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Background: Olfactory dysfunction appears prior to cognitive decline, and thus it has been suggested to be an early predictor of Alzheimer’s disease. However, it is currently not known whether and how olfactory threshold test could serve as a quick screening tool for cognitive impairment. Objective: To define olfactory threshold test for screening cognitive impairment in two independent cohorts. Methods: The participants are comprised of two cohorts in China, 1,139 inpatients with type 2 diabetes mellitus (T2DM, Discovery cohort) and 1,236 community-dwelling elderly (Validation cohort). Olfactory and cognitive functions were evaluated by Connecticut Chemosensory Clinical Research Center test and Mini-Mental State Examination (MMSE), respectively. Regression analyses and receiver operating characteristic (ROC) analyses were carried out to determine the relation and discriminative performance of the olfactory threshold score (OTS) regarding identification of cognition impairment. Results: Regression analysis showed that olfactory deficit (reducing OTS) was correlated with cognitive impairment (reducing MMSE score) in two cohorts. ROC analysis revealed that the OTS could distinguish cognitive impairment from cognitively normal individuals, with mean area under the curve values of 0.71 (0.67, 0.74) and 0.63 (0.60, 0.66), respectively, but it failed to discriminate dementia from mild cognitive impairment. The cut-off point of 3 showed the highest validity for the screening, with the diagnostic accuracy of 73.3% and 69.5%. Conclusion: Reducing OTS is associated with cognitive impairment in T2DM patients and the community-dwelling elderly. Therefore, olfactory threshold test may be used as a readily accessible screening tool for cognitive impairment.

This article selects 10 companies in the financial sector, energy sector and consumption sector, as well as SPX500 index. This paper uses two models, not only the Markowitz model but also the index model, to calculate the correlation coefficient matrix, minimum variance, maximum Sharpe ratio, capital allocation line and so on to analyze the return rate and volatility of 10 specific companies. Four limitations were calculated for Markowitz model and Index model respectively and the two models were compared under the same constraints. Because common financial constraints and specific industries are rarely noticed in reality, the results of this paper reflect the following three aspects: First, in order to strike a balance between risk and return, SPX is an investment worth considering due to its high correlation coefficient; the second is that for certain investors with added constraints, the capital allocation line performs relatively poorly, as does the minimum variance boundary. Thirdly, because the Markowitz model uses stock's covariance while the beta and alpha of stocks are components that the index model uses to construct a portfolio, the results show that under certain risk conditions, Markowitz model is inferior to index model in pursuing maximum return and minimum risk under certain return conditions.

Purpose Quantitative fretting wear prediction is of practical significance for industrial components. This study aims to establish a fretting wear model considering the formation of tribolayers and provide better fretting wear prediction. Design/methodology/approach Based on the characteristics for the formation of tribolayers, the ratio of fretting amplitude to nominal contact area length in the fretting direction is used to characterize their formation and contribution to the wear volume. The wear volume is then associated with the product of the friction energy and the ratio of fretting amplitude to nominal contact area length. Findings Better prediction in the wear volume can be achieved with the proposed fretting wear model by taking the formation of tribolayers into consideration. Originality/value The contribution of the formation of tribolayers to the wear volume is considered in the model and better prediction can be achieved. Peer review The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-01-2023-0004/

An indoor corrosion simulation experiment device was built to explore the influence of dynamic alternating current (AC) interference on the corrosion behavior of pipeline steel under different cathodic protection (CP) levels. When the interference time in each interference cycle is 350 s, the dynamic AC corrosion rate was comparable to the steady AC corrosion rate. For JAC of 30 A/m2, the corrosion rate of the specimen can be controlled below 0.0254 mm/y when the CP current density is higher than 0.06 A/m2. As JAC is greater than or equal to 100 A/m2, with the increase of the CP current density, the corrosion rate of the specimens decreased first, then increased and decreased again. In this paper, the real-time AC/DC potential on the surface of the specimen is monitored, combined with the Pourbaix diagram and the evolution of corrosion product film. The dynamic AC corrosion mechanism under different CP levels was explored.

We study the influence of bank competition on U.S. public borrowers’ accounting conservatism by exploiting the staggered adoption of the Riegle-Neal Interstate Banking and Branching Efficiency Act (IBBEA) of 1994, which increased the threats of new bank entrants and actual bank entry. We find that borrowers’ conditional conservatism fell after IBBEA. Conservatism fell more for firms located in states with weak incumbent banks and states with more out-of-state entrants, especially entrants with better monitoring technologies. The decrease in conservatism partially stems from borrowers’ increased investment and risk-taking incentives. Conservatism fell more for firms relying more on bank loans, especially those that borrowed loans for the first time after IBBEA and for firms having lower dedicated institutional ownership and board independence. We also find that loans included fewer covenants and that bank loan borrowers became less likely to choose Big N auditors and industry specialist auditors after IBBEA. Data Availability: Data are available from the public sources cited in the text. JEL Classifications: G21; G28; K23; M41.

The workload co-location, such as deploying offline analysis workloads with online service workloads on the same node, has become common for modern data centers. Workload co-location deployment improves data center resource utilization significantly. Still, it also introduces resource contention, resulting in the online service’s quality of service fluctuation, which we call performance interference. As the online service is a tail-latency-sensitive workload, the tail-latency metric can reflect the performance interference degree of the co-location workloads at the application level. However, to guide system design and evaluation, quantitatively evaluating the resource contention of the co-located workloads at the system level is also essential. This article proposes a novel metric called System-Level Entropy (SLE). As a system-level metric, SLE can measure quantitatively resource contention of the co-location systems and perform the apples-to-apples comparison between systems. The experimental results show that SLE can accurately reflect the performance interference of workloads and then evaluate the system resource contention. We also demonstrate two case studies of the SLE. We quantify the affinity of different co-location combinations, including three online services and five offline workloads. Furthermore, we evaluate the effects of state-of-the-art isolated mechanisms (the container and the CPU–affinity binding) with these co-location combinations.

Lightweight ceramsite is the core material for building to achieve energy-saving and low-carbon operation. The disposal of remediated soil by Cr (VI)-contaminated waste glass and ceramics after remediation has always been a major problem in the environmental field. Herein, it analyzed the composition and sintering process of the above three solid wastes, after studying the component preparation and firing process, lightweight ceramsites with bulk density and grain density of 626.79 kg/m3 and 1142.56 kg/m3, respectively, were successfully prepared, and the leaching concentration of Cr (VI) was controlled at a low concentration level below 0.06 mg/L. Compared with the conventional ceramsite preparation technology, the method of firing ceramsite by the remediated soil, waste glass and ceramics can effect eliminate the environmental risk of solid waste and effectively reduce the consumption of clay and other resources, which has the technical advantages of safety, reliability, green and low carbon.

The balance of light transmittance, durability and self-cleaning performance of the coating film is the main reason that hinders the wide application of photocatalytic self-cleaning coating on building exterior glass. In this article, TiO2 powder was prepared with different concentrations of tetrabutyl titanate, hydrochloric acid and ethanol; and following with compounded polyvinyl alcohol (PVA) and waterborne polyurethane as adhesives; the mixed composite coating was loaded on the glass surface by spraying method to obtain superhydrophilic glass with self-cleaning properties. The physical and chemical properties of TiO2 composite films were characterized and tested by diffraction, scanning electron microscopy, optical contact angle measuring instrument and photocatalytic testing system. The results showed that the X-ray diffractometer analysis of the powder obtained with different alcohol-ester ratios showed that the crystal synthesis was successful, and the grain size conformed to the nanometer standard. TiO2 dispersion with a concentration of 0.08 g/L, after 30 min of irradiation with an ultraviolet (UV) lamp, the methyl orange added dropwise in the solution can be completely degraded. With the increase of TiO2 concentration, the photocatalytic efficiency increased rapidly, the contact angle decreased, when the TiO2 concentration reached 0.3% and 3% binder compounding, the surface of the composite coating film was still smooth at the nanometer level, the visible light transmittance was between 86.95 and 88.89%, and the contact angle was reduced from the initial 46.49 to 14.89° after 2 h of UV illumination. After 5 repeated degradation experiments and outdoor 180-d standing test, the composite coating film has recyclability and good durability. Therefore, TiO2 composite coating prepared by this method has a wide application prospect in the daily cleaning and subsequent maintenance of building glass.

As the most widely used method for preparing graphene oxide (GO), Hummers' method always involves a key step, that is adding water to concentrated sulfuric acid. We found that if this process is cancelled, the oxidation degree of GO will be significantly reduced. This means that the heat released during concentrated sulfuric acid dilution will promote further oxidation of GO. In this paper, we fully utilize the heat released during concentrated sulfuric acid dilution to develop a new non-heat-source process without any low-/high-temperature auxiliar, exponentially reducing the energy consumption and largely avoiding the frequent temperature control. The result shows that GO prepared by Hummers' method and that prepared by the proposed process show a similar structure, composition, morphology, and defect degree. Meanwhile, the corresponding reduced GO (rGO) obtained after reduction shows similar capacitive behavior. Their specific capacitances are 243.6 F g

Since 2015, when General Secretary Xi Jinping proposed to promote the construction of "Digital China" at the Second World Internet Conference, and now the Fifth Digital China Construction Summit, digital industries have sprung up in China like a spring. Digital government, as an important support for social governance, is being explored and practiced in depth. However, in the process of digital technology continuously empowering the construction of grassroots government, the internal structural contradictions of government organizations are increasingly prominent, which restricts the improvement of digital government governance capacity. This paper selects the digital government construction in Yingzhou District, Fuyang City, Anhui Province, as a research object, focuses on the governance pain points in digital government construction, and explores new paths for the government organizational structure to move towards digitalization.

Objective: Public health emergencies, such as COVID-19, put forward a severe test to the response system of countries all over the world, including China. Especially under such conditions, the establishment and operation of the emergency drug approval system is particularly important. The purpose of this paper is to compare and analyze the emergency drug approval system between China and the United States, and learn from the experience of developed countries to improve China's drug review capability in response to public health emergencies. This paper mainly analyzes the emergency drug approval system of China and the United States under public health emergencies through literature research and comparative analysis theory. Although there are four channels to accelerate the approval of drugs for listing in China, none of them can solve the problem of emergency drug use in the face of public health emergencies, and cannot become the policy basis for the use of unlisted drugs or drugs beyond the instructions. Conclusion: On the basis of maintaining China's own institutional advantages and drawing on foreign experience, this paper puts forward relevant policy recommendations to improve China's emergency drug approval system in the event of public health emergencies.

Objective: This paper aims to provide reference for how to use the concept and method of QbD to control the quality of CAR-T cell therapy products in the commercial production of CAR-T cell therapy products in China, and how to formulate reasonable and effective quality control strategies. Methods: This paper systematically analyzes the industrial development of CAR-T cell therapy products and the concept, application methods and implementation process of QbD in China through literature research and case analysis theory Results: Cell therapy products are a hot area in the research and development of new drugs, but at present, there are no specific regulatory rules in the commercial production of CAR-T cell therapy products in China, the awareness of risk control is weak, and the quality control is unstable, making patients face many risks. Conclusion: Based on the concept of QbD, the quality control strategy of CAR-T cell therapy products was proposed from three dimensions.

Herein, a functional hybrid named metalloporphyrin hemin modified carbon nanotube decorated titanium carbide (Hemin/CNT/Ti

Ashwagandha (W. somnifera L) is a popular ethnomedicinal herb endowed with potential pharmacotherapeutic properties. In this study the ethanol extract (EE) and water extract (WE) of ashwagandha roots were qualitatively analysed using high performance liquid chromatography (HPLC), the results showed EE containing withanoside IV (a), physagulin D (b), 27-hydroxywithanone (c), withanoside V (d), withaferin A (e), withastramonolide (f), withanolide A (g), withanone (h), and withanolide B (i) as major bioactive compounds. Antioxidant potential was studied using four in vitro free radical scavenging assays and EE displayed higher antioxidant effect compared to WE for all assays. The EE also showed enzyme inhibitory effect against lipoxygenase (5-LOX) >cyclooxygenases-1 (COX-1) compared to cyclooxygenases-2 (COX-2) and to that of WE. Furthermore, EE demonstrated a potential cytotoxic effect on proliferation of A549 cells in vitro, showing IC50 values, 394.8 (24 h), 171.9 (48 h) and 126.1 (72 h) μg/mL, respectively. EE extract also exhibited induction of apoptosis in dose dependent manner confirmed with the production of ROS in A549 cells through flow cytometric analysis. The obtained results demonstrated that ashwagandha EE with high concentration of bioactive compounds could act as potential drug candidates against pro-inflammatory enzymes involved in development of inflammation and progression of lung cancer. Further, extensive research is needed to investigate the ashwagandha bioactive compounds responsible for treating inflammation, oxidative stress and lung cancer.

Objective: By introducing the pilot situation of post-market supervision of medical devices purchased by third-party institutions in Jiangsu Province, China, the problems exposed by them were analyzed. At the same time, it draws on relevant advanced experience in the management of EU notified bodies to provide suggestions for optimizing China's follow-up practices and promoting social co-governance supervision. Method: Conduct on-the-spot investigations in Jiangsu Provincial Food and Drug Administration, China, conduct interviews with regulators on the progress of the project, and conduct in-depth communication. A large number of inquiries about the relevant research literature of the EU notified body and the laws and regulations promulgated by the EU, and systematic analysis. Results: In the introduction of third-party agencies to assist post-market supervision of medical devices, the Chinese government still has problems such as lack of relevant laws and regulations, imperfect access mechanisms for third-party agencies, imperfect supervision mechanisms, and backward regulatory informatization construction. Conclusion: Introducing third-party agencies to assist in the supervision of medical devices can effectively ease the pressure on supervision and supplement supervision resources. It is suggested that the Chinese government learn from the management experience of the EU notified bodies, improve the regulatory legal system, introduce relevant regulations, improve the access mechanism of third-party institutions, improve the supervision mechanism, strengthen the construction of supervision informatization, and build a unified supervision platform.

Upper abdominal surgical treatment may reduce respiratory muscle function and mucociliary clearance, which might be a cause of postoperative pulmonary complications (PPCs). Threshold inspiratory muscle training (IMT) may serve as an effective modality to improve respiratory muscle strength and endurance in patients. However, whether this training could help patients with upper abdominal surgery remains to be determined. The aim of the present investigation was to determine the effect of a fully engaged IMT on PPCs and respiratory function in patients undergoing upper abdominal surgery. We hypothesized that the fully engaged IMT could reduce PPCs and improve respiratory muscle function in patients with upper abdominal surgery. This is a randomized controlled trial (RCT) with 28 patients who underwent upper abdominal surgery. Patients were randomly assigned to the control (CLT) group or the IMT group. The CTL group received regular health care. The IMT group received 3 weeks of IMT with 50% of MIP as the initial intensity before the operation. The intensity of MIP increased by 5–10% per week. The IMT was continued for 4 weeks after the operation. The study investigated the outcomes including PPCs, respiratory muscle strength, diaphragmatic function, cardiopulmonary function, and quality of life (QoL). We found that IMT improved respiratory muscle strength and diaphragmatic excursion. IMT also had a beneficial effect on the incidence of postoperative pulmonary complications (PPCs) compared to CLT care. The results from this study revealed that IMT provided positive effects on parameters associated with the respiratory muscle function and reduced the incidence of PPCs. We propose that fully engaged IMT should be a part of clinical management in patients with upper abdominal surgery.KEY MESSAGESThe fully engaged inspiratory muscle training reduces postoperative pulmonary complications rate in patients with upper abdominal surgery.The fully engaged inspiratory muscle training increases maximal inspiratory pressure in patients with upper abdominal surgery.The fully engaged inspiratory muscle training increases diaphragm function in patients with upper abdominal surgery.The fully engaged inspiratory muscle training increases the quality of life in patients with upper abdominal surgery. The fully engaged inspiratory muscle training reduces postoperative pulmonary complications rate in patients with upper abdominal surgery. The fully engaged inspiratory muscle training increases maximal inspiratory pressure in patients with upper abdominal surgery. The fully engaged inspiratory muscle training increases diaphragm function in patients with upper abdominal surgery. The fully engaged inspiratory muscle training increases the quality of life in patients with upper abdominal surgery.

Background Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Material and methods In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

Selexipag, a long-acting and selective prostacyclin (PGI

The typical symptoms of patients with Alzheimer’s disease (AD) are amyloid-β (Aβ) plaques and tau hyperphosphorylation. However, recent studies show that these symptoms are not the cause of the disease but are generated after the pathogenesis. Compared with other types of dementia, AD has the obvious features of pineal gland calcification and decreased melatonin production. The pineal gland is mainly composed of pinealocytes that release melatonin and astrocytes. Astrocytes function to maintain a balanced concentration of calcium ions, provide nerve cell nutrients, and migrate nutrients in vivo. Calcium ions are among the most important neurotransmitters. Once triggered, a calcium wave can be formed between astrocytes to activate other astrocytes to transmit information. Most calcium is stored in the skeleton. Bone tissue is composed mainly of osteocytes, osteoblasts, and osteoclasts. Of these, osteocyte is a kind of astrocyte which regulates the activity of osteoclasts and osteoblasts. The pineal gland is composed mainly of astrocytes; osteocytes are also a kind of astrocyte. Therefore, we conclude that when astrocytes are gradually disabled, calcium may be lost from the bones, prompting osteoporosis. The calcium ions then released into the blood may accumulate and cause ectopic calcification in the pineal gland, which promotes the occurrence of AD. Finally, this study used aspects of drugs and hormones (bone and calcium metabolism hormones and melatonin) to infer the hypothesis, which proposes that astrocyte dysregulation promotes the long-term imbalance of calcium ions in vivo and leads to osteoporosis and AD.

The transformation products of triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) may be more persistent and toxic than their parent compound, yet their occurrence in aquatic environments is poorly understood. In this study, we identified three transformation products in sediment samples from Taihu Lake and compared their concentrations with the parent compound triclosan. Triclosan in Taihu Lake was at low level, ranging from 0.086 to 1.1 ng/L in surface water and 0.0058-8.3 ng/g in sediments. The three detected transformation products included methyl triclosan, chlorinated triclosan derivatives, and methyl chlorinated triclosan derivatives. Those transformation products constituted 0.73-87.5% of the total triclosan (total triclosan is the sum of triclosan, methyl triclosan, chlorinated triclosan derivatives, and methyl chlorinated triclosan derivatives on a molar basis), indicating that the ecological risk of transformation products should be considered in addition to the parent compound. Different transformation products had distinct spatial distributions. Chlorinated triclosan derivatives had the highest concentration in samples from the northwest region (0.016-0.21 ng/g) of the lake and were positively correlated with triclosan, which may indicate the possible transformation from triclosan to chlorinated triclosan derivatives. Methyl triclosan and methyl chlorinated triclosan derivatives were generally higher in samples from the center of the lake (0.22-0.28 ng/g for methyl triclosan and 0.017-0.021 ng/g for methyl chlorinated triclosan derivatives, respectively), indicating the possible occurrence of in situ microbial methylation of triclosan and chlorinated triclosan derivatives and the accumulation of those methylated analogues in Taihu Lake.

Human mitochondrial NAD(P)+-dependent malic enzyme (ME2) is well-known for its role in cell metabolism, which may be involved in cancer or epilepsy. We present potent ME2 inhibitors based on cyro-EM structures that target ME2 enzyme activity. Two structures of ME2-inhibitor complexes demonstrate that 5,5’-Methylenedisalicylic acid (MDSA) and embonic acid (EA) bind allosterically to ME2’s fumarate-binding site. Mutagenesis studies demonstrate that Asn35 and the Gln64-Tyr562 network are required for both inhibitors’ binding. ME2 overexpression increases pyruvate and NADH production while decreasing the cell’s NAD+/NADH ratio; however, ME2 knockdown has the opposite effect. MDSA and EA inhibit pyruvate synthesis and thus increase the NAD+/NADH ratio, implying that these two inhibitors interfere with metabolic changes by inhibiting cellular ME2 activity. ME2 silence or inhibiting ME2 activity with MDSA or EA decreases cellular respiration and ATP synthesis. Our findings suggest that ME2 is crucial for mitochondrial pyruvate and energy metabolism, as well as cellular respiration, and that ME2 inhibitors could be useful in the treatment of cancer or other diseases that involve these processes.