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Abstract The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA. Graphical abstract

Objective(s): Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury.Materials and Methods: Luteolin and 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (20 μmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation.Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

Abstract Background Postoperative cone-beam computed tomography (CBCT) examination is considered a reliable method for clinicians to assess the positions of implants. Nevertheless, CBCT has drawbacks involving radiation exposure and high costs. Moreover, the image quality can be affected by artifacts. Recently, some literature has mentioned a digital registration method (DRM) as an alternative to CBCT for evaluating implant positions. The aim of this clinical study was to verify the accuracy of the DRM compared to CBCT scans in postoperative implant positioning. Materials and methods A total of 36 patients who received anterior maxillary implants were included in this clinical study, involving a total of 48 implants. The study included 24 patients in the single implant group and 12 patients in the dual implant group. The postoperative three-dimensional (3D) positions of implants were obtained using both CBCT and DRM. The DRM included three main steps. Firstly, the postoperative 3D data of the dentition and intraoral scan body (ISB) was obtained through the intraoral scan (IOS). Secondly, a virtual model named registration unit which comprised an implant replica and a matching ISB was created with the help of a lab scanner and reverse engineering software. Thirdly, by superimposing the registration unit and IOS data, the postoperative position of the implant was determined. The accuracy of DRM was evaluated by calculating the Root Mean Square (RMS) values after superimposing the implant positions obtained from DRM with those from postoperative CBCT. The accuracy of DRM was compared between the single implant group and the dual implant group using independent sample t-tests. The superimposition deviations of CBCT and IOS were also evaluated. Results The overall mean RMS was 0.29 ± 0.05 mm. The mean RMS was 0.30 ± 0.03 mm in the single implant group and 0.29 ± 0.06 mm in the dual implant group, with no significant difference (p = 0.27). The overall registration accuracy of the IOS and CBCT data ranged from 0.14 ± 0.05 mm to 0.21 ± 0.08 mm. Conclusion In comparison with the 3D implant positions obtained by CBCT, the implant positions located by the DRM showed clinically acceptable deviation ranges. This method can be used in single and dual implant treatments to assess the implant positions.

The advancement of computers and data explosion have ushered in the third wave of artificial intelligence(AI). AI is an interdisciplinary field that encompasses new ideas, new theories, and new technologies, etc. AI has brought convenience to ophthalmology application and promoted its intelligent, precise, and minimally invasive development. At present, AI has been widely applied in various fields of ophthalmology, especially in oculoplastic surgery. AI has made rapid progress in image detection, facial recognition, etc., and its performance and accuracy have even surpassed humans in some aspects. This article reviews the relevant research and applications of AI in oculoplastic surgery, including ptosis, single eyelid, pouch, eyelid mass, and exophthalmos, and discusses the challenges and opportunities faced by AI in oculoplastic surgery, and provides prospects for its future development, aiming to provide new ideas for the development of AI in oculoplastic surgery.

The incidence of cancer is increasing worldwide and is the most common cause of death. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Cyclin-dependent kinase subunit 2 (CKS2) is involved in cell cycle and proliferation processes, and based on these processes, CKS2 was identified as a cancer gene. CKS2 is expressed in a variety of tissues in the human body, but its abnormal expression is associated with cancer in a variety of systems. CKS2 is generally elevated in cancer, plays a role in almost all aspects of cancer biology (such as cell proliferation, invasion, metastasis, and drug resistance) through multiple mechanisms regulating certain important genes, and is associated with clinicopathological features of patients. In addition, CKS2 expression patterns are closely related to cancer type, stage and other clinical variables. Therefore, CKS2 is considered as a tool for cancer diagnosis and prognosis and may be a promising tumor biomarker and therapeutic target. This article reviews the biological function, mechanism of action and potential clinical significance of CKS2 in cancer, in order to provide a new theoretical basis for clinical molecular diagnosis, molecular targeted therapy and scientific research of cancer.

Immunometabolism has been an emerging hotspot in the fields of tumors, obesity, and atherosclerosis in recent decades, yet few studies have investigated its connection with rheumatoid arthritis (RA). In principle, intracellular metabolic pathways upstream regulated by nutrients and growth factors control the effector functions of immune cells. Dynamic communication and hypermetabolic lesions of immune cells within the inflammatory synovial microenvironment contributes to the development and progression of RA. Hence, targeting metabolic pathways within immune subpopulations and pathological cells may represent novel therapeutic strategies for RA. Natural products constitute a great potential treasury for the research and development of novel drugs targeting RA. Here, we aimed to delineate an atlas of glycolysis, lipid metabolism, amino acid biosynthesis, and nucleotide metabolism in the synovial microenvironment of RA that affect the pathological processes of synovial cells. Meanwhile, therapeutic potentials and pharmacological mechanisms of natural products that are demonstrated to inhibit related key enzymes in the metabolic pathways or reverse the metabolic microenvironment and communication signals were discussed and highlighted.

Abstract The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL−1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram‐negative Porphyromonas gingivalis and Gram‐positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non‐inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near‐complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri‐implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation.

Abstract Background Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by chronic synovitis as well as cartilage and bone destruction. Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant Dichroa febrifuga Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear. Methods This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA. Results Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17 C, p-NF-κB, and MMP9. Conclusion In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.

The global repercussions of the COVID-19 pandemic on economies and public health worldwide have been profound. This study aims to examine the developmental trends of the COVID-19 pandemic, establish predictive models, and provide insights for effective control measures against potential future disease outbreaks. Considering the coexistence of both linear and nonlinear factors in COVID-19 data, conventional single-machine learning and traditional forecasting models encounter challenges in accurately predicting pandemic trends. To enhance the precision of COVID-19 pandemic predictions by integrating linear and nonlinear factors, this study proposes three combined forecasting models: CNN-LSTM-ARIMA, TCN-LSTM-ARIMA, and SSA-LSTM-ARIMA. These models leverage the strengths of deep learning in capturing nonlinear factors and the capabilities of the traditional ARIMA model in handling linear factors. Initially, LSTM and ARIMA models are used to model and predict the COVID-19 pandemic in Quebec, Canada. Subsequently, CNN models, TCN models, and the Sparrow Search Algorithm are employed to integrate predictions from the LSTM and ARIMA models. Comparative analyses of the three combined models, it was found that the CNN-LSTM-ARIMA model exhibits the highest predictive accuracy, with an MSE of 7048.26, RMSE of 83.95, MAE of 61.18, MAPE of 0.16, and $R^{2}$ of 0.95. To validate the applicability and stability of the CNN-LSTM-ARIMA model in predicting COVID-19 pandemics, Italian COVID-19 pandemic data was employed. The three combined forecasting models are established and evaluated using model evaluation metrics. The results affirm that the CNN-LSTM-ARIMA model remains the optimal choice, underscoring its high stability and suitability for COVID-19 pandemic forecasting endeavors.

Abstract Background The lack of access to physical therapists in developing countries and rural areas poses a significant challenge in supervising postsurgical rehabilitation, potentially impeding desirable outcomes following surgical interventions. For this reason, this study aims to evaluate the feasibility, safety, and effectiveness of utilizing a digital rehabilitation program based on computer vision and augmented reality in comparison with traditional care for patients who will undergo isolated meniscus repair, since to date, there is no literature on this topic. Methods This study intends to enroll two groups of participants, each to be provided with informed consent before undergoing randomization into either the experimental or control group. The experimental group will undergo a digital rehabilitation program utilizing computer vision and augmented reality (AR) technology following their surgical procedure, while the control group will receive conventional care, involving in-clinic physical therapy sessions weekly. Both groups will adhere to a standardized rehabilitation protocol over a six-month duration. Follow-up assessments will be conducted at various intervals, including preoperatively, and at 2 weeks, 6 weeks, 12 weeks, and 24 weeks postoperatively. Imaging assessments and return-to-play evaluations will be conducted during the final follow-up. Clinical functionality will be assessed based on improvements in International Knee Documentation Committee (IKDC) and Visual Analog Scale (VAS) scores. Registration number ChiCTR2300070582.

Abstract Due to the advantages of rapid deployment, flexible response and strong invulnerability, unmanned aerial vehicle (UAV) swarm has been widely applied in collaborative warfare and emergency communication. However, UAV swarm in complex environments is prone to chaotic collapse due to obstructions. A UAV swarm obstacle avoidance system model for multi-narrow type obstacles is established. Due to the fact that only one UAV is allowed to pass through each small hole at any given moment, addressing the issue of congestion caused by swarming effects becomes crucial in addition to managing the competitive allocation of multiple UAVs to multiple holes. Aiming at this problem, a dual-game real-time obstacle avoidance scheme is proposed for UAV swarm with multi-narrow type obstacle scenarios, which divides the flight process of the UAV swarm into two stages: maintaining the flight state of the UAV swarm unchanged when no obstacles are encountered, and implementing matching separation and motion state switching by means of dual-game strategy when facing multi-narrow type obstacles, ultimately achieving orderly passage after multiple rounds of games. For the proposed scheme, a dual-game based Flocking (DGF) obstacle avoidance algorithm is proposed. Specifically, the motion state of each UAV obtained from the game is parameterized and integrated with the Flocking algorithm to calculate the motion control input for each UAV. The solution is iteratively obtained until the UAV swarm completes the obstacle avoidance. Simulation results demonstrate that the proposed DGF algorithm not only enables smooth obstacle avoidance for the UAV swarm in multi-narrow type obstacle scenarios, but also effectively resolves the internal chaos problem in the UAV swarm, thereby preventing rigid collisions.

BackgroundLung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer.MethodsWe utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test.ResultsNo significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods.ConclusionGreen tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.

A quantitative investigation of poly(vinyl) chloride (PVC) de-chlorination using Fe2O3, together with the impact of SiO2 addition on the co-pyrolysis of PVC and Fe2O3, was conducted below 673 K in an Ar atmosphere aiming to cut the emission of gaseous Cl⁻ products. It was found that chlorine in PVC can be fixed in FeCl2 by the reaction between PVC and Fe2O3. The co-pyrolysis of PVC and Fe2O3 proceeds in two stages with a temperature boundary of around 543 K. Below 543 K, a direct reaction occurs between PVC and Fe2O3, resulting in a small mass loss ratio and some extent of chlorine fixing ratio in FeCl2. However, above 543 K, PVC starts to decompose to release gaseous H2, HCl, etc., which react with Fe2O3 through two possible pathways to form FeCl2. In Pathway 1, first Fe2O3 is reduced to Fe3O4 by H2, followed by the chlorination of Fe3O4 to FeCl2 by HCl. In Pathway 2, first Fe2O3 is chlorinated to FeCl3 by HCl, followed by the reduction of FeCl3 to FeCl2 by H2. The chlorine fixing ratio in FeCl2 and the volatile generation ratio increase with decreasing PVC content in the initial mixtures. The addition of SiO2 promotes the chlorine fixing ratio in FeCl2 and volatile generation, and the impact gets stronger with decreasing PVC content in the mixtures. The chlorine fixing ratio is increased from 70.8 to 82.6% by SiO2 addition for the mixtures containing 25% PVC, whereas the difference in the chlorine fixing ratio in FeCl2 caused by SiO2 addition is negligible for the mixtures containing 90% PVC. Fayalite (Fe2SiO4) was not detected in the solid residues after the experiments. After separating FeCl2 using water leaching, the filter residue, a composite of iron oxide and conjugated polyene, can be used as a raw material for iron-making.

Abstract Background Computer-aided design and computer-aided manufacturing (CAD-CAM) materials for prosthetic is gaining popularity in dentistry. However, limited information exists regarding the impact of thickness and roughening treatment on the optical properties of contemporary CAD-CAM restorative materials. This study aimed to quantitatively evaluate the translucency and opalescence of six dental CAD-CAM materials in response to different thicknesses and roughening treatments. Methods Six dental CAD-CAM materials, lithium disilicate glass–ceramic (IPS e.max CAD, LS), polymer-infiltrated ceramic (VITA Enamic, VE), resin-nano ceramic glass–ceramic (LAVA Ultimate, LU), polymethyl methacrylate (Telio CAD, TE), and two zirconia reinforced lithium silicate (VITA Suprinity, VS, and Celtra Duo, CD), in shade A2 were prepared as 12 × 12mm2 specimens of four thicknesses (0.5mm, 1.0mm, 1.5mm, and 2.0mm) (N = 240, n = 10). After three different treatments (polished, roughened by SiC P800-grit, and SiC P300-grit), the translucency parameter (TP00) and opalescence parameter (OP) were measured with a spectrophotometer (VITA Easyshade V). The surface roughness was analyzed with a shape measurement laser microscope. The data were analyzed using a MANOVA, post hoc Tukey–Kramer test, the t test, and regression analysis (α = .05). Results The TP00 and OP were significantly influenced by material type, thickness and roughening treatment (P

Objective Lumbar lateral interbody fusion (LLIF) allows placement of large interbody cages while preserving ligamentous structures important for stability. Multiple clinical and biomechanical studies have demonstrated the feasibility of stand-alone LLIF in single-level fusion. We sought to compare the stability of 4-level stand-alone LLIF utilizing wide (26 mm) cages with bilateral pedicle screw and rod fixation. Methods Eight human cadaveric specimens of L1–5 were included. Specimens were attached to a universal testing machine (MTS 30/G). Flexion, extension, and lateral bending were attained by applying a 200 N load at a rate of 2 mm/sec. Axial rotation of ±8° of the specimen was performed at 2°/sec. Three-dimensional specimen motion was recorded using an optical motion-tracking device. Specimens were tested in 4 conditions: (1) intact, (2) bilateral pedicle screws and rods, (3) 26-mm stand-alone LLIF, (4) 26-mm LLIF with bilateral pedicle screws and rods. Results Compared to the stand-alone LLIF, bilateral pedicle screws and rods had 47% less range of motion in flexion-extension (p < 0.001), 21% less in lateral bending (p < 0.05), and 20% less in axial rotation (p = 0.1). The addition of bilateral posterior instrumentation to the stand-alone LLIF resulted in decreases of all 3 planes of motion: 61% in flexion-extension (p < 0.001), 57% in lateral bending (p < 0.001), 22% in axial rotation (p = 0.002). Conclusion Despite the biomechanical advantages associated with the lateral approach and 26 mm wide cages, stand-alone LLIF for 4-level fusion is not equivalent to pedicle screws and rods.

Abstract Background Many studies demonstrated that surgical guides might reduce discrepancies compared with freehand implant placement. This randomized crossover study aimed to assess the effects of approaches, practitioners’ experience and learning sequences on the accuracy of single tooth implantation via digital registration method. No similar study was found. Methods This in vitro randomized crossover study enrolled 60 novice students (Group S) and 10 experienced instructors (Group I). Sixty students were randomly and evenly assigned to two groups (Group SA and SB). In Group SA, 30 students first performed single molar implant on a simulation model freehand (Group SAFH), and then with a CAD/CAM surgical guide (Group SASG). In Group SB, another 30 students first performed guided (Group SBSG) and then freehand (Group SBFH). Ten instructors were also divided into Group IAFH/IASG (n = 5) and IBSG/IBFH (n = 5) following the same rules. The accuracy of implant placement was assessed by the coronal and apical distance (mm) and angular (°) deviations using the digital registration method. T tests and nonparametric tests were used to compare the results among different groups of approaches, experience and sequences. Results For students, the coronal and apical distance and the angular deviations were significantly lower in surgical guide group than freehand group in total and in learning freehand first subgroup, but for learning surgical guide first subgroup the apical distance deviation showed no significant difference between two approaches. For students, the angular deviation of freehand group was significantly lower in learning surgical guide first group than learning freehand first group. For instructors, the coronal and apical distance and angular deviations showed no significant difference between two approaches and two sequences. For freehand approach, the coronal and apical distance and the angular deviations were significantly higher in student group than instructor group, while not significantly different between two groups for surgical guide approach. Conclusions For novices, using a surgical guide for the first implant placement may reduce the potential deviations compared with freehand surgery, and may reach a comparable accuracy with that of specialists. For simple single molar implantation, the surgical guide may not be significantly helpful for experienced specialists.

Osteoporosis is the most common metabolic bone disorder and is characterized by decreased bone density, which has a relationship with the quality of life among the aging population. Previous research has found that activation of the dopamine D1 receptor can improve bone mass formation. SKF38393 is an agonist of dopamine D1 receptors. However, as a small-molecule drug, SKF38393 is unstable and releases quickly. The aim of this study was to prototype polylactic-co-glycolic acid (PLGA)/SKF38393 microspheres and assess their potential osteogenic effects compared to those under the free administration of SKF38393. The cytocompatibility of PLGA/SKF38393 was determined via CCK-8 and live/dead cell staining; the osteogenic effects in vitro were determined with ALP and alizarin red staining, qRT-PCR, and Western blotting; and the in vivo effects were assessed using 25 Balb/c mice. We also used a PCR array to explore the possible signaling pathway changes after employing PLGA/SKF38393. Our experiments demonstrated that the osteogenic effect of D1Rs activated by the PLGA/SKF38393 microsphere was better than that under free administration, both in vitro and in vivo. According to the PCR array, this result might be associated with six signaling pathways (graphical abstract). Ultimately, in this study, we prototyped PLGA/SKF38393, demonstrated its effectiveness, and preliminarily analyzed its mechanism of action.

Wood surface broken defects seriously damage the structure of wooden products, these defects have to be detected and eliminated. However, current defect detection methods based on machine vision have difficulty distinguishing the interference, similar to the broken defects, such as stains and mineral lines, and can result in frequent false detections. To address this issue, a multi-source data fusion network based on U-Net is proposed for wood broken defect detection, combining image and depth data, to suppress the interference and achieve complete segmentation of the defects. To efficiently extract various semantic information of defects, an improved ResNet34 is designed to, respectively, generate multi-level features of the image and depth data, in which the depthwise separable convolution (DSC) and dilated convolution (DC) are introduced to decrease the computational expense and feature redundancy. To take full advantages of two types of data, an adaptive interacting fusion module (AIF) is designed to adaptively integrate them, thereby generating accurate feature representation of the broken defects. The experiments demonstrate that the multi-source data fusion network can effectively improve the detection accuracy of wood broken defects and reduce the false detections of interference, such as stains and mineral lines.

The Tengchong Cenozoic volcano is located near the collision boundary between the Indian and Eurasian plates. The tectonic activity in this area is strong, and the volcano has a potential for eruption. Studying the origin of the Tengchong volcano is important for understanding plate subduction processes and the mechanism of volcano eruption. This review first summarizes the latest researches on the origin of the Tengchong volcano, including new advances in geophysics and geochemistry, and then discusses the magma source and deep dynamic mechanism. These studies have found that the genesis of Tengchong volcanism is mainly related to plate subduction. The subducted residual oceanic plate and the currently subducting Indian plate may both contribute to the source of metasomatic materials. The oceanic plate released melt and fluid to form metasomatized asthenospheric and lithospheric mantles, and Tengchong magma originated from the mixing of lithospheric and asthenosphere mantle melts. The metasomatized lithospheric mantle is characterized by low 3He/4He (< 7.0 Ra) and Nb/La (average of 0.36) ratios as well as high 87Sr/86Sr (average of 0.707928) and La/Yb (average of 22.0) ratios. In contrast, the enriched asthenospheric mantle is characterized by high 3He/4He (> 7.0 Ra) and Nb/La (average of 0.52) ratios with relatively low 87Sr/86Sr (average of 0.706708) and La/Yb (average of 17.0) ratios. The increasing trend of 3He/4He ratios and decreasing trend of 87Sr/86Sr ratios over time suggest that the contribution of the metasomatized lithospheric mantle decreased relative to that of the enriched asthenosphere after the late Pleistocene, reflecting the progressive lithospheric extension and thinning. Tengchong basalts do not show clear correlation between 87Sr/86Sr ratio and SiO2 content, whereas basaltic andesite, andesite, and dacite display positive correlation between 87Sr/86Sr ratio and SiO2 content. This phenomenon indicates that Tengchong basalt suffered limited crustal contamination, while basaltic andesite, andesite, and dacite underwent obvious crustal contamination. Moreover, seismic imaging along with magnetotelluric and geothermal studies revealed several magma chambers (low-speed anomalies) in the crust beneath the Tengchong volcano. However, the size and depth of the magma chambers vary between different studies. The low-velocity bodies in the crust extend downward to the upper mantle, which may indicate that the magma chambers in the crust are fed by hot materials from the upper mantle. However, a consensus on the origin of hot materials has yet to be reached. Seismic tomography studies suggest that hot materials could be generated from the dehydration of the stagnant slab in the mantle transition zone, tearing of the subducted plate, or slab rollback. Differences in seismic imaging results may be caused by the limited observation data, data imaging methods, and the multi-solution of geophysical inversion. The utilization of more data and advanced geophysical methods will help obtain high-resolution imaging results to further constrain the origin of the Tengchong volcano.

Phase-locked loop-based grid-forming converters （PLL-GFCs） can regulate frequency and voltage. However， the transient synchronization stability after their connection to the high-voltage AC power grid is unclear. Therefore， the transient synchronization stability mechanism of the PLL-GFC-based MMC-HVDC （modular multilevel converter-based HVDC） systems is studied. Firstly， the control strategy of the PLL-GFC-based MMC-HVDC systems is introduced， and the power response characteristics are analyzed. Secondly， the grid-connected MMC-HVDC systems' transient synchronization stability model is built. The instability mechanism of the converters after grid faults and the influence of the dynamic changes of the grid current on the transient synchronization stability are studied based on phrase diagram curves. It is concluded that the equilibrium point is crucial to the transient stability after the fault occurs on the inverter-connected power grid. Therefore， an enhancement measure to improve the transient synchronization stability by dynamically adjusting active current command values is proposed. Finally， an electromagnetic transient simulation model is built by PSCAD/EMTDC to verify the correctness of the instability mechanism analysis and the effectiveness of the enhancement measure.

The accurate quantification of transmission limit and grid strength of the multi-infeed LCC-HVDC （line-commutated converter technology-based high-voltage DC） and VSC-HVDC （voltage source converter technology-based high-voltage DC） systems has become one of the critical measures to ensure the stable operation of new power systems. Through the improvement of the grid strength quantification method of the traditional LCC-HVDC AC/DC systems， a short-circuit ratio （SCR） index for quantifying the grid strength of the hybrid DC infeed systems is proposed to analyze the transmission limit of the AC/DC systems. Firstly， a quasi-steady-state （QSS） model of the hybrid DC infeed systems is built under the flow equation. Secondly， the SCR index for evaluating the transmission limit of LCC-HVDC in the hybrid DC infeed systems is obtained by analysis of the relationship between the Jacobian matrix singularity and the power transmission limit of the DC infeed systems. The sensitivity relationship between the index threshold and the operation mode of the VSC-HVDC system is analyzed. Finally， the effectiveness of the SCR index is verified using PSCAD/EMTDC and MATLAB platform. The analysis results show that the VSC-HVDC system is superior in voltage support under the constant voltage control mode at the receiving end. The operation mode of the VSC-HVDC system that exerts less influence on the transmission limit of the LCC-HVDC system can be quantitatively analyzed by the proposed index.

Abstract Background The stiffness of titanium mesh is a double-blade sword to repair larger alveolar ridges defect with excellent space maintenance ability, while invade the surrounding soft tissue and lead to higher mesh exposure rates. Understanding the mechanical of oral mucosa/titanium mesh/bone interface is clinically meaningful. In this study, the above relationship was analyzed by finite elements and verified by setting different keratinized tissue width in oral mucosa. Methods Two three-dimensional finite element models were constructed with 5 mm keratinized tissue in labial mucosa (KM cases) and 0 mm keratinized tissue in labial mucosa (LM cases). Each model was composed of titanium mesh, titanium screws, graft materials, bone, teeth and oral mucosa. After that, a vertical (30 N) loadings were applied from both alveolar ridges direction and labial mucosa direction to stimulate the force from masticatory system. The displacements and von Mises stress of each element at the interfaces were analyzed. Results Little displacements were found for titanium mesh, titanium screws, graft materials, bone and teeth in both LM and KM cases under different loading conditions. The maximum von Mises stress was found around the lingual titanium screw insertion place for those elements in all cases. The keratinized tissue decreased the displacement of oral mucosa, decreased the maximum von Mises stress generated by an alveolar ridges direction load, while increased those stress from labial mucosa direction load. Only the von Mises stress of the KM cases was all lower than the tensile strength of the oral mucosa. Conclusion The mucosa was vulnerable under the increasing stress generated by the force from masticatory system. The adequate buccal keratinized mucosa width are critical factors in reducing the stress beyond the titanium mesh, which might reduce the titanium exposure rate.

Background:. Pancreaticoduodenectomy (PD) has been widely applied in general hospitals in China; however, there is still a lack of unified standards for each surgical technique and procedure. This survey is intended to investigate the current status of digestive tract reconstruction after PD in university hospitals in China. Method:. A cross-sectional survey was conducted among the members of the Young Elite Pancreatic Surgery Club of China by using the Questionnaire for Digestive Tract Reconstruction after Pancreaticoduodenectomy. The questionnaire was disseminated and collected by point-to-point communication via WeChat public platforms. Results:. A total of 73 valid questionnaires were returned from 65 university hospitals in 28 provincial divisions of mainland China. The respondents who performed PD surgery with an annual volume of over 100 cases accounted for 63%. Generally, laparoscopic PD was performed less often than open PD. Child and Whipple reconstructions accounted for 70% and 26%, respectively. The sequence of pancreatoenteric, biliary-enteric, and gastrointestinal reconstruction accounted for 84% of cases. In pancreatoenteric anastomosis, double-layer anastomosis is the most commonly employed type, accounting for approximately 67%, while single-layer anastomosis accounts for 30%. Of the double-layer anastomoses, duct-to-mucosa/dunking (94%/4%) pancreatojejunostomy was performed with duct-mucosa using the Blumgart method (39%) and Cattel-Warren (29%), with continuous/interrupted sutures in the inner layer (69%/31%) and continuous/interrupted sutures in the outer layer (53%/23%). In single-layer anastomosis, continuous/interrupted sutures accounted for 41%/45%. In hepatojejunostomy, single-layer/double-layer suture accounted for 79%/4%, and continuous/interrupted suture accounted for 75%/9%. Forty-six percent of the responding units had not applied double-layer biliary-intestinal anastomosis in the last 3 years, 75% of the responding surgeons chose the anastomosis method according to bile duct diameter, with absorbable/non-absorbable suture accounting for 86%/12%. PD/pylorus-preserving PD accounted for 79%/11% of gastrojejunostomy (GJ) cases, the distance between GJ and hepaticojejunostomy < 30, 30–50, and > 50 cm were 11%, 75%, and 14%, respectively. Antecolic/retrocolic GJ accounted for 71%/23% of cases. Twenty-two percent of GJ cases employed Braun anastomosis, while 55% and 19% of GJ cases used linear cutting staplers/tube-type staplers, respectively; 60%/14% were reinforced/not reinforced via manual suturing after stapler anastomosis. Manual anastomosis in GJ surgery employed absorbable/non-absorbable sutures (91%/9%). Significant differences in reconstruction techniques were detected between different volumes of PD procedures (100/year), regions with different economic development levels, and between north and south China. Conclusion:. Digestive tract reconstruction following PD exists heterogeneity in Chinese university hospitals. Corresponding prospective clinical studies are needed to determine the consensus on pancreatic surgery that meets the clinical reality in China.

Radical innovations can shift the global competitiveness of entire nations. While countries typically struggle to absorb knowledge about novel technologies quickly, in which knowledge tends to be spatially sticky, an important exception is the fast catch-up of the Korean Li-ion battery industry from Japan in the early 2000s. In this paper, we conduct an exploratory case study on this surprising success story. Focussing on patent co-inventions between Korea and Japan, we investigate their significance, as well as underlying types of co-inventions and types of transferred knowledge. To this end, we proceed in four steps: (1) a Poisson regression model; (2) social network analyses; (3) patent inventor tracking and (4) patent coding. Our results indicate that Korean–Japanese co-inventions hold significantly greater influence than other cross-country co-inventions, including with patents without cross-country collaboration. We find a pronounced knowledge-transfer intensity during the early 2000s and observe two types of co-inventions: organisation-level and inventor-level. Predominantly, we observe inventor-level co-inventions, i.e. Korean companies hiring experienced Japanese engineers, that proved important to transferring sticky knowledge. Moreover, while most patents target the design of core battery components, the share of manufacturing patents are—contrary to theoretical expectations—highest during the first half of the observation period. We also discuss our findings and draw implications for policy, industrial and academic players, including industry localisation policies, technology-inherent catch-up strategies and directions for future research.

Abstract Near‐infrared (NIR) fluorescence imaging poses significant superiority over traditional medical imaging for tumor resection, thus having attracted widely attention. However, for tiny tumor residues, it requires relative high sensitivity to determine. Here, based on persistent luminescence nanoparticles (PLNPs), an ultrasensitive nanoprobe with extraordinary tumor imaging result is developed to guide surgical removal. Persistent luminescence (PersL) is quenched in normal tissue by the outer layer of MnO2, and is recovered due to the degradation of MnO2 in tumor microenvironment, significantly improving the sensitivity of tumor imaging. Combined with the absence of background fluorescence in imaging of PLNPs, ultrahigh sensitivity is achieved. In orthotopic breast cancer model, the intraoperative tumor‐to‐normal tissue (T/NT) signal ratio of the nanoprobe is 58.8, about 9 times that of downconversion nanoparticles. The T/NT ratio of residual tumor (

ABSTRACTThe material basis and toxicity of Lithocarpus litseifolius (Hance) Chun (sweet tea), which has many health benefits, are not fully understood. In this study, total water-soluble flavonoids were extracted from sweet tea using optimised methods based on RSM. Its composition and toxicity were investigated by LC–MS and mouse models in vivo. The results showed that the optimum extraction conditions were a liquid/solid ratio of 32.98:1 ml/g, a temperature of 60.69°C, a microwave power of 633.70 W, and a microwave time of 164.08 secs. Among the 33 main components in the extract, five flavonoids constituted more than 73.80% of the total compound content. Total flavonoids were safe after oral administration and alleviated reproductive disorders but were highly toxic after intraperitoneal injection in mice. In summary, under the optimum extraction conditions, the total water-soluble flavonoids were safe after oral administration, but the complex compounds hindered their direct injection.Abbreviations: LLHC: Lithocarpus litseifolius (Hance) Chun; SFD: single-factor design; RSM: response surface methodology; CCD: central composite design; ES: extracted solution; CS concentrated solution; LP: lyophilised powder; LC–MS: liquid chromatography–mass spectrometry; NC: negative control; PH: procaine hydrochloride; CP: cyclophosphamide group.

The quick， accurate and instantaneous evaluation of power limit of transmission section is of great significance to safe， stable and economic operation of power grid. The paper proposes an adaptive method based on a hybrid supervised learning algorithm. Through numerous simulations and analysis of historic operation modes， characteristic extraction， training， and regular updating of AI model， the correct matching relationship between grid operation status and power limit is established for fast， accurate and instantaneous power limit evaluation of the transmission section. The proposed method employs multiple supervised learning forecast algorithms， including deep neural networks， support vector regression， gradient boosting decision tree， and random forest. The hybrid models for power limit forecasting can make best of the advantages of the algorithms. The effectiveness of the method is verified on a 500-bus transmission model with real operation characteristics.

Background: Rapid and reliable diagnostic methods for Aspergillus fumigatus infection are urgently needed. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 13a (Cas13a) has high sensitivity and specificity in the diagnosis of viral infection. However, its potential use in detecting A. fumigatus remains unexplored. A highly sensitive and specific method using the CRISPR/Cas13a system was developed for the reliable and rapid detection of A. fumigatus. Methods: The conserved internal transcribed spacer (ITS) region of A. fumigatus was used to design CRISPR-derived RNA (crRNA) and the corresponding recombinase polymerase amplification (RPA) primer sequence with the T7 promoter for the CRISPR assay. Twenty-five clinical isolates and 43 bronchoalveolar lavage fluid (BALF) remaining from routine examinations of patients with confirmed pulmonary aspergillosis were collected to further validate the CRISPR assay. Results: No amplification signal was observed when genomic DNA from closely clinically related Aspergillus species, such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, as well as Monascus purpureus Went and Escherichia coli, was tested by this assay, and the detection limit for A. fumigatus was 3 copies in a single reaction system. Validation experiments using the 25 clinical isolates demonstrated 91.7% specificity for the A. fumigatus section, and the sensitivity was 100% when first-generation sequencing was used as the standard. There was no significant difference between the PCR and CRISPR methods (P = 1.0), and the diagnosis results of the two methods were consistent (Kappa = 0.459, P = 0.003). Conclusion: The study offers a new validated CRISPR/Cas13a technique for A. fumigatus detection, providing a simple, rapid and affordable test that is ready for application in the diagnosis of A. fumigatus infection.

As the most commonly used antipyretic and analgesic drug, paracetamol (PA) coexists with neurotransmitter dopamine (DA) in real biological samples. Their simultaneous determination is extremely important for human health, but they also interfere with each other. In order to improve the conductivity, adsorption affinity, sensitivity, and selectivity of TiO2-based electrochemical sensor, N-doped carbon@TiO2 double-shelled hollow sphere (H–C/N@TiO2) is designed and synthesized by simple alcoholic and hydrothermal method, using polystyrene sphere (PS) as a template. Meanwhile, TiO2 hollow spheres (H–TiO2) or N-doped carbon hollow spheres (H–C/N) are also prepared by the same method. H–C/N@TiO2 has good conductivity, charge separation, and the highly enhanced and stable current responses for the detection of PA and DA. The detection limit and linear range are 50.0 nmol/L and 0.3–50 μmol/L for PA, 40.0 nmol/L and 0.3–50 μmol/L for DA, respectively, which are better than those of carbon-based sensors. Moreover, this electrochemical sensor, with high selectivity, strong anti-interference, high reliability, and long time durability, can be used for the simultaneous detection of PA and DA in human blood serum and saliva. The high electrochemical performance of H–C/N@TiO2 is attributed to the multi-functional combination of different layers, because of good conductivity, absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.

As the planning and dispatching of new types of power systems become increasingly complicated， dynamic and dubious， it is very challenging to lay down operating mode for power grid that satisfies both security and economic constraints. This process typically requires intensive manual tuning and simulation calculations to search for feasible solutions in a high-dimensional action space that fulfills the requirements on safety and economy of the grid in ground state and fault conditions. Therefore， an approach based on multi-DRL-agent architecture is proposed to describe the problem as a Markov decision process （MDP）. The approach automatically adjusts different types of controllable grid resources by training centralized and distributed multi-DRL-agent to control the power of transmission lines， thus complying with various safety indicators of grid operation. The method is proved to be effective in a power grid model.

The incidence of cancer is increasing globally, and it is the most common cause of death. The identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. SHCSH2 domain-binding protein 1 (SHCBP1) is a protein that specifically binds to the SH2 domain of Src homology–collagen. It participates in the regulation of a variety of signal transduction pathways and can activate a variety of signaling molecules to perform a series of physiological functions. SHCBP1 is expressed in a variety of human tissues, but its abnormal expression in various systems is associated with cancer. SHCBP1 is abnormally expressed in a variety of tumors, and plays roles in almost all aspects of cancer biology (such as cell proliferation, apoptosis prevention, invasion, and metastasis) through various possible mechanisms. Its expression level is related to the clinicopathological characteristics of patients. In addition, the SHCBP1 expression pattern is closely related to cancer type, stage, and other clinical variables. Therefore, SHCBP1 is a promising tumor biomarker for cancer diagnosis and prognosis and a potential therapeutic target. This article reviews the expression, biological functions, mechanisms, and potential clinical significance of SHCBP1 in various human tumors to provide a new theoretical basis for clinical molecular diagnosis, molecular targeted therapy, and scientific research on cancer.

BackgroundAccumulating evidence has revealed that CD8+ T cell exhaustion (Tex) results in worse immunotherapy outcomes. However, the molecular functions and mechanisms of action of Tex in chemoresistance needed to be elucidated.MethodsThe populations of tumor-infiltrating CD8+ T cells (TILCD8Ts) in chemoresistant and chemosensitive groups of the GSE25066 dataset were calculated using CIBERSORT. Differentially expressed genes (DEGs) between TILCD8Ts and other immune cells were explored by integrating 16 immune cell datasets downloaded from the gene expression omnibus (GEO) database. Gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression of TILCD8T-specific upregulated genes were used to construct a chemoresistant TILCD8T signature (cr-TILCD8TSig). Clinical prognostic data, genomic alterations, chemotherapy response, and immunotherapy response were compared between the different cr-TILCD8TSig subgroups in the GSE25066 and the cancer genome atlas breast cancer (TCGA-BRCA) cohorts.ResultsA cr-TILCD8TSig with exhausted features was identified, consisting of seven genes (TCF7, RARRES3, ARL4C, ITK, CDH3, GZMB, and KLRD1), which were identified from 104 TILCD8Ts-specific DEGs. Our results showed that compared to the cr-TILCD8TSig-low subgroup, the -high subgroup had a poorer distant relapse-free survival (DRFS) in the GSE25066 cohort and worse progression-free survival (PFS) in the TCGA-BRCA cohort. Univariate and multivariate Cox regression analyses also demonstrated that cr-TILCD8TSig was an independent prognostic factor in the two independent cohorts. Furthermore, cr-TILCD8TSig-low patients benefited more from chemotherapy and immunotherapy than cr-TILCD8TSig-high patients. Besides, we found cell transmembrane signal transduction and the ECM may provide the molecular basis for resistance to antitumor agents in the cr-TILCD8Sig-high subgroup. For genomic alterations, we revealed that mutations in PIK3CA, DMD, and APOB were more common in the cr-TILCD8Sig-high subgroup than in the cr-TILCD8Sig-low subgroup. A nomogram was finally constructed with good discrimination and calibration.Conclusionscr-TILCD8TSig is a useful tool to independently predict prognosis, chemotherapy response, and immunotherapy outcomes in patients with breast cancer.

Cepola schlegelii (Bleeker 1854) belongs to the genus Cepola in the family Cepolidae and order Priacanthiformes. The complete mitochondrial genome of C. schlegelii was sequenced and analyzed by a high-throughput sequencing approach. The full length of the genome is 17,020 bp, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a non-coding control region (D-loop). Phylogenetic analysis based on complete mitochondrial genomes revealed that C. schlegelii was most closely related to Acanthocepola krusensternii. The complete mitochondrial sequence of C. schlegelii will enrich the mitochondrial genome database and provide useful resources for population genetics and evolution analyses.

Large-scale photovoltaic power connected to the distribution network will raise the voltage at the system nodes， and， in serious cases， the voltage overlimit. Therefore， a voltage regulation strategy based on shunt and series reactors as well as genetic algorithm is proposed. Firstly， the causes of voltage rise in the distribution network and the roles of shunt and series reactors in voltage regulation are analyzed. Then， a reactive power optimization model with the objective of economic optimization is established， and the genetic algorithm is used to solve the optimal reactor configuration scheme. Finally， the effectiveness of the method is verified by simulating the IEEE 33-node system incorporated into a high-power PV plant based on the MATLAB simulation platform.

Background: We presented the performance of a Chinese-made cryptococcal glucuronoxylomannan (GXM) antigen test using serum and bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. Methods: Between February 2017 and January 2019, HIV-negative patients with pulmonary cryptococcosis were recruited and followed-up every three months, including completion of a chest CT examination and collection of serum and BALF samples. Results: Here, thirty-seven confirmed and ten clinically diagnosed patients were recruited. Furthermore, samples from 174 noncryptococcosis patients that may cause false positives were also collected. The sensitivity of a lateral flow assay (LFA) for detecting cryptococcal GXM antigen in serum and BALF samples from confirmed cases was 97% and 95%, respectively, and the specificity was 98.2% and 93%, respectively, and the differences in these values between the BALF and serum samples were not significant. The serum cryptococcal GXM antigen value showed a positive correlation (r: 0.581, p

Abstract Background Nam Dok Mai Mango (Mangifera indica L.) is considered as one of the famous tropical fruits in Thailand with an attractive taste and fragrance. A rapidly powerful comprehensive technique to investigate the aromatic as well as metabolic compounds is required to follow the ripening stage and identification of biomarkers in mango cv. Nam Dok Mai. To date, only a few omics-based studies have been published on the ripening process of mango. The present study aimed to establish an advanced omics-based approach using integrated metabolomics–flavoromic profiles to follow the ripening process of Nam Dok Mai Si Thong mango fruit. Results 56 metabolites and 33 flavor volatile components were detected in Nam Dok Mai Si Thong mango. Palmitic acid shown the highest content in lipid fraction of mango pulp (28%) followed by linolenic acid (25%) and linoleic acid (23%) at various ripening stages during ripening. β-Sitosterol (3.9%), campesterol (2.4%), and sitostanol (2.4%) were higher at day 0 of ripening. Glycine and leucine were highest at day 4 of ripening (3.4 and 3.0%, respectively). The highest sucrose level (48.7%) was observed at 8 days of ripening. Ethyl octanoate (6.2–9.5%) and ethyl decanoate (5.4–6.5%) were significantly higher at days 4 to 8 of ripening. Conclusions Among 19 biomarkers measured, nine metabolites (palmitic acid, linoleic acid, linolenic acids, β-sitosterol, sucrose, citric acid, malic acid, glycine, and leucine), and 2 flavors (ethyl octanoate and ethyl decanoate) showed a good correlation with ripening-associated changes at days 0 to 8 during ripening. The biomarkers identified in this study could be used to track the ripening stages of Nam Dok Mai Si Thong mango. Graphical Abstract

We present observations and timing analyses of 68 millisecond pulsars (MSPs) comprising the 15 yr data set of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). NANOGrav is a pulsar timing array (PTA) experiment that is sensitive to low-frequency gravitational waves (GWs). This is NANOGrav’s fifth public data release, including both “narrowband” and “wideband” time-of-arrival (TOA) measurements and corresponding pulsar timing models. We have added 21 MSPs and extended our timing baselines by 3 yr, now spanning nearly 16 yr for some of our sources. The data were collected using the Arecibo Observatory, the Green Bank Telescope, and the Very Large Array between frequencies of 327 MHz and 3 GHz, with most sources observed approximately monthly. A number of notable methodological and procedural changes were made compared to our previous data sets. These improve the overall quality of the TOA data set and are part of the transition to new pulsar timing and PTA analysis software packages. For the first time, our data products are accompanied by a full suite of software to reproduce data reduction, analysis, and results. Our timing models include a variety of newly detected astrometric and binary pulsar parameters, including several significant improvements to pulsar mass constraints. We find that the time series of 23 pulsars contain detectable levels of red noise, 10 of which are new measurements. In this data set, we find evidence for a stochastic GW background.

ObjectivePulmonary aspergillosis is a rare but challenging pulmonary disease. The conditions of patients with chronic pulmonary aspergillosis (CPA) can be even more complicated. The mortality rate of CPA remains high, and the prognostic factors are not well established due to a high proportion of loss to follow-up. In this study, we aim to explore factors associated with loss to follow-up in CPA patients and their impact on the disease prognosis after withdrawing anti-fungal treatments.MethodsPatients with confirmed CPA, who were admitted to the Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University from March 2017 to November 2019, were enrolled in this prospective study. The enrolled patients were followed up for 6 months after discharge. For loss to follow-up patients, the reasons for loss to follow-up and their prognosis after withdrawing anti-fungal treatments during loss to follow-up were recorded by telephone communication. Multivariate logistic regression analysis was performed to determine factors associated with loss to follow-up.ResultsThe 199 out of 298 screened patients were included in the study. Except for 67 cases with regular follow-up, the rest 132 cases were lost to follow-up. Factors, including age > 60 years (OR = 2.036, P = 0.03), monthly income ≤ $583 (OR = 5.568, P = 0.0001), education ≤ 6 years (OR = 7.474, P = 0.0001), and non-local residence (OR = 5.893, P = 0.0001) were associated with the loss to follow-up according to multivariate logistic regression analysis. The most common reasons for loss to follow-up were economic factors and clinic visit distance. The overall case fatality rate (CFR) within 180 days in patients with regular follow-up and patients who stopped anti-fungal treatment during the loss to follow-up was 0% and 19.65%, respectively.ConclusionThe proportion of loss to follow-up in CPA patients remained high. Age (>60 years), poor financial status, low education, and non-local residence were the key factors associated with the loss to follow-up in this study. Our study reveals the need to optimize the follow-up procedures and improve the patients understanding about the benefits and limitations of follow-up to reduce the CFR.

Abstract A vertical oxide thin-film transistor was developed with interfacial oxidation for low voltage operation. The gate metal was used as a spacer for the definition of the transistor’s channel as well as the gate electrode. After definition of the vertical side wall, an IGZO (In-Ga-Zn Oxide) layer was deposited, followed by the interfacial oxidation to form a thin gate insulator. Ta was used for the gate material due to the low Gibbs free energy and high dielectric constant of tantalum oxide. A 15 nm tantalum oxide layer was obtained by the interfacial oxidation of Ta at 400 °C under oxygen atmosphere. The thin gate oxide made it possible to operate the transistor under 1 V. The low operation voltage enables low power consumption, which is essential for mobile application.

Global climate change and rapid urbanization have placed enormous pressure on the urban ecological environment worldwide. Urban green spaces, which are an important component of urban ecosystems, can maintain ecological and environmental sustainability and benefits, including biodiversity conservation and carbon sequestration. However, land use changes across urban landscapes, especially in plain urban areas with high development pressure, have significantly impacted the carbon sequestration efficiency of urban green spaces. Nevertheless, research examining the impact of land use change and development pressure on urban green spaces and carbon sequestration is relatively scarce. Understanding the carbon sequestration efficiency of urban green spaces and its determining factors will help predict future carbon capture trends within urban ecosystems and formulate more targeted sustainable urban planning and management strategies to improve urban carbon sink efficiency and achieve the goal of carbon neutrality. Therefore, to understand the factors affecting the carbon sequestration efficiency of urban green spaces, this paper used an integrated framework that combined the Carnegie–Ames–Stanford approach (CASA) model, landscape pattern index, multiple linear regression, and Markov–FLUS model. The study explored the impact of urban land use and land cover changes on carbon sequestration within the plain urban areas of Beijing at street scale. The results showed that, at street scale, there was a significant positive and negative correlation between the landscape pattern index and net primary productivity (NPP). In addition, the green spaces located in areas with more complex landscape structures had better carbon sequestration benefits. In addition, multiscenario carbon sequestration efficiency prediction suggested that the sustainable development (SD) scenario could achieve a positive increment of overall NPP. In contrast, the business-as-usual development (BD), the fast development (FD), and the low development (LD) scenarios showed a downward trend in NPP. This paper also proposed strategies for optimizing and enhancing green spaces within urban plain areas. Based on the strategies, the results guide decision making for sustainable urban green space planning that maintains the ecological, economic, and social integrity of urban landscapes during urbanization.

Locating seismic events is a central task for earthquake monitoring. Compared to arrival-based location methods, waveform-based location methods do not require picking phase arrivals and are more suitable for locating seismic events with noisy waveforms. Among waveform-based location methods, one approach is to stack different attributes of P and S waveforms around arrival times corresponding to potential event locations and origin times, and the maximum stacking values are assumed to indicate the correct event location and origin time. In this study, to obtain a high-resolution location image, we improve the waveform-based location method by applying a hybrid multiplicative imaging condition to characteristic functions of seismic waveforms. In our new stacking method, stations are divided into groups; characteristic functions of seismic waveforms recorded at stations in the same group are summed, and then multiplied among groups. We find that this approach can largely eliminate the cumulative effects of noise in the summation process and thus improve the resolution of location images. We test the new method and compare it to three other stacking methods, using both synthetic and real datasets that are related to induced seismicity occurring in petroleum/gas production. The test results confirm that the new stacking method can provide higher-resolution location images than those derived from currently used methods.

Abstract Background With the emergence of three-dimensional (3D) integration technology, analysis of soft tissue displacement and morphological changes after maxillary full-arch implant-supported fixed prostheses can be performed. The aim of this study was to verify the feasibility of the 3D integration method for constructing the relative position of the prostheses and facial soft tissue, evaluate the displacement and morphological variation of the upper lips after maxillary full-arch implant-supported fixed prostheses. Methods Twenty-five maxillary edentulous patients were recruited in this study. At the time of final prosthesis delivery, the 3D prostheses data and three 3D facial profiles were integrated. After method validation, the 3D position changes of seven soft tissue landmarks were used to reflect the 25 upper lips. The variation of four morphological distances were analyzed to reflect the morphological alteration of the upper lips. Two pairs of dentofacial landmarks were used to analyze the sagittal relative position of the prostheses and soft tissue. The included patients were also grouped to determine the impact of sex, upper lip thickness, and length on lip support changes. Results The average distance of the two matched relative reliable forehead regions was only 0.32 mm. The sagittal shifts of labrale superius (LS), stomion (STO), crista philtri left (CPHL) and crista philtri right (CPHR) were 3.44 ± 1.39 mm, 2.52 ± 1.38 mm, 3.04 ± 1.18 mm, and 3.12 ± 1.21 mm, respectively. With the exception of the decrease in the length of subnasale (SN)-LS, the length of cheilion right (CHR)-cheilion left (CHL), CPHR-CPHL, and LS-STO significantly increased. The two pairs of dentofacial landmarks had strong positive movement correlations along the sagittal direction. Patients with thinner and longer lips showed more lip support than those with thicker and shorter lips by a clinically insignificant amount. Conclusions The integration method of 3D facial and dental data showed high repeatability in constructing the dentofacial relative position. The linear equations reflecting dentofacial relative position could aid clinicians in evaluating the restoration effect and estimate the upper lip variation.

Abstract Unsupervised multi‐domain image‐to‐image translation aims to synthesize images among multiple domains without labelled data, which is more general and complicated than one‐to‐one image mapping. However, existing methods mainly focus on reducing the large costs of modelling and do not pay enough attention to the quality of generated images. In some target domains, their translation results may not be expected or even cause the model collapse. To improve the image quality, an effective many‐to‐many mapping framework for unsupervised multi‐domain image‐to‐image translation is proposed. There are two key aspects to the proposed method. The first is a many‐to‐many architecture with only one domain‐shared encoder and several domain‐specialized decoders to effectively and simultaneously translate images across multiple domains. The second is two proposed constraints extended from one‐to‐one mappings to further help improve the generation. All the evaluations demonstrate that the proposed framework is superior to existing methods and provides an effective solution for multi‐domain image‐to‐image translation.

Otitis media (OM) is one of the largest public health problems of children and has devastating impacts in developing countries. The substantial medical and human costs involved have led to research to understand the disease and improve treatment. Animal models of OM have yielded critical information about the immune, inflammatory and genetic mechanisms of OM. However, it is important to link animal studies to human immune and inflammatory responses. In recent years, “humanized” mice have become a valuable tool to study the human immune system in an animal model. Here we describe the first use of humanized mice to study OM. We demonstrate that humanized mice with a sufficient degree of engraftment recapitulate a normal middle ear (ME) inflammatory response to bacterial infection, including the recruitment of human immune cells, and exhibit normal recovery. Moreover, these animals exhibit regulated expression of human-specific immune and inflammatory genes in the ME. In contrast, mice with insufficient engraftment fail to resolve OM. This model has many potential uses in OM research, including using hematopoietic stem cells from patients with differing degrees of OM susceptibility, to understand the role of human immune responses in proneness to this common childhood disease.

Neurological degeneration after neuroinflammation, such as that resulting from Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), and post-traumatic brain injury (TBI), is typically associated with high mortality and morbidity and with permanent cognitive dysfunction, which places a heavy economic burden on families and society. Diagnosing and curing these diseases in their early stages remains a challenge for clinical investigation and treatment. Recent insight into the onset and progression of these diseases highlights the permeability of the blood–brain barrier (BBB). The primary factor that influences BBB structure and function is inflammation, especially the main cytokines including IL-1β, TNFα, and IL-6, the mechanism on the disruption of which are critical component of the aforementioned diseases. Surprisingly, the main cytokines from systematic inflammation can also induce as much worse as from neurological diseases or injuries do. In this review, we will therefore discuss the physiological structure of BBB, the main cytokines including IL-1β, TNFα, IL-6, and their mechanism on the disruption of BBB and recent research about the main cytokines from systematic inflammation inducing the disruption of BBB and cognitive impairment, and we will eventually discuss the need to prevent the disruption of BBB.

Abstract Background The objective of this study was to compare patient-reported outcome measures (PROMs) and clinical outcomes after augmentation with xenogeneic collagen matrix (XCM) or free gingival graft (FGG) during different postoperative phases. Methods Forty-two patients (21 per group) with keratinized mucosa width (KMW) of < 2 mm at buccal implant sites in the posterior mandible were enrolled. All underwent vestibuloplasty and were allocated to either FGG (control) or XCM (test) group. Intraoperative morbidity of pain, stress, nausea, tolerance to time, and acceptance of surgery were evaluated immediately after surgery. The severity and duration of subjective pain, swelling, and bleeding were compared within a 2-week postoperative period. The willingness to retreat and satisfaction were assessed at 6 months. All PROMs were obtained using questionnaires and visual analog scales. The buccal KMW and other peri-implant parameters were also evaluated. Results No significant between-group differences were observed in PROMs immediately after surgery, except acceptance of surgery (0, 0–30.0 vs. 30, 0–50.0, p = 0.025). At 2 weeks, pain severity (46.7 ± 25.9 vs 61.9 ± 20.2, p = 0.040) and duration (5.52 ± 3.57 vs 8.48 ± 2.80, p = 0.005) were significantly lower in the test group, and pain perception during speaking and chewing was significantly higher for FGG, with no significant between-group differences in swelling and bleeding. At 6 months, the test group showed a higher willingness to retreat (76% vs 43%, p = 0.021); however, satisfaction with treatment outcomes was similar in both groups. At 6 months, the gain of KMW was significantly higher in FGG than in XCM (XCM: 1.57 ± 1.69 mm, FGG: 2.68 ± 1.80 mm, p = 0.003). Other peri-implant parameters did not show significant differences. Conclusions Within the limitation of the present nonrandomized study, XCM demonstrated more positive PROMs than FGG during different postoperative phases, mainly for less pain perception during the early healing stage, but was inferior to FGG in terms of gain of KMW. For KMW augmentation in the posterior mandible, XCM may be indicated when patients can bear little pain. Clinical trial registration ChiCTR1900022575 , date of registration: 17/4/2019, retrospectively registered,

Abstract Background Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. Methods Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. Results Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. Conclusion T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.

Abstract Purpose Osseointegration at the titanium surface-bone interface is one of the key factors affecting the success rate of dental implants. However, the titanium surface always forms a passive oxide layer and impacts bone marrow–derived mesenchymal stem cell (BMSC) osteogenic differentiation after exposure to the atmosphere, which further leads to poor osseointegration. Given that wet storage helps prevent titanium aging and that weakly alkaline conditions stimulate BMSC osteogenic differentiation, the aim of the present study was to explore whether sodium bicarbonate, a well-known hydrogen ion (pH) buffer, forms an alkaline microenvironment on titanium surfaces to promote BMSC osteogenic differentiation. Material and methods In this work, sand-blasted and acid-etched (SLA) titanium discs were soaked in 20 mM, 50 mM, 100 mM, and 200 mM sodium bicarbonate at room temperature for 5 min without rinsing. The influence of this surface modification on BMSC adhesion, proliferation, and osteogenic differentiation was measured. Additionally, cellular osteogenic differentiation–associated signaling pathways were evaluated. Results We showed that titanium discs treated with sodium bicarbonate created an extracellular environment with a higher pH for BMSCs than the normal physiological value for 5 days, strongly promoting BMSC osteogenic differentiation via the activation of integrin-focal adhesion kinase-alkaline phosphatase (Itg-FAK-ALP). In addition, the proliferation and adhesion of BMSCs were increased after alkaline treatment. These cellular effects were most significant with 100 mM sodium bicarbonate. Conclusion The results indicated that the titanium surface treated with sodium bicarbonate improved BMSC osteogenic differentiation mainly by creating an alkaline microenvironment, which further activated the Itg-FAK-ALP signaling pathway. Clinical relevance Surfaces modified with 100 mM sodium bicarbonate had the highest initial pH value and thus showed the greatest potential to improve BMSC performance on titanium surfaces, identifying a novel conservation method for dental implants.