Theoretical calculation on degradation mechanism of novel copolyesters under CALB enzyme.

Poly(butylene succinate-co-furandicarboxylate) (PBSF) and poly(butylene adipate-co-furandicarboxylate) (PBAF) are novel furandicarboxylic acid-based biodegradable copolyesters with great potential to replace fossil-derived terephthalic acid-based copolyesters such as poly(butylene succinate-co-terephthalate) (PBST) and poly(butylene adipate-co-terephthalate) (PBAT). In this study, quantum chemistry techniques after molecular dynamics simulations are employed to investigate the degradation mechanism of PBSF and PBAF catalyzed by Candida antarctica lipase B (CALB). Computational analysis indicates that the catalytic reaction follows a four-step mechanism resembling the ping-pong bibi mechanism, with the initial two steps being acylation reactions and the subsequent two being hydrolysis reactions. Notably, the first step of the hydrolysis is identified as the rate-determining step. Moreover, by introducing single-point mutations to expand the substrate entrance tunnel, the catalytic distance of the first acylation step decreases. Additionally, energy barrier of the rate-determining step is decreased in the PBSF system by site-directed mutations on key residues increasing hydrophobicity of the enzyme's active site. This study unprecedently show the substrate binding pocket and hydrophobicity of the enzyme's active site have the potential to be engineered to enhance the degradation of copolyesters catalyzed by CALB.

Enhancing the sodium storage performance of hard carbon by constructing thin carbon coatings via esterification reactions.

Hard carbons derived from pitch are considered a competitive low-cost anode for sodium-ion batteries. However, the preparation of pitch-based hard carbon (PHC) requires the aid of a pre-oxidation strategy, which introduces unnecessary defects and oxygen elements, which leads to low initial Coulombic efficiency (ICE) and poor cycling stability. Herein, we demonstrate a new surface engineering strategy by grafting chemically active glucose molecules on the PHC surface via esterification reactions, which can achieve low-cost nano-scaled carbon coating. Thin glucose coating can be carbonized at a lower temperature, which results in a more closed pore structure and fewer functional groups. The as prepared PHC exhibits a high reversible capacity of 328.5 mAh/g with a high ICE of 92.08 % at 0.02 A/g. It is noteworthy that the PHC can be adapted to a variety of cathode materials for full-cell assembling without pre-sodiation, which maintains the characteristics of high capacity and excellent cycling stability. The performance of resin-based hard carbon coated with a similar method was also improved, demonstrating the universality of the technique.

Prolonged course of Paxlovid administration in a centenarian with COVID-19: A case report.

BACKGROUND: According to the population statistics in 2023, there were 110000 people aged over 100 years in China, and the experience of using Paxlovid (nirmatrelvir/ritonavir) for centenarians is particularly valuable. This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019 (COVID-19) infection. CASE SUMMARY: A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days. During treatment, the patient was complicated with lung infection and heart failure, and nucleic acid remained positive. After expert consultation, a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days. Meanwhile, anti-heart failure and antibiotics were administered; the heart failure and pulmonary infection were improved. Finally, on the 33th day of admission, nucleic acid turned negative, body temperature returned to normal, cough and sputum, fatigue, poor appetite and other symptoms basically improved. The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function, diarrhea, nausea and vomiting, myalgia, chest tightness and other side effects, and was discharged from hospital with good recovery. CONCLUSION: This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.

Electronic Structure Determines Geometry: Bond Length Alternating in Cyclo[2n]carbons.

Structure determines the properties. However, whether electronic structure determines geometry or geometry determines electronic structure seems a philosophical question in a chicken and egg situation, which remains unclear. In this work, by applying density functional theory (DFT) and DMRG(4n,4n)-CASSCF methods, theoretical investigation suggested that the dual antiaromaticity in cyclo[2n]carbons with even n should be attributed to the electron correlation effect, instead of decreased geometric symmetry, which actually exists in all cyclo[2n]carbon molecules and does not point out the essence. Such dual antiaromaticity can be conceptualized as electron correlation-stabilized dual antiaromaticity. Results also showed that DFT is reliable for cyclocarbons larger than C14, but we should be careful when applying it to smaller ones. DFT failed to give the correct structure of C6 compared with density matrix renormalization group results.

Urolithin A promotes the degradation of TMSB10 to deformation F-actin in non-small-cell lung cancer.

BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers and non-small-cell lung cancer (NSCLC) poses major diagnoses. Urolithin A (UA) is a natural compound produced by the gut microbiota through the metabolism of polyphenol ellagitannins (ETs) and ellagic acid (EA), which has been found to inhibit epithelial-mesenchymal transition (EMT) in lung cancer cell lines. However, the mechanism of UA function in NSCLC remains elusive. PROPOSE: This study aimed to investigate the potential effectiveness of UA in NSCLC therapeutic and uncovering its underlying mechanisms. METHODS: Effects of UA treatment, TMSB10 gene knockdown or overexpression on NSCLC cell phenotype were evaluated by availability, transwell assays. The downstream factors and pathways of UA were investigated by proteomics. TMSB10 expression in NSCLC tissues was detected by bioinformatics analysis as well as immunohistochemistry. Confocal imaging, GST pull-down and western blotting investigated the mechanism of UA induced TMSB10 degradation. RESULTS: In the present study, we demonstrated that UA shows an inhibitory role in NSCLC cell proliferation, migration, and invasion. This inhibition is attributed to the accelerated degradation of TMSB10, a biomarker among various cancers, via the autophagy-lysosome pathway. Additionally, knocked down of TMSB10 showed a similar phenotype with UA treatment. The reduction of TMSB10 protein level following decreased ATP level inhibits the F-actin formation for cell migration, thereby disrupting the equilibrium between G-actin-TMSB10 and G-actin-ATP interactions in A549 cells. CONCLUSION: Our results reveal that UA is potential for NSCLC therapeutics through reducing the protein level of TMSB10 to deformation the F-actin.

Clinical research progress on ß-cell dysfunction in T2DM development in the Chinese population.

The prevalence of type-2 diabetes mellitus (T2DM) has increased over 10-fold in the past 40 years in China, which now has the largest T2DM population in the world. Insulin resistance and ß-cell dysfunction are the typical features of T2DM. Although both factors play a role, decreased ß-cell function and ß-cell mass are the predominant factors for progression to T2DM. Considering the differences between Chinese T2DM patients and those of other ethnicities, it is important to characterize ß-cell dysfunction in Chinese patients during T2DM progression. Herein, we reviewed the studies on the relationships between ß-cell function and T2DM progression in the Chinese population and discussed the differences among individuals of varying ethnicities. Meanwhile, we summarized the risk factors and current treatments of T2DM in Chinese individuals and discussed their impacts on ß-cell function with the hope of identifying a better T2DM therapy.

Inhibition of protein disulfide isomerase mitigates steroid-induced osteonecrosis of the femoral head by suppressing osteoclast activity through the reduction of cellular oxidative stress.

Osteonecrosis of the femoral head (ONFH) is a devastating and irreversible hip disease usually associated with increased oxidative stress due to the clinical application of high-dose or long-term glucocorticoids (GCs). Previous publications have demonstrated protein disulfide isomerase (PDI) plays a critical role in regulating cellular production of reactive oxygen species (ROS). We therefore ask whether interfering PDI could affect GCs-stimulated osteoclastogenesis. To test the hypothesis, we conducted bioinformatics and network analysis based on potential gene targets of steroid-induced osteonecrosis of the femoral head (SIONFH) in light of multiple databases and concomitantly verified the associated biological effect via the in vitro model of dexamethasone (DEX)-stimulated osteoclastogenesis. The results revealed 70 potential gene targets for SIONFH intervention, including the P4HB gene that encodes PDI. Further analysis based on network topology-based analysis techniques (NTA), protein-protein interaction (PPI) networks, and mouse cell atlas database identified the importance of PDI in regulating the cellular redox state of osteoclast during ONFH. Western blotting (WB) validations also indicated that PDI may be a positive regulator in the process of DEX-stimulated osteoclastogenesis. Hence, various PDI inhibitors were subjected to molecular docking with PDI and their performances were analyzed, including 3-Methyltoxoflavin (3M) which inhibits PDI expression, and ribostamycin sulfate (RS) which represses PDI chaperone activity. The binding energies of DEX, 3M, and RS to PDI were -5.3547, -4.2324, and -5.9917 kcal/mol, respectively. The Protein-Ligand Interaction Profiler (PLIP) analysis demonstrated that both hydrogen bonds and hydrophobic interactions were the key contributions to the DEX-PDI and 3M-PDI complexes, while only hydrogen bonds were identified as the predominant driving forces in the RS-PDI complex. Subsequent experiments showed that both 3M and RS reduced osteoclast differentiation and bone resorption activity by stifling the expression of osteoclastic markers. This reduction was primarily due to the PDI inhibitors boosting the antioxidant system, thereby reducing the production of intracellular ROS. In conclusion, our results supported PDI's involvement in SIONFH progression by regulating ROS in osteoclasts and highlighted PDI inhibitors may serve as potential options for SIONFH treatment.

Diagnostic performance of the Kaiser score for contrast-enhanced mammography and magnetic resonance imaging in breast masses: A Comparative Study.

RATIONALE AND OBJECTIVES: The Kaiser score (KS) is a simple and intuitive machine-learning derived decision rule for characterizing breast lesions in a clinical setting and screening for breast cancer. The present study aims to investigate the applicability of the KS for contrast-enhanced mammography (CEM) in breast masses, and to compare its diagnostic accuracy with magnetic resonance imaging (MRI). CEM may provide an alternative option for patients with breast masses, especially for those with MRI contraindications. MATERIALS AND METHODS: Two hundred and seventy-five patients with breast enhanced masses were included in the study from May 2019 to September 2022. Patients were further divided into benign and malignant groups based on pathological diagnosis. The CEM and MRI imaging characteristics of these two groups were analyzed statistically. The paired chi-square and Cohen's kappa coefficient (κ) analysis were used to compare imaging characteristics between CEM and MRI. The Breast Imaging Reporting and Data System (BI-RADS) and KS for CEM and MRI were evaluated based on imaging characteristics. The diagnostic performance of BI-RADS and KS for CEM and MRI was assessed and compared using receiver operating characteristic (ROC) analysis and DeLong's test. RESULTS: The imaging characteristics of root sign, time-signal intensity curve (TIC/mTIC), margin, internal enhancement pattern (IEP), edema, apparent diffusion coefficient (ADC) values, and suspicious malignant microcalcifications showed significant differences between benign and malignant lesions (all p ≤ 0.011). The detection rate of root sign and margin showed substantial agreement between CEM and MRI (κ = 0.656, κ = 0.640), but IEP, TIC/mTIC, and edema showed poor agreement (κ = 0.380, κ = 0.320, κ = 0.324). For all lesion analyses, the area under the curves (AUCs) of the KS (0.897 ∼ 0.932) were higher than that of BI-RADS (0.691) in CEM (all p < 0.001). The AUC of KS (calcification)-CEM (0.932) was higher than those of both KS-CEM and KS (edema)-CEM (0.897 and 0.899) (all p < 0.001). For subgroup analyses, the AUCs of the KS (0.875 ∼ 0.876) were higher than that of BI-RADS (0.740) in MRI (all p < 0.001). The AUCs of KS-MRI (0.876) and KS (ADC)-MRI (0.875) were similar to those of KS-CEM (0.878) and KS (edema)-CEM (0.870) (all p > 0.100). The AUC of KS (calcification)-CEM (0.934) was slightly higher than those of both KS-MRI (0.876) and KS (ADC)-MRI (0.875), but no significant difference was observed (p = 0.051; p = 0.071). CONCLUSION: The KS for CEM provided high diagnostic accuracy in distinguishing breast masses, comparable to that of MRI. The application of KS (calcification)-CEM combined with suspicious malignant microcalcifications can improve diagnostic efficiency with an AUC of 0.932 ∼ 0.934. However, edema did not significantly improve performance when using the KS for CEM.

AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation.

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

Prenatal diagnosis of monozygotic twins with phenotypic differences in chromosome 17q12 deletion syndrome.

We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non-genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome.

Biomimetic Multichannel Silk Nerve Conduits With Multicellular Spatiotemporal Distributions for Spinal Cord Injury Repair.

Bioengineered nerve conduits have shown great promise for spinal cord injury (SCI) repair, while their practical values are limited by poor regenerative efficacy and lack of multi-level structural design. Here, inspired by the ingenious anatomy of natural spinal cords, a biomimetic multichannel silk nerve conduit (namely BNC@MSCs/SCs) with multicellular spatiotemporal distributions for effective SCI repair is presented. The biomimetic silk nerve conduit (BNC) with hierarchical channels and aligned pore structures is prepared via a modified directional freeze-casting strategy. Such hierarchical structures provide appropriate space for the mesenchymal stem cells (MSCs) and Schwann cells (SCs) settled in specific channels, which contributes to the generation of BNC@MSCs/SCs resembling the cellular spatiotemporal distributions of natural spinal cords. The in vitro results reveal the facilitated SC migration and MSC differentiation in such BNC@MSCs/SCs multicellular system, which further promotes the tube formation and cell migration of endothelial cells as well as M2 polarization of macrophages. Moreover, BNC@MSCs/SCs can effectively promote the tissue repair and function recovery in SCI rats by attenuating glial scar formation while promoting neuron regeneration and myelin sheath reconstruction. Thus, it is believed that the biomimetic multichannel silk nerve conduits with multicellular spatiotemporal distributions are valuable for SCI repair and other neural tissue regeneration.

Glycated haemoglobin variability and risk of renal function decline in type 2 diabetes mellitus: An updated systematic review and meta-analysis.

OBJECTIVE: To assess the association between glycated haemoglobin (HbA1c) variability and risk of renal function decline in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A comprehensive search was carried out in PubMed, Embase, Web of Science and the Cochrane Library (until 12 March 2024). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines were followed for this meta-analysis. HbA1c variability was presented as indices of the standard deviation (SD), coefficient of variation (CV), HbA1c variability score (HVS) and haemoglobin glycation index (HGI). This meta-analysis was performed using random-effect models. RESULTS: Eighteen studies met the objectives of this meta-analysis. The analyses showed positive associations between HbA1c variability and kidney function decline, with hazard ratio (HR) 1.26 (95% confidence interval [CI] 1.15-1.38) for high versus low SD groups, HR 1.47 (95% CI 1.30-1.65) for CV groups, HR 1.32 (95% CI 1.10-1.57) for HVS groups and HR 1.53 (95% CI 1.05-2.23) for HGI groups. In addition, each 1% increase in SD and CV was linked to kidney function decline, with HR 1.26 (95% CI 1.17-1.35), and 1.13 (95% CI 1.03-1.23), respectively. Also, each 1-SD increase in SD of HbA1c was associated with deterioration in renal function, with HR 1.17 (95% CI 1.07-1.29). CONCLUSIONS: The four HbA1c variability indicators were all positively associated with renal function decline progression; therefore, HbA1c variability might play an important and promising role in guiding glycaemic control targets and predicting kidney function decline progression in T2DM.

Dynamic changes in volatile profiles and bacterial communities during natural fermentation of Mei yu, traditional Chinese fermented fish pieces.

Microbial metabolism is important for the unique flavor formation of Mei yu, a kind of traditional Chinese fermented fish pieces. However, the interactive relationship between microorganisms and flavor components during fermentation is still unclear. In this study, electronic nose and headspace-solid-phase microextraction-gas chromatography-mass spectrometry analysis were performed to identify flavor components in Mei yu during the fermentation, and the absolute microbial quantification was conducted to identify the diversity and succession of microbial communities. During fermentation, there was an increase in the types of volatile compounds. Alcohols, aldehydes, aromatics and esters were the main flavor compounds and significantly increased in Mei yu, while hydrocarbon and aldehydes significantly decreased. The absolute abundances of Lactobacillus, Lactococcus and Weissella increased significantly after 3 days' fermentation, which were closely associated with the productions of 1-nonanol, 2-methoxy-4-vinylphenol, guaiacol, ethyl palmitate and ethyl caprylate that might though pathways related to fatty acid biosynthesis and amino acid metabolism. However, these genera were negatively correlated with the production of indole. Additionally, the total volatile basic nitrogen (TVB-N) levels of Mei yu fermented during 3 days were within the limits of 25 mg TVB-N/100 g fish, with the contents of free amino acids and lipoxygenase activities were significant lower than that of 4 days' fermentation. In view of food safety and flavor, it suggested that the natural fermented Mei yu at room temperature should be controlled within 3 days. This study highlights the application of absolute quantification to microbiome analysis in traditional fermented Mei yu and provides new insights into the roles of microorganisms in flavor formation during fermentation.

Corydaline attenuates osteolysis in rheumatoid arthritis via mitigating reactive oxygen species production and suppressing calcineurin-Nfatc1 signaling.

AIM OF THE STUDY: Osteolysis in Rheumatoid arthritis (RA) is principally provoked by osteoclast hyperactivity. This study aims to employ Corydaline (Cory), a plant extract, as an osteoclast inhibitor in treating RA-inflicted osteolysis while unveiling the corresponding mechanism. MATERIALS AND METHODS: Osteoclasts were derived from mouse bone marrow-derived monocytes (BMMs) stimulated with M-CSF and RANKL. Subsequently, utilizing network pharmacology, we performed a thorough analysis of Cory's molecular structure and discerned its preliminary therapeutic potential. Subsequently, LPS was used to simulate and establish an in vitro model of RA, and the biological effect of Cory on osteoclast behaviors was evaluated through various staining methods, RT-qPCR, and Western blot. In addition, a collagen-induced arthritis (CIA) mouse model was developed to evaluate the therapeutic effects of Cory in vivo. RESULTS: The results from network pharmacology indicated a significant correlation between Cory, oxidative stress, and calcium signaling. Subsequent in vitro experiments demonstrated Cory's capacity to inhibit the formation and function of osteoclast under inflammatory stimuli, thereby protecting against abnormal bone resorption. This effect is achieved by activating the Nrf2 signaling pathway, mitigating the generation of reactive oxygen species (ROS), and modulating the calcineurin-Nfatc1 signaling. Furthermore, this therapeutic effect of Cory on RA-associated osteolysis was proved in CIA mice models. CONCLUSIONS: Cory demonstrates the potential to activate the Nrf2 signaling pathway, effectively countering oxidative stress, and simultaneously inhibit the calcineurin-Nfatc1 signaling pathway to regulate the terminals of calcium signaling. These dual effects collectively reduce osteoclast activity, ultimately contributing to a therapeutic role in RA osteolysis. Therefore, our study presents Cory as a novel pharmaceutical candidate for the prevention and treatment of RA.

Phenomenological investigation of organic modified cements as biocompatible substrates interfacing model marine organisms.

Organic modification can generally endow inorganic materials with novel and promotional characteristics to fit into new functionalities. In this paper, new cement-based composite materials, with Portland cement as the substrate and polyacrylamide (PAM, alone) and PAM/chitosan as the functional components mixed with cement (bulk modified) or served as the surface coating (surface modified), were prepared and engineered as sampling substrates for biofilm and coral co-culture. In comparison to the bulk modified substrate and pure cement material, the surface modified substrate showed a balanced mechanical property, considering both bending and compressive strengths and distinctive surface features toward facilitating biofilm and coral growth, as characterized by spectroscopic, morphological, mechanical, and biofilm and coral co-culture experiments. We, thus, believe that the as-prepared surface modified substrate has the very potential to be applied as a substitute/alternative for the conventional cement material in the construction and engineering of artificial facilities with ecological protection functions.

An expanded database and analytical toolkit for identifying bacterial virulence factors and their associations with chronic diseases.

Virulence factor genes (VFGs) play pivotal roles in bacterial infections and have been identified within the human gut microbiota. However, their involvement in chronic diseases remains poorly understood. Here, we establish an expanded VFG database (VFDB 2.0) consisting of 62,332 nonredundant orthologues and alleles of VFGs using species-specific average nucleotide identity ( https://github.com/Wanting-Dong/MetaVF_toolkit/tree/main/databases ). We further develop the MetaVF toolkit, facilitating the precise identification of pathobiont-carried VFGs at the species level. A thorough characterization of VFGs for 5452 commensal isolates from healthy individuals reveals that only 11 of 301 species harbour these factors. Further analyses of VFGs within the gut microbiomes of nine chronic diseases reveal both common and disease-specific VFG features. Notably, in type 2 diabetes patients, long HiFi sequencing confirms that shared VF features are carried by pathobiont strains of Escherichia coli and Klebsiella pneumoniae. These findings underscore the critical importance of identifying and understanding VFGs in microbiome-associated diseases.

Crebanine mitigates glucocorticoid-induced osteonecrosis of the femoral head by restoring bone remodelling homeostasis via attenuating oxidative stress.

The onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long-term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti-inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)-stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX-induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro-CT and histological data, which also showed that CN attenuated MPS-induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs-induced ONFH.

Human exposure risk of organic UV filters: A comprehensive analysis based on primary exposure pathways.

The exposure of organic UV filters has been increasingly confirmed to induce adverse effects on humans. However, the critical exposure pathway and the vulnerable population of organic UV filters are not clearly identified. This paper attempts to evaluate the health risk of commonly used organic UV filters from various exposure routes based on comprehensive analysis strategy. The estimated daily intakes (EDI) and hazard quotient (HQ) values of organic UV filters through four pathways (dermal exposure, indoor dust, indoor air, and drinking water) for various age groups were determined. Although the total HQ values (0.01-0.4) from comprehensive exposure of organic UV filters were below risk threshold (1.0), infants were identified as the most vulnerable population, with EDI (75.71 ng/kg-bw/day) of 2-3 times higher than that of adults. Additionally, the total EDI values of individual exposure pathways were estimated and ranked as follows: indoor air (138.44 ng/kg-bw/day) > sunscreen application (37.2 ng/kg-bw/day) > drinking water (21.87 ng/kg-bw/day) > indoor dust (9.24 ng/kg-bw/day). Moreover, we successfully tailored the Sankey diagram to depict the EDI proportion of individual organic UV filters from four exposure pathways. It was noted that EHMC (ethylhexyl methoxycinnamate) and EHS (ethylhexyl salicylate) dominated the contribution of EDI (72 %) via indoor air exposure routes. This study serves as a crucial reference for enhancing public health risk awareness concerning organic UV filters, with a special focus on the vulnerable populations such as infants and children.

3D Printing of Naturally Derived Adhesive Hemostatic Sponge.

Hydrogel hemostatic sponges have been recognized for its effectiveness in wound treatment due to its excellent biocompatibility, degradability, as well as multi-facet functionalities. Current research focuses on optimizing the composition and structure of the sponge to enhance its therapeutic effectiveness. Here, we propose an adhesive hydrogel made from purely natural substances extracted from okra and Panax notoginseng. We utilize 3-dimensional (3D) printing technology to fabricate the hemostatic hydrogel scaffold, incorporating gelatin into the hydrogel and refining the mixing ratio. The interaction between gelatin and okra polyphenols contributes to successful injectability as well as stability of the printed scaffold. The okra in the scaffold exhibits favorable adhesion and hemostatic effects, and the total saponins of Panax notoginseng facilitate angiogenesis. Through in vitro experiments, we have substantiated the scaffold's excellent stability, adhesion, biocompatibility, and angiogenesis-promoting ability. Furthermore, in vivo experiments have demonstrated its dual functionality in rapid hemostasis and wound repair. These features suggest that the 3D-printed, natural substance-derived hydrogel scaffolds have valuable potential in wound healing and related applications.