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Background The purpose of this study was to clinically evaluate the safety and effectiveness of the electromagnetic navigation (EMN) system designed for computed tomography (CT)-guided synchronous percutaneous lung biopsy and microwave ablation (MWA) of pulmonary nodules.Methods This prospective, single-center, single-arm clinical cohort study was conducted in Beijing Hospital from March 2023 to May 2023. Patients who underwent CT-guided synchronous percutaneous lung biopsy and MWA via the EMN system were prospectively enrolled in our study. All the interventional procedures were performed by the same interventional radiologist. The technical success rate, the technical efficacy rates of biopsy and MWA were assessed as the primary outcomes. Preoperative, intraoperative, and postoperative variables were also recorded and analyzed for each patient.Results A total of 48 patients were enrolled in the study. The technical success rate was 100%. The technical efficacy rate of biopsy was 95.8% (46/48), and the technical efficacy rate of WMA was 100% (48/48) with no recurrence during follow-up. The total and subpleural needle trajectory length and distance error were 8.3 ± 2.6 cm, 3.6 ± 1.6 cm, and 1.84 ± 1.08 mm, respectively. The median numbers of needle adjustments and CT acquisitions were 1 (range 1–3) and 3 (range 3–5), respectively. The time to reach the target and procedure time were 4.4 ± 1.7 and 19.7 ± 5.2 min, respectively. The dose length product was 748.8 ± 221.8 mGy*cm. The median postoperative hospital stay was 1 (range 1–7) days. No major complications (grade ≥3) occurred and only seven minor complications (14.6%) occurred, including six cases of pneumothorax and one case of hemoptysis. The radiologists achieved high satisfaction scores after surgery.Conclusion The EMN system is feasible, safe and effective for CT-guided synchronous percutaneous lung biopsy and MWA of pulmonary nodules.

PurposeTo explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved.MethodsNew Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA).ResultsDifferent molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following.ConclusionsIn the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.

Abstract Efficient upconversion electroluminescence is highly desirable for a broad range of optoelectronic applications, yet to date, it has been reported only for ensemble systems, while the upconversion electroluminescence efficiency remains very low for single-molecule emitters. Here we report on the observation of anomalously bright single-molecule upconversion electroluminescence, with emission efficiencies improved by more than one order of magnitude over previous studies, and even stronger than normal-bias electroluminescence. Intuitively, the improvement is achieved via engineering the energy-level alignments at the molecule−substrate interface so as to activate an efficient spin-triplet mediated upconversion electroluminescence mechanism that only involves pure carrier injection steps. We further validate the intuitive picture with the construction of delicate electroluminescence diagrams for the excitation of single-molecule electroluminescence, allowing to readily identify the prerequisite conditions for producing efficient upconversion electroluminescence. These findings provide deep insights into the microscopic mechanism of single-molecule upconversion electroluminescence and organic electroluminescence in general.

This paper aims to study bounded algebras in another perspective-dual ideals of bounded $ L $-algebras. As the dual concept of ideals in $ L $-algebras, dual ideals are designed to characterize some significant properties of bounded $ L $-algebras. We begin by providing a definition of dual ideals and discussing the relationships between ideals and dual ideals. Then, we prove that these dual ideals induce congruence relations and quotient $ L $-algebras on bounded $ L $-algebras. Naturally, in order to construct the first isomorphism theorem between bounded $ L $-algebras, the relationship between dual ideals and morphisms between bounded $ L $-algebras is investigated and that the kernels of any morphisms between bounded $ L $-algebras are dual ideals is proven. Fortunately, although the first isomorphism theorem between arbitrary bounded $ L $-algebras fails to be proven when using dual ideals, the theorem was proven when the range of morphism was good. Another main purpose of this study is to use dual ideals to characterize several kinds of bounded $ L $-algebras. Therefore, first, the properties of dual ideals in some special bounded $ L $-algebras are studied; then, some special bounded $ L $-algebras are characterized by dual ideals. For example, a good $ L $-algebra is a $ CL $-algebra if and only if every dual ideal is $ C $ dual ideal is proven.

Abstract Purpose To compare the genomic testing based on specimens obtained from percutaneous core-needle biopsy (CNB) before and immediately after coaxial microwave ablation (MWA) in solid non-small cell lung cancer (NSCLC), and to investigate the diagnostic performance of CNB immediately after coaxial MWA in solid NSCLC. Methods Coaxial MWA and CNB were performed for NSCLC patients, with a power of 30 or 40 watts (W) in MWA between the pre- and post-ablation CNB, followed by continuous ablation after the second CNB on demand. The paired specimens derived from the same patient were compared for pathological diagnosis and genomic testing. DNA/RNA extracted from the paired specimens were also compared. Results A total of 33 NSCLC patients with solid lesions were included. There were two patients (6.1%) without atypical cells and three patients (9.1%) who had the technical failure of genomic testing in post-ablation CNB. The concordance rate of pathological diagnosis between the twice CNB was 93.9% (kappa = 0.852), while that of genomic testing was 90.9% (kappa = 0.891). For the comparisons of DNA/RNA extracted from pre- and post-ablation CNB in 30 patients, no significant difference was found when the MWA between twice CNB has a power of 30 or 40 W and ablation time within five minutes (P = 0.174). Conclusions If the pre-ablation CNB presented with a high risk of pneumothorax or hemorrhage, the post-ablation CNB could be performed to achieve accurate pathological diagnosis and genomic testing and the maximum effect of ablation, which might allow for the diagnosis of genomic testing in 90.9% of solid NSCLC.

During tunnel excavation, the stress of the surrounding rock is redistributed, leading to a local stress concentration around the tunnel. In addition, blasting excavation and other factors lead to a strength reduction of rock mass around the tunnel and eventually form a relaxation fracture zone (loosening zone). If supporting measures are not adopted in time during tunnel excavation, the rock strength in the loosening zone will be further reduced and eventually lead to overall instability and collapse. To simulate the bolt/cable supporting effect on the loosening zone and surrounding intact rock, a block–particle–bar coupling algorithm based on penalty springs is proposed. This coupling algorithm is based on the continuum–discontinuum element method (CDEM). CDEM is a dynamic, explicit solution algorithm based on a generalized Lagrange system. A strict controlling equation is established by the Lagrange energy system, and an explicit iterative solution of the dynamic relaxation method is used to realize a unified description of continuous and discontinuous media. The progressive failure of a solid is analyzed through the fracture of the bond between the blocks or particles. Using CDEM, the entire process of the solid from continuous deformation to fracture and movement can be simulated. In the block–particle–bar coupled algorithm, discrete particle clusters are adopted to represent the broken rock mass inside the loosening zone around the tunnel, block elements are used to represent the intact rock mass outside the loosening region, and bar elements are introduced to describe the supporting structures, such as bolts and cables. A contact coupling mode is adopted between particles and blocks, one normal spring and two tangential springs are constructed, and brittle Mohr–Coulomb fracture constitutive law and tensile fracture constitutive law are introduced to represent contact behavior. To realize the transmission of force and displacement, the interpolation coupling approach is adopted between the elements of bars and the elements of discrete particles or blocks. In this coupling mode, penalty springs Sgn and Sgs along and perpendicular to the axis of the bar, respectively, are established. Sgn and Sgs are mainly used to describe the pulling and pushing effect and the lateral compression effect between the bar and the surrounding rock, respectively. The coupling algorithm described in this paper is adopted to simulate the elastic field of a circular shield tunnel, rectangular tunnel reinforced by prestressed rock bolts, reinforcement of full-anchored rock bolts on surrounding rock, and the tunnel support effect in a jointed rock mass. The results of the four numerical cases show the accuracy and rationality of the coupling algorithm. Using this proposed algorithm, the progressive failure process of rock tunnels under high ground stress and the supporting process by lining and bolt (cable) can be accurately simulated.

Scaffolding is widely used in construction, maintenance, and other activities as a temporary support structure. However, strong winds frequently cause scaffolding structures to collapse. Thus, the influence of wind load on the performance of such temporary support systems cannot be ignored. During the 2022 Beijing Winter Olympics, the scaffolding at the National Alpine Skiing Center in Yanqing District faced challenges from high-altitude winds. This study evaluated its performance under a wind speed of 33 m/s using ANSYS Workbench. The result show that the maximum wind speed of Model A is 55 m/s, which occurs at the connection between the channel plate and the stand plate. And the maximum wind speeds of Model B and Model C are 47 m/s and 43 m/s, respectively, which both occur at the top of the stand. Compared with Model A and Model B, the wind pressure, stress, and displacement of Model C are larger, in which the negative pressure of Model C is below −3600 Pa and the positive pressure is above 600 Pa at the position of the connection between the stand plate and the rod. The stress at the connection between the channel plate and the stand plate is more than three times of that of the other positions of the plate, and the displacement of the stand plate can reach 68 mm in some areas. Therefore, optimizing the connection part, considering local wind direction when arranging, and placing windproof measures can all reduce the impact of strong winds on the scaffolding.

AbstractBackground and Purpose Microwave ablation (MWA) is a promising modality that needs to be further investigated for cystic lesions. The present study aimed to determine the effects of MWA on cysts and cystic neoplasms with a tissue-mimicking model.Methods Twenty New Zealand White rabbits were randomly divided into Group A (cyst mimic models, n = 10, φ = 5 cm) and Group B (cystic neoplasm mimicking models, n = 10, φ = 5 cm). For each group, ex vivo rabbit healthy bladder and VX2-implanted tumor bladder were fixed and embedded in agarose gel to mimic cyst and cystic neoplasm. In the MWA experimental subgroups, microwave antennas guided by computed tomography (CT) were introduced into these models. A system thermometer was placed at the outer edge of the bladder wall to monitor temperature changes. Immediately after MWA, ex vivo rabbit healthy bladders and VX2-implanted tumor bladders were harvested for gross anatomy and prepared for pathological evaluation.Results A total of twenty cyst and cystic neoplasm mimicking models were successfully developed. Ninety percent of the MWA procedures were successful, and no peri-procedural complications were encountered. The temperature of the cystic wall increased with duration in both MWA experimental subgroups and an effective ablation temperature (>60 °C) was achieved. Pathological examination of the cyst and cystic neoplasm mimic models revealed degenerative necrosis of the bladder wall mucosal epithelial cells, loss of bladder wall tissue structure and coagulative necrosis of VX2 tumor cells.Conclusion Our data indicate that MWA could cause thermal damage to the tissue structure of cyst and cystic neoplasm, and it is an effective technique for treating cystic diseases.HIGHLIGHTSex vivo rabbit healthy bladder and VX2-implanted tumor bladder were fixed and embedded in agarose gel to mimic cyst and cystic neoplasm.The temperature of the cystic wall increased with MWA duration and an effective ablation temperature (> 60 °C) was achieved.MWA could cause thermal damage to the tissue structure of the cyst and cystic neoplasm and it is effective in treating cystic diseases, as assessed by histopathology.

Purpose Spinal cord injury (SCI) destroys the sensorimotor pathway and induces brain plasticity. However, the effect of treatment-induced spinal cord tissue regeneration on brain functional reorganization remains unclear. This study was designed to investigate the large-scale functional interactions in the brains of adult female Rhesus monkeys with injured and regenerated thoracic spinal cord.Materials and methods Resting-state functional magnetic resonance imaging (fMRI) combined with Granger Causality analysis (GCA) and motor behaviour analysis were used to assess the causal interaction between sensorimotor cortices, and calculate the relationship between causal interaction and hindlimb stepping in nine Rhesus monkeys undergoing lesion-induced spontaneous recovery (injured, n = 4) and neurotrophin-3/chitosan transplantation-induced regeneration (NT3-chitosan, n = 5) after SCI.Results The results showed that the injured and NT3-chitosan-treated animals had distinct spatiotemporal features of brain functional reorganization. The spontaneous recovery followed the model of “early intra-hemispheric reorganization dominant, late inter-hemispheric reorganization dominant”, whereas regenerative therapy animals showed the opposite trend. Although the variation degree of information flow intensity was consistent, the tendency and the relationship between local neuronal activity properties and coupling strength were different between the two groups. In addition, the injured and NT3-chitosan-treated animals had similar motor adjustments but various relationship modes between motor performance and information flow intensity.Conclusions Our findings show that brain functional reorganization induced by regeneration therapy differed from spontaneous recovery after SCI. The influence of unique changes in brain plasticity on the therapeutic effects of future regeneration therapy strategies should be considered. Key messagesNeural regeneration elicited a unique spatiotemporal mode of brain functional reorganization in the spinal cord injured monkeys, and that regeneration does not simply reverse the process of brain plasticity induced by spinal cord injury (SCI).Independent “properties of local activity – intensity of information flow” relationships between the injured and treated animals indicating that spontaneous recovery and regenerative therapy exerted different effects on the reorganization of the motor network after SCI.A specific information flow from the left thalamus to the right insular can serve as an indicator to reflect a heterogeneous “information flow – motor performance” relationship between injured and treated animals at similar motor adjustments.

Summary: Graph theory-based analysis describes the brain as a complex network. Only a few studies have examined modular composition and functional connectivity (FC) between modules in patients with spinal cord injury (SCI). Little is known about the longitudinal changes in hubs and topological properties at the modular level after SCI and treatment. We analyzed differences in FC and nodal metrics reflecting modular interaction to investigate brain reorganization after SCI-induced compensation and neurotrophin-3 (NT3)–chitosan-induced regeneration. Mean inter-modular FC and participation coefficient of areas related to motor coordination were significantly higher in the treatment animals than in the SCI-only ones at the late stage. The magnocellular part of the red nucleus may reflect the best difference in brain reorganization after SCI and therapy. Treatment can enhance information flows between regions and promote the integration of motor functions to return to normal. These findings may reveal the information processing of disrupted network modules.

Although autogenous nerve transplantation is the gold standard for treating peripheral nerve defects of considerable length, it still has some shortcomings, such as insufficient donors and secondary injury. Composite chitosan scaffolds loaded with controlled release of nerve growth factor can promote neuronal survival and axonal regeneration after short-segment sciatic nerve defects. However, the effects on extended nerve defects remain poorly understood. In this study, we used chitosan scaffolds loaded with nerve growth factor for 8 weeks to repair long-segment (20 mm) sciatic nerve defects in adult rats. The results showed that treatment markedly promoted the recovery of motor and sensory functions. The regenerated sciatic nerve not only reconnected with neurons but neural circuits with the central nervous system were also reconstructed. In addition, the regenerated sciatic nerve reconnected the motor endplate with the target muscle. Therefore, this novel biomimetic scaffold can promote the regeneration of extended sciatic nerve defects and reconstruct functional circuits. This provides a promising method for the clinical treatment of extended peripheral nerve injury. This study was approved by the Animal Ethics Committee of Capital Medical University, China (approval No. AEEI-2017-033) on March 21, 2017.

Abstract Background The aim of the study was to explore the outcomes of computed tomography‐guided microwave ablation (MWA) in non‐small cell lung cancer (NSCLC) patients with adjacent lobe invasion (ALI), and to compare the outcomes of ALI‐NSCLC and non‐ALI NSCLC patients after MWA. Methods A total of 319 NSCLC patients and 366 tumors treated with MWA were included in the study, comprising 34 ALI‐NSCLC patients and 285 non‐ALI NSCLC patients. Complications, local recurrence rates, progression‐free survival (PFS), and overall survival (OS) were compared. Logistic regression analyses were used to investigate the correlation between ALI and the occurrence of pneumothorax after MWA. Results The mean tumor diameter of ablated tumors was 3.6 ± 2.2 cm. There were 95 (29.8%) NSCLC patients in which pneumothorax occurred after MWA, and all patients recovered. Of these, the ALI group had a significantly higher incidence rate of pneumothorax than the non‐ALI group (52.9% vs. 27.0%, p = 0.002). The median PFS and OS for the ALI group were 12.0 ± 10.2 and 15.5 ± 9.5 months, respectively, and that of the non‐ALI group were 13.0 ± 10.6 and 17.0 ± 11.1 months, respectively, and no significant difference was found in PFS (p = 0.329) nor OS (p = 0.394) between the two groups. Local recurrence rates for ALI and non‐ALI groups were 29.4% and 20.7%, respectively, and no significant difference was found (p = 0.244). Logistic regression analyses revealed that ALI can increase the risk of pneumothorax (hazard ratio [HR], 2.867; p = 0.012). Conclusions MWA is an effective and safe approach for ALI‐NSCLC treatment. Although ALI can increase the risk of pneumothorax, ALI‐NSCLC patients reveal a comparable outcome to non‐ALI NSCLC patients after MWA.

Global path planning is the key technology of mobile robot outdoor work,and global path planning algorithm is mainly used in geographical scenarios to predict the outdoor environment.In the face of the complex outdoor environment,the robot optimizes the algorithm to improve real-time obstacle avoidance of robot path planning,path smoothness,planning effectiveness,which has become the core content in the research of global path planning algorithm.Depending on the degree of intelligent algorithm,the global path planning algorithm for mobile robot is divided into traditional global path planning algorithm and the bionic intelligent global path planning algorithm.Then,this paper further expounds the current practical multi-objective path planning algorithm,introduces several typical optimizations of each algorithm,and summarizes and analyzes the advantages and disadvantages of the improved algorithm.Finally,this paper discusses the future development trend of global path algorithm,and points out four aspects of future research and development,which are optimizing the performance of the conventional algorithm for path planning,various existing algorithms advantage integration,complex environment dynamic obstacle avoidance and improving map representation methods adapting to diverse environment.

Abstract Addressing microstructure-property relations of polymer nanocomposites is vital for designing advanced dielectrics for electrostatic energy storage. Here, we develop an integrated phase-field model to simulate the dielectric response, charge transport, and breakdown process of polymer nanocomposites. Subsequently, based on 6615 high-throughput calculation results, a machine learning strategy is schemed to evaluate the capability of energy storage. We find that parallel perovskite nanosheets prefer to block and then drive charges to migrate along with the interfaces in x-y plane, which could significantly improve the breakdown strength of polymer nanocomposites. To verify our predictions, we fabricate a polymer nanocomposite P(VDF-HFP)/Ca2Nb3O10, whose highest discharged energy density almost doubles to 35.9 J cm−3 compared with the pristine polymer, mainly benefit from the improved breakdown strength of 853 MV m−1. This work opens a horizon to exploit the great potential of 2D perovskite nanosheets for a wide range of applications of flexible dielectrics with the requirement of high voltage endurance.

Objectives To explore the outcomes of CT-guided percutaneous microwave ablation (MWA) in non-small cell lung cancer (NSCLC) patients, and then develop an effective nomogram to predict the survival. Methods NSCLC patients treated with MWA were randomly allocated to either the training cohort or the validation cohort (3:1). The primary outcome measurement was overall survival (OS), whose predictors were identified by univariate and multivariate analyses in the training cohort. Then, a predictive nomogram was developed to predict the OS, with the predictive accuracy evaluated by C-statistic and receiver operating characteristic in both the training and validation cohorts. Results A total of 234 patients (training cohort: n = 176; validation cohort: n = 58) and 271 tumors with a median OS of 17.0 ± 12.2 months were included. The predictors selected into the nomogram included tumor diameter (hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.37-3.30; p

Objectives To develop an effective nomogram and artificial neural network (ANN) model for predicting pleural effusion after percutaneous microwave ablation (MWA) in lung malignancy (LM) patients. Methods LM patients treated with MWA were randomly allocated to either the training cohort or the validation cohort (7:3). The predictors of pleural effusion identified by univariable and multivariable analyses in the training cohort were used to develop a nomogram and ANN model. The C-statistic was used to evaluate the predictive accuracy in both the training and validation cohorts. Results A total of 496 patients (training cohort: n = 357; validation cohort: n = 139) were enrolled in this study. The predictors selected into the nomogram for pleural effusion included the maximum power (hazard ratio [HR], 1.060; 95% confidence interval [CI], 1.022–1.100, p = 0.002), the number of pleural punctures (HR, 2.280; 95% CI, 1.103–4.722; p = 0.026) and the minimum distance from needle to pleura (HR, 0.840; 95% CI, 0.775–0.899; p 0.16) on the nomogram should be monitored for pleural effusion.

Objectives To develop an effective nomogram model for predicting the local progression after computed tomography-guided microwave ablation (MWA) in non-small cell lung cancer (NSCLC) patients. Methods NSCLC patients treated with MWA were randomly allocated to either the training cohort or the validation cohort (4:1). The predictors of local progression identified by univariable and multivariable analyses in the training cohort were used to develop a nomogram model. The C-statistic was used to evaluate the predictive accuracy in both the training and validation cohorts. Results A total of 304 patients (training cohort: n = 250; validation cohort: n = 54) were included in this study. The predictors selected into the nomogram for local progression included the tumor subtypes (odds ratio [OR], 2.494; 95% confidence interval [CI], 1.415–4.396, p = 0.002), vessels ≥3 mm in direct contact with tumor (OR, 2.750; 95% CI, 1.263–5.988; p = 0.011), tumor diameter (OR, 2.252; 95% CI, 1.034–4.903; p = 0.041) and location (OR, 2.442; 95% CI, 1.201–4.965; p = 0.014). The C-statistic showed good predictive performance in both cohorts, with a C-statistic of 0.777 (95% CI, 0.707–0.848) internally and 0.712 (95% CI, 0.570–0.855) externally (training cohort and validation cohort, respectively). The optimal cutoff value for the risk of local progression was 0.39. Conclusions Tumor subtypes, vessels ≥3 mm in direct contact with the tumor, tumor diameter and location were predictors of local progression after MWA in NSCLC patients. The nomogram model could effectively predict the risk of local progression after MWA. Patients showing a high risk (>0.39) on the nomogram should be monitored for local progression.

Objectives To develop effective nomograms for predicting pneumothorax and delayed pneumothorax after microwave ablation (MWA) in lung malignancy (LM) patients. Methods LM patients treated with MWA were randomly allocated to a training or validation cohort at a ratio of 7:3. The predictors of pneumothorax identified by univariate and multivariate analyses in the training cohort were used to develop a predictive nomogram. The C-statistic was used to evaluate predictive accuracy in both cohorts. A second nomogram for predicting delayed pneumothorax was developed and validated using identical methods. Results A total of 552 patients (training cohort: n = 402; validation cohort: n = 150) were included; of these patients, 27.9% (154/552) developed pneumothorax, with immediate and delayed pneumothorax occurring in 18.8% (104/552) and 9.1% (50/552), respectively. The predictors selected for the nomogram of pneumothorax were emphysema (hazard ratio [HR], 6.543; p

Abstract In tauopathies, memory impairment positively strongly correlates with the amount of abnormal tau aggregates; however, how tau accumulation induces synapse impairment is unclear. Recently, we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1 (STAT1) to inhibit the transcription of synaptic N-methyl-D-aspartate receptors (NMDARs). Here, overexpressing human P301L mutant tau (P301L-hTau) increased the phosphorylated level of Signal Transduction and Activator of Transcription-3 (STAT3) at Tyr705 by JAK2, which would promote STAT3 translocate into the nucleus and activate STAT3. However, STAT3 was found mainly located in the cytoplasm. Further study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm, and thus inhibited the nuclear translocation and inactivation of STAT3. Knockdown of STAT3 in STAT3flox/flox mice mimicked P301L-hTau-induced suppression of NMDARs expression, synaptic and memory impairments. Overexpressing STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs expression. Further study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs promoters. These findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression, revealed a novel mechanism for tau-associated synapse and cognition deficits, and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.

BackgroundOseltamivir resistance in influenza virus (IFV) has been of widespread concern. An increase in the frequency of viruses with reduced inhibition was observed. Whether oseltamivir is effective is uncertain. We conducted this study to understand the real-world situation in northern China and the clinical efficacy for patients with IFV infection after the use of oseltamivir.MethodsThe longitudinal study was performed on influenza-like illness (ILI) cases in a tertiary general hospital in Beijing, China during the flu season of 2018–2019. All ILI cases (≥18 years) were recruited into the study. We analyzed the effect of the oseltamivir therapy on the number of clinic visits, hospitalization frequency, and the duration of fever and cough.ResultsA total of 689 ILI patients were recruited in this study with 355 in the oseltamivir therapy group and 334 in the supportive therapy group. Among the ILI patients, 388 patients were detected for IFV infection (364 IFV-A and 24 IFV-B) and divided into two groups with or without the oseltamivir therapy (302 vs. 86). There were no significant differences in the basic characteristics between the oseltamivir and supportive therapy groups in the ILI patients or in the IFV positive patients (all p

PurposeTo compare the outcomes of drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) with and without microwave ablation (MWA) for the treatment of advanced and standard treatment-refractory/ineligible non-small cell lung cancer (ASTRI-NSCLC).Materials and MethodsA total of 77 ASTRI-NSCLC patients who received DEB-BACE combined with MWA (group A; n = 28) or DEB-BACE alone (group B; n = 49) were included. Clinical outcomes were compared between groups A and B. Kaplan–Meier methods were used to compare the median progression-free survival (PFS) or overall survival (OS) between the two groups. Univariate and multivariate Cox proportional hazards analyses were used to investigate the predictors of OS for ASTRI-NSCLC treated with DEB-BACE.ResultsNo severe adverse event was found in both groups. Pneumothorax was the predominant MWA-related complication in group A, with an incidence rate of 32.1% (9/28). Meanwhile, no significant difference was found in DEB-BACE-related complications between groups A and B. The overall disease control rate (DCR) was 61.0% (47/77), with a significantly higher DCR in group A (85.7% vs. 46.9%, P = 0.002). The median PFS in groups A and B was 7.0 and 4.0 months, respectively, with a significant difference (P = 0.037). The median OS in groups A and B was both 8.0 months, with no significant difference (P = 0.318). The 6-month PFS and OS rates in groups A and B were 75.0% and 78.6%, 22.4% and 59.2%, respectively, while the 12-month PFS and OS rates in groups A and B were 17.9% and 28.6%, 14.3% and 22.4%, respectively. Of these, a significantly higher 6-month PFS rate was found in group A (75.0% vs. 22.4%; P < 0.001). The cycles of DEB-BACE/bronchial artery infusion chemotherapy [hazard ratio (HR): 0.363; 95% confidence interval (CI): 0.202–0.655; P = 0.001] and postoperative immunotherapy (HR: 0.219; 95% CI: 0.085–0.561; P = 0.002) were identified as the predictors of OS in ASTRI-NSCLC treated with DEB-BACE.ConclusionMWA sequentially combined with DEB-BACE was superior to DEB-BACE alone in the local control of ASTRI-NSCLC. Although the combination therapy reveals a trend of prolonging the OS, long-term prognosis warrants an investigation with a longer follow-up.

Chinese breast cancer patients have not been well represented in clinical sequencing studies. Here the authors analyse the mutational landscape of 1,134 Chinese breast cancer patients, finding actionable targets and a higher prevalence of p53 and Hippo pathway mutations compared to Western cohorts.

Abstract Background Pregnancy-associated breast cancer (PABC) is an aggressive disease, and since Chinese authority began to encourage childbearing in 2015, the incidence of PABC has increased. This study investigated the characteristics and survival of PABC patients. Methods Patients with PABC who underwent surgery at Fudan University, Shanghai Cancer Center between 2005 and 2018 were enrolled. Data concerning the tumor characteristics, maternal state (whether first or non-first pregnancy) and survival outcome were recorded. Pearson Chi-square tests were used to compare the characteristics of the tumors, and Kaplan-Meier methods were used to perform the survival analysis. Results Overall, 203 PABC patients were recruited. Since 2015, 65.5% of non-first pregnant women were diagnosed with breast cancer, it’s 5.7 fold of the incidence of PABC in non-first pregnant women. No significant differences in tumor characteristics were observed between the patients who were in their first pregnancy and those in non-first pregnancy. Among the entire PABC population, luminal B breast cancer accounted for the largest proportion (38.4%), followed by triple-negative breast cancer (TNBC, 30.0%). The distribution of the molecular subtypes of PABC and non-PABC differed (P

Abstract Background Few studies have discussed the contradictory roles of mutated‐PI3Kα in HER2‐positive (HER2+) breast cancer. Thus, we characterised the adaptive roles of PI3Kα mutations among HER2+ tumour progression. Methods We conducted prospective clinical sequencing of 1923 Chinese breast cancer patients and illustrated the clinical significance of PIK3CA mutations in locally advanced and advanced HER2+ cohort. A high‐throughput PIK3CA mutations‐barcoding screen was performed to reveal impactful mutation sites in tumour growth and drug responses. Results PIK3CA mutations acted as a protective factor in treatment‐naïve patients; however, advanced/locally advanced patients harbouring mutated‐PI3Kα exhibited a higher progressive disease rate (100% vs. 15%, p = .000053) and a lower objective response rate (81.7% vs. 95.4%, p = .0008) in response to trastuzumab‐based therapy. Meanwhile, patients exhibiting anti‐HER2 resistance had a relatively high variant allele fraction (VAF) of PIK3CA mutations; we defined the VAF > 12.23% as a predictor of poor anti‐HER2 neoadjuvant treatment efficacy. Pooled mutations screen revealed that specific PI3Kα mutation alleles mediated own biological effects. PIK3CA functional mutations suppressed the growth of HER2+ cells, but conferred anti‐HER2 resistance, which can be reversed by the PI3Kα‐specific inhibitor BYL719. Conclusions We proposed adaptive treatment strategies that the mutated PIK3CA and amplified ERBB2 should be concomitantly inhibited when exposing to continuous anti‐HER2 therapy, while the combination of anti‐HER2 and anti‐PI3Kα treatment was not essential for anti‐HER2 treatment‐naïve patients. These findings improve the understanding of genomics‐guided treatment in the different progressions of HER2+ breast cancer.

Human gut microbiome research, especially gut microbiome, has been developing at a considerable pace over the last decades, driven by a rapid technological advancement. The emergence of high-throughput technologies, such as genomics, transcriptomics, and others, has afforded the generation of large volumes of data, and in relation to specific pathologies such as different cancer types. The current review identifies high-throughput technologies as they have been implemented in the study of microbiome and cancer. Four main thematic areas have emerged: the characterization of microbial diversity and composition, microbial functional analyses, biomarker prediction, and, lastly, potential therapeutic applications. The majority of studies identified focus on the microbiome diversity characterization, which is reaching technological maturity, while the remaining three thematic areas could be described as emerging.

Abstract Background Strong evidence comparing effectiveness between nephron-sparing intervention (NSI) and active surveillance (AS) is lacking. Thus, we aim to compare the outcomes of survival, including cancer-specific survival (CSS), overall survival (OS), and cardiovascular-specific survival (CVSS), in patients with renal masses who underwent NSI or AS. Methods A systematic literature search of PubMed, Web of Science, and EMBASE was performed for citations published prior to September 2018 that described NSI, partial nephrectomy and thermal ablation included, and AS for patients with renal masses and a standard meta-analysis on survival outcomes was then conducted. Results The meta-analysis included seven studies containing 5809 patients. The results comparing NSI with AS were as follows: CSS (hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.46–0.89, P

We prepared 300-nm GeTe thin films on (111)-oriented and piezoelectrically active 0.71 Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-0.29 PT) single-crystal substrates by the pulsed laser deposition and investigated the effects of in situ electric-field-controllable non-180° ferroelastic domain switching of the PMN-0.29 PT on the electronic properties of the GeTe films. The in-plane strain of the PMN-0.29 PT could be modulated continuously and reversibly by electric fields in a nonvolatile manner and could be effectively transferred to the GeTe films. Based on this, we realized reversible and nonvolatile resistance switching and obtained multilevel stable nonvolatile resistance states with good stability and endurance at T = 300 K by applying appropriate asymmetrical bipolar electric fields to the PMN-0.29 PT(111) substrates along the thickness direction. Such heterostructures may be used for multilevel data storage that allows each unit to store multiple bits of information and thus improve the memory density. Our investigation would be beneficial for the fabrication of nonvolatile memory devices using PMN-xPT-based heterostructures. Keywords: Ferroelastic strain, Electronic transport, PMN-PT, Heterostructure, Strain effect

The stress condition of tunnel surrounding rock mass is complex. The stress concentration of in situ brittle rock mass caused by excavation results in localized damage evolution parallel to the free face, which is called surface instability. The rock wall shows the transition characteristics of the failure mode with the distance from the surface to the depth. Low strength surface instability and transition failure modes of the tunnel’s rock wall are common in deep condition but cylindrical specimens cannot simulate stress state of rock wall surface well in conventional rock mechanics tests. This paper conducted the indoor experimental study of the biaxial stress state and studied the surface instability of samples. An indoor test device for the simulation of transitional surface failure of the rock wall was developed. Through a biaxial stress loading test on the rectangular rock sample, the damage process and crack development of rock samples were analyzed, and the law of stress and strain related to the failure mode transition was characterized as well. Based on test results and strength analysis, an explanation of the failure theory and its corresponding model are proposed based on the maximum strain strength theory. Furthermore, this paper concludes that the failure mode of surface instability presents transition feature from brittle to ductile with the increase of distance from the surface to depth.

Abstract Background Inflammation has been implicated in the development of cardiovascular disease. We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension. Methods Prehypertensive rats were induced by 8% salt diet. The rats on high-salt diet for 1 month were administered a specific NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. ELISA, western blotting, immunohistochemistry, and flow cytometry were used to measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection, respectively. Results NLRP3 expression in PVN was increased significantly in prehypertensive rats, accompanied by increased number of microglia, CD4+, CD8+ T cell, and CD8+ microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1 significantly increased. The balance between 67-kDa isoform of glutamate decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure, reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters. Blood pressure and inflammatory markers were upregulated after termination of central blockage NLRP3. Conclusions Salt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters.

In this paper, a new robust adaptive control method has been proposed for nonlinear systems with uncertainties. This method combines the advantages of self-tuning control and sliding mode control. A simple parameterization model is first derived based on a linear dynamic model and unmodeled dynamics. Based on a modified sliding surface, the design procedure is based on the indirect adaptive control concept. This controller consists of four parts: 1) the system parameters estimation; 2) the unmodeled dynamics estimation; 3) the weighting polynomials updating; and 4) the control law calculation. The key merits of this controller are as follows: 1) the controller is applicable to non-minimum phase and open-loop unstable systems; 2) the estimation of the unmodeled dynamics is introduced as a feedback compensation control to improve the response; and 3) the strict stability condition is eliminated and a desirable performance is ensured during a wide operation region. Moreover, the control problem of a shape memory alloy actuator system is considered. In the literature, the mechanism model-based controllers have been extensively reported to address this issue. As an alternative, we describe this plant as a gray-box model. The adaptation algorithm and the control law have been implemented through the Beckhoff controller. The experimental results have demonstrated that the proposed controller has wider applicability than some existing methods.

The hydroxyl of the gem-grade forsterite from Pakistan was measured by the polarized spectra at room temperature to 1000 °C, showing four unambiguous absorption bands at 3612, 3597, 3579, and 3566 cm−1. Here, we report angle-resolved polarized IR spectroscopy of the crystal-oriented forsterite, which were heated at 1 bar up to 1000 °C in situ to investigate the hydrogen diffusion character. The peak positions of the IR absorbance at 3579 cm−1, 3597 cm−1, and 3566 cm−1 of forsterite decreased linearly depending on the temperature, while the 3612 cm−1 is stable. We discuss that the dipole orientation of the hydroxyl is analyzed by a pleochroic scheme of the integrated absorbance vs. sample to polarizer angle. Our data suggest that the temperature effect cannot be ignored since the absorption coefficients and absorbance band positions of OH may alter.

Abstract Background Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli’s disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli’s disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli’s syndrome. The combination of Abernethy malformation and Caroli’s syndrome has not been reported previously. Case presentation We present the case of a 23-year-old female who was found to have both type II Abernethy malformation and Caroli’s syndrome. Radiological imaging was performed, including computed tomography with three-dimensional reconstruction and magnetic resonance imaging with (magnetic resonance cholangiopancreatography (MRCP), which revealed a side-to-side portocaval shunt, intrahepatic bile duct dilation, congenital hepatic fibrosis, and renal cysts. In addition, PKHD1 (polycystic kidney and hepatic disease 1) gene mutational analysis revealed a paternally inherited heterozygous missense mutation (c.1877A > G, p.Lys626Arg). A liver biopsy confirmed the pathological features of Caroli’s syndrome. Conclusions To our knowledge, this is the first reported case of a patient with both type II Abernethy malformation and Caroli’s syndrome diagnosed using a comprehensive approach that included imaging, mutational analysis, and liver biopsy. Additionally, this is the second reported case to date of an Asian patient presenting with liver and renal disorders with the same paternally inherited PKHD1 missense mutation.

Abstract Background The impairment of histone acetylation is causally linked to the cognitive decline in Alzheimer’s disease (AD). In addition to histone acetyltransferases (HATs) and histone deacetylases (HDACs), inhibitor of acetyltransferases (INHAT) can also regulate histone acetylation. As a key component of INHAT, level of ANP32A is selectively upregulated in the brain of AD patients. Here we investigated whether downregulating ANP32A can rescue AD-like synapse and memory deficits. Methods RFP-labeled lentiviral ANP32A-shRNA was infused stereotaxically into the hippocampal CA3 region of the human tau transgenic mice (termed htau). The spatial learning and memory were assessed by Morris water maze (MWM). The synaptic function was measured by electrophysiological recording and the spine density was detected by Golgi staining. RT-PCR and Western blotting were used to detect the mRNA and protein levels. Results Elevation of ANP32 in htau transgenic mice was correlated with learning deficits, while the hippocampal infusion of lenti-siANP32A to downregulate ANP32A in 12 m-old htau mice could rescue memory loss. Further studies demonstrated that downregulating ANP32A restored synapse morphology and the function. In the brain of htau mice, the acetylated histone decreased while knockdown ANP32A unmasked histone for a robust acetylation with reduced INHAT complex formation. Downregulating of ANP32A also attenuated AD-like tau hyperphosphorylation. Finally, several AD-associated risk factors, including tau accumulation, β-amyloid and H2O2 exposure, increased ANP32A by activating CCAAT/enhancer binding protein-β (C/EBPβ). Conclusion We conclude that downregulating ANP32A rescues synaptic plasticity and memory ability by reducing INHAT formation and unmasking histone for hyperacetylation. Our findings reveal novel mechanisms for AD memory loss and potential molecular markers for protection.

Background:. The spectrum of abnormal behaviors in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been described, but its practical meaning, namely its impact on caregiver burden, has not been clearly documented in Chinese population. This study aimed to assess the distribution of abnormal behaviors in Chinese population, and to analyze the relationship between behavior changes and caregiver burden. Methods:. Sixty-five patients with ALS/MND have been consecutively enrolled into registry platform of Peking Union Medical College Hospital. An investigation was performed to these patients and their caregivers using the revised ALS function rating scale, Frontal Behavioral Inventory-ALS version, the Frontal Assessment Battery, and the Caregiver Burden Inventory. Results:. Twenty-eight (43.1%) patients displayed abnormal behaviors of varying degrees, with one fulfilling the diagnostic criteria of frontotemporal lobe degeneration. Irritability, logopenia, and inflexibility ranked top 3 of abnormal behavior list. Correlation analysis revealed that the degree of behavioral change and frontal cognitive status were significantly associated with caregiver burden, with more extensive impact from disinhibitive behaviors. Analysis of covariance analysis showed that after associated factors were corrected, caregivers of patients with moderate to severe behavior change reported significantly heavier developmental burden, physical burden, and total burden than those with no behavioral change. Conclusions:. Neurobehavioral symptoms could present in around 40% of Chinese patients with ALS/MND, and the distribution of these behaviors was also unique. Besides, abnormal behaviors were highly related to caregivers’ burden.

Background: Dysfunctional spinal circuit may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). The purpose of this study was to use F waves for assessment of segmental motoneuronal excitability following upper motor neuron (UMN) dysfunctions in ALS. Methods: We studied the F waves of 152 ulnar nerves recorded from abductor digiti minimi in 82 patients with ALS. Two groups of hands were defined based on the presence or absence of pyramidal signs in the same upper limb. The group with pyramidal signs in the upper limbs was designated as the P group, and the group without pyramidal signs in the upper limbs was designated as the NP group. Results: The mean (P < 0.001), median (P < 0.001) and maximum (P = 0.035) F wave amplitudes, mean (P < 0.001), median (P < 0.001) and maximum (P = 0.003) F/M amplitude ratio, index repeating neuron (P < 0.001) and index repeater F waves (P < 0.001) of the P group were significantly increased compared with the NP group. No significant differences were identified for F wave chronodispersion (P = 0.628), mean F wave latency (P = 0.151), minimum F wave latency (P = 0.211), maximum F wave latency (P = 0.199), F wave persistence (P = 0.738), F wave duration (P = 0.152), F wave conduction velocity (P = 0.813) and number of giant F waves (P = 0.072) between the two groups. Conclusions: In this study, increased F wave amplitude, F/M amplitude ratio and number of repeater F waves reflected enhanced segmental motoneuronal excitability following UMN dysfunctions in ALS.

Background: Shikonin is a major active chemical component extracted from Lithospermi Radix, an effective traditional herb in various types of wound healing. Shikonin can accelerate granulomatous tissue formation by the rat cotton pellet method and induce neovascularization in granulomatous tissue. The purpose of the study was to investigate its mechanism of action in human skin cells. Methods: MTS assay was used to measure cell growth. The collagen type I (COL1 ) mRNA expression and procollagen type I C-peptide (PIP) production were detected by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Immunofluorescence and western blot analyses were carried out to investigate nuclear factor-κB (NF-κB) signaling pathway. Cell-based proteasome activity assay was used to determine proteasome activity. Results: In this study, we found that 10 μmol/L shikonin stimulated the growth of normal human keratinocytes and 1 μmol/L shikonin promoted growth of human dermal fibroblasts. However, shikonin did not directly induce COL1 mRNA expression and PIP production in dermal fibroblasts in vitro. In addition, 1 μmol/L shikonin inhibited translocation of NF-κB p65 from cytoplasm to nucleus induced by tumor necrosis factor-α stimulation in dermal fibroblasts. Furthermore, shikonin inhibited chymotrypsin-like activity of proteasome and was associated with accumulation of phosphorylated inhibitor κB-α in dermal fibroblasts. Conclusions: These results suggested that shikonin may promote wound healing via its cell growth promoting activity and suppress skin inflammation via inhibitory activity on proteasome. Thus, shikonin may be a potential therapeutic reagent both in wound healing and inflammatory skin diseases.