Alpha-fetoprotein and APRI as predictive markers for patients with Type C hepatitis B-related acute-on-chronic liver failure: a retrospective study.

BACKGROUND: Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF. METHOD: Patients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model. RESULTS: A total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH-ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer. CONCLUSIONS: A new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.

Can energy saving and emission reduction policies promote green transformation of industrial enterprises--The Case of China.

In the context of the continued advancement of the green economy transition, the proactive pursuit of carbon emissions reduction and the early attainment of carbon neutrality goals have emerged as essential components in promoting high-quality economic development. Not only does it contribute to the creation of a community of human destiny, but it is also vital to the realization of sustainable development for human civilization. A dynamic evolutionary game model, which encompasses the interactions among government, enterprises, and the public, was constructed to examine the inherent impact mechanisms of the behavior of three players on the development of a green economy under the context of energy saving and emission reduction subsidies. The results showed that the incentive and punishment mechanisms served as effective tools for harmonizing the interests of system members. Within the mechanisms, the public demonstrated a higher sensitivity to rewards, while enterprises exhibited greater responsiveness to fines. Consequently, the government could influence the behavior of enterprises by incentivizing the public to serve as a third-party inquiry and oversight body. Simultaneously, the government could encourage enterprises to expedite green technology innovation by employing a combination of incentive and punishment mechanisms.

First report of leaf spot disease caused by Pseudopithomyces chartarum on Lonicera caerulea L. in Heilongjiang Province, China.

Blue honeysuckle (Lonicera caerulea L.) cultivation has gradually expanded in China but continues to be limited by challenges such as leaf spot disease. Between September 2022 and September 2023, a leaf spot disease was observed on approximately 30% of 'Lanjingling' blue honeysuckles grown in a 2.66 ha field (a total of about 11,000 plants) in Jiamusi city (130.47°E, 46.16°N), Heilongjiang Province, China. Affected plants displayed brown necrotic lesions on their leaves that gradually expanded in area until the leaves fell off the plant entirely. Small, 3 to 4 mm segments of infected tissue from 50 randomly selected leaves were surface sterilized with 75% ethanol for 30 s and 5% sodium hypochlorite (NaOCl) for 3 min, rinsed three times with sterile distilled water, dried on paper towels, and plated in 9 cm Petri dishes containing potato dextrose agar (PDA) (Yan et al. 2022). Five pathogens (LD-232, LD-233, LD-234, LD-235, and LD-236) were isolated on PDA and displayed a conidia morphology consistent with Pseudopithomyces spp. (Perelló et al. 2017). The fungal colonies on PDA were villiform, white, and whorled and had sparse aerial mycelium on the surface with black conidiomata. The conidia were obpyriform and dark brown, had 0 to 3 transverse and 0 to 1 longitudinal septa, and measured 9.00 to 15.30 µm × 5.70 to 9.30 µm in size (n = 50). Genomic DNA was extracted from a representative isolate, LD-232, for molecular verification and PCR amplification was performed with ITS1/ITS4 (White et al. 1990), LROR/LR7 (Carbone and Kohn 1999), and RPB2-5F2/RPB2-7CR (Liu et al. 1999) primers. Sequences of LD-232 ITS (OR835654), LSU (OR835652), and RPB2 (OR859769) revealed 99.8% (530/531 nt), 98.8% (639/647 nt), and 99.8% (1015/1017 nt) shared identity with Pseudopithomyces chartarum sequences (OP269600, OP237014, and MK434892), respectively (Wu et al. 2023). Bayesian inference (BI) was used to construct the phylogenies using Mr. Bayes v. 3.2.7 to confirm the identity of the isolates (Ariyawansa et al. 2015). Phylogenetic trees cannot be constructed based on the genes' concatenated sequences because selective strains do not have complete rDNA-ITS, LSU, and RPB2 sequences. Therefore, based on the morphological characteristics and molecular phylogeny, LD-232 was identified as P. chartarum (Perelló et al. 2017; Wu et al. 2023). A pathogenicity test was performed with six healthy, two-year-old 'Lanjingling' blue honeysuckle plants. Three plants were inoculated by spraying the LD-232 conidial suspension (1 × 106 spores/ml) or clean water as an experimental control condition (Wu et al. 2023; Yan et al. 2023). All plants were cultured in a greenhouse at 28℃ under a 12-h light/dark cycle, and each experiment was replicated three times. Typical leaf spot symptoms were observed on inoculated leaves after 10 days. The same pathogens were reisolated from infected leaves, displayed the same morphological and molecular traits, and were again identified as P. chartarum, confirming Koch's postulate. P. chartarum previously caused leaf spot disease on Tetrapanax papyrifer in China (Wu et al. 2023). To our knowledge, this is the first report of blue honeysuckle leaf spot caused by P. chartarum in China. Identification of P. chartarum as a disease agent on blue honeysuckle will help guide future management of leaf diseases for this economically important small fruit tree.

Suppression of OsSAUR2 gene expression immobilizes soil arsenic bioavailability by modulating root exudation and rhizosphere microbial assembly in rice.

One of the factors influencing the behavior of arsenic (As) in environment is microbial-mediated As transformation. However, the detailed regulatory role of gene expression on the changes of root exudation, rhizosphere microorganisms, and soil As occurrence forms remains unclear. In this study, we evidence that loss-of-function of OsSAUR2 gene, a member of the SMALL AUXIN-UP RNA family in rice, results in significantly higher As uptake in roots but greatly lower As accumulation in grains via affecting the expression of OsLsi1, OsLsi2 in roots and OsABCC1 in stems. Further, the alteration of OsSAUR2 expression extensively affects the metabolomic of root exudation, and thereby leading to the variations in the composition of rhizosphere microbial communities in rice. The microbial community in the rhizosphere of Ossaur2 plants strongly immobilizes the occurrence forms of As in soil. Interestingly, Homovanillic acid (HA) and 3-Coumaric acid (CA), two differential metabolites screened from root exudation, can facilitate soil iron reduction, enhance As bioavailability, and stimulate As uptake and accumulation in rice. These findings add our further understanding in the relationship of OsSAUR2 expression with the release of root exudation and rhizosphere microbial assembly under As stress in rice, and provide potential rice genetic resources and root exudation in phytoremediation of As-contaminated paddy soil.

Exploring the Conformational Ensembles of Protein-Protein Complex with Transformer-Based Generative Model.

Protein-protein interactions are the basis of many protein functions, and understanding the contact and conformational changes of protein-protein interactions is crucial for linking the protein structure to biological function. Although difficult to detect experimentally, molecular dynamics (MD) simulations are widely used to study the conformational ensembles and dynamics of protein-protein complexes, but there are significant limitations in sampling efficiency and computational costs. In this study, a generative neural network was trained on protein-protein complex conformations obtained from molecular simulations to directly generate novel conformations with physical realism. We demonstrated the use of a deep learning model based on the transformer architecture to explore the conformational ensembles of protein-protein complexes through MD simulations. The results showed that the learned latent space can be used to generate unsampled conformations of protein-protein complexes for obtaining new conformations complementing pre-existing ones, which can be used as an exploratory tool for the analysis and enhancement of molecular simulations of protein-protein complexes.

X-ray Structure-Guided Discovery of a Potent Benzimidazole Glutaminyl Cyclase Inhibitor That Shows Activity in a Parkinson's Disease Mouse Model.

The secretory glutaminyl cyclase (sQC) and Golgi-resident glutaminyl cyclase (gQC) are responsible for N-terminal protein pyroglutamation and associated with various human diseases. Although several sQC/gQC inhibitors have been reported, only one inhibitor, PQ912, is currently undergoing clinic trials for the treatment of Alzheimer's disease. We report an X-ray crystal structure of sQC complexed with PQ912, revealing that the benzimidazole makes "anchor" interactions with the active site zinc ion and catalytic triad. Structure-guided design and optimization led to a series of new benzimidazole derivatives exhibiting nanomolar inhibition for both sQC and gQC. In a MPTP-induced Parkinson's disease (PD) mouse model, BI-43 manifested efficacy in mitigating locomotor deficits through reversing dopaminergic neuronal loss, reducing microglia, and decreasing levels of the sQC/gQC substrates, α-synuclein, and CCL2. This study not only offers structural basis and new leads for drug discovery targeting sQC/gQC but also provides evidence supporting sQC/gQC as potential targets for PD treatment.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome.

BACKGROUND: G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. METHODS: The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. RESULTS: Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes' transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy's efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. CONCLUSION: This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy.

Reproductive factors and cardiometabolic disease among middle-aged and older women: a nationwide study from CHARLS.

Background: Cardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014-2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years. Methods: The CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects. Results: Of 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0-1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714-0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027-1.357). Age at menarche of 16-18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749-0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006-1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values. Conclusions: Our findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.

BCKDK modification enhances the anticancer efficacy of CAR-T cells by reprogramming branched chain amino acid metabolism.

Altered branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, are frequently observed in patients with advanced cancer. We evaluated the efficacy of chimeric antigen receptor (CAR) T cell-mediated cancer cell lysis potential in the immune microenvironment of BCAA supplementation and deletion. BCAA supplementation increased cancer cell killing percentage, while accelerating BCAA catabolism and decreasing BCAA transporter decreased cancer cell lysis efficacy. We thus designed BCKDK engineering CAR T cells for the reprogramming of BCAA metabolism in the tumor microenvironment based on the genotype and phenotype modification. BCKDK overexpression (OE) in CAR-T cells significantly improved cancer cell lysis, while BCKDK knockout (KO) resulted in inferior lysis potential. In an in vivo experiment, BCKDK-OE CAR-T cell treatment significantly prolonged the survival of mice bearing NALM6-GL cancer cells, with the differentiation of central memory cells and an increasing proportion of CAR-T cells in the peripheral circulation. BCKDK-KO CAR-T cell treatment resulted in shorter survival and a decreasing percentage of CAR-T cells in the peripheral circulation. In conclusion, BCKDK-engineered CAR-T cells exert a distinct phenotype for superior anticancer efficiency.

CGRP as a potential mediator for the sexually dimorphic responses to traumatic brain injury.

BACKGROUND: The outcomes of traumatic brain injury (TBI) exhibit variance contingent upon biological sex. Although female sex hormones exert neuroprotective effects, the administration of estrogen and progesterone has not yielded conclusive results. Hence, it is conceivable that additional mediators, distinct from female sex hormones, merit consideration due to their potential differential impact on TBI outcomes. Calcitonin gene-related peptide (CGRP) exhibits sexually dimorphic expression and demonstrates neuroprotective effects in acute brain injuries. In this study, we aimed to examine sex-based variations in TBI structural and functional outcomes with respect to CGRP expression. METHODS: Male and female Sprague Dawley rats were exposed to controlled cortical impact to induce severe TBI, followed by interventions with and without CGRP inhibition. In the acute phase of TBI, the study centered on elucidating the influence of CGRP on oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and endothelial nitric oxide synthase (eNOS) signaling in the peri-impact tissue. Subsequently, during the chronic phase of TBI, the investigation expanded to evaluate CGRP expression in relation to lesion volume, microvascular dysfunction, and white matter injury, as well as working and spatial memory, anxiety-like, and depression-like behaviors in subjects of both sexes. RESULTS: Female rats exhibited elevated levels of CGRP in the peri-impact brain tissue during both baseline conditions and in the acute and chronic phases of TBI, in comparison to age-matched male counterparts. Enhanced CGRP levels in specific brain sub-regions among female rats correlated with superior structural and functional outcomes following TBI compared to their male counterparts. CGRP inhibition induced heightened oxidative stress and a reduction in the expression of Nrf2 and eNOS in both male and female rats, with the observed alteration being more pronounced in females than in males. CONCLUSIONS: This study marks the inaugural identification of CGRP as a downstream mediator contributing to the sexually dimorphic response observed in TBI outcomes.

Investigating sex disparities in traumatic brain injury (TBI) is crucial for the advancement of precision therapeutics. Despite the neuroprotective effects demonstrated by female sex hormones, the administration of estrogen and progesterone has not produced conclusive results. Therefore, it is conceivable that additional mediators, separate from female sex hormones, warrant consideration due to their potential differential influence on TBI outcomes. In this study, we examined sex-related variations in calcitonin gene-related peptide (CGRP) expression in peri-impact brain tissue and investigated its potential implications on associated TBI outcomes. CGRP exhibits sexually dimorphic expression and exerts a multifaceted influence on diverse physiological processes that contribute to the pathophysiology of TBI. Our findings reveal that female rats exhibit heightened CGRP levels at both baseline and post-TBI within specific brain sub-regions, thereby contributing to superior structural and functional outcomes compared to their age-matched male counterparts. Additionally, we identified substantial sex-based variations in mechanisms modulated by CGRP pertaining to oxidative stress and microvascular dysfunction. The disparities in CGRP levels may be crucial for comprehending the advantageous outcomes noted in female TBI. Therefore, elucidating the sex-related distinctions in CGRP within TBI brains could pave the way for improved management and treatment strategies for TBI in both male and female individuals.

Al(OTf)3-Catalyzed Regioselective N2-Arylation of Tetrazoles with Diazo Compounds.

Regioselective methods to access alkylated tetrazoles still remain a challenging goal. Herein, we describe a novel regioselective protocol for N2-arylation of tetrazoles with diazo compounds using inexpensive Al(OTf)3. This reaction could be conducted under mild conditions to access a diverse array of alkylated tetrazoles with 2-substituted tetrazoles as the major products, demonstrating a comprehensive range of substrate compatibility and excellent functional group compatibility. Mechanistic studies revealed a carbene-free process in this reaction procedure. Furthermore, the scale-up reaction and transformations of the N2-arylation of tetrazole products demonstrated the potential of this strategy.

miR-4685-3p Alleviates Human Brain Microvascular Endothelial Cells Injury by Regulating MMP9.

OBJECTIVE: Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury. METHODS: We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9. RESULTS: The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression. CONCLUSION: Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.

Growth increase and gonadal dysfunction of the lined seahorse triggered by zinc exposure.

Seahorses are characterized by unique characteristics such as a male pregnancy reproductive strategy and grasping preferences, which make these species vulnerable to various environmental risks. Zinc (Zn) is one of the most frequently occurring toxic elements in coastal waters; however, little is known about the effect of Zn exposure on seahorses. In the present study, line seahorses (Hippocampus erectus) were exposed to waterborne Zn (0.2 and 1.0 mg/L) and the impact on growth and gonadal development was investigated. Zn exposure induced growth improvement, but also led to gonadal dysfunction in the lined seahorse. Female seahorses exhibited high testosterone levels, immature follicles, and weight increase after Zn exposure, which is the typical characteristics of a polycystic ovary syndrome (PCOS)-like phenotype. Transcriptomic data suggested that the Zn-induced growth promotion resulted from the dysregulated expression of fat accumulation genes. Further investigation of gene expression profiles in the brain, ovaries, and testes indicated that Zn affected the expression of genes involved in growth, immunity, tissue remodeling, and gonadal development by regulating serum steroid hormone levels and androgen receptor expression. This study not only clarifies the complex impact of Zn on seahorses using physiological, histological, and molecular evidence but can also provide new insights into the mechanism underlying PCOS in reproductive-aged women. Moreover, this work demonstrates the risk of the common practice of Zn supplementation in the aquaculture industry as the consequent growth yield may not represent a healthy condition.

Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.

Protein profile of circulating extracellular vesicles reveals biomarker candidates for diagnosis of post-traumatic deep vein thrombosis.

BACKGROUND AND OBJECTIVE: Deep vein thrombosis (DVT) is a common complication after trauma and mostly without specific symptoms. Timely diagnosis and early appropriate treatment measures can prevent further development of thrombosis for patients with traumatic lower extremity fractures. Although extracellular vesicles (EVs) are confirmed as promising disease biomarkers, little is known about the role of altered levels and composition in the diagnosis of post-traumatic DVT. METHOD: The levels of circulating EVs subgroups were measured using flow cytometry. Isolated EVs were characterized and subjected to proteomics analysis to screen for differentially expressed proteins (DEPs) between DVT and non-DVT patients. Regularized logistic regression analysis based on L2 penalty terms using R's caret package was applied to build a model for DVT diagnosis. RESULTS: Compared to non-DVT patients, DVT patients had higher circulating hepatocyte-derived EVs (hEVs) with good predictive value for post-traumatic DVT diagnosis. The results of the proteomic analysis showed that differentially expressed proteins (DEPs) of circulating EVs between the DVT group and non-DVT group were enriched in the complement and coagulation cascade. Finally, an integrated model of five biomarkers including SERPING1, C8G, CFH, FIX, and hEVs level was established for post-traumatic DVT diagnosis with robust identification of the traumatic patients with and without DVT (AUC 0.972). CONCLUSION: Post-traumatic DVT patients had changed levels and composition of circulating EVs compared to non-DVT patients and healthy controls. Circulating EVs may acquire pathological protein signatures and become potential biomarkers for identifying subjects' post-traumatic DVT.

Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty: a prospective, double-blind, pilot, randomised controlled trial.

Background: Postoperative sleep disturbance (PSD) is a common and serious postoperative complication and is associated with poor postoperative outcomes. Aims: This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on PSD in older patients undergoing lower limb major arthroplasty. Methods: In this prospective, double-blind, pilot, randomised, sham-controlled trial, patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS (a-tDCS) or sham tDCS (s-tDCS). The primary outcomes were the objective sleep measures on postoperative nights (N) 1 and N2. Results: 116 inpatients were assessed for eligibility, and a total of 92 patients were enrolled; 47 received a-tDCS and 45 received s-tDCS. tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups; the respective comparisons were as follows: the promotion of rapid eye movement (REM) sleep time on N1 (64.5 (33.5-105.5) vs 19.0 (0.0, 45.0) min, F=20.10, p<0.001) and N2 (75.0 (36.0-120.8) vs 30.0 (1.3-59.3) min, F=12.55, p<0.001); the total sleep time on N1 (506.0 (408.0-561.0) vs 392.0 (243.0-483.5) min, F=14.13, p<0.001) and N2 (488.5 (455.5-548.5) vs 346.0 (286.5-517.5) min, F=7.36, p=0.007); the deep sleep time on N1 (130.0 (103.3-177.0) vs 42.5 (9.8-100.8) min, F=24.4, p<0.001) and N2 (103.5 (46.0-154.8) vs 57.5 (23.3-106.5) min, F=8.4, p=0.004); and the percentages of light sleep and REM sleep on N1 and N2 (p<0.05 for each). The postoperative depression and anxiety scores did not differ significantly between the two groups. No significant adverse events were reported. Conclusion: In older patients undergoing lower limb major arthroplasty, a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures. However, this benefit was temporary and was not maintained over time.