The complete chloroplast genome sequence of Zanthoxylum ailanthoides Sieb. et. Zucc (Rutaceae): an important medicinal plant.

Zanthoxylum ailanthoides is a deciduous tree, with important medicinal and economic values. The complete chloroplast genome sequence of Z. ailanthoides was assembled and the phylogenetic relationship to other species was inferred in this study. The chloroplast genome is 157,209 bp in length, including two inverted repeats of 26,408 bp, a large single-copy of 86,099 bp and a small single copy of 18,294 bp. Moreover, the chloroplast genome contains 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the chloroplast genome is 38.4%. The phylogenetic analysis indicated that Z. ailanthoides was grouped with a clade containing the species of Z. multijugum, Z. calcicola, Z. oxyphyllum, Z. stenophyllum, and the genus was closely related to Phellodendron. This study contributes to a better understanding of the phylogenetic relationships among Zanthoxylum species.

Treatment for Resistant Hypertension Under the Guidance of Pharmacogenomics: A Randomised Controlled Open-Label Trial.

OBJECTIVE: To evaluate the efficacy and safety of pharmacogenomics (PGx)-guided treatment in individuals with resistant hypertension (RH). STUDY DESIGN: Randomised controlled open-label study. Place and Duration of the Study: Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China, from June 2019 to November 2021. METHODOLOGY: The study assigned RH patients to two groups. The intervention group (IG) received 12 weeks of PGx-guided treatment, while the control group (CG) followed a consensus-based approach. Examining 10 genes and their alleles with 31 antihypertensive drugs in the IG, the study provided specific medication advice. The primary outcome measured the difference in office systolic blood pressure (SBP) change from baseline at 12 weeks. Secondary outcomes included changes in diastolic blood pressure (DBP), hepatic and renal function, and major adverse cardiovascular events. RESULTS: Fifty-nine patients from the First Hospital of China Medical University participated, with 29 in the IG and 30 in the CG. Significant differences were noted in SBP reduction (IG: 31.26 ± 18.64 mmHg; CG: 14.61 ± 17.74 mmHg; p=0.001) and DBP reduction (IG: 19.61 ± 17.32 mmHg; CG: 7.81 ± 11.23 mmHg; p = 0.003) after 12 weeks. One IG patient had a heart attack, and one CG subject developed heart failure. At week 12, hepatic insufficiency was observed in one IG patient and six CG patients, while renal insufficiency occurred in five patients of both groups. CONCLUSION: Treatment guided by PGx demonstrated significant reductions in both SBP and DBP compared to consensus-based treatment. KEY WORDS: Resistant hypertension, Treatment, Pharmacogenomics, Clinical study.

Two-dimensional topological semimetals: an emerging candidate for terahertz detectors and on-chip integration.

The importance of terahertz (THz) detection lies in its ability to provide detailed information in a non-destructive manner, making it a valuable tool across various domains including spectroscopy, communication, and security. The ongoing development of THz detectors aims to enhance their sensitivity, resolution and integration into compact and portable devices such as handheld scanners or integrated communication chips. Generally, two-dimensional (2D) materials are considered potential candidates for device miniaturization but detecting THz radiation using 2D semiconductors is generally difficult due to the ultra-small photon energy. However, this challenge is being addressed by the advent of topological semimetals (TSM) with zero-bandgap characteristics. These semimetals offer low-energy excitations in proximity to the Dirac point, which is particularly important for applications requiring a broad detection range. Their distinctive band structures with linear energy-momentum dispersion near the Fermi level also lead to high electron mobility and low effective mass. The presence of topologically protected dissipationless conducting channels and self-powered response provides a basis for low-energy integration. In order to establish paradigms for semimetal-based THz detectors, this review initially offers an analytical summary of THz detection principles. Then, the review demonstrates the distinct design of devices, the excellent performance derived from the topological surface state and unique band structures in TSM. Finally, we outline the prospective avenues for on-chip integration of TSM-based THz detectors. We believe this review can promote further research on the new generation of THz detectors and facilitate advancements in THz imaging, spectroscopy, and communication systems.

Arbuscular mycorrhizal fungi offset NH3 emissions in temperate meadow soil under simulated warming and nitrogen deposition.

Most soil ammonia (NH3) emissions originate from soil nitrogen (N) that has been in the form of exchangeable ammonium. Emitted NH3 not only induces nutrient loss but also has adverse effects on the cycling of N and accelerates global warming. There is evidence that arbuscular mycorrhizal (AM) fungi can alleviate N loss by reducing N2O emissions in N-limited ecosystems, however, some studies have also found that global changes, such as warming and N deposition, can affect the growth and development of AM fungi and alter their functionality. Up to now, the impact of AM fungi on NH3 emissions, and whether global changes reduce the AM fungi's contribution to NH3 emissions reduction, has remained unclear. In this study, we examined how warming, N addition, and AM fungi alter NH3 emissions from high pH saline soils typical of a temperate meadow through a controlled microscopic experiment. The results showed that warming significantly increased soil NH3 emissions, but N addition and combined warming plus N addition had no impact. Inoculations with AM fungi strongly reduced NH3 emissions both under warming and N addition, but AM fungi effects were more pronounced under warming than following N addition. Inoculation with AM fungi reduced soil NH4+-N content and soil pH, and increased plant N content and soil net N mineralization rate while increasing the abundance of ammonia-oxidizing bacterial (AOB) gene. Structural equation modeling (SEM) shows that the regulation of NH3 emissions by AM fungi may be related to soil NH4+-N content and soil pH. These findings highlight that AM fungi can reduce N loss in the form of NH3 by increasing N turnover and uptake under global changes; thus, AM fungi play a vital role in alleviating the aggravation of N loss caused by global changes and in mitigating environmental pollution in the future.

Superiority of FAPI-PET/CT for examining multiple malignant tumors: a retrospective study.

To compare the diagnostic value of [18F]-AlF-NOTA-FAPI-04 PET/CT and [18F]-FDG PET/CT for primary and metastatic lesions in different types of tumors. A retrospective analysis was conducted on 51 patients with 11 different types of tumors. Among them, 20 patients underwent PET/CT, and 31 patients underwent restaging. The patients were diagnosed using [18F]-AlF-NOTA-FAPI-04 PET/CT and [18F]-FDG PET/CT scan techniques, and adverse reactions were recorded. Thickness of primary lesions, metastasis, and lymph node involvement were analyzed and confirmed by histological analysis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of [18F]-AlF-NOTA-FAPI-04 PET/CT and [18F]-FDG PET/CT were calculated. Neither [18F]-AlF-NOTA-FAPI-04 PET/CT nor [18F]-FDG PET/CT scan techniques caused adverse reactions in the patients. [18F]-AlF-NOTA-FAPI-04 PET/CT performed well in detecting recurrence, with a positive rate of 100%, higher than 71.0% of [18F]-FDG PET/CT. Compared with [18F]-FDG PET/CT, [18F]-AlF-NOTA-FAPI-04 PET/CT identified 6 types of malignant tumors more clearly, and could improve the detection rate of primary and metastatic tumors (97.0% vs. 84.8%, P<0.001). [18F]-AlF-NOTA-FAPI-04 PET/CT exhibited a higher sensitivity for detecting lymph node (81.8% vs. 50.0%, P<0.05) than [18F]-FDG PET/CT. Additionally, [18F]-AlF-NOTA-FAPI-04 PET/CT demonstrated higher diagnostic sensitivity (67.39% vs. 58.7%, P=0.387) and accuracy (82.14% vs. 60.71%, P=0.377) for detecting metastatic lesions compared to [18F]-FDG PET/CT. [18F]-AlF-NOTA-FAPI-04 PET/CT outperforms [18F]-FDG PET/CT in diagnosing primary and metastatic lesions across various types of tumors, especially in identifying lymph node, visceral, and peritoneal metastases. It can improve diagnostic efficiency and accuracy, thereby positively influencing clinical decision-making for optimal patient management.

Alternating BiI3-BiI van der Waals Photodetector with Low Dark Current and High-Performance Photodetection.

The emerging two-dimensional (2D) van der Waals (vdW) materials and their heterostructures hold great promise for optoelectronics and photonic applications beyond strictly lattice-matching constraints and grade interfaces. However, previous photodetectors and optoelectronic devices rely on relatively simple vdW heterostructures with one or two blocks. The realization of high-order heterostructures has been exponentially challenging due to conventional layer-by-layer arduous restacking or sequential synthesis. In this study, we present an approach involving the direct exfoliation of high-quality BiI3-BiI heterostructure nanosheets with alternating blocks, derived from solution-grown binary heterocrystals. These heterostructure-based photodetectors offer several notable advantages. Leveraging the "active layer energetics" of BiI layers and the establishment of a significant depletion region, our photodetector demonstrates a significant reduction in dark current compared with pure BiI3 devices. Specifically, the photodetector achieves an extraordinarily low dark current (<9.2 × 10-14 A at 5 V bias voltage), an impressive detectivity of 8.8 × 1012 Jones at 638 nm, and a rapid response time of 3.82 µs. These characteristics surpass the performance of other metal-semiconductor-metal (MSM) photodetectors based on various 2D materials and structures at visible wavelengths. Moreover, our heterostructure exhibits a broad-band photoresponse, covering the visible, near-infrared (NIR)-I, and NIR-II regions. In addition to these promising results, our heterostructure also demonstrated the potential for flexible and imaging applications. Overall, our study highlights the potential of alternating vdW heterostructures for future optoelectronics with low power consumption, fast response, and flexible requirements.

Functional characterization of obscure puffer ToNK-lysin: A novel immunomodulator possessing anti-bacterial and anti-inflammatory properties.

NK-lysins are one of the most abundant antimicrobial peptides produced by cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs), and identified as a new class of intrinsically disordered proteins, playing critical roles in the cell-mediated cytotoxicity response, as well as immunomodulatory and antimicrobial activities upon a significant range of pathogens. In the present study, an NK-lysin was identified from Obscure puffer Takifugu obscurus (ToNK-lysin). The open reading frame of ToNK-lysin sequence spans 423 bp, encoding a peptide with 140 amino acids which shares a moderate residue identity (18%-60%) with NK-lysin of mammals and other teleost species. Phylogenetic analysis revealed that ToNK-lysin was most closely related to NK-lysins from the Pleuronectiformes (Bastard halibut Paralichthys olivaceus and Pacific halibut Hippoglossus stenolepis). Comprehensive computational analysis revealed that ToNK-lysin have substantial level of intrinsic disorder, which might be contribute to its multifunction. The transcripts of the ToNK-lysin were detected in multiple examined tissues and most abundant in gills. After bacterial and Poly I:C challenge, the transcriptional levels of ToNK-lysin were significantly up-regulated in the head kidney, liver and spleen at different time points. The recombinant ToNK-lysin showed significant antibacterial activity against Vibrio harveyi and Escherichia coli, and the ToNK-lysin treatment not only reduced the bacterial loads in liver and head kidney, but also alleviated the pathogen-mediated upregulation of immune-related genes. In addition, the co-incubation with rToNK-lysin protein remarkably degraded bacterial genomic DNA, suggesting the potential mechanism of ToNK-lysin against microbes. These results suggest that ToNK-lysin possess antibacterial and immunoregulatory function both in vivo and in vitro, which may allow it a potential applicability to the aquaculture industry.

Effects of Freezing Raw Yak Milk on the Fermentation Performance and Storage Quality of Yogurt.

In this study, the effects of freezing yak milk at -20 °C and -40 °C for 30, 90 and 180 days on the fermentation characteristics and storage quality of the corresponding yogurt were discussed. The results showed that, compared with that of yogurt made from fresh yak milk, the lactic acid bacteria (LAB) growth and acid production rate of the yogurt in the -20 °C group decreased at 90 d. The water-holding capacity, viscosity and hardness decreased during storage, and a sour taste was prominent, while no significant changes were observed in the -40 °C group. At 180 d of freezing, the post-acidification of the yogurt in the -20 °C and -40 °C groups increased after 21 d of storage. Compared with the -40 °C group, the -20 °C group showed a significant decrease in LAB counts, a decrease in pH value to 3.63-3.80 and poor texture and sensory quality.

Fluorescence-guided surgical system using holographic display: from phantom studies to canine patients.

Significance: Holographic display technology is a promising area of research that can lead to significant advancements in cancer surgery. We present the benefits of combining bioinspired multispectral imaging technology with holographic goggles for fluorescence-guided cancer surgery. Through a series of experiments with 43D-printed phantoms, small animal models of cancer, and surgeries on canine patients with head and neck cancer, we showcase the advantages of this holistic approach. Aim: The aim of our study is to demonstrate the feasibility and potential benefits of utilizing holographic display for fluorescence-guided surgery through a series of experiments involving 3D-printed phantoms and canine patients with head and neck cancer. Approach: We explore the integration of a bioinspired camera with a mixed reality headset to project fluorescent images as holograms onto a see-through display, and we demonstrate the potential benefits of this technology through benchtop and in vivo animal studies. Results: Our complete imaging and holographic display system showcased improved delineation of fluorescent targets in phantoms compared with the 2D monitor display approach and easy integration into the veterinarian surgical workflow. Conclusions: Based on our findings, it is evident that our comprehensive approach, which combines a bioinspired multispectral imaging sensor with holographic goggles, holds promise in enhancing the presentation of fluorescent information to surgeons during intraoperative scenarios while minimizing disruptions.

Upregulation of SOX9 promotes the self-renewal and tumorigenicity of cervical cancer through activating the Wnt/ß-catenin signaling pathway.

Sry-box9 (SOX9) maintains stem cell properties and plays crucial roles in many cancers. However, whether SOX9 is correlated with cervical cancer cell stemness and its detailed mechanism remains obscure. We studied the relationship between SOX9 and prognosis of cervical cancer through public database, and SOX9 was related to poor prognosis of cervical cancer. Elevated SOX9 expression enhanced the self-renewal properties and promotes tumorigenicity in cervical cancer. Overexpression of SOX9 could promote the expression of stem cell-related factors in cervical cancer cells and xenografts. Meanwhile, overexpression of SOX9 could also enhance the expressions of FZD10, ß-catenin, and c-Myc in cervical cancer cells and xenografts, while inhibiting the expression of DDK1. The activation of Wnt pathway by chir-99 021 raised the tumor spheroid ability of SOX9 knockdown HeLa cells. In addition, SOX9 could transcriptional inhibit DKK1 and activate FZD10 and MYC by binding to their promoters to affect the Wnt/ß-catenin pathway. These results demonstrated SOX9 regulated the self-renewal and tumorigenicity of cervical cancer through Wnt/ß-catenin pathway by directly transcriptional activation of FZD10, MYC and transcriptional inhibition of DKK1.

Differentiating thymic epithelial tumors from mediastinal lymphomas: preoperative nomograms based on PET/CT radiomic features to minimize unnecessary anterior mediastinal surgery.

PURPOSE: Clinical feasibility nomograms were developed to facilitate the differentiation between thymic epithelial tumors (TETs) and mediastinal lymphomas (MLs), aiming to minimize the occurrence of non-therapeutic thymectomy. METHODS: A total of 255 patients diagnosed with TETs or MLs underwent pre-treatment 18F-FDG PET/CT. Comprehensive clinical and imaging data were collected, including age, gender, lactate dehydrogenase (LDH) level, pathological results, presence of myasthenia gravis symptoms, B symptoms, mass size, location, morphology, margins, density, and metabolic parameters derived from PET/CT. Radiomic features were extracted from the region of interest (ROI) of the primary lesion. Feature selection techniques were employed to identify the most discriminative subset of features. Machine learning methods were utilized to build candidate models, which were subsequently evaluated based on their area under the curve (AUC). Finally, nomograms were constructed using the optimal model to provide a clinical tool for improved diagnostic accuracy. The performance of the radiomic models was evaluated by their calibration, discrimination, and clinical utility. RESULTS: Several independent risk factors were identified for distinguishing TETs from MLs, including average standardized uptake value (SUVavg), LDH, age, mass size, and radiomic score (rad-score). Significance was observed in differentiating the two types of tumors based on these factors. The best clinical efficacy was demonstrated by the combined model, with an impressive AUC of 0.954. Decision curve analysis and calibration curves indicated that the combined model was clinically advantageous for discriminating TETs from MLs. Besides, the results of external validation showed a sensitivity of 0.8 and a specificity of 0.78. CONCLUSION: Preoperatively, the differentiation of TETs from MLs can be facilitated by the utilization of the combined clinical information and radiomics model. This approach holds promise in minimizing the occurrence of unnecessary anterior mediastinal surgeries.

Development and validation of 18F-FDG PET/CT radiomics-based nomogram to predict visceral pleural invasion in solid lung adenocarcinoma.

OBJECTIVES: This study aimed to establish a radiomics model based on 18F-FDG PET/CT images to predict visceral pleural invasion (VPI) of solid lung adenocarcinoma preoperatively. METHODS: We retrospectively enrolled 165 solid lung adenocarcinoma patients confirmed by histopathology with 18F-FDG PET/CT images. Patients were divided into training and validation at a ratio of 0.7. To find significant VPI predictors, we collected clinicopathological information and metabolic parameters measured from PET/CT images. Three-dimensional (3D) radiomics features were extracted from each PET and CT volume of interest (VOI). Receiver operating characteristic (ROC) curve was performed to determine the performance of the model. Accuracy, sensitivity, specificity and area under curve (AUC) were calculated. Finally, their performance was evaluated by concordance index (C-index) and decision curve analysis (DCA) in training and validation cohorts. RESULTS: 165 patients were divided into training cohort (n = 116) and validation cohort (n = 49). Multivariate analysis showed that histology grade, maximum standardized uptake value (SUVmax), distance from the lesion to the pleura (DLP) and the radiomics features had statistically significant differences between patients with and without VPI (P < 0.05). A nomogram was developed based on the logistic regression method. The accuracy of ROC curve analysis of this model was 75.86% in the training cohort (AUC: 0.867; C-index: 0.867; sensitivity: 0.694; specificity: 0.889) and the accuracy rate in validation cohort was 71.55% (AUC: 0.889; C-index: 0.819; sensitivity: 0.654; specificity: 0.739). CONCLUSIONS: A PET/CT-based radiomics model was developed with SUVmax, histology grade, DLP, and radiomics features. It can be easily used for individualized VPI prediction.

Suitable fertilization can improve maize growth and nutrient utilization in ridge-furrow rainfall harvesting cropland in semiarid area.

The ridge-furrow rainfall harvesting system (RFRH) improved the water shortages, and reasonable fertilization can promote nutrient uptake and utilization of crops, leading to better yield in semi-arid regions. This holds significant practical significance for improving fertilization strategies and reducing the application of chemical fertilizers in semi-arid areas. This field study was conducted to investigate the effects of different fertilization rates on maize growth, fertilizer use efficiency, and grain yield under the ridge-furrow rainfall harvesting system during 2013-2016 in semiarid region of China. Therefore, a four-year localization field experiment was conducted with four fertilizer treatments: RN (N 0 kg hm-2, P2O5 0 kg hm-2), RL (N 150 kg hm-2, P2O5 75 kg hm-2), RM (N 300 kg hm-2, P2O5 150 kg hm-2), and RH (N 450 kg hm-2, P2O5 225 kg hm-2). The results showed that the total dry matter accumulation of maize increased with the fertilizer application rate. The nitrogen accumulation was highest under the RM treatment after harvest, average increase by 1.41% and 22.02% (P<0.05) compared to the RH and RL, respectively, whereas the phosphorus accumulation was increased with the fertilizer application rate. The nitrogen and phosphorus use efficiency both decreased gradually with the fertilization rate increased, where the maximum efficiency was observed under the RL. With the increase of fertilizer application rate, the maize grain yield initially increased and then decreased. Under linear fitting, the grain yield, biomass yield, hundred-kernel weight, and ear-grain number all showed a parabolic trend with the increase of fertilization rate. Based on comprehensive consideration, the recommended moderate fertilization rate (N 300 kg hm-2, P2O5 150 kg hm-2) is suitable for the ridge furrow rainfall harvesting system in semiarid region, and the fertilization rate can be appropriately reduced according to the rainfall.

Redox-responsive self-assembled podophyllotoxin twin drug nanoparticles for enhanced intracellular drug delivery.

Podophyllotoxin (PPT) is an active natural pharmaceutical component with potent anticancer activity. However, due to its poor water solubility and serious side effects, its medical applications are limited. In this work, we synthesized a series of PPT dimers, which can be self-assembled into stable nanoparticles of 124-152 nm in aqueous solution and can significantly increase the solubility of PPT in aqueous solution. In addition, PPT dimer nanoparticles exhibited high drug loading capacity (>80%) and could store at 4 °C in aqueous state with good stability for at least 30 d.In vitrorelease studies showed that nanoparticles with disulfide bonds (SS NPs) can quickly release (about 96.5% drug released within 24 h) the conjugated drug in PBS buffer (pH = 7.4) in the presence of DTT. Cell endocytosis experiments showed that SS NPs enhanced cell uptake (18.56 times higher than PPT for Molm-13, 10.29 times for A2780S and 9.81 times for A2780T) and maintained antitumor effect against human ovarian tumor cells (A2780S and resistant A2780T) and human breast cancer cells (MCF-7). In addition, the endocytosis mechanism of SS NPs was revealed that these nanoparticles were mainly up-taken by macropinocytosis-mediated endocytosis. We believe that these PPT dimer-based nanoparticles will become an alternative formula for PPT, moreover the assembly behavior of PPT dimer can be extended to other therapeutic drugs.

Proteomic profiling of single extracellular vesicles reveals colocalization of SARS-CoV-2 with a CD81/integrin-rich EV subpopulation in sputum from COVID-19 severe patients.

Background: The global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic. Methods: We collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2. Result: Transmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-ß, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins. Conclusions: These results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs.

Single-Exosome Profiling Identifies ITGB3+ and ITGAM+ Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer.

Tumor metastasis is a hallmark of colorectal cancer (CRC), in which exosome plays a crucial role with its function in intercellular communication. Plasma exosomes were collected from healthy control (HC) donors, localized primary CRC and liver-metastatic CRC patients. We performed proximity barcoding assay (PBA) for single-exosome analysis, which enabled us to identify the alteration in exosome subpopulations associated with CRC progression. By in vitro and in vivo experiments, the biological impact of these subpopulations on cancer proliferation, migration, invasion, and metastasis was investigated. The potential application of exosomes as diagnostic biomarkers was evaluated in 2 independent validation cohorts by PBA. Twelve distinct exosome subpopulations were determined. We found 2 distinctly abundant subpopulations: one ITGB3-positive and the other ITGAM-positive. The ITGB3-positive cluster is rich in liver-metastatic CRC, compared to both HC group and primary CRC group. On the contrary, ITGAM-positive exosomes show a large-scale increase in plasma of HC group, compared to both primary CRC and metastatic CRC groups. Notably, both discovery cohort and validation cohort verified ITGB3+ exosomes as potential diagnostic biomarker. ITGB3+ exosomes promote proliferation, migration, and invasion capability of CRC. In contrast, ITGAM+ exosomes suppress CRC development. Moreover, we also provide evidence that one of the sources of ITGAM+ exosomes is macrophage. ITGB3+ exosomes and ITGAM+ exosomes are proven 2 potential diagnostic, prognostic, and therapeutic biomarkers for management of CRC.

Ultraviolet-Visible-Short-Wavelength Infrared Broadband and Fast-Response Photodetectors Enabled by Individual Monocrystalline Perovskite Nanoplate.

Perovskite-based photodetectors exhibit potential applications in communication, neuromorphic chips, and biomedical imaging due to their outstanding photoelectric properties and facile manufacturability. However, few of perovskite-based photodetectors focus on ultraviolet-visible-short-wavelength infrared (UV-Vis-SWIR) broadband photodetection because of the relatively large bandgap. Moreover, such broadband photodetectors with individual nanocrystal channel featuring monolithic integration with functional electronic/optical components have hardly been explored. Herein, an individual monocrystalline MAPbBr3 nanoplate-based photodetector is demonstrated that simultaneously achieves efficient UV-Vis-SWIR detection and fast-response. Nanoplate photodetectors (NPDs) are prepared by assembling single nanoplate on adjacent gold electrodes. NPDs exhibit high external quantum efficiency (EQE) and detectivity of 1200% and 5.37 × 1012 Jones, as well as fast response with rise time of 80 µs. Notably, NPDs simultaneously achieve high EQE and fast response, exceeding most perovskite devices with multi-nanocrystal channel. Benefiting from the high specific surface area of nanoplate with surface-trap-assisted absorption, NPDs achieve high performance in the near-infrared and SWIR spectral region of 850-1450 nm. Unencapsulated devices show outstanding UV-laser-irradiation endurance and decent periodicity and repeatability after 29-day-storage in atmospheric environment. Finally, imaging applications are demonstrated. This work verifies the potential of perovskite-based broadband photodetection, and stimulates the monolithic integration of various perovskite-based devices.

Joint equalization of EEPN, RSOP, and CD with the sliding window assisted extended Kalman filter for a high baud rate Stokes vector direct detection system.

Equalization-enhanced phase noise (EEPN) has emerged as one of the major impairments that cannot be ignored for a high baud rate Stokes vector direct detection (SVDD) system. When EEPN interacts with the rotation of state-of-polarization (RSOP) and chromatic dispersion (CD), the joint impairment effects become even more complicated. To achieve the joint equalization of EEPN, RSOP, and CD impairments of a high baud rate SVDD system, this paper first derives a joint impairment model of these three kinds of impairments, and then proposes a joint equalization scheme of EEPN, RSOP, and CD with a sliding window assisted extended Kalman filter (SWA-EKF). The SWA-EKF scheme first tracks RSOP in the time domain, subsequently compensates CD in the frequency domain, and finally performs EEPN mitigation in the time domain again. The effectiveness of the proposed scheme has been verified by a 60 GBaud SVDD-16QAM simulation system. The results show that when these three impairments are jointly equalized, the SWA-EKF scheme can track RSOP as fast as 3 Mrad/s, cumulative dispersion up to 1600 ps/nm, and EEPN caused by laser linewidth up to 3 MHz. In addition, with an optical signal-to-noise ratio penalty of 0.3 dB, it could increase 35 G baud rate under 3 MHz laser linewidth for the SVDD system. More importantly, its total complexity can be reduced to an order of O(N log N).

SNAI2 Attenuated the Stem-like Phenotype by Reducing the Expansion of EPCAMhigh Cells in Cervical Cancer Cells.

SNAI2 (Snai2) is a zinc-finger transcriptional repressor that belongs to the Snail family. The accumulated evidence suggests that SNAI2 exhibits biphasic effects on regulating a stem-like phenotype in various types of cells, both normal and malignant. In this study, by exogenously expressing SNAI2 in SiHa cells, SNAI2 exhibited the capacity to inhibit a stem-like phenotype in cervical cancer cells. The SNAI2-overexpressing cells inhibited cell growth, tumorsphere formation, tumor growth, enhanced sensitivity to cisplatin, reduced stem cell-related factors' expression, and lowered tumor initiating frequency. In addition, the EPCAMhigh cells sorted from SiHa cells exhibited an enhanced capacity to maintain a stem-like phenotype. Further study demonstrated that the trans-suppression of EPCAM expression by SNAI2 led to blockage of the nuclear translocation of ß-catenin, as well as reduction in SOX2 and c-Myc expression in SiHa and HeLa cells, but induction in SNAI2 knockdown cells (CaSki), which would be responsible for the attenuation of the stem-like phenotype in cervical cancer cells mediated by SNAI2. All of these results demonstrated that SNAI2 could attenuate the stem-like phenotype in cervical cancer cells through the EPCAM/ß-catenin axis.

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.