Solution-Phase Synthesis of KCl Nanocrystals Templated by PEO-PPO-PEO Triblock Copolymers Micelles.

The current work introduces the synthesis of inorganic salt nano/micro-crystals during the reduction of hydrogen tetrachloroaurate(III) by Pluronic triblock copolymers (P123, PEO20-PPO70-PEO20). The morphologies and component were confirmed using an electron microscope with an electronic differential system (EDS), and the crystal structures were determined with X-ray diffraction (XRD). The morphologies highly depend on the concentrations of Pluronic and pH values. The mean size of the nanocrystal and hollow micro-crystal were controlled typically in the range of 32-150 nm (side length) and 1.4 µm, respectively. Different from the electrospray-ionization (EI) method, a model in which KCl forms a supersaturated solution in the micellar core of Pluronic is used to explain the formation process. This work provides the new insight that inorganic salt nanocrystals could be synthesized with the template of micelles in pure aqueous solutions.

Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance.

Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and the immunosuppressive nature of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components of the TME. M2-like TAMs are essential in facilitating tumor metastasis as well as augmenting the drug resistance of tumors. This review encapsulates the mechanisms that M2-like TAMs use to promote tumor drug resistance. We also describe the emerging therapeutic strategies that are currently targeting M2-like TAMs in combination with other antitumor drugs, with some still undergoing clinical trial evaluation. Furthermore, we summarize and analyze various existing approaches for developing novel drugs that target M2-like TAMs to overcome tumor resistance, highlighting how targeting M2-like TAMs can effectively stop tumor growth, metastasis, and overcome tumor drug resistance.

Invasive mucinous adenocarcinoma of the lung with bronchorrhea - A marked reduction volume of sputum after SARS-CoV-2 infection.

Bronchorrhea is a watery sputum volume of at least 100 mL/day, which is commonly associated with lung malignancies. We report a 57-year-old woman was admitted to the hospital with a cough, profuse sputum. Chest CTs showed crazy paving pattern and lung nodules. Cell nests were visible on the Thinprep Cytologic Test. The case was considered an invasive mucinous adenocarcinoma of the lung combined with bronchorrhea. Significantly, the sputum volume declined rapidly and did not rise again when the patient was diagnosed with COVID-19 and treated with nirmatrelvir/ritonavir. This case is suggestive of studies related to regulatory mediators associated with bronchorrhea.

An ovalbumin fusion strategy to increase recombinant protein secretion in chicken eggs.

Maternal secretion of recombinant proteins into chicken eggs may provide a viable approach for pharmaceutical production but remains limited by poor secretion efficiency through the membrane of oviduct cells, despite high expression levels. Here, we used site-specific integration of an EGFP fused to the OVAL gene by a rigid linker, (EAAAK)3, at the endogenous ovalbumin locus in chicken primordial germ cells to generate OVAL-E3-EGFP transgenic chickens, with transgenic chickens expressing CMV immediate enhancer/ß-actin-driven EGFP (CAG-EGFP) as a non-secreted control. In OVAL-E3-EGFP chickens, EGFP protein produced in maternal oviducts accumulates to high levels in eggs, but not in eggs of CAG-EGFP chickens. These results indicated that the secretion of foreign proteins can be substantially increased through fusion to the highly secreted endogenous ovalbumin. This study describes a basis for high yield recombinant protein expression in chicken eggs, enabling rapid and scalable production of numerous pharmaceutical proteins or metabolites.

Development and validation of a combined nomogram for predicting perineural invasion status in rectal cancer via computed tomography-based radiomics.

AIM: This study aimed to create and validate a clinic-radiomics nomogram based on computed tomography (CT) imaging for predicting preoperative perineural invasion (PNI) of rectal cancer (RC). MATERIAL AND METHODS: This study enrolled 303 patients with RC who were divided into training (n = 242) and test datasets (n = 61) in an 8:2 ratio with all their clinical outcomes. A total of 3,296 radiomic features were extracted from CT images. Five machine learning (ML) models (logistic regression (LR)/K-nearest neighbor (KNN)/multilayer perceptron (MLP)/support vector machine (SVM)/light gradient boosting machine (LightGBM)) were developed using radiomic features derived from the arterial and venous phase images, and the model with the best diagnostic performance was selected. By combining the radiomics and clinical signatures, a fused nomogram model was constructed. RESULTS: After using the Mann-Whitney U-test and least absolute shrinkage and selection operator (LASSO) to remove redundant features, the MLP model proved to be the most efficient among the five ML models. The fusion nomogram based on MLP prediction probability further improves the ability to predict the PNI status. The area under the curve (AUC) of the training and test sets was 0.883 and 0.889, respectively, which were higher than those of the clinical (training set, AUC = 0.710; test set, AUC = 0.762) and radiomic models (training set, AUC = 0.840; test set, AUC = 0.834). CONCLUSIONS: The clinical-radiomics combined nomogram model based on enhanced CT images efficiently predicted the PNI status of patients with RC.

Characterization of translocon proteins in the type III secretion system of Lawsonia intracellularis.

Lawsonia intracellularis, the etiologic agent of proliferative enteropathy (PE), is an obligate intracellular Gram-negative bacterium possessing a type III secretion system (T3SS), which enables the pathogen to translocate effector proteins into targeted host cells to modulate their functions. T3SS is a syringe-like apparatus consisting of a base, an extracellular needle, a tip, and a translocon. The translocon proteins assembled by two hydrophobic membrane proteins can form pores in the host-cell membrane, and therefore play an essential role in the function of T3SS. To date, little is known about the T3SS and translocon proteins of L. intracellularis. In this study, we first analyzed the conservation of the T3S apparatus between L. intracellularis and Yersinia, and characterized the putative T3S hydrophobic major translocon protein LI1158 and minor translocon protein LI1159 in the L. intracellularis genome. Then, by using Yersinia pseudotuberculosis as a surrogate system, we found that the full-length LI1158 and LI1159 proteins, but not the putative class II chaperone LI1157, were secreted in a - Ca2+ and T3SS-dependent manner and the secretion signal was located at the N terminus (aa 1-40). Furthermore, yeast-two hybrid experiments revealed that LI1158 and LI1159 could self-interact, and LI1159 could interact with LI1157. However, unlike CPn0809 and YopB, which are the major hydrophobic translocon proteins of the T3SS of C. pneumoniae and Yersinia, respectively, full-length LI1158 was non-toxic to both yeast and Escherichia coli cells, but full-length LI1159 showed certain toxicity to E. coli cells. Taken together, despite some differences from the findings in other bacteria, our results demonstrate that LI1158 and LI1159 may be the translocon proteins of L. intracellularis T3SS, and probably play important roles in the translocation of effector proteins at the early pathogen infection stage.

[Discussion on the status quo and solutions to the prevention and control of birth defects among primary obstetricians and gynecologists in the era of molecular genetic testing].

Birth defects are an important factor for the quality of newborn population. With the development of molecular genetic technology, an increasing number of genetic disorders leading to birth defects can now be detected. The lack of the knowledge for the basics and clinical applications of molecular genetic techniques have emerged as a shortcoming for primary care physicians who have formed the first tier prevention for birth defects. Currently, government has paid more attention to the above problems and formulated more training programs for primary obstetricians and gynecologists, e.g., "Prenatal Screening and Prenatal Diagnosis Post Training Program", "National Birth Defects Training Program", "National Primary Obstetrician Training Program". To some extent, such programs have met the urgent need for birth defect prevention in primary hospitals. But at the same time, some problems have also emerged. For instance, the knowledge for birth defects among primary obstetricians and gynecologists is poor, and there is lack of young personnel. This article has aimed to discuss the strategies to systematically improve the ability for preventing birth defects among primary care physicians by analyzing the obstacles and challenges for primary obstetricians and gynecologists in the era of molecular genetic testing.

High-sensitivity self-powered photodetector based on an in-situ prepared CsPbBr3 microwire/InGaN heterojunction.

Low-dimensional CsPbBr3 perovskite materials have gained widespread attention, derived from their remarkable properties and potential for numerous optoelectronic applications. Herein, the sample of CsPbBr3 microwires were prepared horizontally onto n-type InGaN film substrate using an in-plane solution growth method. The resulting CsPbBr3 microwire/InGaN heterojunction allows for the achievement of a highly sensitive and broadband photodetector. Particularly for the implementation in a self-supplying manner, the best-performing photodetector can achieve a superior On/Off ratio of 4.6×105, the largest responsivity ∼ 800.0 mA/W, a maximum detectivity surpassing 4.6× 1012 Jones, and a high external quantum efficiency approaching 86.5% upon 405 nm light illumination. A rapid response time (∼ 4.48 ms/7.68 ms) was also achieved. The as-designed CsPbBr3 microwire/InGaN heterojunction device without any encapsulation exhibits superior comprehensive stability. Besides, the device featuring as a single pixel imaging unit can readily detect simple images under broadband light illumination with a high spatial resolution, acknowledging its outstanding imaging capability. The robust photodetection properties could be derived from the intense absorption of CsPbBr3 MWs and high-efficiency charge carriers transporting toward the in-situ formed CsPbBr3/InGaN heterointerface. The results may offer an available strategy for the in-situ construction of best-performing low-dimensional perovskite heterojunction optoelectronic devices.

The nucleolar protein NIFK accelerates the progression of colorectal cancer via activating MYC pathway.

This study aimed to explore the function of nucleolar protein interacting with the FHA domain of MKI67 (NIFK) on colorectal cancer (CRC) and its associated molecular mechanisms. NIFK was upregulated in CRC tissues and cells. NIFK silencing resulted in reduced cell growth and metastasis, as well as in promoted apoptosis in CRC cells. Moreover, NIFK silencing was also confirmed to inhibit lipid accumulation and decrease fatty acid synthesis via downregulating lipogenic enzymes in CRC cells. Gene set enrichment analysis and western blot co-verified that NIFK silencing inhibited MYC proto-oncogene, bHLH transcription factor (MYC) pathway in CRC cells. In addition, we also revealed that NIFK silencing function on cell growth, apoptosis, metastasis, and fatty acid metabolism in CRC might be cancelled after c-MYC overexpression. Silencing NIFK could inhibit cell growth and metastasis, and promoted apoptosis, as well as regulated fatty acid metabolism by inhibiting MYC pathway in CRC.

A novel artificial intelligence model for fetal facial profile marker measurement during the first trimester.

BACKGROUND: To study the validity of an artificial intelligence (AI) model for measuring fetal facial profile markers, and to evaluate the clinical value of the AI model for identifying fetal abnormalities during the first trimester. METHODS: This retrospective study used two-dimensional mid-sagittal fetal profile images taken during singleton pregnancies at 11-13+ 6 weeks of gestation. We measured the facial profile markers, including inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial-maxillary angle (FMA), frontal space (FS) distance, and profile line (PL) distance using AI and manual measurements. Semantic segmentation and landmark localization were used to develop an AI model to measure the selected markers and evaluate the diagnostic value for fetal abnormalities. The consistency between AI and manual measurements was compared using intraclass correlation coefficients (ICC). The diagnostic value of facial markers measured using the AI model during fetal abnormality screening was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 2372 normal fetuses and 37 with abnormalities were observed, including 18 with trisomy 21, 7 with trisomy 18, and 12 with CLP. Among them, 1872 normal fetuses were used for AI model training and validation, and the remaining 500 normal fetuses and all fetuses with abnormalities were used for clinical testing. The ICCs (95%CI) of the IFA, MNM angle, FMA, FS distance, and PL distance between the AI and manual measurement for the 500 normal fetuses were 0.812 (0.780-0.840), 0.760 (0.720-0.795), 0.766 (0.727-0.800), 0.807 (0.775-0.836), and 0.798 (0.764-0.828), respectively. IFA clinically significantly identified trisomy 21 and trisomy 18, with areas under the ROC curve (AUC) of 0.686 (95%CI, 0.585-0.788) and 0.729 (95%CI, 0.621-0.837), respectively. FMA effectively predicted trisomy 18, with an AUC of 0.904 (95%CI, 0.842-0.966). MNM angle and FS distance exhibited good predictive value in CLP, with AUCs of 0.738 (95%CI, 0.573-0.902) and 0.677 (95%CI, 0.494-0.859), respectively. CONCLUSIONS: The consistency of fetal facial profile marker measurements between the AI and manual measurement was good during the first trimester. The AI model is a convenient and effective tool for the early screen for fetal trisomy 21, trisomy 18, and CLP, which can be generalized to first-trimester scanning (FTS).

UR-Net: An Integrated ResUNet and Attention Based Image Enhancement and Classification Network for Stain-Free White Blood Cells.

The differential count of white blood cells (WBCs) can effectively provide disease information for patients. Existing stained microscopic WBC classification usually requires complex sample-preparation steps, and is easily affected by external conditions such as illumination. In contrast, the inconspicuous nuclei of stain-free WBCs also bring great challenges to WBC classification. As such, image enhancement, as one of the preprocessing methods of image classification, is essential in improving the image qualities of stain-free WBCs. However, traditional or existing convolutional neural network (CNN)-based image enhancement techniques are typically designed as standalone modules aimed at improving the perceptual quality of humans, without considering their impact on advanced computer vision tasks of classification. Therefore, this work proposes a novel model, UR-Net, which consists of an image enhancement network framed by ResUNet with an attention mechanism and a ResNet classification network. The enhancement model is integrated into the classification model for joint training to improve the classification performance for stain-free WBCs. The experimental results demonstrate that compared to the models without image enhancement and previous enhancement and classification models, our proposed model achieved a best classification performance of 83.34% on our stain-free WBC dataset.

Association between CTLA4 + 49A/G polymorphism and risk of hepatocellular carcinoma: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to compile the data examining the association between the CTLA4 + 49 A/G polymorphism and the risk for HCC. Multiple databases were systematically searched for eligible studies and the pooled odds ratios (ORs) were generated using five genetic models. Pooled data from 11 studies with 3,055 HCC patients and 3,450 controls found no statistically significant association between the polymorphism and HCC risk, both overall and in subgroup analyses. In conclusion, the current meta-analysis shows that the CTLA4 + 49 A/G polymorphism is not significantly associated with the risk of developing HCC.

Recent advances in deformation-assisted microfluidic cell sorting technologies.

Cell sorting is an essential prerequisite for cell research and has great value in life science and clinical studies. Among the many microfluidic cell sorting technologies, label-free methods based on the size of different cell types have been widely studied. However, the heterogeneity in size for cells of the same type and the inevitable size overlap between different types of cells would result in performance degradation in size-based sorting. To tackle such challenges, deformation-assisted technologies are receiving more attention recently. Cell deformability is an inherent biophysical marker of cells that reflects the changes in their internal structures and physiological states. It provides additional dimensional information for cell sorting besides size. Therefore, in this review, we summarize the recent advances in deformation-assisted microfluidic cell sorting technologies. According to how the deformability is characterized and the form in which the force acts, the technologies can be divided into two categories: (1) the indirect category including transit-time-based and image-based methods, and (2) the direct category including microstructure-based and hydrodynamics-based methods. Finally, the separation performance and the application scenarios of each method, the existing challenges and future outlook are discussed. Deformation-assisted microfluidic cell sorting technologies are expected to realize greater potential in the label-free analysis of cells.

Cationic and anionic defect decoration of CoO through Cu dopants and oxygen vacancy for a High­Performance supercapacitor.

CoO has attracted increasing attention as an electrochemical energy storage owing to its excellent redox activity and high theoretical specific capacitance. However, its low inherent electrical conductivity results in sluggish reaction kinetics, and the poor rate capability of CoO limits its widespread applications. Herein, a multiple-defect strategy of engineering oxygen vacancies and Cu-ion dopants into the low-crystalline CoO nanowires (Ov-Cu-CoO) is successfully applied. Because of the advantage of the dual defect synergetic effect, the electronic structure and charge distribution are effectively modulated, thus enhancing the electrical conductivity and enriched redox chemistry. The obtained Ov-Cu-CoO electrode exhibits a high specific capacity of 1388.6 F⋅g-1 at a current density of 1 A⋅g-1, an ultrahigh rate performance (81.2% of the capacitance retained at 20 A⋅g-1) and excellent cycling stability (101.1% after 10,000 cycles). Moreover, an asymmetric supercapacitor device with Ov-Cu-CoO as the positive electrode having a high energy density of 44.1 W⋅h⋅kg-1 at a power density of 800 W⋅kg-1, and can still remain 27.2 W⋅h⋅kg-1 at a power density of 16 kW⋅kg-1. This study demonstrates an effective strategy to enhance electrochemical performance of CoO that can be easy applied to other transition metal oxides.

Role of marine algal blooms in the release of arsenic at the sediment-seawater interface: Evidence from microcosm experiments.

Algal blooms can aggravate arsenic (As) release from sediments and thus pose a pollution risk in the marine environment. However, the driving mechanism of algal blooms on sedimentary As cycling remains unclear. This study undertakes the first comprehensive examination of As release mechanisms under algal bloom conditions based on the evidence provided by temporal and depth profile changes of As species in the overlying water column, porewater and sediment, as well as As-related functional genes over the course of a 30-day incubation experiment using algal addition. The higher rate of increase of dissolved total As (dTAs) concentrations in a high biomass algal group (HAG) than an experimental control group (CG) suggested that algal degradation promoted the release of sedimentary As. The solid phase in all experimental groups remained rich in As(V), while in porewater As(III) and As(V) were the dominant As species during the initial rapid and subsequent slow degradation phases of organic matter, respectively, indicating that microbial reduction of As(V) and Fe(III) controlled the release of As during these two periods. A pronounced increase in arrA gene copies, and not a corresponding increase in the Geobacter copies, in HAG relative to CG supported the notion that algal blooms promoted microbial As(V) reduction. Additionally, the lower concentration of dissolved As(III) and cumulative dTAs flux in the sterilized-HAG treatment than in the sterilized-CG one further suggested that geochemically-mediated processes were not the main pathways of As release. Finally, it is estimated that summer algal blooms in the Changjiang Estuary can cause the release of 1440 kg of sedimentary As into the overlying water.

Successful Liver Transplantation From a Deceased Donor With Congenital Extrahepatic Portosystemic Shunt: A Case Report.

Congenital extrahepatic portosystemic shunt belongs to a family of rare vascular abnormalities. We present a case of congenital extrahepatic portosystemic shunt occurring in a 42-year-old man who died of cerebral hemorrhage and donated his liver. His portal vein angiography revealed that the main portal vein communicated with the left renal vein, suggesting a portosystemic shunt. A liver biopsy showed that the liver tissue structure was normal. His liver was not involved, and the transplantation was carried out smoothly. The recipient recovered smoothly, and the function of the transplanted liver was good.

Chinese and Western Integrative Medicine for Stage IIIb-IVb Non-Small Cell Lung Cancer: Design and Rationale of a Multi-center, Prospective Registry (NSCLC-Chinese and Western Integrative Medicine cohort).

INTRODUCTION: This planned multicenter observational study will evaluate the overall survival of those undergoing integrated Chinese and Western medicine for stage IIIb-IVb non-small cell lung cancer and analyze the factors related to the prognosis. METHOD AND ANALYSIS: The prospective cohort will enroll patients with stage IIIb-IVb NSCLC from March 1, 2019, to December 31, 2025, and follow them for 5 years. We plan to collect data on the patients' demographics, treatment, overall survival, and factors related to the prognosis. ETHICS AND DISSEMINATION: The institutional review board and ethics committee reviewed the study protocol. All patients will provide informed consent before enrollment.Trial registration number: ChiCTR1900021430.

Analytical and experimental study of a valveless piezoelectric micropump with high flowrate and pressure load.

Miniaturized gas pumps based on electromagnetic effect have been intensively studied and widely applied in industries. However, the electromagnetic effect-based gas pumps normally have large sizes, high levels of noises and high power consumption, thus they are not suitable for wearable/portable applications. Herein, we propose a high-flowrate and high-pressure load valveless piezoelectric micropump with dimensions of 16 mm*16 mm*5 mm. The working frequency, vibration mode and displacement of the piezoelectric actuator, the velocity of gas flow, and the volume flowrate of the micropump are analyzed using the finite element analysis method. The maximum vibration amplitude of the piezoelectric actuator reaches ~29.4 µm. The output gas flowrate of the pump is approximately 135 mL/min, and the maximum output pressure exceeds 40 kPa. Then, a prototype of the piezoelectric micropump is fabricated. Results show that performance of the micropump is highly consistent with the numerical analysis with a high flowrate and pressure load, demonstrated its great potential for wearable/portable applications, especially for blood pressure monitoring.

Identification of the active compounds in the Yi-Fei-San-Jie formula using a comprehensive strategy based on cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology techniques.

BACKGROUND: Chinese herbal formulae has multiple active constituents and targets, and the good clinical response is encouraging more scientists to explore the bio-active ingredients in such complex systems. Yi-Fei-San-Jie formula (YFSJF) is commonly used to treat patients with lung cancer in South China; however, its bio-active ingredients remain unknown. PURPOSE: We investigated the bio-active ingredients of the YFSJF using a novel comprehensive strategy. METHODS: A549 cell extraction coupled with ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was used for the screening of potential bio-active ingredients. Network pharmacology approach and molecular dynamics simulation were performed for the screening of targets. Surface plasmon resonance (SPR) assay and molecular biology techniques were used to verify the targets. RESULTS: Nine A549 cell membrane-binding compounds were identified through cell extraction/UPLC-MS/MS. Five compounds, namely ginsenoside Ro, ginsenoside Rb1, ginsenoside Rc, peimisine, and peimine were cytotoxic to A549 cells, and they were considered the bio-active ingredients of the YFSJF in vitro. Network pharmacology analysis revealed that TGFBR2 is the key target and the TGFß pathway is the key pathway targeted by YFSJF in non-small cell lung cancer. Peimisine showed an affinity to TGFBR2 using molecular docking and dynamic stimulation, which was confirmed using surface plasmon resonance spectroscopy. The molecular biology-based analysis further confirmed that peimisine targets TGFBR2 and can reverse A549 epithelial-mesenchymal transition by inhibiting the TGFß pathway. CONCLUSION: Taken together, cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology-based analysis comprise a feasible strategy to explore active ingredients in YFSJF.