[Molecular study of an individual with Bel subtype due to a novel c.620T>C variant].

OBJECTIVE: To explore the molecular basis for an individual with Bel subtype of the ABO blood type due to a novel c.620T>C variant gene, and assess its impact on the structure of GTB transferase. METHODS: An individual who had visited the First Affiliated Hospital of Zhengzhou University on February 11, 2023 was selected as the study subject. ABO phenotyping was initially conducted with serological methods, which was followed by direct sequencing of 7 exons of the ABO gene. Subsequently, single-strand sequencing was carried out by using allele-specific primers, and the variant in the B transferase was homology-modeled using the Modeller software. The impact of the variant on the transferase's spatial structure was analyzed with the PyMOL software. RESULTS: The serological phenotype of the patient was identified as the Bel subtype. Direct sequencing revealed that she has harbored a novel c.620T>C variant, resulting in a p.Leu207Pro substitution in the polypeptide chain. Combined with single-strand sequencing, her genotype was ultimately determined as ABO*BELnew/ABO*O.01.02. Three-dimensional protein structure modeling showed that, compared with the wild type, the distance of one hydrogen bond between Proline and Glycine at position 272 has increased, along with disappearance of another hydrogen bond. CONCLUSION: The novel c.620T>C (p.Leu207Pro) variant of B allele may affect the structural stability of the glycosyltransferase. The weakened enzyme activity in turn may lead to reduced B antigen expression, manifesting as the Bel subtype by serological analysis.

Exogenous silicon applied at appropriate concentrations is effective at improving tomato nutritional and flavor qualities.

Silicon can mitigate biotic and abiotic stresses in various plants; however, its effects on tomato quality under normal growth conditions are remain unclear. We used a randomized design with four Si treatments, CON (0 mmol/L), T1 (0.6 mmol/L), T2 (1.2 mmol/L), and T3 (1.8 mmol/L) on tomato fruit components Chlorogenic acid and rutin, among polyphenolic components, were increased by 56.99% and 20.31%, respectively, with T2 treatment compared to CON concentrations. T2 increased the sugar-acid ratio by 19.21%, compared to that with the CON treatment, and increased fruit Ca and Mg contents, compared to those with other treatments, improving the characteristic aroma. Furthermore, silicon application reduced the abscisic acid content by 112%, promoting ripening. Endogenous gibberellin, auxin, and salicylic acid, which retard fruit ripening and softening, were increased by 34.96%, 14.56%, and 35.21%, respectively. These findings have far-reaching implications for exogenous Si applications to enrich tomato nutritional and flavor qualities.

Caffeine Impaired Acupuncture Analgesia in Inflammatory Pain by Blocking Adenosine A1 Receptor.

Caffeine consumption inhibits acupuncture analgesic effects by blocking adenosine signaling. However, existing evidence remains controversial. Hence, this study aimed to examine the adenosine A1 receptor (A1R) role in moderate-dose caffeine-induced abolishing effect on acupuncture analgesia using A1R knockout mice (A1R-/-). We assessed the role of A1R in physiological sensory perception and its interaction with caffeine by measuring mechanical and thermal pain thresholds and administering A1R and adenosine 2A receptor antagonists in wild-type (WT) and A1R-/- mice. Formalin- and complete Freund's adjuvant (CFA)-induced inflammatory pain models were recruited to explore moderate-dose caffeine effect on pain perception and acupuncture analgesia in WT and A1R-/- mice. Moreover, a C-fiber reflex electromyogram in the biceps femoris was conducted to validate the role of A1R in the caffeine-induced blockade of acupuncture analgesia. We found that A1R was dispensable for physiological sensory perception and formalin- and CFA-induced hypersensitivity. However, genetic deletion of A1R impaired the antinociceptive effect of acupuncture in A1R-/- mice under physiological or inflammatory pain conditions. Acute moderate-dose caffeine administration induced mechanical and thermal hyperalgesia under physiological conditions but not in formalin- and CFA-induced inflammatory pain. Moreover, caffeine significantly inhibited electroacupuncture (EA) analgesia in physiological and inflammatory pain in WT mice, comparable to that of A1R antagonists. Conversely, A1R deletion impaired the EA analgesic effect and decreased the caffeine-induced inhibitory effect on EA analgesia in physiological conditions and inflammatory pain. Moderate-dose caffeine administration diminished the EA-induced antinociceptive effect by blocking A1R. Overall, our study suggested that caffeine consumption should be avoided during acupuncture treatment. PERSPECTIVE: Moderate-dose caffeine injection attenuated EA-induced antinociceptive effect in formalin- and CFA-induced inflammatory pain mice models by blocking A1R. This highlights the importance of monitoring caffeine intake during acupuncture treatment.

Unbiased Single-Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation.

Aplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T-cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single-cell RNA-seq, along with multi-omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+ CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T-cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL-4, IL-6, and IL-13), GM-SCF, and IL-1ß. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T-cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12-TNFRSF12A, TNF-TNFRSF1A, and granzyme-gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities.

Targeted single-cell RNA sequencing analysis reveals metabolic reprogramming and the ferroptosis-resistant state in hematologic malignancies.

Hematologic malignancies are the most common hematopoietic diseases and a major public health concern. However, the mechanisms underlying myeloid tumors remain unknown owing to the intricate interplay between mutations and diverse clonal evolution patterns, as evidenced by the analysis of bulk cell-derived omics data. Several single-cell omics techniques have been used to characterize the hierarchies and altered immune microenvironments of hematologic malignancies. The comprehensive single-cell atlas of hematologic malignancies provides novel opportunities for personalized combinatorial targeted treatments, avoiding unwanted chemo-toxicity. In the present study, we performed transcriptome sequencing by combining single-cell RNA sequencing (scRNA-seq) with a targeted oncogenic gene panel for acute myeloid leukemia, overcoming the limitations of scRNA-seq in detecting oncogenic mutations. The distribution of oncogenic IDH1, IDH2, and KRAS mutations in each cell type was identified in the bone marrow (BM) samples of each patient. Our findings suggest that ferroptosis and metabolic reprogramming are involved in the tumorigenesis and chemotherapy resistance of oncogenic mutation-carrying cells. Biological progression via IDH1, IDH2, and KRAS mutations arrests hematopoietic maturation. Our study findings provide a rationale for using primary BM cells for personalized treatment in clinical settings.

Acylhydrazone-derived whole pectin-based hydrogel as an injectable drug delivery system.

Injectable hydrogel-based drug delivery systems have attracted more and more attention due to their sustained-release performance, biocompatibility, and 3D network. The present study showed whole pectin-based hydrogel as an injectable drug delivery system, which was developed from oxidized pectin (OP) and diacylhydrazine adipate-functionalized pectin (Pec-ADH) via acylhydrazone linkage. The as-prepared hydrogels were characterized by 1H NMR, FT-IR, and SEM techniques. The equilibrium swelling ratio of obtained hydrogel (i.e., sample gel 5) was up to 4306.65 % in the distilled water, which was higher than that in PBS with different pH values. Increasing the pH of the swelling media, the swelling ratio of all hydrogels decreased significantly. The results that involved the swelling properties indicated the salt- and pH-responsiveness of the as-prepared hydrogels. The drug release study presented that 5-FU can be persistently released for more than 12 h without sudden release. Moreover, the whole pectin-based hydrogel presented high cytocompatibility toward L929 cell lines, and the drug delivery system showed a high inhibitory effect on MCF-7 cell lines. All these results manifested that the acylhydrazone-derived whole pectin-based hydrogel was an excellent candidate for injectable drug delivery systems.

A NIR-II Photoactivatable "ROS Bomb" with High-Density Cu2 O-Supported MoS2 Nanoflowers for Anticancer Therapy.

The fast conversion of hydrogen peroxide (H2 O2 ) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near-infrared light in the second region (NIR-II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high-density copper-based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high-density cuprous (Cu2 O) supported molybdenum disulfide (MoS2 ) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR-II light irradiation, the ROS intensity and maximum reaction velocity (Vmax ) produced by MC NFs are 21.6 and 33.8 times that of the non-irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre-weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS-based cancer therapy.

CCL17 acts as an antitumor chemokine in micromilieu-driven immune skewing.

BACKGROUND: Chemokines are critical players in the local immune responses to tumors. CCL17 (thymus and activation-regulated chemokine, TARC) and CCL22 (macrophage-derived chemokine, MDC) can attract CCR4-bearing cells involving the immune landscape of cancer. However, their direct roles and functional states in tumors remain largely unclear. METHODS: We analyzed the lymphoma-related scRNA-seq and bulk RNA-seq datasets and identified the CCL17/CCL22-CCR4 axis as the unique participant of the tumor microenvironment. Then we edited the A20 lymphoma cell line to express CCL17 and CCL22 and assessed their function using three mouse models (Balb/C mouse, Nude mouse, and NSG mouse). In addition, we retrospectively checked the relationship between the CCL17/CCL22-CCR4 axis and the survival rates of cancer patients. RESULTS: The active CCL17/CCL22-CCR4 axis is a distinctive feature of the Hodgkin lymphoma microenvironment. CCR4 is widely expressed in immune cells but highly exists on the surface of NK, NKT, and Treg cells. The tumor model of Balb/C mice showed that CCL17 acts as an anti-tumor chemokine mediated by activated T cell response. In addition, the tumor model of Nude mice showed that CCL17 recruits NK cells for inhibiting lymphoma growth and enhances the NK-cDC1 interaction for resisting IL4i1-mediated immunosuppression. Interestingly, CCL17-mediated antitumor immune responses depend on lymphoid lineages but not mainly myeloid ones. Furthermore, we found CCL17/CCL22-CCR4 axis cannot be regarded as biomarkers of poor prognosis in most cancer types from the TCGA database. CONCLUSION: We provided direct evidence of antitumor functions of CCL17 mediated by the recruitment of conventional T cells, NKT cells, and NK cells. Clinical survival outcomes of target gene (CCL17, CCL22, and CCR4) expression also identified that CCL17/CCL22-CCR4 axis is not a marker of poor prognosis.

Photoluminescence Sensing of Soluble Lead in Children's Crayons Using Perovskite Nanocrystal In Situ Growth on an Aluminum Hydroxide Layer.

In this study, a fluorescence sensing approach for lead ion (Pb2+) was developed using in situ growth of methylamine lead bromine (MAPbBr3) perovskite on an aluminum hydroxide (Al(OH)3) thin layer. The Al(OH)3 thin layer could be obtained on a glass slide by liquid phase deposition and is of a large specific surface area and insoluble in water. After sulfhydryl functionalization, the Al(OH)3 thin layer reveals effective adsorption and excellent enrichment ability to Pb2+ and is additionally used as the substrate for the in situ growth of lead halogen perovskite. The fluorescence sensing of Pb2+ could be realized by the fluorescence intensity of lead halogen perovskite on the Al(OH)3 layer. The linear relationship between the fluorescence intensity and the concentration of Pb2+ was found in the range from 80 to 1500 mg/kg. The detection limit of Pb2+ is found to be 40 mg/kg, which is lower than the maximum permission of lead residue in student products (90 mg/kg) stipulated by the National Standard of the People's Republic of China (GB21027-2020). After being grinded and pre-treated, soluble lead in watercolor paint and crayon samples can be extracted by the sulfhydryl functionalization Al(OH)3 layer, then lead halogen perovskite can be generated in situ on the layer to achieve the fluorescence sensing for the determination of soluble lead in the samples.

Research Progress of Traditional Chinese Medicine Monomers in Reversing Multidrug Resistance of Breast Cancer.

Breast cancer is a malignant disease with an increasing incidence. Chemotherapy is still an important means for breast cancer treatment, but multidrug resistance (MDR) greatly limits its clinical application. Therefore, the high-efficiency MDR reversal agents are urgently needed. Traditional Chinese medicine (TCM) monomers have unique advantages in reversing chemotherapeutic MDR because of its low toxicity, high efficiency, and ability to impact multiple targets. This review firstly summarizes the major mechanisms of MDR in breast cancer, including the reduced accumulation of intracellular chemotherapeutic drugs, the promoted inactivation of intracellular chemotherapeutic drugs, and the enhanced damage repair ability of DNA, etc., and secondly highlights the research progress of 15 kinds of TCM monomers, including curcumin, resveratrol, emodin, apigenin, tetrandrine, gambogic acid, matrine, paeonol, schisandrin B, [Formula: see text]-elemene, astragaloside IV, berberine, puerarin, tanshinone IIA, and quercetin, in reversing MDR of breast cancer. This review also provides the suggestion for the future research of MDR reversal agents in breast cancer.

Multi-antigen spherical nucleic acid cancer vaccines.

Cancer vaccines must activate multiple immune cell types to be effective against aggressive tumours. Here we report the impact of the structural presentation of two antigenic peptides on immune responses at the transcriptomic, cellular and organismal levels. We used spherical nucleic acid (SNA) nanoparticles to investigate how the spatial distribution and placement of two antigen classes affect antigen processing, cytokine production and the induction of memory. Compared with single-antigen SNAs, a single dual-antigen SNA elicited a 30% increase in antigen-specific T cell activation and a two-fold increase in T cell proliferation. Antigen placement within dual-antigen SNAs altered the gene expression of T cells and tumour growth. Specifically, dual-antigen SNAs encapsulating antigens targeting helper T cells and with externally conjugated antigens targeting cytotoxic T cells elevated antitumour genetic pathways, stalling lymphoma tumours in mice. Additionally, when combined with the checkpoint inhibitor anti-programmed-cell-death protein-1 in a mouse model of melanoma, a specific antigen arrangement within dual-antigen SNAs suppressed tumour growth and increased the levels of circulating memory T cells. The structural design of multi-antigen vaccines substantially impacts their efficacy.

Macrophage-derived exosomal miR-4532 promotes endothelial cells injury by targeting SP1 and NF-κB P65 signalling activation.

Atherosclerosis is a complex pathological process involving macrophages, endothelial cells and vascular smooth muscle cells that can lead to ischemic heart disease; however, the mechanisms underlying cell-to-cell communication in atherosclerosis are poorly understood. In this study, we focused on the role of exosomal miRNAs in crosstalk between macrophages and endothelial cells and explored the rarely studied molecular mechanisms involved. Our in vitro result showed that macrophage-derived exosomal miR-4532 significantly disrupted human umbilical vein endothelial cells (HUVECs) function by targeting SP1 and downstream NF-κB P65 activation. In turn, increased endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and decreased endothelial nitric oxide synthase (eNOS) expression in HUVECs increased attraction of macrophages, exacerbating foam cell formation and transfer of exosomal miR-4532 to HUVECs. MiR-4532 overexpression significantly promoted endothelial injury and pretreatment with an inhibitor of miR-4532 or GW4869 (exosome inhibitor) could reverse this injury. In conclusion, our data reveal that exosomes have a critical role in crosstalk between HUVECs and macrophages. Further, exosomal miR-4532 transferred from macrophages to HUVECs and targeting specificity protein 1 (SP1) may be a novel therapeutic target in patients with atherosclerosis.

[Effects of melatonin on photosynthetic properties and osmoregulatory substance contents of cucumber seedlings under salt-alkali stress]. / è¤ªé»‘ç´ å¯¹ç›ç¢±å¤åˆèƒè¿«ä¸‹é»„ç“œå¹¼è‹—å ‰åˆç‰¹æ€§å’Œæ¸—é€è°ƒèŠ‚ç‰©è´¨å«é‡çš„å½±å“.

To determine the mitigating effects of exogenous melatonin on salt-alkali stress in cucumber, we mea-sured photosynthetic characteristics and osmoregulatory substance content of cucumber leaves under salt-alkali stress, using 'Xinchun 4' cucumber as the test material and a salt-alkali complex (NaCl:Na2SO4:Na2CO3:NaHCO3 = 1:9:1:9) to simulate stress. The results showed that compared with the normal seedlings, the exogenous application of 10 µmol·L-1 melatonin significantly increased the contents of chlorophyll, soluble sugar, and soluble protein, as well as net photosynthetic rate, stomatal conductance, transpiration rate, photosystem Ⅱ maximum photochemical efficiency, actual photochemical efficiency, apparent photosynthetic electron transfer rate, and photochemical burst coefficient of cucumber seedlings under 40 mmol·L-1 salt-alkali stress, but decreased intercellular CO2 concentration, non-photochemical burst coefficient, and sucrose, fructose, starch, and proline contents by 11.1%, 13.8%, 12.7%, 27.5%, 1.3% and 32.8%, respectively. Moreover, the activities of key enzymes for carbon assimilation (including ribulose-1,5-bisphosphate carboxylase/oxygenase and fructose-1,6-bisphosphate esterase) were significantly increased, whereas the mRNA expression levels of Rubisco subunits (CsrbcS and CsrbcL), CsFBA, CsRCA, CsFBPase and CsTK were downregulated. In conclusion, exogenous melatonin could increase the contents of chlorophyll and osmoregulatory substance, photosynthetic chemical efficiency, and key carbon assimilation enzyme activities of cucumber seedlings under salt-alkali stress, thereby enhance photosynthetic capacity and reduce the stress-induced plant damage. The results would provide theoretical basis for anti-saline plant cultivation.

A Comprehensive Evaluation of Effects on Water-Level Deficits on Tomato Polyphenol Composition, Nutritional Quality and Antioxidant Capacity.

Tomatoes have high nutritional value and abundant bioactive compounds. Moderate water deficit irrigation alters metabolic levels of fruits, improving composition and quality. We investigated the effects of water deficit (T1, T2, T3, and T4) treatments and adequate irrigation (CK) on tomato polyphenol composition, antioxidant capacity, and nutritional quality. Compared with CK, the total flavonoid content increased by 33.66% and 44.73% in T1 and T2, and total phenols increased by 57.64%, 72.22%, and 55.78% in T1, T2, and T3, respectively. The T2 treatment significantly enhanced antioxidant' capacities (ABTS, HSRA, FRAP, and DPPH). There were multiple groups of significant or extremely significant positive correlations between polyphenol components and antioxidant activity. For polyphenols and antioxidant capacity, the classification models divided the treatments: CK and T4 and T1−T3. The contents of soluble solids, soluble protein, vitamin C, and soluble sugar of the treatment groups were higher than those of CK. The soluble sugar positively correlated with sugar−acid ratios. In the PCA-based model, T3 in the first quadrant indicated the best treatment in terms of nutritional quality. Overall, comprehensive rankings using principal component analysis (PCA) revealed T2 > T1 > T3 > T4 > CK. Therefore, the T2 treatment is a suitable for improving quality and antioxidant capacity. This study provides novel insights into improving water-use efficiency and quality in the context of water scarcity worldwide.

[Comparison of effects of routine electroacupuncture and pre-electroacupuncture in improving lung function in acute lung injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and pre-EA at"Taiyuan"(LU9) on histopathological changes, pulmonary ventilation function, pneodynamics, and contents of TNF-α, IL-1ß and IL-10 in the bronchoalveolar lavage fluid in rats with acute lung injury (ALI), in order to explore their differences of therapeutic effects. METHODS: A total of 92 male SD rats were randomly divided into control, model, routine EA and pre-EA groups, with 23 rats in each group. The ALI rat model was established by instillation of 0.5% lipopolysaccharide solution (5 mg/kg) intratracheally. EA (3 mA, 10 Hz) was applied to bilateral LU9 for 20 min, once 5 h after modeling for rats of the routine EA group, and once on the 1st, 3rd and 5th day respectively before modeling for rats of the pre-EA group. The pulmonary ventilation functions, including dynamic lung compliance (Cdyn), tidal volume (TV)，minute ventilation volume (MV), lung resistance, peak inspiratory flow (PIF), peak expiratory flow (PEF), were measured by using a small animal lung function detection system. The electromyogram (EMG) of the diaphragm muscle was recorded for observing changes of the total integral electromyogram(iEMG), single iEMG and respiration rate. Pathological changes of the lung tissue were scored after H.E. staining. The contents of TNF-α, IL-1ß and IL-10 in the bronchoalveolar lavage fluid were determined by enzyme linked immunosorbent assay. RESULTS: Compared with the control group, the Cdyn, TV, MV and PIF consi-derably decreased (P<0.000 1), and the lung resistance, total iEMG of diaphragm muscle, lung injury score, and contents of TNF-α and IL-1ß were significantly increased (P<0.05, P<0.001, P<0.01) in the model group. In comparison with the model group, the TV, MV and PIF in both routine EA and pre-EA groups,and the Cdyn, total iEMG and single iEMG in the routine EA group, as well as the IL-10 content in the pre-EA group were significantly increased (P<0.01, P<0.001, P<0.05), whereas the lung injury score, and contents of TNF-α and IL-1ß were significantly decreased in the pre-EA group (P<0.05). CONCLUSION: Both pre-EA and routine EA at LU9 can improve the lung function of ALI model rats. Pre-electroacupuncture is related to local immunoregulation, while electroacupuncture is mainly related to the improvement of pulmonary ventilation function and respiratory motility.

O-terminated interface for thickness-insensitive transport properties of aluminum oxide Josephson junctions.

Alumina Josephson junction has demonstrated a tremendous potential to realize superconducting qubits. Further progress towards scalable superconducting qubits urgently needs to be guided by novel analysis mechanisms or methods to reduce the thickness sensitivity of the junction critical current to the tunnel barrier. Here, it is first revealed that the termination mode of AlOx interface plays a crucial role in the uniformity of critical current, and we demonstrate that the O-terminated interface has the lowest resistance sensitivity to thickness. More impressively, we developed atomically structured three-dimensional models and calculated their transport properties using a combination of quantum ballistic transport theory with first-principles DFT and NEGF to examine the effects of the Al2O3 termination mode and thickness variations. This work clarifies that O-terminated interface can effectively improve the resistance uniformity of Josephson junction, offering useful guidance for increasing the yield of fixed-frequency multi-qubit quantum chips which require tight control on qubit frequency.

Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy.

Cancer immunotherapy is a powerful treatment strategy that mobilizes the immune system to fight disease. Cancer vaccination is one form of cancer immunotherapy, where spatiotemporal control of the delivery of tumor-specific antigens, adjuvants, and/or cytokines has been key to successfully activating the immune system. Nanoscale materials that take advantage of chemistry to control the nanoscale structural arrangement, composition, and release of immunostimulatory components have shown significant promise in this regard. In this Outlook, we examine how the nanoscale structure, chemistry, and composition of immunostimulatory compounds can be modulated to maximize immune response and mitigate off-target effects, focusing on spherical nucleic acids as a model system. Furthermore, we emphasize how chemistry and materials science are driving the rational design and development of next-generation cancer vaccines. Finally, we identify gaps in the field that should be addressed moving forward and outline future directions to galvanize researchers from multiple disciplines to help realize the full potential of this form of cancer immunotherapy through chemistry and rational vaccinology.

Case Report: Multimodal Imaging in a Rare Case of Morning Glory Disc Anomaly Complicated With Choroidal Ossification.

Purpose: The authors described a 7-year-old boy who was diagnosed with morning glory disc (MGD) anomaly in the right eye via fundus examination. However, during the head CT examination, a hyperdense choroidal lesion was discovered around the optic disc. Comprehensive investigations revealed that the lesion's characteristics were extremely consistent with choroidal osteoma (CO), so the patient was diagnosed with MGD with CO on his second visit. However, in the subsequent follow-up, the author discovered pigmentary alterations in the retinal pigment epithelium (RPE) in the patient's right eye. Finally, the diagnosis was corrected to MGD with choroidal ossification following a thorough etiological analysis. Meanwhile, the characteristics of choroidal ossification were described in detail through multimodal imaging in this article. Methods: Retrospective review of a case note. Conclusions: Similar to CO, choroidal ossification is the consequence of structured osseous tissue formation regulated by osteoblasts and osteoclasts. It consists of bone trabecular and vascular components and is difficult to be distinguished from CO on imaging examinations. In contrast to the congenital prevalence of CO, there are often incentives for the occurrence of choroidal ossification. These inducements will eventually mediate the inflammation in the eye, resulting in the activation of many cytokines and the production of choroidal ossification. Around one-third of patients with MGD will experience retinal detachment, and in certain cases, the subretinal fluid will be absorbed spontaneously, resulting in alterations to the RPE. These processes can activate inflammatory factors in the eye, bringing about a cascade of abnormalities, including the development of CO. Therefore, the proper diagnosis of disease should not be made exclusively on the basis of the imaging findings. A thorough analysis of the epidemiology and etiology is crucial.

Comparative efficacy and safety of antivascular endothelial growth factors for central retinal vein occlusion: A protocol for systematic review and network meta-analysis.

BACKGROUND: Central retinal vein occlusion (CRVO) is one of the most common retinal vascular diseases, which is closely related to systemic diseases like hypertension, diabetes and arteriosclerosis. Due of its blinding, it will seriously reduce the quality of life. Macular edema (ME) caused by CRVO is one of the serious complications of visual impairment. We found that the severity of ME in CRVO was positively associated with vascular endothelial growth factor (VEGF) in the anterior chamber. With the accelerated pace of modern life and the changed dietary structure, the incidence of this disease will continue to rise. Therefore, it is of great practical significance to seek effective treatment methods. Intraocular injection of anti-VEGF can effectively alleviate ME and improve visual acuity, showing excellent clinical application prospects. In recent years, there have been some new understandings and advances on the etiology and treatment methods of the present disease, such as the deepening into the molecular biology and gene level. Clinical studies on the efficacy of the disease have emerging. Therefore, a network meta-analysis (NMA) of anti-VEGF treatment for CRVO is particularly necessary to systematically compare its efficacy. METHODS: The two reviewers will comprehensively retrieved electronic databases such as PubMed, The Cochrane Library, Wanfang database, Web of Science, Chinese Scientifific Journals Database, EMBASE, China National Knowledge Infrastructure, and China BioMedical Literature. A randomized controlled trial for CRVO against VEGF between January 2010 and June 2021 was included according to the relevant content of the study. In addition, 2 researchers will screen the literature to assess the risk bias for the included articles. We will evaluate the collected evidence and data using a Bayesian NMA method, and analyzed it with STATA and WinBUGS software. RESULTS: Anti-VEGF is one of the effective methods for ME in CRVO patients, accordingly, this study will evaluate its efficacy and safety using a Bayesian NMA system. CONCLUSION: This study can provide an effective rationale for the clinical application of anti-VEGF for CRVO, contribute to the treatment of CRVO and patient condition rehabilitation in clinical work. ETHICS AND DISSEMINATION: Do not require. INPLASY REGISTRATION NUMBER: INPLASY2021110073.

Chemically Tuning the Antigen Release Kinetics from Spherical Nucleic Acids Maximizes Immune Stimulation.

Cancer vaccine structure is emerging as an important design factor that offers tunable parameters to enhance the targeted immune response. We report the impact of altering the antigen release rate from spherical nucleic acid (SNA) vaccines-nanoparticles with a liposomal core and surface-anchored adjuvant DNA-on immune stimulation. Peptide antigens were incorporated into SNAs using either a nonreducible linker or one of a series of reduction-triggered traceless linkers that release the native peptide at rates controlled by their substitution pattern. Compared with a nonreducible linkage, the traceless attachment of antigens resulted in lower EC50 of T cell proliferation in vitro and greater dendritic cell (DC) activation and higher T cell killing ability in vivo. Traceless linker fragmentation rates affected the rates of antigen presentation by DCs and were correlated with the in vitro potencies of SNAs. Antigen release was correlated with the ex vivo -log(EC50), and more rapid antigen release resulted in an order of magnitude improvement in the EC50 and earlier and greater antigen presentation over the same time-period. In vivo, increasing the rate of antigen release resulted in higher T cell activation and target killing. These findings provide fundamental insights into and underscore the importance of vaccine structure.