Dual-Region Computed Tomography Radiomics-Based Machine Learning Predicts Subcarinal Lymph Node Metastasis in Patients with Non-small Cell Lung Cancer.

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.

Linearization of wavelength sweeping lasers for the construction of 4-D FMCW LiDAR images of slow-moving objects using baseband beat note signals.

A FMCW LiDAR system of both the distributed feedback laser and external cavity laser is established in baseband beat notes, rather than up-conversion to an intermediate frequency to exclude flicker noise. Meanwhile, utilizing fast-scanning MEMS mirrors, high-quality real-time (1 fps) 4-D images of the slow-moving object (10 mm/s) can be directly constructed at the baseband with a central frequency as low as 100 kHz and a small Doppler shift. The proposed LiDAR architecture based on such a low-frequency baseband significantly improves the optical power budget on the transmitter side and eliminates the costly high-speed sampling circuits on the receiver side.

Deep Learning Detection and Segmentation of Brain Arteriovenous Malformation on Magnetic Resonance Angiography.

BACKGROUND: The delineation of brain arteriovenous malformations (bAVMs) is crucial for subsequent treatment planning. Manual segmentation is time-consuming and labor-intensive. Applying deep learning to automatically detect and segment bAVM might help to improve clinical practice efficiency. PURPOSE: To develop an approach for detecting bAVM and segmenting its nidus on Time-of-flight magnetic resonance angiography using deep learning methods. STUDY TYPE: Retrospective. SUBJECTS: 221 bAVM patients aged 7-79 underwent radiosurgery from 2003 to 2020. They were split into 177 training, 22 validation, and 22 test data. FIELD STRENGTH/SEQUENCE: 1.5 T, Time-of-flight magnetic resonance angiography based on 3D gradient echo. ASSESSMENT: The YOLOv5 and YOLOv8 algorithms were utilized to detect bAVM lesions and the U-Net and U-Net++ models to segment the nidus from the bounding boxes. The mean average precision, F1, precision, and recall were used to assess the model performance on the bAVM detection. To evaluate the model's performance on nidus segmentation, the Dice coefficient and balanced average Hausdorff distance (rbAHD) were employed. STATISTICAL TESTS: The Student's t-test was used to test the cross-validation results (P < 0.05). The Wilcoxon rank test was applied to compare the median for the reference values and the model inference results (P < 0.05). RESULTS: The detection results demonstrated that the model with pretraining and augmentation performed optimally. The U-Net++ with random dilation mechanism resulted in higher Dice and lower rbAHD, compared to that without that mechanism, across varying dilated bounding box conditions (P < 0.05). When combining detection and segmentation, the Dice and rbAHD were statistically different from the references calculated using the detected bounding boxes (P < 0.05). For the detected lesions in the test dataset, it showed the highest Dice of 0.82 and the lowest rbAHD of 5.3%. DATA CONCLUSION: This study showed that pretraining and data augmentation improved YOLO detection performance. Properly limiting lesion ranges allows for adequate bAVM segmentation. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Allergenicity of alternative proteins: research hotspots, new findings, evaluation strategies, regulatory status, and future trends: a bibliometric analysis.

As the world population rises, the demand for protein increases, leading to a widening gap in protein supply. There is an unprecedented interest in the development of alternative proteins, but their allergenicity has raised consumer concerns. This review aims to highlight and correlate the current research status of allergenicity studies on alternative proteins based on previously published studies. Current research keywords, hotspots and trends in alternative protein sensitization were analyzed using a mixed-method approach that combined bibliometric analysis and literature review. According to the bibliometric analysis, current research is primarily focused on food science, agriculture, and immunology. There are significant variations in the type and amount of allergens found in alternative proteins. A significant amount of research has been focused on studying plant-based proteins and the cross-reactivity of insect proteins. The allergenicity of alternative proteins has not been studied extensively or in depth. The allergenicity of other alternative proteins and the underlying mechanisms warrant further study. In addition, the lack of a standardized allergy assessment strategy calls for additional efforts by international organizations and collaborations among different countries. This review provides new research and regulatory perspectives for the safe utilization of alternative proteins in human food systems.

Standalone deep learning versus experts for diagnosis lung cancer on chest computed tomography: a systematic review.

PURPOSE: To compare the diagnostic performance of standalone deep learning (DL) algorithms and human experts in lung cancer detection on chest computed tomography (CT) scans. MATERIALS AND METHODS: This study searched for studies on PubMed, Embase, and Web of Science from their inception until November 2023. We focused on adult lung cancer patients and compared the efficacy of DL algorithms and expert radiologists in disease diagnosis on CT scans. Quality assessment was performed using QUADAS-2, QUADAS-C, and CLAIM. Bivariate random-effects and subgroup analyses were performed for tasks (malignancy classification vs invasiveness classification), imaging modalities (CT vs low-dose CT [LDCT] vs high-resolution CT), study region, software used, and publication year. RESULTS: We included 20 studies on various aspects of lung cancer diagnosis on CT scans. Quantitatively, DL algorithms exhibited superior sensitivity (82%) and specificity (75%) compared to human experts (sensitivity 81%, specificity 69%). However, the difference in specificity was statistically significant, whereas the difference in sensitivity was not statistically significant. The DL algorithms' performance varied across different imaging modalities and tasks, demonstrating the need for tailored optimization of DL algorithms. Notably, DL algorithms matched experts in sensitivity on standard CT, surpassing them in specificity, but showed higher sensitivity with lower specificity on LDCT scans. CONCLUSION: DL algorithms demonstrated improved accuracy over human readers in malignancy and invasiveness classification on CT scans. However, their performance varies by imaging modality, underlining the importance of continued research to fully assess DL algorithms' diagnostic effectiveness in lung cancer. CLINICAL RELEVANCE STATEMENT: DL algorithms have the potential to refine lung cancer diagnosis on CT, matching human sensitivity and surpassing in specificity. These findings call for further DL optimization across imaging modalities, aiming to advance clinical diagnostics and patient outcomes. KEY POINTS: Lung cancer diagnosis by CT is challenging and can be improved with AI integration. DL shows higher accuracy in lung cancer detection on CT than human experts. Enhanced DL accuracy could lead to improved lung cancer diagnosis and outcomes.

Paired Electrolysis-Enabled Arylation of Quinoxalin-2(1H)-ones.

The first paired electrolysis-enabled arylation of quinoxalin-2(1H)-ones was achieved using cyanoarenes as the arylation reagents. A variety of 3-arylquinoxalin-2(1H)-ones with various important functional groups were obtained in moderate to good yields under metal- and chemical oxidant-free conditions. With a pair of reductive and oxidative processes occurring among the substrates and reaction intermediates, the power consumption can be dramatically reduced.

The integrated analysis and underlying mechanisms of FNDC5 on diabetic induced cognitive deficits.

OBJECTIVES: Chronic hyperglycemia is considered as an important factor to promote the neurodegenerative process of brain, and the synaptic plasticity as well as heterogeneity of hippocampal cells are thought to be associated with cognitive dysfunction in the early process of neurodegeneration. To date, fibronectin type III domain-containing protein 5 (FNDC5) has been highlighted its protective role in multiple neurodegenerative diseases. However, the potential molecular and cellular mechanisms of FNDC5 on synaptic plasticity regulation in cognitive impairment (CI) induced by diabetics are still need to known. METHODS/DESIGN: To investigate the heterogeneity and synaptic plasticity of hippocampus in animals with CI state induced by hyperglycemia, and explore the potential role of FNDC5 involved in this process. Firstly, the single cell sequencing was performed based on the hippocampal tissue from db diabetic mice induced CI and normal health control mice by ex vivo experiments; and then the integrated analysis and observations validation using Quantitative Real-time PCR, western blot as well as other in vitro studies. RESULTS: We observed and clarified the sub-cluster of type IC spiral ganglion neurons expressed marker genes as Trmp3 and sub-cluster of astrocytes with marker gene as Atp1a2 in hippocampal cells from diabetic animals induced CI and the effect of those on neuron-glial communication. We also found that FNDC5\BDNF-Trk axis was involved in the synaptic plasticity regulation of hippocampus. In high glucose induced brain injury model in vitro, we investigated that FNDC5 significantly regulates BDNF expression and that over-expression of FNDC5 up-regulated BDNF expression (p < 0.05) and can also significantly increase the expression of synapsin-1 (p < 0.05), which is related to synaptic plasticity, In addition, the unbalanced methylation level between H3K4 and H3K9 in Fndc5 gene promoter correlated with significantly down-regulated expression of FNDC5 (p < 0.05) in the hyperglycemia state. CONCLUSION: The current study revealed that the synaptic plasticity of hippocampal cells in hyperglycemia might be regulated by FNDC5\BDNF-Trk axis, playing the protective role in the process of CI induced by hyperglycemia and providing a target for the early treatment of hyperglycemia induced cognitive dysfunction in clinic.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Chronic vascular pathogenesis results in the reduced serum Metrnl levels in ischemic stroke patients.

Metrnl is a secreted protein involved in neurite outgrowth, insulin sensitivity, immunoinflammatory responses, blood lipids and endothelial protection. In this study, we investigated the role of Metrnl in ischemic stroke. Fifty-eight ischemic stroke patients (28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset) and 20 healthy controls were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls. Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels. Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels. Metrnl was correlated with some metabolic, inflammatory and clotting parameters. Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke. In order to elucidate the mechanisms underlying the reduced serum Metrnl levels, we established animal models of ischemic stroke in normal mice, atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion (MCAO) using intraluminal filament or electrocoagulation. We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice, whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels. Metrnl knockout did not affect acute ischemic stroke injury and death. We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke. Metrnl is a potential target for prevention of ischemic stroke.

Generation of the stable propagation Bessel beam and the axial multifoci beam with pure phase elements.

A recently proposed method is upgraded to convert two amplitude phase modulation systems (APMSs) to pure phase elements (PPEs), for generating the stable propagation Bessel beam and the axial multifoci beam, respectively. Phase functions of the PPEs are presented analytically. Numerical simulations by the complete Rayleigh-Sommerfeld method demonstrate that the converted PPE has implemented the same optical functionalities as the corresponding APMS, in either the longitudinal or the transverse direction. Compared with the traditional APMS, the converted PPE possesses many advantages such as fabrication process simplification, system complexity reduction, production cost conservation, alignment error avoidance, and experimental precision enhancement. These inherent advantages position the PPE as an ideal choice and driving force behind further advancements in optical system technology.

Pancreatic cancer cluster region identified in BRCA2.

Pancreatic cancer has a poor prognosis. Lack of diagnostic markers prevents its early diagnosis and treatment. Pathogenic germline variation in BRCA1 and BRCA2 (BRCA) is genetic predisposition for cancer. The location of variants in different regions in BRCA is non-randomly enriched in different types of cancer as shown by the breast cancer cluster region (BCCR), ovarian cancer cluster region (OCCR) and prostate cancer cluster region (PrCCR). Although pathogenic BRCA variation also contributes to pancreatic cancer, no pancreatic cancer cluster region (PcCCR) in BRCA1 or BRCA2 has been identified due to the relatively low incidence of pancreatic cancer and the lack of sufficient variation data from pancreatic cancer. Through comprehensive data mining, we identified 215 BRCA pathogenic variants (PVs) (71 in BRCA1 and 144 in BRCA2) from 27 118 pancreatic cancer cases. Through mapping the variants, we identified a region non-randomly enriched in pancreatic cancer between BRCA2 c.3515 and c.6787. This region contained 59 BRCA2 PVs and included 57% of pancreatic cancer cases (95% CI 43% to 70%). The PcCCR did not overlap with the BCCR and PrCCR but overlapped with the BRCA2 OCCR, highlighting that this region may play similar aetiological roles in pancreatic cancer and ovarian cancer.

MagicTouch PTA Sirolimus-Coated Balloon for Femoropopliteal and Below-the-Knee Disease: 3-Year Outcomes of the XTOSI Trial.

BACKGROUND: Sirolimus-coated balloon (SCB) is a potential treatment option for peripheral arterial disease (PAD). There are currently no long-term clinical data for this novel treatment for PAD. We present the 3-year results of the first-in-human study of MagicTouch PTA SCB for treatment of PAD for both femoropopliteal and below-the-knee arteries. METHODS: The XTOSI pilot study is a prospective, single-arm, open-label, single-center trial evaluating MagicTouch PTA SCB for symptomatic PAD. Assessments through 3 years included freedom from clinically driven target lesion revascularization (CD-TLR), freedom from major amputation, amputation-free survival (AFS), overall survival, and ulcer-free status. RESULTS: At 3 years, the overall freedom from CD-TLR was 84.4%, freedom from major amputation was 86.1%, AFS was 63.3%, overall survival was 63.3%, and ulcer-free status in remaining survivors with intact limbs was 100%. For femoropopliteal lesions, at 3 years, the freedom from CD-TLR was 92.9%, freedom from major amputation was 93.3%, AFS was 70%, and overall survival was 70%. For below-the-knee lesions, at 3 years, the freedom from CD-TLR was 77.8%, freedom from major amputation was 81.0%, AFS was 58.6%, and overall survival was 58.6%. CONCLUSIONS: SCB in the XTOSI pilot study showed promising clinical results sustained to 3 years, and no long-term safety concerns were raised. Randomized trials are currently ongoing to investigate the safety and efficacy of SCB for treatment of PAD.

Analysis of risk factors related to early implant failure: A retrospective study.

STATEMENT OF PROBLEM: Factors influencing early implant failure (failure during the healing period) in the rehabilitation and restoration of oral function in partially edentulous patients are unclear. PURPOSE: The purpose of this clinical study was to investigate several factors that may be associated with early implant failure. MATERIAL AND METHODS: This retrospective study was conducted on 3247 implants in 2061 patients between 2009 and 2022. Patient-related and surgery-related factors, including smoking; sex; diabetes; bone grafting; implant length, diameter, and design; adjacent teeth; and insertion torque, were manually retrieved and analyzed. Using univariate and multivariate analyses, a generalized estimating equation (GEE) model with chi-squared tests was employed to evaluate factors related to early implant failure (the failure before restoration) (α=.05). RESULTS: The mean ±standard deviation age of the study patients was 49.2 ±15.0 years (range 18 to 91). Ninety-nine implants (3.05%) failed during the healing period. Three factors were statistically significant regarding early implant failure: smoking (odds ratio [OR]=1.92, P=.008), implant design (tapered implants) (OR=1.84, P=.007), and implant length <10 mm (OR=2.98, P=.011). Factors including diabetes, bone grafting, anatomic location, adjacent teeth (endodontic therapy in the adjacent teeth and the distance between implant and adjacent teeth), healing method, and insertion torque did not exhibit a statistically significant higher early implant failure rate. Ninety-three sites with failed implants received new implants, and 6 of these 93 implants failed during the healing period. CONCLUSIONS: Within the limitation of sample size, smokers, implant length (<10 mm), and implant design (tapered implant) exhibited higher risk of early implant failure in this retrospective study. Implant insertion torque, healing method, adjacent teeth, and diabetes did not significantly influence the risk of early implant failure.

Chemokines in colon cancer progression.

Colon cancer is a major human cancer accounting for about a tenth of all cancer cases thus making it among the top three cancers in terms of incidence as well as mortality. Metastasis to distant organs, particularly to liver, is the primary reason for associated mortality. Chemokines, the chemo-attractants for various immune cells, have increasingly been reported to be involved in cancer initiation and progression, including in colon cancer. Here we discuss the available knowledge on the role of several chemokines, such as, CCL2, CCL3, CCL5, CXCL1, CXCL2, CXCL8 in colon cancer progression. CCL20 is one chemokine with emerging evidence for its role in influencing colon cancer tumor microenvironment through the documents effects on fibroblasts, macrophages and immune cells. We focus on CCL20 and its receptor CCR6 as promising factors that affect multiple levels of colon cancer progression. They interact with several cytokines and TLR receptors leading to increased aggressiveness, as supported by multitude of evidence from in vitro, in vivo studies as well as human patient samples. CCL20-CCR6 bring about their biological effects through regulation of several signaling pathways, including, ERK and NF-κB pathways, in addition to the epithelial-mesenchymal transition. Signaling involving CCL20-CCR6 has profound effect on colon cancer hepatic metastasis. Combined with elevated CCL20 levels in colon tumors and metastatic patients, the above information points to a need for further evaluation of chemokines as diagnostic and/or prognostic biomarkers.

Modular Access to meta-Substituted Benzenes via Mo-Catalyzed Intermolecular Deoxygenative Benzene Formation.

The substituted benzene derivatives are essential to organic synthesis, medicinal chemistry, and material science. However, the 1,3-di- and 1,3,5-trisubstituted benzenes are far less prevalent in small-molecule drugs than other substitution patterns, likely due to the lack of robust, efficient, and convenient synthetic methods. Here, we report a Mo-catalyzed intermolecular deoxygenative benzene-forming reaction of readily available ynones and allylic amines. A wide range of unsymmetric and unfunctionalized 1,3-di- and 1,3,5-trisubstituted benzenes were obtained in up to 88% yield by using a commercially available molybdenum catalyst. The synthetic potential of the method was further illustrated by synthetic transformations, a scale-up synthesis, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this benzene-forming process might proceed through a Mo-catalyzed aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization cascade. This strategy not only provided a facile, robust, and modular approach to various meta-substituted benzene derivatives but also demonstrated the potential of molybdenum catalysis in the challenging intermolecular deoxygenative cross-coupling reactions.

Tailoring Fluorescence-Phosphorescence Emission with a Single Nanocavity.

Realizing the dual emission of fluorescence-phosphorescence in a single system is an extremely important topic in the fields of biological imaging, sensing, and information encryption. However, the phosphorescence process is usually in an inherently "dark state" at room temperature due to the involvement of spin-forbidden transition and the rapid non-radiative decay rate of the triplet state. In this work, we achieved luminescent harvesting of the dark phosphorescence processes by coupling singlet-triplet molecular emitters with a rationally designed plasmonic cavity. The achieved Purcell enhancement effect of over 1000-fold allows for overcoming the triplet forbidden transitions, enabling radiation enhancement with selectable emission wavelengths. Spectral results and theoretical simulations indicate that the fluorescence-phosphorescence peak position can be intelligently tailored in a broad range of wavelengths, from visible to near-infrared. Our study sheds new light on plasmonic tailoring of molecular emission behavior, which is crucial for advancing research on plasmon-tailored fluorescence-phosphorescence spectroscopy in optoelectronics and biomedicine.

Ethnic-specificity, evolution origin and deleteriousness of Asian BRCA variation revealed by over 7500 BRCA variants derived from Asian population.

Pathogenic variation in BRCA1 and BRCA2 (BRCA) causes high risk of breast and ovarian cancer, and BRCA variation data are important markers for BRCA-related clinical cancer applications. However, comprehensive BRCA variation data are lacking from the Asian population despite its large population size, heterogenous genetic background and diversified living environment across the Asia continent. We performed a systematic study on BRCA variation in Asian population including extensive data mining, standardization, annotation and characterization. We identified 7587 BRCA variants from 685 592 Asian individuals in 40 Asia countries and regions, including 1762 clinically actionable pathogenic variants and 4915 functionally unknown variants (https://genemutation.fhs.um.edu.mo/Asian-BRCA/). We observed the highly ethnic-specific nature of Asian BRCA variants between Asian and non-Asian populations and within Asian populations, highlighting that the current European descendant population-based BRCA data is inadequate to reflect BRCA variation in the Asian population. We also provided archeological evidence for the evolutionary origin and arising time of Asian BRCA variation. We further provided structural-based evidence for the deleterious variants enriched within the functionally unknown Asian BRCA variants. The data from our study provide a current view of BRCA variation in the Asian population and a rich resource to guide clinical applications of BRCA-related cancer for the Asian population.

Simultaneous enhancement of the bandwidth and responsivity in high-speed avalanche photodiodes with an optimized flip-chip bonding package.

The enhancement in responsivity of photodiodes (PDs) or avalanche photodiodes (APDs) with the traditional flip-chip bonding package usually comes at the expense of degradation in the optical-to-electrical (O-E) bandwidth due to the increase of parasitic capacitance. In this work, we demonstrate backside-illuminated In0.52Al0.48As based APDs with novel flip-chip bonding packaging designed to relax this fundamental trade-off. The inductance induced peak in the measured O-E frequency response of these well-designed and well-packaged APDs, which can be observed around its 3-dB bandwidth (∼30 GHz), effectively widens the bandwidth and becomes more pronounced when the active diameter of the APD is aggressively downscaled to as small as 3 µm. With a typical active window diameter of 14 µm, large enough for alignment tolerance and low optical coupling loss, the packaged APD exhibits a moderate damping O-E frequency response with a bandwidth (36 vs. 31 GHz) and responsivity (3.4 vs. 2.3 A/W) superior to those of top-illuminated reference sample under 0.9 Vbr operation, to attain a high millimeter wave output power (0 dBm at 40 GHz) and output current (12.5 mA at +8.8 dBm optical power). The excellent static and dynamic performance of this design open up new possibilities to further improve the sensitivity at the receiver-end of the next-generation of passive optical network (PON) and coherent communication systems.

Thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in Talaromyces marneffei infection.

Macrophage-derived inflammatory cytokines are critical for host defense against Talaromyces marneffei (T. marneffei) infection among HIV/AIDS patients, and excessive inflammatory cytokines are associated with poor outcomes of AIDS-associated talaromycosis. However, the underlying mechanisms of macrophage-caused pyroptosis and cytokine storm are poorly understood. Here, in the T. marneffei-infected mice and macrophages, we show that T. marneffei induced pyroptosis in macrophages through the NLRP3/caspase-1 pathway. The immunomodulatory drug thalidomide could promote the pyroptosis of macrophages infected T. marneffei. In T. marneffei-infected mice, the splenic macrophages underwent increasing pyroptosis as talaromycosis deteriorated. Thalidomide ameliorated inflammation of mice, while amphotericin B (AmB) in combination with thalidomide did not improve overall survival compared with AmB alone. Taken together, our findings suggest that thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in T. marneffei infection.

Ideal suppression of Bessel beam intensity oscillations with a vortex phase plate.

We propose what we believe to be a new kind of diffractive phase element, i.e., vortex phase plate (VPP) with phase singularities along the azimuth direction. Phase function of the proposed VPP is given analytically. Axial intensity oscillations of propagating Bessel beams are ideally suppressed by using the proposed VPP. Compared with the traditional amplitude mask, the proposed VPP takes such advantages as a simpler fabrication procedure and a lower cost.