Photoresponsive Multirole Nanoweapon Camouflaged by Hybrid Cell Membrane Vesicles for Efficient Antibacterial Therapy of Pseudomonas aeruginosa-Infected Pneumonia and Wound.

Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug-loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near-infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti-inflammatory and antibacterial properties in models of P. aeruginosa-infected pneumonia and wounds. Hence, this light-activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections.

Linking the Doping-Induced Trap States to the Concentration of Surface-Reaching Photoexcited Holes in Transition-Metal-Doped TiO2 Nanoparticles.

Transition-metal doping has been demonstrated to be effective for tuning the photocatalytic activity of semiconductors. Nonetheless, the impact of doping-induced trap states on the concentration of surface-reaching photoexcited charges remains a topic of debate. In this study, through time-resolved spectroscopies and kinetic analysis, we found that the concentration of surface-reaching photoholes (Ch+(surf)) in doped TiO2 nanoparticles sensitively relies on the type of dopants and their associated trap states. Among the studied dopants (Fe, Cu, and Co), Fe doping resulted in the most significant increase in Ch+(surf), nearly double that of Co or Cu doping. Fe-doping induced more effective hole trap states, acting as the mediator for interfacial charge transfer, thus accelerating charge separation and consequently enriching Ch+(surf). This work provides valuable insight into understanding and controlling Ch+(surf) in transition-metal-doped TiO2 materials.

PSEENet: A pseudo-siamese neural network incorporating electroencephalography and electrooculography characteristics for heterogeneous sleep staging.

Sleep staging plays a critical role in evaluating the quality of sleep. Currently, most studies are either suffering from dramatic performance drops when coping with varying input modalities or unable to handle heterogeneous signals. To handle heterogeneous signals and guarantee favorable sleep staging performance when a single modality is available, a pseudo-siamese neural network (PSN) to incorporate electroencephalography (EEG), electrooculography (EOG) characteristics is proposed (PSEENet). PSEENet consists of two parts, spatial mapping modules (SMMs) and a weight-shared classifier. SMMs are used to extract high-dimensional features. Meanwhile, joint linkages among multi-modalities are provided by quantifying the similarity of features. Finally, with the cooperation of heterogeneous characteristics, associations within various sleep stages can be established by the classifier. The evaluation of the model is validated on two public datasets, namely, Montreal Archive of Sleep Studies (MASS) and SleepEDFX, and one clinical dataset from Huashan Hospital of Fudan University (HSFU). Experimental results show that the model can handle heterogeneous signals, provide superior results under multimodal signals and show good performance with single modality. PSEENet obtains accuracy of 79.1%, 82.1% with EEG, EEG and EOG on Sleep-EDFX, and significantly improves the accuracy with EOG from 73.7% to 76% by introducing similarity information.

Black Phosphorus Quantum Dot Loaded Bioinspired Nanoplatform Synergized with aPD-L1 for Multimode Cancer Immunotherapy.

Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving the therapeutic efficacy of nanoparticles (NPs). Herein, a multifunctional nanoplatform (BPP@RTL) that precisely targets tumor cells is fabricated by encapsulating ultrasmall phototherapeutic agent black phosphorus quantum dot (BPQD), chemotherapeutic drug paclitaxel (PTX), and immunomodulator PolyMetformin (PM) in hybrid membrane-camouflaged liposomes. Specifically, the hybrid cell membrane coating derived from the fusion of cancer cell membrane and red blood cell membrane displays excellent tumor targeting efficiency and long blood circulation property due to the innate features of both membranes. After collaboration with aPD-L1-based immune checkpoint blockade therapy, a boosted immunotherapeutic effect is obtained due to elevated dendritic cell maturation and T cell activation. Significantly, laser-irradiated BPP@RTL combined with aPD-L1 effectively eliminates primary tumors and inhibits lung metastasis in 4T1 breast tumor model, offering a promising treatment plan to develop personalized antitumor strategy.

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

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

Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.

Mo4+-Doped CuS Nanosheet-Assembled Hollow Spheres for CO2 Electroreduction to Ethanol in a Flow Cell.

Electrocatalytic CO2 reduction reaction (CO2RR) to ethanol has been widely researched for potential commercial application. However, it still faces limited selectivity at a large current density. Herein, Mo4+-doped CuS nanosheet-assembled hollow spheres are constructed to address this issue. Mo4+ ion doping modifies the local electronic environments and diversifies the binding sites of CuS, which increases the coverage of linear *COL and produces bridge *COB for subsequent *COL-*COH coupling toward ethanol production. The optimal Mo9.0%-CuS can electrocatalyze CO2 to ethanol with a faradaic efficiency of 67.5% and a partial current density of 186.5 mA cm-2 at -0.6 V in a flow cell. This work clarifies that doping high valence transition metal ions into Cu-based sulfides can regulate the coverage and configuration of related intermediates for ethanol production during the CO2RR in a flow cell.

Analysis of risk factors, pathogenic bacteria characteristics, and drug resistance of postoperative surgical site infection in adults with limb fractures.

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.

A Daily Diary Study of the Reciprocal Relation between Parental Psychological Aggression and Adolescent Anxiety in China.

The daily reciprocal relations between parental psychological aggression and adolescent anxiety and the heterogeneity, i.e., whether these relations vary across different adolescents, remain unclear. This study examined this issue with a 15-day daily diary study among 326 Chinese adolescents (Mage = 14.53 years, SD = 0.60, 47.2% girls). Dynamic structural equation models revealed that parental psychological aggression co-fluctuated with adolescent anxiety within a day. For lagged associations, only father-driven effects were supported but not mother-driven effects, whereas child-driven effects were supported for both parents. These within-person associations were heterogeneous across adolescents. Moreover, adolescents with more parental psychological aggression reported higher anxiety. This study revealed the reciprocal relations between parental psychological aggression and adolescent anxiety at the micro timescale and also highlighted that the within-person associations were heterogeneous across different adolescents.

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.

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.

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.

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.

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.

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.

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.