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Background: 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., Method: 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., Results: 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., Conclusions: We provide evidence that frailty could increase depression risk independently of cognitive decline. Further research with a larger sample size is necessary., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yang Lv reports financial support was provided by Chongqing Talent Plan. Yang Lv reports financial support was provided by Key Project of Technological Innovation and Application Development of Chongqing Science & Technology Bureau. Yang Lv reports financial support was provided by Science Innovation Programs Led by the Academicians in Chongqing. Yang Lv reports financial support was provided by Chongqing Medical Key Discipline and Regional Medical Key Discipline Development Project. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dental pulp stem cells (DPSC) have shown osteogenic and bone regenerative potential. Improving the in situ bone regeneration potential of DPSC is crucial for their application as seed cells during bone defect reconstruction in clinics. This study aimed to develop DPSC-derived organoid-like microspheroids as effective seeds for bone tissue engineering applications. DPSC osteogenic microspheroids (70 μm diameter) were cultured in a polydimethylsiloxane-mold-based agarose-gel microwell-culture-system with or without cannabidiol (CBD)-treatment. Results of in vitro studies showed higher osteogenic differentiation potential of microspheroids compared with 2D-cultured-DPSC. CBD treatment further improved the osteogenic differentiation potential of microspheroids. The effect of CBD treatment in the osteogenic differentiation of microspheroids was more pronounced compared with that of CBD-treated 2D-cultured-DPSC. Microspheroids showed a higher degree of bone regeneration in nude mice calvarial bone defect compared to 2D-cultured-DPSC. CBD-treated microspheroids showed the most robust in situ bone regenerative potential compared with microspheroids or CBD-treated 2D-cultured-DPSC. According to mRNA sequencing, bioinformatic analysis, and confirmation study, the higher osteogenic potential of CBD-treated microspheroids was mainly attributed to WNT6 upregulation. Taken together, DPSC microspheroids have robust osteogenic potential and can effectively translate the effect of in vitro osteoinductive stimulation during in situ bone regeneration, indicating their application potential during bone defect reconstruction in clinics., (© 2024. The Author(s).)

Background: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited., Methods: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death., Results: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively., Conclusions: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.)., (Copyright © 2024 Massachusetts Medical Society.)

Nitrogen (N), as one of the most abundant mineral elements in rice, not only is the primary limiting factor for rice yield, but also impacts plant disease resistance by modulating plant morphology, regulating biochemical characteristics, as well as enhancing metabolic processes. Bacterial blight, a severe bacterial disease caused by Xanthomonas oryzae pv. oryzae ( Xoo ), significantly impairing rice yield and quality. Previous studies have shown that moderate application of nitrate nitrogen can improve plant disease resistance. However, further exploration is urgently required to investigate the involvement of the nitrate nitrogen signaling pathway in conferring resistance against bacterial leaf blight. In this study, we employed transcriptome sequencing to analyze the differentially expressed genes under various concentrations of nitrate supply duringrice bacterial blight infection. Our research reveals that nitrate nitrogen supply influences rice resistance to bacterial leaf blight. Through transcriptomic profiling of rice leaves inoculated under different nitrate nitrogen concentrations, we identified 4815 differentially expressed genes (DEGs) among four comparison groups, with notable differences in DEG enrichment between low and high nitrate nitrogen conditions, with some members of the NPF family implicated and we preliminarily elucidated the molecular regulatory network in which nitrate nitrogen participates in bacterial leaf blight resistance. Our findings provide a novel insight into a mechanism involving the nitrate nitrogen drive wider defense in rice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Chen, Miao, Ye, Li, Jiang and Chen.)

Background: Sarcopenia and multimorbidity are common in older adults, and most of the available clinical studies have focused on the relationship between specialist disorders and sarcopenia, whereas fewer studies have been conducted on the relationship between sarcopenia and multimorbidity. We therefore wished to explore the relationship between the two., Methods: The study subjects were older patients (aged ≥ 65 years) who were hospitalized at the Department of Geriatrics of the First Affiliated Hospital of Chongqing Medical University between March 2016 and September 2021. Their medical records were collected. Based on the diagnostic criteria of the Asian Sarcopenia Working Group in 2019, the relationship between sarcopenia and multimorbidity was elucidated., Results: 1.A total of 651 older patients aged 65 years and above with 2 or more chronic diseases were investigated in this study, 46.4% were suffering from sarcopenia. 2. Analysis of the relationship between the number of chronic diseases and sarcopenia yielded that the risk of sarcopenia with 4-5 chronic diseases was 1.80 times higher than the risk of 2-3 chronic diseases (OR 1.80, 95%CI 0.29-2.50), and the risk of sarcopenia with ≥ 6 chronic diseases was 5.11 times higher than the risk of 2-3 chronic diseases (OR 5.11, 95% CI 2.97-9.08), which remained statistically significant, after adjusting for relevant factors. 3. The Charlson comorbidity index was associated with skeletal muscle mass index, handgrip strength, and 6-meter walking speed, with scores reaching 5 and above suggesting the possibility of sarcopenia. 4. After adjusting for some covariates among 14 common chronic diseases in older adults, diabetes (OR 3.20, 95% CI 2.01-5.09), cerebrovascular diseases (OR 2.07, 95% CI 1.33-3.22), bone and joint diseases (OR 2.04, 95% CI 1.32-3.14), and malignant tumors (OR 2.65, 95% CI 1.17-6.55) were among those that still a risk factor for the development of sarcopenia., Conclusion: In the hospitalized older adults, the more chronic diseases they have, the higher the prevalence of sarcopenia. When the CCI is 5, attention needs to be paid to the occurrence of sarcopenia in hospitalized older adults., (© 2024. The Author(s).)

Gray mold caused by the necrotrophic fungal pathogen Botrytis cinerea is one of the most destructive diseases in rose (Rosa spp.). Rose infection by B. cinerea leads to severe economic losses due to necrosis, tissue collapse, and rot. In rose, cytokinins (CKs) positively regulate a defense response to B. cinerea, but little is known about the underlying molecular mechanisms. Here, we characterized two ethylene/jasmonic acid-regulated transcription factors, RhEFR005 and RhCCCH12, that bind to the promoter region of PATHOGENESIS-RELATED 10.1 (RhPR10.1) and promote its transcription, leading to decreased susceptibility to B. cinerea. The RhEFR005/RhCCCH12-RhPR10.1 module regulated cytokinin content in rose, and the susceptibility of RhEFR005-, RhCCCH12-, and RhPR10.1-silenced rose petals can be rescued by exogenous CK. In summary, our results reveal that the RhERF005/RhCCCH12-RhPR10.1 module regulates the CK-induced defense response of rose to B. cinerea., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Using event-related potentials (ERPs), this study examined the impact of reward expectations on working memory of emotional faces under different levels of cognitive load in a task combining the N-back paradigm and the reward expectation paradigm. The experiment involved presenting high- or low-reward cues followed by an N-back task for emotional faces with different loads. The accuracy results showed that under a high task load, both reward and emotion effects were significantly observed. However, these effects disappeared under a low task load. Analysis of the ERP data revealed that the early P2 and VPP components exhibited greater responses to fearful faces than to neutral faces. In the later stages, the P3 and LPP components showed greater reactions to high rewards than to low rewards. Additionally, the P2 component was found to be modulated by task load in relation to rewards, the EPN component demonstrated task load modulation with respect to emotions, and the N170 component showed an interaction effect between rewards and emotions. These findings imply that load regulates the reward effect and the emotional superiority effect in the process of working memory for emotional faces. In the cognitive processing of working memory, motivation and emotion jointly influence processing. Emotional factors have a greater impact in the early stage of processing, while motivation factors have a greater impact in the late stage of processing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The petals of ornamental plants such as roses (Rosa spp.) are the most economically important organs. This delicate, short-lived plant tissue is highly susceptible to pathogens, in large part because the walls of petal cells are typically thinner and more flexible compared with leaf cells, allowing the petals to fold and bend without breaking. The cell wall is a dynamic structure that rapidly alters its composition in response to pathogen infection, thereby reinforcing its stability and boosting plant resistance against diseases. However, little is known about how dynamic changes in the cell wall contribute to resistance to Botrytis cinerea in rose petals. Here, we show that the B. cinerea-induced transcription factor RhbZIP17 is required for the defense response of rose petals. RhbZIP17 is associated with phenylpropanoid biosynthesis and binds to the promoter of the lignin biosynthesis gene RhCAD1, activating its expression. Lignin content showed a significant increase under gray mold infection compared with the control. RhCAD1 functions in the metabolic regulation of lignin production and, consequently, disease resistance, as revealed by transient silencing and overexpression in rose petals. The WRKY transcription factor RhWRKY30 is also required to activate RhCAD1 expression and enhance resistance against B. cinerea. We propose that RhbZIP17 and RhWRKY30 increase lignin biosynthesis, improve the resistance of rose petals to B. cinerea, and regulate RhCAD1 expression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Microglia are important cells that act on regulating neuroinflammation and neurofunction after the induction of ischemic stroke (IS). Consequently, the efficient accumulation of drugs within ischemic regions, particularly in microglia, serves as a valuable approach for achieving effective therapy by attenuating microglia-mediated cerebral ischemic injury. In this study, we designed mannose (man)-conjugated luteolin (lut)-loaded platelet-derived exosomes (lut/man-pEXO) as surface engineered multifunctional cascade-delivery drug carriers to target ischemic blood vessels and subsequent microglia to enhance drug accumulation and induce neuroprotection of neurovascular unit (NVU) against IS. The results revealed that as platelets naturally gathered in pathological ischemic cerebral vessels, lut/man-pEXO could bind to platelets and efficiently target ischemic injury sites. Moreover, owing to the selective binding affinity of mannose present in lut/man-pEXO towards the mannose receptor expressed on microglia, lut/man-pEXO exhibited superior microglia-targeting properties, inducing the increased uptake of lut by microglia. As a result, lut/man-pEXO regulated microglia by inhibiting the activation of detrimental M1 and promoting the transition towards the anti-inflammatory type (M2), thus attenuating ischemic damage of NVU by reducing the infarct area, rescuing the damage of blood-brain barrier (BBB) and preventing inflammatory transformation of astrocytes., (© 2023. Controlled Release Society.)

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.

Protein functions are closely related to their subcellular locations. At present, the prediction of protein subcellular locations is one of the most important problems in protein science. The evident defects of traditional methods make it urgent to design methods with high efficiency and low costs. To date, lots of computational methods have been proposed. However, this problem is far from being completely solved. Recently, some multi-label classifiers have been proposed to identify subcellular locations of human, animal, Gram-negative bacterial and eukaryotic proteins. These classifiers adopted the protein features derived from gene ontology information. Although they provided good performance, they can be further improved by adopting more powerful machine learning algorithms. In this study, four improved multi-label classifiers were set up for identification of subcellular locations of the above four protein types. The random k-labelsets (RAKEL) algorithm was used to tackle proteins with multiple locations, and random forest was used as the basic prediction engine. All classifiers were tested by jackknife test, indicating their high performance. Comparisons with previous classifiers further confirmed the superiority of the proposed classifiers.

Malignant melanoma (MM) is a highly aggressive form of skin cancer with increasing global incidence rates, particularly in developed countries. Variations in the prevalence and quality of care provided to patients with melanoma exist across different regions and across different sex and age. Assessing the global burden of melanoma and evaluating the quality of care can provide valuable insights for developing targeted interventions in certain underperforming regions and improving patient outcomes. This study aimed to systematically analyze the Global Burden of Disease Study from 1990 to 2019 to assess the quality of care for skin malignant melanoma on a global scale. We conducted a comprehensive literature review and extracted data on melanoma incidence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Disease Study. We incorporated these variables using principal component analysis (PCA) to form an informative single variable of quality of care index (QCI) and analyzed its spatial-temporal variations as well as disparities across age, sex and socio-demographic index (SDI). The overall Quality of Care Index (QCI) for melanoma improved from 82.81 in 1990 to 91.29 in 2019. The QCI score showed a positive correlation with socioeconomic status across regions. Australia ranked highest in QCI (99.96), while Central African Republic, and Kiribati had the lowest scores. China and Saudi Arabia showed significant QCI improvement, while the QCI of the Democratic People's Republic of Korea, Zimbabwe, and Guam decreased from 1990 to 2019. The highest QCI scores were observed in the age groups of 20-39 years old (93.40-94.65). Gender disparities narrowed globally in these three decades, but lower Socio-demographic Index (SDI) regions showed increased gender inequities. Our findings highlighted the spatial-temporal variations in the quality of care of MM as well as its disparities across different SDI levels, age groups and sex. These findings offer valuable insights and guidance for implementing focused interventions and resource allocation to enhance the quality of care and overall outcomes for MM worldwide, especially for underperforming regions., (© 2023. The Author(s).)

Molybdenum carbide (Mo 2 CT x MXene) did not possess suitable properties for supercapacitors. Herein, a short oxidation method of Mo 2 CT x in air at moderately high temperatures is proposed for fabricating a Mo 2 C/MoO 3 heterostructure. The stability of Mo 2 CT x in air up to 700 °C and the phase transition at higher temperatures are confirmed. Such a heterostructure is beneficial in reducing the diffusion energy barrier of H + . In the aqueous system, the Mo 2 C/MoO 3 electrode delivers a capacitance of up to 811 F g -1 . A fully assembled symmetric solid-state supercapacitor delivers 224 F g -1 with an excellent retention rate of 91.05% after 7500 cycles. Besides, the supercapacitor can work at the low temperature of -60°, showing good low-temperature properties. The approach presented in this work opens a promising way to turn a neglected MXene, assumed to be unsuitable for supercapacitors, into one of the top-performing supercapacitor electrodes.

As a novel protein knockdown tool, proteolysis targeting chimeras (PROTACs) can induce potent degradation of target proteins by hijacking E3 ubiquitin ligases. However, the uncontrollable protein disruption of PROTACs is prone to cause "off-target" toxicity after systemic administration. Herein, we designed a photocaged-PROTAC (phoBET1) and loaded it in UCNPs-based mesoporous silica nanoparticles (UMSNs) to construct a NIR light-activatable PROTAC nanocage (UMSNs@phoBET1) for controllable target protein degradation. Upon NIR light (980 nm) irradiation, UMSNs@phoBET1 nanocages could be activated to release active PROTAC via a controlled pattern for degrading bromodomain-containing protein 4 (BRD4) and inducing MV-4-11 cancer cell apoptosis. In vivo experiments demonstrated that UMSNs@phoBET1 nanocages were capable of responding to NIR light in tumor tissues to achieve BRD4 degradation and effectively suppress tumor growth. This NIR light-activatable PROTAC nanoplatform compensates for the current shortcomings of short-wavelength light-controlled PROTACs and presents a paradigm for the precise regulation of PROTACs in living tissues.

β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCF β-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of IκBα and its phosphorylated form. Hence, they inhibited the activation of the transcription activity of NF-κB, indicating the effective inhibition of β-TrCP by the hit compounds in cells. Next, we performed an in silico analysis of the hit compounds to determine the important moieties of the hit compounds. Carboxyl groups of NPL62020-01 and NPL42040-01 and hydroxyl groups of NPD5943 created hydrogen bonds with β-TrCP similar to those created by intrinsic target phosphopeptides of β-TrCP. Our findings enhance our knowledge of useful small molecule ligands of β-TrCP and the importance of residues that can be ligands of β-TrCP., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2023 Liu et al.)

Unpredicted human organ level toxicity remains one of the major reasons for drug clinical failure. There is a critical need for cost-efficient strategies in the early stages of drug development for human toxicity assessment. At present, artificial intelligence methods are popularly regarded as a promising solution in chemical toxicology. Thus, we provided comprehensive in silico prediction models for eight significant human organ level toxicity end points using machine learning, deep learning, and transfer learning algorithms. In this work, our results showed that the graph-based deep learning approach was generally better than the conventional machine learning models, and good performances were observed for most of the human organ level toxicity end points in this study. In addition, we found that the transfer learning algorithm could improve model performance for skin sensitization end point using source domain of in vivo acute toxicity data and in vitro data of the Tox21 project. It can be concluded that our models can provide useful guidance for the rapid identification of the compounds with human organ level toxicity for drug discovery.

In this study, pristine kiwi peel (KP) and nitric acid modified kiwi peel (NA-KP) based adsorbents were prepared and evaluated for selective removal of cationic dye. The morphology and chemical structure of KP and NA-KP were fully characterized and compared, and results showed nitric acid modification introduced more functional groups. Moreover, the adsorption kinetics and isotherms of malachite green (MG) by KP and NA-KP were investigated and discussed. The results showed that the adsorption process of MG onto KP followed a pseudo-second-order kinetic model and the Langmuir isotherm model, while the adsorption process of MG onto NA-KP followed a pseudo-first-order kinetic model and the Freundlich isotherm model. Notably, the Langmuir maximum adsorption capacity of NA-KP was 580.61 mg g -1 , which was superior to that of KP (297.15 mg g -1 ). Furthermore, thermodynamic studies demonstrated the feasible, spontaneous, and endothermic nature of the adsorption process of MG by NA-KP. Importantly, NA-KP showed superior selectivity to KP towards cationic dye MG against anionic dye methyl orange (MO). When the molar ratio of MG/MO was 1:1, the separation factor (α MG/MO ) of NA-KP was 698.10, which was 5.93 times of KP. In addition, hydrogen bonding, π-π interactions, and electrostatic interaction played important roles during the MG adsorption process by NA-KP. This work provided a low-cost, eco-friendly, and efficient option for the selective removal of cationic dye from dyeing wastewater.

Background: Wall associated kinase (WAK) and WAK-like (WAKL) are typical pattern recognition receptors act as the first sentry of plant defense. But little of WAK/WAKL family is known in Rosaceae., Results: In this study, 131 WAK/WAKL genes from apple, peach and strawberry were identified using a bioinformatics approach. Together with 68 RcWAK/RcWAKL in rose, we performed a comparative analysis of 199 WAK/WAKL in four Rosaceae crops. The phylogenetic analysis divided all the WAK/WAKL into five clades. Among them, the cis-elements of Clade II and Clade V promoters were enriched in jasmonic acid (JA) signaling and abiotic stress, respectively. And this can also be verified by the rose transcriptome responding to different hormone treatments. WAK/WAKL families have experienced a considerable proportion of purifying selection during evolution, but still 26 amino acid sites evolved under positive selection, which focused on extracellular conserved domains. WAK/WAKL genes presented collinearity relationship within and between crops, throughout four crops we mined four orthologous groups (OGs). The WAK/WAKL genes in OG1 and OG4 were speculated to involve in plant-Botrytis cinerea interaction, which were validated in rose via VIGS as well as strawberry by qRT-PCR., Conclusions: These results not only provide genetic resources and valuable information for the evolutionary relationship of WAK/WAKL gene family, but also offer a reference for future in-depth studies of Rosaceae WAK/WAKL genes., (© 2023. The Author(s).)

Non-line-of-sight (NLOS) imaging aims at reconstructing targets obscured from the direct line of sight. Existing NLOS imaging algorithms require dense measurements at regular grid points in a large area of the relay surface, which severely hinders their availability to variable relay scenarios in practical applications such as robotic vision, autonomous driving, rescue operations and remote sensing. In this work, we propose a Bayesian framework for NLOS imaging without specific requirements on the spatial pattern of illumination and detection points. By introducing virtual confocal signals, we design a confocal complemented signal-object collaborative regularization (CC-SOCR) algorithm for high-quality reconstructions. Our approach is capable of reconstructing both the albedo and surface normal of the hidden objects with fine details under general relay settings. Moreover, with a regular relay surface, coarse rather than dense measurements are enough for our approach such that the acquisition time can be reduced significantly. As demonstrated in multiple experiments, the proposed framework substantially extends the application range of NLOS imaging., (© 2023. The Author(s).)

The number of excellent 2D materials is finite for nano optoelectric devices including transistors, diodes, sensors, and so forth, thus the modulation of 2D materials is important to improve the performance of the current eligible 2D materials, and even to transform unqualified 2D materials into eligible 2D materials. Here we develop a fine laser doping strategy based on highly controllable laser direct writing, and investigate its effectivity and practicability by doping multilayer molybdenum ditelluride (MoTe 2 ). Power-gradient laser doping and patterned laser doping, for the first time, are presented for designable and fine doping of 2D materials. The laser-induced polar transition of MoTe 2 indicates good controllability of the method for the carrier concentration distribution in MoTe 2 . Multiple devices with finely tuned energy band structures are demonstrated by means of power-gradient laser doping and patterned laser doping, further illustrating the design capability of a precise energy band in 2D materials.

The pathogenesis of ischemic cerebrovascular disease has revealed that ischemic stroke often leads to deprivation of oxygen, blood-brain barrier (BBB) damage and enhanced inflammatory activation, eventually causing severe brain tissue damage. Herein, we prepared hybrid membrane nanovesicles (YC-1@[RBC-PL] NVs) composed of red blood cell (RBC) membrane and platelet (PL) membrane encapsulating hypoxia inducible factor-1α (HIF-1α) inhibitor YC-1 for contributing to the protection of the neurovascular unit (NVU) in ischemic stroke. YC-1@[RBC-PL] NVs targeted the ischemic brain by the thrombus targeting properties of PL membrane and relieved the hypoxia inside ischemic brain in the presence of YC-1 and catalase in YC-1@[RBC-PL] NVs. Finally, YC-1@[RBC-PL] NVs attenuated ischemic injury to NVU by reducing infarct volume, preserving BBB integrity, and blocking activation of astrocyte and microglia in a middle cerebral artery occlusion/reperfusion (MCAO/R) model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Antibiotics are omnipresent and pseudo-persistent in the environment. Yet, their potential ecological risks under repeated exposure, which is more environmentally relevant, are understudied. Therefore, this study used ofloxacin (OFL) as the probe chemical to investigate the toxic effects of different exposure scenarios-single dose of high concentration (4.0 µg/L) and multiple additions of low concentrations-towards the cyanobacterium Microcystis aeruginosa. Flow cytometry was employed to measure a collection of biomarkers, including endpoints related with biomass, single cell properties and physiological status. Results showed that the single dose of the highest OFL level inhibited cellular growth, chl-a content and cell size of M. aeruginosa. In contrast, OFL induced stronger chl-a autofluorescence and higher doses tended to have more remarkable effects. Repeated low OFL doses can more significantly increase the metabolic activity of M. aeruginosa than a single high dose. Viability and cytoplasmic membrane were not affected by OFL exposure. Oxidative stress was observed for the different exposure scenarios, with fluctuating responses. This study demonstrated the different physiological responses of M. aeruginosa under different OFL exposure scenarios, providing novel insights into the toxicity of antibiotics under repeated exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Rose is an important ornamental plant and a commercial source of natural fragrances and essential oils. However, gray mold is the most serious disease of rose during cultivation and post-harvest. In plants, the bZIP gene family is one of the important families of transcription factors that regulate many biological processes, including pathogen defense, light response, and stress signaling. Although there were reports that bZIPs play a key role in plant pathogen defense, there have been no comprehensive studies or functional analysis of the bZIP gene family in rose (Rosa sp.) yet. In this study, a genome-wide analysis of the bZIP family gene (RcbZIPs) in rose was carried out to investigate their phylogenetic relationships, gene structure, chromosome localizations, collinearity, and the function of RcbZIP17. In the rose genome, 48 RcbZIP genes were identified and divided into 11 subgroups by phylogenetic relationships. Moreover, gene structure analysis agreed with phylogenetic tree grouping. The RcbZIPs were unevenly distributed on all seven chromosomes. The gene duplication events indicated that segmental duplication of the entire genome may play a key role in gene duplication. A Ka/Ks analysis showed that they mainly underwent purifying selection with limited functional differentiation. Gene expression analysis showed that 16 RcbZIPs were significantly differential expressed by Botrytis cinerea infection. It is speculated that these RcbZIPs are candidate genes for regulating the response of rose to gray mold infection. According to virus-induced gene silencing (VIGS) and overexpression (OE) studies, RcbZIP17 was implicated in the resistance of rose to gray mold. This study provides useful information for further study on the function of the bZIP gene family in rose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Vascular disease is the second most common cause of dementia. The prevalence of vascular dementia (VaD) has increased over the past decade. However, there are no licensed treatments for this disease. Carotid atherosclerosis (CAS) is highly prevalent and is the main cause of ischemic stroke and VaD. We studied co-expressed genes to understand the relationships between CAS and VaD and further reveal the potential biomarkers and therapeutic targets of CAS and VaD., Methods: CAS and VaD differentially expressed genes (DEGs) were identified through bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE43292 and GSE122063, respectively. Furthermore, a variety of target prediction methods and network analysis approaches were used to assess the protein-protein interaction (PPI) networks, the Gene Ontology (GO) terms, and the pathway enrichment for DEGs, and the top 7 hub genes, coupled with corresponding predicted miRNAs involved in CAS and VaD, were assessed as well., Result: A total of 60 upregulated DEGs and 159 downregulated DEGs were identified, of which the top 7 hub genes with a high degree of connectivity were selected. Overexpression of these hub genes was associated with CAS and VaD. Finally, the top 7 hub genes were coupled with corresponding predicted miRNAs. hsa-miR-567 and hsa-miR-4652-5p may be significantly associated with CAS and VaD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Huang, Dai, Guo, Lin and Liu.)

The plant hormones cytokinin (CK) and abscisic acid (ABA) play critical and often opposite roles during plant growth, development, and responses to abiotic and biotic stresses. Rose (Rosa sp.) is an economically important ornamental crop sold as cut flowers. Rose petals are extremely susceptible to gray mold disease caused by the necrotrophic fungal pathogen Botrytis cinerea. The infection of rose petals by B. cinerea leads to tissue collapse and rot, causing severe economic losses. In this study, we showed that CK and ABA play opposite roles in the susceptibility of rose to B. cinerea. Treatment with CK enhanced the disease protection of rose petals to B. cinerea, while ABA promoted disease progression. We further demonstrated that rose flowers activate CK-mediated disease protection via a B. cinerea-induced rose transcriptional repressor, Rosa hybrida (Rh)WRKY13, which is an ortholog of Arabidopsis (Arabidopsis thaliana), AtWRKY40. RhWRKY13 binds to promoter regions of the CK degradation gene CKX3 (RhCKX3) and the ABA-response gene ABA insensitive4 (RhABI4), leading to simultaneous inhibition of their expression in rose petals. The increased CK content and reduced ABA responses result in enhanced protection from B. cinerea. Collectively, these data reveal opposite roles for CK and ABA in the susceptibility of rose petals against B. cinerea infection, which is mediated by B. cinerea-induced RhWRKY13 expression., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Novel Bi/Bi 2 MoO 6 /ZnIn 2 S 4 is not only cost-effective compared to noble metals, but also shows superior hydrogen production. Comprehensive characterization illustrated that the S-scheme heterojunction and excellent photon utilization capability of the photocatalyst were the main factors that enhanced its hydrogen production performance. The X-ray photoelectron spectroscopy illustrated the elemental composition of the catalyst and the presence of Bi metal in ternary heterojunction. The photoluminescence and electrochemical characterization proved that S-scheme heterojunction Bi/Bi 2 MoO 6 /ZnIn 2 S 4 promoted the separation of photogenerated carriers. The amount of hydrogen produced by Bi/Bi 2 MoO 6 /ZnIn 2 S 4 was 2306.90 µmol g -1 under visible light illumination for 5 h. It was 4.3, 29.6 and 2.2 times more than those of ZnIn 2 S 4 , Bi 2 MoO 6 /ZnIn 2 S 4 and Pt/ZnIn 2 S 4 , respectively. The excellent hydrogen production activity of the ternary complexes may be attributed to the following: (1) Bi/Bi 2 MoO 6 could replace precious metals to enhance reactive sites of ZnIn 2 S 4 . (2) Metal Bi could produce surface plasmon resonance effect facilitating light absorption, and Bi acted as an electron bridge promoting charge transfer. (3) The charge transfer mechanism of S-scheme heterojunction and hot electrons injection process of Bi metal synergistically drove the photocatalytic hydrogen production. This work provides an innovative method for the construction of visible-light-driven photocatalysts without using precious metals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Sjogren's syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood., Methods: In this study, we used NOD mice model to monitor changes in mice's salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes., Results: We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion., Conclusion: The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting., (© 2022. The Author(s).)

Background: Oral health is associated with the onset and deterioration of cognitive function and physical frailty, which can be improved with appropriate interventions. However, far too little attention has been paid to oral health status of elderly with cognitive frailty. The objective of this study was to investigate the oral health status and potential risk factors of elderly hospitalized patients aged 60 years or older with cognitive frailty., Methods: The participants' assessment data derived from the Comprehensive Geriatric Assessment Database of hospitalized patients from The First Affiliated Hospital of Chongqing Medical University. Data were collected from April 2016 to December 2021. All participants underwent a face-to-face assessment conducted by professional evaluators. Physical frailty was defined by Fried's criteria. Cognitive function was assessed by Mini Mental State Examination (MMSE). The cognitive frailty is characterized by the simultaneous presence of at least 1 Fried's criteria and mild cognitive impairment according to Diagnostic and Statistical Manual of Mental Disorders 5th edition. The oral health was assessed according to 10-item Brief Oral Health Status Examination (BOHSE). The general demographic characteristics, BOHSE scores were compared between the cognitive frailty and non-cognitive frailty (control group). The score of BOHSE and ten items were included in the binary logistic regression analysis. The covariate characteristics were adjusted for a final model with a multivariate analysis., Results: A total of 425 patients (245 females) with cognitive frailty and 491 patients (283 females) with non-cognitive frailty were enrolled in this retrospective study. Univariate analysis showed statistically significant differences in age, education level, living arrangement, diabetes, Body Mass Index (BMI), Pittsburgh Sleep Quality Index (PSQI), depression between the two groups. The total BOHSE score of cognitive frailty was higher than that of the control group (4.35 ± 2.68 vs. 3.64 ± 2.60, Z = 4.07, P < 0.001). The average scores and the proportions of health changes and unhealthy states of tongue, mucosa tissue, gums, natural teeth, dentures, masticatory teeth and oral hygiene in cognitive frailty were greater than those of the control group (all P < 0.05). The binary logistical regression analysis showed that four or more natural teeth decayed or broken was independently associated with cognitive frailty after adjusting the age, gender, education level, living arrangement and BMI, PSQI, diabetes and depression (OR = 1.91, 95%CI: 1.20-3.07, P = 0.007). Additionally, while in the chewing position, those cases with a normal-occlusal-relationship number of less than 11 pairs had a higher risk of cognitive frailty than those with 12 pairs or more., Conclusions: The oral health status of older hospitalized patients over 60 years with cognitive frailty was worse than that of patients with non-cognitive frailty. But only four or more natural teeth decayed or broken and a reduction in chewing pairs were independent risk factors for cognitive frailty., (© 2022. The Author(s).)

Overuse of nitrogen fertilizer in fields has raised production costs, and caused environmental problems. Improving nitrogen use efficiency (NUE) of rice is essential for sustainable agriculture. Here we report the cloning, characterization and roles for rice of OsNPF7.6 , a member of the nitrate transporter 1/peptide transporter family (NPF). The OsNPF7.6 protein is located in the plasma membrane, expressed in each tissue at all stages and is significantly regulated by nitrate in rice. Our study shows that the overexpression of OsNPF7.6 can increase the nitrate uptake rate of rice. Additionally, field experiments showed that OsNPF7.6 overexpression increased the total tiller number per plant and the grain weight per panicle, thereby improving grain yield and agronomic NUE in rice. Thus, OsNPF7.6 can be applied to be a novel target gene for breeding rice varieties with high NUE, and provide a reference for breeding higher yielding rice.

Rose is one of the most important ornamental plants, accounting for one-third of the world's fresh cut flower market. The vase life refers to the period of a cut flower retaining its appearance in a vase. During this period, the rose was subjected to a variety of abiotic and biotic stresses, resulting in a reduction in the life of cut flowers. Numerous studies have been carried out on cut rose, which proves the effects of various plant hormones on post-harvest dehydration, petal senescence and abscission, disease and vase life of cut rose flowers. In addition, the natural or synthetic hormones or its inhibitor have been successfully used in cut flower preservatives to extend the vase life of rose. However, there is still a lack of systematic and in-depth research on the expression of rose genes related to plant hormone response. Here we analyzed the gene expression changes of the rose flower under treatment of 11 different plant hormones or its inhibitors in order to provide reference for rose studies., (© 2022. The Author(s).)

Single-pixel imaging enjoys advantages of low budget, broad spectrum, and high imaging speed. However, existing methods cannot clearly reconstruct the object that is fast rotating or randomly moving. In this work, we put forward an effective method to image a randomly moving object based on geometric moment analysis. To the best of our knowledge, this is the first work that reconstructs the shape and motion state of the target without prior knowledge of the speed or position. By using the cake-cutting order Hadamard illumination patterns and low-order geometric moment patterns, we obtain a high-quality video stream of the target which moves at high and varying translational and rotational speeds. The efficient method as verified by simulation and experimental results has great potential for practical applications such as Brownian motion microscopy and remote sensing.

Long non-coding RNAs (lncRNAs) were found to play important roles in transcriptional, post-transcriptional, and epigenetic gene regulation in various biological processes. However, lncRNAs and their regulatory roles remain poorly studied in horticultural plants. Rose is economically important not only for their wide use as garden and cut flowers but also as important sources of natural fragrance for perfume and cosmetics industry, but presently little was known about the regulatory mechanism of the floral scent production. In this paper, a RNA-Seq analysis with strand-specific libraries, was performed to rose flowers in different flowering stages. The scented variety 'Tianmidemeng' ( Rosa hybrida ) was used as plant material. A total of 13,957 lncRNAs were identified by mining the RNA-Seq data, including 10,887 annotated lncRNAs and 3070 novel lncRNAs. Among them, 10,075 lncRNAs were predicted to possess a total of 29,622 target genes, including 54 synthase genes and 24 transcription factors related to floral scent synthesis. 425 lncRNAs were differentially expressed during the flowering process, among which 19 were differentially expressed among all the three flowering stages. Using weighted correlation network analysis (WGCNA), we correlate the differentially-expressed lncRNAs to synthesis of individual floral scent compounds. Furthermore, regulatory function of one of candidate lncRNAs for floral scent synthesis was verified using VIGS method in the rose. In this study, we were able to show that lncRNAs may play important roles in floral scent production in the rose. This study also improves our understanding of how plants regulate their secondary metabolism by lncRNAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Zhang, Wu, Liu and Zhang.)

Early diagnosis of cognitive impairment is important but difficult. Prediction models may work as an efficient way to identify high risk individuals for this disease. This study aimed to develop a simple and convenient model to identify high-risk individuals of cognitive impairment in the older Chinese inpatients. We enrolled 1300 inpatients aged 60 years or above from the department of geriatrics of the First Affiliated Hospital of Chongqing Medical University during 2013 to 2017. The model for cognitive impairment was established in the developing cohort of 1100 participants and tested in another validating cohort of 200 participants. Logistic regression analyses were used to identify the candidate variables of cognitive impairment. Receiver operating curve was adopted to validate the model. Logistic regression analyses showed that increasing age, diabetes, depression and low educational level were independently associated with cognitive impairment. The model was generated in the following way: P model  = e y /(1 + e y ), where y = -6.874 + 0.088 * age + 0.317 * diabetes + 0.647 * depression + 0.345 * education level. The value of P model indicates the probability of cognitive impairment for each patient. The present model proved to be a reliable marker for identifying people at high risk of cognitive impairment (area under curve = 0.790, 95% CI = 0.728-0.852, p < 0.001). It had a high sensitivity (86.2%) but a relatively low specificity (59.4%). It may be helpful to "recognize" those at high risk of cognitive impairment rather than "rule out" those at low risk of this disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rose is one of the most important ornamental flowers, accounting for approximately one-third of the world's cut flower market. Powdery mildew caused by Podosphera pannosa is a devastating fungal disease in rose, mainly infecting the young leaves and causing serious economic losses. Therefore, a study on the mechanism of the fungus infecting the rose leaves and the possibility to improve resistance hereby is interesting and meaningful. Accordingly, we conducted transcriptome sequencing of rose leaves infected by P. pannosa at different time points to reveal the molecular mechanism of resistance to powdery mildew. The high-quality reads were aligned to the reference genome of Rosa chinensis , yielding 51,230 transcripts. A total of 1,181 differentially expressed genes (DEGs) were identified in leaves during P. pannosa infection at 12, 24, and 48 hpi. The transcription factors of ERF, MYB, bHLH, WRKY, etc ., family were identified among DEGs, and most of them were downregulated during P. pannosa infection. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the hormone signal transduction pathway, especially ethylene signal-related genes, was consistently showing a downregulated expression during powdery mildew infection. More importantly, exogenous 1-MCP (inhibitor of ethylene) treatment could improve the rose leaves' resistance to P. pannosa . In summary, our transcriptome of rose leaf infected by powdery mildew gives universal insights into the complex gene regulatory networks mediating the rose leaf response to P. pannosa , further demonstrating the positive role of 1-MCP in resistance to biotrophic pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Fang, Wang, Cao, Yu, Chen and Zhang.)

Previous studies have found differences in the cognitive and neural mechanisms between cognitive reappraisal and expression suppression in the regulation of various negative emotions and the recognition of regulated stimuli. However, whether these differences are valid for sadness remains unclear. As such, we investigated the effect of cognitive reappraisal and expression suppression on sadness regulation and the recognition of sad scenes adopting event-related potentials (ERPs). Twenty-eight healthy undergraduate and graduate students took part in this study. In the regulation phase, the participants were asked to down-regulation, expressive suppression, or maintain their sad emotion evoked by the sad images, and then to perform an immediately unexpected recognition task involving the regulated images. The behavioral results show that down-regulation reappraisal significantly diminished subjective feelings of sadness, but expressive suppression did not; both strategies impaired the participants' recognition of sad images, and expressive suppression had a greater damaging effect on the recognition of sad images than down-regulation reappraisal. The ERP results indicate that reappraisal (from 300 ms to 1,500 ms after image onset) and expressive suppression (during 300-600 ms) significantly reduced the late positive potential (LPP) induced by sadness. These findings suggest that down-regulation reappraisal and expression suppression can effectively decrease sadness, and that down-regulation reappraisal (relative to expression suppression) is a more effective regulation strategy for sadness. Both strategies impair the recognition of sad scenes, and expression suppression (compared to down-regulation reappraisal) leads to relatively greater impairment in the recognition of sad scenes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Ding, Wang, Wu, Gao and Liu.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Runoff complexity is an important indicator reflecting the sustainability of a watershed ecosystem. In order to explore the multiscale characteristics of runoff complexity and analyze its variation and influencing factors in the Yanhe watershed in China during the period 1991-2020, we established a new analysis method for watershed runoff complexity based on the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) method for the decomposition of multiscale characteristics and the refined composite multiscale entropy ( RCMSE ) method for the quantification of the system complexity. The results show that runoff and its components all present multiscale complexity characteristics that are different from random signals, and the intermediate frequency modes contribute the most to runoff complexity. The runoff complexity of the Yanhe watershed has decreased gradually since 1991, and 2010 was a turning point of runoff complexity, when it changed from a decline to an increase, indicating that the ecological sustainability of this basin has improved since 2010, which was mainly related to the ecological restoration measures of the Grain for Green Project. This study expands the research perspective for analyzing the variation characteristics of runoff at the multiscale, and provides a reference for the study of watershed ecological sustainability and ecological management.

Objective: To investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI)., Methods: A single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid β-protein-40 (Aβ-40), Aβ-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS)., Results: Thirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. -1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. -0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. -0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. -1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD ( p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI ( P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF., Conclusion: Our findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance., Clinical Trial Registration: https://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Zhang, Liu, Zhang, Tang, Song, Long, Yang, Jiang, Li, Liu, Lü and Ding.)

Evidence for the association between vitamin D and risk of recurrent stroke remains sparse and limited. We aimed to assess the relationship between serum circulating 25-hydroxyvitamin D (25(OH)D) level and risk of recurrent stroke in patients with a stroke history, and to identify the optimal 25(OH)D level in relation to lowest recurrent stroke risk. Data from the nationwide prospective United Kingdom Biobank were used for analyses. Primary outcome was time to first stroke recurrence requiring a hospital visit during follow-up. We used Cox proportional hazards regression model with restricted cubic splines to explore 25(OH)D level in relation to recurrent stroke. The dose-response relationship between 25(OH)D and recurrent stroke risk was also estimated, taking the level of 10 nmol/L as reference. A total of 6824 participants (mean age: 60.6 years, 40.8% females) with a baseline stroke were included for analyses. There were 388 (5.7%) recurrent stroke events documented during a mean follow-up of 7.6 years. Using Cox proportional hazards regression model with restricted cubic splines, a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke was found, where the lowest recurrent stroke risk lay at the 25(OH)D level of approximate 60 nmol/L. When compared with 10 nmol/L, a 25(OH)D level of 60 nmol/L was related with a 48% reduction in the recurrent stroke risk (hazard ratio = 0.52, 95% confidence interval: 0.33-0.83). Based on data from a large-scale prospective cohort, we found a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke in patients with a stroke history. Given a lack of exploring the cause-effect relationship in this observational study, more high-quality evidence is needed to further clarify the vitamin D status in relation to recurrent stroke risk.

Background: The role of continuous intravenous administration of tirofiban in endovascular therapy is still unclear. This meta-analysis aims to evaluate the 90-day functional prognosis in acute ischemic stroke patients (AIS) treated by endovascular treatment and intravenous administration of tirofiban., Methods: We searched PubMed, Embase, and CENTRAL databases with the subject terms "tirofiban", "brain ischemia", and some related free words. Inclusion criteria were: (1) cohort study or randomized control trials; (2) AIS patients who received endovascular therapy; (3) the intervention or exposure was intravenous tirofiban monotherapy or combined with intra-arterial tirofiban; (4) containing data on modified Rankin Scale at 90 days and including at least one of the following indicators: mortality, symptomatic intracranial hemorrhage (sICH), intracranial hemorrhage (ICH), and recanalization. A summary odds ratio was calculated., Results: Twelve eligible studies, consisting of 3268 AIS participants, were identified. There was a significant trend of favorable outcomes (measured by mRS at three months) in the tirofiban group (ORs = 1.36; 95% CI = 1.09-1.70). In addition, compared with the non-tirofiban group, intravenous tirofiban was significantly associated with decreased risk of 90-day mortality (ORs = 0.73; 95% CI:0.59-0.89) and increased recanalization rate (ORs = 1.50; 95% CI:1.08-2.09) but no significant difference in rates of sICH (ORs = 0.93; 95% CI = 0.70-1.24) or ICH (ORs = 0.84; 95% CI = 0.62-1.15)., Conclusions: Intravenous tirofiban appears to be safe and effective when used following intra-arterial tirofiban or as monotherapy in AIS patients treated by endovascular therapy, which can improve the 90-day functional outcome, decrease the 90-day mortality and increase the possibility of early recanalization without increasing rates of sICH and ICH., (Copyright © 2022. Published by Elsevier Ltd.)

Aggregation of amyloid in the form of senile plaques is currently considered to be one of the main mechanisms driving the development of Alzheimer's disease (AD). Therefore, targeting amyloid homeostasis is an important treatment strategy for AD. Microglia, as the main immune cells, contribute to endocytosis and clearance of amyloid beta (Aβ) via lysosome mediated degradation. As abnormal lysosomal function in microglia is associated with inefficient clearance of Aβ in AD, we designed bioengineered microglia-targeting exosomes to promote the targeted delivery of gemfibrozil (Gem) and restore the lysosomal activity of microglia in clearing Aβ aggregation. Our results suggested that mannose-modified exosomes laden with Gem (MExo-Gem) can not only bind with Aβ but also specifically target microglia through the interaction between Exo-delivered mannose and mannose receptors expressed in microglia, thus promoting Aβ entry into microglia. Exosomal Gem activated lysosomal activity and accelerated lysosome-mediated clearance of Aβ in microglia. Finally, MExo-Gem improved the learning and memory ability of AD model mice., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The evidence between diurnal temperature range (DTR) and stroke remains controversial and sparse. We aimed to assess the relationship between DTR and emergency ambulance dispatches (EADs) due to stroke, and to explore whether there were effect modifications to the relationship., Methods: A Quasi-Poisson generalized linear regression combined with a distributed lag non-linear model was used to examine the relationship between DTR and EADs for stroke between January 1st 2011 and June 30th 2018 in Guangzhou, China. We estimated the effects of the low DTR and high DTR (defined as DTR below and above 10 °C respectively) on EADs. The effects of minimum, maximum, 5th, 25th, 50th, 75th, and 95th percentiles of DTR compared with the DTR of 10 °C were also analyzed., Results: A total of 20,275 EADs for stroke were included for analyses, among which 17,556 EADs were used in the model further adjusted for age and sex. A quasi-U-shaped relationship between DTR and EADs over lag0-2 days was observed. For the low DTR, per 1 °C decrease in DTR was significantly associated with an increase of 2.64% (RR = 1.03, 95% CI: 1.01-1.04) for EADs, while per 1 °C increase for the high DTR was non-significantly related with an increased risk of EADs (RR = 1.01, 95% CI: 0.90-1.13). Significant effects of the 5th and 25th percentiles of DTR on EADs were found when compared with the DTR of 10 °C. No significant effect modifications by age, sex or season were found to the association between DTR and EADs., Conclusions: We found a quasi-U-shaped relationship between DTR and EADs due to stroke in this study, while age, sex or season did not significantly modify the association between DTR and EADs. More high-quality evidence is needed to further explore and validate the relationship between DTR and stroke., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Non-line-of-sight (NLOS) imaging enables people to see a hidden scene based on multiple interaction information between the object and the carrier. There have been numerous studies focusing on the physical modeling of photon scattering, but few have explored the detection process, which also plays a vital role. In this paper, we put forward a novel, to the best of our knowledge, detection methodology for NLOS imaging based on time-sequential first photon (TSFP) data. We verify the method with both synthetic and experimental data, showing a dramatic reduction in acquisition time cost compared with traditional methods for the same reconstruction quality. This work may contribute to real-time and photon-starved NLOS imaging for practical applications.

Emerging evidence suggests that atherosclerosis, one of the leading phenotypes of cardiovascular diseases, is a chronic inflammatory disease. During the atherosclerotic process, immune cells play critical roles in vascular inflammation and plaque formation. Meanwhile, gastrointestinal disorder is considered a risk factor in mediating the atherosclerotic process. The present study aimed to utilize sivelestat, a selective inhibitor of neutrophil elastase, to investigate its pharmacological benefits on atherosclerosis and disclose the gastrointestinal-vascular interaction. The activation of intestinal neutrophil was increased during atherosclerotic development in Western diet-fed ApoE -/- mice. Administration of sivelestat attenuated atherosclerotic phenotypes, including decreasing toxic lipid accumulation, vascular monocyte infiltration, and inflammatory cytokines. Sivelestat decreased intestinal permeability and endotoxemia in atherosclerotic mice. Mechanistically, sivelestat upregulated the expression of zonula occludens-1 in the atherosclerotic mice and recombinant neutrophil elastase protein-treated intestinal epithelial cells. Meanwhile, treatment of sivelestat suppressed the intestinal expression of inflammatory cytokines and NF-κB activity. In contrast, administration of lipopolysaccharides abolished the anti-atherosclerotic benefits of sivelestat in the Western diet-fed ApoE -/- mice. Further clinical correlation study showed that the circulating endotoxin level and intestinal neutrophil elastase activity were positively correlated with carotid intima-medial thickness in recruited subjects. In conclusion, sivelestat had pharmacological applications in protection against atherosclerosis, and intestinal homeostasis played one of the critical roles in atherosclerotic development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nie, Xiong, Lan, Song, Yu, Chen, Wang, Ren, Chen, Liu and Zhou.)

Grain size is a quantitative trait that is controlled by multiple genes. It is not only a yield trait, but also an important appearance quality of rice. In addition, grain size is easy to be selected in evolution, which is also a significant trait for studying rice evolution. In recent years, many quantitative trait loci (QTL)/genes for rice grain size were isolated by map-based cloning or genome-wide association studies, which revealed the genetic and molecular mechanism of grain size regulation in part. Here, we summarized the QTL/genes cloned for grain size and the regulation mechanism with a view to provide the theoretical basis for improving rice yield and breeding superior varieties.

This study put forward a one-step carbonization method by concentrated sulfuric acid to prepare garlic peel derived biochar, and the synthetic conditions were optimized by L 16 (4 5 ) orthogonal experiments. Notably, in order to study the differences between the proposed synthetic method and the conventional pyrolysis method, the concentrated sulfuric acid carbonized garlic peels biochar (CSGPB) was compared with pyrolysis derived garlic peel biochar (HTGPB) in characterization and adsorption capacities for Enrofloxacin (ENR). Results showed that CSGPB exhibited more graphite-like structures with more active functional groups on the surface, and the equilibrium adsorption capacity of CSGPB (142.3 mg g -1 ) was 13.7 times of HTGPB (10.4 mg g -1 ) under identical conditions. Moreover, the adsorption behaviors including adsorption kinetics, isotherms and thermodynamics of CSGPB for ENR were fully investigated and discussed. Based on the above experiments, density functional theory (DFT) simulations were performed to reveal the interfacial interaction and adsorption mechanism. Results showed π-π interaction between quinolone moieties of ENR and graphite-like structures in CSGPB might be the dominant mechanism. As for the functional groups, the adsorption energies were -40.46, -15.21 and -5.96 kJ mol -1 for -SO 3 H, -OH and -COOH, respectively, which indicated -SO 3 H was the most active functional groups on the surface of CSGPB. This study provided a new sustainable perspective for the design of efficient biochars, and explored the interfacial interaction mechanism of antibiotics removal on biochars., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Xerostomia is a common symptom in menopausal women, suggesting the role of sex steroids in disease development. Shreds of literature had reported the potential use of herbal extracts to relieve xerostomia. However, a cocktail of multiple components in herbal extract makes it difficult to understand the exact mechanism of action. Aquaporin5 (AQP5), the specific aquaporin expressed in salivary glands, plays an important role in salivary secretion as a downstream of estrogen signaling. In this study, we aimed to unravel a single active herbal component as a therapeutic for xerostomia and investigate its mechanism of action. The effects of apigenin (flavonoid), dauricine (alkaloids), protopine (alkaloids), and lentinan (polysaccharides) on AQP5 transcription were screened in vitro . Only apigenin robustly induced AQP5 transcription and expression, and this effect was even robust compared to the effect of estradiol (E2, a positive control). Overexpression of estrogen receptor α (ERα) in the human salivary gland cell line (HSG) upregulated the AQP5 transcription and expression and the knockdown ERα reversed this effect, suggesting the role of ERα signaling on AQP5 activation in HSG cells. Docking results showed apigenin-specific binding sites in ERα. We further analyzed the therapeutic effect of apigenin on ovariectomized mice as a xerostomia model. The saliva secretion in the xerostomia group was reduced to one-third of the sham group, whereas the apigenin or E2 treatment for 12 weeks reversed this effect. Meanwhile, the water consumption in the xerostomia group was augmented obviously compared to the sham group, whereas the water consumption in the apigenin and E2 group was declined to the level of the sham group. Immunohistochemistry of submandibular glands revealed the downregulation of AQP5 expression in xerostomia mice compared to control. Apigenin, or E2 treatment, upregulated AQP5 expression in xerostomia mice. In conclusion, apigenin, a single active component of herbal extract, upregulated AQP5 expression in HSG cells via activation of ERα signaling and restored saliva flow rates in OVX mice. These results revealed apigenin as a single active component of herbal extract with the potential to treat xerostomia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Cao, Pathak, Liu, Mao, Watanabe, Li, Zhang and Li.)