Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Corrigendum: Mutation of Gemin5 causes defective hematopoietic stem/progenitor cells proliferation in zebrafish embryonic hematopoiesis.

[This corrects the article DOI: 10.3389/fcell.2021.670654.].

Radiomics analysis of intratumoral and different peritumoral regions from multiparametric MRI for evaluating HER2 status of breast cancer: A comparative study.

Purpose: To investigate the potential of radiomics signatures (RSs) from intratumoral and peritumoral regions on multiparametric magnetic resonance imaging (MRI) to noninvasively evaluate HER2 status in breast cancer. Method: In this retrospective study, 992 patients with pathologically confirmed breast cancers who underwent preoperative MRI were enrolled. The breast cancer lesions were segmented manually, and the intratumor region of interest (ROIIntra) was dilated by 2, 4, 6 and 8 mm (ROIPeri2mm, ROIPeri4mm, ROIPeri6mm, and ROIPeri8mm, respectively). Quantitative radiomics features were extracted from dynamic contrast-enhanced T1-weighted imaging (DCE-T1), fat-saturated T2-weighted imaging (T2) and diffusion-weighted imaging (DWI). A three-step procedure was performed for feature selection, and RSs were constructed using a support vector machine (SVM) to predict HER2 status. Result: The best single-area RSs for predicting HER2 status were DCE_Peri4mm-RS, T2_Peri4mm-RS, and DWI_Peri4mm-RS, yielding areas under the curve (AUCs) of 0.716 (95% confidence interval (CI), 0.648-0.778), 0.706 (95% CI, 0.637-0.768), and 0.719 (95% CI, 0.651-0.780), respectively, in the test set. The optimal RSs combining intratumoral and peritumoral regions for evaluating HER2 status were DCE-T1_Intra + DCE_Peri4mm-RS, T2_Intra + T2_Peri6mm-RS and DWI_Intra + DWI_Peri4mm-RS, with AUCs of 0.752 (95% CI, 0.686-0.810), 0.754 (95% CI, 0.688-0.812) and 0.725 (95% CI, 0.657-0.786), respectively, in the test set. Combining three sequences in the ROIIntra, ROIPeri2mm, ROIPeri4mm, ROIPeri6mm and ROIPeri8mm areas, the optimal RS was DCE-T1_Peri4mm + T2_Peri4mm + DWI_Peri4mm-RS, achieving an AUC of 0.795 (95% CI, 0.733-0.849) in the test set. Conclusion: This study systematically explored the influence of the intratumoral region, different peritumoral sizes and their combination in radiomics analysis for predicting HER2 status in breast cancer based on multiparametric MRI and found the optimal RS.

Radon and lung cancer: Current status and future prospects.

Beyond tobacco smoking, radon takes its place as the second most significant contributor to lung cancer, excluding hereditary and other biologically related factors. Radon and its byproducts play a pivotal role in exposing humans to elevated levels of natural radiation. Approximately 10-20 % of lung cancer cases worldwide can be attributed to radon exposure, leading to between 3 % and 20 % of all lung cancer-related deaths. Nevertheless, a knowledge gap persists regarding the association between radon and lung cancer, impeding radon risk reduction initiatives globally. This review presents a comprehensive overview of the current state of research in epidemiology, cell biology, dosimetry, and risk modeling concerning radon exposure and its relevance to lung cancer. It also delves into methods for measuring radon concentrations, monitoring radon risk zones, and identifying priorities for future research.

Five undescribed cyclopeptides from Cordyceps militaris.

Ustiloxins I-M (1-5), five undescribed cyclopeptides bearing a 15-membered macrocyclic skeleton, were isolated from Cordyceps militaris. The structures of 1 and 5 were identified by spectroscopic and crystallographic methods, whereas the structures of 2-4 were assigned by spectroscopic and computational approaches. Biological evaluation of all the compounds toward human triple-negative breast cancer cells revealed that compounds 4 and 5 are toxic with IC50 values of 64.29 µM and 28.89 µM, respectively.

Circ-EIF3I Promotes Hepatocellular Carcinoma Progression Through Modulating miR-361-3p/DUSP2 Axis.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of HCC. Previous studies have confirmed that circ-EIF3I plays an important role in the progress of lung cancer. Nevertheless, the biological functions of circ-EIF3I and the underlying mechanisms by which they regulate HCC progression remain unclear. In this study, the regulatory mechanism and targets were studied with bioinformatics analysis, luciferase reporting analysis, transwell migration, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine analysis. In addition, in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circ-EIF3I in HCC. The result shows that the circ-EIF3I expression was increased in HCC cell line, which means that circ-EIF3I plays a role in the progression of HCC. Downregulation of circ-EIF3I suppressed HCC cells' proliferation and migration in both in vivo and in vitro experiments. Bioinformatics and luciferase report analysis confirmed that both miR-361-3p and Dual-specificity phosphatase 2 (DUSP2) were the downstream target of circ-EIF3I. The overexpression of DUSP2 or inhibition of miR-361-3p restored HCC cells' proliferation and migration ability after silence circ-EIF3I. Taken together, our study found that downregulation of circ-EIF3I suppressed the progression of HCC through miR-361-3p/DUSP2 Axis.

Nursing Care of a Child With Delirium Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Case Report.

INTRODUCTION: Children receiving extracorporeal membrane oxygenation are prone to delirium. This case report describes the nursing care of a child with delirium who received venoarterial extracorporeal membrane oxygenation. Relevant interventions and precautions are also discussed. CLINICAL FINDINGS: A 6-year-old girl was admitted to the pediatric intensive care unit with a 2-day history of vomiting and fever. The child underwent cannulation for venoarterial extracorporeal membrane oxygenation. DIAGNOSIS: The child was diagnosed with acute fulminant myocarditis, cardiac shock, and ventricular arrhythmia. INTERVENTIONS: On the third day of extracorporeal membrane oxygenation, bedside nurses began using the Cornell Assessment of Pediatric Delirium to assess the child for delirium symptoms. The team of physicians and nurses incorporated a nonpharmacologic delirium management bundle into pediatric daily care. Delirium screening, analgesia and sedation management, sleep promotion, and family participation were implemented. OUTCOMES: During the 18 days of pediatric intensive care unit hospitalization, the child had 6 days of delirium: 1.5 days of hypoactive delirium, 1.5 days of hyperactive delirium, and 3 days of mixed delirium. The child was successfully discharged home on hospital day 22. CONCLUSION: Caring for a child with delirium receiving venoarterial extracorporeal membrane oxygenation required multidimensional nursing capabilities to prevent and reduce delirium while ensuring safe extracorporeal membrane oxygenation. This report may assist critical care nurses caring for children under similar circumstances.

Ticagrelor regulates the differentiation of MDSCs after acute myocardial infarction to reduce cardiac injury.

Myeloid-derived suppressor cells (MDSCs) are important participants after acute myocardial infarction (AMI), but the role of their different subtypes in AMI remains controversial. The anti-inflammatory effect of ticagrelor in AMI has been discovered. However, the detailed anti-inflammatory mechanism has not been fully demonstrated. In this study, we aimed to determine whether ticagrelor can regulate the differentiation of MDSCs into anti-inflammatory subgroups to exert anti-inflammatory effects after AMI. In vitro experiments revealed no difference in the mRNA and protein expression of P2Y12 receptors on MDSCs and macrophages. Ticagrelor promotes the differentiation of in vitro cultured MDSCs to monocytic-MDSCs (M-MDSCs). A mouse AMI model was established to investigate the anti-inflammatory effects of ticagrelor in vivo after AMI by interfering with the differentiation of MDSCs. On the first day after AMI, spleen-derived polymorphonuclear-MDSCs (PMN-MDSCs) were predominant in the circulation and infarcted heart. Ticagrelor increased the percentage of M-MDSCs in the circulation and infarcted heart of AMI mice in a dose-dependent manner, attenuated cardiac inflammation and increased cardiac contractile function. M-MDSC injection significantly decreased cardiac inflammation levels and improved cardiac function in splenectomized AMI mice compared with PMN-MDSC injection. These data point to a novel anti-inflammatory role for ticagrelor after AMI by interfering with the differentiation of MDSCs.

Blood-Brain Barrier-Penetrating and Lesion-Targeting Nanoplatforms Inspired by the Pathophysiological Features for Synergistic Ischemic Stroke Therapy.

Ischemic stroke is a dreadful vascular disorder that poses enormous threats to the public health. Due to its complicated pathophysiological features, current treatment options after ischemic stroke attack remains unsatisfactory. Insufficient drug delivery to ischemic lesions impeded by the blood-brain barrier (BBB) largely limits the therapeutic efficacy of most anti-stroke agents. Herein, inspired by the rapid BBB penetrability of 4T1 tumor cells upon their brain metastasis and natural roles of platelet in targeting injured vasculatures, a bio-derived nanojacket is developed by fusing 4T1 tumor cell membrane with platelet membrane, which further clothes on the surface of paeonol and polymetformin-loaded liposome to obtain biomimetic nanoplatforms (PP@PCL) for ischemic stroke treatment. The designed PP@PCL could remarkably alleviate ischemia-reperfusion injury by efficiently targeting ischemic lesion, preventing neuroinflammation, scavenging excess reactive oxygen species (ROS), reprogramming microglia phenotypes, and promoting angiogenesis due to the synergistic therapeutic mechanisms that anchor the pathophysiological characteristics of ischemic stroke. As a result, PP@PCL exerts desirable therapeutic efficacy in injured PC12 neuronal cells and rat model of ischemic stroke, which significantly attenuates neuronal apoptosis, reduces infarct volume, and recovers neurological functions, bringing new insights into exploiting promising treatment strategies for cerebral ischemic stroke management.

Chemoimmunotherapeutic Nanogel for Pre- and Postsurgical Treatment of Malignant Melanoma by Reprogramming Tumor-Associated Macrophages.

Surgery is the primary method to treat malignant melanoma; however, the residual microtumors that cannot be resected completely often trigger tumor recurrence, causing tumor-related mortality following melanoma resection. Herein, we developed a feasible strategy based on the combinational chemoimmunotherapy by cross-linking carboxymethyl chitosan (CMCS)-originated polymetformin (PolyMetCMCS) with cystamine to prepare stimuli-responsive nanogel (PMNG) owing to the disulfide bond in cystamine that can be cleaved by the massive glutathione (GSH) in tumor sites. Then, chemotherapeutic agent doxorubicin (DOX) was loaded in PMNG, which was followed by a hyaluronic acid coating to improve the overall biocompatibility and targeting ability of the prepared nanogel (D@HPMNG). Notably, PMNG effectively reshaped the tumor immune microenvironment by reprogramming tumor-associated macrophage phenotypes and recruiting intratumoral CD8+ T cells owing to the inherited immunomodulatory capability of metformin. Consequently, D@HPMNG treatment remarkably suppressed melanoma growth and inhibited its recurrence after surgical resection, proposing a promising solution for overcoming lethal melanoma recurrence.

Successful repair of an encephalocele wound in a child following a car accident: A case report.

Repair of large cranial complex traumas in children is difficult. Notably, children have poorer underlying conditions than adults and are frailer under trauma. In addition, children have more limited treatment options, leading to the need to consider long-term functional and aesthetic outcomes. The present report describes the case of a 2-year-old child weighing 9 kg who experienced a skull fracture with encephalocele after a car accident and had a poor underlying condition. An artificial dura mater combined with bone cement was used to repair the skull, and then a free latissimus dorsi muscle flap (LDMF) combined with a split-thickness skin graft (STSG) was used to cover the wound, allowing the child to overcome the life-threatening situation as soon as possible with a satisfactory outcome. LDMF combined with STSG is an ideal option in repairing head wounds in children. Preoperative imaging and postoperative care also serve an important role in the success of the operation. When the situation is critical, multidisciplinary team treatment can guarantee the safety of the child.

Modular access to chiral bridged piperidine-γ-butyrolactones via catalytic asymmetric allylation/aza-Prins cyclization/lactonization sequences.

Chiral functionalized piperidine and lactone heterocycles are widely spread in natural products and drug candidates with promising pharmacological properties. However, there remains no general asymmetric methodologies that enable rapid assemble both critical biologically important units into one three-dimensional chiral molecule. Herein, we describe a straightforward relay strategy for the construction of enantioenriched bridged piperidine-γ-butyrolactone skeletons incorporating three skipped stereocenters via asymmetric allylic alkylation and aza-Prins cyclization/lactonization sequences. The excellent enantioselectivity control in asymmetric allylation with the simplest allylic precursor is enabled by the synergistic Cu/Ir-catalyzed protocol; the success of aza-Prins cyclization/lactonization can be attributed to the pivotal role of the ester substituent, which acts as a preferential intramolecular nucleophile to terminate the aza-Prins intermediacy of piperid-4-yl cation species. The resulting chiral piperidine-γ-butyrolactone bridged-heterocyclic products show impressive preliminary biological activities against a panel of cancer cell lines.

Rational Design of an α-1,3-Fucosyltransferase for the Biosynthesis of 3-Fucosyllactose in Bacillus subtilis ATCC 6051a via De Novo GDP-l-Fucose Pathway.

3-Fucosyllactose (3-FL) is an important oligosaccharide and nutrient in breast milk that can be synthesized in microbial cells by α-1,3-fucosyltransferase (α-1,3-FucT) using guanosine 5'-diphosphate (GDP)-l-fucose and lactose as substrates. However, the catalytic efficiency of known α-1,3-FucTs from various sources was limited due to their low solubility. To enhance the microbial production of 3-FL, the efficiencies of α-1,3-FucTs were evaluated and in Bacillus subtilis (B. subtilis) chassis cells that had been endowed with a heterologous synthetic pathway for GDP-l-fucose, revealing that the activity of FucTa from Helicobacter pylori (H. pylori) was higher than that of any of other reported homologues. To further improve the catalytic performance of FucTa, a rational design approach was employed, involving intracellular evaluation of the mutational sites of M32 obtained through directed evolution, analysis of the ligand binding site diversity, and protein structure simulation. Among the obtained variants, the FucTa-Y218 K variant exhibited the highest 3-FL yield, reaching 7.55 g/L in the shake flask growth experiment, which was 3.48-fold higher than that achieved by the wild-type enzyme. Subsequent fermentation optimization in a 5 L bioreactor resulted in a remarkable 3-FL production of 36.98 g/L, highlighting the great prospects of the designed enzyme and the strains for industrial applications.

Circumstances affecting patients' euthanasia or medically assisted suicide decisions from the perspectives of patients, relatives, and healthcare professionals: A qualitative systematic review.

This study aims to explore circumstances affecting patients' euthanasia and medically assisted suicide (MAS) decisions from the perspectives of patients, relatives, and healthcare professionals. A qualitative systematic review was performed following PRISMA recommendations. The review protocol is registered in PROSPERO (CRD42022303034). Literature searches were conducted in MEDLINE, EMBASE, CINAHL Complete, Eric, PsycInfo, and citation pearl search in Scopus from 2012 to 2022. In total, 6840 publications were initially retrieved. The analysis included a descriptive numerical summary analysis and a qualitative thematic analysis of 27 publications, resulting in two main themes-Contexts and factors influencing actions and interactions, and Finding support while dealing with resistance in euthanasia and MAS decisions-and related sub-themes. The results illuminated the dynamics in (inter)actions between patients and involved parties that might both impede and facilitate patients' decisions related to euthanasia/MAS, potentially influencing patients' decision-making experiences, and the roles and experiences of involved parties.

Towards Real-Time Sleep Stage Prediction and Online Calibration Based on Architecturally Switchable Deep Learning Models.

Despite the recent advances in automatic sleep staging, few studies have focused on real-time sleep staging to promote the regulation of sleep or the intervention of sleep disorders. In this paper, a novel network named SwSleepNet, that can handle both precisely offline sleep staging, and online sleep stages prediction and calibration is proposed. For offline analysis, the proposed network coordinates sequence broadening module (SBM), sequential CNN (SCNN), squeeze and excitation (SE) block, and sequence consolidation module (SCM) to balance the operational efficiency of the network and the comprehensive feature extraction. For online analysis, only SCNN and SE are involved in predicting the sleep stage within a short-time segment of the recordings. Once more than two successive segments have disparate predictions, the calibration mechanism will be triggered, and contextual information will be involved. In addition, to investigate the appropriate time of the segment that is suitable to predict a sleep stage, segments with five-second, three-second, and two-second data are analyzed. The performance of SwSleepNet is validated on two publicly available datasets Sleep-EDF Expanded and Montreal Archive of Sleep Studies (MASS), and one clinical dataset Huashan Hospital Fudan University (HSFU), with the offline accuracy of 84.5%, 86.7%, and 81.8%, respectively, which outperforms the state-of-the-art methods. Additionally, for the online sleep staging, the dedicated calibration mechanism allows SwSleepNet to achieve high accuracy over 80% on three datasets with the short-time segments, demonstrating the robustness and stability of SwSleepNet. This study presents a real-time sleep staging architecture, which is expected to pave the way for accurate sleep regulation and intervention.

Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ-Hydroxy α-Amino Acids and Small Peptides.

An atom- and step-economical and redox-neutral cascade reaction enabled by asymmetric bimetallic relay catalysis by merging a ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with copper-catalyzed asymmetric Michael addition has been realized. A variety of highly functionalized 2-amino-5-hydroxyvaleric acid esters or peptides bearing 1,4-non-adjacent stereogenic centers have been prepared in high yields with excellent enantio- and diastereoselectivity. Judicious selection and rational modification of the Ru catalysts with careful tuning of the reaction conditions played a pivotal role in stereoselectivity control as well as attenuating undesired α-epimerization, thus enabling a full complement of all four stereoisomers that were otherwise inaccessible in previous work. Concise asymmetric stereodivergent synthesis of the key intermediates for biologically important chiral molecules further showcases the synthetic utility of this methodology.

Complication rates and safety of pulsed dye laser treatment for port-wine stain: a systematic review and meta-analysis.

Pulsed dye laser (PDL) is the most commonly used method for port-wine stain (PWS); however, no studies have reported the safety of PDL. This review aimed to collect and summarize complications reported in relevant literature, assess complication rates in treating PWS with PDL, and explore the relevant influencing factors. A systematic review and meta-analysis were conducted to search for related studies in PubMed, Embase, and the Cochrane Library until August 2022. Two reviewers independently evaluated the risk of bias of included studies. Stata Software version 17.0 was used for the analysis. All complications reported in the literature are divided into acute phase complications and long-term complications. Overall pooled purpura, edema, crusting, blistering, hyperpigmentation, hypopigmentation, and scarring rates were 98.3%, 97.6%, 21.5%, 8.7%, 12.8%, 0.9%, and 0.2%, respectively. Although the acute adverse reactions were found to be common, the long-term permanent complications clearly have a lower frequency, and the occurrence of scarring is much lower than that initially thought. This indicates that effective protective measures after treatment are very important for preventing scar formation. Overall, PDL treatment for PWS shows a high level of safety and low chances of causing long-term complications.

Sodium alginate and chitosan co-modified fucoxanthin liposomes: preparation, bioaccessibility and antioxidant activity.

To improve the stability of fucoxanthin, fucoxanthin liposomes (L) were prepared by the thin-film ultrasound method, and fucoxanthin liposomes were modified with sodium alginate and chitosan by an electrostatic deposition method. The release characteristics of fucoxanthin in different types of liposomes with in vitro gastrointestinal simulation were studied. Under the optimum conditions, the results showed that the encapsulation efficiency of prepared liposomes could reach 88.56 ± 1.40% (m/m), with an average particle size of 295.27 ± 7.28 nm, a Zeta potential of -21.53 ± 2.00 mV, a polydispersity index (PDI) of 0.323 ± 0.007 and a loading capacity of 33.3 ± 0.03% (m/m). Compared with L and chitosan modified fucoxanthin liposomes (CH), sodium alginate and chitosan modified fucoxanthin liposomes (SA-CH) exhibited higher storage stability, in vitro bioaccessibility and antioxidant activity after gastrointestinal digestion. Sodium alginate and chitosan co-modified liposomes can be developed as formulations for encapsulation and delivery of functional ingredients, providing a theoretical basis for developing new fucoxanthin series products.

Short-term effect of coil handle orientations on fMRI-guided rTMS on insomnia: A case report.

Introduction: The coil handle orientation plays a pivotal role in the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). However, there is currently no consensus on the optimal individualized coil handle orientation, especially for non-motor areas. Case presentation: The present case reported a short-term effect of functional connectivity (FC)-guided rTMS with coil handle posterior-anterior 45° (PA45°) and posterior-anterior 135° (PA135°) on a patient with insomnia. Notably, in this case, the PA45° orientation was nearly perpendicular to the adjacent sulcus, while the PA135° orientation was almost parallel to it. Local brain activity and functional connectivity were assessed using resting-state functional magnetic resonance imaging (RS-fMRI). Additionally, motor evoked potentials (MEPs) were captured both pre and post-rTMS sessions. Findings: The coil handle orientation PA45° outperformed the PA135° in both RS-fMRI and MEP outcomes. Moreover, a 9-day rTMS treatment led to discernible improvements in symptoms of depression and anxiety, complemented by a modest enhancement in sleep quality.

M2 Macrophage-Derived Exosomal lncRNA MIR4435-2HG Promotes Progression of Infantile Hemangiomas by Targeting HNRNPA1.

Purpose: Infantile hemangiomas (IHs) are commonly observed benign tumors that can cause serious complications. M2-polarized macrophages in IHs promote disease progression. In this study, we investigated the role of M2 macrophage-derived exosomal lncRNA MIR4435-2HG in IHs. Patients and Methods: Exosomes derived from M2 polarized macrophages were extracted. Next, using cell co-culture or transfection, we investigated whether M2 polarized macrophage-derived exosomes (M2-exos) can transport MIR4435-2HG to regulate the proliferation, migration, invasion, and angiogenesis of hemangioma-derived endothelial cells (HemECs). RNA-seq and RNA pull-down assays were performed to identify targets and regulatory pathways of MIR4435-2HG. We explored the possible mechanisms through which MIR4435-2HG regulates the biological function of HemECs. Results: M2-exos significantly enhanced the proliferation, migration, invasion, and angiogenesis of HemECs. Thus, HemECs uptake M2-exos and promote biological functions through the inclusion of MIR4435-2HG. RNA-seq and RNA pull-down experiments confirmed that MIR4435-2HG regulates of HNRNPA1 expression and directly binds to HNRNPA1, consequently affecting the NF-κB signal pathway. Conclusion: MIR4435-2HG of M2-exos promotes the progression of IHs and enhances the proliferation, migration, invasion, and angiogenesis of HemECs by directly binding to HNRNPA1. This study not only reveals the mechanism of interaction between M2 macrophages and HemECs, but also provides a promising therapeutic target for IHs.