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Accumulating studies have suggested that targeting transcription factor EB (TFEB), an essential regulator of autophagy‐lysosomal pathway (ALP), is promising for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, potent and specific small molecule TFEB activators are not available at present. Previously, we identified a novel TFEB activator named curcumin analog C1 which directly binds to and activates TFEB. In this study, we systematically investigated the efficacy of curcumin analog C1 in three AD animal models that represent beta‐amyloid precursor protein (APP) pathology (5xFAD mice), tauopathy (P301S mice) and the APP/Tau combined pathology (3xTg‐AD mice). We found that C1 efficiently activated TFEB, enhanced autophagy and lysosomal activity, and reduced APP, APP C‐terminal fragments (CTF‐β/α), β‐amyloid peptides and Tau aggregates in these models accompanied by improved synaptic and cognitive function. Knockdown of TFEB and inhibition of lysosomal activity significantly inhibited the effects of C1 on APP and Tau degradation in vitro. In summary, curcumin analog C1 is a potent TFEB activator with promise for the prevention or treatment of AD. A small molecule activator of transcription factor EB (TFEB) promotes the degradation of beta‐amyloid precursor protein (APP) fragments, β‐amyloid peptides (Aβ), and phosphorylated MAPT/Tau aggregates in three transgenic mice models of Alzheimer's disease (P301S, 5xFAD, and 3xTg) and prevents memory impairments.

Technical advancements significantly improve earlier diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various factors. We develop an artificial intelligence assistive diagnostic solution, AIATBS, to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria. We train AIATBS with >81,000 retrospective samples. It integrates YOLOv3 for target detection, Xception and Patch-based models to boost target classification, and U-net for nucleus segmentation. We integrate XGBoost and a logical decision tree with these models to optimize the parameters given by the learning process, and we develop a complete cervical liquid-based cytology smear TBS diagnostic system which also includes a quality control solution. We validate the optimized system with >34,000 multicenter prospective samples and achieve better sensitivity compared to senior cytologists, yet retain high specificity while achieving a speed of <180s/slide. Our system is adaptive to sample preparation using different standards, staining protocols and scanners. Technical advancements have significantly improved early diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various practical factors. Here, the authors develop an artificial intelligence assistive diagnostic solution to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria in a large multicenter study.

Mortise and tenon joints are widely used in the building and furniture industries because of their excellent mechanical and eco-friendly properties. In real-life cases, there are usually many available alternative structures for a joint area, it is a challenge to select a proper structure from massively available alternatives. This paper aims to select a proper multiple attribute decision-making method based on massive alternatives and unreliable, uncertain and subjective information. Pugh’s controlled convergence, rough number, Z-number, consistency theory and Shannon entropy are integrated and proposed an improved rough Z-number Multi-Attributive Border Approximation Area Comparison (MABAC) method. Firstly, Pugh’s controlled convergence is a selection method, simple and rapid, presented in the first phase to eliminate most of the alternatives. In the second phase, an integrated method is proposed. The consistency theory, distance measurement and the Z-number are initially aggregated to calculate the expert weight. The entropy method is then presented to determine the criteria weight. The alternatives are then ranked and the optimal mortise and tenon joint is selected based on the rough Z-number MABAC method. A real-life case is presented, and the proposed method is implemented in the joint of a bucket cabinet. Finally, the efficiency and effectiveness of the proposed method are proved by the case, sensitivity analysis and related comparisons.

A hydrothermal route is reported for the preparation of a composite consisting of sheet-like glucose-derived carbon and nickel oxide nanoparticles. The nanocomposites were prepared at different annealing temperatures and exploited as electrode materials for amperometric ( i - t ) determination of hydrazine (N 2 H 4 ) and hydrogen peroxide (H 2 O 2 ) at trace levels. The performances of the sensors were assessed by cyclic voltammetry and amperometry detection using a rotating disk electrode (RDE) technique. The modified electrode annealed at ca. 300 °C was found to exhibit the best electrocatalytic performance in terms of sensitive and selective detection of N 2 H 4 and H 2 O 2 even in the presence of interfering species. The electrode is inexpensive, robust, easy to prepare in large batches, highly stable, and has a low overpotential. H 2 O 2 can be sensed, best at a working voltage of typically 0.13 V vs Ag/AgCl; rotationg speed 1200 rpm) over a wide concentration range (0.01 to 3.9 µM) with a detection limit of 1.5 nM. N 2 H 4 can be sensed, best at a working voltage of typically 0.0 V within the concentration range from 0.5 μM to 12 mM with an excellent detection limit of 1.5 µM. Thus, this cost-effective and robust modified electrode, which may be readily prepared in large batch quantity, represents a practical platform for industrial sensing. Graphical abstract Schematic of the hydrothermal method for synthesis of carbon and nickel oxide nanoparticle composites (GCD/NiO-150, GCD/NiO-300, and GCD/NiO-450). The composite was used for the electro-oxidation of hydrazine (N 2 H 4 ) and hydrogen peroxide (H 2 O 2 ) by cyclic voltammetry and amperometry ( i-t ).

A better understanding of the roles of rare earth (RE) in heterogeneous catalysts is crucial for improving the properties of catalysts in petro-chemical industry. Fluid catalytic cracking (FCC) catalysts containing RE-incorporated Y zeolites with excellent stability and activity are continuously used to improve the conversion of heavy oil into transportation fuels. In this paper, the effect mechanism of Lanthanum (La) on stability and acidity of Y zeolites are elucidated in conjunction with their influences on catalytic performance. The improvement on stability of La-incorporated Y zeolites can be attributed to the La incorporation which bonds strongly with framework O2 and O3 atoms and strengthens the interaction between framework Al and its neighbouring O atoms. It is the enhanced stability restrains the release of framework Al and the formation of extra-framework Al, hence leads to a decrease of total L acid amount and an increase of total B acid amount, especially a clear increase in medium strength B acid amount (with 31 P NMR/TMPO chemical shifts at 62 and 58) and a significant decrease in strong B acid amount (with 31 P NMR/TMPO chemical shifts at 70 and 65) with the incorporation of La into Y zeolites. However, the total acid amount decreases significantly when La 2 O 3 content is high. The increase of B acid amount and improved stability of LaHY zeolites, boost the conversion ability and isomerization ability of heavy oil, while resulting in poor olefins selectivity and coke selectivity caused by the enhancement of hydrogen transfer reactions. Therefore, Y zeolite containing appropriate La 2 O 3 content should be considered to enhance heavy oil cracking ability while boosting light olefins production and optimizing coke selectivity. Graphic Abstract

HighlightsA multicomponent Co@CNTs|Ru catalyst has been rationally designed, in which Co nanoparticles are in-situ confined inside CNTs while trace Ru loading is uniformly deposited on their exterior walls.Co and Ru nanoparticles spatially confined by the inner and outer surface of CNTs, respectively, would induce charge redistribution and a synergistic electron coupling.Co@CNTs|Ru catalyst exhibits an unprecedented hydrogen evolution reaction (HER) activity in all pH-range, representing a new record among all the previously reported HER catalysts.Exploring highly active but inexpensive electrocatalysts for the hydrogen evolution reaction (HER) is of critical importance for hydrogen production from electrochemical water splitting. Herein, we report a multicomponent catalyst with exceptional activity and durability for HER, in which cobalt nanoparticles were in-situ confined inside bamboo-like carbon nanotubes (CNTs) while ultralow ruthenium loading (~ 2.6 µg per electrode area ~ cm−2) is uniformly deposited on their exterior walls (Co@CNTsǀRu). The atomic-scale structural investigations and theoretical calculations indicate that the confined inner Co and loaded outer Ru would induce charge redistribution and a synergistic electron coupling, not only optimizing the adsorption energy of H intermediates (ΔGH*) but also facilitating the electron/mass transfer. The as-developed Co@CNTsǀRu composite catalyst requires overpotentials of only 10, 32, and 63 mV to afford a current density of 10 mA cm−2 in alkaline, acidic and neutral media, respectively, representing top-level catalytic activity among all reported HER catalysts. The current work may open a new insight into the rational design of carbon-supported metal catalysts for practical applications.

Background Previous research has overlooked the role of self-perceived aging in the psychological well-being of older adults with multiple chronic conditions, and few studies have analyzed specific symptom interactions from a symptom network perspective. Our study aimed to explore the structure of the network among self-perceived aging, depression, and anxiety in community-dwelling older adults with multiple chronic conditions. Methods This was a cross-sectional survey conducted using convenience sampling from four prefecture-level cities in Jiangsu Province, China, between November 2022 and May 2023. A total of 478 participants were included in the analysis. The Brief Ageing Perceptions Questionnaire (B-APQ) and the Depression Anxiety and Stress Scales-21 (DASS-21) were used to assess self-perceived aging, depression, and anxiety among older adults. Network analysis was performed using R to explore the interrelationships among symptoms in the network and identify the core symptoms and bridge symptoms. Results Network analysis revealed that, after controlling for covariates, the node S5 (‘Emotional-Representations’) had the highest strength, followed by D7 (‘Meaningless’), S2 (‘Consequences-Positive’), S1 (‘Consequences and Control Negative’), and D6 (‘Worthless’). Furthermore, based on the bridge strength values, A5 (‘Panic’), D7 (‘Meaningless’), and S5 (‘Emotional-Representations’) were identified as bridge symptoms connecting self-perceived aging, depression, and anxiety. The study also identified several strong edge weight, most of which were linked to core symptoms and bridge symptoms. Conclusion The study suggests that targeting “Emotional-Representations” as a core symptom can be effective in addressing psychological issues in older adults with multiple chronic conditions. Furthermore, preventing and inhibiting bridge symptoms such as “panic,” “Meaningless,” and “Emotional-Representations” could be potentially effective prevent widespread activation of symptoms (e.g., from self-perceived aging to depression).

Background In China, about 18.70% of the population aged 60 years and older are at risk of low personal mastery as well as anxiety and depression for a variety of reasons. The purpose of this study was to construct a symptom network model of the relationship between anxiety, depression, and personal mastery in community-dwelling older adults and to identify central and bridge symptoms in this network. Methods Depression, anxiety, and personal mastery were measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Personal Mastery Scale (PMS), respectively. A total of 501 older adults in 16 communities in Changzhou and Zhenjiang, Jiangsu Province, China, were surveyed by using a combination of stratified sampling and convenience sampling methods. The R language was used to construct the network. Results (1) The network structure of anxiety–depression–personal mastery was stable, with “Nervousness” (node GAD1, strength = 1.38), “Sad mood” (node PHQ2, strength = 1.22), \" Inability to change” (node PMS2, strength = 1.01) and “Involuntarily” (node PMS3, strength = 0.95) as the central symptoms. (2) “Irritability” (node GAD6, bridge strength = 0.743), “Sad mood” (node PHQ2, bridge strength = 0.655), and “Trouble relaxing” (node GAD4, bridge strength = 0.550) were the bridge symptoms connecting anxiety, depressive symptoms, and personal mastery. (3) In the network comparison test (NCT), residence, somatic chronic comorbidity and gender had no significant effect on network structure. Conclusions The construction of the anxiety–depression–personal mastery network structure opens up new possibilities for mechanisms of action and intervention formulation for psychological disorders in community-dwelling older adults. The identification of central symptoms (e.g., nervousness, sad mood, inability to change, involuntarily) and bridge symptoms (e.g., irritability, sad mood, trouble relaxing) in community-dwelling older adults with anxiety, depression, and low sense of mastery can provide a scientific basis for the development of precise interventions.

A facile hydrothermal route for the synthesis of ordered NiWO 4 nanocrystals, which show promising applications as high performance non-enzymatic glucose sensor is reported. The NiWO 4 -modified electrodes showed excellent sensitivity (269.6 μA mM −1  cm −2 ) and low detection limit (0.18 μM) for detection of glucose with desirable selectivity, stability and tolerance to interference, rendering their prospective applications as cost-effective, enzyme-free glucose sensors.

After spinal cord transection injury, the inflammatory microenvironment formed at the injury site, and the cascade of effects generated by secondary injury, results in limited regeneration of injured axons and the apoptosis of neurons in the sensorimotor cortex (SMC). It is crucial to reverse these adverse processes for the recovery of voluntary movement. The mechanism of transcranial intermittent theta-burst stimulation (iTBS) as a new non-invasive neural regulation paradigm in promoting axonal regeneration and motor function repair was explored by means of a severe spinal cord transection. Rats underwent spinal cord transection and 2 mm resection of spinal cord at T10 level. Four groups were studied: Normal (no lesion), Control (lesion with no treatment), sham iTBS (lesion and no functional treatment) and experimental, exposed to transcranial iTBS, 72 h after spinal lesion. Each rat received treatment once a day for 5 days a week; behavioral tests were administered one a week. Inflammation, neuronal apoptosis, neuroprotective effects, regeneration and synaptic plasticity after spinal cord injury (SCI) were determined by immunofluorescence staining, western blotting and mRNA sequencing. For each rat, anterograde tracings were acquired from the SMC or the long descending propriospinal neurons and tested for cortical motor evoked potentials (CMEPs). Regeneration of the corticospinal tract (CST) and 5-hydroxytryptamine (5-HT) nerve fibers were analyzed 10 weeks after SCI. When compared to the Control group, the iTBS group showed a reduced inflammatory response and reduced levels of neuronal apoptosis in the SMC when tested 2 weeks after treatment. Four weeks after SCI, the neuroimmune microenvironment at the injury site had improved in the iTBS group, and neuroprotective effects were evident, including the promotion of axonal regeneration and synaptic plasticity. After 8 weeks of iTBS treatment, there was a significant increase in CST regeneration in the region rostral to the site of injury. Furthermore, there was a significant increase in the number of 5-HT nerve fibers at the center of the injury site and the long descending propriospinal tract (LDPT) fibers in the region caudal to the site of injury. Moreover, CMEPs and hindlimb motor function were significantly improved. Neuronal activation and neural tracing further verified that iTBS had the potential to provide neuroprotective effects during the early stages of SCI and induce regeneration effects related to the descending motor pathways (CST, 5-HT and LDPT). Furthermore, our results revealed key relationships between neural pathway activation, neuroimmune regulation, neuroprotection and axonal regeneration, as well as the interaction network of key genes.