Benzothiazole derivatives as histone deacetylase inhibitors for the treatment of autosomal dominant polycystic kidney disease.

Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). The selected compound significantly prevented cyst formation and expansion in an in vitro cyst model and was efficacious in reducing cyst growth in both an embryonic kidney cyst model and an in vivo ADPKD mouse model. Our results provided compelling evidence that compound 26 represents a new HDAC inhibitor for the treatment of ADPKD.

PHD finger protein 10 promotes cell proliferation by regulating CD44 transcription in gastric cancer.

PHD finger protein 10 (PHF10) plays an important role in the tumorigenesis of gastric cancer (GC). However, clinical significance and underlying molecular mechanisms about PHF10 is unclear. In the article, it suggested that PHF10 involved in tumor progression and metastasis based on the analysis of datasets and 190 cases of tumor tissues in GC. And PHF10 provided the diagnostic value with areas under the receiver operating characteristics curve of 0.71 ± 0.069. Then we established GC cell lines MKN28 with PHF10 overexpression and SGC7901 with PHF10 knockdown. CCK8 assay and tumor xenograft experiment showed that upregulation of PHF10 could promote MKN28 cell proliferation, while PHF10 knockdown would inhibit the proliferation of SGC7901 in vitro and vivo. Nevertheless, PHF10 could upregulate CD44 mRNA expression by acting on its promoter at the level of transcription. This effect could be associated with BRG, BAF155 and SNF5, which were conserved subunits of switch/sucrose non-fermentable (SWI/SNF) complex. In conclusion, PHF10 targeting CD44 plays an essential part during the modulation of proliferation of GC cell and may offer a new therapeutic direction for GC.

Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia.

BACKGROUND: Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. METHODS: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. RESULTS: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P  <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. CONCLUSION: The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Asymmetric synthesis of P-stereogenic phosphindane oxides via kinetic resolution and their biological activity.

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Morphological characteristics of femoral neck fractures in young and middle-aged population: a retrospective descriptive study.

BACKGROUND: A understanding of morphological characteristics are important to femoral neck fractures (FNFs) resulting in high rates of complications in the young and middle-aged adults and the detailed data is lack in the literature. We aimed to report on the detailed morphological characteristics and the relationship between them in young and middle-aged adults with femoral neck fractures (FNFs). METHODS: The postoperative CT images of one hundred and fifty-two adults with FNFs were retrospectively reviewed. After image standardization, morphological characteristics including fracture orientation, cortex comminution, and intraosseous bone defects were measured and analyzed. Additionally, the distribution and correlation of these morphological features were analyzed using Pauwels classification, the right angle of the neck axis (VNA) classification, and the anteromedial oblique angle (AMA). RESULTS: Pauwels III fractures accounted for approximately half (55.2%) of the FNFs analyzed. Pauwels II and III could be detected in all four VNA types, and the distribution of the Pauwels types in VNA classification showed significant differences (χ2 = 106.363, p < 0.001). The VNA (9.0° ± 12.1) showed positive correlation with the neck-shaft angle (139.5° ± 6.3) and modified Pauwels angle (49.8° ± 10.6) (r = 0.441, r = 0.855, all p < 0.001). Cortical comminutions were commonly observed in the posterior (86.7%) and the inferior (80.7%). AMAs within the cases without posterior and inferior cortex comminutions were significantly larger than those with comminution (t = 2.594, 2.1196; p = 0.01, 0.036), but no difference could be detected after the AMA being divided into three groups (< 85°, 85°-95°, > 95°). The MPA, VNA and AMA of the group with an intraosseous defect were significantly different compared with those without (t = 2.847, 2.314, 2.268; p = 0.005, 0.022,0.025). The incidence of intraosseous defects within the groups with coronal and axial cortex comminutions were significantly higher than those within the groups without comminutions (χ2 = 34.87, 25.303; p < 0.001). CONCLUSIONS: The present study highlights the morphological diversity and complexity within FNFs in young and middle-aged adults, which allows for more accurate simulation of FNF patterns in the future biomechanical studies.

Thiophenpiperazine amide derivatives as new dual MOR and σ1R ligands for the treatment of pain.

A new series of thiophenpiperazine amide derivatives as potent dual ligands for the µ-opioid (MOR) and sigma-1 (σ1R) receptors are reported. Compound 23 exhibited good affinity to σ1R (Ki = 44.7 ± 7.05 nM) and high selectivity to σ2R. Furthermore, Compound 23 exerted MOR agonism and σ1R antagonism and potent analgesic activity in animal moldes (the abdominal constriction test (ED50 = 3.83 mg/kg) and carrageenan-induced inflammatory hyperalgesia model (ED50 = 5.23 mg/kg)). We obtained new dual ligands that might serve as starting points for preparing targeted tools. Furthermore, 23 may be a useful chemical probe for understanding more fully analgesic effects associated with MOR agonism and σ1R antagonism.

A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer.

INTRODUCTION: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC). METHODS: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC. RESULTS: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection. CONCLUSIONS: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs. PROSPERO REGISTRATION: CRD42021274120.

BPTF Drives Gastric Cancer Resistance to EGFR Inhibitor by Epigenetically Regulating the C-MYC/PLCG1/Perk Axis.

Erlotinib, an EGFR tyrosine kinase inhibitor, is used for treating patients with cancer exhibiting EGFR overexpression or mutation. However, the response rate of erlotinib is low among patients with gastric cancer (GC). The findings of this study illustrated that the overexpression of bromodomain PHD finger transcription factor (BPTF) is partially responsible for erlotinib resistance in GC, and the combination of the BPTF inhibitor AU-1 with erlotinib synergistically inhibited tumor growth both in vivo and in vitro. AU-1 inhibited the epigenetic function of BPTF and decreased the transcriptional activity of c-MYC on PLCG1 by attenuating chromosome accessibility of the PLCG1 promoter region, thus decreasing the expression of p-PLCG1 and p-Erk and eventually improving the sensitivity of GC cells to erlotinib. In patient-derived xenograft (PDX) models, AU-1 monotherapy exhibited remarkable tumor-inhibiting activity and is synergistic anti-tumor effects when combined with erlotinib. Altogether, the findings illustrate that BPTF affects the responsiveness of GC to erlotinib by epigenetically regulating the c-MYC/PLCG1/pErk axis, and the combination of BPTF inhibitors and erlotinib is a viable therapeutic approach for GC.

Cognitive Performance in Patients With Sporadic Vestibular Schwannoma.

BACKGROUND: To date, few data are available on the cognitive function of patients with vestibular schwannoma (VS) before treatment. OBJECTIVE: To provide a cognitive profile of patients with VS. METHODS: This cross-sectional observational study recruited 75 patients with an untreated VS and 60 age-, sex-, and education-matched healthy control subjects. A set of neuropsychological tests were administered to each participant. RESULTS: Compared with the matched controls, patients with VS exhibited impaired general cognitive function, memory, psychomotor speed, visuospatial ability, attention and processing speed, and executive function. The subgroup analyses displayed that patients with severe-to-profound unilateral hearing loss were more cognitively impaired than patients with no-to-moderate unilateral hearing loss. In addition, patients with right-sided VS scored worse than those with left-sided VS on tests of memory, attention and processing speed, and executive function. No differences were observed in cognitive performance between patients with or without brainstem compression and those with or without tinnitus. We also found that worse hearing and longer hearing loss duration were associated with poorer cognitive performance in patients with VS. CONCLUSION: The findings of this study provide evidence for cognitive impairment in patients with untreated VS. It can thus be said that including cognitive assessment in the routine clinical management of patients with VS may facilitate more appropriate clinical decision-making and improve patients' quality of life.

Analysis of volatile short-chain fatty acids in the gas phase using secondary electrospray ionization coupled to mass spectrometry.

Quantification of metabolites present within exhaled breath is a major challenge for on-line breath analysis. It is also important for gauging the analytical performance, accuracy, reproducibility, reliability, and stability of the measuring technology. Short-chain fatty acids (SCFAs) are of high interest for nutrition and health. Their quantification enables a deep mechanistic understanding of a wide range of biological processes and metabolic pathways, while their high volatility makes them an attractive target for breath analysis. This article reports, for the first time, the development and testing of a modular, dynamic vapor generator for the qualitative and quantitative analysis of volatile SCFAs in the gaseous phase using a secondary electrospray ionization (SESI) source coupled to a high-resolution mass spectrometer. Representative compounds tested included acetic acid, propionic acid, butyric acid, pentanoic acid and hexanoic acid. Gas-phase experiments were performed both in dry and humid (95% relative humidity) conditions from ppt to low ppb concentrations. The results obtained exhibited excellent linearity within the examined concentration range, low limits of detection and quantification down to the lower ppt area. Mixture effects were also investigated and are presented.

Association of Preoperative Vascular Wall Imaging Patterns and Surgical Outcomes in Patients With Unruptured Intracranial Saccular Aneurysms.

BACKGROUND: MR vascular wall imaging (VWI) may have prognostic value in patients with unruptured intracranial aneurysms (UIAs). OBJECTIVE: To evaluate the value of VWI as a predictor of surgical outcome in patients with UIAs. METHODS: This prospective cohort study evaluated surgical outcomes in consecutive patients with UIAs who underwent surgical clipping at a single center. All participants underwent high-resolution VWI and were followed for at least 6 months. The primary clinical outcome was modified Rankin scale (mRS) score 6 months after surgery. RESULTS: The number of patients in the no wall enhancement, uniform wall enhancement (UWE), and focal wall enhancement (FWE) groups was 37, 145, and 154, respectively. Incidence of postoperative complications was 15.5% in the FWE group, 12.4% in the UWE group, and 5.4% in the no wall enhancement group. The proportion of patients with mRS score >2 at the 6-month follow-up was significantly higher in the FWE group than in the UWE group (14.3% vs 6.9%; P = .0389). In the multivariate analysis, FWE (odds ratio, 2.573; 95% CI 1.001-6.612) and positive proximal artery remodeling (odds ratio, 10.56; 95% CI 2.237-49.83) were independent predictors of mRS score >2 at the 6-month follow-up. CONCLUSION: Preoperative VWI can improve the surgeon's understanding of aneurysm pathological structure. Type of aneurysmal wall enhancement on VWI is associated with clinical outcome and incidence of salvage anastomosis and surgical complications.

DKK1 as a robust predictor for adjuvant platinum chemotherapy benefit in resectable pStage II-III gastric cancer.

BACKGROUND: Adjuvant chemotherapy (ACT) with 5-FU alone or 5-FU plus platinum after curative surgery improves the prognosis of pStage II-III gastric cancer (GC). However, only a subset of patients benefits from adjuvant platinum. To avoid the side effects of platinum, it is significant to accurately screen the patients who would benefit maximally with this treatment. The present study aimed to assess the value of DKK1 in predicting the benefit of adjuvant platinum chemotherapy in patients with pStage II -III GC. METHODS: Platinum sensitivity-related genes were screened by bioinformatics. DKK1 expression in 380 GC specimens was detected by immunohistochemistry (IHC) staining, and the correlation with adjuvant platinum-specific benefits were analyzed. RESULTS: DKK1 was screened as the most significant platinum sensitivity-related gene. In patients with DKK1high GC, the estimated absolute 5-year overall survival (OS) benefits from adjuvant platinum for pStage II-III, II, IIIA, IIIB, and IIIC were 25.5%, 17.3%, 36.4%, 29.2% and 31.1%, respectively, and the estimated absolute 5-year disease-free survival (DFS) benefits in the corresponding stages were 27.4%, 17.5%, 36.7%, 29.7% and 31.5%, respectively. These benefits were significantly higher than those in the same TNM stage without adjusting for DKK1 status. The performance of DKK1 was independent of the TNM stage and other clinicopathological variables. Similar results were obtained in the TCGA and ACRG cohorts. Furthermore, nomograms were constructed to predict the survival benefits in DKK1 subgroups. CONCLUSIONS: The stratification strategy based on DKK1 status is more precise than the TNM staging system for the selection of pStage II-III GC patients suitable for platinum-containing ACT.

Telehealth System Based on the Ontology Design of a Diabetes Management Pathway Model in China: Development and Usability Study.

BACKGROUND: Diabetes needs to be under control through management and intervention. Management of diabetes through mobile health is a practical approach; however, most diabetes mobile health management systems do not meet expectations, which may be because of the lack of standardized management processes in the systems and the lack of intervention implementation recommendations in the management knowledge base. OBJECTIVE: In this study, we aimed to construct a diabetes management care pathway suitable for the actual situation in China to express the diabetes management care pathway using ontology and develop a diabetes closed-loop system based on the construction results of the diabetes management pathway and apply it practically. METHODS: This study proposes a diabetes management care pathway model in which the management process of diabetes is divided into 9 management tasks, and the Diabetes Care Pathway Ontology (DCPO) is constructed to represent the knowledge contained in this pathway model. A telehealth system, which can support the comprehensive management of patients with diabetes while providing active intervention by physicians, was designed and developed based on the DCPO. A retrospective study was performed based on the data records extracted from the system to analyze the usability and treatment effects of the DCPO. RESULTS: The diabetes management pathway ontology constructed in this study contains 119 newly added classes, 28 object properties, 58 data properties, 81 individuals, 426 axioms, and 192 Semantic Web Rule Language rules. The developed mobile medical system was applied to 272 patients with diabetes. Within 3 months, the average fasting blood glucose of the patients decreased by 1.34 mmol/L (P=.003), and the average 2-hour postprandial blood glucose decreased by 2.63 mmol/L (P=.003); the average systolic and diastolic blood pressures decreased by 11.84 mmHg (P=.02) and 8.8 mmHg (P=.02), respectively. In patients who received physician interventions owing to abnormal attention or low-compliance warnings, the average fasting blood glucose decreased by 2.45 mmol/L (P=.003), and the average 2-hour postprandial blood glucose decreased by 2.89 mmol/L (P=.003) in all patients with diabetes; the average systolic and diastolic blood pressure decreased by 20.06 mmHg (P=.02) and 17.37 mmHg (P=.02), respectively, in patients with both hypertension and diabetes during the 3-month management period. CONCLUSIONS: This study helps guide the timing and content of interactive interventions between physicians and patients and regulates physicians' medical service behavior. Different management plans are formulated for physicians and patients according to different characteristics to comprehensively manage various cardiovascular risk factors. The application of the DCPO in the diabetes management system can provide effective and adequate management support for patients with diabetes and those with both diabetes and hypertension.

miR-29c inhibits metastasis of gastric cancer cells by targeting VEGFA.

Background: Gastric cancer (GC) is characterized by tissue invasion and metastasis, which lead to an aggressive and highly lethal disease. However, the underlying molecular mechanism remains largely unclear. Although multiple miRNAs are known to regulate crucial cellular events during cancer metastasis, their individual roles are still not fully described. Methods: miR-29c overexpressed cell lines were constructed. The wound healing, migration and invasion assays were performed to investigate the effect of miR-29c on metastasis of GC. HUVECs proliferation and tube formation assays were used to test the ability of angiogenesis of miR-29c. The target gene VEGFA was predicted by bioinformatic algorithms and validated by luciferase activity assay. Peritoneal spreading and pulmonary metastasis mice models were applied in vivo. Results: In the current study, we report the results that introduction of exogenous miR-29c inhibits GC cell migration, invasion and angiogenesis. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) properties are participated in the miR-29c mediated cell metastasis. Furthermore, by performing tumor metastasis PCR array and luciferase reporter assay, we find that the expression of VEGFA is regulated by miR-29c through direct targeting of its 3'-UTR. In addition, we show that the VEGFA/VEGFR2/ERK pathway is involved in this process. Conclusion: These data taken together reveal the crucial functions of miR-29c-VEGFA/VEGFR2/ERK signaling axis in the metastasis progression of GC via regulating EMT and CSCs properties, which make them potential targets for clinical intervention in GC.

[Design and application of a new heat-and-moisture exchanger with anti-splash sputum suctioning function].

In the emergency department, open endotracheal suctioning for mechanically ventilated patients with endotracheal intubation will lead to the spread of respiratory droplets and aerosols, polluting the surrounding environment and medical staff. The traditional heat-and-moisture exchanger has the effect of warming and humidifying, and can block pathogenic microorganisms, but it does not have the function of inserting a sputum suction tube. When the heat-and-moisture exchanger is pulled out for sputum suction, it is easy to cause sputum splash, which pollutes the surrounding environment and medical personnel. The addition of closed sputum suction devices will increase the economic burden on patients. Thus, the medical staff of emergency department of the First People's Hospital of Tongxiang City of Zhejiang Province designed a new type of heat-and-moisture exchanger with anti-splash sputum suctioning function and obtained the National Utility Model Patent of China (ZL 2021 2 0017615.0). The new heat-and-moisture exchanger is mainly composed of a receiving cavity, a connecting tube, a sputum suction tube intubation tube, a sealing valve, etc. The disposable sputum suction tube can be used to insert sputum suction, and at the same time, it can prevent the secretion from splashing to ensure sealing. The patent combines the humidification and pathogen blocking functions of the heat-and-moisture exchanger with the anti-splash sputum suctioning function, which is suitable for use in the emergency and critical care medicine departments and has clinically practical value.

Deep Learning in Ischemic Stroke Imaging Analysis: A Comprehensive Review.

Ischemic stroke is a cerebrovascular disease with a high morbidity and mortality rate, which poses a serious challenge to human health and life. Meanwhile, the management of ischemic stroke remains highly dependent on manual visual analysis of noncontrast computed tomography (CT) or magnetic resonance imaging (MRI). However, artifacts and noise of the equipment as well as the radiologist experience play a significant role on diagnostic accuracy. To overcome these defects, the number of computer-aided diagnostic (CAD) methods for ischemic stroke is increasing substantially during the past decade. Particularly, deep learning models with massive data learning capabilities are recognized as powerful auxiliary tools for the acute intervention and guiding prognosis of ischemic stroke. To select appropriate interventions, facilitate clinical practice, and improve the clinical outcomes of patients, this review firstly surveys the current state-of-the-art deep learning technology. Then, we summarized the major applications in acute ischemic stroke imaging, particularly in exploring the potential function of stroke diagnosis and multimodal prognostication. Finally, we sketched out the current problems and prospects.

Association between CDH1 methylation and esophageal cancer risk: a meta-analysis and bioinformatics study.

OBJECTIVE: The aim is to evaluate the association of CDH1 methylation with esophageal cancer (EC) risk. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify relevant articles. Pooled odds ratios (ORs) with 95% confidence interval (CI) were estimated using the fixed- or random-effects models. The pooled sensitivity and specificity were calculated to assess the diagnostic value of CDH1 methylation for EC. The results of the meta-analysis were validated using The Cancer Genome Atlas and Gene Expression Omnibus databases. RESULTS: Thirteen studies consisting of 1,633 samples were included. A high CDH1 methylation was significantly associated with an increased risk of EC (OR = 10.40, 95% CI = 6.29-17.18). Furthermore, CDH1 methylation status was related to tumor status, lymph node status, and metastasis. For the diagnosis of EC, the pooled sensitivity and specificity of CDH1 methylation were 0.57 (95% CI = 0.39-0.74) and 0.89 (95% CI = 0.81-0.94), respectively. Bioinformatics analysis showed that CDH1 methylation occurred more frequently in EC tissues than in normal controls, in good agreement with the results of the meta-analysis. CONCLUSION: A significant association was found between CDH1 methylation and EC risk. We therefore suggest that CDH1 methylation can serve as a promising diagnostic marker for EC.

Biomechanical evaluation of compression buttress screw and medial plate fixation for the treatment of vertical femoral neck fractures.

OBJECTIVE: To compare the biomechanical properties of compression buttress screw (CBS) fixation with three plate fixation methods for the treatment of vertical femoral neck fractures (FNFs). METHODS: A total of forty synthetic femoral models with simulated Pauwels type III fractures (angle of 70°) were equally assigned to one of four fixation groups: CBS fixation, anteromedial plate fixation (AMP), medial buttress plate fixation (MBP) and medial buttress plate fixation without proximal screw (MBPw). Within each group, half of the specimens were randomly assigned to two loading settings, an axial compression loading test and a hip-flexion torsion test. RESULTS: There were no significant differences in axial load to failure, axial stiffness, torsional strength, or torsional stiffness when comparing CBS with MBP (p>0.05). In the axial compression loading test, both CBS and MBP showed higher load to failure and axial stiffness than MBPw (p<0.05). In torsional testing, AMP exhibited superior torsional strength and torsional stiffness than both MBPw and MBP (all p<0.05) and a higher torsional strength than CBS fixation (p<0.05). There were no significant differences in torsional stiffness between the CBS and AMP fixation groups (p>0.05). CONCLUSION: The biomechanical parameters of CBS fixation are comparable to that of AMP and MBP, and demonstrate superior axial stiffness than MBPw fixation. Although the CBS method for surgical fixation of vertical FNF holds promise as a less invasive surgical technique than plate fixation with similar biomechanical assessments, further clinical evaluation is warranted.

Mechanical Bistability in Kerr-modified Cavity Magnomechanics.

Bistable mechanical vibration is observed in a cavity magnomechanical system, which consists of a microwave cavity mode, a magnon mode, and a mechanical vibration mode of a ferrimagnetic yttrium-iron-garnet sphere. The bistability manifests itself in both the mechanical frequency and linewidth under a strong microwave drive field, which simultaneously activates three different kinds of nonlinearities, namely, magnetostriction, magnon self-Kerr, and magnon-phonon cross-Kerr nonlinearities. The magnon-phonon cross-Kerr nonlinearity is first predicted and measured in magnomechanics. The system enters a regime where Kerr-type nonlinearities strongly modify the conventional cavity magnomechanics that possesses only a radiation-pressure-like magnomechanical coupling. Three different kinds of nonlinearities are identified and distinguished in the experiment. Our Letter demonstrates a new mechanism for achieving mechanical bistability by combining magnetostriction and Kerr-type nonlinearities, and indicates that such Kerr-modified cavity magnomechanics provides a unique platform for studying many distinct nonlinearities in a single experiment.