Discovering Effective Chiral Dipeptides against Aß(1-42) Aggregation by the Computational Screening Strategy.

The ß-sheet-breaker (BSB) peptides inhibiting amyloidogenic aggregation have been extensively studied. However, the inhibition efficacy of ultrashort chiral dipeptides remains inadequately understood. In this study, we proposed a computational screening strategy to identify chiral dipeptides as BSB with optimal antiaggregation performance against Aß(1-42) aggregation. We constructed a complete dipeptide library encompassing all possible chiral sequence arrangements and then filtered the library by cascaded molecular docking-molecular dynamics (MD) simulation. Our screening strategy discovered dipeptide DWDP (superscript for chirality) that displayed strong interactions with Aß fibrils and inhibitory effects on Aß aggregation, validated by subsequent experiments. Mechanistic investigation by both MD and replica-exchange molecular dynamics (REMD) simulations revealed that DWDP interacts with Aß by hydrophobic contacts and hydrogen bonds and thus inhibits Aß intermolecular contacts and salt bridge formation, therefore inhibiting Aß aggregation and disrupting Aß aggregates. Totally, our strategy presents a viable approach to discover potential dipeptides with effective antiaggregation ability as potential therapeutic agents for Alzheimer's disease.

Ship emission variations during the COVID-19 from global and continental perspectives.

The COVID-19 pandemic and the International Maritime Organization's (IMO) 2020 fuel-switching policy have profoundly impacted global maritime activities, leading to unprecedented changes in shipping emissions. This study aimed to examine the effects from different scales and investigate the underlying drivers. The big data model Ship Emission Inventory Model (SEIM) was updated and applied to analyze the spatiotemporal pattern of global ship emissions as well as the main contributors in 2019 and 2020. Overall, ships emitted NOx, CO, HC, CO2, and N2O declined by 7.4 %-13.8 %, while SO2, PM2.5, and BC declined by 40.9 %-81.9 % in 2020 compared with 2019. The decline in CO2 emissions indicated a comparable reduction across vessel tonnages. Ship emissions occurring at cruising status accounted for over 90 % of the ship's CO2 emission reduction. Container ships, chemical tankers, and Ro-Ro vessels were the primary contributors to the emission reductions, with container ships alone responsible for 39.4 % of the CO2 decrease. The ship's CO2 emissions variations revealed the decline-rebound patterns in response to the pandemic. Asian-related routes saw emissions drop in February 2020, followed by a rebound in May, while European and American routes experienced declines starting in May, with a recovery in August. Further analysis of CO2 emission in Exclusive Economic Zones (EEZs) showed high temporal consistency between vessel CO2 emissions, sailing speeds, and international trade volumes across continents, and exhibited heterogeneity in main contributing ship type of emission reduction on continental scale. Our study reveals the short-term fluctuation characteristics of global ship emissions during the pandemic, particularly focusing on their spatiotemporal evolution and the inherent disparities. The results highlight the correlation between global ship emissions and trade, as well as the operational status of ships, and their rigidity.

A comparative study on the toxic effects of lead pollution and nanoplastic-lead mixed pollution on red drum and their detoxification strategies.

Nanoplastics and heavy metals pose various adverse effects on marine organisms. However, the combined toxicity of nanoplastics and lead pollution to marine fish is not fully understood. This study investigates the toxic effects and detoxification strategies of lead pollution (p07) compared to nanoplastic-lead mixed pollution (m07) in red drum during exposure and recovery phases. Under m07 pollution, the maximum lead content in muscle was 22.61 mg/kg, which was significantly higher than the 15.82 mg/kg observed under p07 pollution. This finding demonstrated that nanoplastics significantly enhance lead accumulation, leading to more severe toxic effects on red drum. Histological analyses revealed that lipid droplets in the liver and epithelial lifting in the gills were the primary lesion types. During the exposure periods, red drum primarily detoxified lead through cellular renewal and the removal of damaged proteins under p07 pollution. Conversely, under m07 pollution, detoxification relied on cellular senescence, apoptosis, endocytosis, and the removal of damaged proteins. In the recovery phases, red drum predominantly recovered through cell proliferation and antioxidant responses under p07 pollution. Under m07 pollution, the focus shifted to functional protein synthesis, apoptosis, endocytosis, and lipid metabolism. This study offers valuable insights into the monitoring and management of combined environmental pollution.

Ankaflavin and Monascin Prevent Fibrillogenesis of Hen Egg White Lysozyme: Focus on Noncovalent and Covalent Interactions.

Misfolding and amyloid fibrillogenesis of proteins have close relationships with several neurodegenerative diseases. The present work investigates the inhibitive activities of ankaflavin (AK) and monascin (MS), two yellow pigments separated from Monascus-fermented rice, on hen egg white lysozyme (HEWL) fibrillation. The results demonstrated that AK/MS suppressed HEWL fibrillation through interfering with the nucleation period and AK was more potent. Fluorescence quenching and in silico docking studies revealed that AK/MS bond to HEWL by the formation of noncovalent forces with some critical amino acid residues that tend to form fibrils. Compared to those of AK, hydrogen bonding interactions between MS and Asn46, Trp62, and Trp63 residues in HEWL were slightly weaker. Besides, the covalent interaction between MS and HEWL with the binding site of Arg68 was found. These observations offered reasonable explanations for the difference in the mechanisms of AK and MS inhibiting HEWL fibrillogenesis. In a word, all data acquired herein indicated AK/MS as potent candidates for the improvement and treatment of neurological disorders.

Myocardial work in idiopathic premature ventricular contractions: Assessing left ventricular function and prognosis.

BACKGROUND: Premature ventricular contractions (PVCs) can lead to impairment of left ventricular function. The noninvasive myocardial work technique, which incorporates left ventricular afterload, represents a new method for assessing left ventricular functional. AIM: The aim of this study is to explore the value of noninvasive myocardial work technique in assessing left ventricular systolic function in patients with PVCs. METHODS: Compare the clinical data, two-dimensional echocardiography parameters, and myocardial work parameters of 66 patients with PVCs and 35 healthy volunteers and explore the relevant risk factors for postoperative recurrence in patients with PVCs. RESULTS: In patients with PVCs compared to the control group, they exhibit enlargement of left atrial diameter (LAD) and left ventricular internal dimension in diastole (LVIDd), as well as thickening of the left ventricular wall. The global work waste (GWW) increases, while the global work efficiency (GWE) decreases. There is a significant negative correlation between the PVC burden and GWE (r = -0.70, p <0.01), and a significant positive correlation between the PVC burden and GWW (r = 0.58, p <0.01). GWE is a sensitive indicator for predicting the recurrence of PVCs after radiofrequency ablation. Patients with GWE <91.5%, global longitudinal strain (GLS) <15.5%, and ejection fraction (EF) <62.5% have a higher postoperative recurrence rate. CONCLUSION: PVCs can cause impairment of left ventricular systolic function. GWE is the most sensitive indicator for predicting postoperative recurrence in patients with PVCs. Patients with GWE <91.5%, GLS <15.5%, and EF <62.5% have a higher postoperative recurrence rate.

L-methionine and the L-type Ca2+ channel agonist BAY K 8644 collaboratively contribute to the reduction of depressive-like behavior in mice.

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.

Performance-constrained multi-objective optimization of antennas for miniaturization design.

The miniaturization of antennas is crucial as it improves the integration of wireless communication system. In order to achieve miniaturization of antennas, a performance-constrained multi-objective optimization method (PCMOM) considering the size and return loss is proposed. In the PCMOM method, an optimization strategy based on a multi-port network model is introduced, enabling the formation of antennas with various structures. Furthermore, we integrate the constraint of return loss performance into the non-dominated sorting genetic algorithm II (NSGA-II), eliminating solutions that do not meet performance requirements. Three pixel antennas are designed using the PCMOM method and two of them are fabricated. Experimental results demonstrate that the proposed PCMOM method can effectively address the complex trade-off issues in antenna miniaturization design.

Role of the GalNAc-galectin pathway in the healing of premature rupture of membranes.

BACKGROUND: Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. METHODS: An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. RESULTS: GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05). CONCLUSIONS: GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

Nanofluidic Thermoelectric Transducer with Ultrahigh and Tunable Sensitivity.

Thermosensitive transient receptor potential (thermoTRP) ion channels can transduce external thermal stimuli to neural electrical signals, allowing organisms to detect and respond to changes in environmental temperature. Reproducing such ionic machinery holds promise for advancing the design of highly efficient low-grade thermal energy harvesters and ultrasensitive thermal sensors. However, there still exist challenges for artificial nanofluidic architectures to achieve comparable thermoelectric performance. Here, we report nanofluidic thermoelectric transducers with ultrahigh and tunable sensitivities controlled by electrostatic gating in graphene nanochannels. The equivalent Seebeck coefficient can be significantly boosted and reaches 1 order of magnitude higher than the current state of the art, even beyond thermoTRP ion channels. The improvement is attributed to substantial slippage on the highly charged graphene surface, leading to enhanced electrokinetic ion transport inside the graphene channel, which is confirmed by a scaling theory for thermoelectric coupling as well as molecular dynamic simulations. The dependence of the nanofluidic thermoelectric on the concentration, channel size, and cation types is also investigated to further clarify the underlying mechanism.

Risk factors for hospitalization-associated disability among older patients: A systematic review and meta-analysis.

BACKGROUND: The outcomes of older patients are significantly limited by hospitalization-associated disability (HAD), and there are currently few available management options for HAD. This review aimed to identify and quantify the risk factors for HAD, to provide reliable evidence for developing a HAD prevention program centered on risk factor management among older patients. METHODS: The MEDLINE, Embase, PsycINFO, CINAHL, and PubMed databases were searched in March 2024 to identify cross-sectional and cohort studies that used multivariable analysis to examine risk factors for HAD among older patients. RESULTS: We screened 883 studies, 21 of which met our inclusion criteria. Our findings revealed a substantial association between various risk factors and HAD among older patients. Specifically, advanced age, female sex, Caucasian ethnicity, comorbidity burden, better activities of daily living at admission, dementia diagnosis, and longer lengths of stay were significant risk factors for HAD. Furthermore, frailty, poor physical function, immobility, and delirium were identified as confirmed risk factors for HAD among older patients. CONCLUSIONS: This review provided a comprehensive synthesis of available evidence on risk factors for HAD among older patients, serving as a valuable guide for the development of HAD prevention strategies both prior to and during hospitalization.

Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predicts Cachexia and Prognosis in Hepatocellular Carcinoma Patients.

OBJECTIVE: Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis. METHODS: Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS. RESULTS: Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0-4 vs. 5-6 points) (OR, 9.20; 95% CI: 4.68-18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13-7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0-4 vs. 5-6 points) (HR, 1.73; 95% CI: 1.19-2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0-4 points group had shorter OS than those in the FLIS 5-6 points group [20 months (95% CI, 14.7-25.3) vs. 43 months (95% CI, 27.7-58.3); P=0.001]. CONCLUSION: Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.

Dissection of Targeting Molecular Mechanisms of Celastrol-induced Nephrotoxicity via A Combined Deconvolution Strategy of Chemoproteomics and Metabolomics.

Celastrol (Cel), derived from the traditional herb Tripterygium wilfordii Hook. f., has anti-inflammatory, anti-tumor, and immunoregulatory activities. Renal dysfunction, including acute renal failure, has been reported in patients following the administration of Cel-relative medications. However, the functional mechanism of nephrotoxicity caused by Cel is unknown. This study featured combined use of activity-based protein profiling and metabolomics analysis to distinguish the targets of the nephrotoxic effects of Cel. Results suggest that Cel may bind directly to several critical enzymes participating in metabolism and mitochondrial functions. These enzymes include voltage-dependent anion-selective channel protein 1 (essential for maintaining mitochondrial configurational and functional stability), pyruvate carboxylase (involved in sugar isomerization and the tricarboxylic acid cycle), fatty acid synthase (related to ß-oxidation of fatty acids), and pyruvate kinase M2 (associated with aerobic respiration). Proteomics and metabolomics analysis confirmed that Cel-targeted proteins disrupt some metabolic biosynthetic processes and promote mitochondrial dysfunction. Ultimately, Cel aggravated kidney cell apoptosis. These cumulative results deliver an insight into the potential mechanisms of Cel-caused nephrotoxicity. They may also facilitate development of antagonistic drugs to mitigate the harmful effects of Cel on the kidneys and improve its clinical applications.

Machine learning-assisted diagnosis of parotid tumor by using contrast-enhanced CT imaging features.

PURPOSE: This study aims to develop a machine learning diagnostic model for parotid gland tumors based on preoperative contrast-enhanced CT imaging features to assist in clinical decision-making. MATERIALS AND METHODS: Clinical data and contrast-enhanced CT images of 144 patients with parotid gland tumors from the Peking University School of Stomatology Hospital, collected from January 2019 to December 2022, were gathered. The 3D slicer software was utilized to accurately annotate the tumor regions, followed by exploring the correlation between multiple preoperative contrast-enhanced CT imaging features and the benign or malignant nature of the tumor, as well as the type of benign tumor. A prediction model was constructed using the k-nearest neighbors (KNN) algorithm. RESULTS: Through feature selection, four key features-morphology, adjacent structure invasion, boundary, and suspicious cervical lymph node metastasis-were identified as crucial in preoperative discrimination between benign and malignant tumors. The KNN prediction model achieved an accuracy rate of 94.44 %. Additionally, six features including arterial phase CT value, age, delayed phase CT value, pre-contrast CT value, venous phase CT value, and gender, were also significant in the classification of benign tumors, with a KNN prediction model accuracy of 95.24 %. CONCLUSION: The machine learning model based on preoperative contrast-enhanced CT imaging features can effectively discriminate between benign and malignant parotid gland tumors and classify benign tumors, providing valuable reference information for clinicians.

Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer.

The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC. SIGNIFICANCE: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.

Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis.

Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.

Three-Dimensional Morphological Changes in the Upper Airway After Maxillary Reconstruction With an Anterolateral Thigh Flap.

BACKGROUND: Reconstruction of maxillary defects may lead to changes in the upper airway. These changes may cause postoperative airway obstruction issues. PURPOSE: The purpose was to evaluate the postoperative changes in the upper airway following maxillary reconstruction with an anterolateral thigh flap (ALTF) and to identify the factors associated with these changes. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study involved 26 patients who underwent maxillectomy for maxillary tumors, followed by reconstruction using an ALTF. Patients with a history of upper respiratory system disease and sleep-disorder breathing were excluded. PREDICTOR VARIABLE: The predictor variable was the residual rate of ALTF volume (ALTF-RS), calculated as the ratio of ALTF volume at 6 months postsurgery (T2) to that at 2 weeks postsurgery (T1). THE OUTCOME VARIABLES: The outcome variables were the upper airway parameters. The upper airway was assessed at 3 time points: 1 week preoperatively (T0), T1, and T2. Ratios were used to represent airway changes over time. COVARIATES: The covariates are age, sex, Brown classification, body mass index, hypertension, neck dissection, and tracheostomy, etc. ANALYSES: Airway measurement differences between the three time points were analyzed by one-way analysis of variance. Pearson correlation and Spearman correlation analysis were used to analyze the correlation coefficients between airway changes and ALTF-RS. Statistical significance was established at a P value < .05. RESULTS: The sample included 26 subjects with a mean age of 55.6 ± 15.2 years and 15/26 (57.7%) were male. Compared to T0, the nasopharyngeal and retropalatal airway volumes at T1 significantly decreased (P < .05) but recovered or surpassed preoperative levels by T2. The minimum cross-sectional airway area significantly decreased by T1 (P < .05), but increased by T2 (P < .05). The narrowest airway section was predominantly in the palatopharyngeal airway. The airway changes of T2/T1 and ALTF-RS were not correlated (P > .05) except for anterior-inferior point of the 4th cervical vertebra cross-sectional area (P < .05). CONCLUSION AND RELEVANCE: The volumetric changes in the airway were not associated with ALTF-RS. The substantial narrowing of minimum cross-sectional airway area at T1 emphasized the need for vigilant airway management in these patients.

Global patterns and determinants of the initial concentrations of litter carbon components.

Plant litter is an important carbon (C) and nutrient pool in terrestrial ecosystems. The C components in plant litter are important because they regulate plant litter decomposition rate, but little is known on the global patterns and determinants of their concentrations in freshly fallen plant litter. Here, we quantified the concentrations of leaf litter C components (i.e., carbohydrate, polyphenol, tannin, and condensed tannin) with 864 measurements from 161 independent publications. We found that (1) the mean concentrations of leaf litter carbohydrate, polyphenol, tannin and condensed tannin were 27.7, 6.08, 8.84 and 5.7 %, respectively; (2) the concentrations of leaf litter C components were affected by taxonomic division, mycorrhizal association, life form, and/or leaf shedding strategy; (3) soil property had similar impacts on the concentrations of the four C compounds, while the influence of mean annual temperature and precipitation varied; and (4) elevation had opposing effects on carbohydrate and polyphenol concentrations, but not on that of tannin and condensed tannin, and only carbohydrate concentration was strongly affected by absolute latitude. In general, our results clearly show the global patterns and drivers of the concentrations of litter C compounds, providing new insights into the role of litter decomposition in global C dynamics.

OsUVR8b, rather than OsUVR8a, plays a predominant role in rice UVR8-mediated UV-B response.

UV RESISTANCE LOCUS 8 (UVR8) has been identified in Arabidopsis thaliana as the receptor mediating responses to UV-B radiation. However, UVR8-mediated UV-B signaling pathways in rice, which possesses two proteins (UVR8a and UVR8b) with high identities to AtUVR8, remain largely unknown. Here, UVR8a/b were found to be predominantly expressed in rice leaves and leaf sheaths, while the levels of UVR8b transcript and UVR8b protein were both higher than those of UVR8a. Compared to wild-type (WT) plants, uvr8b and uvr8a uvr8b rice mutants exposed to UV-B showed reduced UV-B-induced growth inhibition and upregulation of CHS and HY5 transcripts alongside UV-B acclimation. However, uvr8a mutant was similar to WT plants and exhibited changes comparable with WT. Overexpressing OsUVR8a/b enhanced UV-B-induced growth inhibition and acclimation to UV-B. UV-B was able to enhance the interaction between E3 ubiquitin ligase OsCOP1 and OsUVR8a/b, whereas the interaction of the homologous protein of Arabidopsis REPRESSOR OF UV-B PHOTOMORPHOGENESIS2 (AtRUP2) in rice with OsUVR8a/b was independent of UV-B. Additionally, OsUVR8a/b proteins were also found in the nucleus and cytoplasm even in the absence of UV-B. The abundance of OsUVR8 monomer showed an invisible change in the leaves of rice seedlings transferred from white light to that supplemented with UV-B, even though UV-B was able to weaken the interactions between OsUVR8a and OsUVR8b homo and heterodimers. Therefore, both OsUVR8a and OsUVR8b, which have different localization and response patterns compared with AtUVR8, function in the response of rice to UV-B radiation, whereas OsUVR8b plays a predominant role in this process.

Structural basis for linker histone H5-nucleosome binding and chromatin fiber compaction.

The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.

Postoperative facial prediction for mandibular defect based on surface mesh deformation.

OBJECTIVES: This study aims to introduce a novel predictive model for the post-operative facial contours of patients with mandibular defect, addressing limitations in current methodologies that fail to preserve geometric features and lack interpretability. METHODS: Utilizing surface mesh theory and deep learning, our model diverges from traditional point cloud approaches by employing surface triangular mesh grids. We extract latent variables using a Mesh Convolutional Restricted Boltzmann Machines (MCRBM) model to generate a three-dimensional deformation field, aiming to enhance geometric information preservation and interpretability. RESULTS: Experimental evaluations of our model demonstrate a prediction accuracy of 91.2 %, which represents a significant improvement over traditional machine learning-based methods. CONCLUSIONS: The proposed model offers a promising new tool for pre-operative planning in oral and maxillofacial surgery. It significantly enhances the accuracy of post-operative facial contour predictions for mandibular defect reconstructions, providing substantial advancements over previous approaches.