Association of Circulating Long-Chain Free Fatty Acids and Incident Diabetes Risk Among Normoglycemic Chinese Adults: A Prospective Nested Case-Control Study.

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVE: Our study aims to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1 and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95%CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18 to 26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95%CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR[95%CI]: 0.85[0.76-0.94]), PUFAs 20:4 (0.84[0.75-0.94]) and 24:2 (0.87[0.78-0.97]) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 [0.61-0.99] (P= 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

Comparison of treatment effects between clear aligners and fixed appliances in patients treated with miniscrew-assisted molar distalization.

OBJECTIVES: The biomechanics in achieving molar distalization may differ between fixed appliances and clear aligners in the control of tooth movement. The objective of this study was to compare the treatment effects between clear aligners (CA) and fixed appliances (FA) in patients treated with miniscrew-assisted molar distalization. METHODS: The sample consisted of 46 subjects with mild-to-moderate crowding. A total of 22 patients treated with clear aligners (age, 25.66 ±â€…6.11 years old) and 24 patients treated with fixed appliances (age, 24.04 ±â€…4.95 years old) for miniscrew-assisted molar distalization were included in this study. The dental and skeletal changes were evaluated by the pre- and post-treatment lateral cephalograms. RESULTS: Significant changes were found with the vertical variables SN-OP angle (2.24 ±â€…3.22°, P < .05) and SN-MP angle (0.73 ±â€…1.15°, P < .05) for the FA group when compared with the CA group (SN-OP angle 0.41 ±â€…2.26° and SN-MP angle -0.21 ±â€…1.38°, P > .05). Both treatment groups achieved a 2-3 mm. molar distalization with significant intrusion of the upper molars. The CA group showed significantly less distal tipping of molars (U6^PP angle -2.29 ±â€…3.29° and L6^MP angle -2.92 ±â€…2.49°, P < .05) compared to the FA group (-5.24 ±â€…4.28° and -5.53 ±â€…5.03°, P < .05). In addition, significant retraction and lingual inclination of the upper and lower incisors were found in both groups. LIMITATIONS: The changes of tooth position were evaluated by 2D lateral cephalograms, not 3D measurements. CONCLUSIONS: Compared to fixed appliances, clear aligners seemed to have better control of vertical dimension and distal tipping of molars in patients treated with miniscrew-assisted molar distalization.

Utilizing stem cell-secreted molecules as a versatile toolbox for skin regenerative medicine.

Stem cells are recognized as an important target and tool in regenerative engineering. In this study, we explored the feasibility of engineering amniotic fluid-derived mesenchymal stem cell-secreted molecules (afMSC-SMs) as a versatile bioactive material for skin regenerative medicine applications in a time- and cost-efficient and straightforward manner. afMSC-SMs, obtained in powder form through ethanol precipitation, effectively contributed to preserving the self-renewal capacity and differentiation potential of primary human keratinocytes (pKCs) in a xeno-free environment, offering a potential alternative to traditional culture methods for their long-term in vitro expansion, and allowed them to reconstitute a fully stratified epithelium sheet on human dermal fibroblasts. Furthermore, we demonstrated the flexibility of afMSC-SMs in wound healing and hair regrowth through injectable hydrogel and nanogel-mediated transdermal delivery systems, respectively, expanding the pool of regenerative applications. This cell-free approach may offer several potential advantages, including streamlined manufacturing processes, scalability, controlled formulation, longer shelf lives, and mitigation of risks associated with living cell transplantation. Accordingly, afMSC-SMs could serve as a promising therapeutic toolbox for advancing cell-free regenerative medicine, simplifying their broad applicability in various clinical settings.

Comparison of craniomaxillofacial morphology in children with unilateral cleft lip and palate treated with/without presurgical nasoalveolar molding - a retrospective study with a mean age of 5 years.

OBJECTIVES: To three-dimensionally assess differences in craniomaxillofacial skeletal development in patients with operated unilateral cleft lip and palate (UCLP) treated with/without presurgical nasoalveolar molding (PNAM) with a mean age of 5 years. MATERIALS AND METHODS: Cone-beam CT radiographs of 30 patients with UCLP who had undergone PNAM and 34 patients with UCLP who did not receive PNAM were analyzed. The data were stored in DICOM file format and were imported into the Dolphin Imaging program for 3D image reconstruction and landmark identification. 33 landmarks, 17 linear and three angular variables representing craniofacial morphology were analyzed and compared by using the Mann-Whitney U tests. RESULTS: The vast majority of linear variables and 3D coordinates of landmark points reflecting craniofacial skeletal symmetry were not significantly different between the two groups. In terms of craniofacial skeletal development, the PNAM group had a significantly smaller anterior nasal spine offset in the midsagittal plane and a greater maxillary length compared to the non-PNAM group. CONCLUSIONS: Evaluations performed in early childhood showed that treatment with/without PNAM in the neonatal period was not a major factor influencing craniomaxillofacial hard tissue development in patients with UCLP; moreover, PNAM treatment showed significant correction of skeletal deviation at the base of the nose. CLINICAL RELEVANCE: Follow-up in early childhood has shown that PNAM treatment administered during the neonatal stage does not impede maxillary development and has benefits in correcting nasal floor deviation. It is a viable option for improving nasal deformity in children with unilateral cleft lip and palate.

Experimental Study on the Response of Cracked Sandstone to the Intermediate Principal Stress Coupled with Pore Pressure.

Underground fractured rock masses are susceptible to failure under the combined influence of true triaxial stresses and pore pressure, posing severe threats to personnel and production safety of underground engineering. To investigate the influence of intermediate principal stress (σ2) on the mechanical and water diffusion volume change (ΔV) characteristics during the failure process of cracked rocks under stable pore pressure, this study conducted true triaxial strength experiments on cracked sandstone with stable pore pressure. The results demonstrated that with the increase of σ2, crack initiation stress (σci), crack damage stress (σcd) and the peak stress (σ1,peak) of cracked sandstone initially increase and then decrease. Conversely, ΔV tends to decrease first and then increase with the increase of σ2. This inverse relationship indicates that under elevated σ2, the decreased strength of cracked rock could lead to an increase in ΔV, which may increase the probability of water inrush disasters. The findings of this study provide a theoretical reference for the stability of rock mass engineering and the prevention of water inrush disasters.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Triply Interlocked [2]catenanes: Rational Synthesis, Reversible Conversion Studies and Unprecedented Application in Photothermal Responsive Elastomer.

Triply interlocked [2]catenane complexes featuring two identical, mechanically interlocked units are extraordinarily rare chemical compounds, whose properties and applications remain open to detailed studies. Herein, we introduce the rational design of a new ligand precursor, L1, suitable for the synthesis of six triply interlocked [2]catenanes by coordination-driven self-assembly. The interlocked compounds can be reversibly converted into the corresponding simple triangular prism metallacage by addition of H2O or DMF solvents to their CH3OH solutions, thereby demonstrating the importance of π···π stacking and hydrogen bonding interactions in the formation of triply interlocked [2]catenanes. Moreover, extensive studies have been conducted to assess the remarkable photothermal conversion performance. Complex 6a, exhibiting outstanding photothermal conversion performance (conversion efficiency in solution : 31.82%), is used to prepare novel photoresponsive elastomer in combination with thermally activated liquid crystal elastomer. The resultant material displays robust response to near-infrared (NIR) laser and the capability of completely reforming the shape and reversible actuation, paving the way for the application of half-sandwich organometallic units in photo-responsive smart materials.

Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

Haploidentical hematopoietic stem cell transplantation as a first-line treatment for paediatric severe aplastic anemia: a single-center research.

MRD-HSCT is the first-line therapy for children with SAA, while it is not easy to find a compatible donor due to the Chinese one-child policy. IST has a high recurrence rate, a risk of clonal transformation. Thus, Haplo-HSCT, as a first-line treatment, has gradually attracted clinicians' attention. To evaluate the efficacy of Haplo-HSCT in children with SAA, we performed a retrospective study (2006.06-2021.01) of 210 patients with AA who received HSCT or IST in Beijing Children's Hospital. The OS and FFS rates were analyzed to evaluate the efficacy of Haplo-HSCT and IST. We found that from 2006 to 2021, 3- and 5-year cumulative survival rates were both 85.3% in the first-line Haplo group, 98.1% and 96.8% in the first-line IST group, both 85.7% in the ATG group (P = 0.866), both 100% in the ATG + TPO group (P = 0.016), and 99.1% and 97.2% in the ATG + eltrombopag group (P = 0.056). 3- and 5-year cumulative FFS rates were both 85.3% in the first-line Haplo-HSCT group and 67.5% and 66.2% in the first-line IST group (P = 0.033). Therefore, we believe that Haplo-HSCT can be a first-line treatment for paediatric SAA.

Enhanced Iturin A Production of Engineered Bacillus amyloliquefaciens by Knockout of Endogenous Plasmid and Rap Phosphatase Genes.

Iturin A biosynthesis has garnered considerable interest, yet bottlenecks persist in its low productivity in wild strains and the ability to engineer Bacillus amyloliquefaciens producers. This study reveals that deleting the endogenous plasmid, plas1, from the wild-type B. amyloliquefaciens HM618 notably enhances iturin A synthesis, likely related to the effect of the Rap phosphatase gene within plas1. Furthermore, inactivating Rap phosphatase-related genes (rapC, rapF, and rapH) in the genome of the strain also improved the iturin A level and specific productivity while reducing cell growth. Strategic rap genes and plasmid elimination achieved a synergistic balance between cell growth and iturin A production. Engineered strain HM-DR13 exhibited an increase in iturin A level to 849.9 mg/L within 48 h, significantly shortening the production period. These insights underscore the critical roles of endogenous plasmids and Rap phosphatases in iturin A biosynthesis, presenting a novel engineering strategy to optimize iturin A production in B. amyloliquefaciens.

Comprehensive analysis of metal(loid)s and associated metal(loid) resistance genes in atmospheric particulate matter.

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

Porphyrin-based covalent organic frameworks from design, synthesis to biological applications.

Covalent organic frameworks (COFs) constitute a class of highly functional porous materials composed of lightweight elements interconnected by covalent bonds, characterized by structural order, high crystallinity, and large specific surface area. The integration of naturally occurring porphyrin molecules, renowned for their inherent rigidity and conjugate planarity, as building blocks in COFs has garnered significant attention. This strategic incorporation addresses the limitations associated with free-standing porphyrins, resulting in the creation of well-organized porous crystal structures with molecular-level directional arrangements. The unique optical, electrical, and biochemical properties inherent to porphyrin molecules endow these COFs with diversified applications, particularly in the realm of biology. This review comprehensively explores the synthesis and modulation strategies employed in the development of porphyrin-based COFs and delves into their multifaceted applications in biological contexts. A chronological depiction of the evolution from design to application is presented, accompanied by an analysis of the existing challenges. Furthermore, this review offers directional guidance for the structural design of porphyrin-based COFs and underscores their promising prospects in the field of biology.

Prognostic value of pathological nodal burden after neoadjuvant chemotherapy in initially cN0-1 breast cancer patients: a dual-center, 10-year survival analysis.

Background: There is an interest in performing de-escalating axillary surgery after neoadjuvant chemotherapy (NAC). However, the significance of residual axillary node disease after NAC has not been well studied. Objectives: To investigate the pathological residual axillary lymph node tumor burden (ypN) of patients with initial clinical nodal stage cN0-1 breast cancer after NAC and determine its prognostic value. Design: Initial cN0-1 breast cancer patients who received NAC followed by axillary surgery at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University between January 2011 and December 2019 were included. Methods: Survival outcomes were compared according to different clinical and pathological stage and nodal response to NAC. The main outcomes were disease-free survival (DFS) and overall survival (OS). Factors associated with survival were defined by Cox regression analysis. Results: A total of 911 patients were included, among whom 260 had cN0 and 651 had cN1 tumors. After NAC, 410 patients were ypN0, and another 501 were ypN+. The median follow-up time was 63 months. There was no significant difference in DFS or OS between the cN0 and cN1 groups in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+) and HR-/HER2- subtypes; instead, ypN status was significantly related to DFS and OS. In HR+/HER2- subtype, both cN and ypN stages did not show significant survival differences, but the ypN number and the nodal response to NAC showed significant prognostic value (p < 0.05). Among HR-/HER2+ patients, all cN status, ypN status, ypN number, and nodal response were significantly associated with survival (p < 0.05). Furthermore, tumor biology, axillary surgery, ypN status, pathological tumor size, and radiotherapy were independent prognostic factors for DFS and OS. Conclusion: The ypN status after NAC provide more prognostic information than the initial cN stage in cN0-1 patients, and the surgical axillary staging after NAC may have high clinical value.

Dendritic boron and nitrogen doped high-entropy alloy porous carbon fibers for high-efficiency hydrogen evolution reaction.

Among various electrocatalysts, high-entropy alloys (HEAs) have gained significant attention for their unique properties and excellent catalytic activity in the hydrogen evolution reaction (HER). However, the precise synthesis of HEA catalysts in small sizes remains challenging, which limits further improvement in their catalytic performance. In this study, boron- and nitrogen-doped HEA porous carbon nanofibers (HE-BN/PCNF) with an in situ-grown dendritic structure were successfully prepared, inspired by the germination and growth of tree branches. Furthermore, the dendritic fibers constrained the growth of HEA particles, leading to the synthesis of quantum dot-sized (1.67 nm) HEA particles, which also provide a pathway for designing HEA quantum dots in the future. This work provides design ideas and guiding suggestions for the preparation of borated HEA fibers with different elemental combinations and for the application of dendritic nanofibers in various fields.

Dam inundation reduces ecosystem multifunctionality following riparian afforestation in the Three Gorges Reservoir Region.

Afforestation is an acknowledged method for rehabilitating deteriorated riparian ecosystems, presenting multiple functions to alleviate the repercussions of river damming and climate change. However, how ecosystem multifunctionality (EMF) responds to inundation in riparian afforestation ecosystems remains relatively unexplored. Thus, this article aimed to disclose how EMF alters with varying inundation intensities and to elucidate the key drivers of this variation based on riparian reforestation experiments in the Three Gorges Reservoir Region in China. Our EMF analysis encompassed wood production, carbon storage, nutrient cycling, decomposition, and water regulation under different inundation intensities. We examined their correlation with soil properties and microbial diversity. The results indicated a substantial reduction in EMF with heightened inundation intensity, which was primarily due to the decline in most individual functions. Notably, soil bacterial diversity (23.02%), soil properties such as oxidation-reduction potential (ORP, 11.75%), and temperature (5.85%) emerged as pivotal variables elucidating EMF changes under varying inundation intensities. Soil bacterial diversity and ORP declined as inundation intensified but were positively associated with EMF. In contrast, soil temperature rose with increased inundation intensity and exhibited a negative correlation with EMF. Further insights gleaned from structural equation modeling revealed that inundation reduced EMF directly and indirectly by reducing soil ORP and bacterial diversity and increasing soil temperature. This work underscores the adverse effects of dam inundation on riparian EMF and the crucial role soil characteristics and microbial diversity play in mediating EMF in response to inundation. These insights are pivotal for the conservation of biodiversity and functioning following afforestation in dam-induced riparian habitats.

Interior decorative volatile organic compounds exposure induces sleep disorders through aberrant branched chain amino acid transaminase 2 mediated glutamatergic signaling resulting from a neuroinflammatory cascade.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.

Allosteric Regulation and Inhibition of Coronavirus 3CLpro Revealed by HDX-MS.

Coronavirus (CoV) infections have caused contagious and fatal respiratory diseases in humans worldwide. CoV 3-chymotrypsin-like proteases (3CLpro or Mpro) play an important role in viral maturation, and maintenance of their dimeric conformation is crucial for viral activity. Therefore, allosterically regulated dimerization of 3CLpro can be employed as a drug development target. Here, we investigated the allosteric regulatory mechanism of 3CLpro dimerization by using hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) technology. We found that the FLAG tag directly coupled to the N-finger of 3CLpro significantly increased HDX kinetics at the dimer interface, and 3CLpro transformed from a dimer to a monomer. The 3CLpro mutants of SARS-CoV-2, which are monomeric, also exhibited increased deuterium exchange. Binding of the allosteric inhibitor Gastrodenol to most betacoronavirus 3CLpros led to increased allosteric deuterium exchange, resulting in the monomeric conformation of the CoV 3CLpro upon binding. Molecular dynamics (MD) simulation analysis further indicated the molecular mechanism of action of Gastrodenol on CoV 3CLpro: binding of Gastrodenol to SARS-CoV-2 3CLpro destroyed the hydrogen bond in the dimer interface. These results suggest that Gastrodenol may be a potential broad-spectrum anti-betacoronavirus drug.

Silk fibroin-based hemostatic powders with instant and robust adhesion performance for sutureless sealing of gastrointestinal defects.

Powder-based hemostatic technology has offered unprecedented opportunities in surgical sealing and repair of irregularly shaped and noncompressible wounds. Despite their routine use, existing clinical hemostatic powders are challenged either by poor mechanical properties or inadequate adhesion to bleeding tissues in biological environments. Here, inspired by the mussel foot proteins' fusion assembly strategy, a novel silk fibroin-based hemostatic powder (named as SF/PEG/TA) with instant and robust adhesion performance is developed. Upon absorbing interfacial liquids, the SF/PEG/TA powders rapidly swell into micro-gels and subsequently contact with each other to transform into a macroscopically homogeneous hydrogel in situ, strengthening its interfacial bonding with various substrates in fluidic environments. The in vitro and in vivo results show that the SF/PEG/TA powder possesses ease of use, good biocompatibility, strong antibacterial activities, and effective blood clotting abilities. The superior hemostatic sealing capability of the SF/PEG/TA powder is demonstrated in the rat liver, heart, and gastrointestinal injury models. Moreover, in vivo investigation of rat skin incision and gastrointestinal perforation models validates that the SF/PEG/TA powder promotes wound healing and tissue regeneration. Taken together, compared to existing clinical hemostatic powders, the proposed SF/PEG/TA powder with superior wound treatment capabilities has high potential for clinical hemostasis and emergency rescue.

Achilles tendon assessment on quantitative MRI: Sources of variability and relationships to tendinopathy.

Quantitative MRI (qMRI) measures are useful in assessing musculoskeletal tissues, but application to tendon has been limited. The purposes of this study were to optimize, identify sources of variability, and establish reproducibility of qMRI to assess Achilles tendon. Additionally, preliminarily estimates of effect of tendon pathology on qMRI metrics and structure-function relationships between qMRI measures and ankle performance were examined. T1, T1ρ, T2, and T2* maps of the Achilles tendon were obtained using a 3T MRI scanner. In participants with asymptomatic tendons (n = 21), MRI procedures were repeated twice, and region of interest selection was performed by three raters. Variance decomposition and reproducibility statistics were completed. To estimate the effect of pathology, qMRI measures from individuals with asymptomatic tendons were compared to qMRI measures from a pilot group of individuals with Achilles tendinopathy (n = 7). Relationships between qMRI and ankle performance measures were assessed. Between-participant variation accounted for the majority of variability (46.7%-64.0%) in all qMRI measures except T2*. ICCs met or exceeded 0.7 for all qMRI measures when averaged across raters or scans. Relaxation times were significantly longer in tendinopathic tendons (mean (SD) T1: 977.8 (208.6) ms, T1ρ: 35.4 (7.1) ms, T2: 42.8 (7.9) ms, T2*: 14.1 (7.6) ms, n = 7) compared to asymptomatic control tendons (T1: 691.7 (32.4) ms, T1ρ: 24.0 (3.6) ms, T2: 24.4 (7.5) ms, T2*: 9.5 (3.4) ms, n = 21) (p < 0.011 for all comparisons). T1 related to functional performance measures in symptomatic and asymptomatic groups. Study findings suggest that qMRI is reliable to assess the Achilles tendon. qMRI quantitatively assesses the presence of tendon pathology and relates to functional performance outcomes, supporting the utility of incorporating qMRI in research and clinic.

ROF-2 as an Aggregation-Induced Emission (AIE) Probe for Multi-Target Amyloid Detection and Screening of Amyloid Inhibitors.

Misfolding and aggregation of amyloid peptides into ß-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation-induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported. As an amyloid probe, ROF2 outperformed ThT, demonstrating its superior sensing capability in monitoring, detecting, and distinguishing amyloid aggregates of different sequences (Amyloid-ß, human islet amyloid polypeptide, or human calcitonin) and sizes (monomers, oligomers, or fibrils). More importantly, the utilization of ROF2 as a screening molecule to identify and repurpose cardiovascular drugs as amyloid inhibitors is introduced. These drugs exhibit potent amyloid inhibition properties, effectively preventing amyloid aggregation and reducing amyloid-induced cytotoxicity both in cells and nematode. The findings present a novel strategy to discovery AIE-based amyloid probes and to be used to repurpose amyloid inhibitors, expanding diagnostic and therapeutic options for neurodegenerative diseases while addressing vascular congestion and amyloid aggregation risks.