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Abstract Background Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. Methods LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. Results A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups. Conclusions Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe.

Abstract Background This study aims to delineate the long-term outcomes and recurrence patterns of locally advanced thoracic esophageal squamous cell carcinoma (TESCC) patients managed with or without postoperative radiotherapy (PORT). Methods A retrospective cohort from two academic centers, encompassing patients who initially underwent esophagectomy and were pathologically staged T3-4, was analyzed. Survival outcomes were constructed using Kaplan–Meier method, with survival significance was evaluated using the log-rank test. Propensity score matching (PSM) was utilized to balance potential selection bias. Results Among the 506 patients, 251 underwent surgery alone and 255 received radiotherapy following radical surgery. With a median follow-up of 49.1 months, PORT significantly improved 5-year overall survival (53.8% vs. 25.3%; p

Abstract Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.

Background: We aimed to assess the value of stereotactic body radiotherapy (SBRT) delivered under the situation of controlled or progressed disease during ICI therapy in advanced or recurrent NSCLC. Methods: We retrospectively collected patients with advanced or recurrent NSCLC who received SBRT concurrently with ICI in our institution between January 2017 and December 2021. Patients were divided into two groups, including those for whom SBRT was delivered initially or to the residual tumors during the first- or later-line ICI treatment (Group 1), and those for whom SBRT was given to the progressed tumors irrespective of first- or later-line ICI treatment (Group 2). Results: A total of 144 patients were included. With median follow-up duration of 25.6 (range: 3.6 to 56.2) months, median progression-free survival (PFS) was 13.7 (95 % CI: 10.4 to 17.1) months and median overall survival (OS) was 52.8 [95 % CI: 30.6 to not available (NA)] months. In Group 1 (n = 78), median PFS was 17.9 (95 % CI: 14.5 to 29.8) months while median OS was not reached and 5-year OS rate was 61.2 %. In Group 2 (n = 66), median PFS was 8.0 (95 % CI: 6.0 to 13.1) months and median OS was 30.6 (95 % CI: 21.5 to NA) months. Conclusions: SBRT combined with ICI demonstrated favorable survival for advanced or recurrent NSCLC, delivered in a controlled-disease situation as well as to progressed diseases with salvage-intent. Future prospective studies are warranted to investigate the optimal SBRT dose regimen and appropriate combination strategy to synergize ICI.

Abstract Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on reducing male fertility is age-dependent and caused by ferroptosis in the testis. The 2-month-old S8/Gss −/− male mice exhibited normal fertility, due to a compensatory increase in GPX4, which prevented the accumulation of ROS. With aging, there was a decline in GPX4 and an increase in ALOX15 levels observed in 8-month-old S8/Gss −/− mice, resulting in the accumulation of ROS, lipid peroxidation, and ultimately testicular ferroptosis. We found that testicular ferroptosis did not affect spermatogonia, but caused meiosis disruption and acrosome heterotopia. Then the resulting aberrant sperm showed lower concentration and abnormal morphology, leading to reduced fertility. Furthermore, these injuries could be functionally rescued by inhibiting ferroptosis through intraperitoneal injection of GSH or Fer-1. In summary, Gss in germ cells play a crucial role in the resistance to oxidative stress injury in aged mice. Our findings deepen the understanding of ferroptosis during spermatogenesis and suggest that inhibiting ferroptosis may be a potential strategy for the treatment of male infertility.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Auditory hair cells (HCs) are the mechanosensory receptors of the cochlea, and HC loss or malfunction can result from genetic defects. Dock4, a member of the Dock180-related protein superfamily, is a guanine nucleotide exchange factor for Rac1, and previous reports have shown that Dock4 mutations are associated with autism spectrum disorder, myelodysplastic syndromes, and tumorigenesis. Here, we found that Dock4 is highly expressed in the cochlear HCs of mice. However, the role of Dock4 in the inner ear has not yet been investigated. Taking advantage of the piggyBac transposon system, Dock4 knockdown (KD) mice were established to explore the role of Dock4 in the cochlea. Compared to wild-type controls, Dock4 KD mice showed significant hearing impairment from postnatal day 60. Dock4 KD mice showed hair bundle deficits and increased oxidative stress, which eventually led to HC apoptosis, late-onset HC loss, and progressive hearing loss. Furthermore, molecular mechanism studies showed that Rac1/β-catenin signaling was significantly downregulated in Dock4 KD cochleae and that this was the cause for the disorganized stereocilia and increased oxidative stress in HCs. Overall, our work demonstrates that the Dock4/Rac1/β-catenin signaling pathway plays a critical role in the maintenance of auditory HCs and hearing function.

Cavitation limits the efficient and stable operation of rotating machinery. The exploration of control methods for hydrofoil cavitation is important for improving the performance of hydraulic machinery. The leading-edge protuberances of the humpback flipper and the spine structure of the tail fin of sailfish are two common bionic structures for cavitation control; however, the control effects of both have limitations. Accordingly, in this study, a passive control method for hydrofoil cavitation was developed by combining the two bionic structures. With the large eddy simulation method, the cavitation processes of wavy leading-edge hydrofoil, bionic fin spine structure hydrofoil, and novel bionic combined structure hydrofoil were studied under a cavitation number of σ = 0.8. The control mechanisms of the three bionic structures for the hydrofoil cavitation were investigated. The results indicated that the novel bionic combined hydrofoil realised the superposition and complementation of the control effects of the two single bionic structures and achieved a better cavitation inhibition effect, reducing the total volume of cavitation by 43 %. In addition, it enhanced the stability of the flow field and reduced the standard deviation of the pressure coefficient on the suction surface by up to 46.55 %. This research provides theoretical support for the optimisation and modification of the blades of hydraulic machinery, such as propellers and pump turbines.

The dynamic characteristics of running away pump turbines (PTs) with a large head variable amplitude have not been understood thus far, primarily because of two difficulties in simulation and analysis. The first is how to provide accurate time-varying boundary conditions for transient simulation of the turbine runaway process (TRP). The other is how to determine the specific appearance time of each frequency component of the complex pressure fluctuations. This study presented a one- and three-dimensional (1D-3D) coupled approach considering waterway dynamics to provide accurate unsteady boundary conditions for the transient flow simulation of a PT with a large head variable amplitude. The short-time Fourier transformation (STFT) approach was adopted to analyse the time-frequency characteristics of the transient pressures and impeller forces. The study found that the fluctuations of pressures and impeller forces during the TRP of the PT with a large head variable amplitude contained two exclusive fluctuation frequency components. The former was approximately three times the rated rotational frequency of the impeller. The later was a series of integer fold transient rotational frequencies of the impeller, which was irrelevant to the rotor-stator interactions. The findings have important value for controlling the pressure fluctuations during the TRP of PTs.

To understand the fracture properties of the nitrate ester plasticized polyether (NEPE) propellant, single-edge notched tension (SENT) tests were carried out at room temperature (20 °C) under different tensile rates (10–500 mm/min). The mechanical response, crack morphology, evolution path, and crack propagation velocity during the fracture process were studied using a combination of a drawing machine and a high-speed camera. The mode I critical stress intensity factor KIc was calculated to analyze the tensile fracture toughness of the NEPE propellant, and a criterion related to KIc was proposed as a means of determining whether the solid rocket motors can normally work. The experimental results demonstrated that the NEPE propellant exhibited blunting fracture phenomena during crack propagation, resulting in fluctuating crack propagation velocity. The fracture toughness of the NEPE propellant exhibited clear rate dependence. When the tensile rate increased from 10 mm/min to 500 mm/min, the magnitude of the critical stress intensity factor increased by 62.3%. Moreover, numerical studies based on bond-based peridynamic (BBPD) were performed by modeling the fracture process of the NEPE propellant, including the crack propagation speed and the load–displacement curve of the NEPE propellant. The simulation results were then compared with the experiments.

Non-small cell lung cancer (NSCLC) can be detected with enlarged lymph nodes on imaging, but their benignity and malignancy are difficult to determine directly, making it difficult to stage the tumor and design radiotherapy target volumes. The clinical diagnosis of malignant lymph nodes is often based on the short diameter of lymph nodes ≥1 cm or the maximum standard uptake value ≥2.5, but the sensitivity and specificity of these criteria are too low to meet the clinical needs. In recent years, many advances have been made in diagnosing benign and malignant lymph nodes using other imaging parameters, and with the development of radiomics, deep learning and other technologies, models of mining the image information of enlarged lymph node regions further improve the diagnostic accuracy. The purpose of this paper is to review recent advances in imaging-based diagnosis of benign and malignant enlarged lymph nodes in NSCLC for more accurate and noninvasive assessment of lymph node status in clinical practice.

Abstract Selecting the optimal speed for dynamic obstacle avoidance in complex man–machine environments is a challenging problem for mobile robots inspecting hazardous gases. Consideration of personal space is important, especially in a relatively narrow man–machine dynamic environments such as warehouses and laboratories. In this study, human and robot behaviors in man–machine environments are analyzed, and a man–machine social force model is established to study the robot obstacle avoidance speed. Four typical man–machine behavior patterns are investigated to design the robot behavior strategy. Based on the social force model and man–machine behavior patterns, the fuzzy-PID trajectory tracking control method and the autonomous obstacle avoidance behavior strategy of the mobile robot in inspecting hazardous gases in a relatively narrow man–machine dynamic environment are proposed to determine the optimal robot speed for obstacle avoidance. The simulation analysis results show that compared with the traditional PID control method, the proposed controller has a position error of less than 0.098 m, an angle error of less than 0.088 rad, a smaller steady-state error, and a shorter convergence time. The crossing and encountering pattern experiment results show that the proposed behavior strategy ensures that the robot maintains a safe distance from humans while performing trajectory tracking. This research proposes a combination autonomous behavior strategy for mobile robots inspecting hazardous gases, ensuring that the robot maintains the optimal speed to achieve dynamic obstacle avoidance, reducing human anxiety and increasing comfort in a relatively narrow man–machine environment.

Volunteers played an important role throughout the COVID-19 pandemic. This study investigated the characteristics of perceived stress, psychological resilience and work engagement among 910 Chinese volunteers of different ages in the first month of pandemic in Gansu province, China. The present study tested the correlations between perceived stress and work engagement, the mediating role of psychological resilience in the relationship and the differences among age groups. The results of this study showed that work engagement and psychological resilience increased with the age of the volunteers. Work engagement and resilience levels were higher in middle adulthood than in early adulthood. As predicted, perceived stress negatively predicted work engagement. A mediation analysis showed that psychological resilience partially explained the correlations between perceived stress and work engagement. Specifically, the mediating effect of psychological resilience in early adulthood was significant, but not in middle adulthood. Overall, this study demonstrates that work engagement increased with age and was negatively predicted by perceived stress, showing these factors were important for volunteers’ work during COVID-19. Further, for those in early adulthood, psychological resilience mediated this relationship—highlighting another age difference among volunteers during COVID-19.

Abstract Dyslexia is a reading and spelling disorder due to neurodevelopmental abnormalities and is occasionally found to be accompanied by hearing loss, but the reason for the associated deafness remains unclear. This study finds that knockout of the dyslexia susceptibility 1 candidate 1 gene (Dyx1c1−/−) in mice, the best gene for studying dyslexia, causes severe hearing loss, and thus it is a good model for studying the mechanism of dyslexia‐related hearing loss (DRHL). This work finds that the Dyx1c1 gene is highly expressed in the mouse cochlea and that the spontaneous electrical activity of inner hair cells and type I spiral ganglion neurons is altered in the cochleae of Dyx1c1−/− mice. In addition, primary ciliary dyskinesia‐related phenotypes such as situs inversus and disrupted ciliary structure are seen in Dyx1c1−/− mice. In conclusion, this study gives new insights into the mechanism of DRHL in detail and suggests that Dyx1c1 may serve as a potential target for the clinical diagnosis of DRHL.

In order to enhance hydrogen-water isotope exchange performance, a hydrophobic microenvironment was constructed within the catalyst support and a bimetal catalyst was loaded. The catalyst was superhydrophobic, resulting in a significant improvement in performance. Through the adsorption/desorption performance test of water vapor, it was observed that the hydrophobic microenvironment could increase the diffusion rate of the reactant, while metal doping modification could enhance the concentration of the reactant around the active center. Comparatively, the catalytic performance of the catalyst containing the hydrophobic microenvironment was superior to that of the normal hydrophobic catalysts, even when the hydrophobicity was slightly diminished.

Graphene-based carbohydrazide coordination polymers are beneficial for improving solid propellants’ energy level and safety, so the study of their thermal decomposition mechanism is promoted for their wide application. In this paper, graphene oxide (GO) intercalated transition metal (Cu2+, Co2+, and Ni2+) complexes of carbohydrazide (CHZ) have been evaluated by using DSC/TGA apparatus and the TG-FTIR technique. Both isoconversional and combined kinetic methods were employed to calculate the kinetic parameters. The components inside GOCHZ-M would react with each other to cause a large mass loss rate and lead to a larger heat-releasing value than pure GO. The types of metal ions could affect their reaction model. Compared with GO, G-CHZ-Co shows a two-sided effect (stabilization and catalytic) on its decomposition. For G-CHZ-Co, the reaction model of each peak is close to the random 2d nucleation and nucleus growth model.

In order to investigate the effects of plasticizers on the binding energy, solubility parameter and mechanical properties of pBAMO-b-GAP copolymer (the copolymer of 3,3′-bis(azidomethy) oxetane and glycidyl azide polymer), the related copolymer/plasticizer mixed systems were established by molecular dynamics simulations. Besides, the mechanical properties of the formulas based on pBAMO-b-GAP containing the three energetic plasticizers were also studied experimentally. The results showed that all involved energetic plasticizers could be miscible with the pBAMO-b-GAP. The order of binding energy was theoretically found to be pBAMO-b-GAP / BuNENA > pBAMO-b-GAP/ TMETN > pBAMO-b-GAP/ DIANP which was consistent with the trends of the experimental tensile strength values of three mixed materials. Excitedly, the DIANP showed strongest effects among the three plasticizers on improving the toughness of the copolymer according to the calculation of Cauchy pressure and experimental value of elongation. For the pBAMO-b-GAP copolymer, the DIANP could be a promising plasticizer and compolymer/plasticizer mixed system was suitable used as binder in azido polyether-based propellants.

To study the mechanical properties of highly filled hydroxy-terminated polybutadiene (HTPB) propellant with 90 wt% solid fillers, the stress–strain curves of the propellant under different temperatures (−50 to 70 °C) and strain rates (0.000476 to 0.119048 s−1) were obtained by uniaxial tensile test. Moreover, to obtain the glass transition temperature and understand the effect of low temperatures on the mechanical properties of the propellant, DMA experiments were carried out. On this basis, the mechanical response laws of the propellant were analyzed, and the master curves of mechanical properties were established. Furthermore, the fracture features of the propellant under typical loading conditions were obtained by SEM, and the corresponding failure mechanisms were analyzed. The results show that the maximum strength decreases with increasing temperature, while the maximum elongation increases with increasing temperature at the same strain rate. The maximum tensile strength increases with increasing strain rate, while the maximum elongation decreases with increasing strain rate at the same temperature. The maximum tensile strength is lowest with a value of 0.35 MPa when the temperature is 343.15 K and the strain rate is 0.000476 s−1, at which time the maximum elongation reaches the highest with a value of 44%. In terms of failure mechanisms, the propellant shows no particle fracture, and the failure modes of the propellant are mainly matrix tearing and dewetting.

Abstract Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids‐produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5‐HT) and 3‐hydroxyanthranilic acid (3‐HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine‐mediated ferroptosis inhibition. Mechanistically, both 5‐HT and 3‐HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5‐HT via degrading 5‐HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5‐HT treatment. Kynureninase (KYNU), which is essential for 3‐HA production, confers cells resistant to ferroptotic cell death, whereas 3‐hydroxyanthranilate 3,4‐dioxygenase (HAAO) significantly blocks 3‐HA mediated ferroptosis inhibition by consuming 3‐HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti‐ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.

Dendrobium is a traditional medicinal plant, which has a variety of clinical applications in China. It has been reported that Dendrobium contains various bioactive components, mainly including polysaccharides and alkaloids. Previous studies have shown that Dendrobium has pharmacological activities including antiviral, anti-inflammatory, and antioxidant effects, as well as immune regulation. Particularly, the anti-aging functions and neuroprotective effects of Dendrobium have been well characterized in a wide array of cell and animal models. In recent years, the effect of Dendrobium on the liver has emerged as a new direction to explore its therapeutic benefits and has received more and more attention. This review is focused on the beneficial effects of Dendrobium on liver toxicity and various liver disorders, which presumably are attributed to a consequence of an array of modes of action due to its multiple bioactive components, and largely lack mechanistic and pharmacokinetic characterization. A particular emphasis is placed on the potential action mechanisms related to Dendrobium’s liver protection. Research perspectives in regard to the potential therapeutic application for Dendrobium are also discussed in this review.

In the electronic warfare environment, the performance of ground-based radar target search is seriously degraded due to the existence of smeared spectrum (SMSP) jamming. SMSP jamming is generated by the self-defense jammer on the platform, playing an important role in electronic warfare, making traditional radars based on linear frequency modulation (LFM) waveforms face great challenges in searching for targets. To solve this problem, an SMSP mainlobe jamming suppression method based on a frequency diverse array (FDA) multiple-input multiple-output (MIMO) radar is proposed. The proposed method first uses the maximum entropy algorithm to estimate the target angle and eliminate the interference signals from the sidelobe. Then, the range-angle dependence of the FDA-MIMO radar signal is utilized, and the blind source separation (BSS) algorithm is used to separate the mainlobe interference signal and the target signal, avoiding the impact of mainlobe interference on target search. The simulation verifies that the target echo signal can be effectively separated, the similarity coefficient can reach more than 90% and the detection probability of the radar is significantly enhanced at a low signal-to-noise ratio.

5-Nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO) is a representative and insensitive energetic compound mainly used as a component of low vulnerable ammunition, but its decomposition process is not clear up to date. Herein, online photoionization mass spectrometry combined with theoretical simulations was employed to shed light on the thermal decomposition mechanism of NTO. The experimental and calculated results provide evidences for the thermal decomposition of NTO through direct ring rupture and intermolecular hydrogen transfer pathways. The initial decomposition step of NTO single molecule is direct ring rupture, followed by NO2 removal. The remaining structure undergoes C-N bond cleavage leading to HN2 dissociation, the CONCH finally decomposes into CO and HCN. The major products of NTO decomposition include N2, CO2, H2N2, NH3, and the minor products are HN2, H3N3, H2O, which is basically consistent with experiments. The formation mechanism of decomposition products is also discussed in detail and the total decomposition pathways are constructed.

Abstract Background To develop a novel subjective–objective-combined (SOC) grading standard for auto-segmentation for each organ at risk (OAR) in the thorax. Methods A radiation oncologist manually delineated 13 thoracic OARs from computed tomography (CT) images of 40 patients. OAR auto-segmentation accuracy was graded by five geometric objective indexes, including the Dice similarity coefficient (DSC), the difference of the Euclidean distance between centers of mass (ΔCMD), the difference of volume (ΔV), maximum Hausdorff distance (MHD), and average Hausdorff distance (AHD). The grading results were compared with those of the corresponding geometric indexes obtained by geometric objective methods in the other two centers. OAR auto-segmentation accuracy was also graded by our subjective evaluation standard. These grading results were compared with those of DSC. Based on the subjective evaluation standard and the five geometric indexes, the correspondence between the subjective evaluation level and the geometric index range was established for each OAR. Results For ΔCMD, ΔV, and MHD, the grading results of the geometric objective evaluation methods at our center and the other two centers were inconsistent. For DSC and AHD, the grading results of three centers were consistent. Seven OARs’ grading results in the subjective evaluation standard were inconsistent with those of DSC. Six OARs’ grading results in the subjective evaluation standard were consistent with those of DSC. Finally, we proposed a new evaluation method that combined the subjective evaluation level of those OARs with the range of corresponding DSC to determine the grading standard. If the DSC ranges between the adjacent levels did not overlap, the DSC range was used as the grading standard. Otherwise, the mean value of DSC was used as the grading standard. Conclusions A novel OAR-specific SOC grading standard in thorax was developed. The SOC grading standard provides a possible alternative for evaluation of the auto-segmentation accuracy for thoracic OARs.

In recent years, gesture recognition has been widely used in the fields of intelligent driving, virtual reality, and human-computer interaction. With the development of artificial intelligence, deep learning has achieved remarkable success in computer vision. To help researchers better understanding the development status of gesture recognition in video, this article provides a detailed survey of the latest developments in gesture recognition technology for videos based on deep learning. The reviewed methods are broadly categorized into three groups based on the type of neural networks used for recognition: twostream convolutional neural networks, 3D convolutional neural networks, and Long-short Term Memory (LSTM) networks. In this review, we discuss the advantages and limitations of existing technologies, focusing on the feature extraction method of the spatiotemporal structure information in a video sequence, and consider future research directions.

Boron powder is a kind of metal fuel with high gravimetric and volumetric calorific values, which has been widely used in military fields such as solid propellants, high-energy explosives, and pyrotechnics. However, the easily formed liquid oxide layer can adhere to the surface of boron powder and react with the hydroxyl (-OH) group of hydroxyl-terminated polybutadiene (HTPB) binder to form a gel layer that is detrimental to propellant processing and restricts the complete oxidation of boron powder. Therefore, to improve the combustion efficiency of boron powder, the ignition and combustion mechanisms of boron powder have been studied, and surface coating modification strategies have been developed by researchers worldwide, aiming to optimize the surface properties, improve the reaction activity, and promote the energy release of boron powder. In this review, recent studies on the ignition and combustion mechanisms of boron powder are discussed. Moreover, the reported boron powder coating materials are classified according to the chemical structure and reaction mechanism. Additionally, the mechanisms and characteristics of different coating materials are summarized, and the mechanism diagrams of fluoride and metal oxide are provided. Furthermore, promising directions for modification methods and the potential application prospects of boron powder are also proposed.

Abstract Background Whole brain radiotherapy (WBRT) can impair patients’ cognitive function. Hippocampal avoidance during WBRT can potentially prevent this side effect. However, manually delineating the target area is time-consuming and difficult. Here, we proposed a credible approach of automatic hippocampal delineation based on convolutional neural networks. Methods Referring to the hippocampus contouring atlas proposed by RTOG 0933, we manually delineated (MD) the hippocampus on the MRI data sets (3-dimensional T1-weighted with slice thickness of 1 mm, n = 175), which were used to construct a three-dimensional convolutional neural network aiming for the hippocampus automatic delineation (AD). The performance of this AD tool was tested on three cohorts: (a) 3D T1 MRI with 1-mm slice thickness (n = 30); (b) non-3D T1-weighted MRI with 3-mm slice thickness (n = 19); (c) non-3D T1-weighted MRI with 1-mm slice thickness (n = 11). All MRIs confirmed with normal hippocampus has not been violated by any disease. Virtual radiation plans were created for AD and MD hippocampi in cohort c to evaluate the clinical feasibility of the artificial intelligence approach. Statistical analyses were performed using SPSS version 23. P

Background Camrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC.Methods Patients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab.Results From November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality.Conclusions The robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC.Trial registration number ChiCTR1900026240.

Abstract Purpose To analyze patterns of failure in patients with LA-NSCLC who received definitive chemoradiotherapy (CRT) and to build a nomogram for predicting the failure patterns in this population of patients. Materials and methods Clinicopathological data of patients with LA-NSCLC who received definitive chemoradiotherapy and follow-up between 2013 and 2016 in our hospital were collected. The endpoint was the first failure after definitive chemoradiotherapy. With using elastic net regression and 5-fold nested cross-validation, the optimal model with better generalization ability was selected. Based on the selected model and corresponding features, a nomogram prediction model was built. This model was also validated by ROC curves, calibration curve and decision curve analysis (DCA). Results With a median follow-up of 28 months, 100 patients experienced failure. There were 46 and 54 patients who experience local failure and distant failure, respectively. Predictive model including 9 factors (smoking, pathology, location, EGFR mutation, age, tumor diameter, clinical N stage, consolidation chemotherapy and radiation dose) was finally built with the best performance. The average area under the ROC curve (AUC) with 5-fold nested cross-validation was 0.719, which was better than any factors alone. The calibration curve revealed a satisfactory consistency between the predicted distant failure rates and the actual observations. DCA showed most of the threshold probabilities in this model were with good net benefits. Conclusion Clinicopathological factors could collaboratively predict failure patterns in patients with LA-NSCLC who are receiving definitive chemoradiotherapy. A nomogram was built and validated based on these factors, showing a potential predictive value in clinical practice.

The mechanical properties of HTPE/PEG interpenetrating polymer network (IPN) binders were systemically studied with molecular dynamics (MDs) simulations and experiments. In this study, an algorithm was used to construct the crosslinking interpenetrating polymer network models and then the mechanical behaviors of Hydroxyl-terminated polyethylene glycol-tetrahydrofuran co-polyether/poly ethylene glycol (HTPE/PEG) IPN models were analyzed at a molecular scale. Firstly, glass transition temperatures (Tg), mean square displacement (MSD) and mechanical properties of IPN crosslinked model simulations showed that better thermomechanical parameters appeared at low temperatures, which were in good agreement with the experimental methods, including dynamic mechanical analysis and uniaxial tensile. Then bond-length distribution was performed to verify the crosslinked structures between prepolymers and curing agents. FTIR-ATR spectra analysis of four IPN binder specimens also gave a convictive result to the special interpenetrating polymer network of polyether polyurethane binders. Cohesive energy density and friction-free volume explained how the micro-structures of IPN crosslinked models and the force of inter-molecule chains affected the mechanical behaviors of the HTPE/PEG polyurethane matrix. Lastly, the morphology of IPN binder specimen tensile fracture indicated the mechanism at different temperatures. These studies were helpful in understanding the mechanical properties of HTPE/PEG interpenetrating polymer network binders and provide molecular insight into mechanisms of mechanical behaviors, which would guide the property improvement of HTPE propellant.

The mechanical properties of HTPE binders have been systemically studied through combining the microstructure molecular simulations with macroscopic experiments. In this study, the crosslinking structures of HTPE binders were established by a computational procedure. Based on the optimized crosslinking models, the mechanical properties and the glass transition temperatures (Tg) of HTPE/N-100, HTPE/HDI, HTPE/TDI, and HTPE/IPDI binder systems were simulated; specifically, the Tg were 245.758 K, 244.573 K, 254.877 K, and 240.588 K, respectively. Then the bond-length distributions, conformation properties, cohesive energy densities, and fraction free volume were investigated to analyze how the microstructures of the crosslinking models influenced the mechanical properties of HTPE binders. Simultaneously, FTIR-ATR spectra analysis of HTPE binders proved that the special peaks, such as -NH and -NCO, could be seen in the crosslinking polyurethane structures synthesized between prepolymers and curing agents. The dynamic mechanical analysis was carried out, and it found that the Tg of HTPE/N-100, HTPE/HDI, HTPE/TDI, and HTPE/IPDI binder systems were −68.18 °C, −68.63 °C, −65.67 °C, and −68.66 °C, respectively. In addition, the uniaxial tension verified that both the ultimate stress and Young’s modulus of HTPE binder systems declined with the rising temperatures, while the strains at break presented a fluctuant variation. When it was closer to glass temperatures, especially −40 °C, the mechanical properties of HTPE binders were more prominent. The morphology of the fractured surface revealed that the failure modes of HTPE binders were mainly intermolecular slipping and molecular chain breakage. In a word, the experimental results were prospectively satisfied using the simulations, which confirmed the accuracy of the crosslinking models between prepolymers and curing agents. This study could provide a scientific option for the HTPE binder systems and guide the design of polyurethanes for composite solid propellant applications.

BackgroundWe aimed to analyze the first progression sites of first-line tyrosine kinase inhibitor (TKI) treatment for EGFR-mutant lung adenocarcinoma patients with systemic metastasis to recognize the potential candidates who might benefit from radiotherapy and establish a radiomic-based model to predict the first progression sites.Materials and MethodsWe retrospectively collected the clinical information and pre-treatment chest CT images of patients in Shanghai Chest Hospital from 2013 to 2017. All patients were diagnosed with stage IV EGFR-mutant lung adenocarcinoma and received TKI as first-line treatment. The first progression sites and survival were analyzed. The pre-treatment chest non-contrast CT images were utilized to establish a radiomic-based model to predict the first progression sites.ResultsWe totally collected 233 patients with systemic metastasis, among whom, there were 84 (36.1%) and 149 (63.9%) patients developing first progression in original lesions (OP) and new lesions (NP), respectively. The PFS and OS of patients with OP were longer than those with NP (PFS 11 months vs. 8 months, p = 0.03, OS 50 months vs. 35 months, p = 0.046). For 67.9% of the patients with OF, disease progressed within five sites (oligoprogression). The radiomic-based model could predict the progression sites with an AUC value of 0.736, a specificity of 0.60, and a sensitivity of 0.750 in the independent validation set.ConclusionAmong patients with systemic metastasis, there were 36.1% of patients developing OP at first progression who had a better prognosis than those developing NP. Patients with OP may be potential candidates who might benefit from radiotherapy. Radiomics is a useful method to distinguish patients developing OP and could provide some indications for radiotherapy.

The small muscle protein, x-linked (SMPX) encodes a small protein containing 88 amino acids. Malfunction of this protein can cause a sex-linked non-syndromic hearing loss, named X-linked deafness 4 (DFNX4). Herein, we reported a point mutation and a frameshift mutation in two Chinese families who developed gradual hearing loss with age. To explore the impaired sites in the hearing system and the mechanism of DFNX4, we established and validated an Smpx null mouse model using CRISPR-Cas9. By analyzing auditory brainstem response (ABR), male Smpx null mice showed a progressive hearing loss starting from high frequency at the 3rd month. Hearing loss in female mice was milder and occurred later compared to male mice, which was very similar to human beings. Through morphological analyses of mice cochleas, we found the hair cell bundles progressively degenerated from the shortest row. Cellular edema occurred at the end phase of stereocilia degeneration, followed by cell death. By transfecting exogenous fluorescent Smpx into living hair cells, Smpx was observed to be expressed in stereocilia. Through noise exposure, it was shown that Smpx might participate in maintaining hair cell bundles. This Smpx knock-out mouse might be used as a suitable model to explore the pathology of DFNX4.

ObjectiveThe advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the durability of response to ICIs, the vast majority of patients will later develop progression. However, the failure patterns of ICI treatment are unknown. Here, our study explored the failure patterns in advanced NSCLC patients treated with ICIs.MethodsA cohort of 156 IIIB or IV NSCLC patients treated with first-/second-line ICIs were retrospectively analyzed. Patients who experienced clinical benefit and then developed progression were identified. The disease progression patterns were divided into three categories: progression in new sites, progression in existing sites, and combined progression. The number of progression sites was also recorded.ResultsBefore the cutoff date, 91 (77.1%) patients had experienced disease progression; 34% of patients had progressed in the last 9 months of the first year. Fifty-three (58.2%) patients had developed progression at existing lesions, and 56 (61.5%) patients had shown ≤2 progression sites (oligo-progression). In patients with oligo-progression, the median time of disease progression was 8.23 months and the counterpart (systemic progression) was 5.97 months. The oligo-progression patients showed prolonged median overall survival (27.23 months) compared with patients with systemic progression (18.87 months).ConclusionsFailure patterns of ICI therapy were predominantly “existing” sites, and the most common lesions of progression were the lung and lymph nodes. Most patients experienced oligo-progression which occurred later than systemic progression and showed prolonged overall survival. The control of the local lesions might be beneficial to improve ICI treatment efficacy.

Macrophages are the main intrinsic immune cells in the cochlea; they can be activated and play a complicated role after cochlear injury. Many studies have shown that the number of macrophages and their morphological characteristics within the major cochlear partitions undergo significant changes under various pathological conditions including acoustic trauma, ototoxic drug treatment, age-related cochlear degeneration, selective hair cell (HC) and spiral ganglion neuron (SGN) elimination, and surgery. However, the exact role of these macrophages after cochlear injury is still unclear. Regulating the migration and activity of macrophages may be a therapeutic approach to reduce the risk or magnitude of trauma-induced hearing loss, and this review highlights the role of macrophages on the peripheral auditory structures of the cochlea and elucidate the mechanisms of macrophage injury and the strategies to reduce the injury by regulating macrophage.

ObjectivesThis study aimed to show the advantages of each stereotactic radiosurgery (SRS) treatment option for single small brain metastasis among Gamma Knife (GK), Cone-based VMAT (Cone-VMAT), and MLC-based CRT (MLC-CRT) plans.Materials and MethodsGK, Cone-VMAT, and MLC-CRT SRS plans were retrospectively generated for 11 patients with single small brain metastasis whose volume of gross tumor volume (GTV) ranged from 0.18 to 0.76 cc (median volume 0.60 cc). Dosimetric parameters, treatment efficiency, and biological parameters of the three techniques were compared and evaluated. The metric variation with the planning target volume (PTV) was also studied.ResultsThe conformity index (CI) was similar in GK and MLC-CRT plans, higher than Cone-VMAT. Cone-VMAT achieved comparable volume covered by 12 Gy (V12) and gradient index (GI) as GK, lower than MLC-CRT. The heterogeneity index (HI) of GK, Cone-VMAT, and MLC-CRT decreased sequentially. GK gave the lowest volume covered by 3 Gy (V3) and 6 Gy (V6), while MLC-CRT got the highest. The beam-on time and treatment time of GK, Cone-VMAT, and MLC-CRT decreased in turn. Tumor control probability (TCP) of all three SRS plans was greater than 98%, and normal tissue complication probability (NTCP) of all organs at risk (OARs) was below 0.01%. GK and Cone-VMAT resulted in superior TCP and NTCP of the normal brain tissue than MLC-CRT. The relative value of Cone-VMAT and GK for all metrics hardly changed with the target volume. Except for the unchanged HI and TCP, the other results of MLC-CRT with respect to GK improved as the target volume increased. MLC-CRT could produce higher CI than GK and Cone-VMAT when the target volume increased above 2 and 1.44 cc, respectively.ConclusionFor single small brain metastases, Cone-VMAT may be used as an alternative to GK-free centers. In addition to the advantage of short treatment time, MLC-CRT showed superiority in CI as the target volume increased. Treatment centers can choose appropriate SRS technique on a case-by-case basis according to institutional conditions and patients’ individual needs.

Modern pharmacological studies have demonstrated that Dendrobium nobile Lindl. Alkaloids (DNLA), the main active ingredients of Dendrobium nobile, is valuable as an anti-aging and neuroprotective herbal medicine. The present study was designed to determine whether DNLA confers protective function over neurotoxicant manganese (Mn)-induced cytotoxicity and the mechanism involved. Our results showed that pretreatment of PC12 cells with DNLA alleviated cell toxicity induced by Mn and improved mitochondrial respiratory capacity and oxidative status. Mn treatment increased apoptotic cell death along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein, all of which were noticeably reversed by DNLA. Furthermore, DNLA significantly abolished the decrease in protein levels of both PINK1 and Parkin, and mitigated the increased expression of autophagy marker LC3-II and accumulation of p62 caused by Mn. These results demonstrate that DNLA inhibits Mn induced cytotoxicity, which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.

BackgroundFor stage IV patients harboring EGFR mutations, there is a differential response to the first-line TKI treatment. We constructed three-dimensional convolutional neural networks (CNN) with deep transfer learning to stratify patients into subgroups with different response and progression risks.Materials and MethodsFrom 2013 to 2017, 339 patients with EGFR mutation receiving first-line TKI treatment were included. Progression-free survival (PFS) time and progression patterns were confirmed by routine follow-up and restaging examinations. Patients were divided into two subgroups according to the median PFS ( 9 months). We developed a PFS prediction model and a progression pattern classification model using transfer learning from a pre-trained EGFR mutation classification 3D CNN. Clinical features were fused with the 3D CNN to build the final hybrid prediction model. The performance was quantified using area under receiver operating characteristic curve (AUC), and model performance was compared by AUCs with Delong test.ResultsThe PFS prediction CNN showed an AUC of 0.744 (95% CI, 0.645–0.843) in the independent validation set and the hybrid model of CNNs and clinical features showed an AUC of 0.771 (95% CI, 0.676–0.866), which are significantly better than clinical features-based model (AUC, 0.624, P

BackgroundTo develop and validate a deep learning–based model on CT images for the malignancy and invasiveness prediction of pulmonary subsolid nodules (SSNs).Materials and MethodsThis study retrospectively collected patients with pulmonary SSNs treated by surgery in our hospital from 2012 to 2018. Postoperative pathology was used as the diagnostic reference standard. Three-dimensional convolutional neural network (3D CNN) models were constructed using preoperative CT images to predict the malignancy and invasiveness of SSNs. Then, an observer reader study conducted by two thoracic radiologists was used to compare with the CNN model. The diagnostic power of the models was evaluated with receiver operating characteristic curve (ROC) analysis.ResultsA total of 2,614 patients were finally included and randomly divided for training (60.9%), validation (19.1%), and testing (20%). For the benign and malignant classification, the best 3D CNN model achieved a satisfactory AUC of 0.913 (95% CI: 0.885–0.940), sensitivity of 86.1%, and specificity of 83.8% at the optimal decision point, which outperformed all observer readers’ performance (AUC: 0.846±0.031). For pre-invasive and invasive classification of malignant SSNs, the 3D CNN also achieved satisfactory AUC of 0.908 (95% CI: 0.877–0.939), sensitivity of 87.4%, and specificity of 80.8%.ConclusionThe deep-learning model showed its potential to accurately identify the malignancy and invasiveness of SSNs and thus can help surgeons make treatment decisions.

Aminoglycosides, a class of clinically important drugs, are widely used worldwide against gram-negative bacterial infections. However, there is growing evidence that aminoglycosides can cause hearing loss or balance problems. In this article, we mainly introduce the main mechanism of ototoxicity induced by aminoglycosides. Genetic analysis showed that the susceptibility of aminoglycosides was attributable to mutations in mtDNA, especially A1555G and C1494T mutations in 12S rRNA. In addition, the overexpression of NMDA receptors and the formation of free radicals also play an important role. Understanding the mechanism of ototoxicity induced by aminoglycosides is helpful to develop new therapeutic methods to protect hearing. In this article, the prevention methods of ototoxicity induced by aminoglycosides were introduced from the upstream and downstream aspects.

Abstract. Autophagy, a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway, is an important mechanism for cellular self-protection in eukaryotes. Autophagy plays essential roles in cell survival, renewal, material reuse and the maintenance of homeostasis. This paper reviews recent advances in understanding the physiological function of autophagy and its possible roles in auditory diseases. We focused our review on original publications on animal models, drug models, and molecular mechanisms of hearing impairment involved in the dysregulation of autophagy. As research on the mechanisms of autophagy has deepened, it has become obvious that autophagy plays essential roles not only in cell survival, but the occurrence and development of a variety of auditory-related disorder, including aminoglycoside-induced hearing loss, age-related hearing loss, and noise-induced hearing loss. While clinical treatment of such conditions via regulation of the development of autophagy is a novel idea, more time is needed to fully elucidate the specific regulatory pathways and modes of autophagy in auditory diseases. The continued study of the mechanisms and regulation of autophagy in auditory diseases will be of great significance for the future treatment and prevention of these conditions.

To compare CNN models implemented using different strategies in the CT assessment of EGFR mutation status in patients with lung adenocarcinoma. 1,010 consecutive lung adenocarcinoma patients with known EGFR mutation status were randomly divided into a training set (n = 810) and a testing set (n = 200). The CNN models were constructed based on ResNet-101 architecture but implemented using different strategies: dimension filters (2D/3D), input sizes (small/middle/large and their fusion), slicing methods (transverse plane only and arbitrary multi-view planes), and training approaches (from scratch and fine-tuning a pre-trained CNN). The performance of the CNN models was compared using AUC. The fusion approach yielded consistently better performance than other input sizes, although the effect often did not reach statistical significance. Multi-view slicing was significantly superior to the transverse method when fine-tuning a pre-trained 2D CNN but not a CNN trained from scratch. The 3D CNN was significantly better than the 2D transverse plane method but only marginally better than the multi-view slicing method when trained from scratch. The highest performance (AUC = 0.838) was achieved for the fine-tuned 2D CNN model when built using the fusion input size and multi-view slicing method. The assessment of EGFR mutation status in patients is more accurate when CNN models use more spatial information and are fine-tuned by transfer learning. Our finding of the implementation strategy of a CNN model could be a guide to other medical 3D images applications. Compared with other published studies which used medical images to identify EGFR mutation status, our CNN model achieved the best performance in the biggest patient cohort.

The resource-aware design is of great importance for the distributed multiple-input multiple-output (MIMO) radar in military applications, where multiple missions need to be fully and simultaneously performed constrained by the resource budget. Aiming at the joint of tracking existing targets and detecting new threats, a sensor scheduling integrated with power and bandwidth allocation strategy is put forward. The predicted posterior Cramer-Rao lower bound (PCRLB) in the worst case and the probability of detection are integrated as the optimization metric. Since such a problem is NP-hard, a modified particle swarm optimization (MPSO) for the sensor selection; embed with the greedy idea for the power and bandwidth allocation, is proposed for the solution exploration. The numerical simulations demonstrate that the MPSO is capable of providing close performance to the exhaustive search based method. More importantly, it possesses a lower computational burden and achieves better results compared with multi-start local search (MSLS)-based method.

Rotenone (ROT) is an environmental neurotoxin which has been demonstrated to cause characteristic loss of dopamine (DA) neurons in Parkinson’s disease (PD). Icariin (ICA) is a flavonoid glucoside isolated from Herba Epimedii that has been shown to display neuroprotective functions. The present study evaluated protective effects of ICA on ROT-induced neurotoxicity and determined the modulation of ICA on the regulation of autophagy in vivo and in vitro. Rats were treated with ROT (1.0 mg/kg/day) with a co-administration of ICA (15 or 30 mg/kg/day) for 5 weeks. Immunohistochemical analysis showed a significant loss in DA neurons in the substantia nigra (SN) of rats treated with ROT, accompanied by an increase in the accumulation of α-synuclein and a compromised mitochondrial respiration. However, co-administration of ICA potently ameliorated the ROT-induced neuronal cell injury and improved mitochondrial function and decreased the accumulation of α-synuclein. ROT treatment resulted in a decrease in the protein expression of LC3-II and Beclin-1, and an increase in the protein level of P62, and upregulated the activation of mammalian target of rapamycin (mTOR), whereas ICA significantly reversed these aberrant changes caused by ROT. Furthermore, the neuroprotective effect of ICA was further verified in PC12 cells. Cells treated with ROT displayed an increased cytotoxicity and a decreased oxygen consumption which were rescued by the presence of ICA. Furthermore, ROT decreased the protein expression level of LC3-II, enhanced Beclin-1 expression, and activated phosphorylation of mTOR, whereas ICA markedly reversed this dysregulation of autophagy caused by ROT in the PC12 cells. Collectively, these results suggest that ICA mediated activation of autophagic flux confers a neuroprotective action on ROT-induced neurotoxicity. Keywords: Icariin, Rotenone, Neurotoxicity, Mitochondrial function, Autophagy

This review paper provides insights the into current developments in additive manufacturing (AM) techniques. The comprehensive presentations about AM methods, material properties (i.e., irradiation damage, as-built defects, residual stresses and fatigue fracture), experiments, numerical simulations and standards are discussed as well as their advantages and shortages for the application in the field of nuclear reactor. Meanwhile, some recommendations that need to be focused on are presented to advance the development and application of AM techniques in nuclear reactors. The knowledge included in this paper can serve as a baseline to tailor the limitations, utilize the superiorities and promote the wide feasibilities of the AM techniques for wide application in the field of nuclear reactors.

Endolymphatic potential (EP) is the main driving force behind the sensory transduction of hearing, and K+ is the main charge carrier. Kir5.1 is a K+ transporter that plays a significant role in maintaining EP homeostasis, but the expression pattern and role of Kir5.1 (which is encoded by the Kcnj16 gene) in the mouse auditory system has remained unclear. In this study, we found that Kir5.1 was expressed in the mouse cochlea. We checked the inner ear morphology and measured auditory function in Kcnj16–/– mice and found that loss of Kcnj16 did not appear to affect the development of hair cells. There was no significant difference in auditory function between Kcnj16–/– mice and wild-type littermates, although the expression of Kcnma1, Kcnq4, and Kcne1 were significantly decreased in the Kcnj16–/– mice. Additionally, no significant differences were found in the number or distribution of ribbon synapses between the Kcnj16–/– and wild-type mice. In summary, our results suggest that the Kcnj16 gene is not essential for auditory function in mice.