Hypoperfusion intensity ratio and hemorrhagic transformation in patients with successful recanalization after thrombectomy.

BACKGROUND AND PURPOSE: Hemorrhagic transformation remains a potentially devastating complication of acute ischemic stroke. We aimed to evaluate whether the hypoperfusion intensity ratio (HIR), a parameter derived from CT perfusion imaging, is associated with the development of hemorrhagic transformation in patients with anterior large-artery occlusion who had undergone thrombectomy. MATERIALS AND METHODS: We retrospectively reviewed data from consecutive acute ischemic stroke patients who had achieved successful recanalization (thrombolysis in cerebral infarction score ≥ 2b) between January 2020 and December 2023. HIR was defined as the ratio of the volume of lesions with a time-to-maximum (TMax) > 6 s to those with a Tmax > 10 s delay. The primary outcome, based on the European Cooperative Acute Stroke Study, was hemorrhagic transformation (HT), diagnosed by follow-up imaging assessment in 24 h windows, and radiologically classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH). The secondary outcome was a 3-month mRS score of ≥3. RESULTS: Among 168 patients, 35/168 developed hemorrhagic transformation HT; 14/168 developed hemorrhagic infarction HI, and 21/168 developed parenchymal hematoma PH. After adjusting the latent covariates, increased hypoperfusion intensity ratio (per 0.1, adjusted OR [aOR] 1.68, 95% CI 1.26-2.25), ASPECTS (aOR 0.44, 95% CI 0.27-0.72), onset-to-puncture (aOR 1.01, 95% CI 1.00-1.02), and cardioembolism (aOR 5.6, 95% CI 1.59-19.7) were associated with hemorrhagic transformation in multivariable regression. The receiver operating characteristic curve indicated that HIR can predict HT accurately (area under the curve = 0.81; 95% CI, 0.738-0.882; P < 0.001) and predict PH (area under the curve = 0.801; 95% CI, 0.727-0.875; P < 0.001). CONCLUSIONS: Upon admission, hypoperfusion intensity ratio, an imaging parameter, predicted hemorrhagic transformation after reperfusion therapy in this patient population.ABBREVIATIONS: HT = hemorrhagic transformation; HIR = hypoperfusion intensity ratio; LVO = left vessel occlusion; EVT = endovascular thrombectomy; AIS = arterial ischemic stroke; OTP = onset-to-puncture; HI = hemorrhagic infarction; PH = parenchymal hematoma.

Exploration of the influence of GOLGA8B on prostate cancer progression and the resistance of castration-resistant prostate cancer to cabazitaxel.

Castration-resistant prostate cancer (CRPC) represents the final stage of prostate cancer (PCa). Cabazitaxel, a taxane chemotherapy drug, is used in treating CRPC. However, patients with CRPC eventually develop resistance to cabazitaxel, and the underlying mechanism remains unclear. Here, we aimed to investigate potential genetic alterations that may play a role in CRPC resistance to cabazitaxel. Using microarray data from the GSE158494 dataset, we identified ten critical genes (CXCL8, ITGB8, CLIP4, MAP1B, WIPI1, MMP13, CXCL1, C1S, GOLGA8B, and CXCL6) associated with CRPC cell resistance to cabazitaxel. The potential function of these key genes in PCa progression was analyzed using different databases, including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA). Our findings revealed altered expression of these genes in the development of PCa. Furthermore, CXCL1 and GOLGA8B were found to influence the disease-free survival (DFS) status of patients with PCa, with GOLGA8B affecting the overall prognosis in patients with PCa. Additionally, GOLGA8B expression was associated with the infiltration of various immune cells in PCa, and it was upregulated in clinical PCa and CRPC samples. Through CCK-8 assays, we established that GOLGA8B could influence the sensitivity of CRPC cells to cabazitaxel and docetaxel. In conclusion, we identified GOLGA8B as a crucial gene that influences PCa progression and contributes to CRPC resistance to cabazitaxel.

Characteristics of Acid Leaching and Vibration Coupling Desorption of Gas-Saturated Coking Coal.

Permeability is a key factor affecting efficient gas drainage from coal seams, and acidification and vibration shock are effective means to increase permeability in original low-permeability coal seams. To study the gas desorption characteristics of coking coal under the coupling effect of mining disturbance and acidification permeability enhancement, taking the coal seam of Shoushan No. 1 coal as the research object, a self-built adsorption-desorption vibration test platform was used. Acid leaching vibration coupling desorption experiments at vibration frequencies of 0, 30, 60, and 100 Hz were conducted on selected particle coals with particle sizes of 0.18-0.25 and 1-3 mm. The experimental results show that the gas desorption amount of particle coal with the same particle size first increases and then decreases with the increase of vibration frequency, among which the desorption effect is the best under 60 Hz vibration condition. Under the condition of fixed vibration frequency, the desorption amount, initial desorption velocity, and velocity attenuation coefficient of particle coal increase as the particle size decreases. Under the same particle size and vibration frequency conditions, the acid leaching and vibration of coal samples have a synergistic effect on gas desorption, which is manifested in the promotion of gas desorption on the outer surface of the coal sample and the surface of open macropores. The research can provide theoretical reference for coal seam acidification and permeability enhancement under the influence of mining disturbance.

Self-assembly of peptide nanocapsules by a solvent concentration gradient.

Biological systems can create materials with intricate structures and specialized functions. In comparison, precise control of structures in human-made materials has been challenging. Here we report on insect cuticle peptides that spontaneously form nanocapsules through a single-step solvent exchange process, where the concentration gradient resulting from the mixing of water and acetone drives the localization and self-assembly of the peptides into hollow nanocapsules. The underlying driving force is found to be the intrinsic affinity of the peptides for a particular solvent concentration, while the diffusion of water and acetone creates a gradient interface that triggers peptide localization and self-assembly. This gradient-mediated self-assembly offers a transformative pathway towards simple generation of drug delivery systems based on peptide nanocapsules.

Maresin-1 Attenuates Sepsis-Associated Acute Kidney Injury via Suppressing Inflammation, Endoplasmic Reticulum Stress and Pyroptosis by Activating the AMPK/SIRT3 Pathway.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation. Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay. Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1ß and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1ß also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1's protective effects in septic mice. Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.

Association of serum albumin with heart failure mortality with NYHA class IV in Chinese patients: Insights from PhysioNet database (version 1.3).

BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.

Tough, self-healing and injectable dynamic nanocomposite hydrogel based on gelatin and sodium alginate.

Biomacromolecules based injectable and self-healing hydrogels possessing high mechanical properties have widespread potential in biomedical field. However, dynamic features are usually inversely proportional to toughness. It is challenging to simultaneously endow these properties to the dynamic hydrogels. Here, we fabricated an injectable nanocomposite hydrogel (CS-NPs@OSA-l-Gtn) stimultaneously possessing excellent autonomous self-healing performance and high mechanical strength by doping chitosan nanoparticles (CS-NPs) into dynamic polymer networks of oxidized sodium alginate (OSA) and gelatin (Gtn) in the presence of borax. The synergistic effect of the multiple reversible interactions combining dynamic covalent bonds (i.e., imine bond and borate ester bond) and noncovalent interactions (i.e., electrostatic interaction and hydrogen bond) provide effective energy dissipation to endure high fatigue resistance and cyclic loading. The dynamic hydrogel exhibited excellent mechanical properties like maximum 2.43 MPa compressive strength, 493.91 % fracture strain, and 89.54 kJ/m3 toughness. Moreover, the integrated hydrogel after injection and self-healing could withstand 150 successive compressive cycles. Besides, the bovine serum albumin embedded in CS-NPs could be sustainably released from the nanocomposite hydrogel for 12 days. This study proposes a novel strategy to synthesize an injectable and self-healing hydrogel combined with excellent mechanical properties for designing high-strength natural carriers with sustained protein delivery.

Removal of inflammatory factors and prognosis of patients with septic shock complicated with acute kidney injury by hemodiafiltration combined with HA330-II hemoperfusion.

INTRODUCTION: To explore the effect of CRRT using CVVHDF + HP on the removal of inflammatory mediators in patients with septic shock complicated with AKI. METHODS: A total of 20 patients between January 1, 2018, and December 31, 2021, were included. The patients were randomly divided into the treatment group (CVVHDF + HP) and the control group (CVVHDF). Changes in inflammatory factors, including IL-1ß, IL-6, IL-8, TNF-α, PCT, and CRP were compared. Other observed measures were also analyzed, for example, Lac, Scr, BUN, SOFA, and norepinephrine (NE) dosage. The clinical outcomes of both groups were followed up for 28 days. RESULTS: The IL-6 and PCT levels in the treatment group were significantly lower (p = 0.005, 0.007). Although the IL-1ß, TNFα, and CRP levels in the treatment group decreased, there were no statistical differences (p > 0.05). There were significant differences in Lac, SOFA, and NE dosage levels between both groups (p = 0.023, 0.01, 0.023). Survival analysis showed that the 28-day survival rate was significantly higher in the treatment group. CONCLUSION: CRRT using CVVHDF+HP can effectively remove inflammatory factors and improve the prognosis of patients.

Research on a novel water-cooling multi-cylinder magnetorheological transmission device.

Power transmission is an important application for magnetorheological (MR) fluid, and the cylinder-type power transmission device is a novel transmission form due to its high stability, higher transmission torque, and large ratio of power to mass. This work designed a novel multi-cylinder transmission device with a water-cooling channel because the MR transmission device, especially high-power MR transmission device, inevitably works in the high-temperature environment. Based on Ohm's law and electromagnetism theory, the magnetic circuit in the novel MR transmission device is designed, and the magnetoresistance was calculated. The finite element method is used to analyze the magnetic field in the device to ensure that the magnetic field in the working gap of MR fluid is strong enough for the MR effects. The temperature of the MR fluid inside the device is analyzed by the finite element method in the natural cooling state and the water-cooling state, respectively, so as to obtain the performance of water cooling. The novel MR transmission device is manufactured to verify its power transmission capability and heat-dissipation performance. The experimental results show that the novel device can transmit a maximum torque of 70 N m, consistent with the rated torque. In addition, compared with natural cooling, the water cooling makes the temperature of the MR fluid to drop by 32.7% under the same working condition. This is the first time that the cooling channel is set up in the cylinder-type MR transmission device, which will provide a solution for the higher power transmission capacity by MR fluid.

Glycolysis related lncRNA SNHG3 / miR-139-5p / PKM2 axis promotes castration-resistant prostate cancer (CRPC) development and enzalutamide resistance.

Although androgen deprivation therapy (ADT) by the anti-androgen drug enzalutamide (Enz) may improve the survival level of patients with castration-resistant prostate cancer (CRPC), most patients may eventually fail due to the acquired resistance. The reprogramming of glucose metabolism is one type of the paramount hallmarks of cancers. PKM2 (Pyruvate kinase isozyme typeM2) is a speed-limiting enzyme in the glycolytic mechanism, and has high expression in a variety of cancers. Emerging evidence has unveiled that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have impact on tumor development and therapeutic efficacy by regulating PKM2 expression. Herein, we found that lncRNA SNHG3, a highly expressed lncRNA in CRPC via bioinformatics analysis, promoted the invasive ability and the Enz resistance of the PCa cells. KEGG pathway enrichment analysis indicated that glucose metabolic process was tightly correlated with lncRNA SNHG3 level, suggesting lncRNA SNHG3 may affect glucose metabolism. Indeed, glucose uptake and lactate content determinations confirmed that lncRNA SNHG3 promoted the process of glycolysis. Mechanistic dissection demonstrated that lncRNA SNHG3 facilitated the advance of CRPC by adjusting the expression of PKM2. Further explorations unraveled the role of lncRNA SNHG3 as a 'sponge' of miR-139-5p and released its binding with PKM2 mRNA, leading to PKM2 up-regulation. Together, Our studies suggest that lncRNA SNHG3 / miR-139-5p / PKM2 pathway promotes the development of CRPC via regulating glycolysis process and provides valuable insight into a novel therapeutic approach for the disordered disease.

Musculoskeletal adverse events induced by immune checkpoint inhibitors: a large-scale pharmacovigilance study.

Background: The musculoskeletal toxicity of immune checkpoint inhibitors (ICIs) is receiving increasing attention with clinical experience. Nevertheless, the absence of a systematic investigation into the musculoskeletal toxicity profile of ICIs currently results in the under-recognition of associated adverse events. Further and more comprehensive investigations are warranted to delineate the musculoskeletal toxicity profile of ICIs and characterize these adverse events. Material and methods: The present study employed the FDA Adverse Event Reporting System database to collect adverse events between January 2010 and March 2021. We utilized both the reporting odds ratio and the Bayesian confidence propagation neural network algorithms to identify suspected musculoskeletal adverse events induced by ICIs. Subsequently, the clinical characteristics and comorbidities of the major musculoskeletal adverse events were analyzed. The risk of causing these events with combination therapy versus monotherapy was compared using logistic regression model and Ω shrinkage measure model. Results: The musculoskeletal toxicity induced by ICIs primarily involves muscle tissue, including neuromuscular junctions, fascia, tendons, and tendon sheaths, as well as joints, spine, and bones, including cartilage. The toxicity profile of PD-1/PD-L1 and CTLA-4 inhibitors varies, wherein the PD-1 inhibitor pembrolizumab exhibits a heightened overall risk of inducing musculoskeletal adverse events. The major ICIs-induce musculoskeletal adverse events, encompassing conditions such as myositis, neuromyopathy (including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Guillain-Barré syndrome, and Chronic inflammatory demyelinating polyradiculoneuropathy), arthritis, fractures, myelitis, spinal stenosis, Sjogren's syndrome, fasciitis, tenosynovitis, rhabdomyolysis, rheumatoid myalgia, and chondrocalcinosis. Our study provides clinical characteristics and comorbidities of the major ICIs-induced musculoskeletal adverse events. Furthermore, the combination therapy of nivolumab and ipilimumab does not result in a statistically significant escalation of the risk associated with the major musculoskeletal adverse events. Conclusion: Immune checkpoint inhibitors administration triggers a range of musculoskeletal adverse events, warranting the optimization of their management during clinical practice.

CYP19A1 is downregulated by BRD4 and suppresses castration-resistant prostate cancer cell invasion and proliferation by decreasing AR expression.

Castration-resistant prostate cancer (CRPC) is the final stage of prostate cancer (PCa). As the main androgen in males, testosterone, and its androgen receptor (AR) play an important role in CRPC. The enzyme that catalyzes testosterone, aromatase, can be influenced by CYP19A1 activity - thus possibly affecting both AR expression and CRPC. However, the function of CYP19A1 in CRPC remains unclear. Using data derived from public databases and clinical samples, we analyzed the expression of CYP19A1 in PCa and CRPC specimens. The effect of CYP19A1 on cell invasion and proliferation was investigated in vitro and in vivo; while its function in metabolizing testosterone was detected in vitro. The effect of BRD4 on CYP19A1 and AR was investigated by qRT-PCR and western blot; whereas the effect of JQ1 on cells was assessed based on the IC50 value. We found that CYP19A1 was downregulated in CRPC samples and cells which correlated with a decrease in CRPC cell invasion and proliferation, and an increase in AR expression. Inversely, CYP19A1 affected CRPC cell invasion and proliferation by suppressing the expression of AR which may be attributed to the metabolism of testosterone by CYP19A1. Moreover, the BRD4 inhibitor JQ1 induced the CYP19A1 expression and suppressed the AR expression. Following BRD4 knockdown, CYP19A1 showed higher expression while AR expression was decreased. Our findings demonstrated that CYP19A1 could reduce CRPC cell invasion and proliferation by targeting AR, and this process could be regulated by BRD4. CYP19A1 may be a potential therapeutic target and enhance BRD4 inhibition in treating CRPC.

Abnormal maxillary sinus diagnosing on CBCT images via object detection and 'straight-forward' classification deep learning strategy.

BACKGROUND: Pathological maxillary sinus would affect implant treatment and even result in failure of maxillary sinus lift and implant surgery. However, the maxillary sinus abnormalities are challenging to be diagnosed through CBCT images, especially for young dentists or dentists in grassroots medical institutions without systematical education of general medicine. OBJECTIVES: To develop a deep-learning-based screening model incorporating object detection and 'straight-forward' classification strategy to screen out maxillary sinus abnormalities on CBCT images. METHODS: The large area of background noise outside maxillary sinus would affect the generalisation and prediction accuracy of the model, and the diversity and imbalanced distribution of imaging manifestations may bring challenges to intellectualization. Thus we adopted an object detection to limit model's observation zone and 'straight-forward' classification strategy with various tuning methods to adapt to dental clinical need and extract typical features of diverse manifestations so that turn the task into a 'normal-or-not' classification. RESULTS: We successfully constructed a deep-learning model consist of well-trained detector and diagnostor module. This model achieved ideal AUROC and AUPRC of 0.953 and 0.887, reaching more than 90% accuracy at optimal cut-off. McNemar and Kappa test verified no statistical difference and high consistency between the prediction and ground truth. Dentist-model comparison test showed the model's statistically higher diagnostic performance than dental students. Visualisation method confirmed the model's effectiveness in region recognition and feature extraction. CONCLUSION: The deep-learning model incorporating object detection and straightforward classification strategy could achieve satisfying predictive performance for screening maxillary sinus abnormalities on CBCT images.

Anaesthesia-related mortality within 24 h following 9,391,669 anaesthetics in 10 cities in Hubei Province, China: a serial cross-sectional study.

Background: The mortality risk related to anaesthesia in China remains poorly characterized. The objective of this study was to evaluate the anaesthesia-related mortality in terms of its incidence, changes, causes and preventability in Hubei, China, between 2017 and 2021 using a series of annual surveys. Methods: We prospectively collected information on patient, surgical, anaesthesia, and hospital characteristics for 9,391,669 anaesthesia procedures performed between 2017 and 2021 in 10 cities within Hubei Province, China. Anaesthesia-related death was defined as death that deemed to be entirely or partially attributable to anaesthesia, occurring within 24 h following anaesthesia administration. All fatalities were scrutinized consecutively to determine their root causes and preventability. The incidence and patterns of anaesthesia-related deaths were analysed from 2017 to 2021. A mixed-effects model with a Poisson link function was fitted to evaluate the city-level annual changes in risk-adjusted incidence of anaesthesia-related deaths. Findings: 600 cases of anaesthetic deaths occurred from 2017 to 2021, yielding an incidence of 6.4 per 100,000 anaesthesia procedures [95% confidence interval (95% CI): 5.9, 6.9], and most were preventable (71.3%). There was a significant decrease from 2017 to 2021, in the incidences of anaesthesia-related death across all patients, those with American Society of Anaesthesiologists physical status (ASAPS) ≥III, and those who had general anaesthesia, with a percentage reduction of 57.6%, 59.1%, and 55.9%, respectively. The risk-adjusted annual changes indicated significant downward trends for the incidence of anaesthetic mortality from 2017 to 2018, 2019, 2020, and 2021. For instance, the risk-adjusted annual changes for the anaesthetic mortality incidence from 2017 to 2021 was -2.5 (95% CI: -1.4, -4.7). Interpretation: In this large, comprehensive database study conducted in Central China, the anaesthesia-related death incidence was 6.4 per 100,000. Notably, the incidence of anaesthesia-related deaths decreased between 2017 and 2021. However, further in-depth analysis is needed to understand the extent to which these trends represent a change in patient safety. Funding: Innovation and optimization of perioperative respiratory system management strategy (Hubei Technological Innovation Special Fund, 2019ACA167).

An immunogenic cell death-related classification predicts prognosis and response to immunotherapy in kidney renal clear cell carcinoma.

Introduction: Immunogenic cell death (ICD) is a form of regulated cell death that activates an adaptive immune response in an immunocompetent host and is particularly sensitive to antigens from tumor cells. Kidney clear cell carcinoma (KIRC) is an immunogenic tumor with extensive tumor heterogeneity. However, no reliable predictive biomarkers have been identified to reflect the immune microenvironment and therapeutic response of KIRC. Methods: Therefore, we used the CIBERSORT and ESTIMATE algorithms to define three ICD clusters based on the expression of ICD-related genes in 661 KIRC patients. Subsequently, we identified three different ICD gene clusters based on the overlap of differentially expressed genes (DEGs) within the ICD clusters. In addition, principal component analysis (PCA) was performed to calculate the ICD scores. Results: The results showed that patients with reduced ICD scores had a poorer prognosis and reduced transcript levels of immune checkpoint genes regulated with T cell differentiation. Furthermore, the ICD score was negatively correlated with the tumor mutation burden (TMB) value of KICD. patients with higher ICD scores showed clinical benefits and advantages of immunotherapy, indicating that the ICD score is an accurate and valid predictor to assess the effect of immunotherapy. Discussion: Overall, our study presents a comprehensive KICD immune-related ICD landscape that can provide guidance for current immunotherapy and predict patient prognosis to help physicians make judgments about the patient's disease and treatment modalities, and can guide current research on immunotherapy strategies for KICD.

Manufacture of titanium alloy materials with bioactive sandblasted surfaces and evaluation of osseointegration properties.

Titanium alloys are some of the most important orthopedic implant materials currently available. However, their lack of bioactivity and osteoinductivity limits their osseointegration properties, resulting in suboptimal osseointegration between titanium alloy materials and bone interfaces. In this study, we used a novel sandblasting surface modification process to manufacture titanium alloy materials with bioactive sandblasted surfaces and systematically characterized their surface morphology and physicochemical properties. We also analyzed and evaluated the osseointegration between titanium alloy materials with bioactive sandblasted surfaces and bone interfaces by in vitro experiments with co-culture of osteoblasts and in vivo experiments with a rabbit model. In our in vitro experiments, the proliferation, differentiation, and mineralization of the osteoblasts on the surfaces of the materials with bioactive sandblasted surfaces were better than those in the control group. In addition, our in vivo experiments showed that the titanium alloy materials with bioactive sandblasted surfaces were able to promote the growth of trabecular bone on their surfaces compared to controls. These results indicate that the novel titanium alloy material with bioactive sandblasted surface has satisfactory bioactivity and osteoinductivity and exhibit good osseointegration properties, resulting in improved osseointegration between the material and bone interface. This work lays a foundation for subsequent clinical application research into titanium alloy materials with bioactive sandblasted surfaces.

Toll-like receptor 4: A potential therapeutic target for multiple human diseases.

The immune response plays a pivotal role in the pathogenesis of diseases. Toll-like receptor 4 (TLR4), as an intrinsic immune receptor, exhibits widespread in vivo expression and its dysregulation significantly contributes to the onset of various diseases, encompassing cardiovascular disorders, neoplastic conditions, and inflammatory ailments. This comprehensive review centers on elucidating the architectural and distributive characteristics of TLR4, its conventional signaling pathways, and its mode of action in diverse disease contexts. Ultimately, this review aims to propose novel avenues and therapeutic targets for clinical intervention.

A Study Based on Network Pharmacology Decoding the Multi-Target Mechanism of Duhuo Jisheng Decoction for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) poses a grim public health impact. Duhuo Jisheng Decoction (DJD), a traditional Chinese medicine formula, has recently received significant attention for its efficacy and safety in treating IDD. However, the pathological processes of IDD in which DJD interferes and molecular mechanism involved are poorly understood, which brings difficulties to the clinical practice of DJD for the treatment of IDD. This study systematically investigated the underlying mechanism of DJD treatment of IDD. Network pharmacology approaches were employed, integrating molecular docking and random walk with restart (RWR) algorithm, to identify key compounds and targets for DJD in the treatment of IDD. Bioinformatics approaches were used to further explore the biological insights in DJD treatment of IDD. The analysis identifies AKT1, PIK3R1, CHUK, ALB, TP53, MYC, NR3C1, IL1B, ERBB2, CAV1, CTNNB1, AR, IGF2, and ESR1 as key targets. Responses to mechanical stress, oxidative stress, cellular inflammatory responses, autophagy, and apoptosis are identified as the critical biological processes involved in DJD treatment of IDD. The regulation of DJD targets in extracellular matrix components, ion channel regulation, transcriptional regulation, synthesis and metabolic regulation of reactive oxygen products in the respiratory chain and mitochondria, fatty acid oxidation, the metabolism of Arachidonic acid, and regulation of Rho and Ras protein activation are found to be potential mechanisms in disc tissue response to mechanical stress and oxidative stress. MAPK, PI3K/AKT, and NF-κB signaling pathways are identified as vital signaling pathways for DJD to treat IDD. Quercetin and Kaempferol are assigned a central position in the treatment of IDD. This study contributes to a more comprehensive understanding of the mechanism of DJD in treating IDD. It provides a reference for applying natural products to delay the pathological process of IDD.

A Novel Magnetorheological Fluid with High-Temperature Resistance.

A magnetorheological fluid (MR fluid) is mainly composed of soft magnetic particles, surfactants, and the base carrier fluid. Among these, soft magnetic particles and the base carrier fluid influence the MR fluid significantly in a high-temperature environment. Therefore, a study was carried out to investigate the changes in the properties of soft magnetic particles and base carrier fluids in high-temperature environments. On this basis, a novel magnetorheological fluid with high-temperature resistance was prepared, and the novel magnetorheological fluid had excellent sedimentation stability, of which the sedimentation rate was only 4.42% after heat treatment at 150 °C followed by one-week placement. At 30 °C, the shear yield stress of the novel fluid was 9.47 kPa under the magnetic field of 817 mT: higher than the general magnetorheological fluid with the same mass fraction. Moreover, its shear yield stress was less affected by the high-temperature environment, reducing by only 4.03% from 10 °C to 70 °C. The novel MR fluid can be applied to a high-temperature environment, effectively expanding the application range of MR fluid.

Identification and validation of MSMB as a critical gene for prostate cancer development in obese people.

Prostate cancer (PCA) is one of the most common types of cancer and can seriously endanger the health of older men. Obesity is prevalent all around the world and triggered by lots of factors such as diet, environment and fat metabolism disorder can cause many neoplasms, including PCA. Evidence suggests that genetic changes increase the risk of PCA and obesity. However, the specific obesity-related genes leading to PCA are unknown. Obesity-related genes associated with PCA were identified and analyzed though three public electronic databases: Gene Expression Omnibus, The Cancer Genome Atlas, and Chinese Prostate Cancer Genome and Epigenome Atlas. The effect of obesity-related genes in PCA were analyzed using clinical data from different databases, while associations with immune cells were determined by TIMER web tool. The expression and function of obesity-related genes were verified using clinical samples from obese patients with PCA and PCA cells. We found that four genes, MSMB, BMP5, THBS4, and POPDC3, may lead to PCA occurrence in patients with obesity. In Gene Expression Omnibus database, MSMB and BMP5 were downregulated, while THBS4 and POPDC3 were upregulated. This trend was mainly preserved in the other electronic databases. We also discovered MSMB and THBS4 can affect PCA progression, and all these genes were risk factors for castration-resistant prostate cancer. Moreover, MSMB can impact disease-free survival status of patients with PCA. These obesity-related genes were also correlated with immune cells and immune cell infiltration in PCA. We further uncovered that MSMB was downregulated in clinical PCA and castration-resistant prostate cancer samples from patients with obesity and MSMB decreased PCA cells proliferation. These results indicate that MSMB is essential for PCA development in people with obesity and can be a biomarker for predicting PCA occurrence and progression in obese people.