Network-based approach for drug repurposing against mpox.

The current outbreak of mpox presents a significant threat to the global community. However, the lack of mpox-specific drugs necessitates the identification of additional candidates for clinical trials. In this study, a network medicine framework was used to investigate poxviruses-human interactions to identify potential drugs effective against the mpox virus (MPXV). The results indicated that poxviruses preferentially target hubs on the human interactome, and that these virally-targeted proteins (VTPs) tend to aggregate together within specific modules. Comorbidity analysis revealed that mpox is closely related to immune system diseases. Based on predicted drug-target interactions, 268 drugs were identified using the network proximity approach, among which 23 drugs displaying the least side-effects and significant proximity to MPXV were selected as the final candidates. Lastly, specific drugs were explored based on VTPs, differentially expressed proteins, and intermediate nodes, corresponding to different categories. These findings provide novel insights that can contribute to a deeper understanding of the pathogenesis of MPXV and development of ready-to-use treatment strategies based on drug repurposing.

Global pattern and determinant for interaction of seasonal influenza viruses.

BACKGROUND: The prevalence of different types/subtypes varies across seasons and countries for seasonal influenza viruses, indicating underlying interactions between types/subtypes. The global interaction patterns and determinants for seasonal influenza types/subtypes need to be explored. METHODS: Influenza epidemiological surveillance data, as well as multidimensional data that include population-related, environment-related, and virus-related factors from 55 countries worldwide were used to explore type/subtype interactions based on Spearman correlation coefficient. The machine learning method Extreme Gradient Boosting (XGBoost) and interpretable framework SHapley Additive exPlanation (SHAP) were utilized to quantify contributing factors and their effects on interactions among influenza types/subtypes. Additionally, causal relationships between types/subtypes were also explored based on Convergent Cross-mapping (CCM). RESULTS: A consistent globally negative correlation exists between influenza A/H3N2 and A/H1N1. Meanwhile, interactions between influenza A (A/H3N2, A/H1N1) and B show significant differences across countries, primarily influenced by population-related factors. Influenza A has a stronger driving force than influenza B, and A/H3N2 has a stronger driving force than A/H1N1. CONCLUSION: The research elucidated the globally complex and heterogeneous interaction patterns among influenza type/subtypes, identifying key factors shaping their interactions. This sheds light on better seasonal influenza prediction and model construction, informing targeted prevention strategies and ultimately reducing the global burden of seasonal influenza.

Characterizing the antigenic evolution of pandemic influenza A (H1N1) pdm09 from 2009 to 2023.

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09.

Promoting the Calcified Roasting of Vanadium Slag Based on the CeO2-Catalytic Oxidation Mechanism.

Calcification roasting-acid leaching is a clean, efficient, and environmentally friendly process, but in the roasting process, the local temperature is often too high, the heat release is not timely, and the heat transfer is blocked. Furthermore, the material is easy to sinter, which affects the final vanadium extraction effect. In this paper, a small amount of CeO2 was introduced in the roasting process of vanadium slag to promote the calcified roasting. The results showed that the vanadium leaching rate reached 93.17% with the addition of 0.1 wt % CeO2 at a roasting temperature of 750 °C, which was higher than that obtained without CeO2 addition (90.00%). The results of XPS, XRD, and SEM-EDS analyses confirmed that adding CeO2 to the roasted clinker significantly increased the proportion of pentavalent vanadium to the total vanadium by up to 28.64%. O2-TPD analysis revealed an enhanced chemisorbed oxygen with the CeO2-assisted roasting, indicated the activation of oxygen by CeO2, and resulted in an enhanced oxidation of vanadium. The work in this paper establishes an alternative route for catalytic oxidation-enhanced vanadium slag roasting, which can improve the utilization of vanadium slag at relatively lower temperatures under the action of CeO2 and is of positive significance in solving the problems of sintering and energy consumption in the roasting process.

Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis.

Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.

Alterations in CX3CL1 Levels and Its Role in Viral Pathogenesis.

CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.

Integrated metabolome and transcriptome analyses reveal the role of BoGSTF12 in anthocyanin accumulation in Chinese kale (Brassica oleracea var. alboglabra).

BACKGROUND: The vivid red, purple, and blue hues that are observed in a variety of plant fruits, flowers, and leaves are produced by anthocyanins, which are naturally occurring pigments produced by a series of biochemical processes occurring inside the plant cells. The purple-stalked Chinese kale, a popular vegetable that contains anthocyanins, has many health benefits but needs to be investigated further to identify the genes involved in the anthocyanin biosynthesis and translocation in this vegetable. RESULTS: In this study, the purple- and green-stalked Chinese kale were examined using integrative transcriptome and metabolome analyses. The content of anthocyanins such as cyanidin-3-O-(6″-O-feruloyl) sophoroside-5-O-glucoside, cyanidin-3,5-O-diglucoside (cyanin), and cyanidin-3-O-(6″-O-p-hydroxybenzoyl) sophoroside-5-O-glucoside were considerably higher in purple-stalked Chinese kale than in its green-stalked relative. RNA-seq analysis indicated that 23 important anthocyanin biosynthesis genes, including 3 PAL, 2 C4H, 3 4CL, 3 CHS, 1 CHI, 1 F3H, 2 FLS, 2 F3'H, 1 DFR, 3 ANS, and 2 UFGT, along with the transcription factor BoMYB114, were significantly differentially expressed between the purple- and green-stalked varieties. Results of analyzing the expression levels of 11 genes involved in anthocyanin production using qRT-PCR further supported our findings. Association analysis between genes and metabolites revealed a strong correlation between BoGSTF12 and anthocyanin. We overexpressed BoGSTF12 in Arabidopsis thaliana tt19, an anthocyanin transport mutant, and this rescued the anthocyanin-loss phenotype in the stem and rosette leaves, indicating BoGSTF12 encodes an anthocyanin transporter that affects the accumulation of anthocyanins. CONCLUSION: This work represents a key step forward in our understanding of the molecular processes underlying anthocyanin production in Chinese kale. Our comprehensive metabolomic and transcriptome analyses provide important insights into the regulatory system that controls anthocyanin production and transport, while providing a foundation for further research to elucidate the physiological importance of the metabolites found in this nutritionally significant vegetable.

[Advances in the role and mechanism of NK cell immune response mediated by NKG2A-HLA-E axis in viral infectious diseases].

Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E. The studies have shown that HLA-E is overexpressed on virus-infected cells and forms a complex with peptides derived from viral proteins. The interaction of HLA-E and NKG2A can regulate the functions of NK cells, participateing the pathogenesis process of virus infectious diseases. This review outlines the characteristics of the molecular interaction between NKG2A and HLA-E, as well as the mechanisms of NKG2A-HLA-E axis in regulating NK cell responses.

Spatiotemporal genotype replacement of H5N8 avian influenza viruses contributed to H5N1 emergence in 2021/2022 panzootic.

Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic.IMPORTANCESince 2020, highly pathogenic avian influenza (HPAI) H5 subtype variants of clade 2.3.4.4b have spread across continents, posing unprecedented threats globally. However, the factors promoting the genesis and spread of H5 HPAI viruses remain unclear. Here, we found that the spatiotemporal genotype replacement of H5N8 HPAI viruses contributed to the emergence of the H5N1 variant that caused the 2021/2022 panzootic, and the viral evolution in poultry of Egypt and surrounding area and autumn bird migration from the Russia-Kazakhstan region to Europe are important drivers of the emergence of the 2020-2022 H5 panzootic. These findings provide important targets for early warning and could help control the current and future HPAI epidemics.

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction.

Gestational diabetes mellitus (GDM) is a gestational disorder characterized by hyperglycemia, that can lead to dysfunction of diverse cells in the body, especially the immune cells. It has been reported that immune cells, specifically natural killer (NK) cells, play a crucial role in normal pregnancy. However, it remains unknown how hyperglycemia affects NK cell dysfunction thus participates in the development of GDM. In this experiment, GDM mice were induced by an intraperitoneal injection of streptozotocin (STZ) after pregnancy and it has been found that the intrauterine growth restriction occurred in mice with STZ-induced GDM, accompanied by the changed proportion and function of NK cells. The percentage of cytotoxic CD27-CD11b+ NK cells was significantly increased, while the proportion of nourished CD27-CD11b- NK cells was significantly reduced in the decidua of GDM mice. Likewise, the same trend appeared in the peripheral blood NK cell subsets of GDM patients. What's more, after intrauterine reinfusion of NK cells to GDM mice, the fetal growth restriction was alleviated and the proportion of NK cells was restored. Our findings provide a theoretical and experimental basis for further exploring the pathogenesis of GDM.

A novel and efficient murine model for investigating tendon-to-bone healing.

BACKGROUND: Tendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident. METHODS: In our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests. RESULTS: Histological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively. CONCLUSIONS: Our results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing.

Comparative Metabolome and Transcriptome Analyses Reveal the Regulatory Mechanism of Purple Leafstalk Production in Taro (Colocasia esculenta L. Schott).

Taro is a plant in the Araceae family, and its leafstalk possesses significant botanical and culinary value owing to its noteworthy medicinal and nutritional attributes. Leafstalk colour is an essential attribute that significantly influences its desirability and appeal to both breeders and consumers. However, limited information is available about the underlying mechanism responsible for the taro plant's colouration. Thus, the purpose of the current study was to elucidate the information on purple leafstalks in taro through comprehensive metabolome and transcriptome analysis. In total, 187 flavonoids, including 10 anthocyanins, were identified. Among the various compounds analysed, it was observed that the concentrations of five anthocyanins (keracyanin chloride (cyanidin 3-O-rutinoside chloride), cyanidin 3-O-glucoside, tulipanin (delphinidin 3-rutinoside chloride), idaein chloride (cyanidin 3-O-galactoside), and cyanidin chloride) were found to be higher in purple taro leafstalk compared to green taro leafstalk. Furthermore, a total of 3330 differentially expressed genes (DEGs) were identified by transcriptome analysis. Subsequently, the correlation network analysis was performed to investigate the relationship between the expression levels of these differentially expressed genes and the content of anthocyanin. There were 18 DEGs encoding nine enzymes detected as the fundamental structural genes contributing to anthocyanin biosynthesis, along with seven transcription factors (3 MYB and 4 bHLH) that may be promising candidate modulators of the anthocyanin biosynthesis process in purple taro leafstalk. The findings of the current investigation not only provide a comprehensive transcriptional code, but also give information on anthocyanin metabolites as well as beneficial insights into the colour mechanism of purple taro leafstalk.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Fermented rice bran supplementation attenuates colonic injury through modulating intestinal aryl hydrocarbon receptor and innate lymphoid cells in mice with dextran sodium sulfate-induced acute colitis.

This study investigated the effects of fermented rice bran (FRB) on modulating intestinal aryl hydrocarbon receptor (AhR) expression, innate lymphoid cell (ILC)3 populations, the fecal microbiota distribution, and their associations with dextran sodium sulfate (DSS)-induced acute colitis. C57BL/6 mice were assigned to four groups: 1) NC group, normal mice fed the AIN-93M diet; 2) FRB group, normal mice fed a diet supplemented with 5% FRB; 3) NCD group, DSS-treated mice fed AIN-93M; 4) FRBD group, DSS-treated mice fed a 5% FRB-supplemented diet. DSS was administered for 5 d and followed by 5 d for recovery. At the end of the experiment, mice were sacrificed. Their blood and intestinal tissues were collected. Results showed that there were no differences in colonic biological parameters and function between the NC and FRB groups. Similar fecal microbiota diversity was noted between these two groups. Compared to the non-DSS-treated groups, DSS administration led to increased intestinal permeability, enhanced inflammatory cytokine production and disease severity, whereas tight junctions and AhR, interleukin (IL)-22 expressions were downregulated, and the ILC3 population had decreased. Also, gut microbiota diversity differs from the non-DSS-treated groups and more detrimental bacterial populations exist when compared to the FRBD group. FRB supplementation in DSS-treated mice attenuated fecal microbial dysbiosis, decreased intestinal permeability, improved the barrier integrity, upregulated AhR and IL-22 expression, maintained the ILC3 population, and pathologically mitigated colonic injury. These findings suggest enhanced ILC3- and AhR-mediated functions may be partly responsible for the anti-colitis effects of FRB supplementation in DSS-induced colitis.

Cytokine profiles and virological markers highlight distinctive immune statuses, and effectivenesses and limitations of NAs across different courses of chronic HBV infection.

PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.

PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy.

Calcific tendinopathy (CT) is defined by the progressive accumulation of calcium crystals in tendonic regions that results in severe pain in patients. The etiology of CT is not fully elucidated. In this study, we elucidate the role of PPP1R3A in CT. A significant decrease in PPP1R3A expression was observed in CT patient tissues, which was further confirmed in tissues from a CT-induced rat model. Overexpression of PPP1R3A ex vivo reduced the expression of osteo/chondrogenic markers OCN and Sox9, improved tendon tissue architecture, and reduced intracellular Ca2+ levels. Overexpression of SERCA2 and knockdown of Piezo1 decreased expression of osteo/chondrogenic markers and intracellular calcium in PPP1R3A-knockdown tendon cells. Lastly, PPP1R3A expression was regulated at the posttranscriptional level by binding of HuR. Collectively, the present study indicates that PPP1R3A plays an important role in regulating calcium homeostasis in tendon cells via Piezo1/SERCA2, rendering it a promising target for therapeutic interventions of CT.

Comparative Transcriptome Analysis of Purple and Green Flowering Chinese Cabbage and Functional Analyses of BrMYB114 Gene.

Flowering Chinese cabbage (Brassica rapa var. parachinensis) is one of the most popular vegetables in the south of China. As an antioxidant, anthocyanin is an important quality trait in vegetables, and the gene related to anthocyanin biosynthesis in purple flowering Chinese cabbage is also important. In this study, two flowering Chinese cabbage with extreme colors in the stem were used as materials for transcriptome analysis. RNA-seq analysis showed that 6811 differentially expressed genes (DEGs) were identified, including 295 transcription factors. Phenylpropanoid biosynthesis, flavone and flavanol biosynthesis, and flavonoid biosynthesis pathways were found to be significantly enriched in the purple flowering Chinese cabbage. A total of 25 DEGs associated with anthocyanin biosynthesis were found at a higher expression in purple flowering Chinese cabbage than in green flowering Chinese cabbage. Bioinformatics analysis shows that BrMYB114 is a candidate gene for the regulation of anthocyanin biosynthesis, and heterologous expression analysis of BrMYB114 in Nicotiana benthamiana indicates that BrMYB114 functions in anthocyanin biosynthesis. Therefore, our findings provide vital evidence for elucidating the molecular mechanism in the purple stem in flowering Chinese cabbage.

The physio-biochemical characterization reflected different calcium utilization efficiency between the sensitive and tolerant peanut accessions under calcium deficiency.

Peanut yield in southern China is usually limited by calcium deficiency in soil. Most previous studies have found that small-seed varieties showed higher tolerance than large-seed varieties (e.g. Virginia type) under calcium deficiency, however, our preliminary research found that sensitive varieties also existed in small-seed counterparts. Few studies have been conducted to characterize low-calcium tolerance among small-seed germplasms with genetic diversity, and the differences in physiological characteristics between sensitive and tolerant varieties has not been reported yet. Thus, in order to better understand such differences, the current study firstly collected and characterized a diversity germplasm panel consisting of 50 small-seed peanut genotypes via a 2-year field trial, followed by the physiological characterization in sensitive (HN032) and tolerant (HN035) peanut genotypes under calcium deficiency. As a result, the adverse effects brought by calcium deficiency on calcium uptake and distribution in HN032 was much larger than HN035. In details, calcium uptake in the aboveground part (leaves and stems) was reduced by 16.17% and 33.66%, while in the underground part (roots and pods), it was reduced by 13.69% and 68.09% under calcium deficiency for HN035 and HN032, respectively; The calcium distribution rate in the pods of HN035 was 2.74 times higher than HN032. The utilization efficiency of calcium in the pods of HN035 was 1.68 and 1.37 times than that of HN032 under calcium deficiency and sufficiency, respectively. In addition, under calcium deficiency conditions, the activities of antioxidant enzymes SOD, POD, and CAT, as well as the MDA content, were significantly increased in the leaves of HN032, peanut yield was significantly reduced by 22.75%. However, there were no significant changes in the activities of antioxidant enzymes, MDA content, and peanut yield in HN035. Therefore, higher calcium absorption and utilization efficiency may be the key factors maintaining peanut yield in calcium-deficient conditions for tolerant genotypes. This study lays a solid foundation for selecting low-calcium tolerant varieties in future peanut breeding.

Characterizing the dynamics of BCR repertoire from repeated influenza vaccination.

Yearly epidemics of seasonal influenza cause an enormous disease burden around the globe. An understanding of the rules behind the immune response with repeated vaccination still presents a significant challenge, which would be helpful for optimizing the vaccination strategy. In this study, 34 healthy volunteers with 16 vaccinated were recruited, and the dynamics of the BCR repertoire for consecutive vaccinations in two seasons were tracked. In terms of diversity, length, network, V and J gene segments usage, somatic hypermutation (SHM) rate and isotype, it was found that the overall changes were stronger in the acute phase of the first vaccination than the second vaccination. However, the V gene segments of IGHV4-39, IGHV3-9, IGHV3-7 and IGHV1-69 were amplified in the acute phase of the first vaccination, with IGHV3-7 dominant. On the other hand, for the second vaccination, the changes were dominated by IGHV1-69, with potential for coding broad neutralizing antibody. Additional analysis indicates that the application of V gene segment for IGHV3-7 in the acute phase of the first vaccination was due to the elevated usage of isotypes IgM and IgG3. While for IGHV1-69 in the second vaccination, it was contributed by isotypes IgG1 and IgG2. Finally, 41 public BCR clusters were identified in the vaccine group, with both IGHV3-7 and IGHV1-69 were involved and representative complementarity determining region 3 (CDR3) motifs were characterized. This study provides insights into the immune response dynamics following repeated influenza vaccination in humans and can inform universal vaccine design and vaccine strategies in the future.

Increased blood CD226- inflammatory monocytes with low antigen presenting potential correlate positively with severity of hemorrhagic fever with renal syndrome.

BACKGROUND: Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity. MATERIALS AND METHODS: Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection. RESULTS: The proportion of CD226- iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (p < 0.0001). In the acute phase, the proportion of CD226- iMOs increased more in patients with more severe HFRS and correlated positively with HTNV load and negatively with platelet count. Notably, CD226- iMOs expressed lower levels of HLA-DR/DP/DQ and CD80 than CD226+ iMOs, and overexpression CD226 could enhance the expression of HLA-DR/DP/DQ and CD80. In a mouse model, HTNV also induced the expansion of CD226- macrophages, with decreased expression of I-A/I-E and CD80. CONCLUSIONS: CD226- iMOs increased during HTNV infection and the decrease in CD226 hampered the expression of HLA-DR/DP/DQ and CD80, which may promote the immune escape of HTNV and exacerbate clinical symptoms.