A clinical study of the local injection of a freshly manufactured 35 kDa hyaluronan fragment for treating chronic wounds.

This study manufactured a 35 kDa hyaluronan fragment (HA35) by enzymatically degrading high-molecular-weight HA using hyaluronidase PH20 derived from bovine testis. The research then examined the therapeutic efficacy of locally administered, tissue-permeable HA35 in alleviating chronic wounds and their associated neuropathic pain. For 20 patients with nonhealing wounds and associated pain lasting over three months, 100 mg of HA35 was injected daily into the healthy skin surrounding the chronic wound for 10 days. Self-assessments before and after treatment indicated that HA35 significantly enhanced wound healing. This was evidenced by the formation of fresh granulation tissue on the wounds (p < 0.0001); reduced darkness, redness, dryness, and damage in the skin surrounding the wounds (p < 0.0001), and a decrease in wound size (p < 0.001). Remarkably, HA35 injections alleviated pain associated with chronic wounds within 24 hours (p < 0.0001). It can be concluded that the low-molecular-weight hyaluronan fragment HA35 potentially enhances the immune response and angiogenesis during wound healing.

Joint extraction of wheat germplasm information entity relationship based on deep character and word fusion.

The verified text data of wheat varieties is an important component of wheat germplasm information. To automatically obtain a structured description of the phenotypic and genetic characteristics of wheat varieties, the aim at solve the issues of fuzzy entity boundaries and overlapping relationships in unstructured wheat variety approval data, WGIE-DCWF (joint extraction model of wheat germplasm information entity relationship based on deep character and word fusion) was proposed. The encoding layer of the model deeply fused word semantic information and character information using the Transformer encoder of BERT. This allowed for the cascading fusion of contextual semantic feature information to achieve rich character vector representation and improve the recognition ability of entity features. The triple extraction layer of the model established a cascading pointer network, extracted the head entity, extracted the tail entity according to the relationship category, and decoded the output triplet. This approach improved the model's capability to extract overlapping relationships. The experimental results demonstrated that the WGIE-DCWF model performed exceptionally well on both the WGD (wheat germplasm dataset) and the public dataset DuIE. The WGIE-DCWF model not only achieved high performance on the evaluation datasets but also demonstrated good generalization. This provided valuable technical support for the construction of a wheat germplasm information knowledge base and is of great significance for wheat breeding, genetic research, cultivation management, and agricultural production.

The extracellular cyclophilin A-integrin ß2 complex as a therapeutic target of viral pneumonia.

The acute respiratory virus infection can induce uncontrolled inflammatory responses, such as cytokine storm and viral pneumonia, which are the major causes of death in clinical cases. Cyclophilin A (CypA) is mainly distributed in the cytoplasm of resting cells and released into the extracellular space in response to inflammatory stimuli. Extracellular CypA (eCypA) is upregulated and promotes inflammatory response in severe COVID-19 patients. However, how eCypA promotes virus-induced inflammatory response remains elusive. Here, we observe that eCypA is induced by influenza A and B viruses and SARS-CoV-2 in cells, mice, or patients. Anti-CypA mAb reduces pro-inflammatory cytokines production, leukocytes infiltration, and lung injury in virus-infected mice. Mechanistically, eCypA binding to integrin ß2 triggers integrin activation, thereby facilitating leukocyte trafficking and cytokines production via the focal adhesion kinase (FAK)/GTPase and FAK/ERK/P65 pathways, respectively. These functions are suppressed by the anti-CypA mAb that specifically blocks eCypA-integrin ß2 interaction. Overall, our findings reveal that eCypA-integrin ß2 signaling mediates virus-induced inflammatory response, indicating that eCypA is a potential target for antibody therapy against viral pneumonia.

Prior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses.

Immunity to infectious diseases is predominantly studied by measuring immune responses towards a single pathogen, although co-infections are common. In-depth mechanisms on how co-infections impact anti-viral immunity are lacking, but are highly relevant to treatment and prevention. We established a mouse model of co-infection with unrelated viruses, influenza A (IAV) and Semliki Forest virus (SFV), causing disease in different organ systems. SFV infection eight days before IAV infection results in prolonged IAV replication, elevated cytokine/chemokine levels and exacerbated lung pathology. This is associated with impaired lung IAV-specific CD8+ T cell responses, stemming from suboptimal CD8+ T cell activation and proliferation in draining lymph nodes, and dendritic cell paralysis. Prior SFV infection leads to increased blood brain barrier permeability and presence of IAV RNA in brain, associated with increased trafficking of IAV-specific CD8+ T cells and establishment of long-term tissue-resident memory. Relative to lung IAV-specific CD8+ T cells, brain memory IAV-specific CD8+ T cells have increased TCR repertoire diversity within immunodominant DbNP366+CD8+ and DbPA224+CD8+ responses, featuring suboptimal TCR clonotypes. Overall, our study demonstrates that infection with an unrelated neurotropic virus perturbs IAV-specific immune responses and exacerbates IAV disease. Our work provides key insights into therapy and vaccine regimens directed against unrelated pathogens.

Weakly Polarized Organic Cation-Modified Hydrated Vanadium Oxides for High-Energy Efficiency Aqueous Zinc-Ion Batteries.

Vanadium oxides, particularly hydrated forms like V2O5·nH2O (VOH), stand out as promising cathode candidates for aqueous zinc ion batteries due to their adjustable layered structure, unique electronic characteristics, and high theoretical capacities. However, challenges such as vanadium dissolution, sluggish Zn2+ diffusion kinetics, and low operating voltage still hinder their direct application. In this study, we present a novel vanadium oxide ([C6H6N(CH3)3]1.08V8O20·0.06H2O, TMPA-VOH), developed by pre-inserting trimethylphenylammonium (TMPA+) cations into VOH. The incorporation of weakly polarized organic cations capitalizes on both ionic pre-intercalation and molecular pre-intercalation effects, resulting in a phase and morphology transition, an expansion of the interlayer distance, extrusion of weakly bonded interlayer water, and a substantial increase in V4+ content. These modifications synergistically reduce the electrostatic interactions between Zn2+ and the V-O lattice, enhancing structural stability and reaction kinetics during cycling. As a result, TMPA-VOH achieves an elevated open circuit voltage and operation voltage, exhibits a large specific capacity (451 mAh g-1 at 0.1 A g-1) coupled with high energy efficiency (89%), the significantly-reduced battery polarization, and outstanding rate capability and cycling stability. The concept introduced in this study holds great promise for the development of high-performance oxide-based energy storage materials.

Characterization, Bioactivity, and Biodistribution of 35 kDa Hyaluronan Fragment.

It has been reported that hyaluronic acid (HA) with a 35 kDa molecular weight (HA35) acts biologically to protect tissue from injury, but its biological properties are not yet fully characterized. This study aimed to evaluate the cellular effects and biodistribution of HA35 compared to HA with a 1600 kDa molecular weight (HA1600). We assessed the effects of HA35 and HA1600 on cell migration, NO and ROS generation, and gene expression in cultured macrophages, microglia, and lymphocytes. HA35 was separately radiolabeled with 99mTc and 125I and administered to C57BL/6J mice for in vivo biodistribution imaging. In vitro studies indicated that HA35 and HA1600 similarly enhanced cell migration through HA receptor binding mechanisms, reduced the generation of NO and ROS, and upregulated gene expression profiles related to cell signaling pathways in immune cells. HA35 showed a more pronounced effect in regulating a broader range of genes in macrophages and microglia than HA1600. Upon intradermal or intravenous administration, radiolabeled HA35 rapidly accumulated in the liver, spleen, and lymph nodes. In conclusion, HA35 not only exhibits effects on cellular bioactivity comparable to those of HA1600 but also exerts biological effects on a broader range of immune cell gene expression. The findings herein offer valuable insights for further research into the therapeutic potential of HA35 in inflammation-mediated tissue injury.

Impact of the gene polymorphisms in the renin-angiotensin system on cardiomyopathy risk: A meta-analysis.

Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.

A comparison analysis of the somatic mutations in early-onset gastric cancer and traditional gastric cancer.

BACKGROUND: Early onset gastric cancer (EOGC) has been on the rise in recent years and differs slightly in pathology from traditional gastric cancer (TGC). Somatic mutations have an essential role in the development of gastric cancer. We aimed to investigate these two types of gastric cancers at the level of somatic mutations and to further understanding of gastric cancer development. METHODS: Somatic mutation, copy number variation (CNV), and clinical information were obtained from TCGA and UCSC Xena. Samples were divided into EOGC (< 50 years old, N = 28) and TGC (≥ 50 years old, N = 395) groups based on age. R packages "maftools" and "sigminer" were used to identify mutation signatures, while CNV information was processed using GISTIC2.0. RESULTS: CDH1(21 %, P = 0.030) and ARID1A (28 %, P = 0.014) were more common in EOGC and TGC, respectively. The mutation frequency of ARID1A increased with age, while the opposite was true for CDH1. Sex, Lauren classifications, tumor mutation burden levels, mutation status of TP53, MUC6, NIPBL, KRAS, and copy number variation of the WOOX can affect the activity of the mutant signature. CONCLUSIONS: Early-onset gastric cancer and traditional gastric cancer have distinct somatic mutation signatures, each with its own relatively specific high-frequency mutated genes, and the gene's mutation frequency correlates with age. Several clinical factors and genetic status affect the activity of some mutational features in gastric cancer in both groups.

Global burden of stomach cancer attributable to smoking from 1990 to 2019 and predictions to 2044.

OBJECTIVES: This study aimed to assess the global temporal trends of stomach cancer attributable to smoking from 1990 to 2019 and to predict the global burden by 2044. STUDY DESIGN: This was a comprehensive analysis based on data provided by the Global Burden of Disease Study 2019. METHODS: Based on the Global Burden of Disease Study 2019, mortality, disability-adjusted life years (DALYs), and corresponding age-standardised rates of stomach cancer attributable to smoking by sociodemographic index (SDI), region, country, sex, and age were used to assess temporal trends from 1990 to 2019 by calculating the average annual percentage change (AAPC). In addition, the global burden of stomach cancer attributable to smoking up to 2044 was predicted using age-period-cohort models. RESULTS: Globally, in 2019, 17.96% of stomach cancer deaths (1.72 million) and 17.15% of stomach cancer DALYs (38.13 million) were attributable to smoking, representing an increase compared to 1990; however, smoking-attributable age-standardised rates of mortality (ASMRs) and DALYs (ASDRs) significantly declined to 2.12/100,000 and 45.82/100,000 in 2019, respectively. While stomach cancer ASMR and ASDR attributable to smoking decreased in all regions and in most countries, they increased by >10% in some countries. A positive correlation was found between SDI and age-standardised rates (rASMR = 0.28, P < 0.01; rASDR = 0.29, P < 0.01). By 2044, although global age-standardised rates for smoking-attributable stomach cancer are predicted to decline, deaths and DALYs are estimated to increase to 2.22 million and 42.14 million, respectively. CONCLUSIONS: Stomach cancer deaths and DALYs attributable to smoking have increased over the past 30 years and will continue to increase. Consequently, targeted prevention efforts and tobacco-control strategies need to be further developed and improved.

Predicting the therapeutic efficacy of AIT for asthma using clinical characteristics, serum allergen detection metrics, and machine learning techniques.

Bronchial asthma is a prevalent non-communicable disease among children. The study collected clinical data from 390 children aged 4-17 years with asthma, with or without rhinitis, who received allergen immunotherapy (AIT). Combining these data, this paper proposed a predictive framework for the efficacy of mite subcutaneous immunotherapy in asthma based on machine learning techniques. Introducing the dispersed foraging strategy into the Salp Swarm Algorithm (SSA), a new improved algorithm named DFSSA is proposed. This algorithm effectively alleviates the imbalance between search speed and traversal caused by the fixed partitioning pattern in traditional SSA. Utilizing the fusion of boosting algorithm and kernel extreme learning machine, an AIT performance prediction model was established. To further investigate the effectiveness of the DFSSA-KELM model, this study conducted an auxiliary diagnostic experiment using the immunotherapy predictive medical data collected by the hospital. The findings indicate that selected indicators, such as blood basophil count, sIgE/tIgE (Der p) and sIgE/tIgE (Der f), play a crucial role in predicting treatment outcome. The classification results showed an accuracy of 87.18% and a sensitivity of 93.55%, indicating that the prediction model is an effective and accurate intelligent tool for evaluating the efficacy of AIT.

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M158-66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αß signatures. Suboptimal TCRαß signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections.

Three-dimensional model construction and wind simulation of different tree species in farmland shelter.

Protective forests are the ecological barriers of oases in arid sand areas and can effectively prevent and control wind and sand hazards. The structural characteristics of individual trees, as the basic unit of protective forests, are the key factors affecting the protective benefits. With the typical leafless tree species of Ulan Buh Desert oasis, i.e., Populus alba var. pyramidalis, Populus nigra var. thevestina, and Populus popularis, as the research objects, and by using the ground-based LiDAR and through computational fluid dynamics (CFD), we fully explored the structural characteristics of individual trees and their surrounding aerodynamic characteristics on the basis of real 3D models. We further established the relationship between structural parameters of individual trees and wind field index. The results showed that combining AdQSM and MeshLab to build tree models had high accuracy. The wind field around the individual trees could be roughly divided into six regions, including the attenuation zone of the windward side of the plant, the acceleration zone at the top of the plant, the eddy zone, the calm zone, the transition zone, and the recovery zone of leeward side of the plant. The pressure field around individual trees showed a gradual change of high pressure on the windward side to low pressure on the leeward side. Horizontally, in the range of 20% to 50% reduction in relative wind speed, the effective protection distances were 0.21H-1.51H, 0.20H-0.91H, and 0.25H-1.64H (H was the corresponding tree height) for P. alba var. pyramidalis, P. nigra var. thevestina, and P. popularis, corresponding to effective protection areas of 18-294, 15-227, and 18-261 m2, respectively. The maximum wind speed decay rate in the vertical direction was at 0.3H height for P. alba var. pyramidalis and P. popularis, and was reflected at 0.5H height for P. nigra var. thevestina. The correlation and stepwise regression analysis of the single tree structure parameters with the wind field indicators clearly indicated that optical porosity and volume porosity dominated the protection effect. Among the wind field factors, the best regression models related to the porous coefficient were screened for three factors, including diameter at breast height, tree surface area, and optical porosity. The regression variables screened for effective protection distance and effective protection area differed among the classes.

Assessment of Anxiety, Depression, and Sleep Quality in Mothers of Children with Atopic Dermatitis: A Qualitative Questionnaire Study.

Purpose: To compare the anxiety, depression and sleep quality of mothers of healthy control children and mothers of children with atopic dermatitis (AD) of varying severity, both before and after treatment. Methods: A total of 120 parent-child dyads participated in the study. These dyads were divided into four subgroups of 30 patients each: mild AD, moderate AD, severe AD, and control groups. The children's symptoms, their mothers' psychological status, and their mothers' sleep quality were evaluated using the Scoring of Atopic Dermatitis (SCORAD), the Hospital Anxiety and Depression Scale (HADS), and the Pittsburgh Sleep Quality Index (PSQI), respectively, before and after a one-month comprehensive treatment. Results: SCORAD, representing differences in severity of children's AD, decreased significantly after one month's treatment (p < 0.001). Anxiety in mothers significantly decreased in all AD severity groups after treatment (p < 0.05). However, for depression, only the mothers in the mild and moderate AD groups showed a decrease after treatment (p < 0.05). The PSQI total score also decreased in the mild AD group after treatment (p < 0.05). Conclusion: The most severe effect was seen in the psychology and sleep quality of mothers of children with severe AD. After one month of treatment, the psychological health and sleep quality of the mothers in the mild AD group significantly improved, while those of mothers in the moderate and severe AD groups showed partial improvement.

Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites.

Maturation rates of malaria parasites within red blood cells (RBCs) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. Here, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide (LPS), or by ongoing acute Plasmodium infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. Importantly, plasma from LPS-conditioned or acutely infected mice directly inhibited parasite maturation during in vitro culture, which was not rescued by supplementation, suggesting the emergence of inhibitory factors in plasma. Metabolomic assessments confirmed substantial alterations to the plasma of LPS-conditioned and acutely infected mice, and identified a small number of candidate inhibitory metabolites. Finally, we confirmed rapid parasite responses to systemic host inflammation in vivo using parasite scRNA-seq, noting broad impairment in transcriptional activity and translational capacity specifically in trophozoites but not rings or schizonts. Thus, we provide evidence that systemic host inflammation rapidly triggered transcriptional alterations in circulating blood-stage Plasmodium trophozoites and predict candidate inhibitory metabolites in the plasma that may impair parasite maturation in vivo. IMPORTANCE Malaria parasites cyclically invade, multiply, and burst out of red blood cells. We found that a strong inflammatory response can cause changes to the composition of host plasma, which directly slows down parasite maturation. Thus, our work highlights a new mechanism that limits malaria parasite growth in the bloodstream.

Improving the Cycling Stability of Aqueous Zinc-Ion Batteries by Preintercalation of Polyaniline in Hydrated Vanadium Oxide.

This paper reports the synthesis and characterization of hydrated vanadium oxide (VOH) and chemically preintercalated polyanilines in VOH, labeled as PAVO-H as the cathode material for aqueous zinc-ion batteries. Synthesized PAVO-H has a high surface area and rod-shaped morphology. PAVO-H has an increased interlayer distance of 13.36 Å. PAVO-H offers high specific capacities of 330 and 225 mAh g-1 at 50 mA g-1 and 4 A g-1 of current densities, respectively, with a 92% capacity retention rate of over 3000 cycles. The preintercalation of polyaniline is likely to catalyze the redox reaction and facilitate and simplify transport kinetics. It is also possible that the preintercalation of polyaniline permits the insertion of large hydrated Zn ions and reduces the formation of zinc basic salts.

Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations.

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.

Assessment on the declining degree of farmland shelter forest in a desert oasis based on LiDAR and hyperspectrum imagery.

We examined the growth decline and health status of farmland protective forest belt (Populus alba var. pyramidalis and Populus simonii shelterbelts) in Ulanbuh Desert Oasis by using airborne hyperspectral and ground-based LiDAR to collect the hyperspectral images and point cloud data of the whole forest belt respectively. Through correlation analysis and stepwise regression analysis, we constructed the evaluation model of the decline degree of farmland protection forest with the spectral differential value, vegetation index, and forest structure parameters as independent variables and the tree canopy dead branch index of the field survey as dependent variables. We further tested the accuracy of the model. The results showed that the evaluation accuracy of the decline degree of P. alba var. pyramidalis and P. simonii by LiDAR method was better than that by hyperspectral method, and that the evaluation accuracy of the combined LiDAR and hyperspectral method was the highest. Using the LiDAR method, hyperspectral method, the combined method, the optimal model of P. alba var. pyramidalis was all light gradient boosting machine model, with the overall classification accuracy being 0.75, 0.68, 0.80, and Kappa coefficient being 0.58, 0.43, 0.66, respectively. The optimal model of P. simonii was random forest model, random forest model, and multilayer perceptron model, with the overall classification accuracy being 0.76, 0.62, 0.81, and Kappa coefficient being 0.60, 0.34, 0.71, respectively. This research method could accurately check and monitor the decline of plantations.

Robust SARS-CoV-2 T cell responses with common TCRαß motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells.

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.

Anti-Inflammatory and Antioxidant Effects of Liposoluble C60 at the Cellular, Molecular, and Whole-Animal Levels.

Introduction: Liposoluble carbon-60 (C60) has potential applications in many fields, including cosmetics, medical devices, and medicine, but its specific mechanism of action remains unclear. This study explored whether liposoluble C60 could be delivered to human organs, tissues, and cells through blood, extracellular fluid, and cell culture fluid and whether it exerts anti-inflammatory and antioxidant effects at the molecular, cellular, and whole-animal levels. Methods: At the cellular level, we mixed C60 dissolved in grape seed oil with cell culture medium containing 10% serum and investigated its effects on tumor necrosis factor-α (TNF-α) release, migration, phagocytosis, respiratory burst, and apoptosis in freshly isolated human neutrophils. At the molecular level, we mixed a trace amount of C60 dissolved in grape seed oil with aqueous and ethanolic solutions and studied its antioxidant effect. At the animal level, we investigated the inhibitory effect of C60 on the serum inflammatory marker C-reactive protein (CRP) in beagle dogs after oral administration of C60 dissolved in grape seed oil. Results: The results showed that the trace amount of C60 dissolved in grape seed oil significantly inhibited TNF-α release, cell migration, phagocytosis, and respiratory burst in freshly isolated human neutrophils. In addition, the trace amount of C60 dissolved in grape seed oil had a significant scavenging effect on superoxide free radicals and 1,1-diphenyl-2-trinitrophenylhydrazine free radicals. Oral administration of C60 dissolved in grape seed oil markedly reduced the level of the serum inflammatory marker CRP in beagle dogs. Conclusion: In summary, a trace amount of hydrophobic C60 in hydrophilic media effectively produced anti-inflammatory and antioxidant effects in cells and animals. C60 dissolved in grape seed oil is a novel anti-inflammatory and antioxidant drug candidate.

Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).

Background: Hyaluronic acid (HA) and HA fragments interact with a variety of human body receptors and are involved in the regulation of various physiological functions and leukocyte trafficking in the body. Accordingly, the development of an injectable HA fragment with good tissue permeability, the identification of its indications, and molecular mechanisms are of great significance for its clinical application. The previous studies showed that the clinical effects of injectable 35kDa B-HA result from B-HA binding to multiple receptors in different cells, tissues, and organs. This study lays the foundation for further studies on the comprehensive clinical effects of injectable B-HA. Methods: We elaborated on the production process, bioactivity assay, efficacy analyses, and safety evaluation of an injectable novel HA fragment with an average molecular weight of 35 kDa (35 kDa B-HA), produced by recombinant human hyaluronidase PH20 digestion. Results: The results showed that 35 kDa B-HA induced human erythrocyte aggregation (rouleaux formation) and accelerated erythrocyte sedimentation rates through the CD44 receptor. B-HA application and injection treatment significantly promoted the removal of mononuclear cells from the site of inflammation and into the lymphatic circulation. At a low concentration, 35 kDa B-HA inhibited production of reactive oxygen species and tumor necrosis factor by neutrophils; at a higher concentration, 35 kDa B-HA promoted the migration of monocytes. Furthermore, 35 kDa B-HA significantly inhibited the migration of neutrophils with or without lipopolysaccharide treatment, suggesting that in local tissues, higher concentrations of 35 kDa B-HA have antiinflammatory effects. After 99mTc radiolabeled 35 kDa B-HA was intravenously injected into mice, it quickly entered into the spleen, liver, lungs, kidneys and other organs through the blood circulation. Conclusion: This study demonstrated that the HA fragment B-HA has good tissue permeability and antiinflammatory effects, laying a theoretical foundation for further clinical studies.