Navigating the B vitamins: Dietary diversity, microbial synthesis, and human health.

B vitamins are intricately involved in various physiological processes vital for health. Their significance is complicated by the heterogeneous landscape of B vitamin distribution in diets and the contributions of the gut microbiota. Here, we delve into the impact of these factors on B vitamins and introduce strategies, with a focus on microbiota-based therapeutic options, to enhance their availability for improved well-being. Additionally, we provide an ecological and evolutionary perspective on the importance of B vitamins to human-microbiota interactions. In the dynamic realms of nutrition and microbiome science, these essential micronutrients continue to play a fundamental role in our understanding of disease development.

Free-breathing simultaneous native myocardial T1, T2 and T1ρ mapping with Cartesian acquisition and dictionary matching.

BACKGROUND: T1, T2 and T1ρ are well-recognized parameters for quantitative cardiac MRI. Simultaneous estimation of these parameters allows for comprehensive myocardial tissue characterization, such as myocardial fibrosis and edema. However, conventional techniques either quantify the parameters individually with separate breath-hold acquisitions, which may result in unregistered parameter maps, or estimate multiple parameters in a prolonged breath-hold acquisition, which may be intolerable to patients. We propose a free-breathing multi-parametric mapping (FB-MultiMap) technique that provides co-registered myocardial T1, T2 and T1ρ maps in a single efficient acquisition. METHODS: The proposed FB-MultiMap performs electrocardiogram-triggered single-shot Cartesian acquisition over 16 consecutive cardiac cycles, where inversion, T2 and T1ρ preparations are introduced for varying contrasts. A diaphragmatic navigator was used for prospective through-plane motion correction and the in-plane motion was corrected retrospectively with a group-wise image registration method. Quantitative mapping was conducted through dictionary matching of the motion corrected images, where the subject-specific dictionary was created using Bloch simulations for a range of T1, T2 and T1ρ values, as well as B1 factors to account for B1 inhomogeneities. The FB-MultiMap was optimized and validated in numerical simulations, phantom experiments, and in vivo imaging of 15 healthy subjects and six patients with suspected cardiac diseases. RESULTS: The phantom T1, T2 and T1ρ values estimated with FB-MultiMap agreed well with reference measurements with no dependency on heart rate. In healthy subjects, FB-MultiMap T1 was higher than MOLLI T1 mapping (1218 ± 50 ms vs. 1166 ± 38 ms, p < 0.001). The myocardial T2 and T1ρ estimated with FB-MultiMap were lower compared to the mapping with T2- or T1ρ-prepared 2D balanced steady-state free precession (T2: 41.2 ± 2.8 ms vs. 42.5 ± 3.1 ms, p = 0.06; T1ρ: 45.3 ± 4.4 ms vs. 50.2 ± 4.0, p < 0.001). The pathological changes in myocardial parameters measured with FB-MultiMap were consistent with conventional techniques in all patients. CONCLUSION: The proposed free-breathing multi-parametric mapping technique provides co-registered myocardial T1, T2 and T1ρ maps in 16 heartbeats, achieving similar mapping quality to conventional breath-hold mapping methods.

A dual-stage partially interpretable neural network for joint suppression of bSSFP banding and flow artifacts in non-phase-cycled cine imaging.

PURPOSE: To develop a partially interpretable neural network for joint suppression of banding and flow artifacts in non-phase-cycled bSSFP cine imaging. METHODS: A dual-stage neural network consisting of a voxel-identification (VI) sub-network and artifact-suppression (AS) sub-network is proposed. The VI sub-network provides identification of artifacts, which guides artifact suppression and improves interpretability. The AS sub-network reduces banding and flow artifacts. Short-axis cine images of 12 frequency offsets from 28 healthy subjects were used to train and test the dual-stage network. An additional 77 patients were retrospectively enrolled to evaluate its clinical generalizability. For healthy subjects, artifact suppression performance was analyzed by comparison with traditional phase cycling. The partial interpretability provided by the VI sub-network was analyzed via correlation analysis. Generalizability was evaluated for cine obtained with different sequence parameters and scanners. For patients, artifact suppression performance and partial interpretability of the network were qualitatively evaluated by 3 clinicians. Cardiac function before and after artifact suppression was assessed via left ventricular ejection fraction (LVEF). RESULTS: For the healthy subjects, visual inspection and quantitative analysis found a considerable reduction of banding and flow artifacts by the proposed network. Compared with traditional phase cycling, the proposed network improved flow artifact scores (4.57 ± 0.23 vs 3.40 ± 0.38, P = 0.002) and overall image quality (4.33 ± 0.22 vs 3.60 ± 0.38, P = 0.002). The VI sub-network well identified the location of banding and flow artifacts in the original movie and significantly correlated with the change of signal intensities in these regions. Changes of imaging parameters or the scanner did not cause a significant change of overall image quality relative to the baseline dataset, suggesting a good generalizability. For the patients, qualitative analysis showed a significant improvement of banding artifacts (4.01 ± 0.50 vs 2.77 ± 0.40, P < 0.001), flow artifacts (4.22 ± 0.38 vs 2.97 ± 0.57, P < 0.001), and image quality (3.91 ± 0.45 vs 2.60 ± 0.43, P < 0.001) relative to the original cine. The artifact suppression slightly reduced the LVEF (mean bias = -1.25%, P = 0.01). CONCLUSIONS: The dual-stage network simultaneously reduces banding and flow artifacts in bSSFP cine imaging with a partial interpretability, sparing the need for sequence modification. The method can be easily deployed in a clinical setting to identify artifacts and improve cine image quality.

Two different isoforms of osteopontin modulate myelination and axonal integrity.

Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform-specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN-KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs-iOPN-KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN-KO mice compared to control mice. Accordingly, adult OPN-KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin-related proteins. In contrast, neonatal oligodendrocytes from OLs-iOPN-KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs-iOPN-KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform-specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.

Association between insulin resistance and cardiac remodeling in HER2-positive breast cancer patients: a real-world study.

BACKGROUND: Insulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice. METHODS: HER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements (baseline, 6, 12, and 18 months) after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored. RESULTS: Of 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups (P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (r = 0.178, P = 0.003). No significant association (all P > 0.10) was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006). CONCLUSION: Insulin resistance was associated with left atrial adverse remodeling (LAAR) in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.

Microbial metabolites in chronic heart failure and its common comorbidities.

This study aimed to identify microbial signatures that contribute to the shared etiologies between chronic heart failure (CHF), type 2 diabetes, and chronic kidney disease. The serum levels of 151 microbial metabolites were measured in 260 individuals from the Risk Evaluation and Management of heart failure cohort, and it was found that those metabolites varied by an order of 105 fold. Out of 96 metabolites associated with the three cardiometabolic diseases, most were validated in two geographically independent cohorts. In all three cohorts, 16 metabolites including imidazole propionate (ImP) consistently showed significant differences. Notably, baseline ImP levels were three times higher in the Chinese compared with the Swedish cohorts and increased by 1.1-1.6 fold with each additional CHF comorbidity in the Chinese population. Cellular experiments further supported a causal link between ImP and distinct CHF relevant phenotypes. Additionally, key microbial metabolite-based risk scores were superior in CHF prognosis than the traditional Framingham or Get with the Guidelines-Heart Failure risk scores. Interactive visualization of these specific metabolite-disease links is available on our omics data server (https://omicsdata.org/Apps/REM-HF/).

Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation.

Background Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESULTS Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure-volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF-like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non-heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e' velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. Conclusions Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain-derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self-compensatory mechanism.

Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin.

Silymarin has been used for improving hepatic damage and lipid disorders, but its action mechanism remains to be clarified. Here, we investigate the contributions of the gut microbiota to the improvement of liver lipid metabolism by silymarin. We find i) strong and significant microbial shifts upon silymarin but not silibinin treatment; ii) over 60% variations of liver fat are explained by silymarin-induced bacterial B12 production in male rats but not in male germ-free mice; iii) fecal microbiota transplantation confirms their protective roles against liver fat accumulation; iv) upregulation of one-carbon metabolism and fatty acid degradation pathways are observed based on the liver transcriptome analyses; and v) in humans the delta changes of serum B12 associate negatively with the fluctuations of serum triglycerides. Overall, we reveal a mechanism of action underpinning the lipid-lowering effect of silymarin via the gut microbiota and its vitamin B12 producing capabilities.

Recommendation of Business Models for Agriculture-Related Platforms Based on Deep Learning.

Agriculture is a basic and pillar industry. With the integration and development of Internet+, platform economy, and various industries, the business model of agriculture-related platforms is also constantly innovating. In this context, it is necessary to recommend suitable business models for different types of agriculture-related platforms. Based on the characteristics of agriculture-related platforms and various business models, this paper proposes a business model recommendation algorithm based on radial basis function neural network (RBFNN). This method trains the RBFNN model with the goal of maximizing the correlation between agricultural-related platforms and business models. In the application stage, for a specific agriculture-related platform, after inputting its characteristic parameters, a suitable business model can be recommended. In the experiment, the proposed method is tested and verified with relevant data, and the results show the effectiveness of the method.

Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis.

Transketolase (Tkt), an enzyme in pentose phosphate pathway, has been reported to regulate genome instability and cell survival in cancers. Yet, the role of Tkt after myocardial ischemic injury remains to be elucidated. Label-free proteomics revealed dramatic elevation of Tkt in murine hearts after myocardial infarction (MI). Lentivirus-mediated Tkt knockdown ameliorated cardiomyocyte apoptosis and preserved the systolic function after myocardial ischemic injury. In contrast, Tkt overexpression led to the opposite effects. Inducible conditional cardiomyocyte Tkt-knockout mice were generated, and cardiomyocyte-expressed Tkt was found to play an intrinsic role in the ischemic heart failure of these model mice. Furthermore, through luciferase assay and chromatin immunoprecipitation, Tkt was shown to be a direct target of transcription factor Krüppel-like factor 5 (Klf5). In cardiomyocytes under ischemic stress, Tkt redistributed into the nucleus. By binding with the full-length poly(ADP-ribose) polymerase 1 (Parp1), facilitating its cleavage, and activating apoptosis inducible factor (Aif) subsequently, nuclear Tkt demonstrated its non-metabolic functions. Overall, our study confirmed that elevated nuclear Tkt plays a noncanonical role in promoting cardiomyocyte apoptosis via the cleaved Parp1/Aif pathway, leading to the deterioration of cardiac dysfunction.

Efficacy of ifosfamide combined with liposome doxorubicin on osteosarcoma and its effects on serum IL-10, TNF-α, and IFN-γ in patients with osteosarcoma.

OBJECTIVE: To evaluate the effects of ifosfamide combined with liposome doxorubicin on osteosarcoma (OS) and its effects on serum IL-10, TNF-α, and IFN-γ in patients with OS. METHODS: A total of 86 patients with OS who received chemotherapy in Honghui Hospital, Xi'an Jiaotong University from Jan. 2017 to Dec. 2019 were enrolled. Patients treated by conventional doxorubicin + ifosfamide were assigned to the regular group (n=40). Others treated by liposome doxorubicin + ifosfamide were assigned to the research group (n=46). The clinical efficacy, 2-year survival rate, and adverse reactions of the two groups were evaluated and compared. ELISA was adopted for quantification of tumor specific growth factor (TSGF), vascular endothelial growth factor (VEGF), erb-b2 receptor tyrosine kinase 3 (ERBB3), tumor necrosis factor-α (TNF-α), interferon-gamma-γ (IFN-γ), and interleukin-10 (IL-10). The EORTC Quality of Life Questionnaire (QLQ-C30) was adopted to evaluate a patient's life quality. RESULTS: The research group showed a higher total effective rate and a higher 2-year survival rate than the regular group, but lower incidences of liver and kidney function injury, thrombocytopenia, and cardiotoxicity than the regular group. After therapy, lower levels of serum TSGF, VEGF, ERBB3, and TNF-α were found in the research group than those in the regular group. Higher levels of IFN-γ and IL-10 were found in the former than those in the latter. The research group got higher scores of QLQ-C30 than the regular group. CONCLUSION: Liposome doxorubicin + ifosfamide can improve the clinical efficacy on patients with OS and improve their recovery and life quality.

Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure.

ABSTRACT: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.

Aspergillus niger changes the chemical form of uranium to decrease its biotoxicity, restricts its movement in plant and increase the growth of Syngonium podophyllum.

Aspergillus niger (A. niger) and Syngonium podophyllum (S. podophyllum) have been used for wastewater treatment, and have exhibited a promising application in recent years. To determine the effects of A. niger on uranium enrichment and uranium stress antagonism of S. podophyllum, the S. podophyllum-A. niger combined system was established, and hydroponic remediation experiments were carried out with uranium-containing wastewater. The results revealed that the bioaugmentation of A. niger could increase the biomass of S. podophyllum by 5-7%, reverse the process of U(VI) reduction induced by S. podophyllum, and increase the bioconcentration factor (BCF) and translocation factor (TF) of S. podophyllum to uranium by 35-41 and 0.01-0.06, respectively, thereby improving the reduction of uranium in wastewater. Moreover, A. niger could promote the cell wall immobilization and the subcellular compartmentalization of uranium in the root of S. podophyllum, reduce the phytotoxicity of uranium entering root cells, and inhibit the calcium efflux from root cells, thereby withdrawing the stress of uranium on S. podophyllum.

Influence of APOA5 Locus on the Treatment Efficacy of Three Statins: Evidence From a Randomized Pilot Study in Chinese Subjects.

Pharmacogenetics or pharmacogenomics approaches are important for addressing the individual variabilities of drug efficacy especially in the era of precision medicine. One particular interesting gene to investigate is APOA5, which has been repeatedly linked with the inter-individual variations of serum triglycerides. Here, we explored APOA5-statin interactions in 195 Chinese subjects randomized to rosuvastatin (5-10 mg/day), atorvastatin (10-20 mg/day), or simvastatin (40 mg/day) for 12 weeks by performing a targeted genotyping analysis of the APOA5 promoter SNP rs662799 (-1131T > C). There were no significant differences between the treatment arms for any of the statin-induced changes in clinical biomarkers. Reductions in LDL cholesterol were influenced by the APOA5 genotype in all three treatment groups. By contrast, changes in HDL cholesterol, and triglycerides were only affected by the APOA5 genotype in the atorvastatin and simvastatin groups and not in the rosuvastatin group. Our results suggest that future studies may need to consider stratifying subjects not only by genetic background but also by prescribed statin type.

Platelet-rich plasma shows beneficial effects for patients with knee osteoarthritis by suppressing inflammatory factors.

Knee osteoarthritis is a degenerative disease that may develop due ageing, obesity, strain, congenital abnormal joints, joint deformity or trauma. It is caused by many factors, such as degradation of articular cartilage injury, joint edge and subchondral bone hyperplasia of reactivity. Platelet-rich plasma (PRP) is an autologous blood sample that contains highly concentrated platelets and multiple cell growth factors. PRP promotes synovial cell proliferation and differentiation and may recover cartilage morphology. In the present study, the clinical efficacy of PRP was investigated in patients with knee osteoarthritis aged between 18 and 30 years in a phase-III clinical study. Following an 8-week baseline, patients with knee osteoarthritis were randomized into once-weekly, double-blind treatment with PRP (2-14 ml) or placebo groups. The results indicated that patients with osteoarthritis treated with PRP had modulated plasma concentrations of inflammatory factors and pro-angiogenic factors compared with the placebo group. Treatment responses were assessed by median percent reduction in inflammatory and pro-angiogenic factors and these improved with PRP treatment compared with the placebo. Clinical data indicated that PRP alleviated knee osteoarthritis and reduced humoral and cellular immune responses that led to beneficial effects on histological parameters. Inflammation was significantly alleviated in patients receiving PRP compared with the placebo group. The most common treatment-emergent adverse events in the presence of PRP were hypertension and proteinuria. In conclusion, treatment with PRP for patients with knee osteoarthritis presented beneficial effects in alleviating joint inflammation, cartilage destruction and bone damage, and repairing joint tissue. These results suggested that PRP may be a potential therapeutic agent for knee osteoarthritis.

γδ T Cells Contribute to Injury in the Developing Brain.

Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurologic disabilities. Inflammation contributes to perinatal brain injury development, but the essential mediators that lead to early-life brain injury remain largely unknown. Neonates have reduced capacity for mounting conventional αßT-cell responses. However, γδT cells are already functionally competent during early development and are important in early-life immunity. We investigated the potential contribution of γδT cells to preterm brain injury using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury-the hypoxic-ischemic mouse model and a fetal sheep asphyxia model. Large numbers of γδT cells were observed in the brains of mice, sheep, and postmortem preterm infants after injury, and depletion of γδT cells provided protection in the mouse model. The common γδT-cell-associated cytokines interferon-γ and IL-17A were not detectable in the brain. Although there were increased mRNA levels of Il17f and Il22 in the mouse brains after injury, neither IL-17F nor IL-22 cytokines contributed to preterm brain injury. These findings highlight unique features of injury in the developing brain, where, unlike injury in the mature brain, γδT cells function as initiators of injury independently of common γδT-cell-associated cytokines. This finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.

γδT cells but not αßT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice.

BACKGROUND: Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. METHODS: In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αßT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd -/-, lacking γδT cells), and TCRα-deficient (Tcra -/-, lacking αßT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. RESULTS: White matter development was normal in Tcrd -/- and Tcrα -/- compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα -/- mice, but not in the Tcrd -/- mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcrα -/- mice, but no such effect was observed in Tcrd -/- mice. CONCLUSIONS: Our results suggest that γδT cells but not αßT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.

Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.

The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.

Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season.

The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbidity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-like strains) and HK14 (A/Hong Kong/5738/2014-like strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in mainland China, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an important role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.

Computational analysis of antigenic epitopes of avian influenza A (H7N9) viruses.

Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin (HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread concern. However, evolution of the antigenicity of this virus is not well understood. Here, we inferred the antigenic epitopes of the HA protein from all H7 viruses, based on the five well-characterized HA epitopes of the human H3N2 virus. By comparing the two major H7 phylogenetic lineages, i.e., the Eurasian lineage and the North American lineage, we found that epitopes A and B are more frequently mutated in the Eurasian lineage, while epitopes B and C are more frequently mutated in the North American lineage. Furthermore, we found that the novel H7N9 virus (derived from the Eurasian lineage) isolated in China in the year 2013, contains six frequently mutated sites on epitopes that include site 135, which is located in the receptor binding domain. This indicates that the novel H7N9 virus that infects human may already have been subjected to gradual immune pressure and receptor-binding variation. Our results not only provide insights into the antigenic evolution of the H7 virus but may also help in the selection of suitable vaccine strains.