Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection.

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-ß1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1ß) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

CENPA facilitates glioma stem cell stemness and suppress ferroptosis to accelerate glioblastoma multiforme progression by promoting GBP2 transcription.

The function of glioma stem cells (GSCs) is closely related to the progression of glioblastoma multiforme (GBM). Centromere protein A (CENPA) has been confirmed to be related to the poor prognosis of GBM patients. However, whether CENPA regulates GSCs function to mediate GBM progression is still unclear. GSCs were isolated from GBM cells. The expression of CENPA and guanylate-binding protein 2 (GBP2) was examined by quantitative real-time PCR and western blot. GSCs proliferation and stemness were assessed using EdU assay and sphere formation assay. Cell ferroptosis was evaluated by detecting related factors. The interaction between CENPA and GBP2 was analyzed by ChIP assay and dual-luciferase reporter assay. Animal experiments were conducted to measure the effect of CENPA knockdown on the tumorigenicity of GSCs in vivo. CENPA was upregulated in GBM tissues and GSCs. CENPA knockdown inhibited GSCs proliferation, stemnness, and promoted ferroptosis. GBP2 was overexpressed in GBM tissues and GSCs, and CENPA enhanced GBP2 transcription by binding to its promoter region. CENPA overexpression accelerated GSCs proliferation and stemnness and suppressed ferroptosis, while GBP2 knockdown reversed these effects. Downregulation of CENPA reduced the tumorigenicity of GSCs by decreasing GBP2 expression in vivo. In conclusion, CENPA enhanced GBP2 transcription to increase its expression, thus accelerating GSCs proliferation and stemnness and repressing ferroptosis. Our findings promote a new idea for GBM treatment.

Inhibition of the TCF12/VSIG4 axis by palbociclib diminishes the proliferation and migration of glioma cells and decreases the M2 polarization of glioma-associated microglia.

The CDK4/CDK6 inhibitor palbociclib has shown the encouraging promise in the treatment of glioma. Here, we elucidated how palbociclib exerts suppressive functions in the M2 polarization of glioma-related microglia and the progression of glioma. Xenograft experiments were used to evaluate the function in vivo. The mRNA levels of transcription factor 12 (TCF12) and VSIG4 were detected by RT-qPCR, and their protein levels were assessed by immunoblotting. Cell migration was tested by wound-healing assay. Cell cycle distribution and M1/M2 microglia phenotype analysis were performed by flow cytometry. The levels of IFN-γ, TNF-α, IL-6，and TGF-ß were measured by ELISA. The TCF12/VSIG4 association was verified by luciferase reporter and chromatin immunoprecipitation (ChIP) assays. In U251 and LN229 glioma cells, TCF12 and VSIG4 were overexpressed, and palbociclib reduced their expression levels. TCF12 upregulation enhanced the proliferation and migration of glioma cells and the M2 polarization of glioma-associated microglia in vitro as well as the tumorigenicity of U251 glioma cells in vivo, which could be reversed by palbociclib. Mechanistically, TCF12 could enhance VSIG4 transcription and expression by binding to the VSIG4 promoter. TCF12 deficiency led to repression in glioma cell proliferation and migration as well as microglia M2 polarization, which could be abolished by increased VSIG4 expression. Our study reveals the novel TCF12/VSIG4 axis responsible for the efficacy of palbociclib in combating glioma, offering a rationale for the application of palbociclib in glioma treatment.

A clinical-radiomic-pathomic model for prognosis prediction in patients with hepatocellular carcinoma after radical resection.

PURPOSE: Radical surgery, the first-line treatment for patients with hepatocellular cancer (HCC), faces the dilemma of high early recurrence rates and the inability to predict effectively. We aim to develop and validate a multimodal model combining clinical, radiomics, and pathomics features to predict the risk of early recurrence. MATERIALS AND METHODS: We recruited HCC patients who underwent radical surgery and collected their preoperative clinical information, enhanced computed tomography (CT) images, and whole slide images (WSI) of hematoxylin and eosin (H & E) stained biopsy sections. After feature screening analysis, independent clinical, radiomics, and pathomics features closely associated with early recurrence were identified. Next, we built 16 models using four combination data composed of three type features, four machine learning algorithms, and 5-fold cross-validation to assess the performance and predictive power of the comparative models. RESULTS: Between January 2016 and December 2020, we recruited 107 HCC patients, of whom 45.8% (49/107) experienced early recurrence. After analysis, we identified two clinical features, two radiomics features, and three pathomics features associated with early recurrence. Multimodal machine learning models showed better predictive performance than bimodal models. Moreover, the SVM algorithm showed the best prediction results among the multimodal models. The average area under the curve (AUC), accuracy (ACC), sensitivity, and specificity were 0.863, 0.784, 0.731, and 0.826, respectively. Finally, we constructed a comprehensive nomogram using clinical features, a radiomics score and a pathomics score to provide a reference for predicting the risk of early recurrence. CONCLUSIONS: The multimodal models can be used as a primary tool for oncologists to predict the risk of early recurrence after radical HCC surgery, which will help optimize and personalize treatment strategies.

Huang Zhen mycoplasm polysaccharides mitigate nonalcoholic fatty liver disease induced by a high-fat diet in mice: Evidence from hepatic metabolomics.

HZMP-1 is a new polysaccharide isolated from Huang Zhen mycoplasm that contains seven monosaccharides, and it has an average molecular weight of 16.817 kDa. Its structural characteristics indicate that the surface of HZMP-1 is dense and rough, with some irregular protrusions. Animal experiments have shown that HZMP-1 can enhance liver protection, affect lipid-lowering indicators by reducing those related to lipid accumulation and damage in the serum and liver, upregulate genes that accelerate liver lipid oxidation and transport, downregulate genes that promote lipid deposition in the liver, increase the expression of lipid degradation proteins in the liver, and reduce the expression of lipid synthesis proteins. The improvement effect of HZMP-1 on NAFLD was further demonstrated using metabolomics methods. The results of this study indicated that HZMP-1 extracted from Huang Zhen mycoplasm significantly alleviates HFD-induced NAFLD in mice and has good potential for preventing and treating NAFLD.

A combined model using pre-treatment CT radiomics and clinicopathological features of non-small cell lung cancer to predict major pathological responses after neoadjuvant chemoimmunotherapy.

OBJECTIVE: To investigate the relationship between clinical pathological characteristics, pretreatment CT radiomics, and major pathologic response (MPR) of non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy, and to establish a combined model to predict the major pathologic response of neoadjuvant chemoimmunotherapy. METHODS: A retrospective study of 211 patients with NSCLC who underwent neoadjuvant chemoimmunotherapy and surgical treatment from January 2019 to April 2021 was conducted. The patients were divided into two groups: the MPR group and the non-MPR group. Pre-treatment CT images were segmented using ITK SNAP software to extract radiomics features using Python software. Then a radiomics model, a clinical model, and a combined model were constructed and validated using a receiver operating characteristic (ROC) curve. Finally, Delong's test was used to compare the three models. RESULTS: The radiomics model achieved an AUC of 0.70 (95 % CI: 0.62-0.78) in the training group and 0.60 (95 % CI: 0.45-0.76) in the validation group. RECIST assessment results were screened from all clinical characteristics as independent factors for MPR with multivariate logistic regression analysis. The AUC of the clinical model for predicting MPR was 0.66 (95 % CI: 0.59-0.73) in the training group and 0.77 (95 % CI: 0.66-0.87) in the validation group. The combined model with combined radiomics and clinicopathological characteristics achieved an AUC was 0.76 (95 % CI: 0.68-0.84) in the training group, and 0.80 (95 % CI: 0.67-0.92) in the validation group. Delong's test showed that the AUC of the combined model was significantly higher than that of the radiomics model alone in both the training group (P = 0.0067) and the validation group (P = 0.0009).The calibration curve showed good agreement between predicted and actual MPR. Clinical decision curve analysis showed that the combined model was superior to radiomics alone. CONCLUSIONS: Radiomics model can predict MPR in NSCLC after neoadjuvant chemoimmunotherapy with similar accuracy to RECIST assessment criteria. The combined model based on pretreatment CT radiomics and clinicopathological features showed better predictive power than independent radiomics model or independent clinicopathological features, suggesting that it may be more useful for guiding personalized neoadjuvant chemoimmunotherapy treatment strategies.

Nlrp6 protects from corticosterone-induced NSPC ferroptosis by modulating RIG-1/MAVS-mediated mitophagy.

Hippocampal neural stem/progenitor cells (NSPCs) are highly vulnerable to different stress stimuli, resulting in adult neurogenesis decline and eventual cognitive defects. Our previous study demonstrated that NOD-like receptor family pyrin domain-containing 6 (Nlrp6) highly expressed in NSPCs played a critical role in sustaining hippocampal neurogenesis to resist stress-induced depression, but the underlying mechnistms are still unclear. Here, we found that Nlrp6 depletion led to cognitive defects and hippocampal NSPC loss in mice. RNA-sequencing analysis of the primary NSPCs revealed that Nlrp6 deficiency altered gene expression profiles of mitochondrial energy generation and ferroptotic process. Upon siNlrp6 transfection, as well as corticosterone (CORT) exposure, downregulation of Nlrp6 suppressed retinoic acid-inducible gene I (RIG-1)/mitochondrial antiviral signaling proteins (MAVS)-mediated autophagy, but drove NSPC ferroptotic death. More interesting, short chain fatty acids (SCFAs) upregulated Nlrp6 expression and promoted RIG-1/MAVS-mediated mitophagy, preventing CORT-induced NSPC ferroptosis. Our study further demonstrates that Nlrp6 should be a sensor for RIG-1/MAVS-mediated mitophagy and play a critical role in maintain mitochondrial homeostasis of hippocampal NSPCs. These results suggests that Nlrp6 should be a potential drug target to combat neurodegenerative diseases relative with chronic stress.

Microstructure and Mechanical Properties of Refill Friction Stir Spot-Welded Joints of 2A12Al and 7B04Al: Effects of Tool Size and Welding Parameters.

To solve problems in dissimilarly light metal joints, refilled friction stir spot welding (RFSSW) is proposed instead of resistance spot welding. However, rotation speed, dwell time, plunge depth, and the diameter of welding tools all have a great influence on joints, which brings great challenges in optimizing welding parameters to ensure their mechanical properties. In this study, the 1.5 mm thick 2A12Al and 2 mm thick 7B04Al lap joints were prepared by Taguchi orthogonal experiment design and RFSSW. The welding tool (shoulder) diameters were 5 mm and 7 mm, respectively. The macro/microstructures of the cross-section, the geometrical characteristics of the effective welding depth (EWD), the stir zone area (SZA), and the stir zone volume (SZV) were characterized. The shear strength and failure mode of the lap joint were analyzed using an optical microscope. It was found that EWD, SZA, and SZV had a good correlation with tensile-shear force. The optimal welding parameters of 5 mm diameter joints are 1500 rpm of rotation speed, 2.5 mm of plunge depth, and 0 s of dwell time, which for 7 mm joints are 1200 rpm, 1.5 mm, and 2 s. The tensile-shear force of 5 mm and 7 mm joints welded with these optical parameters was 4965 N and 5920 N, respectively. At the same time, the 5 mm diameter joints had better strength and strength stability.

A functional variant of ALDH1A2 is associated with hand osteoarthritis in the Chinese population.

Genome-wide association study identified common variants within the ALDH1A2 gene as the susceptible loci of hand osteoarthritis (HOA) in UK and Iceland populations. Located in chromosome 15, ALDH1A2 encodes aldehyde dehydrogenase family 1 member A2, which is an enzyme that catalyses the synthesis of retinoic acid from retinaldehyde. Our purposes were to replicate the association of functional variant in ALDH1A2 with the development of HOA in the Chinese population. Variant rs12915901 of ALDH1A2 was genotyped in 872 HOA patients and 1223 healthy controls. Subchondral bone samples were collected from 40 patients who had undergone a trapeziectomy, and the tissue expression of ALDH1A2 was analysed. The chi-square analysis was used to compare the frequency of genotype and risk allele between the HOA cases and controls. The Student t test was used to compare the mRNA expression of ALDH1A2 between patients with genotype AA/AG and those with genotype GG. The frequency of genotype AA was significantly higher in HOA patients than in the controls (7.6% vs. 5.1%, p = .01). The frequency of allele A was significantly higher in the patients than in the controls (28.9% vs. 24.6%, p = .005). The mRNA expression of ALDH1A2 was 1.31-folds higher in patients with genotype GG than in the patients with genotype AA/AG (0.000617 ± 0.000231 vs. 0.000471 ± 0.000198, p = .04). Variant rs12915901 of ALDH1A2 contributed to the susceptibility of HOA in the Chinese population. Allele A of rs12915901 can add to the risk of HOA possibly via down-regulation of ALDH1A2 expression.

A multicenter clinical AI system study for detection and diagnosis of focal liver lesions.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Genetic polymorphism of KIAA1217 is functionally associated with lumbar disc herniation in the Chinese population.

BACKGROUND: Genetic polymorphism of KIAA1217 has been reported to be associated with lumbar disc herniation (LDH) in different populations such as Japanese population and Finnish population. This study aimed to explore whether the genetic polymorphism of KIAA1217 is functionally associated with LDH in Chinese population. METHODS: SNP rs16924573 of KIAA1217 was genotyped in 1272 patients and 1248 healthy controls. The mRNA expression of KIAA1217 in the intervertebral disc was analyzed for 84 patients and 32 controls. The differences of genotype and allele distributions between LDH patients and healthy controls were evaluated using the Chi-square test. One-way ANOVA test was used to compare the relationship between genotypes and tissue expression of KIAA1217. RESULTS: Patients were found to have significantly higher frequency of genotype GG of rs16924573 than the controls (64.2% vs. 52.8%, p<0.001). The frequency of allele G was remarkably higher in the patients than in the controls (79.8% vs. 73.2%, p<0.001), with an OR of 1.45 (95% confidential interval=1.27-1.66). Compared with the controls, LDH patients were observed to have significantly decreased expression of KIAA1217. Patients with genotype GG had remarkably lower mRNA expression of KIAA1217 than those with genotype AG or AA (p=0.01). CONCLUSIONS: SNP rs16924573 of KIAA1217 could be functionally associated with LDH in the Chinese population. More in vivo and vitro experiments need to be carried out to further clarify the regulatory mechanism of functional variants in KIAA1217.

Realization of Gapped and Ungapped Photonic Topological Anderson Insulators.

It is commonly believed that topologically nontrivial one-dimensional systems support edge states rather than bulk states at zero energy. In this work, we find an unanticipated case of topological Anderson insulator (TAI) phase where two bulk modes are degenerate at zero energy, in addition to degenerate edge modes. We term this "ungapped TAI" to distinguish it from the previously known gapped TAIs. Our experimental realization of both gapped and ungapped TAIs relies on coupled photonic resonators, in which the disorder in coupling is judiciously engineered by adjusting the spacing between the resonators. By measuring the local density of states both in the bulk and at the edges, we demonstrate the existence of these two types of TAIs, together forming a TAI plateau in the phase diagram. Our experimental findings are well supported by theoretical analysis. In the ungapped TAI phase, we observe stable coexistence of topological edge states and localized bulk states at zero energy, highlighting the distinction between TAIs and traditional topological insulators.

Transcription factor CaHDZ15 promotes pepper basal thermotolerance by activating HEAT SHOCK FACTORA6a.

High temperature stress (HTS) is a serious threat to plant growth and development and to crop production in the context of global warming, and plant response to HTS is largely regulated at the transcriptional level by the actions of various transcription factors (TFs). However, whether and how homeodomain-leucine zipper (HD-Zip) TFs are involved in thermotolerance are unclear. Herein, we functionally characterized a pepper (Capsicum annuum) HD-Zip I TF CaHDZ15. CaHDZ15 expression was upregulated by HTS and abscisic acid in basal thermotolerance via loss- and gain-of-function assays by virus-induced gene silencing in pepper and overexpression in Nicotiana benthamiana plants. CaHDZ15 acted positively in pepper basal thermotolerance by directly targeting and activating HEAT SHOCK FACTORA6a (HSFA6a), which further activated CaHSFA2. In addition, CaHDZ15 interacted with HEAT SHOCK PROTEIN 70-2 (CaHsp70-2) and glyceraldehyde-3-phosphate dehydrogenase1 (CaGAPC1), both of which positively affected pepper thermotolerance. CaHsp70-2 and CaGAPC1 promoted CaHDZ15 binding to the promoter of CaHSFA6a, thus enhancing its transcription. Furthermore, CaHDZ15 and CaGAPC1 were protected from 26S proteasome-mediated degradation by CaHsp70-2 via physical interaction. These results collectively indicate that CaHDZ15, modulated by the interacting partners CaGAPC1 and CaHsp70-2, promotes basal thermotolerance by directly activating the transcript of CaHSFA6a. Thus, a molecular linkage is established among CaHsp70-2, CaGAPC1, and CaHDZ15 to transcriptionally modulate CaHSFA6a in pepper thermotolerance.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population.

BACKGROUND: In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. METHODS: SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. RESULTS: There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). CONCLUSIONS: Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Flanked Block-Interchange Distance on Strings.

Rearrangement sorting problems impact profoundly in measuring genome similarities and tracing historic scenarios of species. However, recent studies on genome rearrangement mechanisms disclosed a statistically significant evidence, repeats are situated at the ends of rearrangement relevant segments and stay unchanged before and after rearrangements.To reflect the principle behind this evidence, we propose flanked block-interchange, an operation on strings that exchanges two substrings flanked by identical left and right symbols in a string. The flanked block-interchange distance problem is formulated as finding a shortest sequence of flanked block-interchanges to transform a string into the other. We propose a sufficient and necessary condition for deciding whether two strings can be transformed into each other by flanked block-interchanges. This condition is linear time verifiable. Under this condition for two strings, we present a [Formula: see text]-approximation algorithm for the flanked block-interchange distance problem where each symbol occurs at most k times in a string and a polynomial algorithm for this problem where each symbol occurs at most twice in a string. We show that the problem of flanked block-interchange distance is NP-hard at last.

Techno-functional properties of active film based on guar gum-propolis and its application for "Nanguo" pears preservation.

Guar gum (GG) composite films, incorporating the ethanolic extract of propolis (EEP), were prepared and subjected to a comprehensive investigation of their functional characteristics. The addition of EEP resulted in a discernible enhancement in the opacity, moisture barrier capacity, and elongation at break. Incorporating EEP led to a noteworthy increase in the total phenolic and total flavonoid content of the films, resulting in superior antioxidant capacity upon GG-EEP films. Remarkably, the addition of 5 % EEP yielded noteworthy outcomes, manifesting in a DPPH radical scavenging rate of 47.60 % and the ABTS radical scavenging rate of 94.87 %, as well as FRAP and cupric reducing power of 331.98 mmol FeSO4-7H2O kg-1 and 56.95 µg TE mg-1, respectively. In addition, GG-EEP films demonstrated antifungal effect against Penicillium expansum and Aspergillus niger, along with a sustained antibacterial effect against Escherichia coli and Staphylococcus aureus. GG-EEP films had superior inhibitory ability against Gram-positive bacteria than Gram-negative bacteria. Crucially, GG-EEP composite films played a pivotal role in reducing both lesion diameter and depth, concurrently mitigating weight loss and firmness decline during the storage period of "Nanguo" pears. Therefore, GG-EEP composite films have the considerable potential to serve as advanced and effective active packaging materials for food preservation.

Study on boiling heat transfer characteristics of R410A outside horizontal tube under swaying condition.

To investigate the boiling characteristics of flow outside the R410A tube under swaying conditions, this article conducts numerical simulation and experimental research on the flow boiling heat transfer of R410A outside a horizontal tube. The results show that when the swing frequency increased from 0.2 to 2 Hz, the sway amplitude is 0.03 m, the heat flux on the inner wall of the runner remains unchanged, and the mass flow rate increases from 85 to 170 kg/(m2·s), which makes the heat transfer coefficient of the working fluid in the annular area increases significantly. Keeping the inlet mass flow rate unchanged, the heat flux on the inner wall of the flow channel increases from 25 to 35 kW/m2, the heat transfer coefficient of the working fluid in the annular area has also improved, but under high heat flux conditions, the working fluid is evaporated and dried, its heat transfer coefficient increases less than in low heat flux conditions. When the sway amplitude increases from 0.02 to 0.07 m, the sway frequency is 0.2 Hz and 2 Hz respectively, and the heat transfer coefficient of the working fluid shows a downward trend as a whole. The studies provide a reference for heat exchanger design suitable for offshore swaying conditions.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Level pinning of anti-PT-symmetric circuits for efficient wireless power transfer.

Wireless power transfer (WPT) technology based on magnetic resonance (a basic physical phenomenon) can directly transfer energy from the source to the load without wires and other physical contacts, and has been successfully applied to implantable medical devices, electric vehicles, robotic arms and other fields. However, due to the frequency splitting of near-field coupling, the resonant WPT system has some unique limitations, such as poor transmission stability and low efficiency. Here, we propose anti-resonance with level pinning for high-performance WPT. By introducing the anti-resonance mode into the basic WPT platform, we uncover the competition between dissipative coupling and coherent coupling to achieve novel level pinning, and construct an effective anti-parity-time (anti-PT)-symmetric non-Hermitian system that is superior to previous PT-symmetric WPT schemes. On the one hand, the eigenvalue of the anti-PT-symmetric system at resonance frequency is always pure real in both strong and weak coupling regions, and can be used to overcome the transmission efficiency decrease caused by weak coupling, as brought about by, for example, a large size ratio of the transmitter to receiver, or a long transmission distance. On the other hand, due to the level pinning effect of the two kinds of coupling mechanisms, the working frequency of the system is guaranteed to be locked, so frequency tracking is not required when the position and size of the receiver change. Even if the system deviates from the matching condition, an efficient WPT can be realized, thereby demonstrating the robustness of the level pinning. The experimental results show that when the size ratio of the transmitter coil to the receiver coil is 4.29 (which is in the weak coupling region), the transfer efficiency of the anti-PT-symmetric system is nearly 4.3 (3.2) times higher than that of the PT-symmetric system when the matching conditions are satisfied (deviated). With the miniaturization and integration of devices in mind, a synthetic anti-PT-symmetric system is used to realize a robust WPT. Anti-PT-symmetric WPT technology based on the synthetic dimension not only provides a good research platform for the study of abundant non-Hermitian physics, but also provides a means of going beyond traditional near-field applications with resonance mechanisms, such as resonance imaging, wireless sensing and photonic routing.