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Michelia xinningia is an evergreen garden plant with attractive and fragrant flowers. Michelia exhibits both interspecific and intraspecific phenotypic variability. However, the genetic diversity of M. xinningia has not been thoroughly investigated. This study analyzed the first chloroplast genome of M. xinningia, which was 160,082 bp, including a large single-copy (LSC) region of 88,112 bp, a small single-copy (SSC) region of 18,798 bp, and a pair of inverted repeat (IRs) regions of 26,586 bp. It contained 133 genes, including 87 protein-coding genes, 38 transfer RNA genes, and eight ribosomal RNA genes. Phylogenetic analysis showed that M. xinningia formed a close relationship with M. foveolata. This study will provide an opportunity to investigate genetic variation and could be useful for both species identification and conservation.

Abstract Background Pain is a relatively common complication after hook-wire puncture localization. However, the problem of pain occurrence following this localization procedure has not been sufficiently examined. In this prospective study, we aimed to investigate the incidence and risk factors associated with acute pain after preoperative CT-guided hook-wire puncture localization of pulmonary nodules. Methods Clinical data were collected prospectively from patients with small pulmonary nodules who underwent preoperative CT-guided hook-wire puncture localization between May 2022 and May 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients were divided into two groups on the basis of the presence or absence of moderate-to-severe pain following the localization process. Univariate logistic analysis was conducted to analyse the clinical data of the two groups. Subsequently, the significant variables (P

Objectives: With the depletion of easily recoverable oil reservoirs, the focus of oil and gas exploration and development in China has shifted to "two deeps and non-conventional" oil and gas fields. This transformation is not only accompanied by a significant increase in well depth and more complex formation challenges but also presents more stringent requirements for the design and construction of drilling engineering, which directly leads to a significant extension of the drilling cycle. The length of the drilling cycle is a key factor in determining drilling costs. Therefore, for a long time, scholars have been committed to improving the mechanical penetration rate and the durability of polycrystalline diamond composite (PDC) bits. The main purpose of this study is to analyze geological characteristics in depth, accurately match and optimize the design of special-shaped teeth in PDC drill bits, in order to significantly reduce the risk of drill bit failure and greatly improve mechanical drilling speed and footage. Given the wide application of PDC bits in hard rock drilling and their key impact on the cost and efficiency of drilling operations, this study focuses on the design and optimization of ridge-shaped PDC teeth, aiming to explore more suitable tooth structures for specific geological conditions through scientific testing and comparative analysis. This will promote innovation and efficiency improvements in drilling technology. Methods: Based on round teeth, the wear resistance, impact resistance, and rock-breaking effect of three types of ridge-shaped teeth were systematically tested. First, the wear resistance and impact resistance of three typical ridge-shaped PDC teeth—namely the 165 axe-shaped, 135 axe-shaped, and three-edged cutters—were tested to quantitatively evaluate their mechanical properties. Subsequently, granite was selected as the representative rock sample, and the single-tooth cutting tests were conducted with three different penetration depths to simulate the cutting effect under various drilling pressures during actual drilling. Additionally, a full-size bit simulation drilling test was designed to evaluate the drilling performance of each tooth shape under different pressures, and the data were compared with those of round teeth. This series of tests aimed to fully reveal the advantages and disadvantages of ridge-shaped PDC teeth in terms of wear resistance, impact resistance, and rock-breaking effectiveness. Results: The test results show that the three ridge-shaped PDC cutters significantly outperform the round teeth in terms of wear resistance. The 135 axe-shaped cutter, with the smallest ridge angle, exhibited the greatest improvement in wear resistance, indicating that the ridge design enhances the durability of PDC cutters and bits. In terms of impact resistance, the 165 axe-shaped cutter and the three-edged cutter performed excellently and could effectively withstand high impact loads, while the 135 axe-shaped cutter had relatively weaker impact resistance due to insufficient support at the impact point. Further analysis of the cutting force data revealed that the tangential force and normal forces of ridge-shaped cutters were lower than those of round cutters at the same cutting depth. The smaller the ridge angle, the smaller the cutting force, which indicates that the ridge design helps reduce cutting resistance and improve drilling efficiency. The full-size drill bit simulation drilling test results showed that the 135 axe-shaped cutter achieved the fastest mechanical drilling speed and is suitable for high-pressure operations. The three-edged cutter performed better in the low-pressure range (≤ 20 kN), while the round teeth had the slowest drilling speed and a lower suitable drilling pressure range. Additionally, the variation in ridge tooth angle not only affects the impact resistance but also directly influences the rock-breaking effect by altering the stress distribution within the rock. Conclusions: Through systematic testing and comparative analysis, this study has verified the significant advantages of ridge-shaped PDC cutters in improving drilling efficiency and reducing the risk of drill bit failure. Specifically, the ridge design effectively enhances the wear resistance and impact resistance of the drill bit while reducing cutting force and increasing mechanical drilling speed. The performance differences of the various ridge-shaped cutters under different drilling pressure conditions provide a scientific basis for the flexible selection of drill bit types based on formation conditions during drilling operations. In the future, further optimization of ridge-shaped PDC cutter designs, especially for specific formation conditions, will be an important direction for improving mechanical drilling speeds and reducing operational costs.

Objective To investigate longitudinal changes in plantar pressure examinations and plain radiographs and to assess the correlations between these two modalities in pediatric patients with flexible flatfoot (FFF). Methods Pediatric patients diagnosed with FFF were analyzed in this retrospective cohort study. Medical records were reviewed to collect data on plain radiographs and plantar pressure examinations. Changes in radiographic angles and plantar pressure parameters were analyzed over a follow-up period exceeding 1 year. Statistical analyses included paired t-test, Wilcoxon signed rank test, and Spearman’s correlation analysis. Results A total of 52 subjects was included in the plantar pressure analysis, with a mean age of 9.9 years at the first visit and a median follow-up duration of 52 months. The lateral tarso-first metatarsal angle decreased by 1.3° (p

Abstract Background Abnormal posture is known to affect the efficacy of exercise therapy for musculoskeletal diseases. However, no studies to date have examined the effect of exercise programs should take into account the posture of the upper body in patients with rotator cuff disease. This study aimed to assess how rotator cuff and corrective exercises impact shoulder function and muscle strength post-arthroscopic rotator cuff repair surgery, providing tailored rehabilitation programs for patients with forward posture. Methods Ninety male patients who underwent arthroscopic rotator cuff repair participated in this study. The patients were randomly divided into three groups corrective exercise group (CEG, n = 29), rotator cuff exercise group (REG, n = 27), and control group (CG, n = 28). Each group was instructed to apply different exercise programs to correct posture and enhance rotator cuff strength. All patients were checked by the American Shoulder and Elbow Surgeons (ASES) score, Constant score and muscle strength, and range of motion preoperatively and postoperatively at 6 months and 1 year. Results ASES shoulder function scores showed significant difference between the three groups (p = 0.002, F = 7.03), indicating that the corrective exercise program was more beneficial than rotator cuff exercises (p = 0.009, F = 3.78). A significant intergroup difference in mean Constant score was also noted (p = 0.025, F = 3.86), while a statistically significant interaction between time and group was observed (p = 0.032, F = 2.96). Conclusions These results suggested that a corrective exercise program can improve shoulder muscle strength and function after rotator cuff repair in male patients with a forward shoulder posture.

Abstract Objective We aim to investigate the association between prognosis and outcomes following myocardial ischemia-reperfusion injury, as well as peripheral blood levels of NLRP3 and the triglyceride-glucose index (TyG). Methods A total of 100 patients who underwent emergency coronary intervention following myocardial infarction confirmed by coronary angiography at our hospital between October 2021 and May 2023 were included in this study. Patients were stratified into two groups based on their prognoses: the control group (n = 73), which did not experience new myocardial infarctions or require hospitalization for heart failure or suffer sudden cardiac death post-interventional treatment; and the observation group (n = 27), which experienced one or more cardiovascular events post-treatment. Patient demographics were obtained from clinical records while biochemical analyses assessed peripheral blood triglycerides, blood glucose levels, and TyG index. Additionally, ELISA measurements determined levels of NLRP3 as well as inflammatory factors IL-6, TNF-α, and CRP in peripheral blood samples. Cardiac function was evaluated according to NYHA standards. Univariable Cox regression analysis identified factors influencing patient prognosis while Pearson correlation analysis examined relationships among prognosis, outcomes following myocardial ischemia-reperfusion injury, TyG index, and peripheral blood NLRP3. Results No significant differences were observed in the general characteristics between the two patient groups (P > 0.05). However, the observation group exhibited higher levels of peripheral blood triglycerides, blood glucose, and TyG index compared to the control group (P

Abstract Understanding the interface between nanomaterials and lipoproteins is crucial for gaining insights into their impact on lipoprotein structure and lipid metabolism. Here, we use graphene oxide (GOs) nanosheets as a controlled carbon nanomaterial model to study how surface properties influence lipoprotein corona formation and show that GOs have strong binding affinity with low-density lipoprotein (LDL). We use advanced techniques including X-ray reflectivity, circular dichroism, and molecular simulations to explore the interfacial interactions between GOs and LDL. Specifically, hydrophobic GOs preferentially associate with LDL’s lipid components, whereas hydrophilic GOs tend to bind with apolipoproteins. Furthermore, these GOs distinctly modulate a variety of lipid metabolism pathways, including LDL recognition, uptake, hydrolysis, efflux, and lipid droplet formation. This study underscores the importance of structure analysis at the nano-biomolecule interface, emphasizing how nanomaterials’ surface properties critically influence cellular lipid metabolism. These insights will inspire the design and application of future biocompatible nanomaterials and nanomedicines.

Abstract Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics.

Abstract Background Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms of m6A-related regulators in HCC cell ferroptosis remain unclear. Methods By examining a series of m6A modification enzymes upon ferroptosis induction or inhibition, we identified METTL16 as a novel ferroptotic repressor in HCC cells. The roles of METTL16 on ferroptosis and HCC development were investigated in multiple cell lines, human HCC organoids, subcutaneous xenografts and MYC/Trp53−/− HCC model in hepatocyte-specific Mettl16 knockout and overexpression mice. The underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay and Mass Spectrometry. The clinical significance and relevance were evaluated in human samples. Results High METTL16 expression confers ferroptosis resistance in HCC cells and mouse models, and promotes cell viability and tumor progression. Mechanistically, METTL16 collaborates with IGF2BP2 to modulate SENP3 mRNA stability in an m6A-dependent manner, and the latter impedes the proteasome-mediated ubiquitination degradation of Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF expression facilitates the chelation of free iron and reduces liable iron pool level. SENP3 and LTF are implicated in METTL16-mediated HCC progression and anti-ferroptotic effects both in vivo and in vitro. Clinically, METTL16 and SENP3 expression were positively correlated, and high METTL16 and SENP3 expression predicts poor prognosis in human HCC samples. Conclusions Our study reveals a new METTL16-SENP3-LTF signaling axis regulating ferroptosis and driving HCC development. Targeting this axis is a promising strategy for sensitizing ferroptosis and against HCC.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Abstract Organic molecules with dynamic covalent-bonding characteristics have attracted much attention for their important role in constructing stimulus-responsive smart materials. However, it is difficult to realize sensitive and reversible covalent bond cleavage/formation through external stimuli in the aggregated state of molecules. Herein, a series of 2,3-diphenylmaleonitriles (DPMNs) with photoinduced π-bond cleavage properties have been designed and synthesized to construct the dynamic covalent bond materials. The cis-form 2,3-diphenylmaleonitriles (Z-DPMNs) exhibit significant photochromism in both solid and solution states under ultraviolet light and visible light. The photochromism stems from the photoinduced π-bond splitting of Z-DPMNs, resulting in a transition from the closed-shell to open-shell structure. Moreover, the twisted structure and molecular stacking of Z-DPMNs, the push-pull electron effect of substituents, and the external factors including temperature and solvent polarity have important effects on the dynamic conversion of π-bonds. Based on the sensitive and reversible optical performance transformation, Z-DPMNs can be applied as safety ink in anti-counterfeiting, information encryption and storage systems. This work not only provides an approach for constructing dynamic covalent bonds but also greatly enriches stimulus-responsive materials.

The complete chloroplast genome sequence of Sassafras randaiense (Hayata) Rehder, 1920, a subtropical tree in the family Lauraceae, was determined. For a better understanding of the differences between S. randaiense and S. tzumu, the complete chloroplast genome of S. randaiense was sequenced and analyzed. The complete chloroplast genome is 151,781 bp in length, consisting of a pair of inverted repeat (IR) regions of 20,114 bp, one large single-copy (LSC) region of 92,740 bp, and one small single-copy (SSC) region of 18,813 bp. The overall GC content of the complete chloroplast genome is 39.2%. Further, maximum-likelihood phylogenetic analysis was conducted using 31 complete plastome sequences, which support that S. randaiense and S. tzumu are nested among the members of Cinnamomum, suggesting that Sassafras belongs to Cinnamomum.

Abstract Objectives This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. Methods We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. Results Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6–83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13–0.28). In subgroup analysis, the age subgroup was split into

Abstract Background Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. Methods The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague–Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. Results The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. Conclusion NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Bubble dynamics is paramount in comprehending the heat transfer mechanisms of flow boiling in the microchannel within ultrasonic field, which is regarded as a promising method to confront challenges of thermal management posed by microelectronic devices. Nevertheless, the impact of ultrasound on bubble behaviors and its underlying mechanisms remain largely unexplored. This study first delves into the effect of ultrasonic parameters on bubble dynamic behaviors and associated mechanisms, subsequently further analyzing the forces acting on bubbles through the constructed force model. The findings suggest that although growth force serves as the significant resistance, the primary Bjerknes force dominates the rapid detachment of bubbles. The secondary Bjerknes force results in the bubble only sliding along the bottom wall rather than lifting off. Furthermore, the elevated ultrasonic pressure amplitude resulting from augmenting ultrasonic power induces a substantial increase in the critical detachment diameter and growth rate by 55.49 % and 59.42 %, respectively. The enhanced primary Bjerknes force, attributed to the rise in ultrasonic frequency, leads to a 71.42 % increase in sliding velocity and a 46.45 % reduction in growth time. The positive impacts arising from ultrasonic power and frequency are anticipated to notably enhance the thermal performance of microchannels. Besides, surface tension acts as the resistance and diminishes slightly with an augmentation of the boiling number, resulting in a moderate variation in sliding velocity and growth time.

Accurately predicting travel destinations in a city from partial trajectories is crucial for many location-based services. This task faces two challenges: data sparsity and the complex probability distribution of destinations. Previous studies neglected the fusion of spatiotemporal features and urban contexts, which limited their effectiveness in characterizing trajectory patterns and exacerbated data sparsity issues. Most methods either predicted a single destination or the probability of each predefined sub-region, but they struggled with the modifiable areal unit problem. To address these problems, we propose an approach based on the diffusion probabilistic model, comprising a trajectory encoder and a diffusion decoder. The trajectory encoder extracts four embeddings to represent spatiotemporal features and urban contexts, integrating them using an attention mechanism to mitigate data sparsity. The diffusion decoder recovers the complex destination probability distribution and predicts multiple candidate destinations without predefined regional units, effectively addressing the modifiable areal unit problem. Experiments on driving trajectories in Shenzhen, China, show an average improvement of 10.80% across four metrics compared to state-of-the-art methods. We also observed the influence of trajectory length and origin location on prediction accuracy. The results validate the importance of modeling destination probability distributions, as well as integrating spatiotemporal features and urban contexts.