Revealing the Effect of the [CoO]6 Microstructure in Pseudocapacitance by Controlled Delithium of LiCoO2.

Revealing the in-depth structure-property relationship and designing specific capacity electrodes are particularly important for supercapacitors. Despite many efforts made to tune the composition and electronic structure of cobalt oxide for pseudocapacitance, insight into the [CoO]6 octahedron from the microstructure is still insufficient. Herein, we present a tunable [CoO]6 octahedron microstructure in LiCoO2 by a chemical delithiation process. The c-strained strain of the [CoO]6 octahedron is induced to form higher valence Co ions, and the (003) crystalline layer spacing increases to allow more rapid participation of OH- in the redox reaction. Interestingly, the specific capacity of L0.75CO2 is nearly four times higher than that of LiCoO2 at 10 mA g-1. The enhanced activity originated from the asymmetric strain [CoO]6 octahedra, resulting in enhanced electronic conductivity and Co-O hybridization for accelerated redox kinetics. This finding provides new insights into the modification strategy for pseudocapacitive transition metal oxides.

Cadherin-5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node-like pacemaker cells by regulating ß-catenin.

Our study was conducted to investigate whether cadherin-5 (CDH5), a vascular endothelial cell adhesion glycoprotein, could facilitate the differentiation of human induced pluripotent stem cells (hiPSCs) into sinoatrial node-like pacemaker cells (SANLPCs), following previous findings of silk-fibroin hydrogel-induced direct conversion of quiescent cardiomyocytes into pacemaker cells in rats through the activation of CDH5. In this study, the differentiating hiPSCs were treated with CDH5 (40 ng/mL) between Day 5 and 7 during cardiomyocytes differentiation. The findings in the present study demonstrated that CDH5 stimulated the expression of pacemaker-specific markers while suppressing markers associated with working cardiomyocytes, resulting in an increased proportion of SANLPCs among hiPSCs-derived cardiomyocytes (hiPSC-CMs) population. Moreover, CDH5 induced typical electrophysiological characteristics resembling cardiac pacemaker cells in hiPSC-CMs. Further mechanistic investigations revealed that the enriched differentiation of hiPSCs into SANLPCs induced by CDH5 was partially reversed by iCRT14, an inhibitor of ß-catenin. Therefore, based on the aforementioned findings, it could be inferred that the regulation of ß-catenin by CDH5 played a crucial role in promoting the enriched differentiation of hiPSCs into SANLPCs, which presents a novel avenue for the construction of biological pacemakers in forthcoming research.

HMOX1-overexpressing mesenchymal stem cell-derived exosomes facilitate diabetic wound healing by promoting angiogenesis and fibroblast function.

Many scholars have suggested that exosomes (Exos) can carry active molecules to induce angiogenesis and thus accelerate diabetic wound healing. Heme oxygenase-1 (HO-1) encoded by the gene HMOX1 promotes wound healing in DM by enhancing angiogenesis. Nevertheless, whether HMOX1 regulates wound healing in DM through mesenchymal stem cell-derived exosomes (MSC-Exos) remains to be further explored. The primary isolated- and cultured-cells expressed MSC-specific marker proteins, and had low immunogenicity and multi-differentiation potential, which means that MSCs were successfully isolated in this study. Notably, HO-1 protein expression was significantly higher in Exo-HMOX1 than in Exos, indicating that HMOX1 could be delivered to Exos as an MSCs-secreted protein. After verifying the -Exo structure, fibroblasts, keratinocytes, and human umbilical vein endothelial cells (HUVECs) were incubated with Exo-HMOX1 or Exo, and the findings displayed that Exo-HMOX1 introduction promoted the proliferation and migration of fibroblasts, keratinocytes and the angiogenic ability of HUVECs in vitro study. After establishing diabetic wound model mice, PBS, Exo, and Exo-HMOX1 were subcutaneously injected into multiple sites on the 1st, 3rd, 7th, and 14th day, DM injected with Exo-HMOX1 showed faster wound healing, re-epithelialization, collagen deposition, and angiogenesis than those in PBS and Exo groups in vitro study. In summary, Exo-HMOX1 could enhance the activity of fibroblasts, keratinocytes, and HUVEC, and accelerate wound healing by promoting angiogenesis in DM.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Kinetochore deterioration concommitant with centromere weakening during aging in mouse oocyte meiosis-I.

Age-related oocyte aneuploidy occurs as a result of chromosome segregation errors in female meiosis-I and meiosis-II, and is caused by a progressive age-related deterioration of the chromosome segregation machinery. Here, we assess the impact of age upon the kinetochore, the multi-protein structure that forms the link between the chromosome and spindle microtubules. We find that in meiosis-I the outer kinetochore assembles at germinal vesicle breakdown, but that a substantially smaller outer kinetochore is assembled in oocytes from aged mice. We show this correlates with a weaker centromere in aged oocytes and, using nuclear transfer approaches to generate young-aged hybrid oocytes, we show that outer kinetochore assembly always mirrors the status of the centromere, regardless of cytoplasmic age. Finally, we show that weaker kinetochores in aged oocytes are associated with thinner microtubule bundles, that are more likely to be mis-attached. We conclude that progressive loss of the centromere with advancing maternal age underpins a loss of the outer kinetochore in meiosis-I, which likely contributes to chromosome segregation fallibility in oocytes from older females.

iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency.

BACKGROUND: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. METHODS: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. RESULTS: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. CONCLUSIONS: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.

Extracellular Matrix Stiffness Regulates Microvascular Stability by Controlling Endothelial Paracrine Signaling to Determine Pericyte Fate.

BACKGROUND: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, ECM (extracellular matrix) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel 2-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue. This study investigated how ECM stiffness regulated microvascular ECs, pericytes, and their interactions. METHODS: Primary microvessels were cultured in the TGM2D medium (tubular microvascular growth medium on 2-dimensional substrates). Stiff ECM was prepared by incubating ECM solution in regular culture dishes for 1 hour followed by PBS wash. Soft ECM with Young modulus of ≈6 kPa was used unless otherwise noted. Bone grafts were prepared from the rat skull. Immunostaining, RNA sequencing, RT-qPCR (real-time quantitative polymerase chain reaction), Western blotting, and knockdown experiments were performed on the cells. RESULTS: Primary microvascular pericytes differentiated into myofibroblasts (NG2+αSMA+) on stiff ECM, even with the TGFß (transforming growth factor beta) signaling inhibitor A83-01. Soft ECM and A83-01 cooperatively maintained microvascular stability while inhibiting pericyte-myofibroblast differentiation (NG2+αSMA-/low). We thus defined 2 pericyte subpopulations: primary (NG2+αSMA-/low) and activated (NG2+αSMA+) pericytes. Soft ECM promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation in vivo. As integrins are the major mechanosensor, we performed RT-qPCR screening of integrin family members and found Itgb1 (integrin ß1) was the major subunit downregulated by soft ECM and A83-01 treatment. Knocking down Itgb1 suppressed myofibroblast differentiation on stiff ECM. Interestingly, ITGB1 phosphorylation (Y783) was mainly located on microvascular ECs on stiff ECM, which promoted EC secretion of paracrine factors, including CTGF (connective tissue growth factor), to induce pericyte-myofibroblast differentiation. CTGF knockdown or monoclonal antibody treatment partially reduced myofibroblast differentiation, implying the participation of multiple pathways in fibrosis formation. CONCLUSIONS: ECM stiffness and TGFß signaling cooperatively regulate microvascular stability and pericyte-myofibroblast differentiation. Stiff ECM promotes EC ITGB1 phosphorylation (Y783) and CTGF secretion, which induces pericyte-myofibroblast differentiation.

Assembly of Functional Co(II) Metal-Organic Frameworks through a Mixed Ligand Strategy: Structure and Photocatalytic Degradation Properties.

Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (•O2-, •OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.

Two 2D Metal-Organic Frameworks Based on Purine Carboxylic Acid Ligands for Photocatalytic Oxidation of Sulfides and CO2 Chemical Fixation.

Two two-dimensional (2D) layered metal-organic frameworks (MOFs), namely, {[Yb(L)(H2O)2NO3]·2H2O}n (Yb-MOF) and [Er(L)(H2O)3Cl]n (Er-MOF) (H2L = 5-((6H-purin-6-yl)amino)isophthalic acid), were constructed by a solvothermal method and characterized. The catalytic performance study showed that the Yb-MOF could efficiently catalyze the oxidation of sulfides to sulfoxides under 15 W light-emitting diode (LED) blue light irradiation. Electron paramagnetic resonance spectroscopy and free-radical trapping experiments demonstrated that the photocatalytic reaction process involved •O2-, and the corresponding mechanism was proposed. Moreover, Er-MOF exhibited good catalytic efficiency and excellent substrate tolerance in the cycloaddition reaction of CO2, and the reaction conditions were mild. After 5 cycles, the catalytic activities of two MOFs did not significantly decrease, and the framework structures remained unchanged. Therefore, the Yb-MOF and Er-MOF were considered efficient and stable heterogeneous catalysts.

The short- and long-term effects of community-family-doctor-based type 2 diabetes self-management interventions.

OBJECTIVES: The popularity of contracted family doctor services in China has been growing in recent years, but community-family-doctor-based type 2 diabetes mellitus (T2DM) intervention programs have yet to be adequately studied. This study was to evaluate the short- and long-term effects of community-family-doctor-based self-management interventions for T2DM and to explore strategies for long-term glycemic control. STUDY DESIGN: This was a randomized controlled trial. METHODS: A total of 144 eligible participants were randomly assigned to intervention and control groups. The control group received only routine community diabetes care, and the intervention group received community-family-doctor-based interventions involving the same standard of care. The interventions lasted for 3 months, and the follow-up was continued for 15 months. Intention-to-treat analysis and generalized estimation equations were then used to determine the short- and long-term effects of the interventions on glycated hemoglobin (HbA1c), diabetes self-management, and medication adherence. RESULTS: There were statistically significantly greater improvements in all aspects of the intervention group after 3 months of intervention. Compared with baseline, changes in the attitude (ß = 0.384, 95% confidence interval [CI; 0.194, 0.574], P < 0.001), practice (ß = 1.751, 95% CI [0.762, 2.739], P = 0.001), and knowledge, attitudes, practice total scores (ß = 2.338, 95% CI [0.682, 3.995], P = 0.006) of patients in the intervention group were statistically significant after 15 months, and the HbA1c (8.19 ± 1.73%), knowledge (16.42 ± 3.21), and medication adherence (5.53 ± 1.76) scores were slightly better than those at baseline, although not statistically significant (P > 0.05). CONCLUSIONS: T2DM self-management interventions based on community family doctors improved patients' HbA1c, diabetes self-management, and medication adherence, did not do so significantly in the long term.

Combined Genioplasty and External Oblique Line Grafting: An Innovative Method to Improve Lower Facial Contour.

BACKGROUND: Microgenia and the accompanying plump cheeks or hamster-like facial contour are all unattractive appearances among the Asian. Genioplasty with autogenous bone grafting is one of the effective ways to improve microgenia, in which a suitable donor area with less additional damage, lower infection rate, and more excellent effect is crucial. METHODS: Patients who had undergone genioplasty and autogenous external oblique line grafting (G-EOL) were followed up. The operation-related complications, preoperative, and long-term follow-up 3-dimensional spiral computed tomography (3D-CT) were collected and analyzed. RESULTS: Eight female patients who had received G-EOL and received 1 to 3 years of follow-up were included in this study. There were no short-term or long-term complications. CT data of bone of 8 patients and CT data of soft tissue of 6 patients at the preoperative and long term were compared. Through comparing CT data, the width at the level of the intersection of EOL and mandibular body, and the protrusion of the bony chin had improved significantly; the P values were all <0.001. Through measuring the soft tissue and analyzing the data, the ratio of lower and middle facial width, and the distance from the lower lip to Ricketts' line were all improved, with the P values 0.042 and 0.001, respectively. CONCLUSIONS: For patients with microgenia and hamster-like facial contour, the combination of genioplasty and autogenous external oblique line grafting is innovative and effective in improving both the front and side contour of the lower face simultaneously, with excellent stability, bone healing, and low complication rates.

AMELX Mutations and Genotype-Phenotype Correlation in X-Linked Amelogenesis Imperfecta.

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype-phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5' truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3' truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins.

Proteomic and metabonomic analysis uncovering Enterovirus A71 reprogramming host cell metabolic pathway.

Enterovirus A71 (EV71) infection can cause hand, foot, and mouth disease (HFMD) and severe neurological complications in children. However, the biological processes regulated by EV71 remain poorly understood. Herein, proteomics and metabonomics studies were conducted to uncover the mechanism of EV71 infection in rhabdomyosarcoma (RD) cells and identify potential drug targets. Differential expressed proteins from enriched membrane were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics technology. Twenty-six differential proteins with 1.5-fold (p < 0.05) change were detected, including 14 upregulated proteins and 12 downregulated proteins. The upregulated proteins are mainly involved in metabolic process, especially in the glycolysis pathway. Alpha-enolase (ENO1) protein was found to increase with temporal dependence following EV71 infection. The targeted metabolomics analysis revealed that glucose absorption and glycolysis metabolites were increased after EV71 infection. The glycolysis pathway was inhibited by knocking down ENO1 or the use of a glycolysis inhibitor (dichloroacetic acid [DCA]); and we found that EV71 infection was inhibited by depleting ENO1 or using DCA. Our study indicates that EV71 may reprogram glucose metabolism by activating glycolysis, and EV71 infection can be inhibited by interrupting the glycolysis pathway. ENO1 may be a potential target against EV71, and DCA could act as an inhibitor of EV71.

Initiation and duration of folic acid supplementation in preventing congenital malformations.

BACKGROUND: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. METHODS: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. RESULTS: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. CONCLUSIONS: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

GS6.1 controls kernel size and plant architecture in rice.

MAIN CONCLUSION: A novel QTL GS6.1 increases yield per plant by controlling kernel size, plant architecture, and kernel filling in rice. Kernel size and plant architecture are critical agronomic traits that greatly influence kernel yield in rice. Using the single-segment substitution lines (SSSLs) with an indica cultivar Huajingxian74 as a recipient parent and American Jasmine as a donor parent, we identified a novel quantitative trait locus (QTL), named GS6.1. Near isogenic line-GS6.1 (NIL-GS6.1) produces long and narrow kernels by regulating cell length and width in the spikelet hulls, thus increasing the 1000-kernel weight. Compared with the control, the plant height, panicles per plant, panicle length, kernels per plant, secondary branches per panicle, and yield per plant of NIL-GS6.1 are increased. In addition, GS6.1 regulates the kernel filling rate. GS6.1 controls kernel size by modulating the transcription levels of part of EXPANSINs, kernel filling-related genes, and kernel size-related genes. These results indicate that GS6.1 might be beneficial for improving kernel yield and plant architecture in rice breeding by molecular design.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

Non-invasive molecular imaging for precision diagnosis of metastatic lymph nodes: opportunities from preclinical to clinical applications.

Lymph node metastasis is an indicator of the invasiveness and aggressiveness of cancer. It is a vital prognostic factor in clinical staging of the disease and therapeutic decision-making. Patients with positive metastatic lymph nodes are likely to develop recurrent disease, distant metastasis, and succumb to death in the coming few years. Lymph node dissection and histological analysis are needed to detect whether regional lymph nodes have been infiltrated by cancer cells and determine the likely outcome of treatment and the patient's chances of survival. However, these procedures are invasive, and tissue biopsies are prone to sampling error. In recent years, advanced molecular imaging with novel imaging probes has provided new technologies that are contributing to comprehensive management of cancer, including non-invasive investigation of lymphatic drainage from tumors, identifying metastatic lymph nodes, and guiding surgeons to operate efficiently in patients with complex lesions. In this review, first, we outline the current status of different molecular imaging modalities applied for lymph node metastasis management. Second, we summarize the multi-functional imaging probes applied with the different imaging modalities as well as applications of cancer lymph node metastasis from preclinical studies to clinical translations. Third, we describe the limitations that must be considered in the field of molecular imaging for improved detection of lymph node metastasis. Finally, we propose future directions for molecular imaging technology that will allow more personalized treatment plans for patients with lymph node metastasis.

Sensitive and quantitative in vivo analysis of PD-L1 using magnetic particle imaging and imaging-guided immunotherapy.

PURPOSE: The programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) expression correlate with the immunotherapeutic response rate. The sensitive and non-invasive imaging of immune checkpoint biomarkers is favorable for the accurate detection and characterization, image-guided immunotherapy in cancer precision medicine. Magnetic particle imaging (MPI), as a novel and emerging imaging modality, possesses the advantages of high sensitivity, no image depth limitation, positive contrast, and absence of radiation. Hence, in this study, we performed the pioneer investigation of monitoring PD-L1 expression using MPI and the MPI-guided immunotherapy. METHODS: We developed anti-PD-L1 antibody (aPDL1)-conjugated magnetic fluorescent hybrid nanoparticles (MFNPs-aPDL1) and utilized MPI in combination with fluorescence imaging (FMI) to dynamically monitor and quantify PD-L1 expression in various tumors with different PD-L1 expression levels. The ex vivo real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescence staining analysis were further performed to validate the in vivo imaging observation. Moreover, the MPI was further performed for the guidance of immunotherapy. RESULTS: Our data showed that PD-L1 expression can be specifically and sensitively monitored and quantified using MPI and FMI imaging methods, which were validated by ex vivo qPCR and western blotting analysis. In addition, MPI-guided PD-L1 immunotherapy can enhance the effectiveness of cancer immunotherapy. CONCLUSION: To our best knowledge, this is the pioneer study to utilize MPI in combination with a newly developed MFNPs-aPDL1 imaging probe to dynamically visualize and quantify PD-L1 expression in tumor microenvironment. This imaging strategy may facilitate the clinical optimization of immunotherapy management.

Risk stratification and prognostic value of multi-modal MRI-based radiomics for extranodal nasal-type NK/T-cell lymphoma.

BACKGROUND: Magnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It's important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL. METHODS: Patients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI. RESULTS: The 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients. CONCLUSIONS: The NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.

Betainization of Polydopamine/Polyethylenimine Coating for Universal Zwitterionization.

Biofoulants can adhere to multiple surfaces, degrading the performance of medical devices and industrial facilities and/or causing nosocomial infection. The surface immobilization of zwitterionic materials can prevent the initial attachment of the foulants but lacks extensive implementation. Herein, we propose a facile, universal, two-step surface modification strategy to improve fouling resistance. In the first step, the substrates were immersed in a codeposition solution containing dopamine and branched polyethylenimine (PEI) to form a "primer" layer (PDA/PEI). In the second step, the primer layers were treated with 1,3-propane sultone to betainize primary/secondary/tertiary amine moieties of PEI, generating zwitterions on substrates. After betainization, PS-grafted PDA/PEI (PDA/PEI/S) via a ring-opening alkylation reaction manifested changes in wettability. X-ray photoelectron spectroscopy revealed the presence of zwitterionic moieties on the PDA/PEI/S surfaces. Further investigations using ellipsometry and atomic force microscopy were conducted to scrutinize the relation among the PEI content, film thickness, primer stability, and betainization. As a result, zwitterion-decorated substrates prepared under optimal conditions can exhibit high resistance against bacterial fouling, achieving a 98.5% reduction in bacterial attachment. In addition, the method shows a substrate-independent property, capable of successfully applying it on organic and inorganic substrates. Finally, the newly developed approach shows excellent biocompatibility, displaying no significant difference compared with blank control samples. Overall, we envision that the facile surface modification strategy can further promote the preparation of zwitterion-decorated materials in the future.