A chimeric adenovirus-vectored vaccine based on Beta spike and Delta RBD confers a broad-spectrum neutralization against Omicron-included SARS-CoV-2 variants.

Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5-Beta/Deta vaccine induced robust broad-spectrum neutralization against Omicron BA.5-included variants. IN immunization with Ad5-Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue-resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5-Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5-Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5-Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS-CoV-2 pre-Omicron variants of concern and BA.5-included Omicron subvariants.

The role of neutrophil to lymphocyte ratio in patients with COPD-OSA overlap syndrome.

PURPOSE: The aim of this study is to investigate the role of the neutrophil to lymphocyte ratio (NLR) in patients diagnosed with the chronic obstructive pulmonary disease-obstructive sleep apnea (COPD-OSA) overlap syndrome and comorbid pulmonary hypertension (PH). PATIENTS AND METHODS: We enrolled a consecutive of stable COPD patients and conducted spirometry measurements, nocturnal polysomnography (PSG), and echocardiography for all participants. Clinical laboratory data were collected. RESULTS: A total of 178 patients with stable COPD were enrolled among whom 33.14% (59/178) were diagnosed with OSA. Of the patients with overlap syndrome, 35.59% (21/59) showed comorbid PH, compared to 34.45% (41/119) in COPD patients without OSA. There was no significant difference in the occurrence of PH between COPD with and without OSA. NLR was significantly higher in patients with overlap syndrome compared to those with either disease alone. The difference in NLR between COPD-OSA patients with and without PH was not significant. Correlation analysis revealed that NLR was associated with age, total sleep time spent with oxygen saturation below 90% (T90), CRP, pulmonary artery systolic pressure (PASP), and minimum peripheral capillary oxygen saturation (SpO2min) in all COPD patients. NLR was identified as an independent factor contributing to OSA in COPD. The median cut-off value for detecting OSA in stable COPD was 2.49. However, NLR was not found to be a predictor for PH in COPD-OSA overlap syndrome. CONCLUSIONS: NLR can serve as a predictive marker for comorbid OSA in patients with COPD. NLR is expected to increase its clinical application as a convenient and cost-effective biomarker for COPD-OSA overlap syndrome.

NIR-II Excitable Water-Dispersible Two-Dimensional Conjugated Polymer Nanoplates for In Vivo Two-Photon Luminescence Bioimaging.

While two-dimensional conjugated polymers (2DCPs) have shown great promise in two-photon luminescence (TPL) bioimaging, 2DCP-based TPL imaging agents that can be excited in the second near-infrared window (NIR-II) have rarely been reported so far. Herein, we report two 2DCPs including 2DCP1 and 2DCP2, with octupolar olefin-linked structures for NIR-II-excited bioimaging. The 2DCPs are customized with the fully conjugated donor-acceptor (D-A) linkage and aggregation-induced emission (AIE) active building blocks, leading to good two-photon absorption into the NIR-II window with a 2PACS of ∼64.0 GM per choromophore for both 2DCPs. Moreover, 2DCP1 powders can be exfoliated into water-dispersible nanoplates with a Pluronic F-127 surfactant-assisted temperature-swing method, accompanied by both a drastic reduction of 2PACS throughout the range of 780-1080 nm and a sharp increase of photoluminescence quantum yield to 33.3%. The 2DCP1 nanoplates are subsequently proven to be capable of assisting in visualizing mouse brain vasculatures with a penetration depth of 421 µm and good contrast in vivo, albeit that only 19% of previous 2PACS at 1040 nm is preserved. This work not only provides important insights on how to construct NIR-II excitable 2DCPs for TPL bioimaging but also how to investigate the exfoliation-photophysical property correlation of 2DCPs, which should aid in future research on developing highly efficient TPL bioimaging agents.

The effect of genetic variation and mRNA expression of interleukin-17A gene on susceptibility to asthma.

Analyzing the genetic variation and mRNA expression of interleukin-17A (IL-17A) gene and its impact on asthma susceptibility was the purpose of this study. 120 asthma patients were selected as the asthma group, and another 120 healthy individuals who underwent physical examination were selected as the health group; Compare the cytokine levels and mRNA expression of IL-17A between two groups, as well as the clinical indicator total immunoglobulin E (TIgE) levels; The genotype and allele distribution frequency of IL-17A Single-nucleotide polymorphism locus rs2275913 and rs8193036 were compared between the two groups; Compare the serum IL-17A and TIgE levels of different genotypes at rs2275913 and rs8193036 loci; and logistic regression was used to evaluate the impact of IL-17A on asthma susceptibility. The serum levels of IL-17A, TIgE, and IL-17AmRNA expression in the asthma group were higher than those in the healthy group (P<0.05). There were three genotypes of AA, AG and GG at rs2275913 locus, and the frequency distribution between the two groups was significant (P<0.05), and the frequency of A Allele frequency in asthma group was higher than that in healthy group (P<0.05). There are three genotypes of CC, CT, and TT at the rs8193036 locus, and there was no significant difference in the frequency distribution between the two groups (P>0.05). There is no difference in the frequency distribution of alleles C and T between the two groups (P>0.05). The levels of IL-17A and TIgE in the rs2275913AA genotype were higher than those in the AG and GG genotypes (P<0.05); There was no difference in IL-17A and TIgE levels among different genotypes of rs8193036 (P>0.05). The rs2275913 polymorphism was associated with asthma susceptibility and is an independent risk parameter for asthma susceptibility. Upregulation of serum IL-17A and TIgE, as well as overexpression of IL-17A mRNA, were closely related to asthma susceptibility in asthma patients. The rs2275913 polymorphism had a significant role in increasing the risk of asthma, and variant allele A may be a susceptibility factor for increasing asthma risk.

NIR-IIb fluorescence-image guided synergistic surgery/starvation/chemodynamic therapy: an innovative treatment paradigm for malignant non-small cell lung cancers.

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce3+ doped in the core and 100% Yb3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H2O2 to boost the CDT mediated by the Mn2+ and Cu2+, which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics.

Functional Trait Responses of Sophora alopecuroides L. Seedlings to Diverse Environmental Stresses in the Desert Steppe of Ningxia, China.

The seedling stage of plants is a crucial and vulnerable period in population and community dynamics. Despite this, studies on how plant traits respond to different environmental stresses often tend to overlook this early stage. Our study focused on Sophora alopecuroides L. seedlings in Ningxia Yanchi desert steppe, analyzing the effects of sand burial, salinity, and drought on their key aboveground and belowground traits. The results showed that sand burial significantly negatively affected stem biomass (SB), leaf biomass (LB), stem diameter (SD), leaf length (LL), leaf width (LW), leaf area (LA), and total root volume (RV), but positively influenced total root length (RL). As sand burial depth increased, SB, LB, SD, LL, LW, LA, RV, root biomass (RB), RV, and lateral root numbers (LRN) significantly decreased. Salinity stress negatively affected SB, LB, SD, LL, LW, LA, RB, RL, and RV, with these traits declining as the stress concentration increased. Drought stress had a positive effect on SD and LL, with both traits showing an increase as the intensity of the drought stress intensified; however, it adversely affected RL. In Ningxia Yanchi desert steppe, salinity stress had the most significant effect on the traits of S. alopecuroides seedlings, followed by sand burial, with drought having the least significant effect. This study provides essential theoretical support for understanding how S. alopecuroides seedlings cope with environmental stresses in their early life stages.

BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.

Bruton's tyrosine kinase (BTK) is an essential component of multiple signaling pathways that regulate B cell and myeloid cell proliferation, survival, and functions, making it a promising therapeutic target for various B cell malignancies and inflammatory diseases. Five small molecule inhibitors have shown remarkable efficacy and have been approved to treat different types of hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib. The first-in-class agent, ibrutinib, has created a new era of chemotherapy-free treatment of B cell malignancies. Ibrutinib is so popular and became the fourth top-selling cancer drug worldwide in 2021. To reduce the off-target effects and overcome the acquired resistance of ibrutinib, significant efforts have been made in developing highly selective second- and third-generation BTK inhibitors and various combination approaches. Over the past few years, BTK inhibitors have also been repurposed for the treatment of inflammatory diseases. Promising data have been obtained from preclinical and early-phase clinical studies. In this review, we summarized current progress in applying BTK inhibitors in the treatment of hematological malignancies and inflammatory disorders, highlighting available results from clinical studies.

Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging.

BACKGROUND: Therapy with genetically modified mesenchymal stem cells (MSCs) has clinical translation promise. Optimizing the targeting migratory ability of MSCs relies on accurate imaging of the distribution and extravasation kinetics of MSCs, and the corresponding imaging results could be used to predict therapeutic outcomes and guide the optimization of the treatment program. Among the different imaging modalities, second near-infrared (NIR-II) optical-resolution photoacoustic microscopy (OR-PAM) has merits, including a fine resolution, a deep penetration, a high sensitivity, and a large signal-to-background ratio. It would be an ideal candidate for precise monitoring of MSCs, although it has not been tested for this purpose so far. RESULTS: Penetrating peptide-decorated conjugated polymer nanoparticles (TAT-CPNPs) with strong NIR-II absorbance were used to label chemokine-receptor genetically modified MSCs, which were subsequently evaluated under intravital NIR-II OR-PAM regarding their targeting migratory ability. Based on the upregulation of chemokine (C-X-C motif) ligand 10 in the inflamed ears of contact hypersensitivity mice, MSCs with overexpression of corresponding receptor, chemokine (C-X-C motif) receptor 3 (Cxcr3) were successfully generated (MSCCxcr3). TAT-CPNPs labeling enabled NIR-II photoacoustic imaging to discern MSCCxcr3 covered by 1.2 cm of chicken breast tissue. Longitudinal OR-PAM imaging revealed enhanced inflammation-targeting migration of MSCCxcr3 over time attributed to Cxcr3 gene modification, which was further validated by histological analysis. CONCLUSIONS: TAT-CPNPs-assisted NIR-II PA imaging is promising for monitoring distribution and extravasation kinetics of MSCs, which would greatly facilitate optimizing MSC-based therapy.

Insight into soil nitrogen and phosphorus availability and agricultural sustainability by plant growth-promoting rhizobacteria.

Nitrogen and phosphorus are critical for the vegetation ecosystem and two of the most insufficient nutrients in the soil. In agriculture practice, many chemical fertilizers are being applied to soil to improve soil nutrients and yield. This farming procedure poses considerable environmental risks which affect agricultural sustainability. As robust soil microorganisms, plant growth-promoting rhizobacteria (PGPR) have emerged as an environmentally friendly way of maintaining and improving the soil's available nitrogen and phosphorus. As a special PGPR, rhizospheric diazotrophs can fix nitrogen in the rhizosphere and promote plant growth. However, the mechanisms and influences of rhizospheric nitrogen fixation (NF) are not well researched as symbiotic NF lacks summarizing. Phosphate-solubilizing bacteria (PSB) are important members of PGPR. They can dissolve both insoluble mineral and organic phosphate in soil and enhance the phosphorus uptake of plants. The application of PSB can significantly increase plant biomass and yield. Co-inoculating PSB with other PGPR shows better performance in plant growth promotion, and the mechanisms are more complicated. Here, we provide a comprehensive review of rhizospheric NF and phosphate solubilization by PGPR. Deeper genetic insights would provide a better understanding of the NF mechanisms of PGPR, and co-inoculation with rhizospheric diazotrophs and PSB strains would be a strategy in enhancing the sustainability of soil nutrients.

Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy.

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

An animal experiment study on the application of indocyanine green angiography in the harvest of multi-angiosome perforator flap.

Background: This study sought to explore the application value of indocyanine green angiography (ICGA) in the harvest of multi-angiosome perforator flap and the effect of low molecular weight heparin (LMWH) on the survival of postoperative flap. Methods: Twenty-four SD male rats were selected to construct a three-angiosome perforator flap model with the unilateral iliolumbar artery perforator. They were randomly divided into two groups: the control group was injected with indocyanine green (ICG) into the femoral vein during the operation, and the fluorescence signal was collected and quantitatively analyzed using Real-Time Image Guided System to determine the intraoperative fluorescence imaging length. The experimental group was injected subcutaneously with LMWH (400 U/kg) after 0.5 h postoperatively, and the control group was injected with the same amount of normal saline. The injection was repeated at the same time each day from 0 to 7 days postoperatively. After the flap was sutured in situ, ICGA was performed at 0, 1, 3, 5, and 7 days postoperatively to observe the vascular structure of the two groups of flaps. The flap survival length of the control group was counted at 7 days postoperatively, and the correlation between the intraoperative fluorescence imaging length and the survival length at 7 days postoperatively was calculated. The proportion of distal necrosis of the flaps between the two groups was compared at 7 days postoperatively. Results: The average length of intraoperative fluorescence imaging in the control group was 6.29±0.50 cm, and the survival length of the flap at 7 days postoperatively was 8.24±0.52 cm. The actual survival length was higher than the intraoperative fluorescence imaging length, with a ratio of 1.31±0.08. The difference was statistically significant (P<0.05). At 7 days postoperatively, the flap necrosis ratio of experimental group and control group were 10.92%±1.30% and 19.11%±1.19%, and the flap necrosis ratio of experimental group was lower than that of control group (P<0.001). Conclusions: ICGA can locate the position of perforator, and can be used to predict and observe the length of distal survival of multi-angiosome perforator flap postoperatively. LMWH can promote the distal survival of flap and reduce flap necrosis.

The level of carbon dioxide is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic primary central sleep apnea: a case report.

Primary central sleep apnea is classified as nonhypercapnic central sleep apnea. High loop gain, lower CO2 reserves, and other reasons can lead to hypocapnia in patients who develop intermittent hyperventilation during sleep. Therefore, it is necessary to monitor nocturnal CO2 level for these patients. We report a female patient diagnosed with nonhypercapnic primary central sleep apnea who complained of snoring, apnea, and excessive daytime sleepiness. With the monitoring of transcutaneous partial pressure of CO2, manual noninvasive ventilation pressure titration was performed with continuous positive airway pressure, bilevel positive airway pressure in a spontaneous-timed mode, and adaptive servo-ventilation mode for 3 nights, respectively. Only adaptive servo-ventilation mode could stabilize the transcutaneous partial pressure of CO2 above the apneic threshold (approximately 40 mm Hg) with successfully eliminating central apnea events. It is concluded that the level of CO2 is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic central sleep apnea. CITATION: Han X, Zhao D, Wang J, Wang Y, Dong L, Chen B-y. The level of carbon dioxide is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic primary central sleep apnea: a case report. J Clin Sleep Med. 2022;18(1):319-324.

Ikaros Proteins in Tumor: Current Perspectives and New Developments.

Ikaros is a zinc finger transcription factor (TF) of the Krüppel family member, which significantly regulates normal lymphopoiesis and tumorigenesis. Ikaros can directly initiate or suppress tumor suppressors or oncogenes, consequently regulating the survival and proliferation of cancer cells. Over recent decades, a series of studies have been devoted to exploring and clarifying the relationship between Ikaros and associated tumors. Therapeutic strategies targeting Ikaros have shown promising therapeutic effects in both pre-clinical and clinical trials. Nevertheless, the increasingly prominent problem of drug resistance targeted to Ikaros and its analog is gradually appearing in our field of vision. This article reviews the role of Ikaros in tumorigenesis, the mechanism of drug resistance, the progress of targeting Ikaros in both pre-clinical and clinical trials, and the potential use of associated therapy in cancer therapy.

Application of CT-Based Radiomics in Discriminating Pancreatic Cystadenomas From Pancreatic Neuroendocrine Tumors Using Machine Learning Methods.

OBJECTIVES: The purpose of this study aimed at investigating the reliability of radiomics features extracted from contrast-enhanced CT in differentiating pancreatic cystadenomas from pancreatic neuroendocrine tumors (PNETs) using machine-learning methods. METHODS: In this study, a total number of 120 patients, including 66 pancreatic cystadenomas patients and 54 PNETs patients were enrolled. Forty-eight radiomic features were extracted from contrast-enhanced CT images using LIFEx software. Five feature selection methods were adopted to determine the appropriate features for classifiers. Then, nine machine learning classifiers were employed to build predictive models. The performance of the forty-five models was evaluated with area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score in the testing group. RESULTS: The predictive models exhibited reliable ability of differentiating pancreatic cystadenomas from PNETs when combined with suitable selection methods. A combination of DC as the selection method and RF as the classifier, as well as Xgboost+RF, demonstrated the best discriminative ability, with the highest AUC of 0.997 in the testing group. CONCLUSIONS: Radiomics-based machine learning methods might be a noninvasive tool to assist in differentiating pancreatic cystadenomas and PNETs.

Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p.

BACKGROUND: Apigenin (API) is a naturally occurring plant-derived flavone, which is abundantly present in common fruits and vegetables, and shows little or no toxicity of daily diet. The treatment of colorectal cancer is limited by high recurrence rate and multidrug resistance. PURPOSE: The purpose of this study was to explore the potential therapeutic effect and possible mechanisms of API on colorectal cancer cells. METHODS: Cell proliferation and apoptosis of human colon cancer cell line HCT116 was assessed after API treatment. A comprehensive transcriptome profile of API-treated HCT116 cells was acquired by high-throughput sequencing. The regulation of miRNA215-5p and E2F1/3 were identified by bioinformatics analyses. An inhibitor of miRNA215-5p, inhibitor 215, was applied to confirm the role of this microRNA played in the anti-cancer effect of API. Luciferase reporter gene assay was performed to identify targeting relationship between miRNA215-5p and E2F1/3. RESULT: API significantly promoted cell apoptosis and anti-proliferation of HCT116 cells in a dose-dependent manner. Bioinformatics analyses identified several altered miRNAs among which the expression of miRNA-215-5p showed markedly increased. Meanwhile, the expression of E2F1 and E2F3 was decreased by API, which was associated with miRNA215-5p. Luciferase reporter gene assay showed miRNA-215-5p could directly bind to 3' UTR of E2F1/3. Inhibition of miRNA-215-5p significantly inhibited apoptosis and cell cycle arrest at G0/G1 phase induced by API. CONCLUSIONS: The result of this study confirmed the anti-cancer effect of API on human colorectal cancer cells and investigated the underlying mechanism by a comprehensive transcriptome profile of API-treated cells.

Targeting CXCR2 inhibits the progression of lung cancer and promotes therapeutic effect of cisplatin.

BACKGROUND: Drug-resistance and severe side effects of chemotherapeutic agents result in unsatisfied survival of patients with lung cancer. CXCLs/CXCR2 axis plays an important role in progression of cancer including lung cancer. However, the specific anti-cancer mechanism of targeting CXCR2 remains unclear. METHODS: Immunohistochemical analysis of CXCR2 was performed on the microarray of tumor tissues of clinical lung adenocarcinoma and lung squamous cell carcinoma patients. CCK8 test, TUNEL immunofluorescence staining, PI-Annexin V staining, ß-galactosidase staining, and Western blot were used to verify the role of CXCR2 in vitro. Animal models of tail vein and subcutaneous injection were applied to investigate the therapeutic role of targeting CXCR2. Flow cytometry, qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry analysis were performed for further mechanistic investigation. RESULTS: The expression of CXCR2 was elevated in both human lung cancer stroma and tumor cells, which was associated with patients' prognosis. Inhibition of CXCR2 promoted apoptosis, senescence, epithelial-to-mesenchymal transition (EMT), and anti-proliferation of lung cancer cells. In vivo study showed that tumor-associated neutrophils (TANs) were significantly infiltrate into tumor tissues of mouse model, with up-regulated CXCLs/CXCR2 signaling and suppressive molecules, including Arg-1 and TGF-ß. SB225002, a selective inhibitor of CXCR2 showed promising therapeutic effect, and significantly reduced infiltration of neutrophils and enhanced anti-tumor T cell activity via promoting CD8+ T cell activation. Meanwhile, blockade of CXCR2 could enhance therapeutic effect of cisplatin via regulation of neutrophils infiltration. CONCLUSIONS: Our finds verify the therapeutic effects of targeting CXCR2 in lung cancer and uncover the potential mechanism for the increased sensitivity to chemotherapeutic agents by antagonists of CXCR2.

Distinct Characteristics of COVID-19 Infection in Children.

SARS-CoV-2, a member of the family coronaviridae, has triggered a lethal pandemic termed coronavirus disease 2019 (COVID-19). Pediatric patients, mainly from families with a cluster of infection or a history of exposure to epidemic areas, get infected via direct contacts or air-borne droplets. Children (aged below 18 years) are susceptible to COVID-19, with an average incubation period of about 6.5 days. Most cases present asymptomatic or common cold symptoms such as fever, cough, and myalgia or fatigue, which is milder than adult patients. Besides, most abnormal laboratory and radiologic findings in children with COVID-19 are non-specific. Since no specific chemotherapeutic agents have been approved for children, timely preventive methods could effectively forestall the transmission of SARS-CoV-2. To date, mostly studied cases have been adults with COVID-19, whereas data on pediatrics patients remain poorly defined. We herein conducted a literature review for papers published in PubMed and medRxiv (preprints) between December 2019 and December 2020 that reported on pediatrics patients (aged below 18 years) with a confirmed COVID-19 diagnosis. In this review, we summarized and discussed the pathogenesis, epidemiology, and clinical management of COVID-19 in pediatrics patients to improve our understanding of this new disease in children.

mRNA vaccine: a potential therapeutic strategy.

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

Effects of F-, Cl-, Br-, NO3-, and SO42- on the colloidal stability of Fe3O4 nanoparticles in the aqueous phase.

The effect of ions on the colloidal behavior of magnetic nanoparticles (MNPs) is an important factor for determining the dispersibility of MNPs. Compared with the effects of cations and organic matter, the effect of anions on MNPs has rarely been studied. Hence, in this study, the effect of anions on the aggregation of Fe3O4 MNPs in the aqueous phase was investigated using F-, Cl-, Br-, NO3-, and SO42-. The results indicated that the effect of anions on the colloidal behavior of the MNPs varied widely depending on their valence state, concentration, hydration ability, solution pH, and the magnetic force between the MNPs. Specifically, at pH 5.0, the anions were mainly adsorbed on the particle surface by electrostatic attraction, decreasing the electrostatic repulsion between the MNPs and causing an aggregation of the particles in the order of SO42- > F- > Br- > Cl- ≈ NO3-. At pH 9.0, anions strengthened the suspension of the MNPs at low ionic strength (IS) (≤5); however, with increasing IS, an aggregation of the MNPs in the following order was formed: NO3- > Cl- > Br- ≥ F- > SO42-. This was a result of the combined effects of the IS of solution, hydrability, and polarizability of the anions. Furthermore, the Derjaguin-Landau-Vervey-Overbeek (DLVO) theory can explain the colloidal behavior of MNPs in the presence of magnetic forces, but it fails to differentiate the MNP behaviors between monovalent anions because the effects of ionic hydrability and polarizability are not considered. Distinctively, the secondary minimum between the MNPs particles were induced via magnetic attraction and played a critical role in adjusting the colloidal stability of the MNPs. Overall, these results indicate that specific ionic effects and magnetic attraction are important for interpreting the colloidal stability of MNPs in aqueous conditions.

[Global research hotspots on oncology-bibliometric analysis based on the ESI hot papers].

With the increasing global burden of various cancer, an abundance of papers emerged every year in the research hotspots of oncology, covering a wide range of research types and topics. In order to facilitate interested readers to quickly grasp the frontier and hotspots of cancer research, it would be helpful to sort out and summarize the research topic in a timely manner. According to the classification of disciplines, we screened the Essential Science Indicators (ESI) hot papers released in 2019 for the ones in the oncology field, utilized methods such as bibliometrics, statistical description, hierarchical induction, analysis and interpretation to further reveal the context and characteristics of research in the field of oncology, summarized the latest progresses and future directions in the field, and provided information and hints for the trajectory of future research. A total of 549 papers were included, which were mainly from the field of clinical medicine; the country with the most publications was the United States, while China ranked the fourth in terms of contribution; the research institution with the highest number of published papers was University of Texas system; N Engl J Med published the most papers, with contribution also from highly influential journals in the field of oncology such as Lancet Oncol, J Clin Oncol, JAMA Oncol and Cancer Discov. Oncology remained the most popular research topic in the medical research and spanned a wide spectrum of sub-topics. In this study, we demonstrated and sorted out research frontiers in the field of oncology in 12 different research directions including the basic cancer research, cancer epidemiology, and various tumors types related to different systems and organs.