[Finite element analysis of anatomic plate fixation for proximal clavicular fractures].

OBJECTIVE: To explore establishment and finite element analysis of personalized proximal clavicular anatomical plate screw fixation model. METHODS: A 40-year-old male healthy volunteer was selected and the finite element analysis modules of 3D reconstruction software Mimics 15.01, Hypermesh 2019 and Abaqus 2020 were used. The finite element model of anatomic plate at the proximal clavicle was established, and a vertical load of 250 N was applied to the distal end of long axis of clavicle about 15 mm, then the overall structure, plate and screw displacement cloud image, Mises stress distribution were observed. RESULTS: The displacement distribution of the overall structure shows the maximum displacement was distributed on the distal clavicle. Under the four conditions of normal upper limb weight, longitudinal clavicle fracture, oblique fracture and shoulder impact violence during fall, longitudinal clavicle fracture and oblique fracture, the maximum displacement were 1.04 mm, 1.03 mm, 1.35 mm and 1.33 mm, respectively. The displacement cloud map of titanium alloy steel plate showed the largest displacement was distributed near the distal clavicular bone, and the maximum displacement were 0.89 mm, 0.88 mm, 1.10 mm and 1.09 mm, respectively. The displacement cloud map of titanium alloy screw showed the largest displacement was distributed at the root of the distal screw, and the maximum displacement were 0.88 mm, 0.87 mm, 1.08 mm and 1.06 mm, respectively. Mises stress distribution showed the maximum stress was mainly distributed on titanium alloy plates and screws, and the stress on the clavicle was very small. Mises stress distribution cloud showed the maximum Mises stress was distributed at the second row of screw holes near the clavicle, and the maximum Mises stress were 673.1, 678.1, 648.5, 654.4 MPa, respectively. The maximum stresses of titanium alloy screws were 414.5, 417.4, 415.8 and 419.7 MPa, respectively. CONCLUSION: The biomechanical changes of personalized proximal clavicular anatomical plates are demonstrated by using 3D finite element method to provide biomechanical data for personalized proximal clavicular anatomical plates.

Visible-Light-Promoted Reduction of Nitroarenes with Formate Salts as Reductants.

A visible-light-promoted reduction of nitrobenzenes using formate salts as the reductant was developed. A wide range of nitrobenzenes can be converted into aniline products in a transition metal free fashion. Mechanistic studies revealed that radical species (carbon dioxide radical anion and thiol radical) are key intermediates for the transformation. We anticipate that this method will provide a valuable and green strategy for the reduction of nitrobenzenes.

Boron nitride quantum dots supported hollow NH2-MIL-125 drive photo-Fenton-PMS system for photocatalytic tetracycline degradation: Contribution of tannic acid etching.

NH2-MIL-125(Ti) materials had great potential for photocatalytic applications but had low activity due to exciton effect and narrow absorption range of visible light. The surface oxygen-containing negative functional groups of boron nitride quantum dots (BNQDs) could overcome these defects, but due to the low load capacity, a higher specific surface area of the substrate was usually required. In this paper, a hollow Ti-MOF material was developed by etching technology. The hollow structure formed by tannic acid etching broadened the absorption range of visable light and provided more alternative surfaces for loading BNQDs. The 85.2% of high tetracycline (TC) removal efficiency for the best sample (BNQDs-5@20-Ti-MOF + PMS) was obtained, which was about 56.8 and 1.9 times of the 20-Ti-MOF and BNQDs-5@20-Ti-MOF, respectively. BNQDs-5@20-Ti-MOF + PMS system showed a great TC degradation efficiency in a wide pH range (pH = 5-9). In addition, reaction temperature and the inorganic ions did not show significant inhibition effect for TC removal. Both free radical and non-free radical pathways were involved in the TC degration by BNQDs-5@20-Ti-MOF + PMS system, among which O2•- and 1O2 played the key roles. Interestingly, multiple 1O2 production paths contributed to the high efficiency and stability of BNQDs-5@20-Ti-MOF + PMS system. This study revealed a reasonable combination of Ti-MOF and BNQDs, which provided a new efficient photocatalyst for environmental remediation.

Foliar application of silicon and selenium reduce the toxicity of cadmium to soybeans.

Silicon (Si) and selenium (Se), two environmental protection materials, which are beneficial to plant growth and stress resistance, can also alleviate crop stress induced by heavy metals. However, the effects of Si, Se and their interactions in reducing cadmium (Cd) toxicity and the related mechanisms require further elucidation. Hence, this study implemented a foliar application of Si and Se on soybean (Glycine max L.) that subjected to Cd-induced stress with four treatments (sole/combined application of Si, Se, no fertilizer treatment). The results demonstrated that Si and Se showed effective mitigation of Cd toxicity on soybeans mainly by promoting growth, enhancing photosynthesis, maintaining root vigor, improving antioxidant capacity, alleviating oxidative damage, altering the storage form, subcellular distribution of Cd in soybeans, and was more noticeable when combined overall (Si+Se＞Se＞Si). Si+Se increased root activity by 28% and CAT activity in leaves by 130.65%. Overall, the combined application of Si and Se exhibited a pronounced synergistic effect in enhancing the healthy growth of soybean plants under Cd pollution, with a more prominent impact observed following the second fertilization.

Antibacterial and cytotoxic metabolites produced by Streptomyces tanashiensis BYF-112 isolated from Odontotermes formosanus.

Chemical investigations of the termite-associated Streptomyces tanashiensis BYF-112 resulted in the discovery of four novel alkaloid derivatives: vegfrecines A and B (1 and 2), exfoliazone A (3), and venezueline H (7), in addition to nine known metabolites (4-6, 8-13). The structures of these compounds were elucidated through comprehensive spectroscopic analysis and comparison with existing literature data. Antibacterial assays revealed that viridomycin A (11) exhibited potent antibacterial activity against Staphylococcus aureus, with a zone of inhibition (ZOI) of 12.67 mm, in comparison to a ZOI of 17.67 mm for the positive control gentamicin sulfate. Viridomycin A (11) showed moderate activity against Micrococcus tetragenus and Pseudomonas syringae pv. actinidae, with ZOI values of 15.50 and 14.33 mm, respectively, which were inferior to those of gentamicin sulfate (34.67 and 24.00 mm). Viridomycin F (12) also exhibited moderate antibacterial effects against S. aureus, M. tetragenus, and P. syringae pv. actinidae, with ZOI values of 8.33, 16.50, and 10.83 mm, respectively. Cytotoxicity assays demonstrated that viridobruunine A (5), exfoliazone (6), viridomycin A (11), and X-14881E (13) exhibited significant cytotoxicity against human malignant melanoma (A375), ovarian cancer (SKOV-3), and gastric cancer (MGC-803) cell lines, with IC50 values ranging from 4.61 to 19.28 µmol·L-1. Furthermore, bioinformatic analysis of the complete genome of S. tanashiensis suggested a putative biosynthetic gene cluster (BGC) responsible for the production of compounds 1-12. These findings indicate that the secondary metabolites of insect-associated S. tanashiensis BYF-112 hold promise as potential sources of novel antibacterial and anticancer agents.

Bulk and single-cell RNA-seq analyses reveals canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy.

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

Protocol for the neonatal intracerebroventricular delivery of adeno-associated viral vectors for brain restoration of MECP2 for Rett syndrome.

Here, we present a protocol for neonatal intracerebroventricular (ICV) delivery of adeno-associated viral vectors (AAVs), achieving gene therapy for a Rett syndrome mouse model. We describe steps for preparing mouse lines, replacing foster mothers, sex typing, and genotyping. We then detail procedures for ICV delivery and validation through immunofluorescent and immunoblot techniques. This protocol is also applicable to preclinical gene therapy research that targets the neonatal mouse brain for other neurodevelopmental disorders. For complete details on the use and execution of this protocol, please refer to Yang et al.1.

Base-Promoted Ring Expansion Reaction of 4-Quinolones To Access Benzazepinones.

4-Quinolone derivatives undergo an unexpected ring expansion reaction with α-halo esters/phosphonates/sulfones in the presence of a base, such as NaH, to produce novel benzazepinones. Under these mild and transition-metal-free conditions, most substrates gave moderate to excellent yields. The reaction could be applied in gram-scale synthesis of drug-like molecules that greatly accelerated our structure-activity relationship studies. A plausible mechanism was proposed.

Multilayer Fused Correntropy Reprsenstation for Fault Diagnosis of Mechanical Equipment.

Fault diagnosis is vital for improving the reliability and safety of mechanical equipment. Existing fault diagnosis methods require a large number of samples for model training. However, in real-world environments, mechanical equipment usually operates under healthy conditions during most of its service life, resulting in a scarcity of fault samples. To solve this problem, a novel multilayer fusion correntropy representation method combined with a support vector machine is proposed for the fault diagnosis of mechanical equipment. First, the monitoring signal is expanded into multilayer signal components using wavelet packet decomposition. Then, the correlation between the signal components of each layer is expressed by correntropy, and the corresponding correntropy matrix is constructed. After performing the matrix logarithm operator, all correntropy matrices composed of correntropy values are fused into a vector, which is viewed as a feature of the signal. Finally, a support vector machine is established using small samples to realize fault classification. The effectiveness of the proposed method is validated on four public datasets. The results indicate that compared with other methods, the proposed method has advantages in terms of diagnosis accuracy and noise immunity ability.

Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

Association of the panimmune-inflammatory value (PIV) with all-cause and cardiovascular mortality in maintenance hemodialysis patients: a propensity score matching retrospective study.

PURPOSE: The panimmune-inflammatory value (PIV) is a novel inflammatory indicator. However, its role in maintenance hemodialysis (MHD) remains unclear. Our goal was to explore the predictive value of PIV for cardiovascular and all-cause mortality in MHD patients. METHODS: In this retrospective cohort study, 507 patients receiving MHD between November 2017 and December 2022 were enrolled. The PIV value was calculated as follows: neutrophil count × monocyte count × platelet count/lymphocyte count. Patients were divided into two groups on the basis of the median PIV. Propensity score matching (PSM) was used to adjust for imbalances in baseline information between groups. Kaplan‒Meier curves, Cox regression, the Fine‒Gray competing risk model, and restricted cubic spline (RCS) curves were used to analyze the relationship between PIV and mortality. RESULTS: By the end of follow-up, 126 deaths had occurred, 91 of which were due to cardiovascular disease. The Kaplan‒Meier curves demonstrated that MHD patients with higher PIV levels had a poorer prognosis for all-cause death (p = 0.019). PIV levels were linked to all-cause death in multivariate Cox proportional risk regression (HR = 1.76; 95% CI 1.14, 2.72; p = 0.011). The Fine‒Gray model revealed a greater cumulative incidence of cardiovascular death in the higher PIV group (p = 0.035). PIV levels were linked to cardiovascular mortality in the Fine‒Gray competing risk model (HR = 2.06; 95% CI 1.25, 3.42; p = 0.005). The RCS revealed a nonlinear relationship between PIV and mortality risk (p < 0.05). Using 63 years of age as the threshold, we observed a multiplicative interaction effect between age and PIV for all-cause mortality (p = 0.006). CONCLUSION: In MHD patients, PIV is an independent hazard factor for cardiovascular-related mortality and all-cause mortality.

Sprouting facilitates the antiglycative effect of black soybean (Glycine max (L.) Merr.) by promoting the accumulation of isoflavones.

The exposure of advanced glycation end products (AGEs) can induce chronic inflammation, oxidative stress, and accelerated aging, contributing the onset and progression of many diseases especially diabetic complications. Therefore, the searching of antiglycative foods is of practical significance, which may serve as a strategy in the attenuation of AGEs-associated diseases. In this study, we evaluated the antiglycative potential of some beans and bean sprouts that were common in our daily life. The results revealed that sprouting enhanced the antiglycative activity of beans, with black soybean sprouts demonstrating the highest efficacy (4.92-fold higher than the unsprouted beans). To assess practical implications, we examined the antiglycative activity of black soybean sprouts in pork soup, a popular food model that incorporates sprouts. Our findings confirmed the inhibitory effect on a dose-dependent manner. Through open column fractionation, we identified isoflavones and soyasaponin Bb as the candidates responsible for these effects. Additionally, compare to the unsprouted black soybeans, we found significant increases in the levels of antioxidative properties (2.51-fold), total phenolics (7.28-fold), isoflavones, and soyasaponin Bb during the sprouting process. Further studies determined that genistein, genistin, and daidzin were the major antiglycative compounds in black soybean sprouts. Collectively, this study emphasizes the benefits of sprouted beans and offers foundation for the development of functional sprouting foods.

CUL1 exacerbates glucocorticoid-induced osteoporosis by enhancing ASAP1 ubiquitination.

BACKGROUND: Glucocorticoid-induced osteoporosis is a leading secondary cause of osteoporosis. Cullin-1 (CUL1) levels are abnormally elevated in patients with osteoporosis, but the underlying mechanism remains unclear. The purpose of this study was to elucidate the mechanism of action of CUL1 in a glucocorticoid (dexamethasone, Dex)-induced osteoporosis model. METHODS: C57BL/6J mice were intraperitoneally injected with Dex to establish an osteoporosis model. Mouse femur bone injury and bone formation were detected using hematoxylin-eosin or Masson staining. Apoptosis and cell cycle distribution were determined by flow cytometry. Alkaline phosphatase (ALP) activity and calcified nodules were monitored using ALP and Alizarin Red S staining. The molecular mechanism was validated by co-immunoprecipitation (Co-IP) and ubiquitination assays. RESULTS: CUL1 expression was enhanced in the Dex-induced osteoporosis mouse model. CUL1 silencing moderated the Dex-induced cell proliferation and osteogenesis inhibition. Moreover, CUL1 promoted the ubiquitination and degradation of ASAP1 via the SKP1-CUL1-F-box (SCF)-FBXW7 complex. CUL1 induced apoptosis and repressed osteogenesis by ASAP1. CUL1 silencing alleviated the Dex-induced osteoporosis in mice. CONCLUSION: CUL1 suppressed osteoblast proliferation and osteogenesis by promoting ASAP1 ubiquitination via the SCF-FBXW7 complex in glucocorticoid-induced osteoporosis.

Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1ß, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.

HOXA1 promotes epithelial-mesenchymal transition and malignant characteristics of laryngeal squamous cell carcinoma.

Despite considerable advancements in the diagnosis and treatment of LSCC, there has been no significant improvement in survival rate. Consequently, identifying molecular targets for this cancer is of paramount importance. HOXA1, a constituent of the homeobox transcription factor cluster, plays a role in the development of various types of cancer. Nevertheless, the specific function and mechanism of HOXA1 in LSCC remains unclear. This study aimed to clarify the impact of HOXA1 on the advancement of LSCC and uncover its underlying mechanism. Our findings indicate that HOXA1 exhibits a significantly elevated expression level in LSCC. Suppression of HOXA1 inhibited the proliferation of LSCC cells. Furthermore, the ablation of HOXA1 triggered the apoptosis of LSCC cells and inhibited EMT. Functionally, HOXA1 has a role in initiating the activation of the PI3K/AKT/mTOR pathway in LSCC cells. In summary, HOXA1 significantly contributes to the EMT of LSCC cells via the PI3K/AKT/mTOR signaling pathway, thereby facilitating the proliferation and motility of LSCC cells. Consequently, HOXA1 presents itself as a viable therapeutic target for LSCC interventions.

Network pharmacology-based study on the mechanism of action of Trollius chinensis capsule in the treatment of upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. METHODS: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. RESULTS: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. CONCLUSION: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.

Conditional generative adversarial network-assisted system for radiation-free evaluation of scoliosis using a single smartphone photograph: a model development and validation study.

Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

Hydroxychloroquine and a low antiresorptive activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects.

Osteoporosis remains incurable. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation, while the anabolic agent, teriparatide, does not inhibit bone resorption, and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects. Thus, there is an unmet need to develop dual antiresorptive and anabolic agents to prevent and treat osteoporosis. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited marrow fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis.

Effects of Surface Crack Shape on Fracture Behavior of Oil Pipelines Based on the MMC Criterion.

This study employs a hybrid numerical-experimental calibration method based on phenomena to determine the fracture parameters of the Modified Mohr-Coulomb (MMC) model. Using a self-developed VUMAT subroutine and the element deletion technique, the fracture process of a wide plate pipeline is thoroughly analyzed. This study investigates the impact of various crack shapes on the fracture response under tensile loading and the influence of surface crack size on the initiation location of a wide plate. These results demonstrate the calibrated MMC fracture model's accurate prediction of the toughness fracture behavior of X80 pipeline steel. Under equal area conditions of the dangerous section, circular cracks exhibit lower bearing capacity compared to elliptical cracks. Elliptical cracks predominantly propagate in the thickness direction, whereas circular cracks show nearly uniform growth in all directions. Furthermore, when the crack depth is less than half of the wall thickness, the damage accumulation value at the midpoint of the crack front is maximized; conversely, when the crack front is closer to the internal measurement point of the wide plate, the damage accumulation value is maximized.

Exploring the sensory acceptance, physicochemical properties, and phenolamide leaching characteristics of rose tea.

The consumption of rose tea has gained popularity due to its unique flavor and health benefits. In particular, previous data exemplified the protective role of N1, N5, N10-(E)-tri-p-coumaroylspermidine (ETCS; a phenolamide) against alcohol-induced hepatic injuries. This study evaluated the customer acceptance and physicochemical properties of eight rose tea varieties that available in the market. In general, Qianye rose (Rosa centifolia) exhibits better flavor and taste, while Hetian rose (Rosa damascena Mill.) has the highest ETCS level. Moreover, a negative correlation between ETCS content and both vitamin C and anthocyanins content in rose is observed. Additionally, the optimal brewing conditions for rose tea is 95 °C mineral water for 5 min in a thermos bottle, based on ETCS level in the infusion. And rose tea can be brewed for at least three times. Collectively, our findings provide valuable insights for rose tea drinkers and individuals interested in the dietary hepatic-protective benefits.