Recent advances in delivery of transdermal nutrients: A review.

Nutrients provide vital functions in the body for sustained health, which have been shown to be related to the incidence, prevention and treatment of disease. However, limited bioavailability, loss of targeting specificity and the increased hepatic metabolism limit the utilization of nutrients. In this review, we highlight transdermal absorption of nutrients, which represents an opportunity to allow great use of many nutrients with promising human health benefits. Moreover, we describe how the various types of permeation enhancers are increasingly exploited for transdermal nutrient delivery. Chemical penetration enhancers, carrier systems and physical techniques for transdermal nutrient delivery are described, with a focus on combinatorial approaches. Although there are many carrier systems and physical techniques currently in development, with some tools currently in advanced clinical trials, relatively few products have achieved full translation to clinical practice. Challenges and further developments of these tools are discussed here in this review. This review will be useful to researchers interested in transdermal applications of permeation enhancers for the efficient delivery of nutrients, providing a reference for supporting the need to take more account of specific nutritional needs in specific states.

Antioxidant Carbon Dots Nanozymes Alleviate Stress-induced Depression by Modulating Gut Microbiota.

Depression is a debilitating mental illness that severely threatens millions of individuals and public health. Because of the multifactorial etiologies, there is currently no cure for depression; thus, it is urgently imperative to find alternative antidepressants and strategies. Growing evidence underscores the prominent role of oxidative stress as key pathological hallmarks of depression, making oxidative stress a potential therapeutic target. In this study, we report a N-doped carbon dot nanozyme (CDzyme) with excellent antioxidant capacity for treating depression by remodeling redox homeostasis and gut microbiota. The CDzymes prepared via microwave-assisted fast polymerization of histidine and glucose exhibit superior biocompatibility. Benefiting from the unique structure, CDzymes can provide abundant electrons, hydrogen atoms, and protons for reducing reactions, as well as catalytic sites to mimic redox enzymes. These mechanisms collaborating endow CDzymes with broad-spectrum antioxidant capacity to scavenge reactive oxygen and nitrogen species (•OH, O2-•, H2O2, ONOO-), and oxygen/nitrogen centered free radicals. A depression animal model was established by chronic unpredictable mild stress (CUMS) to evaluate the therapeutic efficacy of CDzymes from the behavioral, physiological, and biochemical index and intestinal flora assessments. CDzymes can remarkably improve depression-like behaviors and key neurotransmitters produced in hippocampus tissues and restore the gut microbiota compositions and the amino acid metabolic functions, proving the potential in treating depression through the intestinal-brain axis system. This study will facilitate the development of intestinal flora dysbiosis nanomedicines and treatment strategies for depression and other oxidative stress related multifactorial diseases.

T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass.

BACKGROUND: children who undergo CPB operations are at an elevated risk of infection due to immunosuppression. This study aims to investigate the association between lymphopenia following CPB and early postoperative infection in children. METHODS: A retrospective analysis including 41 children under 2 years old underwent CPB. Among them, 9 subjects had an early postoperative infection, and 32 subjects were period-matched without infection. Inflammatory cytokines, serum CRP and PCT values were measured in plasma, additionally, circulating total leucocyte and lymphocyte subpopulations were counted. RESULTS: Infected subjects exhibited significantly higher levels of inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1ß and TNF-α, than non-infected subjects after CPB. Additionally, lower absolute number of lymphocyte and their subpopulations CD3+ T cells, CD4+ T-helper cells and CD8+cytotoxic T-cells, were observed in infected subjects. The impairment of T-cells Immune was found to be associated with higher levels of inflammatory cytokines IL-10. The ROC demonstrated that the absolute number of CD3+ T-cells <1934/ul, CD4+ T helper cells <1203/ul and CD8+cytotoxic T-cells <327/ul were associated with early postoperative infection. CONCLUSION: Higher levels of inflammatory cytokines resulted in T-cells lymphopenia after CPB, which significantly increasing the risk of postoperative infection in infants and young children. IMPACT: Infection complications after cardiopulmonary bypass (CPB) in pediatric CHD patients are serious issues, identifing the infection from after CPB remains a challenging. CPB can release numerous inflammatory cytokines associated with T cells lymphopenia, which increases the risk of postoperative infection after surgery. Monitoring T cells lymphopenia maybe more beneficial to predict early postoperative infection than C-reactive protein and procalcitonin.

Analysis of pathogenic variants in 605 Chinese children with non-syndromic cardiac conotruncal defects based on targeted sequencing.

OBJECTIVE: Deleterious genetic variants comprise one cause of cardiac conotruncal defects (CTDs). Genes associated with CTDs are gradually being identified. In the present study, we aimed to explore the profile of genetic variants of CTD-associated genes in Chinese patients with non-syndromic CTDs. METHODS: Thirty-nine CTD-related genes were selected after reviewing published articles in NCBI, HGMD, OMIM, and HPO. In total, 605 patients with non-syndromic CTDs and 300 healthy controls, all of Han ethnicity, were recruited. High-throughput targeted sequencing was used to detect genetic variants in the protein-coding regions of genes. We performed rigorous variant-level filtrations to identify potentially damaging variants (Dvars) using prediction programs including CADD, SIFT, PolyPhen-2, and MutationTaster. RESULT: Dvars were detected in 66.7% (26/39) of the targeted CTD-associated genes. In total, 11.07% (67/605) of patients with non-syndromic CTDs were found to carry one or more Dvars in targeted CTD-associated genes. Dvars in FOXH1, TBX2, NFATC1, FOXC2, and FOXC1 were common in the CTD cohort (1.5% [9/605], 1.2% [7/605], 1.2% [7/605], 1% [6/605], and 0.5% [3/605], respectively). CONCLUSION: Targeted exon sequencing is a cost-effective approach for the genetic diagnosis of CTDs. Our findings contribute to an understanding of the genetic architecture of non-syndromic CTDs.

Structure Characterization and Dye Adsorption Properties of Modified Fiber from Wheat Bran.

The fibers from four wheat varieties (FT, XW 26, XW 45, and KW 1701) were selected and chemically modified with NaOH, epichlorohydrin, and dimethylamine to improve the adsorption capacity for anionic dye. The structure of the fibers with or without modification was characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectrometry. The modified products were studied from the aspects of adsorption capacities, adsorption kinetics, and thermodynamics to provide a reference for the utilization of wheat bran. By SEM, more porous and irregular structures were found on the modified fibers. The XRD results showed that the crystals from the original fibers were destroyed in the modification process. The changes in fibers' infrared spectra before and after modification suggested that quaternary ammonium salts were probably formed in the modification process. The maximum adsorption capacity of wheat bran fibers for Congo red within 120 min was 20 mg/g for the unmodified fiber (XW 26) and 93.46 mg/g for the modified one (XW 45). The adsorption kinetics of Congo red by modified wheat bran fiber was in accord with the pseudo-second-order kinetic model at 40 °C, 50 °C, and 60 °C, indicating that the adsorption process might be mainly dominated by chemisorption. The adsorption was more consistent with the Langmuir isothermal adsorption model, implying that this process was monolayer adsorption. The thermodynamic parameters suggested that the adsorption occurred spontaneously, and the temperature increase was favorable to the adsorption. As mentioned above, this study proved that the wheat bran fiber could possess good adsorption capacities for anion dye after chemical modification.

The association of gestational age and birthweight with blood pressure, cardiac structure, and function in 4 years old: a prospective birth cohort study.

BACKGROUND: Current evidence relating birthweight and gestational age to cardiovascular risk is conflicting. Whether these factors have independent or interactive impacts on cardiovascular parameters during early childhood remains unclear. The goal of this study was to explore whether there were any independent and interactive effects of gestational age and birthweight on blood pressure, left ventricle (LV) structure, and function in 4 years old. METHODS: This study included 1194 children in the Shanghai Birth Cohort from 2013 to 2016. Information about the mothers and children was recorded at time of birth using a questionnaire. Follow-up measurements, including anthropometric, blood pressure, and echocardiography, were taken between 2018 and 2021, when the children were 4 years old. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of birthweight and gestational age with cardiovascular measurements. RESULTS: Gestational age had a significant negative correlation with both systolic blood pressure [ß = - 0.41, 95% CI: (- 0.76, - 0.07)] and mean arterial pressure [ß = - 0.36, 95%CI: (- 0.66, - 0.07)]. The risk of prehypertension decreased with increased gestational age [OR = 0.54, 95% CI: (0.32, 0.93)]. The relationship between birthweight with blood pressure was U-shape (P for non-linear < 0.001). The wall thickness, volume, mass, and cardiac output of LV increased with birthweight, though the ejection fraction [ß = - 1.02, 95% CI: (- 1.76, - 0.27)] and shorten fraction [ß = 0.72, 95% CI: (- 1.31, - 0.14)] decreased with birthweight. The risk of LV hypertrophy was not associated with birthweight [OR = 1.59, 95% CI: (0.68, 3.73)]. CONCLUSIONS: In this study, we found different associations of birthweight and gestational age with cardiovascular measurements in the offspring at 4 years old. Gestational age influenced blood pressure independent of birthweight. Heart size and function at 4 years old was influenced mostly by birthweight and not by gestational age.

Tumor necrosis factor-α stimulation endothelial-to-mesenchymal transition during cardiac fibrosis via endothelin-1 signaling.

Cardiac fibrosis is an important pathological change after myocardial infarction (MI). High concentration of tumor necrosis factor-α (TNF-α) contributes to cardiac fibrosis, and TNF-α has been demonstrated to be involved in transforming growth factor-ß1-induced endothelial-to-mesenchymal transition (EndMT). However, the role and molecular mechanisms of TNF-α during cardiac fibrosis remain largely unexplored. In this study, we demonstrated that TNF-α and endothelin-1 (ET-1) were upregulated in cardiac fibrosis after MI, and genes associated with EndMT were also upregulated. An in vitro model of EndMT demonstrated that TNF-α promoted EndMT by upregulation of vimentin and α-smooth muscle actin, and which strongly increased ET-1 expression. ET-1 promoted TNF-α-induced expression of gene program through phosphorylation levels of SMAD family member 2, while subsequent inhibition of ET-1 almost abolished the effect of TNF-α during the process of EndMT. In summary, these findings demonstrated that ET-1 is involved in the EndMT induced by TNF-α during cardiac fibrosis.

pH-responsive dual-enzyme mimics based on hollow metal organic framework-derivatives ß-Co(OH)2 for multiple colorimetric assays.

A hollow metal organic framework derivative ß-Co(OH)2 has been prepared, which possesses oxidase and peroxidase-like activities. Oxidase-like activity is derived from the generation of free radicals, and peroxidase-like activity is related to the electron transfer process. Unlike other nanozymes with dual enzyme-like activities, ß-Co(OH)2 possesses pH-responsive enzyme-like activities, among which the ß-Co(OH)2 exhibits superior oxidase and peroxidase-like activities under pH of 4 and 6, respectively, which could avoid mutual interference between multiple enzymes. Based on the phenomenon that enzyme-like activities of ß-Co(OH)2 can catalyze colorless TMB to generate blue oxidized TMB (oxTMB) with absorption peak at 652 nm, the sensors integrating total antioxidant capacity and H2O2 quantification were developed. The oxidase-like activity-based colorimetric system has a sensitive response to ascorbic acid, Trolox, and gallic acid, in which the limit of detection for those antioxidant substances was 0.54 µM, 1.26 µM, and 14.34 µM, respectively. The sensors based on peroxidase-like activity had low limit of detection of 1.42 µM for H2O2 and a linear range of 5-1000 µM. The proposed method can be well applied to the detection of the total antioxidant capacity of kiwi, Vc tables, orange and tea extract with high accuracy, and H2O2 determination in milk and glucose detection in beverages with satisfactory recovery (within 97-106%).

Silver nanoparticles deposited carbon microspheres nanozyme with enhanced peroxidase-like catalysis for colorimetric detection of Hg2+ in seafood.

Novel methods for high-performance detection of Hg2+ in seafood are critical for ensuring food safety and human health. Herein, Ag nanoparticles (Ag NPs) were successfully deposited on carbon microspheres (CMs) to form Ag NPs-CMs nanocomplex. The proposed Ag NPs-CMs could oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidation state TMB (oxTMB) in the presence of hydrogen peroxide (H2O2) and had a significant UV-vis absorption peak at 652 nm. The excellent peroxidase-like activity was attributed to the increased electrostatic attraction of CMs and the catalytic synergistic effect. After adding Hg2+, the catalytic activity of Ag NPs-CMs was specifically enhanced and the Michaelis-Menten constant (Km) decreased from 0.067 to 0.052 mmol/L due to the formation of Ag-Hg amalgam which produced more superoxide anions (O2•-) and hydroxyl radicals (•OH). The linear response ranges for Hg2+ were 2~833 nmol/L and 2.5~40 µmol/L, with the low detection limit of 1.10 nmol/L. This method was applied to detect Hg2+ in seafood with satisfactory recoveries of 95.65~106.56%. A hydrogel kit was designed for portable detection of Hg2+, and the response range was 0.5~5 µmol/L. This work provides a reliable method for visual Hg2+ detection in seafood as well as a feasible strategy for the design of high-performance nanozymes.

SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma.

Pulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

The impact of nucleic acid testing to detect human immunodeficiency virus, hepatitis C virus, and hepatitis B virus yields from a single blood center in China with 10-years review.

BACKGROUND: Since 2010, the Blood Center of Zhejiang province, China, has conducted a pilot nucleic acid amplification testing (NAT) screening of blood donors for Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV). This study aims to assess the results of NAT testing over 10 years to establish the effects and factors influencing NAT yields of HBV, HCV, and HIV. METHODS: Blood donations from seven different blood services were screened for HBV DNA, HCV RNA, and HIV RNA using 6 mini pools (6MP) or individual donation (ID)-NAT method between August 1, 2010, and December 31, 2019, at the NAT centralized screening center. We compared 3 transcription-mediated amplification (TMA) assays and 2 polymerase chain reaction (PCR) assays. Further, HBV, HCV, and HIV NAT yields were calculated and donor characteristics and prevalence of HBV NAT yields analyzed. Donors with HCV and HIV NAT yield were also followed up. RESULTS: 1916.31 per million donations were NAT screening positive overall. The NAT yields for HBV, HCV, HIV and non-discriminating reactive were 1062.90 per million, 0.97 per million, 1.45 per million, and 850.99 per million, respectively, which varied in the seven blood services and different years. HBV NAT yields were higher than those of HCV and HIV and varied across demographic groups. Risk factors included being male, old age, low education level, and first-time donors. We found no differences in NAT yields of HBV, HCV, and HIV between the 3 TMA and 2 PCR assays; nonetheless, statistically, significant differences were noted between the five assays. CONCLUSION: In summary, NAT screening in blood donations reduces the risk of transfusion-transmitted infections and shortens the window period for serological marker screening. Therefore, a sensitive NAT screening method, ID-NAT workflow, and recruitment of regular low-risk donors are critical for blood safety.

PEX1 is a mediator of α1-adrenergic signaling attenuating doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a potent chemotherapeutic agent used for cancer treatment, however, DOX-induced cardiotoxicity is a serious clinical problem because it causes acute and chronic heart dysfunction. Many studies have indicated that the α1-adrenergic receptor protects the heart from pathologic stress through activation survival signaling, however, the mechanism remains largely unknown. Previous studies have detected that the phenylephrine-induced complex-1 (PEX1) transcription factor, also known as zinc-finger protein 260 (Zfp260), is an effector of α1-adrenergic signaling in cardiac hypertrophy. Our present study aimed to investigate the role and underlying mechanism of PEX1 in cardiomyocyte survival during DOX-induced cardiotoxicity. Mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. We found that PEX1 expression was downregulated in DOX-treated murine hearts. PEX1 deficiency resulted in increased apoptosis, and conversely, PEX1 overexpression alleviated apoptosis induced by DOX in primary cardiomyocytes, as well as upregulated antiapoptotic genes such as BCL-2 and BCL-XL. Mechanistically, we identified that PEX1 might exert its antiapoptosis effect by playing a pivotal role in the action of α1-adrenergic signaling activation, which depends on the presence of GATA-4. Based on these findings, we supposed that PEX1 may be a novel transcription factor involved in cardiac cell survival and a promising candidate target for DOX-induced cardiotoxicity.

Evaluation of acute kidney injury by urinary tissue inhibitor metalloproteinases-2 and insulin-like growth factor-binding protein 7 after pediatric cardiac surgery.

BACKGROUND: With adult patients, the measurement of [TIMP-2]*[IGFBP7] can predict the risk of moderate to severe AKI within 12 h of testing. In pediatrics, however, the performance of [TIMP-2]*[IGFBP7] as a predictor of AKI was less studied and yet to be widely utilized in clinical practice. This study was conducted to validate the utility of [TIMP-2]*[IGFBP7] as an earlier biomarker for AKI prediction in Chinese infants and small children. METHODS: We measured urinary [TIMP-2]*[IGFBP7] using NEPHROCHECK® at eight perioperative time points in 230 patients undergoing complex cardiac surgery and evaluated the performance of [TIMP-2]*[IGFBP7] for predicting severe AKI within 72 h of surgery. RESULTS: A total of 50 (22%) of 230 developed AKI stages 2-3 within 72 h after CPB initiation. In the AKI stage 2-3 patients, two patterns of serum creatinine (SCr) elevations were observed. The patients with only a transient increase in SCr within 24 h (< 24 h, early AKI 2-3) did not experience a worse outcome than patients in AKI stage 0-1. AKI stage 2-3 patients with SCr elevation after 24 h (24-72 h, late AKI 2-3), as well as AKI dialysis patients (together designated severe AKI), did experience worse outcomes. Compared to AKI stages 0-1, significant elevations of [TIMP-2]*[IGFBP7] values were observed in severe AKI patients at hours T2, T4, T12, and T24 following CPB initiation. The AUC for predicting severe AKI with [TIMP-2]*[IGFBP7] at T2 (AUC = 0.76) and maximum T2/T24 (AUC = 0.80) are higher than other time points. The addition of the NEPHROCHECK® test to the postoperative parameters improved the risk assessment of severe AKI. CONCLUSIONS: Multiple AKI phenotypes (early versus late AKI) were identified after pediatric complex cardiac surgery according to SCr-based AKI definition. Urinary [TIMP-2]*[IGFBP7] predicts late severe AKI (but not early AKI) as early as 2 h following CPB initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Human activities have opposing effects on distributions of narrow-ranged and widespread plant species in China.

Human activities have shaped large-scale distributions of many species, driving both range contractions and expansions. Species differ naturally in range size, with small-range species concentrated in particular geographic areas and potentially deviating ecologically from widespread species. Hence, species' responses to human activities may be influenced by their geographic range sizes, but if and how this happens are poorly understood. Here, we use a comprehensive distribution database and species distribution modeling to examine if and how human activities have affected the extent to which 9,701 vascular plants fill their climatic potential ranges in China. We find that narrow-ranged species have lower range filling and widespread species have higher range filling in the human-dominated southeastern part of China, compared with their counterparts distributed in the less human-influenced northwestern part. Variations in range filling across species and space are strongly associated with indicators of human activities (human population density, human footprint, and proportion of cropland) even after controlling for alternative drivers. Importantly, narrow-ranged and widespread species show negative and positive range-filling relationships to these human indicators, respectively. Our results illustrate that floras risk biotic homogenization as a consequence of anthropogenic activities, with narrow-ranged species becoming replaced by widespread species. Because narrow-ranged species are more numerous than widespread species in nature, negative impacts of human activities will be prevalent. Our findings highlight the importance of establishing more protected areas and zones of reduced human activities to safeguard the rich flora of China.

Carbon dots@Cu metal-organic frameworks hybrids for ratiometric fluorescent determination of pesticide thiophanate-methyl.

A dual-emission fluorescent (FL) probe was constructed by coordinating Cu2+ of copper metal-organic frameworks (Cu-MOFs) with - COO- group of carbon dots (CDs) for pesticide thiophanate-methyl (TM) determination. TM was recognized by organic ligands (H2BDC and H2BDC-NH2) of Cu-MOFs via π stacking. Due to the higher affinity of Cu2+ to TM than ligands and CDs, TM chelated with Cu2+ to form TM-Cu complex. Thus coordination of Cu-MOFs was damaged and the ligands were released resulting in the FL intensity increase of Cu-MOFs (F430). And also CDs were released from CDs@Cu-MOFs hybrids and electron transfer from CDs to CuMOFs was inhibited, leading to the FL intensity increase of CDs (F600). The FL intensity ratio (F430/F600) showed a good linear relationship with TM concentrations of 0.0307-0.769 µmol L-1 with a limit of detection (LOD) of ~ 3.67 nmol L-1. The probe was successfully applied to detect TM in spiked food samples with satisfactory recoveries of 93.1-113%. Additionally, visual detection of TM was achieved according to the fluorescence color variation from blue to carmine, indicating promising application of CDs@Cu-MOFs probe.

Avilamycin production enhancement by mutagenesis and fermentation optimization in Streptomyces viridochromogenes.

Avilamycin, an excellent growth-promoting feed additive, produced by Streptomyces viridochromogenes, was widely used to promote the growth of poultry by inhibiting Gram-positive bacteria. In this work, the methods of combinational mutagenesis of UV (Ultraviolet) and ARTP (Atmospheric and room temperature plasma), and rational screening by high concentrations of CaCl2 were utilized to promote the production of avilamycin. The avilamycin high-yielding mutant strains of Z-6 (29.31 mg/L), A-9 (36.84 mg/L) and F-23 (45.73 mg/L) were screened out, with yields of avilamycin improved by 57.92%, 98.49% and 146.39%, respectively, compared with the wild strain (WT). The performance comparison showed that Z-6, A-9 and F-23 mutant strains had stronger abilities of substrate consumption, cell growth and antibiotic synthesis than WT. Furthermore, the composition of fermentation medium, inoculation parameters, supplementation strategies of oxygen vectors, glucose and precursors (L-valine, D-xylose and sodium acetate) had been optimized and the avilamycin yield of the mutant strain F-23 was significantly enhanced by 41.87% by fermentation optimization. In summary, the strategy of increasing the production of avilamycin in S. viridochromogenes in this work might provide an alternative method to enhance the synthesis of secondary metabolites in other Streptomyces.

Characteristic of HBV nucleic acid amplification testing yields from blood donors in China.

BACKGROUND: Nucleic acid amplification testing (NAT) for blood screening has been previously performed in some countries to determine NAT yields. The current study sought to explore the non-discriminating reactive NAT yields using individual-NAT (ID-NAT) and characteristics of HBV NAT yields through a 10-year retrospective analysis in Zhejiang, China. METHODS: Blood donations were analyzed using individual-NAT mode by the transcription-mediated amplification (TMA) method. Supplementary HBV serological tests were performed using chemiluminescent immunoassay, and HBV viral load assay was performed by real-time polymerase chain reaction. Follow-up studies were performed in partial donors with low HBV viral loads. RESULTS: Non-discriminating reactive NAT yields and HBV NAT yields varied in different years. The yields ranged from 853.73 per million to 2018.68 per million and 624.60 per million to 1669.50 per million, respectively. In the 476 NAT yields, 19 were probable window periods (WP), 33 probable occult hepatitis B virus infections (OBIs), 409 were confirmed OBIs and 15 were chronic HBV infections. ID-NAT results were categorized in four groups, and the findings showed that the levels of HBV DNA viral loads were different in the four different groups (χ2 = 275.02, p < 0.01). HBV viral load distribution was significantly different between anti-HBs positive and anti-HBc positive samples (χ2 = 49.429, p < 0.01). Notably, only 42.03% donors were NAT repeated positive in the 138 repeat donors' follow up tests. CONCLUSION: NAT screening of blood donations can reduce the risk of transfusion-transmitted HBV infections. Positive proportions of anti-HBs and anti-HBc are correlated with the HBV viral load level. However, low level of viral load donors pose risks in HBV NAT assays, and show fluctuating state for HBV viral load and leads to non-repeated NAT results during follow up studies.

Immunity improvement and gut microbiota remodeling of mice by wheat germ globulin.

The wheat germ protein (WG) and it's proteolytic peptide have a variety of biological activities. Our previous work showed that WG could improve immunity of the immunosuppressive mice established by cyclophosphamide. However, in the healthy condition and normal diet, as a supplementary food, the effects of immunity improvement and gut microbiota remodeling by the wheat germ globulin has not been studied yet. Here, we reported that WG could improve the immunity and remodel the gut microbiota of the mice, as a potentially safe functional supplementary food for the first time. The increase of interleukin-6 (IL-6) and the decrease of tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10) indicated that WG could enhance the levels of activated T cells and monocytes and anti-inflammatory ability, meanwhile, the significant increase of immunoglobin G (lgG) and the notable decrease of the immunoglobin M (lgM) and immunoglobin A (lgA) illustrated that WG could improve immunity by promoting the differentiation and maturation process of B cells, compared with the NC group (normal control group). 16S rRNA sequencing showed WG could remodel the gut microbiota. At the phylum level, the Bacteroidetes were reduced and Firmicutes were increased in WG group, compared with NC group. At the genus level, the SCFA producing genera of unclassified_f_Lachnospiraceae, Blautia and especially the Roseburia (increased more than threefold) increased notably. Further, the level changes of cytokines and immunoglobulins were associated with the gut microbiota. This work showed that WG could improve immunity and has potential application value as an immune-enhancing functional food.

[Type of sperm DNA strand breaks in infertile men and its clinical implication].

OBJECTIVE: To observe the characteristics of sperm single-stranded DNA breaks (SSB) and double-stranded DNA breaks (DSB) in infertile men, explore the association of DSB with male infertility, and provide a new observation index and idea for the diagnosis and treatment of the disease. METHODS: This study involved 60 infertile men (infertility group) and 30 normal healthy males with infertile wives (control group). We comparatively analyzed the seminal parameters of the two groups, determined sperm concentration and viability using the computer aided sperm analysis system, measured the sperm survival rate by hypoosmotic swelling (HOS) test, examined sperm morphology by Diff-Quick staining, and detected sperm DNA damage by two-tail comet assay. RESULTS: Nine two-tail comet models were established for detecting sperm DNA integrity. Comparisons between the fertility and control groups showed that the sperm DNA fragmentation index (DFI) was (33.8 ± 13.1) vs (16.3 ± 7.9)% (P < 0.01), the SSB-DFI was (19.2 ± 11.4) vs (14.9 ± 7.6)% (P > 0.05), the SSB-DFI/DFI was (56.8 ± 32.4) vs (91.4 ± 27.8)% (P < 0.01), the DSB-DFI was (23.9 +13.4) vs (6.1 ± 2.7)% (P < 0.01), and the DSB-DFI/DFI was (70.8 ± 19.5) vs (37.4 ± 11.3)% (P < 0.01). The optimal cut-off value of DSB-DFI/DFI in the diagnosis of male infertility was 39.5%, with the AUG, sensitivity, and specificity of 0.969, 98.3%, and 90%; that of DSB-DFI was 15.85%, with the AUC, sensitivity, and specificity of 0.912, 86.7%, and 80%; and that of DFI was 18.65%; with the AUC, sensitivity, and specificity of 0.861, 90%, 70%, respectively. In the infertile men, neither SSB-DFI nor SSB-DFI/DFI exhibited any correlation with semen parameters (P > 0.05); DFI was correlated negatively with the percentage of progressively motile sperm, sperm survival rate, and the percentage of morphologically normal sperm (P < 0.05 or P < 0.01), but not correlated with sperm concentration (P > 0.05); both DSB-DFI and DSB-DFI/DFI showed a negative correlation with sperm concentration, sperm survival rate, and the percentages of progressively motile sperm and morphologically normal sperm (P < 0.05 or P < 0.01). CONCLUSION: Double-stranded, rather than single-stranded DNA breaks, may be a factor inducing male infertility. The type of sperm DNA strand damage is of much reference value for the assessment of male fertility.

Effects of heat-moisture treatment on structural characteristics and in vitro digestibility of A- and B-type wheat starch.

In this study, A- and B-type wheat starch granules (AWS and BWS) were separated and modified by heat-moisture treatment (HMT) with different moisture content (10 %-40 %). The effects of HMT on the structure characteristics and digestibility of raw/cooked AWS and BWS were investigated by SEM, FT-IR, XRD, DSC, TGA and NMR. SEM and FT-IR results showed that BWS was more sensitive to HMT than AWS. Interestingly, crystalline conformation of AWS and BWS changed from A type to A + V type after HMT, and the relative crystallinity (V-type) of starch increased to 2.7 % and 3.4 %, respectively. XRD and NMR results verified the formation of V-type crystalline structure. The resistant starch (RS) content of cooked starch was increased, especially for BWS (from 11.46 % to 28.29 %). Compared to the cooked starch, the RS content of raw AWS and BWS was affected by relative crystallinity and the size of starch granules. Furthermore, structure characteristics and digestion kinetics results indicated that the digestion rate of cooked AWS increased due to the deconstruction of starch chains, opposite to BWS (because of the more V-type crystals). The results enrich our understanding of the mechanism of digestion subjected to HMT by different grain sizes of the same wheat starch.