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Several studies have reported that patients harboring MET-ex14 skipping benefit from MET tyrosine kinase inhibitors (TKIs) such as crizotinib, however, the overall response of crizotinib was 32% in these patients. Therefore, the clinical outcome of patients harboring different MET 14 skipping subtypes are worthy to be concern. Based on NGS analysis, we described a lung adenocarcinoma patient harboring a MET c.3028 + 2 T A mutation which was predicted to lead to MET-ex14 skipping. Moreover, we performed IHC and qPCR to verify this variant. Then the patient treated with crizotinib and achieved good therapeutic effect. This mutation is firstly verified not only by multiple methodologies, but also by clinical effect. Our finding expands the spectrum of MET 14 exon skipping variant and maybe offer available application basis of MET inhibitor to patients harboring MET c. 3028 + 2 T A/C/G. Importantly, targeted NGS analysis could improve detection of MET alterations in routine practice.

Melamine contains three aromatic nitrogen atoms and three free amino groups, which have great adsorption potential for heavy metallic ions in wastewater. The sorption performances of melamine for Cu(II) and Pb(II) ( They are denoted as Cu&Pb) were studied. Some major effects such as adsorption time, original concentration, and temperature on its adsorption performances were studied. The effects confirmed that melamine had true adsorption for Cu&Pb, and higher selectivity for the adsorption of Cu&Pb in a binary blended system. The adsorption amount of Pb(II) on melamine reached 4.91 mg/g at pH 5, adsorption equilibrium time of 12 h, and temperature of 55 °C, while the sorption amount of Cu(II) was only 2.70 mg/g, with a difference of about 1.8 times. The adsorption mechanism shows that the sorption of Cu&Pb on melamine follows the Lagergren quasi-second-order kinetic model. This result indicates that the mixture of Cu&Pb can be separated by stepwise processes from a binary mixed system.

Lysozymes in human urine have crucial clinical significance as an indicator of renal tubular and glomerular diseases. Most lysozyme detection methods rely on the enzyme-linked immunosorbent assay (ELISA), which is usually a tedious procedure. Meanwhile, aptamer sensors and fluorescence-based techniques for lysozyme detection have emerged in recent studies. However, these methods are time-consuming and highly complex in operation, and some even require exorbitant reagents and instruments, which restricts real-time clinical monitoring as diagnostic approaches. Therefore, a rapid and low-cost lysozyme detection method with facile preparation is still in demand for modern precision medicine. Herein, we propose a magnetoelastic (ME) immunosensor for lysozyme detection by detecting changes in resonance frequency under a magnetostrictive effect. The detection system is composed of a magnetoelastic chip with an immobilized lysozyme antibody, a solenoid coil, and a vector network analyzer. Since the ME sensor is ultrasensitive to mass change, the frequency offset caused by mass change can be utilized to detect the content of lysozyme. The immunosensor is evaluated to possess superior sensitivity of 138 Hz/μg mL-1 in terms of the resonance frequency shift (RFS). In addition, our sensor displays an outstanding performance in specificity experiments and shows a relatively lower detection limit (1.26 ng/mL) than other conventional lysozyme detection methods (such as ELISA, chemiluminescence assay, fluorescence, and aptamer biosensors).

As an emerging cancer treatment strategy, photothermal therapy (PTT) is precise, controllable, minimally invasive, low cost and less toxic side effects, thus photothermal transduction agents have been extensively investigated in recent years. Noble metal nanomaterials with unique localized surface plasmon resonance (LSPR) effects are particularly suitable as photothermal transduction agent, but the currently developed precious noble metal nano photothermal transduction agents face serious problems such as complex synthesis process, poor photothermal performance and high biotoxicity. Moreover, the large amount of reactive oxygen species (ROS) produced during PTT treatment could cause irreversible damage to the healthy tissues surrounding the tumor. In this work, we deposited platinum (Pt) on the tips of gold nanorods (AuNRs) to form dumbbell-shaped Au-Pt bimetallic nanorods (AuPtNRs), and functionalized AuPtNRs with biocompatible polydopamine (PDA) to obtain AuPt@PDA. With 808 nm laser irradiation, the prepared AuPt@PDA exhibited excellent photothermal stability, and its photothermal conversion efficiency (PCE) reached 81.78%, which was significantly higher than that of AuNRs (52.32%) and AuPtNRs (78.76%). With low cytotoxicity, AuPt@PDA decreased cell viability from 91.12% to 39.36% after PTT on cancer cells in vitro, while significantly reducing intracellular ROS levels generated by heat stress. Therefore, the excellent photothermal properties, high cancer cell killing and ROS scavenging activity of AuPt@PDA in PTT could be an ideal candidate for improving therapeutic efficacy while reducing the risk of toxic side effects due to heat stress-induced ROS formation.

Anaplastic Lymphoma Kinase (ALK) fusion is an important driver mutation and therapeutic target. At present, more than 20 fusion partners for ALK in NSCLC have been reported. However, ALK intergenic-breakpoint fusions confound fusion detection and target treatment. Here, we reported a 53-year-old early-stage lung adenocarcinoma patient with an MIR548AD-ALK intergenic fusion and was verified by immunohistochemical staining (IHC). In early-stage NSCLC, compared with other clinically relevant driver mutations, ALK fusions were associated with a trend toward poor disease outcomes. Our Next-generation sequencing (NGS) and IHC results may indicate the prognosis of the patient and provide an alternative treatment option for postoperative recurrence.

Geological disasters have caused enormous damage to human beings and the economy in China. Chinese government pay great effort on geological disaster relief. Usually, the efficiency of the disaster rescue is the first priority to be considered. Takeing the historical analysis of China's geological disaster rescue as the main line ,in this paper, we developed a slacks-based measure data envelopment analysis (SBM-DEA) model to evaluate the performance of 18 geological disasters relief during 2015–2019 in China, which are used to examine the performance of the geological disasters rescue activities. The results show that though the capabilities of geo-disaster relief is continuous improvement from 2015 to 2019, China’s geological disasters rescue system is still at the primary stage. Especially, the efficiency of landslide rescue operation is pretty low. We analysis the factors influencing the efficiency and provide several suggestions for capacity improvement of geo-disasters rescue.

Ant colony algorithm can better deal with combinatorial optimization problems, but it is still difficult to balance the solution accuracy and convergence speed facing large-scale TSP. Nowadays, most scholars focus on the route information of better ants for improvement, while ignoring the route information of general ants with a large base. So, this study proposes the multiple ant colony algorithm combining community relationship network (CACO) by collecting route information of all ants and constructing a route relationship network to improve the accuracy of the solution. The network is divided into a number of small communities that reflect the affinity of multiple colony ants to different cities through community detection with modularity. Within the communities, CACO use the excellent roue exploration ability of the ant colony algorithm to identify high-quality route segments, integrating the pheromones of high-quality segments in the communities to provide pheromone feedback to the multiple colony ants for better route exploration. The three parts of route information collection, community detection and pheromone feedback form a feedback loop, which keeps cycling when multiple populations ants explore, and each cycle will drive the result closer to the optimal solution. Meanwhile, CACO proposes a mutual assistance strategy to improve the exploration ability of multiple colony ants by complementing each other according to the different states of superior and inferior populations. To test the performance of CACO, 28 TSP instances are compared with the well-known improved algorithms are compared and results show CACO outperforms other improved algorithms significantly, especially in large-scale TSP.

The composite of gold and PDMS hold remarkable potential for surface stress-based biosensor applicaitons. However, the gold and PDMS in composite suffers from poor compatibility with each other and suppresses the performance of the biosensor. Here, we conduct two-step synthesis of the composite of gold and PDMS by in-situ reduction and glucose reduction of HAuCl4. The composite shows stable conductive gold nanoparticle network (SC-AuNW). In in-situ reduction, Au-seeds are embedded in PDMS surface. Furthermore, AuNPs are also generated inside the PDMS and enhance conductivity. The SC-AuNW plays a crucial role in tunneling conductivity of composite film and exhibits an excellent sensitivity to surface stress. We construct SC-AuNW-PDMS biosensors based on surface stress for glucose detection with a detection limit of 0.021 mM, high repeatability and specificity. Our research can promote the application of flexible conductive films in biosensors for disease diagnosis.

This paper presents an original design for a volume refractive index (RI) sensor for cell concentration detection based on the unique resonant optical tunneling effect (ROTE). In this design, the solution sample is introduced into the ROTE resonant cavity, whose reflection spectrum presents a large shift of its resonant dip in response to the tiny change of the solution RI. Performance calibration using the polystyrene particle solution indicates that the sensitivity is 19,000 nm/RIU and the total Q factor is 620. Experiments with hepatoma cells have obtained sensitivity values as high as 2.53 nm/(amol/ml) and a detection limit of 1.2 × 105 cells/ml. Compared with previously reported optical cell sensors, this original work implements the ROTE mechanism for the first time and presents superior device performance. Thus, the proposed design has a high potential for use in biomedical applications, such as drug discovery, cell research, and medical diagnoses.

Background: With the increasing serious problem of water environment pollution, it is a hot spot to study the high efficient sewage treatment method. Owning to the photosensitization of carbon nanomaterials, carbon doped TiO2 (C-TiO2) has higher photocatalytic activity. Method: Here, we proposed a new method, carbon-assisted method, to prepare C-TiO2 nanomaterials. We first used degreasing cotton as a dispersant to fully absorb the TiCl4 sol. Results: After high-temperature calcination, C-TiO2nanomaterials were obtained. Characterizations results showed that the high specific surface area C-TiO2 nanomaterials in the size of about 50 nm showed a broader light absorption and narrower bandgap spectrum than P25 (commercial TiO2 nanoparticles). Conclusion: The C-TiO2 nanomaterials showed stronger photocatalytic ability than P25.

This paper reported a simple pH-responsive fluorescent therapeutic drug delivery system of doxorubicin (DOX)-loaded carbon dots (CDs) for intracellular drug delivery and track in human gastric cancer cells. Drug loading efficiency of this system was 75.3 wt%. The drug release process of this system followed the first-degree drug delivery model, which was ideal for intravenous injection therapy of cancer. The carboxyl-rich CDs had almost no toxicity to human gastric cancer (MGC-803) and human gastric epithelial (GES-1) cells with the survival rates of over 90%. The CDs-DOX system had about a 2-fold inhibitory effect on MGC-803 cells growth compared to GES-1 cells according to the MTT assay. The cell imaging results showed that the CDs-DOX system could be internalized into the cells efficiently. The intracellular uptake and drug delivery efficiency of this system in GES-1 cells was about 30% of that in the MGC-803 cells. The fluorescent CDs enabled the optical labeling and tracking of the drug delivery process at least 48 h. Because of its specific drug delivery and fluorescence tracking properties, the multifunctional CDs-DOX system possesses potential applications in bioimaging, biolabeling and cancer therapy.

Carbon dots (Cdots) with bright green fluorescence were applied to the rapid and selective cell imaging for a variety of cell lines. Different labeling distributions of hepatoma cells (HepG2) and normal human liver cells (LO2) were achieved using Cdots as imaging agents. For HepG2 cells, the Cdots could rapidly permeate the cell membrane and diffuse into the cytoplasm and nucleus within 3 min, and retained their location in the targets for 24 h. However, the Cdots exhibited bright fluorescence only in the cytoplasm of LO2 cell lines. Moreover, the Cdots were almost non-cytotoxic and exhibited superior photostability over a wide range of pH. Therefore, these Cdots have great potential for rapid, luminous and selective bioimaging applications, and are expected to be used as a nucleus-staining agent in cancer diagnosis. Graphical abstract ᅟ.

e14032 Background: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, which indicated that all IDH mutant diffuse astrocytic tumors are considered a single type (Astrocytoma, IDH-mutant) and are then graded as CNS WHO grade 2, 3, or 4. Besides, the guideline eliminates the term “Glioblastoma (GBM), IDH-mutant”. Moreover, grading is no longer entirely histological, since the presence of CDKN2A/B homozygous deletion results in a CNS WHO grade of 4, even in the absence of microvascular proliferation or necrosis. Therefore, more clinical and genomic characteristics of IDH-mutant astrocytoma under molecular typing need to be further studied. Methods: Adults pathological diagnosed with diffuse astrocytoma and glioblastoma in our Chinese dataset were identified retrospectively. All patients included in the analysis were tested for 131 CNS tumor-related genes (including IDH1/2), chromosomes 1p/19q and chromosomes 7/10. Results: 63 initial diagnosed IDH-mutant diffuse astrocytomas including 46 patients with grade 2-3 and 17 patients with uncertain grade. While, 5.2% of GBM (9/174) harbored IDH1/2 mutation which should be redefined as diffuse astrocytoma, IDH-mutant, WHO 4 grade. And these patients had a high frequency of CDKN2A/B homozygous deletion (88.9%, 8/9). In patients with 2-3 grade and unclear grade, CDKN2A/B homozygous deletion accounted for 18.7% (9/48) and 27.8% (5/18), respectively, which meant the grade of these diffuse astrocytomas should be revised to WHO 4 grade according to guideline. While mutation frequency of crucial prognosis factors in glioma, including chromosomes 7 loss, chromosomes 10 gain, EGFR amplification, PIK3CA/R1, PDGFRA amplification, CDK4 amplification, were 9.7%, 2.8%, 5.6%, 13.9%, 6.9% and 8.3% in all 72 astrocytomas, respectively. In addition, we found 83.3% (5/6) KDR copy number variant were occurred in which initially pathological diagnosed as IDH-mutant GBM. Conclusions: we conducted comprehensive analysis of IDH mutant diffuse astrocytoma. CDKN2A/B homozygous deletion as a specific grade-classified molecular marker could better re-distinguish about 20%-30% 2-3 grade and uncertain grade astrocytoma. KDR copy number variant may be a marker in IDH-mutant astrocytoma to identify the tumor which pathology is closer to GBM.

e21593 Background: Immune checkpoint blockade has shown significant promise as an anticancer treatment and anti–CTLA-4 treatment prolongs overall survival in patients with melanoma. Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF gene family, has been characterised as a prime mediator of lymphangiogenesis and angiogenic growth factors that promote the growth and metastasis of neoplasms. Previous studies provided evidence that VEGF-C correlated with poorer survival in melanoma. We aimed to determine the association of VEGF-C mutations with melanoma survival to immune checkpoint inhibitors (ICI). Methods: Data from Allen study (n = 110, anti- CTLA-4 therapy) was obtained and analyzed. Meanwhile, we extracted skin cutaneous melanoma (SKCM) RNA data from The Cancer Genome Atlas (TCGA). In survival analysis, Kaplan-Meier curves were compared by log-rank test, and the hazard ratio (HR) was determined through a multivariable Cox regression model. Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined in TCGA cohort. Results: In Allen cohort, the frequency of VEGFR-C mutation was 5.45% (6 in 110). Meanwhile, the frequency of VEGFR-C mutation in TCGA cohort was 7.37% (33 in 448). VEGFR-C-mutant (VEGFR-C-mut) group showed a poorer progression-free survival (PFS) (HR, 2.34; 95%CI, 1.01 to 5.4, p = 0.041) and overall survival (OS) (HR, 2.84, 95%CI, 1.22 to 6.62, p = 0.012) than the VEGFR-C-wild (VEGFR-C-wt) group, based on results of the log-rank test and Kaplan-Meier analysis. Moreover, COX proportional hazards model analysis showed VEGFR-C mutation was associated with poorer PFS (HR, 2.54; 95%CI, 1.04-6.25, p = 0.0042;) and OS (HR, 3.25; 95%CI, 1.30-8.12, p = 0.0117) compared with VEGFR-C-wt. In addition, we identified that the levels of naive B cells and resting CD4+ memory T cells were more abundant in VEGFR-C-mut group according to CIBERSORT algorithm. Conclusions: In our study, the frequency of VEGFR-C mutation in melanoma was investigated in Allen and TCGA cohorts, which might provide useful information to guide precision medicine. VEGFR-C mutation may serve as a potential negative predictor of response to anti-CTL4 treatment in melanoma via higher levels of naive B cells and resting CD4+ memory T cells.

e15131 Background: Lung cancer and chronic obstructive pulmonary disease (COPD) often coexist. Lots of clinical and genomic descriptions related lung cancer have been investigated. However, the clinical and genomics characteristics of lung cancer coexisting COPD are still unclear. Herein, we explored the clinical characteristics and somatic mutational landscape of lung cancer coexisting COPD (COPD-LC) and compared with non-COPD Lung cancer (non-COPD-LC). Methods: We retrospectively collected total COPD-LC and non-COPD-LC patients who performed next generation sequencing (NGS) simultaneously from The Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University during December 2018 to August 2021. And collected COPD-LC data from TCGA to further analysis. COPD was defined as incompletely reversible airflow obstruction associated with post-bronchodilator forced expiratory volume in one second (FEV1) and its ratio to forced vital capacity (FEV1/FVC) < 0.7. Results: Of the 139 patients enrolled in the study, 51 were categorized as COPD and 88 as non-COPD. In our clinical cohort, compared with non-COPD-LC, amount of male gender, older age and smoking patients were significantly higher than non-COPD in term of clinical data (all P < 0.01). As for somatic mutation in our cohort, compared with non-COPD-LC, COPD-LC had higher mutation frequency of LRP1B (43% vs 9%, P = 0.001), EPHA5 (24% vs 1%, P = 0.002), PRKDC (14% vs 1%, P = 0.039) and PREX2 (14% vs 0%, P = 0.012), which had relationship with improved tumor immunity. Immunotherapy biomarker of PD-L1 positive expression (62.5% vs 52.0%, P = 0.397) and TMB (P = 0.004) also were higher in COPD group. Whereas, COPD-LC had lower frequency of EGFR (19% vs 50%, P = 0.013). And survival analysis showed in EGFR mutant patients with targeted therapy, COPD-LC had worse PFS than non-COPD-LC (HR = 3.52, 95%CI: 1.27-9.80, P = 0.01). TCGA cohort mutation data differed from the results of our cohort. In addition, RNA data from TCGA indicated COPD-LC increased tumor immunity. Conclusions: In our research, COPD-LC had unique clinical and molecular features. High PD-L1 expression and TMB indicated these patients may benefit from immunotherapy. Notably, mutation difference between Chinese and TCGA cohort and COPD-LC immunotherapy efficacy need prospective further study.

e21517 Background: Melanoma is one of the most aggressive and immunogenic tumors. Current immunotherapies using immune checkpoint inhibitors such as CTLA4 and PD1 to stimulate T cell-mediated tumor killing significantly improved the overall survival of patients with metastatic melanoma. However, the clinical predictors of response to these therapies are still not fully characterized. Previous studies have shown that the high gene expression of Ankyrin repeat domain 36 (ANKRD36) can lead to the occurrence and poor prognosis of colon cancer and kidney cancer. In this study, we aimed to explore the role of ANKRD36 mutation in the prognosis of melanoma immune checkpoint inhibitors (ICIs). Methods: Public data of patients treated with ICIs(ipilimumab) from Van Allen (n = 110) cohort were obtained and analyzed. In survival analysis, Kaplan-Meier curves were compared by log-rank test, and the hazard ratio (HR) was determined through a multivariable Cox regression model. The potential mechanism was subsequently explored through RNA expression data from The Cancer Genome Atlas (TCGA). Results: The frequency of ANKRD36 mutation in the Van Allen cohort and TCGA cohort was 7.2% (8 in 110) and 1.56% (7 in 448) respectively. We further analyzed the Kaplan Meier curve and multiple Cox regression model of the Allen cohort and found that the survival of the mutant type in immunotherapy was significantly shorter than that of the wild-type group (PFS: HR = 3.09 [95% CI: 1.47, 6.51], p = 0.002; OS: HR = 2.33 [95% CI: 1.12, 4.86], p = 0.02). Both mutant type and tumor metastasis would have negative effects on immunotherapy(PFS: HR = 3.66 [95% CI: 1.71, 7.85], p < 0.001***; OS: HR = 3.16 [95% CI: 1.47, 6.82], p = 0.003**). Analysis of the transcriptome data from the TCGA database found that resting CD4 memory T cells is highly expressed in ANKRD36 mutant patients (p = 0.032), which may indicate that the patient's immune system did not activate the anti-tumor immune mechanism. Conclusions: In our study, the frequency of ANKRD36 mutations was investigated in clinical and TCGA cohorts, which may provide useful information for guiding patient treatment. ANKRD36 mutation may be a negative predictor of ICIs in patients with melanoma and play a role in prognosis.

2614 Background: PAK (P21 activated kinase) is a family of serine threonine kinases, that consist of 6 members, PAKs 1-6, which are positioned at an intersection of multiple signaling pathways implicated in oncogenesis. Recent studies have found relationship between mutations of some PAK family genes and antitumor immunity. Here, we explored the associations of PAK family gene mutations with ICI response based on multidimensional data from multiple solid tumors. Methods: An immunotherapy cohort (Broad/Dana-Farber, Nat Genet 2018, N = 249) within 7 types of tumors as discovery stage, was used to explore the association of PAK family genes mutations with tumor mutation burden (TMB) and efficacy of immunotherapy. To further validate the predictive value of PAK family genes, we employed another ICI-treated cohort, MSKCC cohort (Samstein, Nat Genet 2019, n = 1661), as a validation cohort. TMB was calculated as the total count of nonsynonymous mutations in coding sequence. Results: In discovery cohort, compared to that in the PAK-Wt group, longer OS was observed in the PAK-Mut group (mOS: 31.3 vs 15.4 months, HR = 0.59, 95% CI: 0.36 to 0.96, P= 0.03). In addition, PAK-Mut group had higher TMB ( P< 0.001). Median TMB in PAK-Mut group and PAK-Wt group is 17.79 (IQR, 7.45-36.55) Mut/Mb and 5.47 (IQR, 2.46-9.09) Mut/Mb, separately. In validation cohort, PAK-Mut patients also achieved significant improved OS compared with PAK-Wt patients (mOS: 44.0 vs 17.0 months, HR = 0.51, 95% CI: 0.37 to 0.69, P< 0.001). Moreover, multivariable analysis of validation cohort demonstrated that PAK-Mut was associated with better OS (HR = 0.71; 95%CI, 0.52-0.98; P = 0.036), after adjusting for Age, Gender, Metastasis, Treatment, TMB, Cancer type. Compared with PAK-Wt group (median [IQR]: 5.90 [2.95-10.04]), PAK-Mut group (median [IQR]: 21.19 [11.81-43.29]) also had higher TMB ( P< 0.001). Conclusions: The results indicated that PAK family genes mutation was associated with a higher TMB both discovery and validation cohort. Analysis of discover and validation immunotherapy cohort data showed PAK family was associated with better OS. These findings indicate that these genes mutation may serve as a potential predictive biomarker for ICI in solid tumor patients.

In order to decrease the amount of bentonite in the production of oxidized pellets, the addition of HS binder is carried out in response to the problems of wasting of resources, high costing and serious pollution in the production and application of bentonite in China. In this study, the effect of the organic binder in iron ore pellets was characterized by using pelletizing, preheating and roasting experiments; the optimal ratio of HS binder to bentonite was determined. The results showed that combination of bentonite and HS binder can significantly reduce the amount of bentonite. When the ratio of bentonite of HS binder was HS binder dosage 0.2% and bentonite dosage 0.7%, the drop strength of green pellets reached 3.2 times/(0.5 m) and the amount of bentonite reduced the mass of 1.6% compared with that of without HS binder. Under the best preheated roasted conditions, the strength of the preheated ball was 436.9 N/P and the roasted ball strength achieved 2794.3 N/P, which could meet the demands.

Noble metal nanomaterials are particularly suitable as photothermal transduction agents (PTAs) with high photothermal conversion efficiency (PCE) due to local surface plasmon resonance (LSPR). Studies on different gold–platinum (Au–Pt) bimetal nanoparticles exhibiting the LSPR effect have provided a new idea for the synthesis of excellent PTAs. But there is no simple and scalable method for the controllable synthesis of Au–Pt nanoparticles with adjustable LSPR wavelength range. In this work, the effects of Ag+ and K2PtCl4 on the deposition of Pt on the surface of gold nanorods (AuNRs) were investigated. A fast, precise, and controlled synthesis of dumbbell-like Pt-coated AuNRs (Au@Pt NRs) under mild conditions is proposed. The synthesized Au@Pt NRs have a longitudinal LSPR wavelength of 812 nm, which is very close to a common laser wavelength of 808 nm. The Au@Pt NRs exhibit excellent photothermal properties when irradiated with a laser. The temperature increased by more than 36 °C after irradiation for 10 min, with a PCE of about 78.77%, which is much higher than that of AuNRs (57.33%). In addition, even after four on/off cycles, the Au@Pt NRs are able to maintain the photothermal properties and retain their optical properties, indicating that they have excellent photothermal stability and reusability.

With the development of society and the improvement of human environmental awareness, low pollution, high-performance motors have broad application prospects. Series-excited DC motors have the advantages of low cost, strong overload capacity, and easy speed adjustment. They are widely used in various industries. This paper analyzes the working principle of series-excited DC motors and studies the control strategy of series-excited DC motors. According to the control requirements of the motor, the system takes STM32 as the main controller and designs the software and hardware of the control system. The hardware circuit part of the system includes the motor speed detection circuit, power supply circuit, protection circuit, etc. The software part of the system mainly introduces the system programming flow chart. The uC/OS-II operating system is cited in the software design and the programming is based on the operating system.

Superparamagnetic nanoparticles have been widely used as contrast agents in magnetic resonance imaging (MRI). The combined use of multiple imaging modes can provide more accurate information for clinical diagnosis. In this paper, a MRI/fluorescence dual-mode imaging contrast agent was developed by a simple method. The method is to make the fluorescent carbon quantum dots (CDs) adsorbed on the surface of the magnetic composite with pore structure by ultrasonic dispersion. Replacing the traditional methods such as chemical bonding, the fluorescent material is coated on the surface of the composite material. The synthesized composite materials were characterized by the transmission electron microscopy method (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and vibration sample magnetometer (VSM). The results of TEM, FTIR and XPS showed that CDs were successfully coated on the surface of C60@Fe3O4 magnetic composite. The VSM results show that the composite material still maintains superparamagnetism. The cytotoxicity of the material on SMMC-7721 liver cancer cells was detected by the MTT method, and the biocompatibility of the material was verified. By observing the fluorescence distribution in the cell, it is proved that the composite material successfully enters the cell and produces fluorescence. Finally, through the analysis of T2-weighted imaging, it is found that the addition of materials results in an enhanced dark contrast compared to control cells. Therefore, the composite nanomaterials synthesized in this paper can be used as MRI/fluorescence dual-mode imaging contrast agents.

The vast majority of patients with corneal blindness cannot recover their vision due to the serious shortage of donor cornea. However, the technology to construct a feasible corneal substitute is a promising treatment method for corneal blindness. In this paper, methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA) double network (GHDN) hydrogels were prepared by modifying gelatin and hyaluronic acid with methacrylate anhydride (MA). GHDN hydrogel was compared with GelMA single network and HAMA single network hydrogels through characterization experiments of mechanical properties, optical properties, hydrophilicity and in-situ degradation in vitro. At the same time, the biocompatibility of hydrogel was tested by inoculating rabbit corneal epithelial cells (CEpCs) epidermal cells on hydrogels using CCK-8 test, live/dead staining, immunofluorescence staining and qRT-PCR. It was found that the GHDN hydrogel has optical transparency in the visible region, and its mechanical properties are better than those of GelMA and HAMA hydrogels, and its hydrophilicity is similar to that of normal human corneas. The results of in vitro hydrogel culture of CEpCs showed that the proliferation of CEpCs on GHDN hydrogel was two times higher than that of HAMA hydrogel, and the expression of specific marker Cytokeratin 3 (CK3) and Cytokeratin 12 (CK12) could be better maintained on GHDN hydrogel. All the experimental results proved that GHDN hydrogel has good physical properties and biocompatibility and is a potential candidate for corneal tissue engineering scaffolds.

Background: In present, patients with stage IV or recurrent/metastatic non-small cell lung cancer (NSCLC) whose tumors harbor programmed death ligand 1 (PD-L1) expression and active Epidermal Growth Factor Receptor (EGFR) mutations should receive initial EGFR tyrosine kinase inhibitors (TKIs) based on clinical guidelines and practice. However, high PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment advanced EGFR-mutant lung cancer patients, the optimal use of ICI therapy in patients with actionable EGFR mutations remains an important field of ongoing research. Some studies also showed that patients with uncommon EGFR mutations have a good immunotherapy potential.Case prestation: Here, we report a 56-year old advanced squamous cell lung carcinoma (SCC) patient with a rare active mutation in EGFR gene (EGFR p.R748T) and PD-L1 expression who responded well to the immune-chemo combination therapy (pembrolizumab with nab-paclitaxel and nedaplatin). Conclusion: The EGFR R748T mutation is an uncommon active mutation and there is no report about immuno-chemo therapy on patient with EGFR R748T mutation and PD-L1 high expression. The result presented in this case provides a feasible therapy for some patients who harbor rare active EGFR mutations (except for G719X, L861Q, S768I, and Ex20 ins) with high PD-L1 expression.

Photothermal therapy (PTT) is a non-invasive therapy that is widely used in cancer treatment. Gold nanorods (AuNRs) are particularly suitable as a photothermal reagent due to their unique localized surface plasmon resonance (LSPR) properties. However, bare gold nanorods are not stable enough during radiation to collect enough energy to kill tumor cells. In addition, they showed some biologically toxic originated from the poor colloidal stability and surfactants cetyltrimethyl ammonium bromide (CTAB), making it difficult to apply them directly to clinical research. To solve these problems, a novel nanocomposite was structured by coating silica shell and gold nanocluster on the outer layer of the gold nanorod (AuNRs@SiO2@AuNCs). Compared with the bare gold nanorod, the nanocomposite with the core-shell structure showed superior photothermal effect. The photothermal conversion temperature reached 63 °C under a lower irradiation power. The photothermal conversion efficiency was enhanced to 77.6%. Its photothermal performance remained constant after five cycles of near-infrared laser irradiation, indicating excellent photothermal stability. In vitro cell imaging experiments show that AuNRs@SiO2@ AuNCs can effectively enter tumor cells. By 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis, cancer cells can be effectively killed when exposed to a near-infrared laser. During the synthesis process, the silica and gold nanoclusters replaced the toxic CTAB molecular layer on the surface of AuNRs. Therefore, AuNRs@SiO2@AuNCs has good biocompatibility and fluorescence characteristics. These results suggest that such AuNRs@SiO2@AuNCs nanocomposite shows great potential in imaging guided photothermal therapy for cancer.

Supplemental material, sj-pdf-1-pic-10.1177_0954406220929050 for Dynamic-coupling analyses of cells localization by the negative dielectrophoresis by Jianlong Ji, Jingxiao Wang, Liu Wang, Qiang Zhang, Qianqian Duan, Shengbo Sang, Qing Huang, Shanshan Li, Wendong Zhang and Xiaoning Jiang in Proceedings of the Institution of Mechanical Engineers, Part C: Journal of Mechanical Engineering Science

Preparation of zinc carbonate hydroxide microparticles using heating deamination precipitation was investigated. The precipitation reaction conditions are closely related to the morphology and particle size of zinc carbonate hydroxide microparticles. Therefore, it is very important to enhance capability and quality of the process for controlling the product particle size by setting the optimal reaction parameters. In this research, the influence of reaction conditions on the formation of zinc carbonate hydroxide microparticles was studied, such as temperature, zinc ion and total ammonia concentrations, stirring speed, and additive dosage. The relationship between reaction conditions and morphology and particle size of microparticles was confirmed by analyzing particle size and morphology of zinc carbonate hydroxide precipitations at different conditions. The techniques of SEM and LSPSA were used for the characterization of the prepared materials

Amino-rich carbon quantum dots (CDs) were synthesized by hydrothermal treatment of ethylene glycol, glucose and polyethyleneimine. CDs have green fluorescence (excitation/emission peaks 435 nm/515 nm) and can be enhanced by the addition of heparin (Hep). A linear relationship between fluorescence intensity and heparin concentration was observed. The fluorescence turn-on probe used for Hep detection showed a very large detection range of 0.02-16 μM, covering different therapeutic ranges in clinical applications. The probe exhibited an ultra-low detection limit of 0.007 nM.

Background The drugs are easily cleared and lack of targeting in chemotherapy, thus reducing its efficacy. A novel pH- responsive drug delivery system based on carbon quantum dots (CDs) was proposed. CDs have low toxicity and good biocompatibility and can be electrically combined with doxorubicin (DOX). The bovine serum albumin (BSA), an endogenousx substance, could be used as a protein model for constructing a novel lipoprotein-like nanocarrier. In this study, we introduced BSA into the drug delivery system and prepared a stable drug delivery system BSA@CDs-DOX. The system was characterized by UV-Vis, fourier infrared spectroscopy, transmission electron microscopy and fluorescence spectroscopy, and its stability, drug loading efficiency, coating efficiency and drug release in vitro were investigated. The release of drug from the system was tracked by the fluorescence properties of CDs. Results The stability of the BSA@CDs-DOX system was obviously enhanced in various environments. The in vitro release profile was prolonged, and the cumulative release ratio at pH = 5.0 was 7.5 times higher than that at pH = 7.4. The drug side effects on the normal cells were significantly reduced and the killing effect on cancerous cells was improved in longer time. Excellent and sustained migration resistance was observed in 72 h. The drug uptake process and cellular state were evaluated visually in real time until 72 h. Conclusion The stable and sustained release BSA@CDs-DOX system showed good application prospect in chemotherapy of tumors.

Hg2+ is one of the most universal and severe toxic metal pollutants. Here we reported a high-sensitivity and rapid method for detection of Hg2+. The technique was based on the localized surface plasmon resonance property of gold nanorods. Neither modification of gold nanorods nor separation of analyte was necessary. The longitudinal absorption peak of gold nanorods presented a linear blue shift as Hg2+ concentration increased. The blue shift of longitudinal absorption peak was due to the changes of both aspect ratio and medium dielectric constant. The sensor had a wide linear interval ranging from 285 nM to 8.00 μM, the detection limit was as low as 112 nM, and the sensitivity was 30.48 nm μMμ1, which were comparable to the performance of the modified sensors.

Item recommendations aim to predict a list of items (e.g., items on Amazon website) for each user that he or she might like. In fact, implicit feedback, such as transaction records in e-commerce websites and the “likes” behavior in social networks website (e.g., Facebook), has been received more and more attention in the scenarios of item recommendation. The core of the recommender system is the ranking algorithm which exploits the implicit feedback and generates the personalized item list to meet user’s specific preferences. In most of the previous studies, the pairwise personalized ranking techniques empirically achieve better performance than the matrix factorization and adaptive k nearest-neighbor method since the pairwise ranking methods can directly reflect the model user’s ranking preference on items. In most of the recent works, factored item similarity techniques which learn the global item similarity by utilizing two low-dimensional latent factor matrices achieve better performance than other state-of-art top-N methods with predefined similarity, such as cosine similarity. The individual relative preference assumption among observed items and unobserved items are critical for the pairwise ranking methods. As a response, this paper proposes a new and improved preference assumption based on the factored item similarity and individual preference. In addition, a novel recommendation algorithm correspondingly named factored item similarity and Bayesian Personalized Ranking model is designed. The novelty of the algorithm is that it can (1) learn the global item similarity with latent factor models. (2) utilize effective pairwise ranking methods to deal with the item recommendation problems with implicit feedback. (3) assign different item weights on explicit feedback and implicit feedback. Empirical results show that this model outperforms other state-of-the-art top-N recommendation methods on two public datasets in terms of prec@5 and ndcg@5. It can be found that the advantage of FSBPR lies in its ability to exploit implicit feedback and capture global item similarity.

A Disintegrin And Metalloproteinase 12 (ADAM12) is highly expressed in multiple cancers such as breast and cervical cancers and its high expression reduces the overall patient survival rate. ADAM12 has two major splicing variants, the long membrane-anchored form ADAM12L and the short secreted form ADAM12S. However, how they are regulated and whether they are modulated similarly or differently in cells are not clear. Here, we use affinity purification and mass spectrometry to identify the ADAM12S-interacting proteins. Spectral counting and MaxQuant label-free quantification reveal that ADAM12S but not ADAM12L specifically interacts with a subset of endoplasmic reticulum proteins, such as endoplasmin (GRP94), 78 kDa glucose-regulated protein (GRP78), and UDP-glucose:glycoprotein glucosyltransferase I (UGGT1), that regulate the folding and processing of secreted proteins. Further biochemical experiments validate the interaction between ADAM12S and several of its interacting proteins. Computational docking analysis demonstrates that GRP94 preferentially interacts with ADAM12S over ADAM12L. The data also suggest that both the protein expression level and the secretion of ADAM12S are regulated by GRP94 expression and knockdown. Our results reveal a link between these two proteins that are highly expressed in cancer cells. Furthermore, our studies define a new ADAM12S-specific regulator that may contribute to the cancer development. Significance A Disintegrin And Metalloproteinase 12 (ADAM12) is highly expressed in many cancers such as lung, breast, and cervical cancers. ADAM12 has two major splicing variants, the long membrane-anchored form ADAM12L and the short secreted form ADAM12S. However, how they are regulated and whether they are modulated similarly or differently are not completely understood. We use affinity purification and label-free quantitative proteomics to identify the ADAM12S-interacting proteins. Our results reveal that ADAM12S specifically interacts with a subset of endoplasmic reticulum proteins, including endoplasmin (GRP94), UDP-glucose:glycoprotein glucosyltransferase I (UGGT1), and neutral α-glucosidase AB (GANAB). Computer modeling reveals that ADAM12S interacts with the surface amino acids of GRP94 more strongly than ADAM12L. Biochemical experiments further reveal that GRP94 regulates both the protein level and the secretion of ADAM12S. Database mining finds that both GRP94 and ADAM12 are highly expressed in multiple cancers and their high expression is correlated with poor patient survival rate. Taken together, our work discovers a new upstream regulator for ADAM12S, which may contribute to its distinct functions in the regulation of the migration and invasion of cancer cells.

A magnetoelastic (ME) biosensor functionalized by bovine serum albumin (BSA) was firstly developed for the wireless detection of heavy metal ions in solution. The biosensor was fabricated by coating a gold-modified ME ribbon with BSA. Its resonance oscillation and resonance frequency can be actuated and wirelessly monitored through magnetic fields. The combination of heavy metal ions and BSA produces the precipitation adhered to the biosensor surface, resulting in the increase of mass loading, and consequently leads to a decrease in the resonance frequency, corresponding to the concentrations of heavy metal ions. The biosensor was used to separately detect Pb2+, Cd2+ and Cu2+. Its response is linearly proportional to the low concentrations, becoming sub-linear at higher concentrations. Moreover, the SEM, fluorescence microscopy and EDS spectrum analysis proved that the modification and detection process were successful. The biosensor is more sensitive to the heavy metal with larger molecular weight, and has the sensitivity for Pb2+, Cd2+ and Cu2+ of about 9.4 × 107 Hz per mol/L, 7.1 × 107 Hz per mol/L and 4.7 × 107 Hz per mol/L, respectively. The detection limits for Pb2+ and Cd2+ of 3.3 × 10−7 mol/L and 2.4 × 10−7 mol/L, respectively, are lower than the standard limit (GB 8978-1996).

Fine-tuning magnetic states by understanding topological frustration inducing magnetic mechanism should allow greater flexibility for the design of graphene-based spintronics. Based on first-principles calculations, it is predicted that bowtie-shaped graphene nanoflake (GNF) is of spin-polarized ground state exhibiting antiferromagnetic (AFM) ordering between two individual triangular GNFs. It is demonstrated that strength of antiferromagnetic coupling of both symmetric and asymmetric bowtie-shaped GNF displays strong zero-energy-state-orientated behavior due to non-trivial nature of topological frustration, with implications for designing graphene nanostructures with predefined magnetic states. It also proposes a specific example of structures that can serve as nanoscale molecular logic gates composed by asymmetric bowtie-shaped GNFs units, which augment the special antiferromagnetic function through structural configuration of multi-bowtie-shaped GNFs.

A new enhanced fluorescent (FL) ratio probe for Cd2+ detection was developed. The gold nanoclusters (AuNCs) with red FL were used as internal reference FL molecules, and the nitrogen and sulfur co-doped carbon quantum dots (N,S-CDs) with blue FL were used as analysis signal molecules. The FRET effect between AuNCs and N,S-CDs result in the FL quenching. The added Cd2+ interacts with AuNCs to form complexes, and interacts with the oxygen atoms in the hydroxyl and carboxyl groups of N,S-CDs to form a stable complex that made N,S-CDs/AuNCs aggregate and resulted in the FL enhancement. The FL intensities of N,S-CDs (F435) and AuNCs (F630) increased to different degrees after Cd2+ added. The ratio of FL intensity F435/F630 exhibited a good linear relationship with Cd2+ concentration in the range of 0–2.1 µM, and the detection limit in tap water was calculated to be 62 nM. The reliability of the prepared FL ratio probe was also demonstrated in actual water samples.

A PDMS micro-membrane surface stress biosensor with elaborate circular membrane and corresponding electrode design is presented in this paper. A sandwich structure of two integrated circle electrodes with thin PDMS film and interlayer cavity was fabricated and characterized. Highly accurate thickness of deposition and etching of the PDMS membrane were achieved using surface micromachining technology. Furthermore, the fabricated micro-membrane has been characterized in each of the various stages of operation to verify the designed parameters. After the biosensor was coated with a layer of 11-mercaptoundecanonic acid (MUA: SH-(CH2)10-COOH), Staphylococcus aureus ( S. aureus ) was used as the bioanalyte in biological sensing experiments. The dependence of inverse capacitance on the concentration of bacteria follows an approximate linear relationship with a sensitivity of 4.275 × 10 −2 pF −1 bac/ml and a resolution of 0.8 amol/ml, comparatively excellent among recently developed capacitive biosensors. The novel sensor shows promises for future detection of S. aureus or other bioanalytes.

Thrombosis is a main complication of cancer. It can increase the mortality of cancer patients. Therefore, the anticoagulant heparin (Hep) as an adjuvant therapy was introduced to the drug delivery system based on doxorubicin hydrochloride (DOX)-carbon dots (CDs)-Hyaluronic acid (HA), which obviously enhanced the blood compatibility of the system. Drug release process of the CDs-HA-Hep/DOX system was dual-responsive by HA and pH value. Results of in vitro MTT and scratch tests demonstrated that the drug delivery system could targetedly inhibit growth and migration of cancerous cells. In addition, the system allows visual tracking of the drug based on fluorescence of CDs.

Small cell lung cancer (SCLC) accounts for ∼14% of total lung cancer, which is the worldwide leading cause of morbidity and mortality in cancer. Although SCLC can be treated with chemotherapy and radiotherapy, its 5 year survival rate is still below 7%. Therefore, it is essential to discover new molecules and elucidate the underlying mechanisms modulating the tumorigenesis and metastasis of SCLC for the unmet medical needs. The secreted form of A Disintegrin And Metalloproteinase 12 (ADAM12S) is highly expressed in SCLC and promotes the proliferation, migration, and invasion of SCLC cells. However, the underlying molecular mechanism is still elusive. Using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics, we identify 82 ADAM12S-regulated proteins in an SCLC cell line. Our proteomics and biochemical analyses discover that ADAM12S overexpression elevates while ADAM12 knockdown reduces the rate-limiting enzyme hexokinase 1 (HK1) in glycolysis. Through bioinformatics analyses, genetic manipulation, and in vitro assays, we further reveal that ADAM12S promotes the proliferation, colony formation, migration, and invasion of SCLC cells through upregulating HK1. This work links ADAM12S to glucose metabolic pathways in its attribution to the tumorigenesis and metastasis of SCLC cells and might provide valuable information for the exploration of therapeutic intervention for SCLC.

Pyrophosphate-modified carbon quantum dots (PP-CDs) are demonstrated to be a viable fluorescent nanoprobe for mercury(II) (Hg2+) detection. Hg2+ reacts with the pyrophosphate groups on the surface of PP-CDs to form a non-fluorescent complex. This results in quenching of the green fluorescence which has excitation/emission peaks at 400/513 nm. Static quenching is shown to be the dominant mechanism. The probe works in 0.1 μM to 1.4 μM Hg2+ concentration range, and the limit of detection is 2 nM. The PP-CDs were also used to visualize Hg2+ inside human hepatocyte LO2 cells.

Glutathione (GSH) plays critical roles in many physiological processes usually present in live cells, and altered levels have been linked to some clinical pathological conditions. However, current techniques of GSH detection with fluorescence assay strategies remain poorly researched. In this work, branched polyethylenimine-functionalized carbon dots (PEI-CDs) are synthesized by simple hydrothermal treatment of glucose and PEI. The fluorescence of the PEI-CDs could be efficiently quenched by Cu

2598 Background: Mucin (MUC) is a family of high-molecular weight glycoproteins and increased mucin production occurs in many malignant tumors. Recent studies have found relationship between mutations of some MUC family genes and efficacy of immunotherapy. Here, we explored the associations of MUC family genes (MUC2, MUC3A, MUC4, MUC5B, MUC6, MUC12, MUC16, MUC17, MUC19) mutation with ICI response based on multidimensional data from multiple solid tumors. Methods: 15 solid tumor types of TCGA genomic data for 6138 patients was used to evaluate tumor mutational burden (TMB) differences between MUC family genes mutation group and wildtype group. TMB was calculated as the total count of nonsynonymous mutations in coding sequence. Neoantigens of 3039 samples across 11 solid tumor types were obtained from The Cancer Immunome Atlas. A pan-cancer immunotherapy cohort (Broad/Dana-Farber, Nat Genet 2018, N = 249) was used to explore the relationship between mutations of MUC family genes and its efficacy of immunotherapy. Results: The most common mutated MUC genes (frequency > 5%) were MUC16 (25.3%), MUC17 (10.8%), MUC5B (10.5%), MUC4 (8.6%), and MUC2 (5.1%). The data between MUC mutation group and wild type group showed a significant difference (P < 0.01) in TMB. Median TMB across fifteen tumors in MUC mutation group and wild type group is 7.04 mutations per Mb and 2.07 mutations per Mb, separately. The TNB between two group is also showed a significant difference (P < 0.01). Median TNB across nine types tumor in MUC mutation group and wild type group is 121.5 neoantigens and 34.0 neoantigens, separately. A multivariable analysis across the pan-cancer cohort using Cox proportional-hazards regression demonstrated that KMT2C mutation was associated with better OS (hazard ratio, 0.66; 95%CI, 0.45-0.99; P = 0.042), adjusting for sex and cancer type. Conclusions: The results indicated that MUC family genes mutation was associated with a higher TMB and TNB. Analysis of immunotherapy cohort data showed MUC family was associated with better OS. These findings indicate that these genes mutation may serve as a predictive biomarker for ICI in solid tumor patients.

e17019 Background: Ataxia telangiectasia-mutated（ATM）is a serine/threonine kinase involved in DNA-damage repair (DDR) system and regulating cell cycle checkpoints, senescence, and apoptosis. Several clinical studies provide evidence about the DDR-mutated metastatic castration-resistant prostate cancer (mCRPC) benefit from PARP inhibitors (PARPi). However. the efficacy of PARPi was limited for mCRPC patients harboring ATM aberrations. We aimed to determine the association of ATM mutations with clinical and molecular features in patients with mCRPC. Methods: A total of three independent prostate cancer cohorts (MCTP, N = 61; SU2C-PCF, N = 429; MSKCC, N = 451) were used for analysis. We selected patients with characteristics “mCRPC” and “histology type: prostate adenocarcinoma”. Both the somatic and germline pathogenic alterations were analyzed, including single nucleotide variations (SNVs), in-frame insertions or deletions (Indels), frameshifts, homozygous deletions and fusions. The statistical analysis was conducted by R software (v.3.6.2). Results: We merged the three mCRPC cohorts, generating a new cohort consisting of 507 mCRPC patients. The median age was 62 (range, 38.6-89). The number of biopsies was 1-3 per patient. Of the 527 sequenced specimens, 39% were lymph node, 27% were bone, and 14% were liver. Forty percent of the patients had exposed to or on-treatment with next-generation androgen receptor signaling inhibitor (ARSI). A total of 44 patients (8.7%) harbored deleterious variations in ATM, including 10 homozygous deletions. The coexistence mutations were most commonly located in androgen receptor ( AR), followed by TTN/KMT2C/MUC16/TP53. Furthermore, we explored the association of pathogenic ATM alterations with clinical features. Compared with noncarriers of ATM mutations , carriers were diagnosed at a younger age (median: 59 vs 62.4, P = 0.022). In the subgroup from SU2C-PCF cohort, prostate specific antigen (PSA) at diagnosis and the proportion of Gleason score between 8-10 were analyzed, both showed no significant differences between the two groups. Notably, we observed a statistically significant higher TMB in ATM-altered group than ATM wildtype group (median, 2.04 vs 1.61, P = 0.013). Overall survival (OS) was not compared because of the limited clinical outcomes in ATM-mutated population. Conclusions: This study involving 3 cohorts identified the prevalence of pathogenic somatic or germline ATM mutations and explored the association of ATM alterations with both clinical and molecular features. Patients with ATM mutations tended to diagnose prostate cancer at an earlier age. Meanwhile, significantly higher TMB might imply potential immunotherapy opportunities in ATM-altered mCRPC without standard-of-care approaches.