The Cissus quadrangularis genome reveals its adaptive features in an arid habitat.

Cissus quadrangularis is a tetraploid species belonging to the Vitaceae family and is known for the Crassulacean acid metabolism (CAM) pathway in the succulent stem, while the leaves perform C3 photosynthesis. Here, we report a high-quality genome of C. quadrangularis comprising a total size of 679.2 Mb which was phased into two subgenomes. Genome annotation identified 51 857 protein-coding genes, while approximately 47.75% of the genome was composed of repetitive sequences. Gene expression ratios of two subgenomes demonstrated that the sub-A genome as the dominant subgenome played a vital role during the drought tolerance. Genome divergence analysis suggests that the tetraploidization event occurred around 8.9 million years ago. Transcriptome data revealed that pathways related to cutin, suberine, and wax metabolism were enriched in the stem during drought treatment, suggesting that these genes contributed to the drought adaption. Additionally, a subset of CAM-related genes displayed diurnal expression patterns in the succulent stems but not in leaves, indicating that stem-biased expression of existing genes contributed to the CAM evolution. Our findings provide insights into the mechanisms of drought adaptation and photosynthesis transition in plants.

TNF-α: A serological marker for evaluating the severity of hippocampal sclerosis in medial temporal lobe epilepsy?

OBJECTIVE: By analysing the difference in TNF-α levels in the peripheral blood of patients with medial temporal lobe epilepsy (mTLE) with or without hippocampal sclerosis and the correlation between TNF-α and N-acetylaspartate levels in the hippocampus, we explored the relationship between TNF-α and the degree of damage to hippocampal sclerosis neurons in medial temporal lobe epilepsy. METHODS: This is a prospective, population-based study. A total of 71 Patients with medial temporal lobe epilepsy diagnosed by clinical seizures, video-EEG, epileptic sequence MRI, and other imaging examinations were recruited from October 2020 to July 2022 in the Department of Neurology, Affiliated Hospital of Xuzhou Medical University. Twenty age-matched healthy subjects were selected as the control group. The patients were divided into two groups: the medial temporal epilepsy with hippocampal sclerosis group (positive group, mTLE-HS-P group) and the medial temporal epilepsy without hippocampal sclerosis group (negative group, mTLE-HS-N group). The levels of IL-1ß, IL-5, IL-6, IL-8, IL-17, IFN-γ and TNF-α in the peripheral blood of the patients in the three groups were detected by multimicrosphere flow immunofluorescence assay. The level of N-acetylaspartate (NAA) in the hippocampus was measured by 1H-MRS. The differences in cytokine levels among the three groups were analysed, and the correlation between cytokine and NAA levels was analysed. RESULTS: The level of TNF-α in the peripheral blood of the patients in the mTLE-HS-P group was significantly higher than that of the patients in the mTLE-HS-N and healthy control groups, and the level of TNF-α in the patients in the mTLE-HS-N group was significantly higher than that of the patients in the healthy control group. The NAA level in mTLE-HS-P group patients was significantly lower than that of mTLE-HS-N patients and healthy controls, but there was no significant difference between mTLE-HS-N patients and healthy controls (P > 0.05). Spearman correlation analysis showed that TNF-α level (rs = -0.437, P < 0.05) and the longest duration of a single seizure (rs = -0.398, P < 0.05) were negatively correlated with NAA level. Logistic regression analysis showed that there was no significant correlation between the longest duration of a single seizure and hippocampal sclerosis, but TNF-α level was closely related to hippocampal sclerosis in patients with mTLE (OR = 1.315, 95 % CI 1.084-1.595, P = 0.005). CONCLUSION: The level of TNF-α in the peripheral blood of patients with medial temporal lobe epilepsy with hippocampal sclerosis was higher, and it was correlated with NAA and hippocampal sclerosis. The high expression of TNF-α may be of important value in the evaluation of hippocampal sclerosis patients.

Composition of Whole Grain Dietary Fiber and Phenolics and Their Impact on Markers of Inflammation.

Inflammation is an important biological response to any tissue injury. The immune system responds to any stimulus, such as irritation, damage, or infection, by releasing pro-inflammatory cytokines. The overproduction of pro-inflammatory cytokines can lead to several diseases, e.g., cardiovascular diseases, joint disorders, cancer, and allergies. Emerging science suggests that whole grains may lower the markers of inflammation. Whole grains are a significant source of dietary fiber and phenolic acids, which have an inverse association with the risk of inflammation. Both cereals and pseudo-cereals are rich in dietary fiber, e.g., arabinoxylan and ß-glucan, and phenolic acids, e.g., hydroxycinnamic acids and hydroxybenzoic acids, which are predominantly present in the bran layer. However, the biological mechanisms underlying the widely reported association between whole grain consumption and a lower risk of disease are not fully understood. The modulatory effects of whole grains on inflammation are likely to be influenced by several mechanisms including the effect of dietary fiber and phenolic acids. While some of these effects are direct, others involve the gut microbiota, which transforms important bioactive substances into more beneficial metabolites that modulate the inflammatory signaling pathways. Therefore, the purpose of this review is twofold: first, it discusses whole grain dietary fiber and phenolic acids and highlights their potential; second, it examines the health benefits of these components and their impacts on subclinical inflammation markers, including the role of the gut microbiota. Overall, while there is promising evidence for the anti-inflammatory properties of whole grains, further research is needed to understand their effects fully.

Angiographic demonstration of a cutoff sign as an unfavorable prognostic indicator for patients with acute ischemic stroke undergoing mechanical thrombectomy.

OBJECTIVES: The aim was to investigate whether the angiographic demonstration of a cutoff sign on the initial angiogram could predict recanalization and prognosis in acute ischemic stroke patients treated by endovascular thrombectomy. METHODS: The angiographic and clinical data of patients who underwent endovascular treatment from October 2018 to April 2023 were retrospectively reviewed. The pretreatment angiographic appearance of the thrombus's proximal part was assessed and classified as either the cutoff sign (+) or (-). Patients' baseline characteristics and angiographic and clinical outcomes between the two groups were analyzed using propensity score matching. Then, the two commonly used techniques, stent retrieval and contact aspiration, were compared in terms of successful reperfusion and clinical outcome in patients with the cutoff sign. RESULTS: The cutoff sign was observed in 77 (36.2%) of 213 patients. Patients with the cutoff sign were younger and were less likely to have involvement of the anterior circulation. Compared with the cutoff sign (-) group, the cutoff sign (+) group had a significantly longer procedure time (103 versus 80 min, P =0.002) and a lower percentage of 3-month good functional outcomes (18.2% versus 36%, P =0.006). After propensity score matching, the procedure time (100 versus 75 min, P =0.002) and the 3-month good outcome (19.2% versus 41.4%, P =0.004) remained significantly different. No significant differences were observed in the radiological (OR 0.758, 95% CI 0.157 to 3.658; P =0.730) and clinical (OR 0.747, 95% CI 0.147 to 3.787; P =0.725) outcomes between the two techniques. CONCLUSIONS: The cutoff sign might be an unfavorable prognostic indicator in patients undergoing mechanical thrombectomy, and the efficacy of mechanical thrombectomy techniques does not differ in patients positive for the cutoff sign.

An immune-related gene prognostic prediction risk model for neoadjuvant chemoradiotherapy in rectal cancer using artificial intelligence.

Background: This study aimed to establish and validate a prognostic model based on immune-related genes (IRGPM) for predicting disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy, and to elucidate the immune profiles associated with different prognostic outcomes. Methods: Transcriptomic and clinical data were sourced from the Gene Expression Omnibus (GEO) database and the West China Hospital database. We focused on genes from the RNA immune-oncology panel. The elastic net approach was employed to pinpoint immune-related genes significantly impacting DFS. We developed the IRGPM for rectal cancer using the random forest technique. Based on the IRGPM, we calculated prognostic risk scores to categorize patients into high-risk and low-risk groups. Comparative analysis of immune characteristics between these groups was conducted. Results: In this study, 407 LARC samples were analyzed. The elastic net identified a signature of 20 immune-related genes, forming the basis of the IRGPM. Kaplan-Meier survival analysis revealed a lower 5-year DFS in the high-risk group compared to the low-risk group. The receiver operating characteristic (ROC) curve affirmed the model's robust predictive capability. Validation of the model was performed in the GSE190826 cohort and our institution's cohort. Gene expression differences between high-risk and low-risk groups predominantly related to cytokine-cytokine receptor interactions. Notably, the low-risk group exhibited higher immune scores. Further analysis indicated a greater presence of activated B cells, activated CD8 T cells, central memory CD8 T cells, macrophages, T follicular helper cells, and type 2 helper cells in the low-risk group. Additionally, immune checkpoint analysis revealed elevated PDCD1 expression in the low-risk group. Conclusions: The IRGPM, developed through random forest and elastic net methodologies, demonstrates potential in distinguishing DFS among LARC patients receiving standard treatment. Notably, the low-risk group, as defined by the IRGPM, showed enhanced activation of adaptive immune responses within the tumor microenvironment.

Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application.

T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.

Biotransformation of the azo dye reactive orange 16 by Aspergillus flavus A5P1: Performance, genetic background, pathway, and mechanism.

This study reports the strain Aspergillus flavus A5P1 (A5P1), which is with the capable of degrading the azo dye reactive orange 16 (RO16). The mechanism of RO16 degradation by A5P1 was elucidated through genomic analysis, enzymatic analysis, degradation pathway analysis and oxidative stress analysis. Strain A5P1 exhibited aerobic degradation of RO16, with optimal degradation at an initial pH of 3.0. Genomic analysis indicates that strain A5P1 possesses the potential for acid tolerance and degradation of azo dye. Enzymatic analysis, combined with degradation product analysis, demonstrated that extracellular laccase, intracellular lignin peroxidase, and intracellular quinone reductase were likely key enzymes in the RO16 degradation process. Oxidative stress analysis revealed that cell stress responses may participate in the RO16 biotransformation process. The results indicated that the biotransformation of RO16 may involves biological processes such as transmembrane transport of RO16, cometabolism of the strain with RO16, and cell stress responses. These findings shed light on the biodegradation of RO16 by A5P1, indicating A5P1's potential for environmental remediation.

Visible light-promoted anti-biofouling performance of cellulose acetate membrane for reverse osmosis desalination.

Sea water desalination is regarded as a major solution that could alleviate the water scarcity problem. Reverse osmosis (RO) is typically employed to recover fresh water from sea and brackish water via economical means. RO membrane fouling remains a critical issue restricting their widespread application. In this work, a tertiary thiophenal quaternary ammonium salt-based antibacterial agent was covalently reacted with cellulose acetate (CA) to obtain contact-active antibacterial quaternized CA-RO membrane (QCA-RO). The membrane was characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, water contact angle testing, and X-ray diffraction spectroscopy. The obtained QCA-RO membrane displayed good antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus and had bactericidal rates of 99 % in the presence of visible light. Results showed that embedding the quaternary ammonium salt did not cause any significant changes to the morphology, mechanical performance, and thermal stability of the RO membrane. The method described in this work not only produces QCA-RO membranes with good anti-biofilm performance but also presents great potential in seawater desalination.

Developing Lipase Inhibitor as a Novel Approach to Address the Rice Bran Rancidity Issue─A Critical Review.

Rice bran is a valuable byproduct from the food processing industry, which contains abundant protein, essential unsaturated fatty acids, and numerous bioactive compounds. However, its susceptibility to rancidity greatly restricts its wide utilization. Many strategies have been proposed to delay the rancidity of rice bran, but most of them have their respective limitations. Here, we proposed that developing rice ban lipase peptide inhibitors represents an alternative and promising prescription for impeding the rancidity of rice bran, in contrast to the conventional stabilization approaches for rice bran. For this reason, the rancidity mechanisms of rice bran and the research progress of rice bran lipases were discussed. In addition, the feasibility of utilizing in silico screening and phage display, two state-of-the-art technologies, in the design of the related peptide inhibitors was also highlighted. This knowledge is expected to provide a theoretical basis for opening a new avenue for stabilizing rice bran.

Effect of biochars on the immobilization and form of Cadmium (Cd) in simulated Cd deposition of iron rich soils.

Atmospheric deposition of Cd poses a serious threat to ecosystem security. Biochar is widely used for polluted soil remediation, however, whether biochar already applied to the soil can reduce the hazards of newly deposited Cd remains to be studied. Thus, an indoor cultural experiment and static adsorption method were conducted to study the isothermal and kinetic adsorption processes of three types of biochar (rice husk, rubber wood, and tobacco stem biochars) on Cd in iron rich soils and the effect of biochar on the morphological distribution of Cd in the soil and the soil pH. The results showed that the soil with biochar in our study could quickly fix "the new deposited Cd" in the soil in 3 h with the maximum adsorption capacity in rubber wood biochar-treated sample (3227.34 mg/kg）. The addition of all three biochar treatments significantly increased the soil pH and reduced the soil exchange state Cd content, with a 13.69-17.32% increase in the pH and a 13.22-54.39% reduction in the exchange state Cd content when contrasted with the control, which could promote those Cd converting into unavailable Cd (carbonate-bound form Cd, Fe-Mn oxide-bound form Cd, or residual form Cd) for crops. In summary, the addition of three kinds of biochar treatments could effectively reduce the ecological and environmental risk of soil that was contaminated by Cd and could provide a reliable theoretical basis for the effect of biochar on the improvement of the quality of soil that is contaminated by heavy metals.

TIMely connections: APOE4, aging, and Alzheimer's.

How do APOE4 and aging, two of the strongest risk factors for late-onset Alzheimer's disease (AD), promote disease progression? In this issue of Immunity, Millet et al. examine microglia in AD mice bearing different APOE alleles at distinct ages and identify a conserved exhausted-like microglial state enriched in very elderly and APOE4 AD brains.

ER+/PR- phenotype exhibits more aggressive biological features and worse outcome compared with ER+/PR+ phenotype in HER2-negative inflammatory breast cancer.

The loss of progesterone receptor (PR) often predicts worse biological behavior and prognosis in estrogen receptor-positive (ER +) breast cancer. However, the impact of PR status on inflammatory breast cancer (IBC) has not been studied. Therefore, the purpose of our study was to investigate the influence of PR on IBC. Patients with ER+ and HER2-negative IBC were selected from the Surveillance, Epidemiology and End Results database. Pearson's χ2 test was used to compare the clinicopathological characteristics between patients with estrogen receptor-positive/progesterone receptor-positive (ER+/PR +) and patients with estrogen receptor-positive/progesterone receptor-negative (ER+/PR-). Univariate and multivariate analyses were performed to investigate the effects of PR status on the breast cancer-specific survival (BCSS) and overall survival (OS) in IBC. Overall, 1553 patients including 1157 (74.5%) patients with ER+/PR+ and 396 (25.5%) patients with ER+/PR- were analyzed in our study. The patients with ER+/PR- were more likely to be high histological grade (p < 0.001) and liver metastasis (p = 0.045) compared to patients with ER+/PR+. Despite higher chance of receiving chemotherapy (83.6% vs 77.3%, P = 0.008), patients with ER+/PR- showed worse BCSS (5-year BCSS rate, 34.3% vs 51.3%, P < 0.001) and OS (5-year OS rate, 31.3% vs 46.1%, P < 0.001) compared with ER+/PR+ phenotype. Multivariate survival analysis showed that patients with ER+/PR- still had worse BCSS (hazard ratios [HR]: 1.764, 95% confidence intervals [CI] 1.476-2.109, P < 0.001) and OS (HR: 1.675, 95% CI 1.411-1.975, P < 0.001) than ER+/PR+ phenotype. Furthermore, patients with ER+/PR- showed worse outcomes than ER+/PR+ phenotype in most subgroups, especially in patients with younger age (≤ 60 years), lower histological grade, lymph node involved and distant metastasis. Patients with ER+/PR- had more aggressive biological behaviors and worse outcomes than patients with ER+/PR+ in IBC. Stronger treatments maybe needed for IBC patients with ER+/PR-.

Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium.

Quantifying airway smooth muscle (ASM) in patients with asthma raises the possibility of improved and personalized disease management. Endobronchial polarization-sensitive optical coherence tomography (PS-OCT) is a promising quantitative imaging approach that is in the early stages of clinical translation. To date, only animal tissues have been used to assess the accuracy of PS-OCT to quantify absolute (rather than relative) ASM in cross sections with directly matched histological cross sections as validation. We report the use of whole fresh human and pig airways to perform a detailed side-by-side qualitative and quantitative validation of PS-OCT against gold-standard histology. We matched and quantified 120 sections from five human and seven pig (small and large) airways and linked PS-OCT signatures of ASM to the tissue structural appearance in histology. Notably, we found that human cartilage perichondrium can share with ASM the properties of birefringence and circumferential alignment of fibers, making it a significant confounder for ASM detection. Measurements not corrected for perichondrium overestimated ASM content several-fold (P < 0.001, paired t test). After careful exclusion of perichondrium, we found a strong positive correlation (r = 0.96, P < 0.00001) of ASM area measured by PS-OCT and histology, supporting the method's application in human subjects. Matching human histology further indicated that PS-OCT allows conclusions on the intralayer composition and in turn potential contractile capacity of ASM bands. Together these results form a reliable basis for future clinical studies.NEW & NOTEWORTHY Polarization-sensitive optical coherence tomography (PS-OCT) may facilitate in vivo measurement of airway smooth muscle (ASM). We present a quantitative validation correlating absolute ASM area from PS-OCT to directly matched histological cross sections using human tissue. A major confounder for ASM quantification was observed and resolved: fibrous perichondrium surrounding hyaline cartilage in human airways presents a PS-OCT signature similar to ASM for birefringence and optic axis orientation. Findings impact the development of automated methods for ASM segmentation.

Preparation and Characterization of Multielement Composite Oxide Nanomaterials Containing Ce, Zr, Y, and Yb via Continuous Hydrothermal Flow Synthesis.

The synthesis of multielement composite oxide nanomaterials containing Ce, Zr, Y, and Yb was investigated using a micro confined jet mixer reactor operated in continuous mode under supercritical water conditions. The obtained nanoparticles were characterized using ICP-AES, SEM-EDS, FTIR, Raman spectroscopy, XRD, and TEM. All samples exhibited a uniform particle shape and a narrow particle size distribution. An analysis of the d-spacing results using selected electron area diffraction (SAED) patterns confirmed the production of cubic-phase crystals. A BET test was employed to determine the specific surface area of the prepared nanoparticles. OSC and TPR techniques were utilized to characterize the oxygen storage capacity and reduction performance of the obtained samples, with an analysis conducted to determine how the different proportions of elements affected the performance of multielement mixed oxides. The ionic conductivity of multielement composite oxide was measured using alternating current impedance spectroscopy (EIS), and the impact of Y, Ce, and Yb on the electrolyte material's ionic conductivity was analyzed.

An inducible genetic tool for tracking and manipulating specific microglial states in development and disease.

Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative region-associated microglia (PAM) in developing white matter and disease-associated microglia (DAM) prevalent in various neurodegenerative conditions. PAM and DAM share a similar core gene signature and other functional properties. However, the extent of the dynamism and plasticity of these microglial states, as well as their functional significance, remains elusive, partly due to the lack of specific tools. Here, we report the generation of an inducible Cre driver line, Clec7a-CreERT2, designed to target PAM and DAM in the brain parenchyma. Utilizing this tool, we profile labeled cells during development and in several disease models, uncovering convergence and context-dependent differences in PAM/DAM gene expression. Through long-term tracking, we demonstrate surprising levels of plasticity in these microglial states. Lastly, we specifically depleted DAM in cuprizone-induced demyelination, revealing their roles in disease progression and recovery.

Global burden and inequality of autism spectrum disorders: Based on data from the 2019 Global Burden of Disease study.

It is unclear whether the health equity of autism spectrum disorders (ASDs) has changed in different years, regions, and gender. The aims of this study were to provide a comprehensive description of the ASDs burden and provide evidence for improvement in health policies regarding ASDs inequality. This study is a population-based cross-sectional study based on the Global Burden of Disease datasets 1990-2019. We collected detailed information on ASDs between 1990 and 2019 in 204 countries worldwide, derived from the Global Burden of Disease study in 2019. Burden was calculated in terms of the incidence, prevalence and years lived with disability (YLDs). Concentration curves and concentration indices were used to summarize the degree of income-related inequality in the burden of ASDs. The overall age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized YLDs rate (ASYR) of ASDs was 9.3 (95 %UI 7.7-11.1), 369.4 (95 %UI 305.9-441.2), 56.3 (95 %UI 36.8-81.5) per 100,000 people, respectively. The ASIR, ASPR and ASYR of ASDs affected three times as many males as females. The changing trends of age-standardized rates of ASDs showed that the ASIR of ASDs a slow growing trend globally. However, the ASPR and ASYR of ASDs showed a slow decreasing trend globally. All the concentration curves were below the line of equality and statistically significant. There was no significant difference in the age-standardized rate for different years in socio-demographic index-related inequality happened over 29 years (p > 0.05). The global burden of ASDs has remained higher in males and pro-rich, the income-related inequality tended not to change between 1990 and 2019.

Pituitary-immune bidirectional crosstalk under systemic inflammation.

The pituitary gland responds to and modulates immune stress through the hypothalamus-pituitary-adrenal axis. A new study in PLOS Biology reveals unconventional bidirectional communication between hormone-producing cells and the immune system upon systemic inflammation.

The efficacy of hydrogen/oxygen therapy favored the recovery of omicron SARS-CoV-2 variant infection: results of a multicenter, randomized, controlled trial.

Clinical studies had found that hydrogen/oxygen mixed inhalation was beneficial to ameliorate the respiratory symptoms in the adjuvant treatment of patients with COVID-19. We aimed to explore the efficacy of hydrogen/oxygen therapy in favoring the recovery of Omicron SARS-CoV-2 variant infection. There were 64 patients who randomly assigned to receive hydrogen/oxygen inhalation (32 patients) and oxygen inhalation (32 patients). The average shedding duration of Omicron in hydrogen/oxygen group was shorter than oxygen group. The trend of cumulative negative conversion rate of Omicron increased gradually after the third day. The IL-6 levels in hydrogen/oxygen group decreased by 22.8% compared with the baseline. After hydrogen/oxygen mixed gas inhalation, the lymphocyte count increased to 61.1% of the baseline on the 3rd day in the hydrogen/oxygen group. More patients in the hydrogen/oxygen group had resolution of pulmonary lesions. Our study showed the beneficial trends of molecular hydrogen in treating patients with COVID-19, which may offer a prospective solution to adjuvant therapy for COVID-19 Patients.

Hydrogel-Based Macroscopic Click Chemistry.

The click reaction has found good utility across various fields due to the characteristics of high efficiency, atom economy, simple and mild reaction conditions. Click chemistry is usually utilized for connecting components of microscopic level, while it is still unable for joining macroscopic building blocks. Materials consisting of macroscopic building blocks realize the flexible fabrication of three-dimensional structures at macroscopic level, exerting significance on parallel manufactures. In this work, we reported macroscopic click chemistry utilizing hydrogel as macroscopic building blocks. Hydrogels G1 and G2 were prepared by incorporating M1 (N,N'-dimethyl-1,2-ethanediamine) and P1 (alkyne functionalized polyethylene glycol) respectively, where polymer chains formed through diffusion-induced amino-yne click reaction entangled different hydrogel networks together. Additionally, chain-like aggregates and complicated 3D structures such as tetrahedron and quadrangular pyramid were constructed based on the adhesion of the hydrogel blocks. The approach enables us to find more possibilities in the delicate designation of 3D aggregations as well as large-scale manufacturing.

Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine.

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled 122 infected adults and 50 uninfected controls who had been unvaccinated or vaccinated with two or three doses of COVID-19 inactive vaccines and performed integrative analysis of 41-plex CyTOF, RNA-seq, and Olink on their peripheral blood samples. The frequencies of HLA-DRhi classical monocytes, non-classical monocytes, and Th1-like Tem tended to increase, whereas the frequency of Treg was reduced by booster vaccine, and they influenced symptom occurrence in a vaccine dose-dependent manner. Intercorrelation and mechanistic analysis suggested that the booster vaccination induced monocytic training, which would prime monocytic activation and maturation rather than differentiating into myeloid-derived suppressive cells upon Omicron infections. Overall, our study provides insights into how booster vaccination elaborates protective immunity across SARS-CoV-2 variants.