Diminished antiviral innate immune gene expression in the placenta following a maternal SARS-CoV-2 infection.

BACKGROUND: COVID-19 is caused by the SARS-CoV-2 virus and is associated with critical illness requiring hospitalization, maternal mortality, stillbirth, and preterm birth. SARS-CoV-2 has been shown to induce placental pathology. However, substantial gaps exist in our understanding of the pathophysiology of COVID-19 disease in pregnancy and the long-term impact of SARS-CoV-2 on the placenta and fetus. To what extent a SARS-CoV-2 infection of the placenta alters the placental antiviral innate immune response is not well understood. A dysregulated innate immune response in the setting of maternal COVID-19 disease may increase the risk of inflammatory tissue injury or placental compromise and may contribute to deleterious pregnancy outcomes. OBJECTIVE: We sought to determine the impact of a maternal SARS-CoV-2 infection on placental immune response by evaluating gene expression of a panel of 6 antiviral innate immune mediators that act as biomarkers of the antiviral and interferon cytokine response. Our hypothesis was that a SARS-CoV-2 infection during pregnancy would result in an up-regulated placental antiviral innate immune response. STUDY DESIGN: We performed a case-control study on placental tissues (chorionic villous tissues and chorioamniotic membrane) collected from pregnant patients with (N=140) and without (N=24) COVID-19 disease. We performed real-time quantitative polymerase chain reaction and immunohistochemistry, and the placental histopathology was evaluated. Clinical data were abstracted. Fisher exact test, Pearson correlations, and linear regression models were used to examine proportions and continuous data between patients with active (<10 days since diagnosis) vs recovered COVID-19 (>10 days since diagnosis) at the time of delivery. Secondary regression models adjusted for labor status as a covariate and evaluated potential correlation between placental innate immune gene expression and other variables. RESULTS: SARS-CoV-2 viral RNA was detected in placental tissues from 5 women with COVID-19 and from no controls (0/24, 0%). Only 1 of 5 cases with detectable SARS-CoV-2 viral RNA in placental tissues was confirmed to express SARS-CoV-2 nucleocapsid and spike proteins in syncytiotrophoblast cells. We detected a considerably lower gene expression of 5 critical innate immune mediators (IFNB, IFIT1, MXA, IL6, IL1B) in the chorionic villi and chorioamniotic membranes from women with active or recovered COVID-19 than controls, which remained significant after adjustment for labor status. There were minimal correlations between placental gene expression and other studied variables including gestational age at diagnosis, time interval between COVID-19 diagnosis and delivery, prepregnancy body mass index, COVID-19 disease severity, or placental pathology. CONCLUSION: A maternal SARS-CoV-2 infection was associated with an impaired placental innate immune response in chorionic villous tissues and chorioamniotic membranes that was not correlated with gestational age at COVID-19 diagnosis, time interval from COVID-19 diagnosis to delivery, maternal obesity, disease severity, or placental pathology.

Salmonella SiiE prevents an efficient humoral immune memory by interfering with IgG+ plasma cell persistence in the bone marrow.

Serum IgG, which is mainly generated from IgG-secreting plasma cells in the bone marrow (BM), protects our body against various pathogens. We show here that the protein SiiE of Salmonella is both required and sufficient to prevent an efficient humoral immune memory against the pathogen by selectively reducing the number of IgG-secreting plasma cells in the BM. Attenuated SiiE-deficient Salmonella induces high and lasting titers of specific and protective Salmonella-specific IgG and qualifies as an efficient vaccine against Salmonella A SiiE-derived peptide with homology to laminin ß1 is sufficient to ablate IgG-secreting plasma cells from the BM, identifying laminin ß1 as a component of niches for IgG-secreting plasma cells in the BM, and furthermore, qualifies it as a unique therapeutic option to selectively ablate IgG-secreting plasma cells in autoimmune diseases and multiple myeloma.

CIM-Based Smart Pose Detection Sensors.

The majority of digital sensors rely on von Neumann architecture microprocessors to process sampled data. When the sampled data require complex computation for 24×7, the processing element will a consume significant amount of energy and computation resources. Several new sensing algorithms use deep neural network algorithms and consume even more computation resources. High resource consumption prevents such systems for 24×7 deployment although they can deliver impressive results. This work adopts a Computing-In-Memory (CIM) device, which integrates a storage and analog processing unit to eliminate data movement, to process sampled data. This work designs and evaluates the CIM-based sensing framework for human pose recognition. The framework consists of uncertainty-aware training, activation function design, and CIM error model collection. The evaluation results show that the framework can improve the detection accuracy of three poses classification on CIM devices using binary weights from 33.3% to 91.5% while that on ideal CIM is 92.1%. Although on digital systems the accuracy is 98.7% with binary weight and 99.5% with floating weight, the energy consumption of executing 1 convolution layer on a CIM device is only 30,000 to 50,000 times less than the digital sensing system. Such a design can significantly reduce power consumption and enables battery-powered always-on sensors.

Natural Dietary and Herbal Products in Anti-Obesity Treatment.

The prevalence of overweight and obesity is on the rise around the world. Common comorbidities associated with obesity, particularly diabetes, hypertension, and heart disease have an impact on social and financial systems. Appropriate lifestyle and behavior interventions are still the crucial cornerstone to weight loss success, but maintaining such a healthy lifestyle is extremely challenging. Abundant natural materials have been explored for their obesity treatment potential and widely used to promote the development of anti-obesity products. The weight loss segment is one of the major contributors to the overall revenue of the dietary supplements market. In this review, the anti-obesity effects of different dietary or herbal products, and their active ingredients and mechanisms of action against obesity will be discussed.

Improvement in antioxidant activity, angiotensin-converting enzyme inhibitory activity and in vitro cellular properties of fermented pepino milk by Lactobacillus strains containing the glutamate decarboxylase gene.

BACKGROUND: The purpose of this study was to evaluate the functional potential of fermented pepino extract (PE) milk by Lactobacillus strains containing the glutamate decarboxylase (GAD) gene. Three Lactobacillus strains were selected, including L. brevis BCRC 12310, L. casei BCRC 14082 and L. salivarius subsp. salivarius BCRC 14759. The contents of free amino acids, total phenolics content, total carotenoids and the associated functional and antioxidant abilities were analyzed, including angiotensin-converting enzyme (ACE) inhibition activity, 1,1-diphenyl-2-picylhydrazyl (DPPH) radical-scavenging ability and oxygen radical absorbance capacity (ORAC). Cell proliferation of fermented PE milk was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RESULTS: Compared to the unfermented PE, fermented PE milk from Lactobacillus strains with the GAD gene showed higher levels of total phenolics, γ-aminobutyric acid, ACE inhibitory activity, DPPH, and ORAC. The viability of human promyelocytic leukemia cells (HL-60) determined by the MTT method decreased significantly when the cells were incubated with the PE and the fermented PE milk extracts. CONCLUSION: The consumption of fermented PE milk from Lactobacillus strains with the GAD gene is expected to benefit health. Further application as a health food is worthy of investigation. © 2012 Society of Chemical Industry.

Balance of photon management and charge collection from carbon-quantum-dot layers as self-powered broadband photodetectors.

Semiconductor colloidal quantum dots (QDs) have been regarded as promising fluorescent materials for chemical sensing, bio-detection and optical communications; yet it still remains challenging to bring out self-powered photodetectors based solely on QDs because the excited charges within QDs are extremely immobile due to their reduced dimensionalities and they hardly form effective photocurrents. Hence, we have attempted to decouple the light-absorption and charge-transport criteria in order to feature highly-sensitive, rapid-response and self-driven photodetectors based on single-layer carbon QD layers (CQDLs) via facile in situ self-assembling deposition with fine control over thickness. We show explicit dark-current suppression by visualizing charge blocking phenomena and screen effects due to layered CQDL structures, which alleviate the movement of leakage carriers crossing over the CQD interlayers. By examining the distribution of electric fields within CQDLs under light excitation, the spatial dependence of the light-trapping effect within CQDLs was confirmed. These features are strongly associated with the thickness tuning of CQDLs, while 65 nm of CQDL thickness could manifest remarkable photoresponsivity above 9.4 mA W-1 and detectivity above 5.9 × 1012 under broadband light illumination. These results demonstrate the insights gained from an understanding of broadband optoelectronics, which might potentially pave the way for further employment in functional photodetection.

Delaminated MnPS3 with Multiple Layers Coupled with Si Featuring Ultrahigh Detectivity and Environmental Stability for UV Photodetection.

Silicon (Si), the dominant semiconductor in microelectronics yet lacking optoelectronic functionalities in UV regions, has been researched extensively to make revolutionary changes. In this study, the inherent drawback of Si on optoelectronic functionalities in UV regions is potentially overcome through heterostructure coupling of delaminated p-type MnPS3, having bulk, multiple-layer, and few-layer features, with n-type Si. By artificially mimicking the architectures of shrubs with unique UV shading phenomena, the revolutionary multiple-layer MnPS3 structures with staggered stacking configurations trigger outstanding UV photosensing performances, displaying an average EQE value of 1.1 × 103%, average photoresponsivity of 3.1 × 102 A/W, average detectivity of 1.9 × 1014 cm Hz1/2W1-, and average on/off ratio of 1.8 × 103 under 365 nm light. To the best of our knowledge, this is the first attempt toward realizing gate-free MnPS3-based UV photodetectors, while all of the photodetection outcomes are better than those of more sophisticated field-effect transistor (FET) designs, which have remarkable impacts on the practicality and functionality of next-generation UV optoelectronics.

Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates.

Invasive bacterial infections during pregnancy are a major risk factor for preterm birth, stillbirth, and fetal injury. Group B streptococci (GBS) are Gram-positive bacteria that asymptomatically colonize the lower genital tract but infect the amniotic fluid and induce preterm birth or stillbirth. Experimental models that closely emulate human pregnancy are pivotal for the development of successful strategies to prevent these adverse pregnancy outcomes. Using a unique nonhuman primate model that mimics human pregnancy and informs temporal events surrounding amniotic cavity invasion and preterm labor, we show that the animals inoculated with hyaluronidase (HylB)-expressing GBS consistently exhibited microbial invasion into the amniotic cavity, fetal bacteremia, and preterm labor. Although delayed cytokine responses were observed at the maternal-fetal interface, increased prostaglandin and matrix metalloproteinase levels in these animals likely mediated preterm labor. HylB-proficient GBS dampened reactive oxygen species production and exhibited increased resistance to neutrophils compared to an isogenic mutant. Together, these findings demonstrate how a bacterial enzyme promotes GBS amniotic cavity invasion and preterm labor in a model that closely resembles human pregnancy.IMPORTANCE Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury. Understanding how GBS evade host defenses during pregnancy is key to developing improved preventive therapies for these adverse outcomes. In this study, we used a unique nonhuman primate model to show that an enzyme secreted by GBS, hyaluronidase (HylB) promotes bacterial invasion into the amniotic cavity and fetus. Although delayed immune responses were seen at the maternal-fetal interface, animals infected with hyaluronidase-expressing GBS exhibited premature cervical ripening and preterm labor. These observations reveal that HylB is a crucial GBS virulence factor that promotes bacterial invasion and preterm labor in a pregnancy model that closely emulates human pregnancy. Therefore, hyaluronidase inhibitors may be useful in therapeutic strategies against ascending GBS infection.

Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence.

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and ß-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

Enhanced thermal stability of green banana starch by heat-moisture treatment and its ability to reduce body fat accumulation and modulate gut microbiota.

The physicochemical properties (including morphology, pasting, and thermal properties) of resistant starch (RS) in green banana starch were analyzed after the heat-moisture treatment in the presence of citric acid (CAHMT) at different temperatures. Moreover, this study evaluated whether the administration of CAHMT banana starch could reduce body fat accumulation and modulate gut microbiota. Our results demonstrated that the CAHMT process (90 °C) resulted in a higher retention (80.9%) and thermal stability of RS, alteration in the crystalline structure of starch from B-type to A-type, and increased solubility (27.9-fold) and gelatinization temperatures (from 66.26-78.89 °C to 81.48-92.11 °C). A reduction in swelling power (-57.7%) and a loss of pasting viscosity were also noted. Even after a 30 min boil, the retention rate of residual RS (CAHMT at 90 °C) was up to 50% (4.3-fold higher than the control). Rats fed the CAHMT banana starch resulted in significantly (p < 0.05) lower total visceral fat (-18.1%) and Firmicutes to Bacteroidetes ratio as well as higher total fecal short chain fatty acids. The CAHMT process at 90 °C enhanced the thermal stability of banana RS allowing a wider range of applications in functional foods.

A Broad Spectrum Chemokine Inhibitor Prevents Preterm Labor but Not Microbial Invasion of the Amniotic Cavity or Neonatal Morbidity in a Non-human Primate Model.

Leukocyte activation within the chorioamniotic membranes is strongly associated with inflammation and preterm labor (PTL). We hypothesized that prophylaxis with a broad-spectrum chemokine inhibitor (BSCI) would downregulate the inflammatory microenvironment induced by Group B Streptococcus (GBS, Streptococcus agalactiae) to suppress PTL and microbial invasion of the amniotic cavity (MIAC). To correlate BSCI administration with PTL and MIAC, we used a unique chronically catheterized non-human primate model of Group B Streptococcus (GBS)-induced PTL. In the early third trimester (128-138 days gestation; ~29-32 weeks human pregnancy), animals received choriodecidual inoculations of either: (1) saline (N = 6), (2) GBS, 1-5 × 108 colony forming units (CFU)/ml; N = 5), or (3) pre-treatment and daily infusions of a BSCI (10 mg/kg intravenous and intra-amniotic) with GBS (1-5 × 108 CFU/ml; N = 4). We measured amniotic cavity pressure (uterine contraction strength) and sampled amniotic fluid (AF) and maternal blood serially and cord blood at delivery. Cesarean section was performed 3 days post-inoculation or earlier for PTL. Data analysis used Fisher's exact test, Wilcoxon rank sum and one-way ANOVA with Bonferroni correction. Saline inoculation did not induce PTL or infectious sequelae. In contrast, GBS inoculation typically induced PTL (4/5, 80%), MIAC and fetal bacteremia (3/5; 60%). Remarkably, PTL did not occur in the BSCI+GBS group (0/4, 0%; p = 0.02 vs. GBS), despite MIAC and fetal bacteremia in all cases (4/4; 100%). Compared to the GBS group, BSCI prophylaxis was associated with significantly lower cytokine levels including lower IL-8 in amniotic fluid (p = 0.03), TNF-α in fetal plasma (p < 0.05), IFN-α and IL-7 in the fetal lung (p = 0.02) and IL-18, IL-2, and IL-7 in the fetal brain (p = 0.03). Neutrophilic chorioamnionitis was common in the BSCI and GBS groups, but was more severe in the BSCI+GBS group with greater myeloperoxidase staining (granulocyte marker) in the amnion and chorion (p < 0.05 vs. GBS). Collectively, these observations indicate that blocking the chemokine response to infection powerfully suppressed uterine contractility, PTL and the cytokine response, but did not prevent MIAC and fetal pneumonia. Development of PTL immunotherapies should occur in tandem with evaluation for AF microbes and consideration for antibiotic therapy.

Changes in physicochemical properties of corn starch upon modifications by atmospheric pressure plasma jet.

The influences of atmospheric pressure plasma jet on different physicochemical properties of corn starch were evaluated after treated with the plasma jet (30 min) at different strengths (400 W-800 W). Our results demonstrated that residual aging effects of plasma on starch could be eliminated by washing the treated samples with distilled water at a ratio of 1:30, w/v. After plasma and washing treatments, significant (p < 0.05) reductions in pasting properties including peak viscosity, final viscosity, and setback of starch samples (up to -87.1%, -92.0%, and -93.3%, respectively) were observed with increasing plasma intensity. Apparently, plasma jet could increase the solubility and paste clarity of starch sample. Surface morphological characterization illustrated that plasma etching resulted in some physical changes on starch granules. Modifications in these physicochemical properties of corn starch by employing the plasma jet treatment might be useful in food applications requiring starch ingredients of low viscosity and high paste clarity.

Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location.

CD4 T cell memory is fundamental for long-lasting immunity and effective secondary responses following infection or vaccination. We have previously found that memory CD4 T cells specific for systemic antigens preferentially reside in the bone marrow (BM) and arise from splenic CD49b+T-bet+ CD4 T cells. However, how BM-homing memory precursors are generated during an immune reaction is unknown. We show here that BM memory precursors are generated via augmented rates of cell division throughout a primary immune response. Treatment with the cytostatic drug cyclophosphamide or blockade of the CD28/B7 co-stimulatory pathway at the beginning of the contraction phase abrogates the generation of BM memory precursors. We determine that, following a critical number of cell divisions, memory precursors downregulate CCR7 and upregulate IL-2Rß, indicating that loss of CCR7 and gain of IL-2 signal are required for the migration of memory precursors toward the BM.

Application of corona electrical discharge plasma on modifying the physicochemical properties of banana starch indigenous to Taiwan.

Corona electrical discharge (CED) belongs to an atmospheric pressure cold plasma. In this study, raw banana starch (indigenous to Taiwan), which contained resistant starch and amylose at a level of 58.4 g/100 g and 14.5 g/100 g, respectively, was treated by CED at 30 kV/cm, 40 kV/cm, and 50 kV/cm for 3 minutes. After the CED treatment, starch analyses showed that there were no apparent changes in the resistant starch and amylose contents. Only surface and nonpenetrative damage caused by plasma etching at different voltage strengths were observed on the starch granules. The CED treatments reduced the total area of diffraction peak, gelatinization enthalpy (by -21% to -38%), and different pasting behaviors including peak viscosity, breakdown, final viscosity, and setback. The CED treatments were capable of increasing relative crystallinity and gelatinization temperature. This study revealed the potential of CED plasma technology as a tool to modify the characteristics of banana starch.

Effect of antioxidant activity and functional properties of Chingshey purple sweet potato fermented milk by Lactobacillus acidophilus, L. delbrueckii subsp. lactis, and L. gasseri strains.

UNLABELLED: In this study, individual selected lactic acid bacteria strains Lactobacillus acidophilus (LA), L. delbrueckii subsp. lactis (LDL), and L. gasseri (LGA) were grown in Chingshey purple sweet potato (CPSP) substrate/media. CPSP is rich in anthocyanin, which possesses antioxidant activity and in vitro cell assay. The antioxidant ability and functional properties of the fermented milk were examined. High-performance liquid chromatographic (HPLC) method was used to analyze the free amino acid, organic acids, and anthocyanin content. Total phenolic compounds, scavenging effects of 1,1-diphenyl-2-picyl-hydrazyl (DPPH) radicals, and scavenging effects of superoxide anion radicals were determined to evaluate the antioxidant ability of the samples. The cell proliferation of the fermented PSP milk was evaluated by 3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl Tetrazolium Bromide (MTT) assay. The result indicated that the antioxidant ability of the fermented CPSP milk through LA, LDL, and LGA strains was significantly higher than CPSP. The main anthocyanins present in the samples are cyanidin and delphinidin. MTT assay has revealed that incubation with both PSP and fermented CPSP milk prevented the cell death of macrophage-like RAW264.7 cells. The potential health benefit of fermented PSP milk through LA, LDL, and LGA strains makes the further application of CPSP in health food highly worthwhile. PRACTICAL APPLICATION: (1) In our study, we have employed the γ-aminobutyric acid (GABA), organic acid contents, total phenol content, anthocyanins content, DPPH, oxygen radical absorbance capacity, superoxide dismutase activity assay, and cytotoxicity assay to assess the functional properties of fermented CPSP milk by different lactic acid bacteria. (2) Our results have revealed that the fermented CPSP milk samples possess high GABA concentrations, organic acid contents, anthocyanins contents, and antioxidant activity. This will provide potential opportunity to develop different functional food products from fermented CPSP milk. (3) The potential health benefit of fermented CPSP milk makes the further application of CPSP in health food highly worthwhile.