Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

Proteomic and Cellular Characterization of Omicron Breakthrough Infections and a Third Homologous or Heterologous Boosting Vaccination in a Longitudinal Cohort.

The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA2.2 breakthrough infections were enrolled. Serum samples were collected at days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.

Vaccination Shapes Within-Host SARS-CoV-2 Diversity of Omicron BA.2.2 Breakthrough Infection.

BACKGROUND: Low-frequency intrahost single-nucleotide variants of SARS-CoV-2 have been recognized as predictive indicators of selection. However, the impact of vaccination on the intrahost evolution of SARS-CoV-2 remains uncertain at present. METHODS: We investigated the genetic variation of SARS-CoV-2 in individuals who were unvaccinated, partially vaccinated, or fully vaccinated during Shanghai's Omicron BA.2.2 wave. We substantiated the connection between particular amino acid substitutions and immune-mediated selection through a pseudovirus neutralization assay or by cross-verification with the human leukocyte antigen-associated T-cell epitopes. RESULTS: In contrast to those with immunologic naivety or partial vaccination, participants who were fully vaccinated had intrahost variant spectra characterized by reduced diversity. Nevertheless, the distribution of mutations in the fully vaccinated group was enriched in the spike protein. The distribution of intrahost single-nucleotide variants in individuals who were immunocompetent did not demonstrate notable signs of positive selection, in contrast to the observed adaptation in 2 participants who were immunocompromised who had an extended period of viral shedding. CONCLUSIONS: In SARS-CoV-2 infections, vaccine-induced immunity was associated with decreased diversity of within-host variant spectra, with milder inflammatory pathophysiology. The enrichment of mutations in the spike protein gene indicates selection pressure exerted by vaccination on the evolution of SARS-CoV-2.

Therapeutic vaccination with lentiviral vector in HBV-persistent mice and two inactive HBsAg carriers.

BACKGROUND & AIMS: Immunotherapy for chronic hepatitis B virus (HBV) infection has not yet demonstrated sufficient efficacy. We developed a non-integrative lentiviral-vectored therapeutic vaccine for chronic hepatitis B and tested its antiviral effects in HBV-persistent mice and two inactive HBsAg carriers. METHODS: Lentiviral vectors (LVs) encoding the core, preS1, or large HBsAg (LHBs) proteins of HBV were evaluated for immunogenicity in HBV-naïve mice and therapeutic efficacy in a murine model of chronic HBV infection. In addition, two inactive HBsAg carriers each received two doses of 5×107 transduction units (TU) or 1×108 TU of lentiviral-vectored LHBs (LV-LHBs), respectively. The endpoints were safety, LHBs-specific T-cell responses, and serum HBsAg levels during a 24-week follow-up. RESULTS: In the mouse models, LV-LHBs was the most promising in eliciting robust antigen-specific T cells and in reducing the levels of serum HBsAg and viral load. By the end of the 34-week observation period, six out of ten (60%) HBV-persistent mice vaccinated with LV-LHBs achieved serum HBsAg loss and significant depletion of HBV-positive hepatocytes in the liver. In the two inactive HBsAg carriers, vaccination with LV-LHBs induced a considerable increase in the number of peripheral LHBs-specific T cells in one patient, and a weak but detectable response in the other, accompanied by a sustained reduction of HBsAg (-0.31 log10 IU/ml and -0.46 log10 IU/ml, respectively) from baseline to nadir. CONCLUSIONS: A lentiviral-vectored therapeutic vaccine for chronic HBV infection demonstrated the potential to improve HBV-specific T-cell responses and deplete HBV-positive hepatocytes, leading to a sustained loss or reduction of serum HBsAg. IMPACT AND IMPLICATIONS: Chronic HBV infection is characterized by an extremely low number and profound hypo-responsiveness of HBV-specific T cells. Therapeutic vaccines are designed to improve HBV-specific T-cell responses. We show that immunization with a lentiviral-vectored therapeutic HBV vaccine was able to expand HBV-specific T cells in vivo, leading to reductions of HBV-positive hepatocytes and serum HBsAg.

Comprehensive Evaluation of Anti-icing Performance and Operational Efficiency of Superhydrophobic Propellers.

The icing of propellers is a critical factor that affects the safe operation of aircraft. A superhydrophobic surface, with its extremely low wettability, is highly valuable in the field of anti-icing. This study investigates the distribution pattern of ice on propeller surfaces by employing spray coating to create superhydrophobic surfaces. Additionally, it conducts a comparative analysis of thrust and power under icing and non-icing conditions to comprehensively assess the impact of superhydrophobic surfaces on propeller operation efficiency. The results show that superhydrophobic surfaces not only diminish the ice formation area on propeller surfaces but also enhance the traction of propellers under icing conditions, reducing the power consumption of the propeller. The generated thrust can reach up to 1.6 times that of non-superhydrophobic propellers while consuming only one-third of the power. Furthermore, under non-icing conditions, superhydrophobic surfaces exhibit minimal impact on propeller performance.

High-tolerance reconfigurable MZI racetrack resonator on a 3-µm-thick SOI photonics platform.

Integration of resonators impacts the utilization of the 3-µm-thick silicon-on-insulator (SOI) platform in photonics integrated circuits (PICs). We propose an integrated resonator leveraging a deep-etch silicon waveguide. Through the utilization of a tunable coupler based on multimode interferometers (MMIs), the resonator achieves high fabrication tolerance and reconfigurability. In a critical-coupling state, it serves as a filter with an extinction ratio (ER) of 23.5 dB and quality (Q) factor of 3.1×105, operating within the range of 1530-1570 nm. In an extreme over-coupling state, it functions as a large-bandwidth delay line, offering continuous change in delay time of 22 ps, nearly wavelength-independent. This work provides devices to the 3-µm-thick silicon photonics device library, enriching the potential applications of this technology platform.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

Evidence of Residual Ongoing Viral Replication in Chronic Hepatitis B Patients Successfully Treated With Nucleos(t)ide Analogues.

BACKGROUND: Chronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved, even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in patients successfully treated with NAs. METHODS: A series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from patients successfully treated with NAs. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated. RESULTS: Three of 6 successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming proportion of variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated to be from approximately 7.42 weeks to infinite. Hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA in 4 of 7 liver needle biopsies. CONCLUSIONS: We conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas a large proportion of the cccDNA reservoir persists over time.

Molecular epidemiology analysis of symptomatic and asymptomatic norovirus infections in Chinese infants.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

Application of starch-based nanoparticles and cyclodextrin for prebiotics delivery and controlled glucose release in the human gut: a review.

Starches are a major constituent of staple foods and are the main source of energy in the human diet (55-70%). In the gastrointestinal tract, starches are hydrolyzed into glucose by α-amylase and α-glucosidase, which leads to a postprandial glucose elevation. High levels of blood glucose levels over sustained periods may promote type 2 diabetes mellitus (T2DM) and obesity. Increasing consumption of starchy foods with a lower glycemic index may therefore contribute to improved health. In this paper, the preparation and properties of several starch-based nanoparticles (SNPs) and cyclodextrins (CDs) derivatives are reviewed. In particular, we focus on the various mechanisms responsible for the ability of these edible nanomaterials to modulate glucose release and the gut microbiome in the gastrointestinal tract. The probiotic functions are achieved through encapsulation and protection of prebiotics or bioactive components in foods or the human gut. This review therefore provides valuable information that could be used to design functional foods for improving human health and wellbeing.

Advances in preparation, interaction and stimulus responsiveness of protein-based nanodelivery systems.

The improved understanding of the connection between diet and health has led to growing interest in the development of functional foods designed to improve health and wellbeing. Many of the potentially health-promoting bioactive ingredients that food manufacturers would like to incorporate into these products are difficult to utilize because of their chemical instability, poor solubility, or low bioavailability. For this reason, nano-based delivery systems are being developed to overcome these problems. Food proteins possess many functional attributes that make them suitable for formulating various kinds of nanocarriers, including their surface activity, water binding, structuring, emulsification, gelation, and foaming, as well as their nutritional aspects. Proteins-based nanocarriers are therefore useful for introducing bioactive ingredients into functional foods, especially for their targeted delivery in specific applications.This review focusses on the preparation, properties, and applications of protein-based nanocarriers, such as nanoparticles, micelles, nanocages, nanoemulsions, and nanogels. In particular, we focus on the development and application of stimulus-responsive protein-based nanocarriers, which can be used to release bioactive ingredients in response to specific environmental triggers. Finally, we discuss the potential and future challenges in the design and application of these protein-based nanocarriers in the food industry.

Interactions between plant-derived antioxidants and cyclodextrins and their application for improving separation, detection, and food quality issues.

Plant-derived antioxidants (PD-AOs) are important for food preservation, as well as for human health and nutrition. However, the poor chemical stability and water solubility of many PD-AOs currently limit their application as functional ingredients in foods and pharmaceuticals. Moreover, it is often difficult to isolate and detect specific antioxidants in multi-component systems, which again limits their potential in the food and medical industries. In this review, we highlight recent advances in the use of cyclodextrins (CDs) to overcome these limitations by forming simple, modified and competitive host-guest interactions with PD-AO. The host-guest properties of CDs can be used to enhance the separation efficiency of PD-AOs, as well as to improve their dispersion and stability in food systems. Moreover, the competitive complexation properties of CDs with target molecules can be used to selectively isolate PD-AOs from multi-component systems and develop detection technologies for PD-AOs. Overall, CD-antioxidant interactions have great potential for addressing isolation, detection, and food quality issues.

Encapsulation of polyphenols in protein-based nanoparticles: Preparation, properties, and applications.

Polyphenols have a variety of physiological activities, including antioxidant, antimicrobial, and anti-inflammatory properties. However, their applications are often limited because due to the instability of polyphenols. Encapsulation technologies can be employed to overcome these problems and increase the utilization of polyphenols. In this article, the utilization of protein-based nanoparticles for encapsulating polyphenols is reviewed due to their good biocompatibility, biodegradability, and functional attributes. Initially, the various kinds of animal and plant proteins available for forming protein nanoparticles are discussed, as well as the fabrication methods that can be used to assemble these nanoparticles. The molecular interaction mechanisms between proteins and polyphenols are then summarized. Applications of protein-based nanoparticles for encapsulating polyphenols are then discussed, including as nutrient delivery systems, in food packaging materials, and in the creation of functional foods. Finally, areas where further research is need on the development, characterization, and application of protein-based polyphenol-loaded nanoparticles are highlighted.

Health benefits, mechanisms of interaction with food components, and delivery of tea polyphenols: a review.

Tea polyphenols (TPs) are the most important active component of tea and have become a research focus among natural products, thanks to their antioxidant, lipid-lowering, liver-protecting, anti-tumor, and other biological activities. Polyphenols can interact with other food components, such as protein, polysaccharides, lipids, and metal ions to further improve the texture, flavor, and sensory quality of food, and are widely used in food fields, such as food preservatives, antibacterial agents and food packaging. However, the instability of TPs under conditions such as light or heat and their low bioavailability in the gastrointestinal environment also hinder their application in food. In this review, we summarized the health benefits of TPs. In order to better use TPs in food, we analyzed the form and mechanism of interaction between TPs and main food components, such as polysaccharides and proteins. Moreover, we reviewed research into optimizing the applications of TPs in food by bio-based delivery systems, such as liposomes, nanoemulsions, and nanoparticles, so as to improve the stability and bioactivity of TPs in food application. As an effective active ingredient, TPs have great potential to be applied in functional food to produce benefits for human health.

Recent advances in natural gums as additives to help the construction and application of edible biopolymer gels: the example of hydrogels and oleogels.

Novel, innovative approaches like edible gels (hydrogels and oleogels) are important food materials with great scientific interest due to their positive impacts on structural and functional foods and other unique properties. Biopolymers (protein, starch and other polysaccharides) can be excellent and cost-effective materials for the formed edible gels. Recently, natural gums, although also as biopolymers, are preferred as additives to further improve the textural and functional properties of edible gels, which have received extensive attention. However, these studies have not been outlined in previous reviews. In this review, we highlighted the advantages of gums as additives to construct edible gels. Moreover, the various roles (including electrostatic or covalent interactions) for natural gums in regulation of food gel properties (solvent-holding and rheological properties) are highlighted. Finally, the use of natural gums as additives to improve the stability and targeted delivery of phytochemicals in food gels and their application in food systems are summarized. The information covered in this article may be useful for the design of functional foods that can better meet personalized needs of people.

Starch-guest complexes interactions: Molecular mechanisms, effects on starch and functionality.

Starch is a natural, abundant, renewable and biodegradable plant-based polymer that exhibits a variety of functional properties, including the ability to thicken or gel solutions, form films and coatings, and act as encapsulation and delivery vehicles. In this review, we first describe the structure of starch molecules and discuss the mechanisms of their interactions with guest molecules. Then, the effects of starch-guest complexes on gelatinization, retrogradation, rheology and digestion of starch are discussed. Finally, the potential applications of starch-guest complexes in the food industry are highlighted. Starch-guest complexes are formed due to physical forces, especially hydrophobic interactions between non-polar guest molecules and the hydrophobic interiors of amylose helices, as well as hydrogen bonds between some guest molecules and starch. Gelatinization, retrogradation, rheology and digestion of starch-based materials are influenced by complex formation, which has important implications for the utilization of starch as a functional and nutritional ingredient in food products. Controlling these interactions can be used to create novel starch-based food materials with specific functions, such as texture modifiers, delivery systems, edible coatings and films, fat substitutes and blood glucose modulators.

Leukoencephalopathy with calcifications and cysts: A case report with literature review.

Leukoencephalopathy with calcifications and cysts (LCC; OMIM #614561) is a rare disease and at present there are less than 100 cases reported worldwide. Mutations in the SNORD118 gene is now known to be the cause of LCC. We present a case who was heterozygous for the n.70G>A and n.6C>T sequence variants of the SNORD118 gene, variants which to date have not been described. Compared with the cases that we reviewed, our patient had the second longest time to diagnosis (age 56) from onset of symptoms 40 years prior. Moreover, his cousin's family has a high prevalence of epilepsy. This paper reviewed all published reports to date that had descriptive cases involving LCC as well as testing for the SNORD118 gene. Since 1996 only 85 patients have been described in 59 case reports. In this review, we summarize their clinical features, especially central nervous system symptoms, treatment, pathology, and gene testing results.

Associations of parental feeding practices with children's eating behaviors and food preferences: a Chinese cross-sectional study.

BACKGROUND: Childhood inadequate eating behaviors contribute to the epidemic of obesity. Previous research suggests that parental feeding practices are partially associated with development of eating behaviors among children, but the results are inconsistent. The present study was to investigate whether parental feeding practices were associated with eating behaviors and food preferences among Chinese children. METHODS: A cross-sectional study was conducted to collect data from 242 children (ages 7-12) in six-primary schools in Shanghai, China. A series of questionnaires including parental feeding practices and children's eating behaviors have been validated, and were completed by one of parent who has responded for child's daily diet and living. In addition, researchers instructed children to complete the questionnaire of food preference. After adjustment for children's age, sex and BMI status, as well as parental education and family income, the linear regression analysis was used to evaluate relationships of parental feeding practices with children's eating behaviors and food preferences. RESULTS: Parents with boys had higher level of control overeating practice than those with girls. Mothers who responded to child's daily diet and living and completed feeding practices questionnaire used a greater level of emotional feeding practices than fathers. Boys had higher levels of food responsiveness, emotional overeating, enjoyment of food and desire to drink than girls. Boys had different preferences for meat, processed meat products, fast foods, dairy foods, eggs, and snacks and starchy staples & beans from girls. In addition, scores of instrumental feeding practice and preference for meat significantly differed among children with different weight status. Furthermore, parental emotional feeding practice was positively associated with children's emotional undereating (ß 0.54, 95% CI 0.16 to 0.92). There were also positive associations of parental encouragement to eat with children's preference for the processed meat (ß 0.43, 95% CI 0.08 to 0.77). Moreover, instrumental feeding practice was negatively associated with children's fish liking (ß -0.47, 95% CI -0.94 to -0.01). CONCLUSION: The current findings support associations of emotional feeding practice with some children's emotional undereating, as well as parental encouragement to eat and instrumental feeding practice related to preference for processed meat and fish, respectively. Further studies should continue to ascertain these associations using longitudinal designs, and to evaluate efficacy of parental feeding practices impacting developments of healthy eating behaviors and preferences for healthy foods among children by interventional studies.

Utilization of plant extracts to control the safety and quality of fried foods-A review.

Frying is one of the most common methods of preparing foods. However, it may lead to the formation of potentially hazardous substances, such as acrylamide, heterocyclic amines, trans fatty acids, advanced glycation end products, hydroxymethyl furfural and polycyclic aromatic hydrocarbons, and adversely alter the desirable sensory attributes of foods, thereby reducing the safety and quality of fried foods. Currently, the formation of toxic substances is usually reduced by pretreatment of the raw materials, optimization of process parameters, and the use of coatings. However, many of these strategies are not highly effective at inhibiting the formation of these undesirable reaction products. Plant extracts can be used for this purpose because of their abundance, safety, and beneficial functional attributes. In this article, we focus on the potential of using plant extracts to inhibit the formation of hazardous substances, so as to improve the safety of fried food. In addition, we also summarized the effects of plant extracts, which inhibit the production of hazardous substances, on food sensory aspects (flavor, color, texture, and taste). Finally, we highlight areas where further research is required.