Correlational analysis of sarcopenia and multimorbidity among older inpatients.

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.

Two transcription factors, RhERF005 and RhCCCH12, regulate rose resistance to Botrytis cinerea by modulating cytokinin levels.

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 effect of reward expectation on working memory of emotional faces under different levels of cognitive load: an ERP study.

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.

A Fully Automated Mini-Mental State Examination Assessment Model Using Computer Algorithms for Cognitive Screening.

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.

Improved multi-label classifiers for predicting protein subcellular localization.

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.

Transcription factors RhbZIP17 and RhWRKY30 enhance resistance to Botrytis cinerea by increasing lignin content in rose petals.

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.

Modulation of microglial polarization by sequential targeting surface-engineered exosomes improves therapy for ischemic stroke.

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.

High-Temperature Oxidized Mo2CTx MXene for a High-Performance Supercapacitor.

Molybdenum carbide (Mo2CTx MXene) did not possess suitable properties for supercapacitors. Herein, a short oxidation method of Mo2CTx in air at moderately high temperatures is proposed for fabricating a Mo2C/MoO3 heterostructure. The stability of Mo2CTx 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 Mo2C/MoO3 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.

Assessing the quality of care for skin malignant melanoma on a global, regional, and national scale: a systematic analysis of the global burden of disease study from 1990 to 2019.

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.

Isolation and characterization of ß-transducin repeat-containing protein ligands screened using a high-throughput screening system.

ß-transducin repeat-containing protein (ß-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 ß-TrCP useful for the proteolysis targeting chimera (PROTAC) system using ß-TrCP in the future, we developed a high-throughput screening system for small molecule ß-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 SCFß-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 ß-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 ß-TrCP similar to those created by intrinsic target phosphopeptides of ß-TrCP. Our findings enhance our knowledge of useful small molecule ligands of ß-TrCP and the importance of residues that can be ligands of ß-TrCP.

Efficient and Selective Adsorption of Cationic Dye Malachite Green by Kiwi-Peel-Based Biosorbents.

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 (αMG/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.

Comparative Analysis of Chemical Cross-Linking Mass Spectrometry Data Indicates That Protein STY Residues Rarely React with N-Hydroxysuccinimide Ester Cross-Linkers.

When it comes to mass spectrometry data analysis for identification of peptide pairs linked by N-hydroxysuccinimide (NHS) ester cross-linkers, search engines bifurcate in their setting of cross-linkable sites. Some restrict NHS ester cross-linkable sites to lysine (K) and protein N-terminus, referred to as K only for short, whereas others additionally include serine (S), threonine (T), and tyrosine (Y) by default. Here, by setting amino acids with chemically inert side chains such as glycine (G), valine (V), and leucine (L) as cross-linkable sites, which serves as a negative control, we show that software-identified STY-cross-links are only as reliable as GVL-cross-links. This is true across different NHS ester cross-linkers including DSS, DSSO, and DSBU, and across different search engines including MeroX, xiSearch, and pLink. Using a published data set originated from synthetic peptides, we demonstrate that STY-cross-links indeed have a high false discovery rate. Further analysis revealed that depending on the data and the search engine used to analyze the data, up to 65% of the STY-cross-links identified are actually K-K cross-links of the same peptide pairs, up to 61% are actually K-mono-links, and the rest tend to contain short peptides at high risk of false identification.

Near-Infrared-Activatable PROTAC Nanocages for Controllable Target Protein Degradation and On-Demand Antitumor Therapy.

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.

In Silico Prediction of Human Organ Toxicity via Artificial Intelligence Methods.

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.

Non-line-of-sight imaging with arbitrary illumination and detection pattern.

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.

Comparative genomics analysis of WAK/WAKL family in Rosaceae identify candidate WAKs involved in the resistance to Botrytis cinerea.

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.

Laser doping of 2D material for precise energy band design.

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 (MoTe2). 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 MoTe2 indicates good controllability of the method for the carrier concentration distribution in MoTe2. 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.

Biomimetic oxygen-boosted hybrid membrane nanovesicles as the treatment strategy for ischemic stroke with the concept of the neurovascular unit.

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.

Advances in the Study of Probiotics for Immunomodulation and Intervention in Food Allergy.

Food allergies are a serious food safety and public health issue. Soybean, dairy, aquatic, poultry, and nut products are common allergens inducing allergic reactions and adverse symptoms such as atopic dermatitis, allergic eczema, allergic asthma, and allergic rhinitis. Probiotics are assumed as an essential ingredient in maintaining intestinal microorganisms' composition. They have unique physiological roles and therapeutic effects in maintaining the mucosal barrier, immune function, and gastrointestinal tract, inhibiting the invasion of pathogenic bacteria, and preventing diarrhea and food allergies. Multiple pieces of evidence reveal a significant disruptive effect of probiotics on food allergy pathology and progression mechanisms. Thus, this review describes the allergenic proteins as an entry point and briefly describes the application of probiotics in allergenic foods. Then, the role of probiotics in preventing and curing allergic diseases by regulating human immunity through intestinal flora and intestinal barrier, modulating host immune active cells, and improving host amino acid metabolism are described in detail. The anti-allergic role of probiotics in the function and metabolism of the gastrointestinal tract has been comprehensively explored to furnish insights for relieving food allergy symptoms and preventing food allergy.

Correction: Synergistic effect of polysaccharides and flavonoids on lipid and gut microbiota in hyperlipidemic rats.

Correction for 'Synergistic effect of polysaccharides and flavonoids on lipid and gut microbiota in hyperlipidemic rats' by Yun-fei Bai et al., Food Funct., 2023, 14, 921-933, https://doi.org/10.1039/D2FO03031D.