and SARA in TGF-β signaling may be a potential therapeutic target for epilepsy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma is one of the most lethal tumors in the world with a poor prognosis. Thus, an accurate prediction model, which identify patients within high risk of pancreatic adenocarcinoma is needed to adjust the treatment and elevate the prognosis of these patients. Methods: We obtained RNAseq data of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) from UCSC Xena database, identified immune-related lncRNAs (irlncRNAs) by correlation analysis, and identified differential expressed irlncRNAs (DEirlncRNAs) between pancreatic adenocarcinoma tissues from TCGA and normal pancreatic tissues from TCGA and Genotype-Tissue Expression (GTEx). Further univariate and lasso regression analysis were performed to construct prognostic signature model. Then, we calculated the areas under curve and identified the best cut-off value to identify high- and low-risk patients with pancreatic adenocarcinoma. The clinical characteristics, immune cell infiltration, immunosuppressive microenvironment, and chemoresistance were compared between high- and low-risk patients with pancreatic adenocarcinoma. Results: We identified 20 DEirlncRNA pairs and grouped the patients by the best cut-off value. We proved that our prognostic signature model possesses a remarkable efficiency to predict prognosis of PAAD patients. The AUC for ROC curve was 0.905 for 1-year prediction, 0.942 for 2-year prediction, and 0.966 for 3-year prediction. Patients in high-risk group have poor survival rate and worse clinical characteristics. We also proved that patients in high-risk groups were in immunosuppressive status and may be resistant to immunotherapy. Anti-cancer drug evaluation was performed based on in-silico predated tool, such as paclitaxel, sorafenib, and erlotinib, may be suitable for PAAD patients in high-risk group. Conclusions: Overall, our study constructed a novel prognostic risk model based on pairing irlncRNAs, exhibited a promising prediction value in patients with pancreatic adenocarcinoma. Our prognostic risk model may help distinguish PAAD patients suitable for medical treatments. [ABSTRACT FROM AUTHOR]

Public environmental awareness (PEA) is critical to the implementation of environmental policies by governments and product strategies by companies, however, there is less literature discussing its drivers. Environmental information disclosure (EID), as a bottom-up environmental policy, promotes public environmental management. This paper takes the Pollution Information Transparency Index (PITI) as a proxy for the degree of EID and discusses its impact on PEA. Using the PITI of 113 cities and the Baidu index-based PEA for 30 provinces from 2010 to 2019, we find a significant increase in PEA with the widening of EID, and the impacts of EID get larger as the quantile increases. Moreover, the effects of EID on PEA are amplified in areas with heavy pollution, high levels of green innovation, and stringent environmental governance capacities, but are diminished in areas with rampant corruption. The findings of this paper provide recommendations for optimizing EID implementation. • With the expansion of EID, PEA has increased significantly. • The impacts of EID on PEA are amplified in areas with high pollution, green innovation, and strict governance capacities. • The impacts of EID on PEA are diminished in areas with rampant corruption. [ABSTRACT FROM AUTHOR]

Transforming growth factor beta (TGFβ) signaling participates in pathogenesis of epilepsy. TGFβ1, as a transmitter of TGFβ signaling, might be a useful marker for predicting the prognosis of patients with epilepsy. The present study aimed to measure TGFβ1 level in the cerebrospinal fluid (CSF) of patients with drug-resistant epilepsy and non-resistant epilepsy. A total of 43 patients with epilepsy were recruited, 28 were non-resistant epilepsy subgroup, 15 drug-resistant epilepsy subgroup. 11 patients with intracranial infection and 11 individuals with primary headache were used as controls. The concentration of CSF and serum TGFβ1 was measured by enzyme-linked immunosorbent assay. The concentration of CSF-TGFβ1 was 209.26 ± 81.07 pg/ml in the drug-resistant epilepsy subgroup, 121.80 ± 40.32 pg/ml in the non-resistant epilepsy subgroup, 552.17 ± 456.20 pg/ml in intracranial infection control, 133.80 ± 68.55 pg/ml in headache control, respectively. TGFβ1 level was significantly increased in the drug-resistant epilepsy subgroup compared to the non-resistant epilepsy subgroup. TGFβ1 level in intracranial infection control was higher than that in the non-resistant epilepsy subgroup. There was no statistically difference of CSF-TGFβ1 between the non-resistant epilepsy subgroup and headache controls, between the resistant epilepsy subgroup and intracranial infection controls. TGFβ levels are increased in the CSF of patients with drug-resistant epilepsy. High CSF-TGFβ1 levels may be a potential screening biomarker of antiepileptic drug resistance in patients with epilepsy. [ABSTRACT FROM AUTHOR]

This study examined 510 Chinese students' emotional intelligence (EI) and English classroom learning anxiety at three universities in Hangzhou, People's Republic of China. Results obtained from the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF) and the Foreign Language Classroom Anxiety Scale (FLCAS) showed the following results: (a) More than half of the Chinese college students possessed a middle to high level of EI and at least one third experienced language anxiety in English class; (b) Moderate to relatively strong associations were found among students' EI, foreign language anxiety (FLA), English achievement, and self-rated English proficiency; (c) FLA had a significant and partial mediating effect on EI in predicting students' English achievement; and (d) FLA also significantly and partially mediated the relationship between EI and self-rated English proficiency. Results and implications are discussed in the context of the importance of emotional factors affecting the learning of English. [ABSTRACT FROM AUTHOR]

Abstract: The adsorption behaviors of n-hexane vapor onto macroporous and hypercrosslinked polymeric resins were investigated. All adsorption isotherms were nonlinear and well fitted with Dubinin–Astakov equation. The equilibrium adsorption data showed that the adsorption capacities of hypercrosslinked polymeric resin (Hyper-resin) were superior to macroporous polymeric resin (Macro-resin) for lower concentration of n-hexane; however, Macro-resin had higher adsorption capacities than Hyper-resin for higher concentration of hexane. The isosteric enthalpies of adsorption for n-hexane were calculated. The Hyper-resin exhibited much higher values of △H st for n-hexane than Macro-resin at the whole loading studied, indicating that the interaction force of n-hexane adsorption onto Hyper-resin was larger than Macro-resin. The consecutive column adsorption–desorption cycles were carried out to investigate the dynamic adsorption characteristics. The results revealed that the breakthrough adsorption capacities of n-hexane onto the virgin Hyper-resin were about 105% and 43% higher than those onto the virgin Macro-resin when the initial concentrations of n-hexane were 85mg/g and 510mg/g, respectively. Due to higher regeneration efficiency, however, the breakthrough capacities of the regenerated Macro-resin were higher than those of the regenerated Hyper-resin for the adsorption of higher concentration n-hexane. [Copyright &y& Elsevier]

A compact ultra-wideband bandpass filter is presented. The proposed UWB filter consists of a couple of folded parallel lines and a low-pass filter based on defected ground structure. Good bandpass performance and wide rejection characteristics can be achieved by this new structure. One prototype is fabricated to demonstrate the validity of the proposed strategies. The simulated and measured results indicated that the insertion loss is less than 1.5 dB between the 3.1 and 10.5 GHz with a sharp falling edge of 35 dB/GHz and its group delay is less than 0.5 ns in the pass band. The rejection is better than 20 dB from 12.5 to 25 GHz. The total size of the UWB BPF is 0.78 λ × 0.23 λ where λ is the guided wavelength at the center frequency of 7.4 GHz. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26045 [ABSTRACT FROM AUTHOR]

Dual ligands (BSA and L-histidine)-enhanced fluorescence and stability of BSA-CuNCs@L-His was prepared by one-step wet chemical method due to forming the stronger interaction of L-His and Cu and producing bigger diameter CuNCs by coordination-induced aggregation. Subsequently, a new and simple RF-probe was obtained based on doxycycline (DOX) simultaneously adjusting the FL intensities of the CuNCs at 410 and 520 nm. Therefore, the RF-probe could be used for sensitively and selectively monitoring DOX, while other tetracycline antibiotics with similar structures (TCH, OTH and CTH) exhibited little response to the BSA-CuNCs@L-His. In addition, the RF-probe was extended to the assay of DOX in actual samples. [Display omitted] • Studying effect of dual ligands (BSA and L-His) on the QYs and stability of CuNCs. • Detection mechanism of DOX by the RF-probe (BSA-CuNCs@L-His) was discussed. • The RF-probe could monitor sensitively DOX over other tetracycline antibiotics. A water-soluble, stable, simple and dual ligands (bovine serum albumin and L-histidine)-enhanced copper nanoclusters (BSA-CuNCs@L-His) was synthesized by one-step wet chemical method. Interestingly, the introduction of L-His ligand could improve evidently the quantum yields (QYs, 3.47%) and stability of BSA-CuNCs due to forming the stronger interaction of L-His and Cu and producing bigger diameter CuNCs by coordination-induced aggregation. Thus, a new ratiometric fluorescent probe (RF-probe) was successfully exploited for sensitively and selectively mensurating doxycycline (DOX) because DOX could simultaneously regulate the fluorescence (FL) intensities of BSA-CuNCs@L-His at 410 and 520 nm. The FL quenching of BSA-CuNCs@L-His at 410 nm by DOX was mainly originated from the static quenching process, while DOX could bind to Trp-212 in BSA from the skeleton of BSA-CuNCs@L-His by electrostatic interaction causing the appearance of new emission peak at 520 nm. The content of DOX was monitored by the RF-probe with a linear range of 0.05–14.0 μM and a LOD (limit of detection) and LOQ (limit of quantification) of 6.4 and 21.3 nM (at 3σ/slope and 10σ/slope). Moreover, compared to the standard HPLC method, the proposed RF-probe was extended to the detection of DOX in doxycycline hydrochloride (DOXH) tablets, DOXH injections and DOXH capsules with satisfactory results. [ABSTRACT FROM AUTHOR]

Alliance between doping Ag and dual ligands (BSA and TSA)-enhanced fluorescent gold nanoclusters as a probe was prepared by one-step wet chemical synthesis method, and the probe has remarkable selectivity and sensitivity for monitoring VB12/CCH. The fluorescence quenching of the alloy NCs by VB12/CCH comes from Förster resonance energy transfer combined with inner filter effect. [Display omitted] • Enhanced fluorescent AuNCs as a probe was developed. • Discussing effects of doping Ag and dual ligands on the synthesis of AuNCs. • Analyzing fluorescence quenching mechanism of the Au/AgNCs-VB12/CCH system. • The probe was successfully used for monitoring VB12/CCH in real samples. A stable, water-soluble, heightened quantum yields (QYs) Au nanoclusters by the alliance between doping Ag and dual ligands (thiosalicylic acid and bovine serum albumin) (TSA/BSA-Au/AgNCs) was prepared using one-step wet chemical synthesis. The effect of different types of aromatic thiols and the molar ratio of Au-Ag on the photo-luminescence performance of AuNCs was discussed in detail. The alloy NCs is shown to be viable fluorescent method for vitamin B12 (VB12) and chlortetracycline hydrochloride (CCH) assays, and become an excellent temperature sensor in the range of 10–50 °C. The fluorescence (FL) of TSA/BSA-Au/AgNCs was quenched with the addition of VB12 or CCH coming from Förster resonance energy transfer (FRET) combined with inner filter effect (IFE). The method can detect VB12/CCH by fluorometry with a linear response in the range of 0.33–60.0/0.33–60.0 μmol·L−1 and a 71.0/64.0 nmol·L−1 detection limit (at 3σ/slope). Furthermore, the proposed method was extended to the assays of VB12 in mineral water or tablets and CCH in veterinary drug or ointment with satisfactory results. [ABSTRACT FROM AUTHOR]

Abstract: Ti(IV)-functionalized derivatives of mesostructured HMS and MCM-41 silica with 3D wormhole and 1D hexagonal framework structures, respectively, were examined as catalysts for the oxidation of 4-tert-butyltoluene to 4-tert-butylbenzaldehyde using tert-butylhydroperoxide (TBHP) and aqueous hydrogen peroxide as oxidizing agents in acetonitrile solution. In an effort to achieve optimal site-isolation of reactive Ti(IV) centers, functionalization was carried out through the grafting of titanocene dichloride to the framework walls of the pre-assembled mesostructures, followed by calcination. Clear evidence for the undesirable clustering of Ti(IV) centers with increasing Ti(IV) loading was obtained by UV–Vis spectroscopy. Thus, the Ti(IV)-loading in the silica framework was limited to values below 8mol%. Maximal 23.6% and 21.8% conversions of 4-tert-butyltoluene to 4-tert-butylbenzaldehyde with >99% selectivity were observed for 4.8% Ti-HMS and 4.8% Ti-MCM-41 catalysts using TBHP as the oxidant. Substantially lower conversions were obtained with H2O2 as the oxidant due to clustering of Ti(IV) centers under reaction conditions and the catalyzed disproportionation of H2O2 by those clusters. A 2.0% Ti-HMS derivative prepared by direct assembly from tetraethylorthosilicate and tetraisopropylorthotitanate, denoted Ti-HMS(DS), was less active than Ti(IV)-functionalized mesostructures prepared by post-assembly grafting reaction with titanocene dichloride. Direct assembly places too much Ti(IV) at inaccessible positions within the framework walls, whereas grafting ensures optimal access to site-isolated Ti(IV) sites at the pore surfaces. [Copyright &y& Elsevier]

This article discusses an intervention project by means of motivational approaches in a British culture survey course for English majors in mainland China's university classroom context. The intervention uses such motivational theories as attribution and task orientation to motivate the teaching and learning of the EFL course so as to create a cooperative classroom environment. Theoretical bases of the Chinese heritage culture and motivation are examined, specific intervention procedures discussed, relevant data analysed and finally some suggestions regarding the EFL teachers' important role in promoting the quality of EFL education are made. The intervention results show that an innovative pedagogy to motivate students' metacognitive awareness, cognitive and socio‐cognitive ability in cooperative classroom learning situations different from the traditional cramming methods and examinations proves effective. Motivation should be given a central role in promoting China's EFL quality education. [ABSTRACT FROM AUTHOR]

In this paper, a criterion on the semi-simplicity of the cyclotomic Brauer algebras is given. This result can be considered as a generalization of Wenzl''s theorem on Brauer algebras [Ann. of Math. 128 (1988) 173–193], which was known as Hanlon–Wales conjecture before. [Copyright &y& Elsevier]

To facilitate better implementation of flood control and risk mitigation strategies, a model for evaluating the flood defense capability of China is proposed in this study. First, nine indicators such as slope and precipitation intensity are extracted from four aspects: objective inclusiveness, subjective prevention, etc. Secondly, the entropy weight method in the multi-attribute decision making (MADM) model and the improved three-dimensional technique for order preference by similarity to ideal solution (3D-TOPSIS) method were combined to construct a flood defense capacity index evaluation system. Finally, the receiver operating characteristic (ROC) curve and the Taylor plot method were innovatively used to test the model and indicators. The results show that nationwide, there is fine flood defense performance in Shandong, Jiangsu and room for improvement in Guangxi, Chongqing, Tibet and Qinghai. The good representativity of nine indicators selected by the model was verified by the Taylor plot. Simultaneously, the ROC calculated area under the curve (AUC) was 70%, which proved the good problem-solving ability of the MADM-GIS model. An accurate assessment of the sensitivity of flood control capacity in China was achieved, and it is suitable for situations where data is scarce or discontinuous. It provided scientific reference value for the planning and implementation of China's flood defense and disaster reduction projects and emergency safety strategies. [ABSTRACT FROM AUTHOR]

2,3,5,4′-Tetrahydroxystilbene-2-O-β- d -glucoside (TSG) is the key bioactive ingredient extracted from Polygonum multiflorum Thumb. Pharmacological studies suggest that it exerts numerous biological effects, including anti-oxidant, anti-aging, and anti-inflammation. This study aimed at investigating the effect of TSG on diethylnitrosamine (DEN)-induced acute hepatotoxicity and DNA damage. Fifty male C57BL/6 mice were randomly divided into 5 groups (n = 10 each): control, DEN, DEN+TSG (low), DEN+TSG (high) and TSG (high) groups. DEN (100 mg/kg) was injected intraperitoneally (i.p.) alone or with TSG (30 or 60 mg/kg, i.p.) for 5 consecutive days. TSG inhibited liver injury and inflammatory cell infiltration in DEN-treated mice. It also attenuated DEN-induced accumulation of reactive oxygen species (ROS), proinflammatory cytokines, and DNA damage. Moreover, TSG promoted the expression of nuclear erythroid 2-related factor 2 (Nrf2) target antioxidant genes by enhancing Nrf2 protein phosphorylation and nuclear translocation. As major phase I detoxification enzymes, cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 1 subfamily A member 1 (CYP1A1) are responsible for the metabolic activation of DEN. We found that TSG administration inhibited CYP2E1 and CYP1A1 induction in DEN-treated mice. These results indicate that TSG can alleviate DEN-induced acute hepatotoxicity by modulating the Nrf2-related antioxidant system and metabolic activation of DEN. Therefore, TSG might be a promising medication for DEN-induced liver injury treatment. Unlabelled Image [ABSTRACT FROM AUTHOR]

Drought is influenced by numerous factors, and traditional studies have only considered meteorological factors, but human activities are also an important influencing factor. From 1980 to 2010, the reform and opening up and the project of returning farmland to forest have largely changed the land use type of Loess Plateau in Shaanxi. In order to study the influence of land use types on drought in the study area, 8 stations with different land use types were selected based on remote sensing data and meteorological data. Based on univariate linear regression, the response of the drought index SPI to land use types was analyzed sequentially in each of the five time stages. The results showed that from 1980 to 2000, forest had the greatest drought intensity, followed by arable land and town and country. However, the response of arable land to the drought index was the greatest, followed by town and country. Forest had the weakest response to the drought index. From 2000 to 2010, the greatest degree of drought was observed in forest, followed by town and country and arable land. And forest has the strongest response to the drought index, followed by town and country, and finally, arable land. The area of forest, grass and town and country keeps increasing. The area of arable land is decreasing year by year. Land use types are constantly undergoing complex transformations. The drought index responds strongly to the change of both arable land to grass and arable land to town and country, while it responds weakly to the mutual transformation of both grass and town and country. In the areas where meteorological conditions are difficult to change, the local drought is considered to be improved by changing the substrate type. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study used APP/PS1 mice as an animal model of AD and amyloid-β (Aβ)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aβ deposition in mice and apoptosis, respectively. Protein expression was assessed by Western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of Sirt4. Subsequently, the binding of transcription factors to Sirt4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aβ-treated HT-22 cells compared with their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aβ deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD. NEW & NOTEWORTHY: The study reveals that in Alzheimer's disease models, SIRT4 expression increases, contributing to neuronal apoptosis and amyloid-β deposition. Reducing SIRT4 lessens apoptosis and amyloid-β accumulation, improving memory in mice. This process involves the mTOR pathway, regulated by STAT2 transcription factor. These findings suggest targeting the STAT2-SIRT4-mTOR axis as a potential Alzheimer's treatment strategy. [ABSTRACT FROM AUTHOR]

In this paper, a novel meta‐grounded planar bandpass filter is presented, facilitating much broader upper stopband. The proposed filter is comprised of a strip layer on the top, a dielectric laminate in the middle and a meta‐grounding layer on the bottom. The strip on the top consists of three cross‐shaped resonators in cascade. Instead of perfect conducting ground, a meta‐ground, composed by a group of metallic mushroom lattices with different characteristic dimensions, is proposed for broadening the upper stopband. In order to validate the proposed concept, we design and fabricate a prototype filter with a center frequency of 11.6 GHz, which exhibits an extremely broad upper stopband from 17.6 GHz to 72.2 GHz with a rejection level greater than 20 dB. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the effect of miR-21-5p on process of colon adenocarcinoma (COAD) cells and its connection with neural cell adhesion molecule L1 ( CHL1 ). Methods: Different expressions of mRNAs and miRNAs were calculated with microarray analysis. QRT-PCR and western blot were performed to quantify miR-21-5p and CHL1 expression. Flow Cytometry, MTT assay, colony formation assay, transwell assay and ELISA were performed to evaluate propagation and invasiveness of COAD cells. Dual luciferase reporter assay was employed to scrutinize the relationship between miR-21-5P and CHL1. We performed in vivo experiment to detect the impact of miR-21-5p and CHL1 on COAD tumor growth. Results: Expression level of miR-21-5p increased in both COAD tissues and cells. MTT and Cell cycle assay showed that overexpression of miR-21-5p accelerated proliferation of COAD cells. Transwell assay indicated that miR-21-5p promoted cell invasion. The result of dual luciferase reporter assay indicated that miR-21-5p targeted CHL1 directly and inhibited its expression. The result of in vivo experiments showed that down-regulation of miR-21-5p decreased the volume and weight of tumor, while knockdown of CHLI stimulated tumor growth. Conclusions: The overexpression of miR-21-5p can promote propagation and invasiveness of COAD cells through inhibiting the expression of CHL1. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is an irreversible neurodegenerative disease, and astrocytes play a key role in its onset and progression. The aim of this study is to analyze the characteristics of neurotoxic astrocytes and identify novel molecular targets for slowing down the progression of AD. Single-nucleus RNA sequencing (snRNA-seq) data were analyzed from various AD cohorts comprising about 210,654 cells from 53 brain tissue. By integrating snRNA-seq data with bulk RNA-seq data, crucial astrocyte types and genes associated with the prognosis of patients with AD were identified. The expression of neurotoxic astrocyte markers was validated using 5 × FAD and wild-type (WT) mouse models, combined with experiments such as western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence. A group of neurotoxic astrocytes closely related to AD pathology was identified, which were involved in inflammatory responses and pathways related to neuron survival. Combining snRNA and bulk tissue data, ZEP36L, AEBP1, WWTR1, PHYHD1, DST and RASL12 were identified as toxic astrocyte markers closely related to disease severity, significantly elevated in brain tissues of 5 × FAD mice and primary astrocytes treated with Aβ. Among them, WWTR1 was significantly increased in astrocytes of 5 × FAD mice, driving astrocyte inflammatory responses, and has been identified as an important marker of neurotoxic astrocytes. snRNA-seq analysis reveals the biological functions of neurotoxic astrocytes. Six genes related to AD pathology were identified and validated, among which WWTR1 may be a novel marker of neurotoxic astrocytes. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a major public health problem affecting older people. This study aimed to investigate the prevalence and clinical risk factors of insomnia in a representative sample of Chinese elderly (≥ 60 years) in Chongqing. Methods: A cross‐sectional study based on comprehensive geriatric assessment was conducted from January 2013 to February 2014. A questionnaire on sleep status was provided to each patient and insomnia was assessed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria. A multivariate logistic regression model was used to illustrate risk factors correlated with insomnia. Results: Of the total 597 participants, 55.4% suffered from insomnia. The prevalence of insomnia in men and women was 48.2% and 63.2%, respectively. Coronary heart disease, dizziness, chronic pain, anorexia, malnutrition, depression and cognitive decline were identified as risk factors associated with insomnia. Hypertension, diabetes, hyperlipidaemia, headache, age and education level were not observed to be significantly associated with insomnia. Conclusions: Insomnia is highly prevalent among the elderly in Chongqing, and shows a positive correlation to coronary heart disease, dizziness, chronic pain, anorexia, malnutrition, depression, cognitive impairment. Moreover, women are more likely to experience insomnia than men. [ABSTRACT FROM AUTHOR]

(1) Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that threatens the population health of older adults. However, the mechanisms of the altered metabolism involved in AD pathology are poorly understood. The aim of the study was to identify the potential biomarkers of AD and discover the metabolomic changes produced during the progression of the disease. (2) Methods: Gas chromatography–mass spectrometry (GC–MS) was used to measure the concentrations of the serum metabolites in a cohort of subjects with AD (n = 88) and a cognitively normal control (CN) group (n = 85). The patients were classified as very mild (n = 25), mild (n = 27), moderate (n = 25), and severe (n = 11). The serum metabolic profiles were analyzed using multivariate and univariate approaches. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify the potential biomarkers of AD. Biofunctional enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. (3) Results: Our results revealed considerable separation between the AD and CN groups. Six metabolites were identified as potential biomarkers of AD (AUC > 0.85), and the diagnostic model of three metabolites could predict the risk of AD with high accuracy (AUC = 0.984). The metabolic enrichment analysis revealed that carbohydrate metabolism deficiency and the disturbance of amino acid, fatty acid, and lipid metabolism were involved in AD progression. Especially, the pathway analysis highlighted that l−glutamate participated in four crucial nervous system pathways (including the GABAergic synapse, the glutamatergic synapse, retrograde endocannabinoid signaling, and the synaptic vesicle cycle). (4) Conclusions: Carbohydrate metabolism deficiency and amino acid dysregulation, fatty acid, and lipid metabolism disorders were pivotal events in AD progression. Our study may provide novel insights into the role of metabolic disorders in AD pathogenesis and identify new markers for AD diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Based on readily available demographic data, neuropsychological assessment results, and comorbidity data, we aimed to develop and validate a 3-year survival prediction model for patients with cognitive impairment. Methods: In this prospective cohort study, 616 patients with cognitive impairment were included. Demographic information, data on comorbidities, and scores of the Mini-Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL) scale, and Neuropsychiatric Inventory Questionnaire were collected. Survival status was determined via telephone interviews and further verified in the official death register in the third year. A 7:3 ratio was used to divide patients into the training and validation sets. Variables with statistical significance (p < 0.05) in the single-factor analysis were incorporated into the binary logistic regression model. A nomogram was constructed according to multivariate analysis and validated. Results: The final cohort included 587 patients, of whom 525 (89.44%) survived and 62 (10.56%) died. Younger age, higher MMSE score, lower IADL score, absence of disinhibition, and Charlson comorbidity index score ≤ 1 were all associated with 3-year survival. These predictors yielded good discrimination with C-indices of 0.80 (0.73–0.87) and 0.85 (0.77–0.94) in the training and validation cohorts, respectively. According to the Hosmer–Lemeshow test results, neither cohort displayed any statistical significance, and calibration curves displayed a good match between predictions and results. Conclusions: Our study provided further insight into the factors contributing to the survival of patients with cognitive impairment. Clinical Implications: Our model showed good accuracy and discrimination ability, and it can be used at community hospitals or primary care facilities that lack sophisticated equipment. [ABSTRACT FROM AUTHOR]

Background and Aims: Chromoendoscopy with Lugol's staining is used to screen for early esophageal squamous cell carcinoma (ESCC). Its efficacy is greatly limited by unstandardized defoaming preparation. This study aimed to confirm whether pre-procedure oral administration of pronase could improve the diagnostic performance of Lugol chromoendoscopy in high-risk patients being screened for early ESCC. Methods: A total of 955 patients at-risk were prospectively recruited for screening for ESCC. Patients were randomly assigned (1:1) to groups with or without (control group) pronase administration. Endoscopic diagnosis of early ESCC was based on the presence of pink-color sign in Lugol's unstained area, and a biopsy was routinely conducted if the Lugol's unstained lesion was larger than 0.5 cm. The early cancer detection rate was used as the primary endpoint. Results: Pre-procedure oral administration of pronase improved mucosal visibility during Lugol chromoendoscopy (P = 0.008). There were no differences in the number of Lugol's unstained lesions between the 2 groups (23.27% [111/477] vs. 25.11% [120/478], P = 0.508). Meaningfully, the detection rate of ESCC (confirmed by histopathology) was significantly higher in the pronase group than in the control group (27.03% [30/111] vs. 17.50% [21/120], P = 0.041), as well as the detection rate of lesions with pink-color sign during chromoendoscopy (35.14% [39/111] vs. 13.33% [16/120], P < 0.001). The diagnostic performance of Lugol chromoendoscopy had improved with the use of pronase (area under the curve = 0.85 vs. 0.69, P = 0.019), accompanied by an increased sensitivity (86.67% vs. 47.62%, P = 0.004). There was no difference in the adverse events between the 2 groups (P = 0.793). Conclusions: Pre-procedure oral administration of pronase significantly increased the detection rate of early ESCC and optimized the diagnostic performance of Lugol chromoendoscopy, which should be recommended during routine endoscopic screening for early ESCC in high-risk patients. Trial registration: Pronase improves efficacy of Lugol chromoendoscopy screening on esophageal cancerous lesions (NCT02030769). [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model. And palmitic acid (PA) treatment increased the miR-181b expression while decreased SIRT1 expression in HepG2 cells. Further, we identified that SIRT1 is a direct downstream target of miR-181b. Ectopic expression of miR-181b significantly repressed the 3′-UTR reporter activities of SIRT1 in a dose-dependent manner, while the effect of miR-181b was interrupted when the binding site of miR-181b within the SIRT1 3′-UTR was mutated. And overexpression of miR-181b reduced both the mRNA and protein levels of SIRT1 in HepG2 cells. We also found that inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo . And the effect of miR-181b on steatosis was blocked by SIRT1 overexpression. Taken together, our data indicated that increased expression of miR-181b potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target SIRT1. [ABSTRACT FROM AUTHOR]

Irisin is an exercise-induced myokine that alleviates inflammation and obesity. The induction of anti-inflammatory (M2) macrophage is facilitated for treatment of sepsis and associated lung damage. However, whether irisin drives macrophage M2 polarization remains unclear. Here, we found that irisin induced-macrophage anti-inflammatory differentiation in vivo using an LPS-induced septic mice model and in vitro using RAW64.7 cells and bone marrow-derived macrophages (BMDMs). Irisin also promoted the expression, phosphorylation, and nuclear translocation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and nuclear factor-erythroid 2-related factor 2 (Nrf2). Inhibition or knockdown of PPAR-γ and Nrf2 abolished irisin-induced accumulation of M2 macrophage markers, such as interleukin (IL)-10 and Arginase 1. Furthermore, dual-luciferase reporter and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays confirmed that STAT6 boosts PPAR-γ and Nrf2 transcription by binding to their DNA promoters in irisin-stimulated macrophages. In contrast, STAT6 shRNA blocked the irisin-induced activation of Pparγ, Nrf2 , and related downstream genes. Moreover, the interaction of irisin with its ligand integrin αVβ5 remarkably promoted Janus kinase 2 (JAK2) phosphorylation, while inhibition or knockdown of integrin αVβ5 and JAK2 attenuated the activation of STAT6, PPAR-γ, and Nrf2 signaling. Interestingly, co-immunoprecipitation (Co-IP) assay also revealed that the binding between JAK2 and integrin αVβ5 is critical for irisin-induced macrophage anti-inflammatory differentiation by enhancing the activation of the JAK2-STAT6 pathway. In conclusion, irisin boosted M2 macrophage differentiation by inducing JAK2-STAT6-dependent transcriptional activation of the PPAR-γ-related anti-inflammatory system and Nrf2-related antioxidant genes. The findings of this study suggest that the administration of irisin is a novel and promising therapeutic strategy for infectious and inflammatory diseases. [Display omitted] • Irisin drives anti-inflammatory macrophage differentiation. • STAT6 directly promotes the transcription of PPAR-γ and Nrf2 in irisin-treated macrophages. • The binding of JAK2 and irisin membrane ligand integrin αVβ5 enhances the activation of JAK2-STAT6 signaling pathway. • Irisin is a novel therapeutic strategy for infectious, inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Screening cognitive impairment is complex and not an appliance for early screening. Gait performance is strongly associated with cognitive impairment. Objectives: We aimed to explore gait indicators that could potentially screen cognitive dysfunction. Methods: A total of 235 subjects were recruited from June 2021 to June 2022. Four gait tasks, including the walking test, the timed "Up & Go" test (TUG), foot pressure balance (FPB), and one-legged standing with eyes closed test (OLS-EC), were performed. Moreover, in the walking test, participants were instructed to walk at their usual pace for the single-gait test. For the dual-task tests, participants walked at their usual pace while counting backward from 100 by 1s. The data were analyzed by the independent sample t-test, univariate and multivariate logistic regression, a linear trend, stratified and interaction analysis, the receiver operating characteristic (ROC) curve, and Pearson's correlations. Results: Among the 235 participants, 81 (34.5%) were men and 154 (65.5%) were women. The mean age of participants was 72 ± 7.836 years. The control, MCI, mild AD, and severe AD groups had means of 71, 63, 71, and 30, respectively. After adjusting for age, sex, education, and body mass index (BMI), the dual-task toe-off-ground angle (TOA) (odds ratio (OR) = 0.911, 95% confidence interval (CI): 0.847, 0.979), single-task TOA (OR = 0.904, 95% CI: 0.841–0.971), and the timed "Up & Go" time (TUGT) (OR = 1.515, 95% CI: 1.243–1.846) were significantly associated with an increased risk of cognitive impairment. In addition, the trend test and stratified analysis results had no significant differences (all p > 0.05). The area under the roc curve (AUC) values of TOA in the dual-task and TUGT were 0.812 and 0.847, respectively. Additionally, TOA < 36.75° in the dual-task, TOA < 38.90° in the single-task, and TUGT > 9.83 seconds (s) are likely to indicate cognitive impairment. The cognitive assessment scale scores were significantly correlated with TOA (all r > 0.3, p < 0.001) and TUGT (all r > 0.2), respectively. Conclusion: TOA and TUGT scores are, in some circumstances, associated with cognitive impairment; therefore, they can be used as simple initial screenings to identify patients at risk. [ABSTRACT FROM AUTHOR]

Frailty, cognitive decline, and depression are common syndromes among the elderly and are closely interconnected. However, it is still unclear whether the impact of frailty on depression depends on the role of cognitive decline. We conducted the Mendelian randomization (MR) analysis based on the instrumental variables (IVs) from the genome-wide association study (GWAS) databases, and we also performed a cross-sectional study consisting of 1362 older adults aged ≥65 for validation. The results of the multivariable MR analysis showed that frailty significantly increased the risk of depression, even after controlling for the influence of cognitive performance. Conversely, after controlling for frailty, the effect of cognitive performance on depression risk was noticeably reduced. In the cross-sectional study, frailty mediated 24.04 % of the relationship between cognition and depression, and cognition mediated 7.63 % of the relationship between frailty and depression. We provide evidence that frailty could increase depression risk independently of cognitive decline. Further research with a larger sample size is necessary. • Frailty as a more aggressive player for depression risk than cognitive impairment • Independent role of frailty in aggravating depression risk • Mendelian causality between frailty and depression validated by real-world cross-sectional study • Imbalanced co-operation between frailty and cognition in augmenting the prevalence of depression [ABSTRACT FROM AUTHOR]