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Highlights • Evaluation of epilepsy source extent estimation from MEG measurements. • FAST-IRES gave robust location and extent estimation under different noise levels. • Epileptic sources were estimated from interictal discharges in drug-resistant epilepsy patients. • FAST-IRES outperformed LCMV in both simulation and patient data analysis., Non-invasive MEG/EEG source imaging provides valuable information about the epileptogenic brain areas which can be used to aid presurgical planning in focal epilepsy patients suffering from drug-resistant seizures. However, the source extent estimation for electrophysiological source imaging remains to be a challenge and is usually largely dependent on subjective choice. Our recently developed algorithm, fast spatiotemporal iteratively reweighted edge sparsity minimization (FAST-IRES) strategy, has been shown to objectively estimate extended sources from EEG recording, while it has not been applied to MEG recordings. In this work, through extensive numerical experiments and real data analysis in a group of focal drug-resistant epilepsy patients’ interictal spikes, we demonstrated the ability of FAST-IRES algorithm to image the location and extent of underlying epilepsy sources from MEG measurements. Our results indicate the merits of FAST-IRES in imaging the location and extent of epilepsy sources for pre-surgical evaluation from MEG measurements.

Pyemotes zhonghuajia is an ectoparasitoid natural enemy of a wide range of pests such as Lepidoptera, Coleoptera and Hymenoptera. Phthorimaea operculella (Zeller) (PTM) is a worldwide potato pest with serious damage of potato production. Our study showed that one P. zhonghuajia female could kill 1st to 4th instar larvae of PTM, and the lethal time of one P. zhonghuajia female on first to fourth PTM instar larvae were 5.48, 11.33, 23.47 and 2076 min, respectively. The parasitism of 1, 3, 5, 10, and 20 P. zhonghuajia mites could significantly affect the mortality rate of PTM 4th instar larvae and pupae. The parasitism durations (30 and 60 mins) of one P. zhonghuajia female on one PTM fourth instar larva could influence the life history of PTM parental generation but did not influence the life table of PTM offspring generation. Releasing 60, 80, and 100 mites or opisthosoma with mites could reduce the occurrence and consumption of PTM on potatoes the weight loss of the potato tuber. The number of insect dung piles in one potato tuber was significantly decreased by releasing 60, 80, and 100 P. zhonghuajia mites, and releasing 100 mites resulted in the lowest number of insect dung piles. Our results indicate that P. zhonghuajia can significantly affect the population growth of PTM. Future studies should explore the lethal mechanism of P. zhonghuajia and its performance in practical application in the warehouse and field condition.

Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae) is an ectoparasitic mite species with a variety of insects-specific protein toxins, which are harmless to mammals and human. This mite can cause the death of many agricultural and forestry pests which can be 680,000 times greater than its own body weight (Tian et al., 2020; Chen et al., 2021). Exploring its genome will help us understand its parasitic mechanism. PacBio technology was used to sequence the genome of P. zhonghuajia. The genome size of P. zhonghuajia was estimated to be 71.943 Mb, which captured 90.6% of the Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness (Song et al., 2022). A total of 11,183 protein coding genes were annotated with 91.2% BUSCO completeness. Maximum Likelihood phylogenetic tree was constructed using 473 single-copy genes of 12 species including two species of spiders, two species of scorpions and 10 species of mites, of which spiders and scorpions were outgroups. The result shows that Pyemotes zhonghuajia is sister to Tetranychus urticae. An estimate of species divergence time showed that P. zhonghuajia and T. urticae emerged during Triassic (223.43~247.66 Mya). In P. zhonghuajia, there were 621 gene families (containing 1,224 genes) expanded, and 3664 gene families (containing 3,927 genes) contracted. Most importantly, we found that P. zhonghuajia contained three types of toxin proteins, which were neurotoxins, dermonecrotic toxins and agatoxins. Neurotoxin and dermonecrotic toxin-related genes are significantly expanded. The toxin-related gene expression level of one-day-old mites was higher than that of seven-day-pregnant mites, which might explain why one one-day-old mite had such strongly toxin (Chen et al., 2021). We also verified the function of the toxin proteins and explored its effect on insect cells to lay a theoretical foundation for the study and development of biopesticides with multi-target insecticidal toxins (Song et al., 2022).

Cascade transitions of Ho3+:5I6→5I7 and 5I7→5I8 provide a platform for a dual-wavelength mid-infrared (MIR) laser. In this paper, a continuous wave cascade MIR Ho:YLF laser operating at 2.1 and 2.9 µm is realized at room temperature. The total output power of 929 mW with 778 mW at 2.9 µm and 151 mW at 2.1 µm is obtained under the absorbed pump power of 5 W. Compared to the non-cascade mode, 2.9-µm lasing threshold is reduced by 10.3% and the slope efficiency is increased by 76.1% with the supports of cascade lasing at 2.1 µm. However, 2.9-µm lasing is the key population accumulation of the 5I7 level, which thus efficiently reduces the threshold and improves the output power of the 2.1-µm laser. Our results put forward a way for generating cascade dual-wavelength MIR lasing in Ho3+-doped crystals.

The modified Frantz–Nodvik equation considering the pulse repetition rate (PRR) for continuous-wave end-pumped picosecond laser amplifier is theoretically developed for the first time by analogizing Q-switch theory and solving rate equations. Based on the modified Frantz–Nodvik equation, a simple finite-element slice model is established to simulate the output characteristics of the end-pumped high-repetition-rate picosecond amplifier. Moreover, the validity of the theory and model is well verified by the experimental results of a two-staged diode-end-pumped Nd : YVO4 amplifiers using a picosecond fiber laser with adjustable PRRs as the seed source. The agreement between the experimental and theoretical results illustrates that the as-developed pulse amplification theory and model are a powerful tool for designing and optimizing adjustable-high-repetition-rate solid-state picosecond laser amplifiers.

In this paper, we propose a low complexity partial transmit sequence (PTS) method to reduce the peak-to-average power ratio (PAPR) of OFDM signals, which is based on Monte Carlo tree search. Compared to the computation prohibitive exhaustive search, our proposed method can achieve a better tradeoff between PAPR reduction and computing load by cutting down the number of candidate phase vectors to the square of subblocks. Numerical results show that our proposed method reduces the computational complexity of the classic reduced complexity PTS method by 35 times at the cost of 1.16 dB PAPR performance degradation when the subblock number is 8, or achieves a 0.2 dB PAPR performance improvement at half of the computation cost of the classic iterative flipping PTS method.

The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. In addition to KIT, AKT is a relevant target for inhibition, since the PI3K/AKT pathway is crucial for IM-resistant GIST survival. We evaluated the activity of a novel pan-AKT inhibitor, MK-4440 (formerly ARQ 751), as monotherapy and in combination with IM in GIST cell lines and preclinical models with varying IM sensitivities. Dual inhibition of KIT and AKT demonstrated synergistic effects in IM-sensitive and -resistant GIST cell lines. Proteomic analyses revealed upregulation of the tumor suppressor, PDCD4, in combination treated cells. Enhanced PDCD4 expression correlated to increased cell death. In vivo studies revealed superior efficacy of MK-4440/IM combination in an IM-sensitive preclinical model of GIST compared with either single agent. The combination demonstrated limited efficacy in two IM-resistant models, including a GIST patient-derived xenograft model possessing an exon 9 KIT mutation. These studies provide strong rationale for further use of AKT inhibition in combination with IM in primary GIST, however, alternative agents will need to be tested in combination with AKT inhibition in the resistant setting.

Nanozymes are a series of elaborately designed nanomaterials that can mimic the catalytic sites of natural enzymes for reactions. Bypassing the tedious design and preparation of nanomaterial, in this work, we report on a novel just-in-time production system of copper hexacyanoferrate nanoparticles (CHNPs), which act as an oxidase-mimicking nanozyme. This system can rapidly produce CHNPs nanozyme on demand by simply mixing Cu(II) with potassium hexacyanoferrate(III) (K

Summary Members of a disintegrin and metalloproteinases with thrombospondin motif (ADAMTS) family have been implicated in various vascular diseases. However, their functional roles in early embryonic vascular development are unknown. In this study, we showed that Adamts18 is highly expressed at E11.5-E14.5 in cells surrounding the embryonic aortic arch (AOAR) and the common carotid artery (CCA) during branchial arch artery development in mice. Adamts18 deficiency was found to cause abnormal development of AOAR, CCA, and the third and fourth branchial arch appendages, leading to hypoplastic carotid body, thymus, and variation of middle cerebral artery. Adamts18 was shown to affect the accumulation of extracellular matrix (ECM) components, in particular fibronectin (Fn), around AOAR and CCA. As a result of increased Fn accumulation, the Notch3 signaling pathway was activated to promote the differentiation of cranial neural crest cells (CNCCs) to vascular smooth muscle cells. These data indicate that Adamts18-mediated ECM homeostasis is crucial for the differentiation of CNCCs., Graphical abstract, Highlights • Adamts18 is highly expressed during the period of embryonic carotid artery formation • Adamts18 deficiency leads to abnormal AOAR, CCA, MCA branches and carotid appendages • Adamts18 deficiency changes the cerebral infarcted areas in mouse tMCAO model • Adamts18 affects the differentiation of CNCCs to VSMCs by modulating Notch3 pathway, Cell biology; Developmental biology

The use of carbon dots (CDs) with dual emission based on ratiometric fluorescence has been attracting attention in recent times for more accurate ion detection since they help avoid interference from background noise, probe concentration, and complexity. Herein, novel dual-emission nitrogen-doped CDs (NCDs) were prepared by a simple method for Cu2+ and ClO- detection. The NCDs showed excellent anti-interference ability and selectivity for different emissions. In addition, a good linear relationship was observed between the fluorescence intensity (FI) of the NCD solutions in different emissions with Cu2+ (0–90 μM) and ClO− (0–75 μM). The limits of both Cu2+ detection and ClO− were very low, at 17.7 and 11.6 nM, respectively. The NCDs developed herein also showed a good recovery rate in water for Cu2+ and ClO− detection. Hence, they are expected to have a more extensive application prospect in real samples.

Significance Millions of people affected by epilepsy may undergo surgical resection of the epileptic tissues to stop seizures if such epileptic foci can be accurately delineated. High-frequency oscillations (HFOs), existing in electroencephalography, are highly correlated with epileptic brain, which is promising for guiding successful neurosurgery. However, it is unclear whether and how pathological HFOs can be differentiated to localize the epileptogenic tissues given the presence of various nonepileptic high-frequency activities. Here, we show morphological and source imaging evidence that pathological HFOs can be identified by the concurrence of epileptiform spikes. We describe a framework to delineate the underlying epileptogenicity using this biomarker. Our work may offer translational tools to improve treatments by noninvasively demarking pathological activities and hence epileptic foci., High-frequency oscillations (HFOs) are a promising biomarker for localizing epileptogenic brain and guiding successful neurosurgery. However, the utility and translation of noninvasive HFOs, although highly desirable, is impeded by the difficulty in differentiating pathological HFOs from nonepileptiform high-frequency activities and localizing the epileptic tissue using noninvasive scalp recordings, which are typically contaminated with high noise levels. Here, we show that the consistent concurrence of HFOs with epileptiform spikes (pHFOs) provides a tractable means to identify pathological HFOs automatically, and this in turn demarks an epileptiform spike subgroup with higher epileptic relevance than the other spikes in a cohort of 25 temporal epilepsy patients (including a total of 2,967 interictal spikes and 1,477 HFO events). We found significant morphological distinctions of HFOs and spikes in the presence/absence of this concurrent status. We also demonstrated that the proposed pHFO source imaging enhanced localization of epileptogenic tissue by 162% (∼5.36 mm) for concordance with surgical resection and by 186% (∼12.48 mm) with seizure-onset zone determined by invasive studies, compared to conventional spike imaging, and demonstrated superior congruence with the surgical outcomes. Strikingly, the performance of spike imaging was selectively boosted by the presence of spikes with pHFOs, especially in patients with multitype spikes. Our findings suggest that concurrent HFOs and spikes reciprocally discriminate pathological activities, providing a translational tool for noninvasive presurgical diagnosis and postsurgical evaluation in vulnerable patients.

The lack of organic electron transport materials (ETM) with excellent electron transport and device stability is an important problem for the development and commercialization of perovskite solar cells (PSCs). Herein, a ladder-conjugated perylene diimide dimer containing an indacenodithiophene unit, namely IDTT2FPDI, was synthesized in two steps with high yields. In addition, IDTT2FPDI exhibits suitable energy levels, high electron mobility, and an excellent hydrophobicity because of its multiple fused thiophene rings and large ladder-conjugated framework. Compared with inverted PSCs which typically use PCBM as a single electron transport layer (ETL), the device utilizing IDTT2FPDI/PCBM as a double ETL showed a better power conversion efficiency (PCE) of 19.4%. Moreover, the double ETL-based devices exhibited superior stability compared with the single ETL-based devices due to the hydrophobicity of the IDTT2FPDI layer. These results highlight the potential of employing ladder-conjugated PDI dimers as ETMs to obtain high-efficiency and stable PSCs, which shows promise for the development of PSCs.

Room temperature phosphorescent (RTP) carbon dots have attracted considerable interest due to their fundamental importance and potential applications in optoelectronic devices, sensing, bioimaging and document security. The preparation method of RTP carbon dots is based on the formation of the CN (or CO) groups and hydrogen bond. Herein, we have added acrylamide in the reaction system to form hydrogen bonds and stabilize the triplet excitons. Thus, the nontoxic RTP carbon dots (NCDs) were designed and prepared via a one-step hydrothermal method. The nitrogen element (N) in the NCDs can effectively increase their fluorescence intensity, while the produced CN bonds promote the formation of triplet excitons. More importantly, the acrylic amide and the as-generated polyacrylamide (PAM) on the surface of NCDs could easily connect with the as-prepared pyridinic N via the reaction between citric acid and urea, and formed the hydrogen bond that could stablilize the triplet excitons. Hence, NCDs exhibit stable phosphorescence properties. We further show the promising application of the as-prepared aqueous NCDs as a new smart concealed and potential security ink.

Terminal differentiation opposes proliferation in the vast majority of tissue types. As a result, loss of lineage differentiation is a hallmark of aggressive cancers, including soft tissue sarcomas (STS). Consistent with these observations, undifferentiated pleomorphic sarcoma (UPS), an STS subtype devoid of lineage markers, is among the most lethal sarcomas in adults. Though tissue-specific features are lost in these mesenchymal tumors they are most commonly diagnosed in skeletal muscle, and are thought to develop from transformed muscle progenitor cells. We have found that a combination of HDAC (Vorinostat) and BET bromodomain (JQ1) inhibition partially restores differentiation to skeletal muscle UPS cells and tissues, enforcing a myoblast-like identity. Importantly, differentiation is partially contingent upon downregulation of the Hippo pathway transcriptional effector Yes-associated protein 1 (YAP1) and nuclear factor (NF)-κB. Previously, we observed that Vorinostat/JQ1 inactivates YAP1 and restores oscillation of NF-κB in differentiating myoblasts. These effects correlate with reduced tumorigenesis, and enhanced differentiation. However, the mechanisms by which the Hippo/NF-κB axis impact differentiation remained unknown. Here, we report that YAP1 and NF-κB activity suppress circadian clock function, inhibiting differentiation and promoting proliferation. In most tissues, clock activation is antagonized by the unfolded protein response (UPR). However, skeletal muscle differentiation requires both Clock and UPR activity, suggesting the molecular link between them is unique in muscle. In skeletal muscle-derived UPS, we observed that YAP1 suppresses PERK and ATF6-mediated UPR target expression as well as clock genes. These pathways govern metabolic processes, including autophagy, and their disruption shifts metabolism toward cancer cell-associated glycolysis and hyper-proliferation. Treatment with Vorinostat/JQ1 inhibited glycolysis/MTOR signaling, activated the clock, and upregulated the UPR and autophagy via inhibition of YAP1/NF-κB. These findings support the use of epigenetic modulators to treat human UPS. In addition, we identify specific autophagy, UPR, and muscle differentiation-associated genes as potential biomarkers of treatment efficacy and differentiation.

Data evaluating changes in bone mineral density (BMD) in Down syndrome (DS) individuals remains controversial. Therefore, we conducted a systematic review and meta-analysis to better understand associations between BMD and DS. A systematic literature search of PubMed, EMBASE, Web of Science, and the Cochrane Library up until 1st January 2021 was conducted. We used the keywords “bone mineral density” and “Down Syndrome.” Fifteen studies were included. Overall, our results showed a significant decrease in BMD of total body (TB BMD) [MD = − 0.18; 95% CI (− 0.23 and − 0.12), P

Single-crystal fibers (SCFs) have a great application potential in high-power lasers due to their excellent performance. In this work, high-quality and crack-free Yb3+:Lu3Al5O12 (Yb:LuAG) SCFs were successfully fabricated by the micro-pulling-down (&mu, PD) technology. Based on the laser micrometer and the X-ray Laue diffraction results, these Yb:LuAG SCFs have a less than 5% diameter fluctuation and good crystallinity along the axial direction. More importantly, the distribution of Yb ions is proved to be uniform by electron probe microanalysis (EPMA) and the scanning electron microscope (SEM). In the laser experiment, the continuous-wave (CW) output power using a 1 mm diameter Yb:LuAG single-crystal fiber is determined to be 1.96 W, at the central wavelength of 1047 nm, corresponding to a slope efficiency of 13.55%. Meanwhile, by applying a 3 mm diameter Yb:LuAG SCF, we obtain a 4.7 W CW laser output at 1049 nm with the slope efficiency of 22.17%. The beam quality factor M2 is less than 1.1 in both conditions, indicating a good optical quality of the grown fiber. Our results show that the Yb:LuAG SCF is a potential solid-state laser gain medium for 1 &mu, m high-power lasers.

Management of gastrointestinal stromal tumors (GISTs) has been revolutionized by the identification of activating mutations in KIT and PDGFRA and clinical application of RTK inhibitors in advanced disease. Stratification of GISTs into molecularly defined subsets provides insight into clinical behavior and response to approved targeted therapies. Although these RTK inhibitors are effective in most GISTs, resistance remains a significant clinical problem. Development of effective treatment strategies for refractory GISTs requires identification of novel targets to provide additional therapeutic options. Global kinome profiling has the potential to identify critical signaling networks and reveal protein kinases essential in GISTs. Using multiplexed inhibitor beads and mass spectrometry, we explored the majority of the kinome in GIST specimens from the 3 most common molecular subtypes (KIT mutant, PDGFRA mutant, and succinate dehydrogenase deficient) to identify kinase targets. Kinome profiling with loss-of-function assays identified an important role for G2/M tyrosine kinase, Wee1, in GIST cell survival. In vitro and in vivo studies revealed significant efficacy of MK-1775 (Wee1 inhibitor) in combination with avapritinib in KIT mutant and PDGFRA mutant GIST cell lines as well as notable efficacy of MK-1775 as a monotherapy in the engineered PDGFRA mutant line. These studies provide strong preclinical justification for the use of MK-1775 in GIST.

ADAMTS members have been implicated in vascular diseases by degrading extracellular matrix (ECM), but their functional significance in vascular development remains unknown. We now show that the secreted protease ADAMTS18 is produced by mesenchymal cells and fibroblasts surrounding the embryonic aortic arch (AOAR) and the common carotid artery (CCA). ADAMTS18 deficiency leads to aberrant AOAR and CCA, which further disturbs the development of the 3rd and 4th branchial arch appendages, leading to lack of formation of the carotid body, generation of ectopic and hypoplastic thymus, and variation of intracranial vascular branches of CCA. ADAMTS18 was shown to modulate the ECM abundance around AOAR and CCA, in particular fibronectin (Fn). Adamts18 deficiency lead to Fn accumulation, thus activating the Notch3 signaling pathway to promote the differentiation of cranial neural crest cells (CNCCs) to vascular smooth muscle cells. These data disclose that ADAMTS18-mediated ECM homeostasis is crucial for the differentiation of CNCCs.

Monoelemental two-dimensional (2D) group-VA materials have received increasing interest due to their great potential in optoelectronic applications. Despite numerous efforts have been made for their syntheses, the development of effective and better controllable synthetic approaches for the preparation of monoelemental 2D group-VA materials is still in its infancy. In this work, we report a soft-template approach for the synthesis of multilayered antimonene and bismuthene nanosheets in colloidal solutions. We show that the prepared antimonene and bismuthene nanosheets possess a well-defined rhombohedral crystal structure with impressive stability. We elucidate a formation pathway for the 2D nanosheets with small-angle X-ray diffraction (XRD) analysis. We demonstrate that SbCl3 dissolves in alkyl phosphonic acids to form a lamellar structure initially, which is apt for the formation of the final 2D morphology. The present study introduces a general route to synthesizing monoelemental 2D group-VA materials in colloidal solutions and gives a deeper insight into their growth mechanism.

In recent years, metal halide perovskites have been widely investigated to fabricate photodetectors for image sensing due to the excellent photoelectric performance, tunable bandgap, and low-cost solution preparation process. In this review, a comprehensive overview of the recent advances in perovskite photodetectors for image sensing is provided. First, the key performance parameters and the basic device types of photodetectors are briefly introduced. Then, the recent developments of image sensors on the basis of different dimensional perovskite materials, including 0D, 1D, 2D, and 3D perovskite materials, are highlighted. Besides the device structures and photoelectric properties of perovskite image sensors, the preparation methods of perovskite photodetector arrays are also analyzed. Subsequently, the single-pixel imaging of perovskite photodetectors and the strategies to fabricate narrowband perovskite photodetectors for color discrimination are discussed. Finally, the potential challenges and possible solutions for the future development of perovskite image sensors are presented.

In UAVs, optimal control has attracted more and more attention. In this paper, a self-learning adaptive dynamic programming (ADP) architecture based reinforcement learning (RL) is proposed to obtain optimal control for UAVs. 1 Compared with the traditional ADP architecture including two networks, one is used to make policy, and the other is used to evaluate policy, We propose to add a third network to replace external reward signals, that is, the agent can acquire reward signals by itself and do not need to interact with the environment. The proposed self-learning ADP method can improve the control performance by online learning while ensuring the state of the system stable at the equilibrium point. Finally, the proposed control algorithm is applied to quadrotor UAVs, and the experimental results show that the effectiveness of the algorithm.

A modified Frantz-Nodvik (F-N) equation and a simple one-dimensional unfolded slicing model for numerically simulating high-power Innoslab picosecond amplifier are developed for the first time. The anisotropic stimulated emission cross-section of laser crystal, the influence of the tilted optical path, the spatial overlap of the seed and pump laser, as well as the pump absorption saturation effect are considered. Based on the as-developed model, 4-, 6- and 8-pass schemes high-power Nd:YVO4 Innoslab picosecond amplifiers are designed with output powers of 76.2 W, 81.4 W, and 85.5 W, respectively. The experimental results agree well with that of numerical simulation, indicating that our model is a powerful tool and paves a new way for designing and optimizing high-power Innoslab picosecond laser amplifier.

In this research, the complete mitochondrial genome (mitogenome) of Phthorimaea operculella was sequenced and annotated. The mitogenome of P. operculella is 15,269 bp in length and contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosome RNA (12s and 16srRNA) genes and 1 control region. In addition, we used Endoclita signifier as the outgroup to analyze phylogenetic relationship, and the phylogenetic tree showed the sister relationship between P. operculella and Tuta absoluta.

In this study, we sequenced and annotated the complete mitochondrial genome (mitogenome) of Neotoxoptera formosana (Takahashi) (Hemiptera: Aphididae). The complete mitogenome of N. formosana is 15,642 bp in length, and includes 13 protein-coding genes (PCGs), 2 ribosome RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region. The overall base composition was as follows: 45.2% of A, 5.8% of G, 10.5% of C, and 38.4% of T, with a total of A + T content of 83.6%. The phylogenetic tree showed that N. formosana and Myzus persicae were clustered into one branch. This result will enrich the mitogenome of family Aphididae.

Down's syndrome (DS), a common chromosomal disease caused by chromosome 21 trisomy, is the main cause of cognitive impairment in children worldwide. Emerging evidence suggests that the microbiota–gut–brain axis plays a potential role in cognitive impairment. However, data regarding gut microbiota alterations in DS patients remain scarce, especially data from children with DS. This case–control study was conducted to explore the gut microbiota composition in Chinese DS children. Additionally, the potential association between gut microbiota and cognitive function in DS was evaluated. Microbiota communities in the feces of 15 DS subjects and 15 matched controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3–V4 region of 16S rRNA gene. The relationships between gut microbiota composition and DS cognitive function scores were analyzed. The structure and richness of the gut microbiota differed between DS patients and healthy controls. The abundance of Acidaminococcaceae was decreased in DS patients. Moreover, the Kyoto Encyclopedia of Genes and Genomes analysis showed increased modules related to peptidases and pyrimidine metabolism. Overall, we confirmed that gut microbiota alterations occurred in Chinese patients with DS. Additionally, the fecal microbiota was closely related to DS cognitive impairment. Larger cohorts are needed to confirm these findings and to clarify the mechanisms involved. Elucidating these novel findings in the field of microbiota-gut-brain axis will provide a promising strategy for future studies of DS cognitive impairment.

Aims: This study aims to evaluate and validate a simple quantitative ultrasound (US) method for determining the hepatic fat content (HFC) based on the combination of quantitative US hepatic/renal ratio (US-HRR) and quantitative US hepatic echo-intensity attenuation rate (US-HAR) as compared with [1H]-magnetic resonance spectroscopy (1H-MRS).Material and methods: There were a total of 242 subjects recruited in the present study. All subjects were examined for HFC by quantitative US and 1H-MRS methods. The QUS-HRR and QUS-HAR were calculated from ordinary ultrasound images of liver and kidney with a triple modality 3D abdominal phantom using the Image J software.Results: The results found that US-HRR and US-HAR correlated with 1H-MRS HFC (US-HRR: r=0.946, p

Intrusion detection of network traffic is essential in the field of network security. The types of network traffic are diverse. Their attributes are highly correlated at the same time and are continuous in time. However, existing deep learning methods do not use them together for classification. The traditional intrusion detection methods that rely on manual extraction features have problems such as high false positive rate and low recognition performance. This paper proposes a deep learning method DeepIDN that uses the spatial and temporal features of data attributes to perform classification tasks and applies it to intrusion detection. DeepIDN uses a two-dimensional convolution operation to construct a convolutional neural network (CNN) layer to extract the association between data attributes and establish a spatial feature model. Then, by constructing a long short-term memory (LSTM) layer to extract time-related correlation between features, a relational model on time series is established. Finally, using the support vector machine as a classifier, the intrusion detection of network traffic is realized, and the prediction performance is greatly improved. Compared to traditional methods, DeepIDN does not require a lot of data preprocessing workload. The experimental results show that compared with the similar intrusion detection methods, the accuracy of DeepIDN for malicious network traffic judgment is significantly improved, reaching 98.66% training accuracy and 97.15% testing accuracy and higher robustness during the training and testing.

Management of gastrointestinal stromal tumor (GIST) has been revolutionized by the identification of activating mutations in KIT and PDGFRA, and the clinical application of receptor tyrosine kinase (RTK) inhibitors in the advanced disease setting. Stratification of GIST into molecularly defined subsets provides insight into clinical behavior and response to approved targeted therapies. Although these RTK inhibitors are effective in the majority of GIST, resistance to these agents remains a significant clinical problem. Development of effective treatment strategies for refractory GIST subtypes requires identification of novel targets to provide additional therapeutic options. Global kinome profiling has the potential to identify critical signaling networks and reveal protein kinases that are essential in GIST. Using Multiplexed Inhibitor Beads and Mass Spectrometry, we explored the majority of the kinome in GIST specimens from the three most common molecular subtypes to identify novel kinase targets. Kinome profiling revealed distinct signatures in GIST subtypes and identified kinases that are universally activated in all GIST, as well as kinases that are unique to each subtype. Kinome profiling in combination with loss-of-function assays identified a significant role for the G2-M tyrosine kinase, Wee1, in GIST cell survival.In vitroandin vivostudies revealed significant efficacy of MK-1775 (Wee1 inhibitor) in combination with avapritinib inKITandPDGFRA-mutant GIST cell lines, and notable efficacy of MK-1775 as a single agent in thePDGFRA-mutant line. These studies provide strong preclinical justification for the use of MK-1775 in GIST.

Quantum dots of halide perovskite are considered to be the promising candidates for optoelectronic applications. Although many methods have been developed to prepare CsPbX3 (X = Cl, Br, I) nanocrystals, the large-scale synthesis of CsPbX3 nanocrystals remains an outstanding challenge. In this paper, nanocrystals of CsPbBr3 were subjected to one-pot synthesis in octane by using a precursor with a high concentration. CsPbBr3 nanocrystals were obtained in octane dispersion as well as in the precipitation. All obtained nanocrystals were in the CsPbBr3 nanocubes with uniform morphologies and average size of 7.8 nm, and featured the same emission peak and photoluminescence quantum yield (PLQY), which indicated that the concentration of the precursor did not influence the nucleation of the CsPbBr3 nanocrystals. This result implied a large-scale synthesis of the nanocrystals. Following this, ~ 1 g of CsPbBr3 nanocrystals were obtained only in the 10-mL octane solution when the concentration of PbBr2 was up to 0.3 mol/L. This one-pot process was suitable for the large-scale and cost-effective synthesis of CsPbX3 nanocrystals. Besides, the obtained CsPbBr3 nanocrystals were used as probes of the [Zn2+] detection for the first time. It was found that the Zn2+ ions could quench the photoluminescence intensity of CsPbX3 nanocrystals and the quench effect showed high selectivity and high anti-interference.

Electroencephalography (EEG) and magnetoencephalography (MEG) are used to measure brain activity, noninvasively, and are useful tools for brain research and clinical management of brain disorders. Tremendous effort has been made in solving the inverse source imaging problem from EEG/MEG measurements. This is a challenging ill-posed problem, since the number of measurements is much smaller than the number of possible sources in the brain. Various methods have been developed to estimate underlying brain sources from noninvasive EEG/MEG as this can offer insight about the underlying brain electrical activity with significantly improved spatial resolution. In this work, we propose a novel data-driven Source Imaging Framework using deep learning neural networks (SIFNet), where (1) a simulation pipeline is designed to model realistic brain activation and EEG/MEG signals to train generalizable neural networks, (2) and a residual convolutional neural network is trained using the simulated data, capable of estimating source distributions from EEG/MEG recordings. The performance of our proposed SIFNet approach is evaluated in a series of computer simulations, which indicates the excellent performance of SIFNet outperforming conventional weighted minimum norm algorithms that were tested in this work. The SIFNet is further tested by analyzing interictal EEG data recorded in a clinical setting from a focal epilepsy patient. The results of this clinical data analysis indicate accurate localization of epileptogenic activity as validated by the epileptogenic zone clinically determined in this patient. In sum, the proposed SIFNet approach promises to offer an alternative solution to the EEG/MEG inverse source imaging problem, shows promising signs of being robust against measurement noise, and is easy to implement, therefore, being translatable to clinical practice.

Background and Aim Circular RNAs (circRNAs) have been highlighted to exert essential biological functions in papillary thyroid cancer (PTC). The purpose of this study was explore diagnostic utility of circRNAs in PTC patients. Patients and Methods The distinctive expression profile of serum circRNAs was determined by individual quantitative real-time PCR (qRT-PCR) in two independent cohorts of 113 PTC patients, 80 thyroid nodules, and 111 healthy controls (HCs). A combination of circRNAs (circRNA-based combination index) was constructed by logistic regression. Results Individual qRT-PCR identification showed that two circRNAs (circRAPGEF5 and hsa_circ_0058124) were significantly up-regulated in PTC patients compared with HCs and thyroid nodules. Receiver-operating characteristic (ROC) curve analysis suggested that a combination of circRNAs was superior to individual circRNA in distinguishing PTC patients from HCs and thyroid nodules with area under ROC curve of more than 0.80. Furthermore, the combination of circRNAs increased significantly after systematic treatment, suggesting that it could monitor PTC dynamics. Additionally, the combination of circRNAs was independently correlated with PTC presence. Conclusion The combination of these altered circRNAs was correlated with PTC and may serve as a novel diagnostic approach.

With the continuous advancement of the Belt and Road Initiative, countries along the Belt and Road are becoming the most important geo-economic space for China&rsquo, s peaceful rise. This paper constructs a geo-economic model to measure the geo-economic relations between China and countries along the Belt and Road, analyzes the spatial-temporal patterns of geo-economic flow between China and these countries, and discusses the spatial agglomeration of geo-economic flow between China and these countries. The results show that the geo-economic flow between China and the countries along the Belt and Road is increasing and the geo-economic relations between China and these countries are continuing to improve. Trade flow is far greater than investment flow, and China&rsquo, s geo-economic relations with these countries have mainly relied on trade flow. The spatial differentiation of geo-economic flow between China and countries along the Belt and Road is significant. The development of geo-economic relations is unbalanced, and regional powers play an important role. The geo-economic center of gravity of China and countries along the Belt and Road was moving in the northeastern part of India and it first moved to the northwest and then to the southeast. China&rsquo, s geo-economic space has obvious core-peripheral structure characteristics, and Southeast Asia is the core area of China&rsquo, s geo-economic space. China&rsquo, s geo-economic space presents a northwest-southeast pattern in the direction. There has been a significant, positive spatial autocorrelation in geo-economic flow between China and the countries along the Belt and Road, but the overall spatial agglomeration has been weak. The geo-economic flow agglomerations of China and these countries have mainly occurred in Southeast Asia, and the main agglomeration type has been high&ndash, high. The geo-economic activities of China and Southeast Asia had certain spatial spillover effects. To promote the sustainable development of China&rsquo, s geo-economic relations with the countries along the Belt and Road, China should upgrade investment networks with these countries, optimize geo-economic relations with regional powers, and promote the full development of trade flow, investment flow and other geo-economic element flow.

The radiation diffusion problem is a kind of time-dependent nonlinear equations. For solving the radiation diffusion equations, many linear systems are obtained in the nonlinear iterations at each time step. The cost of linear equations dominates the numerical simulation of radiation diffusion applications, such as inertial confinement fusion, etc. Usually, iterative methods are used to solve the linear systems in a real application. Moreover, the solution of the previous nonlinear iteration or the solution of the previous time step is typically used as the initial guess for solving the current linear equations. Because of the strong local character in ICF, with the advancing of nonlinear iteration and time step, the solution of the linear system changes dramatically in some local domain, and changes mildly or even has no change in the rest domain. In this paper, a local character-based method is proposed to solve the linear systems of radiation diffusion problems. The proposed method consists of three steps: firstly, a local domain (algebraic domain) is constructed; secondly, the subsystem on the local domain is solved; and lastly, the whole system will be solved. Two methods are given to construct the local domain. One is based on the spatial gradient, and the other is based on the residual. Numerical tests for a two-dimensional heat conduction model problem, and two real application models, the multi-group radiation diffusion equations and the three temperature energy equations, are conducted. The test results show that the solution time for solving the linear system can be reduced dramatically by using the local character-based method.

Receptor-interacting protein 140 (RIP140) is a transcription co-regulator of several transcription factors and a signal transduction regulator. RIP140 was recently implicated in the regulation of cognitive functions. The gene that encodes RIP140 is located on chromosome 21. An increase in RIP140 expression was observed in the fetal cerebral cortex and hippocampus in Down syndrome patients who exhibited strong cognitive disabilities. We hypothesized that RIP140 overexpression affects cognitive function in adult neural development. The present study used a Cre-dependent adeno-associated virus to selectively overexpress RIP140 in neural stem cells using nestin-Cre mice. RIP140 overexpression efficiency was evaluated at the subgranular zone (SGZ) of the dorsal dentate gyrus (dDG) and the subventricular zone (SVZ) of the lateral ventricles (LVs). Mice with RIP140 overexpression in the SGZ exhibited deficits in cognitive function and spatial learning and memory, measured in the Morris water maze, object-place recognition test, and novel object recognition test. However, overexpression of RIP140 in SVZ only impaired performance in the Morris water maze and novel object recognition test but not in the object-place recognition test. Altogether, these results indicated defects in cognitive functions that were associated with RIP140 overexpression in neural stem cells and revealed a behavioral phenotype that may be used as a framework for further investigating the neuropathogenesis of Down syndrome.

In this paper, we consider local multiscale model reduction for problems with multiple scales in space and time. We developed our approaches within the framework of the Generalized Multiscale Finite Element Method (GMsFEM) using space–time coarse cells. The main idea of GMsFEM is to construct a local snapshot space and a local spectral decomposition in the snapshot space. Previous research in developing multiscale spaces within GMsFEM focused on constructing multiscale spaces and relevant ingredients in space only. In this paper, our main objective is to develop a multiscale model reduction framework within GMsFEM that uses space–time coarse cells. We construct space–time snapshot and offline spaces. We compute these snapshot solutions by solving local problems. A complete snapshot space will use all possible boundary conditions; however, this can be very expensive. We propose using randomized boundary conditions and oversampling (cf. Calo et al., 2016). We construct the local spectral decomposition based on our analysis, as presented in the paper. We present numerical results to confirm our theoretical findings and to show that using our proposed approaches, we can obtain an accurate solution with low dimensional coarse spaces. We discuss using online basis functions constructed in the online stage and using the residual information. Online basis functions use global information via the residual and provide fast convergence to the exact solution provided a sufficient number of offline basis functions. We present numerical studies for our proposed online procedures. We remark that the proposed method is a significant extension compared to existing methods, which use coarse cells in space only because of (1) the parabolic nature of cell solutions, (2) extra degrees of freedom associated with space–time cells, and (3) local boundary conditions in space–time cells.

Dendritic cells (DCs) are professional antigen-presenting cells (APC) that facilitate the development and progression of atherosclerosis. However, DCs also function as novel “switches” between immune activation and immune tolerance and represent a heterogeneous hematopoietic lineage, with cell subsets in different tissues that show a differential morphology, phenotype, and function. Regulatory DCs, depending on their immature state, can be induced by immunosuppressive modulation, which plays an important part in the maintenance of immunologic tolerance via suppression of the immune response. In this review, we describe the current understanding of the generation of regulatory DCs. The novel role of selectins in the modification of DCs in atherosclerosis is also discussed. Keywords: Dendritic cells, Selectins, Atherosclerosis, Immune tolerance

Halide perovskite (CsPbX3, X = Cl, Br, or I) quantum dots have received increasing attention as novel colloidal nanocrystals (NCs). Accurate control of emission bands and NC morphologies are vital prerequisites for most CsPbX3 NC practical applications. Therefore, a facile method of synthesizing CsPbX3 (X = Cl, Br, or I) NCs in the nonpolar solvent octane was developed. The process was conducted in air at ∼ 90 °C to synthesize high-quality CsPbX3 NCs showing 12–44 nm wide emission and high photoluminescence quantum yield, exceeding 90%. An in situ anion-exchange method was developed to tune CsPbX3 NC photoluminescence emission, using PbX2 dissolved in octane as the halide source. NC morphology was controlled by dissolving specific metal–organic salts in the precursor solution prior to nucleation, and nanocubes, nanodots, nanosheets, nanoplatelets, nanorods, and nanowires were obtained following the same general method providing a facile, versatile route to controlling CsPbX3 NC emission bands and morphologies, which will broaden the range of CsPbX3 NC practical applications.

Visceral adiposity is of greater risk than obesity in s.c. adipose tissue for diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is associated with extracellular matrix (ECM) remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted zinc-dependent metalloproteinases that play crucial roles in development and various diseases because of their ECM remodeling activity. ADAMTS18 is an orphan ADAMTS whose function and substrate remain unclear. Herein, we showed that Adamts18 mRNA was abundantly expressed in visceral (gonadal) white adipose tissue (vWAT) during the early stage of development after birth. Adamts18 knockout (KO) mice showed increased body fat percentage and larger adipocyte size in vWAT relative to wild-type littermates. These findings may be partly attributed to ECM remodeling, especially increased expression of laminin 1 and adipokine thrombospondin 1 in vWAT. Attenuated extracellular signal–regulated kinase 1 and 2 activity, along with increased expression of adipocyte-specific transcription factors peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein β, and marker gene Fabp4 , was detected in vWAT of Adamts18 KO mice. Furthermore, Adamts18 KO mice showed early metabolic syndrome, including hyperlipidemia, blood glucose metabolic disorder, and hypertension. ADAMTS18 deficiency promotes atherosclerosis in apolipoprotein E–deficient mice. These results indicate a novel function of ADAMTS18 in vWAT development and associated metabolic disorders.

Perovskite quantum dots emit upconversion photoluminescence (UCPL) excited by long wavelength photons. However, UCPL with different wavelengths and widths are irradiated in perovskite colloidal excited by different energy photons. This study investigated efficient UCPL in colloidal CsPbBrI2 nanocrystals and proposed a simple energy level model to illustrate the UC mechanism. Red-shifted UCPL relative to normal PL was attributed to recombination of carriers from the surface to the valence band and involved a single-photon process, whereas unshifted UCPL was attributed to recombination of carriers from the conduction band to the valence band and involved a two-photon process. Trap states within the valence band played an important role in the UC process. Single photon UC emission occurred when the absorbed photons possessed sufficient energy to excite electrons in deep trap states in CsPbBrI2 nanocrystals. However, when the photons could only excite electrons in shallow trap states, some excited photons wer...

The purpose of this study was to improve the critical current density (Jc) of YBa2Cu3O7−δ (YBCO) superconducting films at high magnetic fields. Thin Y1−xYbxBa2Cu3O7−δ (Y1−xYbxBCO) superconducting films on LaAlO3 substrates were prepared by modified low-fluorine metal organic deposition method (LF-MOD) in order to investigate the effect of Yb substitution on the microstructure and superconducting properties of a YBCO-coated conductor. In this study, single-phased, c-axial-aligned Y1−xYbxBCO films were obtained. Yb doping had a little effect on the critical temperature (Tc) and transition width (ΔT) values of Y1−xYbxBCO films. An abnormal phenomenon was observed that the Jc of Y1−xYbxBCO films at low field was smaller than that of the pure YBCO film, but the Jc of Y1−xYbxBCO films at high field was much greater than that of the undoped YBCO film. Compared to pure YBCO film, the Jc values of Y0.75Yb0.25BCO and Y0.25Yb0.75BCO films were enhanced by a factor of 8 at 8 T, 65 K, which meant that chemical substitution of Yb into the Y site could improve flux pinning significantly under the high magnetic field in Y1−xYbxBCO coated conductors.

Lead halide perovskite nanocrystals with efficient two-photon absorption and ease of achieving population inversion have been recognized as good candidates to achieve frequency up-conversion for biophotonics applications, but suffer from the limitation of the miniaturization of the device and its corresponding poor stability when exposed to atmospheric moisture. Here we demonstrate the miniaturization of plasmonic nanolasers via embedding perovskite quantum dots (QDs) in rationally designed dual-mesoporous silica with gold nanocore. The nanocomposite supports resonant surface plasmon-polaritons (SPPs), which overlap both spatially and spectrally with the CsPbBr3 QDs. The outcoupling between surface plasmon oscillations and photonics modes within a wavelength range completely overcomes the loss of localized surface plasmons, and finally contributes to a novel application of two-photon-pumped nanolasers. Large optical gain under two-photon excitation was observed as a result of resonant energy transfer from excited perovskite QDs to surface plasmon oscillations and stimulated emission of surface plasmons in a luminous mode. The outmost organic–inorganic hybrid shells of the dual-mesoporous silica nanocomposites act as a protective layer of the perovskite QDs against water and endow the nanocomposites with superhydrophobicity. This work provides an alternative inspiration for the design of new two-photon pumped nanolasers.

It is essential to determine the elemental composition of doped functional materials, particularly for nanometer scale semiconductors, to guide synthesis and interpret physical phenomena. This study applied laser induced breakdown spectroscopy (LIBS) for elemental analysis of halides in perovskite type quantum dots, i.e., CsPbX3 nanocrystals (NCs). The optimum LIBS delay time and laser energy were experimentally determined, and small quantities of CsPbX3 NCs (μg) with different Cl/Br ratios and different photoluminescence (PL) properties were measured. Coefficients to correlate weight and LIBS emission intensity ratios for Cl and Br were experimentally determined from CuBr2/CaCl2 mixtures. The measured Cl/Br weight ratios correspond to NC PL emission wavelengths and the supplied amount of PbCl2 precursor. The proposed LIBS approach showed better sensitivity and stability than electron dispersive spectroscopy. Ideal detection accuracy and precision could be realized using LIBS, requiring only trace amounts of NC samples and simple pretreatment processes, with NC integrity retained until the test.

Supercapacitors are a type of commercialized energy storage device that can reserve energy but also show the characteristic of fast charging and discharging speed. The design and construction of all-solid-state flexible asymmetric supercapacitors (ASCs) are promising for wearable electronic devices, while the rational design of electrode materials is one of the most essential parts of this procedure. This work demonstrates a facile hybridization of Bi2O2Se nanosheets (NS) and reduced graphene oxide (rGO). The obtained Bi2O2Se NS/rGO composites show enhanced capacity and stability compared with the singular component of Bi2O2Se NS. Employing the Bi2O2Se NS/rGO composites on carbon cloth (CC) as an anode and a Ni(OH)2/rGO@CC electrode as a cathode, and solid electrolyte PVA-KOH gel as both of the electrolyte and the separator, the fabricated all-solid-state flexible ASC can exhibit a specific capacity of 52.4 mAh g−1 at the current density of 1 ​A ​g−1, and a maximum energy density of 57.9 ​Wh kg−1 ​at a power density of 1.10 ​kW ​kg−1. Meanwhile, the ASC device reveals excellent flexibility and cycling stability, with more than 92% capacity retention after 2000 cycles.

Both surface and bottom of perovskite film suffer from high density of trap-assisted recombination losses in perovskite solar cells; therefore, an effective method suitable for minimizing the trap density of perovskite solar cells (PSCs) both at perovskite/hole transport layer interfaces and perovskite/electron transport layer is urgently required. Herein, a comprehensive passivation strategy for achieving high-performance inverted PSCs was demonstrated. The study shows that the inverted PSCs possess dual increase of efficiency by passivation of the surface and bottom, as well as grain boundaries of perovskite active layer. The unencapsulated PSCs from comprehensive passivation strategy achieved the highest power conversion efficiency of 23.33% with remarkable long-term stability when exposed to illumination and humidity. In addition, this work provides an original method to analyze the distribution of the interfacial trap density and ions accumulation density by using the combination process of capacitance–voltage (C-V) and drive-level capacitance profiling (DLCP) measurements, providing the direct evidence for reducing of trap density and inhibiting of ion accumulation at two interfaces of PSCs.

Summary Greedy algorithm has been widely adopted for the point selection procedure of radial basis function based mesh deformation. However, in large deformation simulations with thousands of points selected, the greedy point selection will be too expensive and thus become a performance bottleneck. To improve the efficiency of the point selection procedure, a parallel multi-selection greedy method has been developed in this paper. Multiple points are selected at each step to accelerate the convergence speed of the greedy algorithm. In addition, two strategies are presented to determine the specific selecting number. The parallelization of the greedy point selection is realized based on a master-slave model, and a hybrid decomposition algorithm is proposed to address the load imbalance problem. Numerical benchmarks show that both our multi-selection method and the parallelization could obviously improve the point selection efficiency. Specifically, total speedups of 20 and 55 are separately obtained for the 3D undulating fish with 106 cell mesh and the 3D rotating hydrofoil with 11 million cell mesh. This article is protected by copyright. All rights reserved.

To investigate the capability of a radiomics model, which was designed to identify histopathologic growth pattern (HGP) of colorectal liver metastases (CRLMs) based on contrast-enhanced multidetector computed tomography (ceMDCT), to predict early response and 1-year progression free survival (PFS) in patients treated with bevacizumab-containing chemotherapy.Patients with unresectable CRLMs who were treated with bevacizumab-containing chemotherapy were included in this multicenter retrospective study. For each target lesion, the radiomics-diagnosed HGP (RAD_HGP) of desmoplastic (D) pattern or replacement (R) pattern was determined. Logistic regression and receiver operating characteristic (ROC) curves were used to assess lesion- and patient-based responses according to morphologic response criteria. One-year PFS was calculated using Kaplan-Meier curves. Hazard ratios for 1-year PFS were obtained through Cox proportional hazard regression analysis.Among 119 study patients, 206 D pattern and 140 R pattern lesions were identified. In patients with multiple lesions, 52 had D pattern, 31 had R pattern, and 36 had mixed (D + R) pattern. The area under the curve value for RAD_HGP in predicting early response was 0.707 for lesion-based analysis and 0.720 for patient-based analysis. Patients with D pattern had a significantly longer PFS than patients with R pattern or mixed pattern (P 0.001). RAD_HGP was the only independent predictor of 1-year PFS.HGP diagnosed using a radiomics model could be used as an effective predictor of PFS for patients with CRLMs treated with bevacizumab-containing chemotherapy.

The coefficient matrices of the linear equation systems arising from the radiation diffusion problems usually have orders of magnitude difference between their off-diagonal entries. While solving these linear equations with a preconditioned iterative method, the entries with small magnitudes may be insignificant to the preconditioner efficiency. In this paper, we use a filter to remove such small entries in the coefficient matrix while constructing the preconditioner. The proposed filter eliminates the small entries first according to a so-called weak dependence matrix, which relies on the conception of the strength of connections in algebraic multigrid. The preconditioner is then built based on the filtered matrix instead of the original one. Four strategies of filtering out entries are designed and investigated. Numerical results for various model-type problems and two real application problems, i.e., the multi-group radiation diffusion equations and the three temperature energy equations, are provided to show the effectiveness of the proposed method. In particular, this paper provides a practical approach to choose a proper parameter in the proposed method, which should help solve linear equation systems of radiation diffusion problems.