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Visually identifying effective bio-markers from human brain networks poses non-trivial challenges to the field of data visualization and analysis. Existing methods in the literature and neuroscience practice are generally limited to the study of individual connectivity features in the brain (e.g., the strength of neural connection among brain regions). Pairwise comparisons between contrasting subject groups (e.g., the diseased and the healthy controls) are normally performed. The underlying neuroimaging and brain network construction process is assumed to have 100% fidelity. Yet, real-world user requirements on brain network visual comparison lean against these assumptions. In this work, we present MV^2Net, a visual analytics system that tightly integrates multi-variate multi-view visualization for brain network comparison with an interactive wrangling mechanism to deal with data uncertainty. On the analysis side, the system integrates multiple extraction methods on diffusion and geometric connectivity features of brain networks, an anomaly detection algorithm for data quality assessment, single- and multi-connection feature selection methods for bio-marker detection. On the visualization side, novel designs are introduced which optimize network comparisons among contrasting subject groups and related connectivity features. Our design provides level-of-detail comparisons, from juxtaposed and explicit-coding views for subject group comparisons, to high-order composite view for correlation of network comparisons, and to fiber tract detail view for voxel-level comparisons. The proposed techniques are inspired and evaluated in expert studies, as well as through case analyses on diffusion and geometric bio-markers of certain neurology diseases. Results in these experiments demonstrate the effectiveness and superiority of MV^2Net over state-of-the-art approaches.

Intentional electromagnetic interference is a serious threat to the safety of electronic devices. Multiple electromagnetic pulses will be coupled and transmitted to electronic devices through the cables. Accumulative effects are generated, which make it easier for damage to occur in the electronic devices. In this article, the working principle of micro-silicon acceleration sensors is introduced. The accumulative effects of multiple pulses on acceleration sensors is studied by a large number of injection experiments. The accumulation trends of multiple pulses with different pulse numbers and intervals are analyzed. The damaged structures inside abnormal sensor amplifiers were observed via optical microscopy and scanning electron microscopy. The experimental results show that the accumulative effect is strengthened with increased pulse number or decreased pulse interval, and the threshold voltage for multiple pulses on the acceleration sensor decreases. The threshold voltage for a single pulse is 321.57 V. When the pulse interval is 1 μs and the pulse number is 5, the threshold voltage for multiple pulses is 163.42 V, which is reduced by 49.12% compared with a single pulse. These results provide a reference for the damage design of electromagnetic pulse weapons.

In this study, the self-powered photodetector based on photovoltaic effect was obtained from BixFeO3 (x = 1, 1.3, 1.5, 1.7) films. In order to study the origin of the photovoltaic effect, the self-polarized structure and defect distribution of the films were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, and piezoelectric force microscopy. In addition, the responsivity (1515 μA/W) and detectivity (1.35Χ1011 Jones) are achieved in the Bi1.5FeO3 film at zero bias after receiving 0.2 mW/cm2 of irradiation light in the wavelength of 500 nm. The rise and decay time of the photocurrent without bias reaches ∼6 ms and ∼15 ms respectively, and did not weaken after a 11 min cycling test. The self-polarized structure and defect dipoles play an important role in the photovoltaic effect of BixFeO3 self-powered photodetector. This work lays a foundation for applications in BixFeO3 self-powered photodetection.

Recommendation systems are gaining popularity with the proliferation of the Internet of People (IoP). The popularity and use of online social networks facilitate integrating these social relationships with recommender systems under a single framework of IoP. This article proposes a new approach for item recommendation based on the diffusion method that combines user relationships in social networks with user-item relationships derived from the IoP. Especially, a resource redistribution process is explored in the user-object network that gives mass diffusion a higher recommendation accuracy and heat conduct a greater diversity by considering the social degree of users whilst calculating the user degree in the network. A tuning parameter is introduced to adjust the weight of resources that the objects finally receives from users based on their social relationships. Finally, extensive experiments conducted on the real-world datasets which contain friendship relationships, demonstrate the efficiencies of our proposed method in achieving notable performance improvements in terms of the recommendation accuracy, service diversity, and practical dependability.

Aims: Lipoprotein (a) deposition in coronary vascular plaques and cerebral vessels is a recognized risk factor for cardiovascular disease, and research supports its role as a “repair factor” in vascular walls weakened by vitamin C deficiency. Background: Humans depend on dietary vitamin C as an important antioxidant and as a cofactor in collagen synthesis, yet are prone to vitamin C deficiency. The brain is the one with the highest vitamin C content, owing to its high oxygen consumption and oxidative stress. It has been shown that brain aging is accompanied by accumulated oxidative damage, which can lead to memory decline and neurological diseases. Objective: Our transgenic mouse, Gulo (-/-); Lp(a)+, presents a unique model for the study of key aspects of human metabolism with respect to a lack of internal vitamin C synthesis and the production of human lipoprotein(a). Methods: This mouse model was used in our study to investigate the effects of prolonged intake of low and high levels of vitamin C, at different ages, on oxidative damage, cholesterol levels and lipoprotein( a) deposition in the brain. Result: The results show that a long-term high vitamin C intake is important in maintaining brain cholesterol homeostasis and preventing oxidative damage in Gulo(-/-);Lp(a)+ mice as they age. Moreover, we observed that the formation of brain lipoprotein(a) deposits was negatively correlated with brain level of vitamin C, thereby confirming its role as a stability factor for an impaired extracellular matrix. Conclusion: Our study emphasizes the critical role of vitamin C in protecting brain health as we age. Other: Our findings show that optimal vitamin C intake from early life to old age is important for brain health as it prevents oxidative stress damage and maintains cholesterol homeostasis in the brain. More importantly, the negative correlation between brain ascorbic levels and the formation of Lp(a) deposit on the choroid plexus further emphasizes the critical role of vitamin C in protecting brain health throughout the normal aging process.

This letter presents a high-performance scandium-doped aluminum nitride (Sc x Al 1-x N, x = 9.5%) piezoelectric MEMS hydrophone. The doping of Sc increases the piezoelectric constants of the piezoelectric sensing layer and hence results in better receive sensitivity for the ScAlN-based piezoelectric MEMS hydrophone. The sensing cells of the MEMS hydrophone sensor are designed in a bioinspired honeycomb structure for achieving high fill-factor and thus a large receive sensitivity. The top electrodes of the sensing cells are split into the inner and outer sections with optimized size ratios for differential readout, which further enhances the sensor’s sensitivity. The receive sensitivity is improved even further by reducing the top oxide thickness on the sensing diaphragm. The best measured receive sensitivity of the reported MEMS hydrophone with differential readout is −164.5 dB (re: 1 V/ $\mu $ Pa). An equivalent noise density as low as 44 dB (re: $1 ~\mu $ Pa/ $\surd $ Hz) at 1kHz is achieved. These metrics are much better than those of state-of-the-art bulk piezoceramic hydrophones as well as other reported piezoelectric MEMS hydrophones.

Background & aims Immunotherapy with hepatitis B virus (HBV)-specific TCR redirected T (HBV-TCR-T) cells in HBV-related hepatocellular carcinoma (HBV-HCC) patients after liver transplantation was reported to be safe and had potential therapeutic efficacy. We aim to investigate the safety of HBV-TCR-T-cell immunotherapy in advanced HBV-HCC patients who had not met the criteria for liver transplantation. Methods We enrolled eight patients with advanced HBV-HCC and adoptively transferred short-lived autologous T cells expressing HBV-specific TCR to perform an open-label, phase 1 dose-escalation study (NCT03899415). The primary endpoint was to evaluate the safety of HBV-TCR-T-cell therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) during the dose-escalation process. The secondary endpoint was to assess the efficacy of HBV-TCR-T-cell therapy by evaluating the anti-tumor responses using RECIST criteria (version 1.1) and the overall survival. Results Adverse events were observed in two participants among the 8 patients enrolled. Only one patient experienced a Grade 3 liver-related adverse event after receiving a dose of 1 × 105 HBV-TCR-T cells/kg, then normalized without interventions with immunosuppressive agents. Among the patients, one achieved a partial response lasting for 27.7 months. Importantly, most of the patients exhibited a reduction or stabilization of circulating HBsAg and HBV DNA levels after HBV-TCR-T-cell infusion, indicating the on-target effects. Conclusions The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC. Clinical trials registration This study was registered at ClinicalTrials.gov (NCT03899415).

This study aimed to compare the sedation and analgesic effects of butorphanol alone and butorphanol in combination with dexmedetomidine on dressing changes in adult burn patients.From June 2016 to May 2019, 44 adult burn patients from our department were enrolled in this prospective, double-blinded study. Their total burn surface area (TBSA) varied from 10% to 30%; and the depth of burn injury ranged from second degree to third degree. The patients were randomized into two groups. In the control group, butorphanol combined with saline was injected into the body via venous route during dressing change. In the observation group, butorphanol in combination with dexmedetomidine was injected. The variation in mean blood pressure, heart rate, respiratory rate, and peripheral oxygen saturation were recorded at various time-points of the procedure. Visual Analogue Scale (VAS) of pain and Ramsay Sedation Scores (RSS) were also recorded at different time points. Consumption of butorphanol and adverse events in these two groups were compared.The mean blood pressure and heart rate were significantly decreased in the observation group before butorphanol injection (P0.05) and before the dressing change (P0.05). The respiratory rates and peripheral oxygen saturation of these two groups showed no significant differences at all time points (P0.05). Patients in the observation group had lower VAS scores during dressing change (P0.05). The RSS Scores in the observation group were higher than those in the control group during (P0.05) and after the dressing change (P0.05). The consumption of butorphanol was more in the control group (P0.05), and the adverse events recorded in the control group were higher (P0.05).Butorphanol combined with dexmedetomidine can reduce analgesic use of butorphanol during dressing change. This combination resulted in a higher sedation score and fewer adverse effects.

This article investigates the dependence of transmitting sensitivity on the top electrode design of piezoelectric micromachined ultrasonic transducers (PMUTs). Two typical top electrodes, namely inner electrode (IE) and outer electrode (OE), are designed and fabricated. The measured transmitting velocities of the fabricated PMUTs at resonance under a drive voltage of 5 $\text{V}_{\mathrm {p-p}}$ (peak-to-peak) are 15.36 mm/s for the IE design and 20.67 mm/s for the OE design with a circular diaphragm and 16.62 mm/s for the IE design and 22.18 mm/s for the OE design with a hexagonal diaphragm. The OE design demonstrates a transmitting velocity improvement of 34.57% for the circular diaphragm and 33.45% for the hexagonal diaphragm. The improvement is due to the fact that the OE design shows higher quality factor ( ${Q}$ ) than the IE counterpart. Moreover, the resonant frequency of the OE design is higher than that of the IE design, which results in a larger acoustic pressure output and hence higher transmitting sensitivity. This work highlights an effective and simple approach for PMUTs to achieve high transmitting sensitivity, which is an important parameter in the applications that require large sound pressures, such as fingerprint imaging, gesture recognition, and ranging.

Chain-die forming can be used to manufacture Advanced High Strength Steels (AHSS) channel components. Flange wrinkling is one of typical defects for chain-die formed products. The purpose of this paper is to investigate the cause of flange wrinkling in chain-die forming of AHSS and to propose a potential method to suppress it. A hat channel product with a curved axis is formed as a benchmark to illustrate the mechanism of flange wrinkling in chain-die forming. When forming such a profile, longitudinal compressive strain of the sheet metal is geometrically necessary, and the compression has to be achieved by plastic wrinkling due to the insufficient restricted boundary condition. Finite element models are established to better understand the complex interaction between the tools and plate. An initial imperfection calculated from the differential equilibrium equations for elastic plates with small deflections is implemented into the finite element model to predict occurrence of the flange wrinkling. In order to eliminate the wrinkling defect, an M-shaped die design is proposed, which intends to provide additional restriction to the sheet metal and increase longitudinal and transversal tension. A three-factor, three-level Design of Experiment (DOE) scheme for the M-shaped die design is conducted. The DOE results show that a benign wrinkling always corresponds to a larger compressive strain and the width of the ears for M-shaped dies is a decisive factor to suppress wrinkling. The verification experiments show that the plastic flange wrinkling is completely eliminated by employing the proposed method.

Rationale:Timely inhibition of inflammation and initiation of resolution are important to repair injured tissues. MST1/2 (mammalian STE20-like protein kinase 1/2) acts as a regulator of macrophage-associated immune responses to bacterial infections. However, the role of MST1/2 in regulating macrophage phenotype and function in myocardial infarction (MI) remains unclear.Objective:To determine the function and underlying mechanism of macrophage MST1/2 in cardiac repair post-MI.Methods and Results:UsingLysMCre-mediatedMst1/2-deficient mice, we found that MST1 deficiency exacerbated cardiac dysfunction after MI. Single-cell RNA sequencing assay indicated that the effect was attributed to a shift of macrophage subtypes from those expressingCxcl2andCd163towardCcl2andCcl4expression. Mass spectrometry identified LTB4 (leukotriene B4) as the lipid mediator that was upregulated in the absence of MST1. We found that MST1 phosphorylated 5-LOX (5-lipoxygenase) at its T218 residue, disrupting the interaction between 5-LOX and 5-LOX-activating protein, resulting in a reduction of LTB4 production. In contrast, a 5-LOXT218Avariant showed no response to MST1. Moreover, treatment of peritoneal macrophages with LTB4 or medium conditioned byMst1-deficient macrophages resulted in highCcl2andCcl4expression and lowCxcl2andCd163expression, except when the cells were co-treated with the BLT1 (LTB4 receptor 1) antagonist CP105696. Furthermore, CP105696 ameliorated cardiac dysfunction inLysMCre-mediatedMst1/2-deficient mice and enhanced cardiac repair in wild-type mice treated with XMU-MP-1 (4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide) after MI.Conclusions:Taken together, our results demonstrate that inhibition of MST1/2 impaired post-MI repair through activating macrophage 5-LOX–LTB4–BLT1 axis.

With the increase of the number of wireless devices, the amount of data that needs to be transmitted in wireless network is also increasing rapidly, which brings great burden to wireless transmission. This means device put forward a high requirement for end-to-end wireless communication performance. Therefore, it is very important to further improve the transmission performance. In this paper, we propose the optimal strategy by combining the coherent beamforming (CB) technique and the successive interference cancellation (SIC) technique for improving the performance of wireless device communication. CB technique can be used for expanding the communication range of wireless transmitters, and SIC technique can be used for improving the receiving ability of wireless receiver. We first give the mathematical model based on CB–SIC, find this model is NP-hard in general and cannot be solved directly. Therefore, we design a heuristic algorithm to obtain an approximate optimal solution. In simulation, we compare CB–SIC wireless network with CB only, SIC only, and interference avoidance network. Simulation results show that the algorithm can improve the end-to-end communication performance of wireless network and data throughput has been greatly improved.

Objective. To explore the predictive value of mean platelet volume (MPV) and plasma N-terminal probrain natriuretic peptide (NT-ProBNP) combined with a simplified Geneva scale for the prognosis of acute pulmonary embolism (APE). Methods. The clinical data of 68 patients with APE admitted to our hospital from October 2017 to October 2019 were collected. According to the prognosis, the patients were divided into a good prognosis group (n = 45) and a poor prognosis group (n = 23). The clinical data, laboratory clinical indexes, and simplified Geneva scale scores were recorded for the two groups. The risk factors of poor prognosis were analyzed by binary multivariate logistic regression analysis; the predictive ability of each index on the prognosis of patients with APE was analyzed by the ROC curve. Results. The incidences of deep vein thrombosis, diabetes, and hyperlipidemia in the poor prognosis group were higher than those in the good prognosis group ( P < 0.05 ). PLT, platelet distribution width (PDW), MPV, and plasma NT-ProBNP in the poor prognosis group were higher than those in the good prognosis group ( P < 0.05 ). The simplified Geneva scale score of the poor prognosis group was higher than that of the good prognosis group ( P < 0.05 ). PDW, MPV, plasma NT-ProBNP, and simplified Geneva scale were all independent risk factors for the poor prognosis of APE patients ( P < 0.05 ). The AUC of MPV in predicting the prognosis of APE patients was 0.818 (95% CI: 0.712–0.925). When the optimal cutoff value was 0.571, the sensitivity was 77.1%, and the specificity was 80.0%. The AUC of plasma NT-ProBNP in predicting the prognosis of APE patients was 0.762 (95% CI: 0.634–0.891). When the optimal cutoff value was 0.475, the sensitivity was 71.5%, and the specificity was 76.0%. The AUC of the simplified Geneva scale in predicting the prognosis of APE patients was 0.749 (95% CI: 0.618–0.879). When the optimal cutoff value was 0.469, the sensitivity was 82.9%, and the specificity was 64.0%. The AUC of MPV and plasma NT-ProBNP combined with the simplified Geneva scale in predicting the prognosis of APE patients was 0.907 (95% CI: 0.826–0.988). When the optimal cutoff value was 0.726, the sensitivity was 88.6%, and the specificity was 84.0%. Conclusion. MPV, plasma NT-ProBNP, and simplified Geneva scale have a certain predictive value for the prognosis of APE. Compared with a single index, the combination of the three indexes has a significant improvement in predicting the prognosis of APE and has better clinical value.

The aim of this study was to determine whether carbohydrate antigen 72–4 (CA72–4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72–4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72–4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72–4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72–4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; P for trend< 0.05). CA72–4 also showed a positive correlation with UACR (r=0.288, P< 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72–4 levels (P for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72–4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72–4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.

Although bundling in public–private partnership (PPP) projects fosters cost savings in the provision of public services, such savings might come at the expense of social benefits due to the low qua...

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system, accounting for approximately 10–15% of kidney cancers in the world. Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with the highest mortality. Surgical resection or puncture of tumor tissue is still an important clinical treatment and diagnosis of ccRCC, but its high recurrence rate and poor prognosis often lead to the short survival period of patients. Hence, the development of novel molecular biomarkers is of great clinical importance. miRNAs are endogenous non-coding small RNAs with a length of 19–24 nt. A growing number of studies have reported that miRNAs, as proto-oncogenes or tumor suppressor genes, play a key role in the development of ccRCC and might be effective diagnostic and prognostic biomarkers. In addition, miRNAs can also predict the efficacy of treatment drug, thus improving the accuracy of clinical medication. Furthermore, non-invasive detection of miRNAs or extracellular vesicles (EV) in body fluids has better convenience and repeatability, which shows remarkable advantages compared with tissue detection. In this review, we summarized the typical miRNAs reported in recent years and place emphasis on evaluating miRNAs in different body fluids to provide reference for the clinical diagnosis and prognosis of ccRCC in the future.

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.

This study examined the visual characteristics of drivers with color weakness to improve their safety while driving. Significantly affected by the traffic environment, drivers with color weakness are not able to recognize traffic lights rapidly and accurately, which endangers traffic safety. In the first part of the research, through a static visual recognition test of color vision using the orthogonal method, the study explored the influence of light intensity, visual recognition distance, and color weakness type on the perception of traffic light colors by participants with color weakness. In the second part, a dynamic visual recognition test of color vision was conducted through simulating the driving environment of urban roads. Eye movement indexes between participants with color weakness and those with normal vision were analyzed by means of different vehicle speeds and time periods. The results indicated that the type of color weakness was the dominant factor affecting visual recognition of traffic lights. The eye movements of participants with deuteranomaly were close to those of people with normal vision, whereas the eye movement index of those with protanomaly and dyserythrochloropsia were significantly different. Distraction, slower responses, and higher color recognition error rates for the traffic lights were major characteristics—all representing risks that increase at night. To reduce the probability of road traffic injury, the driving safety of people with color weakness should be addressed.

Based on the insights into the phenomenon of bound states in the continuum, a novel approach utilizing the momentum-space polarization morphologies of periodic structures to generate vortex beams (VBs) has been proposed. Such periodic structures modulate beams in a nonlocal way and require no precise alignment. However, the efficiency of such an approach has not been analyzed in detail, and the efficiency in previous realizations is far from optimized. Here, we analyze the factors affecting the efficiency of nonlocal VB generation. We show that the maximal efficiency cannot exceed 25% if the periodic structure carries only singlet resonances. To go beyond this limit, we propose two approaches to improve efficiency. We theoretically analyze the mechanisms and verify the approaches by full-wave simulations. Both of the approaches serve to improve the generation efficiency by several folds.

Sub-nanometer armchair graphene nanoribbons (GNRs) with moderate band gap have great potential towards novel nanodevices. GNRs can be synthesized in the confined tubular space of single-walled carbon nanotubes (SWCNTs), in which precursor molecules have been specifically designed to form the GNRs with certain width and edge. However, it is still unexplored how the diameter and metallicity of SWCNTs influence the synthesis of the GNRs. Herein, we applied a series of SWCNTs with different average diameters to study the diameter-dependent synthesis of GNRs. By using Raman spectroscopy and transmission electron microscopy, we found that the width of the GNRs can be tailored by the diameter of the SWCNTs. Especially, the SWCNTs with average diameter of 1.3 nm produced 6 and 7 armchair GNRs with the highest yield, which can be well explained by considering the width of the GNRs and van der Waals radius of hydrogen and carbon atoms. In addition, semiconducting and metallic SWCNTs produced GNRs with different yields, which could attribute to different diameter distributions and density of defects. These results enable the possibility of a high-yield production of certain armchair graphene nanoribbons in large scale, which would benefit future applications as semiconductor with sub-nanometer in width.

The recent materialization carbyne confined to double-walled carbon nanotubes represents a major breakthrough in materials science but the control of its properties remains a major challenge. Here, localized photothermal heating through laser annealing and the possibility to perform Raman spectroscopy in-situ allow fabricating confined carbyne with tailored properties. Transmission electron microscopy shows the confined carbyne can reach about 10 nm in length. Evident interaction between the nanotubes and the confined carbyne alters the tube's diameter. Furthermore, the mechanism to tailor the properties of the confined carbyne could be associated to its corresponding Raman mode. The evolution of the synthesis constricted to the tube under increasing laser power can be monitored step by step from the moment the growth starts until a knock-off threshold is reached. Photothermal annealing represents a real possibility to synthesize carbyne confined to single-chirality carbon nanotubes, which is not entirely feasible otherwise.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field.

With the development of high-speed railways (HSRs), people's lives have become more convenient. At the same time, people are demanding more data services on trains in terms of wireless communications and mobile computation. Recently, Multi-access Edge Computing (MEC), a new computing paradigm, has the great potential to improve the user experience of computing services by placing the cloud infrastructures closer to end-users so that users can offload their computation-intensive and delay-sensitive tasks to the edge servers. In this paper, we concentrate on finding proper data routing paths for each offloaded task and each process result, with the objective of maximizing the network throughput by serving as many tasks as possible while meeting the MEC network resource constraints and the user demand constraints within a finite time horizon of equal time slots. It is challenging because of the unspecific data volume of an offloaded task and handovers of task offloading procedures that may frequently occur. Thus, we first investigate the impact of handovers in uplinks and downlinks. Then we propose a graph-based model to portray the resource availability in the network. Furthermore, a heuristic algorithm is devised, which finds a set of single-source-single-destination delay-constrained shortest paths in a series of auxiliary graphs. Finally, we perform an empirical evaluation of the proposed algorithm by simulations. The simulation results show that the proposed algorithm could achieve a higher network throughput than the other two benchmark heuristics.

To the authors' knowledge, there is no current consensus regarding the optimal interprocedural interval for patients who have undergone bilateral total knee arthroplasty (BTKA). The purpose of this study is to evaluate complication rates and functional outcome in patients who have undergone BTKA (simultaneous or sequential at different time intervals), and to determine an optimal time frame for the second knee. Data from 315 patients who were able to tolerate simultaneous BTKA according to the anaesthesiologist’s preoperative assessment between 2016 and 2020 were analysed retrospectively. According to the operative time interval, they were divided into simultaneous, ≤ 1-month sequential, 1- to 3-month sequential, and ≥ 3-month sequential BTKA groups. The primary outcomes were revision and readmission rates during the follow-up period, and the secondary outcomes were hospital length of stay (LOS), transfusion and postoperative complications. There was no difference in the implant survival or readmission rate between the groups (p > 0.05). Multivariable linear regression showed that interprocedural interval and body mass index (BMI) affected LOS; the LOS of simultaneous BTKA was the shortest (p

Psychostimulant drugs, such as cocaine, inhibit dopamine reuptake via blockading the dopamine transporter (DAT), which is the primary mechanism underpinning their abuse. Atypical DAT inhibitors are dissimilar to cocaine and can block cocaine- or methamphetamine-induced behaviors, supporting their development as part of a treatment regimen for psychostimulant use disorders. When developing these atypical DAT inhibitors as medications, it is necessary to avoid off-target binding that can produce unwanted side effects or toxicities. In particular, the blockade of a potassium channel, human ether-a-go-go (hERG), can lead to potentially lethal ventricular tachycardia. In this study, we established a counter screening platform for DAT and against hERG binding by combining machine learning-based quantitative structure-activity relationship (QSAR) modeling, experimental validation, and molecular modeling and simulations. Our results show that the available data are adequate to establish robust QSAR models, as validated by chemical synthesis and pharmacological evaluation of a validation set of DAT inhibitors. Furthermore, the QSAR models based on subsets of the data according to experimental approaches used have predictive power as well, which opens the door to target specific functional states of a protein. Complementarily, our molecular modeling and simulations identified the structural elements responsible for a pair of DAT inhibitors having opposite binding affinity trends at DAT and hERG, which can be leveraged for rational optimization of lead atypical DAT inhibitors with desired pharmacological properties.

Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, has a very poor prognosis. With increasing knowledge of tumor molecular biology, targeted therapies are becoming increasingly integral to comprehensive GBM treatment strategies. mTOR is a key downstream molecule of the PI3K/Akt signaling pathway, integrating input signals from growth factors, nutrients, and energy sources to regulate cell growth and cell proliferation through multiple cellular responses. mTOR/PI3K dual-targeted therapy has shown promise in managing various cancers. Here, we report that taxifolin, a flavanone commonly found in milk thistle, inhibited mTOR/PI3K, promoted autophagy, and suppressed lipid synthesis in GBM. In silico analysis showed that taxifolin can bind to the rapamycin binding site of mTOR and the catalytic site of PI3K (p110α). In in vitro experiments, taxifolin inhibited mTOR and PI3K activity in five different glioma cell lines. Lastly, we showed that taxifolin suppressed tumors in mice; stimulated expression of autophagy-related genes LC3B-II, Atg7, atg12, and Beclin-1; and inhibited expression of fatty acid synthesis-related genes C/EBPα, PPARγ, FABP4, and FAS. Our observations suggest that taxifolin is potentially a valuable drug for treating GBM.

Aiming at the problem of the serious deformation of the mining roadways in the trapezoidal section of the coal mine, the method of combining theoretical analysis and field application is used to study the surrounding rock control method of the trapezoidal roadways. The conformal mapping function of the trapezoidal roadways is calculated by the theory of complex change, and then from the analytical solution of the tangential stress distributed in the surrounding rock of trapezoidal roadways which is under the influence of the bidirectional unequal pressure, homogeneous, isotropic, and elastic rock mass is obtained. Research studies show that the roof-stress distribution of the trapezoidal roadways is uniform and the confining pressure is small, while the two sidewalls and the floor are opposite. The stress distribution of the two sidewalls and the floor varies greatly, and the stress concentration factor is large. The top corner of the trapezoidal roadways is basically not affected by stress concentration, but the stress concentration coefficient at the bottom corner is relatively large, and reinforcement measures are required in the roadway support. Based on the aforementioned research results, the multisupport scheme of “bolting with wire mesh and anchor cable + W-type steel belt + joist steel shed support + anchor cable grouting” was proposed to the surrounding rock of trapezoidal roadways with large stress caused by mining influence, thus solving the actual mining problem.

The Lanzhou-Xinjiang (Lan-Xin) high-speed railway is one of the principal sections of the railway network in western China, and signal equipment is of great importance in ensuring the safe and efficient operation of the high-speed railway. Over a long period, in the railway operation and maintenance process, the railway signaling and communications department has recorded a large amount of unstructured text information about equipment faults in the form of natural language. However, due to irregularities in the recording methods of these data, it is difficult to use directly. In this paper, a method based on natural language processing (NLP) was adopted to analyze and classify this information. First, the Latent Dirichlet Allocation (LDA) topic model was used to extract the semantic features of the text, which were then expressed in the corresponding topic feature space. Next, the Support Vector Machine (SVM) algorithm was used to construct a signal equipment fault diagnostic model that reduced the impact of sample data imbalance on the classification accuracy. This was compared and analyzed with the traditional Naive Bayes (NB), Logistic Regression (LR), Random Forest (RF), and K-Nearest Neighbor (KNN) algorithms. This study used signal equipment failure text data from the Lan-Xin high-speed railway to conduct experimental analysis and verify the effectiveness of the proposed method. Experiments showed that the accuracy of the SVM classification algorithm could reach 0.84 after being combined with the LDA topic model, which verifies that the natural language processing method can effectively realize the fault diagnosis of signal equipment and has certain guiding significance for the maintenance of field signal equipment.

Chain-die forming is an emerging sheet metal technique for manufacturing advanced high strength steel (AHSS) products. Springback and longitudinal bow are two of the major shape defects in gradual forming. In this study, the springback and longitudinal bow of AHSS in chain-die forming of hat and U profiles are investigated through experiment and finite element simulation. The disparity of springback along the longitudinal direction and disparate longitudinal bow signifies complex deformation processes of chain-die forming. Finite element simulation of the chain-die forming process gives an insight into the formation of non-uniform springback and longitudinal bow. The gradual forming process by one die block after another causes bending and reverse-bending deformation in the web area and the redundant deformation of the sheet metal, which further leads to non-uniform bending moment and accumulated stresses along the longitudinal direction. At the same time, the redundant deformation will also result in the longitudinal strain on the edge, while the downhill deformation decreases the maximum longitudinal strain at the edge and introduces the longitudinal strain on the web. The different non-uniform longitudinal strain distribution along the transversal direction causes disparate longitudinal bow behaviors for chain-die formed AHSS hat and U profiles, downward bowing and upward bowing respectively. By the established model, the disparate springback and longitudinal bow behavior can be determined, which also contribute to the process design for chain-die formed AHSS products.

Objectives Previous literature has shown that chronic diseases and psychological distress are correlated. However, the mediating and moderating mechanisms underlying this relationship have not been sufficiently studied. The purpose of this study was to explore the role played by activities of daily living (ADL) and perceived social support. Method Face-to-face questionnaire-based surveys were conducted with 3250 valid participants (age ≥60 years). Participants were assessed using the Barthel Index, Perceived Social Support Scale, and Depression Anxiety Stress Scale-21. Results 1) Chronic diseases had a significant direct effect on psychological distress in older adults; 2) the relationship between chronic diseases and psychological distress was partially mediated by ADL; and 3) the impact of chronic diseases on psychological distress was significantly moderated by perceived social support. More importantly, perceived social support was a protective factor that could effectively alleviate the adverse effects of chronic diseases on psychological distress. Conclusion The results add to the existing literature by uncovering the underlying mechanisms between chronic diseases and mental health. These findings have implications for early intervention and prevention of mental health problems in older adults.

Androgen receptor (AR) is a major survival factor for prostate cancer. Inflammation is implicated in many cancer types, including prostate cancer. Activation of MAP3K7 (also termed TAK1) and downstream IκB kinase β (IKKβ) by proinflammatory cytokines such as TNFα stimulates NF-κB survival pathways. Paradoxically, MAP3K7 is often deleted in human prostate cancer. Here, we demonstrate that AR protein expression is lower in inflammatory tumor areas compared with non-inflammatory tissues in patients with prostate cancer. Map3k7 knockout increased AR protein levels and activity in the mouse prostate, and MAP3K7 and AR protein levels were inversely correlated in prostate cancer patient specimens. TNFα treatment increased AR protein ubiquitination and proteasomal degradation. Mechanistically, activation of IKKβ by TNFα induced phosphorylation and TRCP1/2 E3 ligase–mediated polyubiquitination and degradation of AR protein. TNFα suppressed prostate cancer proliferation, which could be rescued by blockade of AR degradation. These findings reveal a previously unrecognized tumor suppressive function of the inflammation-activated MAP3K7–IKKβ axis in degrading AR protein. Moreover, they suggest that aberrant elevation of AR protein could be a prognostic biomarker and therapeutic target for MAP3K7-deficient prostate cancer. Significance: This study identifies that MAP3K7–IKKβ signaling plays a tumor-suppressive role in prostate cancer by degrading AR, revealing potential prognostic and therapeutic strategies for MAP3K7-deficient tumors.

To analyze the effects of freeze-thaw cycles and confining pressure on the mechanical properties of red sandstone, through freeze-thaw cycles and triaxial compression tests, full stress-strain curves of different freeze-thaw cycles and different confining pressures were obtained. The degradation degree of red sandstone was quantitatively considered from different mechanical parameters of ultimate stress, elastic modulus, and Poisson’s ratio. Based on summarizing the characteristics of rock under freeze-thaw and load, the total damage variable of rock was determined by the reasonable measurement of freeze-thaw damage variable and load damage variable, and a damage constitutive model under freeze-thaw and load was established. The research showed that the freeze-thaw cycles aggravate the degree of rock damage deterioration, the rock stiffness and strength were reduced, and the characteristics of plastic deformation and ductile failure were more obvious. The confining pressure inhibited red sandstone internal damage, and with the increase of confining pressure, the stiffness and strength and the plastic characteristics were increased. In the overall trend, the mechanical parameters had different sensitivity to the degradation effect of freeze-thaw cycles and confining pressure. Regardless of the increase in the number of freeze-thaw cycles or confining pressure, the strain softening modulus tended to decrease gradually, and red sandstone plastic damage became more obvious after the stress peak. The total damage evolution path of red sandstone reflected the nonlinear influence of freeze-thaw and load on the total damage propagation. The research results provide theoretical support for the improvement of the technology of the effluent coal rock in Balasu Coal Mine.

The understanding of land-use and land-cover change (LUCC) is crucial for the study of global climate change and the terrestrial ecological environment. Sandy land is an important component of the ...

Background Salmonella enterica is a zoonotic pathogen of substantial concern to human and animal health and is a leading cause of morbidity and mortality in people worldwide. Loop-mediated isothermal amplification (LAMP) technology is a new type of nucleic acid amplification technology, which has the characteristics of high specificity, high sensitivity, simple operation, convenience, and low cost. This study aims to establish a rapid detection method for Salmonella based on LAMP technology. Methods Primers were designed for Salmonella's specific conservative invA gene. Through primer screening and optimization of reaction conditions, and a LAMP method for detecting Salmonella with real-time fluorescence and visual observation results was established. The sensitivity and specificity of the method were assessed, and the accuracy was evaluated through the testing of Salmonella-contaminated and non-contaminated clinical samples. Results The optimal reaction temperature of LAMP was 60-65 °C, and the optimal reaction time was 25-30 minutes. The detection limits of real-time fluorescence and visual observation were both 1.4 pg/µL. There was no cross-reactivity observed with 22 non-Salmonella species, and the specificity was 100%. Additionally, 30 samples contaminated with Salmonella, 30 samples not contaminated with Salmonella, and 8 clinical samples identified as positive by bacterial culture and microbial mass spectrometry were tested. The positive coincidence rate of the detection system was 97.4% by real-time fluorescence and 89.5% by visual observation, the negative coincidence rate was 100%, and the total coincidence rate was 98.5% and 94.1%, respectively. Conclusions In the scene of infection, primary hospital, disaster area treatment and other scenarios, the conditions of environment, equipment and personnel was limited, therefore, the established real-time fluorescence and visual lamp method can provide a powerful means for the rapid detection of Salmonella.

Precancerous lesions of gastric cancer are classified by the WHO (2019) into low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia (HGIN), and eminence lesions are adenomas. Gastric adenoma is a benign tumor of the stomach, which is more commonly located in the gastric antrum and gastric body. Usually, there is no obvious clinical manifestation. A 48-year-old man with intermittent abdominal bloating for four months to our hospital. Esophagogastroduodenoscopy revealed a 1.2 cm superficial elevated lesion in the anterior wall of the upper gastric body. The lesion had a whitish color and coarse surface. Biopsy revealed a low-grade intraepithelial neoplasia. Narrow-band imaging with magnifying endoscopy revealed a clear demarcation line with an irregular microsurface pattern. Detection of Helicobacter by the 13C-urea breath test was positive. The patient underwent an endoscopic resection. Histological results revealed gastric adenoma with mixed fundic and pyloric mucosa type, with HGIN. The lesion contained three types of cells: pyloric gland, fundus gland and foveolar epithelium. Helicobacter pylori detection was negative in the lesion. The present case demonstrates a new histological subtype of gastric adenoma. To the best of our knowledge, this is the first case report of gastric adenoma with mixed fundic and pyloric mucosa cell types.

Aim: Glycopyrrolate (GLY) has been widely used to treat chronic obstructive pulmonary disease (COPD). Recent technical advancement significantly improves the drug delivery efficiency. In a clinical dose-range determination study via electronic nebulizer, the starting dose was as low as 3-μg, thus, a bioanalytical method capable of measuring down to sub-pg/ml or fg/ml level was required to characterize pharmacokinetics of GLY. Methods: A straightforward solid-phase extraction coupled with reversed-phase LC-MS/MS method was successfully developed to quantify plasma GLY concentrations of 0.500–250 pg/mL. MS/MS detection was at ESI+ by monitoring m/z 318.3→116.1 for GLY and 321.3→119.1 for the internal standard GLY-d3. Results and Conclusion: The method was validated with adequate selectivity, intra- and inter-assay precision and accuracy, dilution linearity, and sufficient stability for measuring GLY in human plasma. This method has been used for sample analysis of a clinical dose-range finding study (3–50 µg twice daily doses via an electronic nebulizer). The assay exhibited good precision, accuracy, and robustness. Pharmacokinetic analysis showed good dose proportionality over the studied dose range, where Cmax was found to be Y = 1.354*X + 1.968 (r2 = 0.9984), and AUC0-12 h was Y = 4.661*X + 23.32 (r2 = 0.9976). The study clearly demonstrated the importance of an ultrasensitive (500 fg/ml LLOQ) method.

Objectives To explore the correlations among social isolation and symptoms of anxiety and depression among patients with breast cancer in China and to further verify the mediating role of social support in social isolation and symptoms of depression or anxiety. Design A cross‐sectional survey. Settings The cluster sampling method was conducted for 456 female inpatients diagnosed with breast cancer at the Tumor Hospital Affiliated of Harbin Medical University from April 2019–September 2019. Methods Pearson correlation analysis was used for identifying correlations among all the variables. Mediation effect analysis was used to examine the role of social support in social isolation and symptoms of depression or anxiety. Results The results showed a prevalence of 73.26% and 70.44% for anxiety and depression symptoms in patients with breast cancer, respectively. Anxiety was significantly negatively correlated with social support (r = −.334, p

Aims To develop and internally validate a nomogram to predict the risk of death within 6 months of onset of stroke in Chinese. Identifying risk factors with potentially direct effects on the nomogram will improve the quality of risk assessment and help nurses implement preventive measures based on patient‐specific risk factors. Design A retrospective study. Methods We performed a least absolute shrinkage and selection operator (LASSO) regression modelling and multivariate logistic regression analysis to establish a prediction model of death risk in stroke patients within 6 months of onset. LASSO and time‐dependent Cox regression models were further used to analyse the 6‐month survival of stroke patients. Data were collected from 21 October 2013–6 May 2019. Results The independent predictors of the nomogram were Barthel index (odds ratio (OR) = 0.980, 95% confidence interval (CI) = 0.961–0.998, p = .03), platelet/lymphocyte ratio (OR = 1.005, 95% CI = 1.000–1.010, p = .04) and serum albumin (OR = 0.854, 95% CI = 0.774–0.931, p

Objective To analyze the characteristics of foot and ankle deformity with ulceration in patients with spina bifida, to conclude experiences on management with improved Ilizarov method in one stage. Methods 77 cases suffering foot and ankle deformity with ulceration of spina bifida were included from January 2008 to June 2019, in which 30 male and 47 female, aged 6–46 years with an average age of 22.86 years. There were 10 cases on left, 14 on right and 53 on both. The improved Ilizarov method combined soft tissue surgery, bone osteotomy and Ilizarov technique in one stage, by which the ulcer was dressed aseptically and avoid weight bearing preoperatively, no special treatment, no debridement, no flap coverage and no bacterial culture. Antibiotics were given for 3 days routinely, and the dressing was removed 5 days later. If there was exudation, gauze could be used to wrap continually, if there was no swelling and exudation, no need further more caring. General appearance and radiological image of ulcer and deformity were observed during the period of evaluation and treatment, surgical method and complications, foot & ankle function and overall function were evaluated using AOFAS scoring system and special table designed by authors. Results 77 cases were followed up for 6–132 months with an average of 50.5 months. Achilles tendon subcutaneous lengthening was performed in 2 cases, posterior tibial tendon and Achilles tendon simultaneous released for 31cases, subtalar joint arthrodesis 25 cases, calcaneus osteotomy 5 cases, triple osteotomy 28 cases, ankle arthrodesis 19 cases, internal rotation osteotomy of tibia was performed in 1 case and 1 case in external rotation osteotomy. There were 67 cases using Ilizarov fixators and 10 cases using Hybrid fixators for immobilization and correction. Stable feet were obtained and ulcers healed simultaneously when all deformities of foot and ankle had been corrected. The healing time of ulcer was average 26.5 days ranging 7–36 days, and there was no infection or delayed healing occurred in any case. Ankle ankylosis in 25 cases, 3 cases of pin tract infection, 2 wires were broken. The AOFAS score significantly increased from 70.5 ± 4.5 preoperative to 81.6 ± 3.9 postoperative; based special table evaluating, Excellent 28 cases, Good 42 cases, Fair7 cases. Conclusion The patients with foot & ankle deformity and ulceration suffered from spinal bifida can be treated by improved Ilizarov method in one stage, and the results are satisfactory with short treatment period and decreased complications. Translational potential of this article The characteristics of foot and ankle deformity with ulceration inpatients with spina bifida have been analyzed and the experiences on management with improved Ilizarovmethod in one stage have been summarized in this study, which updated treatment concept of neurogenic deformity with ulceration on foot and ankle joint.

We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent FGFR2 fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified FGFR2 extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with FGFR2 p.H167_N173del. Expression of this FGFR2 EID in NIH3T3 cells resulted in constitutive FGFR2 activation, oncogenic transformation, and sensitivity to FGFR inhibitors. Three patients with FGFR2 EIDs were treated with Debio 1347, an oral FGFR1/2/3 inhibitor, and all showed partial responses. One patient developed an acquired L618F FGFR2 kinase domain mutation at disease progression and experienced a further partial response for 17 months to an irreversible FGFR2 inhibitor, futibatinib. Together, these findings reveal FGFR2 EIDs as an alternative mechanism of FGFR2 activation in IHCC that predicts sensitivity to FGFR inhibitors in the clinic.Significance:FGFR2 EIDs are transforming genomic alterations that occur predominantly in patients with IHCC. These FGFR2 EIDs are sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic.This article is highlighted in the In This Issue feature, p. 2355

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1− B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.

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Crizotinib is the first-line drug for non-small cell lung cancer (NSCLC) patients who display anaplastic lymphoma kinase (ALK) rearrangement. With 60% overall response rate, crizotinib significantly prolongs median progression-free survival (ranged 8-10 months) of ALK rearrangement NSCLC patients. However, there are some adverse events from crizotinib, including diarrhea, weakness and nausea. Here, we describe a 47 years old woman with ALK-rearranged NSCLC who developed interstitial pneumonia (IP) induced by crizotinib. A female patient was diagnosed as the left lower lobe adenocarcinoma stage IV (T4N2M1, pleural metastasis) via lung biopsy and was detected wild-type EGFR and 18% ALK gene rearrangement from paraffin section. However, after going through 7 cycles of chemotherapy, she rejected chemotherapy because side effect and still experienced progression of the disease. Subsequently, crizotinib was prescribed as a targeted therapy. After 32 days, visible reduction in size was observed on the pulmonary mass and metastases found in brain and liver, but the patient presented drug-induced level 4 interstitial pneumonia. In a nutshell, the curative effect of crizotinib is worthy of note, but clinicians should also weigh the advantages and disadvantages, prior its usage.