Endometrial stem cells alleviate cisplatin-induced ferroptosis of granulosa cells by regulating Nrf2 expression.

BACKGROUND: Premature ovarian failure (POF) caused by cisplatin is a severe and intractable sequela for young women with cancer who received chemotherapy. Cisplatin causes the dysfunction of granulosa cells and mainly leads to but is not limited to its apoptosis and autophagy. Ferroptosis has been also reported to participate, while little is known about it. Our previous experiment has demonstrated that endometrial stem cells (EnSCs) can repair cisplatin-injured granulosa cells. However, it is still unclear whether EnSCs can play a repair role by acting on ferroptosis. METHODS: Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were applied to detect the expression levels of ferroptosis-related genes. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell viability. Transmission electron microscopy (TEM) was performed to detect ferroptosis in morphology. And the extent of ferroptosis was assessed by ROS, GPx, GSSG and MDA indicators. In vivo, ovarian morphology was presented by HE staining and the protein expression in ovarian tissue was detected by immunohistochemistry. RESULTS: Our results showed that ferroptosis could occur in cisplatin-injured granulosa cells. Ferroptosis inhibitor ferrostatin-1 (Fer-1) and EnSCs partly restored cell viability and mitigated the damage of cisplatin to granulosa cells by inhibiting ferroptosis. Moreover, the repair potential of EnSCs can be markedly blocked by ML385. CONCLUSION: Our study demonstrated that cisplatin could induce ferroptosis in granulosa cells, while EnSCs could inhibit ferroptosis and thus exert repair effects on the cisplatin-induced injury model both in vivo and in vitro. Meanwhile, Nrf2 was validated to participate in this regulatory process and played an essential role.

Common structure of saccades and microsaccades in visual perception.

We obtain large amounts of external information through our eyes, a process often considered analogous to picture mapping onto a camera lens. However, our eyes are never as still as a camera lens, with saccades occurring between fixations and microsaccades occurring within a fixation. Although saccades are agreed to be functional for information sampling in visual perception, it remains unknown if microsaccades have a similar function when eye movement is restricted. Here, we demonstrated that saccades and microsaccades share common spatiotemporal structures in viewing visual objects. Twenty-seven adults viewed faces and houses in free-viewing and fixation-controlled conditions. Both saccades and microsaccades showed distinctive spatiotemporal patterns between face and house viewing that could be discriminated by pattern classifications. The classifications based on saccades and microsaccades could also be mutually generalized. Importantly, individuals who showed more distinctive saccadic patterns between faces and houses also showed more distinctive microsaccadic patterns. Moreover, saccades and microsaccades showed a higher structure similarity for face viewing than house viewing and a common orienting preference for the eye region over the mouth region. These findings suggested a common oculomotor program that is used to optimize information sampling during visual object perception.

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses.

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

Industrial Metaverse for Smart Manufacturing: Model, Architecture, and Applications.

Smart manufacturing has been transforming toward industrial digitalization integrated with various advanced technologies. Metaverse has been evolving as a next-generation paradigm of a digital space extended and augmented by reality. In the metaverse, users are interconnected for various virtual activities. In consideration of advanced possibilities that may be brought by the metaverse, it is envisioned that industrial metaverse should be integrated into smart manufacturing to upgrade industry for more visible, intelligent and efficient production in the future. Therefore, a conceptual model, named IMverse Model, and novel characteristics of the industrial metaverse for smart manufacturing are proposed in this article. Besides, an industrial metaverse architecture, named IMverse Architecture, is proposed involving several key enabling technologies. Typical innovative applications of the industrial metaverse throughout the whole product life cycle for smart manufacturing are presented with insights. Nonetheless, in prospect of future, the industrial metaverse still faces limitations and is far from implementation. Thus, challenges and open issues of the industrial metaverse for smart manufacturing are discussed, then outlook is provided for further research and application.

Mono-UFMylation promotes misfolding-associated secretion of α-synuclein.

Stressed cells secret misfolded proteins lacking signaling sequence via an unconventional protein secretion (UcPS) pathway, but how misfolded proteins are targeted selectively in UcPS is unclear. Here, we report that misfolded UcPS clients are subject to modification by a ubiquitin-like protein named ubiquitin-fold modifier 1 (UFM1). Using α-synuclein (α-Syn) as a UcPS model, we show that mutating the UFMylation sites in α-Syn or genetic inhibition of the UFMylation system mitigates α-Syn secretion, whereas overexpression of UFBP1, a component of the endoplasmic reticulum-associated UFMylation ligase complex, augments α-Syn secretion in mammalian cells and in model organisms. UFM1 itself is cosecreted with α-Syn, and the serum UFM1 level correlates with that of α-Syn. Because UFM1 can be directly recognized by ubiquitin specific peptidase 19 (USP19), a previously established UcPS stimulator known to associate with several chaperoning activities, UFMylation might facilitate substrate engagement by USP19, allowing stringent and regulated selection of misfolded proteins for secretion and proteotoxic stress alleviation.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients.

BACKGROUND: Reflux esophagitis has an increasing prevalence and complex and diverse symptoms. Identifying its risk factors is crucial to understanding the etiology, prevention, and management of the disease. The occurrence of reflux esophagitis may be associated with food reactions, Helicobacter pylori (H. pylori) infection, and metabolic syndromes. AIM: To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin (Ig) G-mediated food intolerance, H. pylori infection, and metabolic syndrome on reflux esophagitis. METHODS: Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled. The patients' basic information, test results, gastroscopy results, H. pylori test results, and IgG-mediated food intolerance results were collected. Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis. Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H. pylori infection affecting reflux esophagitis. RESULTS: A total of 7954 outpatients were included; the prevalence of reflux esophagitis, IgG-mediated food intolerance, H. pylori infection, and metabolic syndrome were 20.84%, 61.77%, 35.91%, and 60.15%, respectively. Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance (OR = 1.688, 95%CI: 1.497-1.903, P < 0.00001) and metabolic syndrome (OR = 1.165, 95%CI: 1.030-1.317, P = 0.01484), and the independent protective factor for reflux esophagitis was H. pylori infection (OR = 0.400, 95%CI: 0.351-0.456, P < 0.00001). IgG-mediated food intolerance had a partially positive mediating effect on H. pylori infection as it was associated with reduced occurrence of reflux esophagitis (P = 0.0200). Metabolic syndrome had a partially negative mediating effect on H. pylori infection and reduced the occurrence of reflux esophagitis (P = 0.0220). CONCLUSION: Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis, while patients with H. pylori infection were at lower risk. IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H. pylori infection; however, metabolic syndrome increased the risk of patients with H. pylori infection developing reflux esophagitis.

The regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor.

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach.

Glioma segmentation based on dense contrastive learning and multimodal features recalibration.

Accurate segmentation of different regions of gliomas from multimodal magnetic resonance (MR) images is crucial for glioma grading and precise diagnosis, but many existing segmentation methods are difficult to effectively utilize multimodal MR image information to recognize accurately the lesion regions with small size, low contrast and irregular shape. To address this issue, this work proposes a novel 3D glioma segmentation model DCL-MANet. DCL-MANet has an architecture of multiple encoders and one single decoder. Each encoder is used to extract MR image features of a given modality. To overcome the entangle problems of multimodal semantic features, a dense contrastive learning (DCL) strategy is presented to extract the modality-specific and common features. Following that, feature recalibration block (RFB) based on modality-wise attention is used to recalibrate the semantic features of each modality, enabling the model to focus on the features that are beneficial for glioma segmentation. These recalibrated features are input into the decoder to obtain the segmentation results. To verify the superiority of the proposed method, we compare it with several state-of-the-art (SOTA) methods in terms of Dice, average symmetric surface distance (ASSD), HD95 and volumetric similarity (Vs). The comparison results show that the average Dice, ASSD, HD95 and Vs of DCL-MANet on all tumor regions are improved at least by 0.66%, 3.47%, 8.94% and 1.07% respectively. For small enhance tumor (ET) region, the corresponding improvement can be up to 0.37%, 7.83%, 11.32%, and 1.35%, respectively. In addition, the ablation results demonstrate the effectiveness of the proposed DCL and RFB, and combining them can significantly increase Dice (1.59%) and Vs (1.54%) while decreasing ASSD (40.51%) and HD95 (45.16%) on ET region. The proposed DCL-MANet could disentangle multimodal features and enhance the semantics of modality-dependent features, providing a potential means to accurately segment small lesion regions in gliomas.

Dynamic projection mapping for non-planar objects with a variable focus lens and visual feedback.

Dynamic projection mapping for moving objects has attracted much attention in recent years. However, conventional approaches have faced some issues, such as the target objects being limited to the moving speed of the objects, the limitation of the narrow depth-of-field optics, and the planar shape objects. This work proposed an adaptive three-dimensional projection prototype, and it could project an always in-focus image on a non-planar object based on liquid lens optics. The location of the non-planar object could be detected, and the mapped projection contents calculated; as a result, a stable "printed" projection mapping should be viewed on a moving object.

Vasorin exocytosed from glioma cells facilitates angiogenesis via VEGFR2/AKT signaling pathway.

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hECs) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. Implications: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.

Direct Observation of Z-Scheme Route in Cu31 S16 /Znx Cd1-x S Heteronanoplates for Highly Efficient Photocatalytic Hydrogen Evolution.

Although photocatalytic hydrogen production from water holds great potential as a renewable and sustainable energy alternative, the practical application of the technology demands cost-effective, simple photocatalytic systems with high efficiency in hydrogen evolution reaction (HER). Herein, the synthesis and characterization of Cu31 S16 /Znx Cd1-x S heterostructured nanoplates (Cu31 S16 /ZnCdS HNPs) as a high photocatalytic system are reported. The cost-effective, hierarchical structures are easily prepared using the Cu31 S16 NPs as the seed by the epitaxial growth of the ZnCdS nanocrystals (NCs). The Cu31 S16 /ZnCdS without the noble metal cocatalyst exhibits a high HER rate of 61.7 mmol g-1  h-1 , which is 8,014 and 17 times higher than that of Cu31 S16 and ZnCdS, respectively, under visible light irradiation. The apparent quantum yield (AQY) of Cu31 S16 /ZnCdS reaches 67.9% at 400 nm with the highest value so far in the reported ZnCdS-based photocatalysts. The excellent activity and stability of the Cu31 S16 /ZnCdS are attributed to the formation of a strong internal electric field (IEF) and the Z-scheme pathway. The comprehensive experiments and theoretical calculations provide the direct evidences of the Z-scheme route. This work may offer a way for the design and development of efficient photocatalysts to achieve solar-to-chemical energy conversion at a practically useful level.

EZH2/G9a interact to mediate drug resistance in non-small-cell lung cancer by regulating the SMAD4/ERK/c-Myc signaling axis.

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.

Effects of non-pharmacological interventions on pain in wound patients during dressing change: A systematic review.

BACKGROUND: Changes to the wound dressing frequently cause pain. Some adverse side effects of pharmacologic pain management may cause problems or even impede wound healing. There is no systematic study of non-pharmacologic therapies for pain during wound dressing changes, despite the gradual promotion of non-pharmacologic pain reduction methods. OBJECTIVES: To give clinical wound pain management a new direction, locating and assessing non-pharmacological interventions regarding pain brought on by wound dressing changes are necessary. METHOD: The researchers conducted a comprehensive literature review on non-pharmacological interventions for pain during wound dressing changes across five databases: PubMed, Web of Science, Medline, Embase, and the Cochrane Library spanning the period from January 2010 to September 2022. The evaluation of literature and data extraction was carried out independently by two researchers, and in cases of disagreement, a third researcher participated in the deliberation. To assess the risk of bias in the literature, the researchers utilised the Cochrane Handbook for Reviews of Interventions, version 5.1.0. RESULTS: In total, 951 people were involved in 11 investigations covering seven non-pharmacological therapies. For pain triggered by dressing changes, virtual reality (VR) distraction, auditory and visual distractions, foot reflexology, religious and spiritual care, and guided imaging demonstrated partially positive effects, with hypnosis therapy and jaw relaxation perhaps having a weak effect. CONCLUSION: The key to managing wounds is pain management. According to our review, there is some indication that non-pharmacologic interventions can help patients feel less discomfort when having their wound dressings changed. However, the evidence supporting this view is weak. It needs to be corroborated by future research studies with multicentre and large samples. To promote and use various non-pharmacologic interventions in the future, it is also necessary to build standardised and homogenised paths for their implementation.

A Millimeter-Wave Broadband Multi-Mode Substrate-Integrated Gap Waveguide Traveling-Wave Antenna with Orbit Angular Momentum.

Orbit angular momentum (OAM) has been considered a new dimension for improving channel capacity in recent years. In this paper, a millimeter-wave broadband multi-mode waveguide traveling-wave antenna with OAM is proposed by innovatively utilizing the transmitted electromagnetic waves (EMWs) characteristic of substrate-integrated gap waveguides (SIGWs) to introduce phase delay, resulting in coupling to the radiate units with a phase jump. Nine "L"-shaped slot radiate elements are cut in a circular order at a certain angle on the SIGW to generate spin angular momentum (SAM) and OAM. To generate more OAM modes and match the antenna, four "Π"-shaped slot radiate units with a 90° relationship to each other are designed in this circular array. The simulation results show that the antenna operates at 28 GHz, with a -10 dB fractional bandwidth (FBW) = 35.7%, ranging from 25.50 to 35.85 GHz and a VSWR ≤ 1.5 dB from 28.60 to 32.0 GHz and 28.60 to 32.0 GHz. The antenna radiates a linear polarization (LP) mode with a gain of 9.3 dBi at 34.0~37.2 GHz, a l = 2 SAM-OAM (i.e., circular polarization OAM (CP-OAM)) mode with 8.04 dBi at 25.90~28.08 GHz, a l = 1 and l = 2 hybrid OAM mode with 5.7 dBi at 28.08~29.67 GHz, a SAM (i.e., left/right hand circular polarization (L/RHCP) mode with 4.6 dBi at 29.67~30.41 GHz, and a LP mode at 30.41~35.85 GHz. In addition, the waveguide transmits energy with a bandwidth ranging from 26.10 to 38.46 GHz. Within the in-band, only a quasi-TEM mode is transmitted with an energy transmission loss |S21| ≤ 2 dB.

A Design Method and Application of Meta-Surface-Based Arbitrary Passband Filter for Terahertz Communication.

A meta-surface-based arbitrary bandwidth filter realization method for terahertz (THz) future communications is presented. The approach involves integrating a meta-surface-based bandstop filter into an ultra-wideband (UWB) bandpass filter and adjusting the operating frequency range of the meta-surface bandstop filter to realize the design of arbitrary bandwidth filters. It effectively addresses the complexity of designing traditional arbitrary bandwidth filters and the challenges in achieving impedance matching. To underscore its practicality, the paper employs silicon substrate integrated gap waveguide (SSIGW) and this method to craft a THz filter. To begin, design equations for electromagnetic band gap (EBG) structures were developed in accordance with the requirements of through-silicon via (TSV) and applied to the design of the SSIGW. Subsequently, this article employs equivalent transmission line models and equivalent circuits to conduct theoretical analyses for both the UWB passband and the meta-surface stopband portions. The proposed THz filter boasts a center frequency of 0.151 THz, a relative bandwidth of 6.9%, insertion loss below 0.68 dB, and stopbands exceeding 20 GHz in both upper and lower ranges. The in-band group delay is 0.119 ± 0.048 ns. Compared to reported THz filters, the SSIGW filter boasts advantages such as low loss and minimal delay, making it even more suitable for future wireless communication.

The functional significance of circRNA/miRNA/mRNA interactions as a regulatory network in lung cancer biology.

Lung cancer, the leading cause of cancer-related deaths, presents significant challenges to patients due to its poor prognosis. Recent research has increasingly implicated circular RNAs in the development and progression of lung cancer. These circular RNAs have been found to impact various aspects of tumor behavior, including proliferation, metastasis, cell cycle regulation, apoptosis, cancer stem cells, therapy response, and the tumor microenvironment. One of the key mechanisms by which circular RNAs exert their influence is through their ability to act as miRNA sponges, sequestering microRNAs and preventing them from targeting other RNA molecules. Accumulating evidence suggests that circular RNAs can function as competing endogenous RNAs, affecting the expression of target mRNAs by sequestering microRNAs. Dysregulation of competing endogenous RNAs networks involving circular RNAs, microRNAs, and mRNAs leads to the aberrant expression of oncogenes and tumor suppressors involved in lung cancer pathogenesis. Understanding the dynamic interplay and molecular mechanisms among circular RNAs, microRNAs, and mRNAs holds great promise for advancing early diagnosis, personalized therapeutic interventions, and improved patient outcomes in lung cancer. Therefore, this study aims to provide an in-depth exploration of the executive roles of circular RNAs/microRNAs/ mRNAs interactions in lung cancer pathogenesis and their potential utility for diagnosing lung cancer, predicting patient prognosis, and guiding targeted therapies. By offering a comprehensive overview of the dysregulation of the axes as driving factors in lung cancer, we aim to pave the way for their translation into clinical practice in the future.

From genomic spectrum of NTRK genes to adverse effects of its inhibitors, a comprehensive genome-based and real-world pharmacovigilance analysis.

Introduction: The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has facilitated the development of precision oncology. Two first-generation NTRK inhibitors (larotrectinib and entrectinib) are currently approved for the treatment of patients with solid tumors harboring NTRK gene fusions. Nevertheless, comprehensive NTRK profiling at the pan-cancer genomic level and real-world studies pertaining to the adverse events of NTRK inhibitors are lacking. Methods: We characterize the genome of NTRK at the pan-cancer level through multi-omics databases such as The Cancer Genome Atlas (TCGA). Through the FDA Adverse Event Reporting System (FAERS) database, we collect reports of entrectinib and larotrectinib-induced adverse events and perform a pharmacovigilance analysis using various disproportionality methods. Results: NTRK1/2/3 expression is lower in most tumor tissues, while they have higher methylation levels. NTRK gene expression has prognostic value in some cancer types, such as breast invasive carcinoma (BRCA). The cancer type with highest NTRK alteration frequency is skin cutaneous melanoma (SKCM) (31.98%). Thyroid carcinoma (THCA) has the largest number of NTRK fusion cases, and the most common fusion pair is ETV6-NTRK3. Adverse drug events (ADEs) obtained from the FAERS database for larotrectinib and entrectinib are 524 and 563, respectively. At the System Organ Class (SOC) level, both drugs have positive signal value for "nervous system disorder". Other positive signals for entrectinib include "cardiac disorders", "metabolism and nutrition disorders", while for larotrectinib, it is "hepatobiliary disorders". The unexpected signals are also listed in detail. ADEs of the two NTRK inhibitors mainly occur in the first month. The median onset time of ADEs for entrectinib and larotrectinib was 16 days (interquartile range [IQR] 6-86.5) and 44 days ([IQR] 7-136), respectively. Conclusion: Our analysis provides a broad molecular view of the NTRK family. The real-world adverse drug event analysis of entrectinib and larotrectinib contributes to more refined medication management.

Volition motivates cognitive performance at the response-execution level by attenuating task-irrelevant motor activations.

Humans express volition by making voluntary choices which, relative to forced choices, can motivate cognitive performance in a variety of tasks. However, a task that requires the generation of motor responses on the basis of external sensory stimulation involves complex underlying cognitive processes, e.g., pre-response processing, response selection, and response execution. The present study investigated how these underlying processes are facilitated by voluntary choice-making. In five experiments, participants were free or forced to choose a task-irrelevant picture from two alternatives, and then completed a conflict task, i.e., Flanker, Stroop, Simon, Stroop-Simon, or Flanker-Simon task, where the conflict effect could occur at different processing levels. Results consistently showed that responses in all tasks were generally faster after voluntary (vs. forced) choices. Importantly, the conflict effect at the response-execution level (i.e., the Simon effect), but not the conflict effect at the pre-response and response-selection levels (i.e., the Flanker and Stroop effects), was reduced by the voluntary choice-making. Model fitting revealed that the peak amplitude of automatic motor activations in the response-execution conflict was smaller after voluntary (vs. forced) choices. These findings suggest that volition motivates subsequent cognitive performance at the response-execution level by attenuating task-irrelevant motor activations.

Adaptive milliseconds tracking and zooming optics based on a high-speed gaze controller and liquid lenses.

The high-speed gaze and high resolution are critical factors for actual monitoring systems. However, the conventional method cannot track and zoom as fast as expected due to the larger inertia and it results in a low resolution due to the digital zoom. In this paper, we proposed a high-speed tracking and zooming optics that is coaxial designed and with an active tracking unit and an optical zooming unit to overcome the above issues. The tracking unit always tracks the object in the center of view by a pan-tilt mirror controller and a visual feedback tracking algorithm within 4 milliseconds response order. The zooming unit can continuously change the magnification from 1X to 2X by three liquid lenses within milliseconds. Besides, the zooming unit provides a compensation algorithm to achieve accurate zoom and focus.