Total Titers Research Articles

Exploring Total Immunoglobulin A's Impact on Non-Biopsy Diagnosis of Celiac Disease: Implications for Diagnostic Accuracy.

In the current debate surrounding the biopsy-free diagnosis of CeD, it is crucial to identify factors influencing the accuracy of results. This study investigated the impact of total IgA on the non-invasive diagnosis of celiac disease (CeD). We retrospectively assessed total IgA titers' influence on the diagnostic accuracy of different tTG-IgA thresholds compared to the upper reference value (UNL). Of 165 included patients, tTG-IgA values at 10× UNL and 6× UNL showed specificity of 82.6% and 73.9% and sensitivity of 49.3% and 69.0%, respectively, in predicting intestinal villous atrophy (Marsh 3). In 130 patients, total IgA levels were known at baseline. These patients were divided into three tertiles according to total IgA, i.e., patients with lower, intermediate, or higher total IgA within the population. For patients with total IgA ≥ 245 mg/dL, using a tTG-IgA cutoff of 6× UNL instead of 10× UNL resulted in decreased specificity from 71.4% to 42.8% and increased sensitivity from 67.6% to 81.1%. For patients with total IgA < 174 mg/dL and between 174 mg/dL and 245 mg/dL, using a tTG-IgA cutoff of 6× UNL instead of 10× UNL maintained specificity (75.0% and 85.7%, respectively) with increased sensitivity (from 46.2% to 64.1% and from 36.1% to 52.8%, respectively). In conclusion, total IgA influences the diagnostic accuracy of a predetermined tTG-IgA cutoff. Greater consideration should be given to total IgA, beyond its deficiency, in evaluating the applicability and accuracy of non-invasive CeD diagnosis.

Changes in Circulating CD44+CD62L− Treg Subsets and CD44−CD62L+ Treg Subsets Reflect the Clinical Status of Patients with Allergic Rhinitis

Introduction: This study clarified the expression changes and clinical significance of CD44+CD62L− Treg and CD44−CD62L+ Treg subsets in the peripheral blood of patients with allergic rhinitis (AR). Methods: The peripheral blood of 39 patients with AR and 42 healthy controls was collected. Clinical data, such as sex, age, IgE titer, allergen screening information and visual analogue scale (VAS) score, were recorded. Changes in serum IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected using the cytometric bead array method. Flow cytometry was used to detect the proportions of Th1, Th2, Th17, TFH, and Th9 cells and the proportions of CD44+CD62L− Treg and CD44−CD62L+ Treg subsets. Correlation analysis was performed between the CD44+CD62L− Treg subsets and the CD44−CD62L+ Treg subsets with clinical indicators (VAS score, total IgE titer), cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ), and Th1/Th2/Th17/TFH/Th9 cell proportions. Results: Compared to the control group, the proportion of total Treg cells and CD44+CD62L− Treg cells in the AR group decreased, and the proportion of CD44−CD62L+ Treg cells increased (p < 0.05). The proportions of CD44+CD62L− Treg cells significantly negatively correlated with Th2 cells (R = −0.5270, p < 0.05) and positively correlated with Treg cytokine IL-10 (R = 0.6447, p < 0.05). In addition, CD44+CD62L− Treg cells negatively correlated with the VAS score (R = −0.4956, p < 0.05), total IgE level (R = −0.4177, p < 0.05) and Th2 cytokine IL-6 level (R = −0.3034, p < 0.05) but positively correlated with the Th1 cytokine IL-2 (R = 0.4331, p < 0.05). In contrast, the proportion of CD44+CD62L− Treg cells significantly positively correlated with the Th2 cells (R = 0.6187, p < 0.05). Moreover, the proportion of CD44−CD62L+ Treg cells positively correlated with the VAS score (R = 0.4060, p < 0.05), total IgE level (R = 0.5224, p < 0.05) and Th2 cytokine IL-4 (R = 0.2647, p < 0.05) and IL-6 levels (R = 0.3824, p < 0.05) but negatively correlated with Th1 cytokine IL-2 (R = −0.3451, p < 0.05) and IL-10 (R = −0.3277, p < 0.05). Conclusion: A greater proportion of CD44+CD62L− Tregs correlated with better reversal of the Th1/Th2 imbalance and milder clinical symptoms in AR patients. The presence of more CD44−CD62L+ Tregs correlated with a weaker immunosuppressive effect on Th2 cells and more severe clinical symptoms in AR patients. These findings provide new perspectives for the treatment and disease monitoring of AR.

Leveraging Immunofocusing and Virus-like Particle Display to Enhance Antibody Responses to the Malaria Blood-Stage Invasion Complex Antigen PfCyRPA.

A vaccine protecting against malaria caused by Plasmodium falciparum is urgently needed. The blood-stage invasion complex PCRCR consists of the five malarial proteins PfPTRAMP, PfCSS, PfRipr, PfCyRPA, and PfRH5. As each subcomponent represents an essential and highly conserved antigen, PCRCR is considered a promising vaccine target. Furthermore, antibodies targeting the complex can block red blood cell invasion by the malaria parasite. However, extremely high titers of neutralizing antibodies are needed for this invasion-blocking effect, and a vaccine based on soluble PfRH5 protein has proven insufficient in inducing a protective response in a clinical trial. Here, we present the results of two approaches to increase the neutralizing antibody titers: (A) immunofocusing and (B) increasing the immunogenicity of the antigen via multivalent display on capsid virus-like particles (cVLPs). The immunofocusing strategies included vaccinating with peptides capable of binding the invasion-blocking anti-PfCyRPA monoclonal antibody CyP1.9, as well as removing non-neutralizing epitopes of PfCyRPA through truncation. Vaccination with PfCyRPA coupled to the AP205 cVLP induced nearly two-fold higher IgG responses compared to vaccinating with soluble PfCyRPA protein. Immunofocusing using a linear peptide greatly increased the neutralizing capacity of the anti-PfCyRPA antibodies. However, significantly lower total anti-PfCyRPA titers were achieved using this strategy. Our results underline the potential of a cVLP-based malaria vaccine including full-length PfCyRPA, which could be combined with other leading malaria vaccine antigens presented on cVLPs.

Biosynthesis of β-nicotinamide mononucleotide from glucose via a new pathway in Bacillus subtilis.

β-nicotinamide mononucleotide (β-NMN) is an essential precursor of nicotinamide adenine dinucleotide (NAD+) and plays a key role in supplying NAD+ and maintaining its levels. Existing methods for NMN production have some limitations, including low substrate availability, complex synthetic routes, and low synthetic efficiency, which result in low titers and high costs. We constructed high-titer, genetically engineered strains that produce NMN through a new pathway. Bacillus subtilis WB600 was used as a safe chassis strain. Multiple strains overexpressing NadE, PncB, and PnuC in various combinations were constructed, and NMN titers of different strains were compared via shake-flask culture. The results revealed that the strain B. subtilis PncB1-PnuC exhibited the highest total and extracellular NMN titers. Subsequently, the engineered strains were cultured in a 5-L fermenter using batch and fed-batch fermentation. B. subtilis PncB1-PnuC achieved an NMN titer of 3,398 mg/L via fed-batch fermentation and glucose supplementation, which was 30.72% higher than that achieved via batch fermentation. This study provides a safe and economical approach for producing NMN on an industrial scale.

Ethanol production from the wood and fruit juice of paper mulberry via simultaneous saccharification and juice co-fermentation under normal and very high gravity conditions

A novel batch simultaneous saccharification and juice co-fermentation (SSJcF) process was investigated using mixtures of PHP (phosphoric acid plus hydrogen peroxide) pretreated wood and fruit juice of paper mulberry tree. All the different substrate mixture configurations evaluated under normal gravity SSJcF (total sugar titer of 180 g/L) significantly improved both ethanol concentration and yield compared to sole simultaneous saccharification and fermentation (SSF) of paper mulberry wood. Among the different mixing ratios, the feedstock mixture with equal sugar content from each substrate resulted in maximum ethanol concentration, yield and productivity of 77.1 g/L, 83.9 % and 1.1 g/L/h, respectively. The external additions of mineral nutrients also had no impact on fermentation performance of the mixture. Furthermore, SSJcF was evaluated under different levels of high gravity (HG) and very high gravity (VHG) conditions. The total sugar titer of 350 g/L at equal contributions from each substrate reached very high ethanol concentration of 147.0 g/L, with yield and productivity of 82.3 % and 1.5 g/L/h, respectively. By implication, the PM wood and fruit juice mixture could serve as suitable low-cost and non-food feedstock alternative to the typical use of sugary and/or starchy feedstocks for VHG fermentation.

Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential.

Microbial-derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have the potential as new therapeutics to target drug-resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low-yield biosynthetic gene clusters in the genus Streptomyces. However, low natural product yields-improvements to which have been hindered by the lack of high throughput methods-have slowed the discovery and development of many potential therapeutics. Here, we describe our efforts to improve yields of landomycins-angucycline family polyketides under investigation as cancer therapeutics-by a genetically modified Streptomyces cyanogenus 136. After simplifying the extraction process from S. cyanogenus cultures, we identified a wavelength at which the major landomycin products are absorbed in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram-positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram-negative bacteria that is likely mediated by the exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced by Streptomyces, as well as the light-absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest.

Carotenoids production by Rhodosporidium paludigenum yeasts: Characterization of chemical composition, antioxidant and antimicrobial properties

The high market potential imposed by natural carotenoids has turned the scientific interest in search for new strains, capable of synthesizing a wide spectrum of these pigments. In this study, Rhodosporidium paludigenum NCYC 2663 and 2664 were investigated for carotenoids production and lipid accumulation utilizing different carbon sources (glucose, fructose, sucrose, mixture of glucose: galactose). Strain R. paludigenum 2663 produced the highest total carotenoids titer (2.21 mg/L) when cultivated on sucrose, together with 4 g/L lipids (30% w/w content) and 7 g/L exopolysaccharides. In the case of R. paludigenum 2664, glucose favored the production of 2.93 mg/L total carotenoids and 1.57 g/L lipids (31.8% w/w content). Analysis of the chemical profile during fermentation revealed that β-carotene was the prominent carotenoid. Strain 2663 co-produced γ-carotene, torulene and torularhodin in lower amounts, whereas 2664 synthesized almost exclusively β-carotene. The produced lipids from strain 2663 were rich in oleic acid, while the presence of linoleic acid was also detected in the lipoic fraction from strain 2664. The obtained carotenoid extracts exhibited antioxidant (IC50 0.14 mg/mL) and high antimicrobial activity, against common bacterial and fungal pathogenic strains. The results of this study are promising for the utilization of biotechnologically produced carotenoids in food applications.

Acetone-Butanol-Ethanol (ABE) fermentation with clostridial co-cultures for enhanced biobutanol production

This study has addressed the issue of enhanced biobutanol production through Consolidated Bioprocessing, with the use of clostridial co-cultures combining C. acetobutylicum (Cac) and C. pasteurianum (Cpa). To begin with, the total Acetone-Butanol-Ethanol (ABE) solvent production and butanol selectivity of individual clostridial cultures grown on different carbon sources present in lignocellulosic hydrolysates. Thereafter, statistical optimization of ABE fermentation with co-culture system was carried out using Box-Behnken design. The optimization variables were Cac to Cpa inoculum ratio (X1 in mL mL−1), sodium concentration in the medium (X2 g L−1), and xylose/glucose ratio (X3 g g−1 L L−1), whereas response variables were butanol titre (Y1 in g L−1), biomass growth (Y2 OD600), total ABE titre (Y3 in g L−1). Maximum values of the response variables with the corresponding set of optimization parameters were as follows: Y1, max = 12.1 ± 0.45 (for X1 = 0.30, X2 = 5.90, X3 = 0), Y2, max = 4.15 ± 0.03 (for X1 = 0.3, X2 = 2.42, X3 = 0.14), Y3, max = 23.1 ± 0.55 (for X1 = 0.46, X2 = 6.36, X3 = 0). The study demonstrated a substantial ≈ 22% and 61% increment in butanol titre in co-culture system compared to individual fermentations with Cac and Cpa grown on pure glucose, respectively.

A case series exploring the human milk polyclonal IgA1 response to repeated SARS-CoV-2 vaccinations by LC-MS based fab profiling.

Upon vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humans will start to produce antibodies targeting virus specific antigens that will end up in circulation. In lactating women such antibodies will also end up in breastmilk, primarily in the form of secretory immunoglobulin A1 (SIgA1), the most abundant immunoglobulin (Ig) in human milk. Here we set out to investigate the SIgA1 clonal repertoire response to repeated SARS-CoV-2 vaccination, using a LC-MS fragment antigen-binding (Fab) clonal profiling approach. We analyzed the breastmilk of six donors from a larger cohort of 109 lactating mothers who received one of three commonly used SARS-CoV-2 vaccines. We quantitatively monitored the SIgA1 Fab clonal profile over 16 timepoints, from just prior to the first vaccination until 15 days after the second vaccination. In all donors, we detected a population of 89-191 vaccine induced clones. These populations were unique to each donor and heterogeneous with respect to individual clonal concentrations, total clonal titer, and population size. The vaccine induced clones were dominated by persistent clones (68%) which came up after the first vaccination and were retained or reoccurred after the second vaccination. However, we also observe transient SIgA1 clones (16%) which dissipated before the second vaccination, and vaccine induced clones which uniquely emerged only after the second vaccination (16%). These distinct populations were observed in all analyzed donors, regardless of the administered vaccine. Our findings suggest that while individual donors have highly unique human milk SIgA1 clonal profiles and a highly personalized SIgA1 response to SARS-CoV-2 vaccination, there are also commonalities in vaccine induced responses.

Production of antiviral “OP7 chimera” defective interfering particles free of infectious virus

Defective interfering particles (DIPs) of influenza A virus (IAV) are suggested for use as broad-spectrum antivirals. We discovered a new type of IAV DIP named “OP7” that carries point mutations in its genome segment (Seg) 7 instead of a deletion as in conventional DIPs (cDIPs). Recently, using genetic engineering tools, we generated “OP7 chimera DIPs” that carry point mutations in Seg 7 plus a deletion in Seg 1. Together with cDIPs, OP7 chimera DIPs were produced in shake flasks in the absence of infectious standard virus (STV), rendering UV inactivation unnecessary. However, only part of the virions harvested were OP7 chimera DIPs (78.7%) and total virus titers were relatively low. Here, we describe the establishment of an OP7 chimera DIP production process applicable for large-scale production. To increase total virus titers, we reduced temperature from 37 to 32 °C during virus replication. Production of almost pure OP7 chimera DIP preparations (99.7%) was achieved with a high titer of 3.24 log10(HAU/100 µL). This corresponded to an 11-fold increase relative to the initial process. Next, this process was transferred to a stirred tank bioreactor resulting in comparable yields. Moreover, DIP harvests purified and concentrated by steric exclusion chromatography displayed an increased interfering efficacy in vitro. Finally, a perfusion process with perfusion rate control was established, resulting in a 79-fold increase in total virus yields compared to the original batch process in shake flasks. Again, a very high purity of OP7 chimera DIPs was obtained. This process could thus be an excellent starting point for good manufacturing practice production of DIPs for use as antivirals.Key points• Scalable cell culture-based process for highly effective antiviral OP7 chimera DIPs• Production of almost pure OP7 chimera DIPs in the absence of infectious virus• Perfusion mode production and purification train results in very high titers

Effect of doubled dose administration of foot-and-mouth disease vaccine against heterologous virus infection in cattle.

Vaccination is a feasible approach for controlling foot-and-mouth disease (FMD). In FMD-free countries, vaccines are stored as a precautionary measure to control potential outbreaks. However, the challenge lies in pre-stocking optimal vaccines against the newly emerging strains. This study examined the potency of pre-stocked vaccines administered at elevated doses during emergencies. We vaccinated the cows with either a single or double trivalent vaccine dose containing two serotype O and one serotype A strains. Subsequently, vaccinated and unvaccinated cows were exposed to virulent strains of serotype O (O/JPN/2010; topotype Southeast Asia/Mya-98 lineage) or A (A/IRN/2016; topotype ASIA/G-VII lineage), which were genetically and antigenically distinct from the vaccine strains. Following challenge infections, all cows that received a single dose vaccination exhibited vesicular lesions with excreted viruses in the oral and nasal discharges. However, a substantial reduction was observed in the total clinical scores and virus titers in the sera and nasal discharges compared to those in the unvaccinated group. Cows receiving a doubled dose vaccination were completely protected from infection with O/JPN/2010 or demonstrated a significant decrease in viral shedding and clinical scores against A/IRN/2016. To note, vesicular lesions harbor significant amounts of viruses; thus, by mitigating their formation, viral transmission can be impeded, thereby slowing viral spread in the field. Furthermore, increasing the vaccine dose induced higher neutralizing antibody titers against heterologous strains. These findings suggest an alternative strategy for the effective management of future epidemics using pre-stocked vaccines.

Integration of genetic engineering and multi-factor fermentation optimization for co-production of carotenoid and DHA in Schizochytrium sp

Schizochytrium sp., a microalga with high lipid content, holds the potential for co-producing docosahexaenoic acid (DHA) and carotenoids. In this study, the ability of Schizochytrium sp. to naturally produce carotenoids was systematically explored. Further, by enhancing the precursor supply of geranylgeranyl diphosphate, regulating carbon source through sugar limitation fermentation and employing a combination of response surface methodology and artificial neural networks to precisely optimize nitrogen sources, a new record of 43-fold increase in β-carotene titer was achieved in the 5L bioreactor (653.2 mg/L). Meanwhile, a high DHA content was maintained (13.4 g/L). Furthermore, the use of corn stover hydrolysate has effectively lowered the production costs of carotenoid and DHA while sustaining elevated production levels (with total carotenoid titer and DHA titer reached 502.0 mg/L and 13.2 g/L, respectively). This study offers an efficient and cost-effective method for the co-production of carotenoid and DHA in Schizochytrium sp..

Dynamics of temporal immune responses in nonhuman primates and humans immunized with COVID-19 vaccines.

We assessed the humoral immune responses to a COVID-19 vaccine in a well-controlled rhesus macaque model compared to humans immunized with two mRNA vaccines over several months post-second dose. The plasma IgG levels against seven coronaviruses (including SARS-CoV-2) and antibody subtypes (IgG 1-4 and IgM) against SARS-CoV-2 were evaluated using multiplex assays. The neutralization capacity of plasma antibodies against the original SAR-CoV-2 isolate and nine variants was evaluated in vaccinated humans and non-human primates. Immunization of macaques and humans with SARS-CoV-2 vaccines induced a robust neutralizing antibody response. In non-SIV-infected adult macaques immunized with an adenoviral vector expressing S-RBD (n = 7) or N protein (n = 3), elevated levels of IgG and neutralizing antibodies were detected 2 weeks post-second dose. Immune responses to the S-RBD vaccine in SIV-infected adult macaques (n = 2) were similar to the non-SIV-infected animals. Adult humans immunized with Pfizer (n = 35) or Moderna (n = 18) vaccines developed IgG and neutralizing antibodies at 4 weeks post-second dose. In both vaccine groups, IgG 1 was the predominant subtype, followed by IgG 3. The IgG levels, including total and IgG 1,2,3 elicited by the Moderna vaccine, were significantly higher than the corresponding levels elicited by the Pfizer vaccine at 4 weeks post-second dose. A significant correlation was observed between the plasma total IgG antibody levels and neutralization titers in both macaques and humans. Furthermore, broad-spectrum neutralization antibodies against several variants of SARS-CoV-2 were detected in the plasma of both macaques and humans after two vaccinations.

Multicopy Chromosome Integration and Deletion of Negative Global Regulators Significantly Increased the Heterologous Production of Aborycin in Streptomyces coelicolor.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.

Wolbachia interferes with Zika virus replication by hijacking cholesterol metabolism in mosquito cells.

Zika virus is a member of the arbovirus Flaviviridae family transmitted by Aedes mosquitos and it is associated with microcephaly in infants born to infected mothers. Wolbachia is an intracellular gram-negative alpha-proteobacteria that infects many species of arthropods, including mosquitos. The presence of Wolbachia in mosquitos has been shown to control the vector population and suppress arbovirus transmission. One mechanism of Wolbachia-mediated interference with virus replication is competition over host resources between Wolbachia and the virus. We hypothesize that cholesterol metabolism is involved in Wolbachia-mediated virus suppression due to its important role in Zika virus replication. In this study, we determined that Wolbachia impacted virus replication by altering cholesterol biosynthesis in Aedes albopictus C6/36 cells, diverting resources from the host cell mevalonate (MVA) pathway to fulfill the needs of the bacteria. This resulted in a decrease of total cholesterol, increased Wolbachia loads, and decreased viral titers. Inhibition of the MVA pathway using fluvastatin decreased total cholesterol and viral titers, mimicking the effects of Wolbachia on the virus in Wolbachia-free cells. We also found that Wolbachia-infected cells had depleted lipid droplets, the main component of which is cholesterol esters. We confirmed that cholesterol esterases were upregulated in response to virus infection in C6/36 cells. Functional analysis showed that alteration of cholesterol metabolism simulated Wolbachia-mediated inhibition of virus infection in C6/36 cells. Our study provides a mechanism behind Wolbachia-induced interference of arbovirus replication and could help advance strategies to control arbovirus pathogens in insect vectors and human infections. IMPORTANCE Arthropod-borne viruses are emerging pathogens that are spread widely by mosquitos. Zika virus is an arbovirus that can infect humans and be transmitted from an infected mother to the fetus, potentially leading to microcephaly in infants. One promising strategy to prevent disease caused by arboviruses is to target the insect vector population. Recent field studies have shown that mosquito populations infected with Wolbachia bacteria suppress arbovirus replication and transmission. Here, we describe how intracellular bacteria redirect resources within their host cells and suppress Zika virus replication at the cellular level. Understanding the mechanism behind Wolbachia-induced interference of arbovirus replication could help advance strategies to control arbovirus pathogens in insect vectors and human populations.

Cellulase cocktail saccharification and fermentation of jackfruit waste for biobutanol production: Statistical optimization and techno‐economic analysis

AbstractJackfruit (Artocarpus heterophyllus Lam) waste (JFW), a lignocellulosic biomass, is a potential raw material that can be tapped to produce energy and valuable products for human use. In the present work, biobutanol production was studied using jackfruit waste. Initially, the jackfruit waste was pretreated using acid and alkaline agents and hydrolyzed to produce fermentable sugars. The hydrolyzed jackfruit waste was fermented using Clostridium acetobutylicum NCIM 2877 to produce biobutanol. Among the studied pretreatments, sulfuric acid pretreatment produced a maximum sugar yield of 84.21 ± 2.6 mggds−1 in the acid liquor. Enzyme hydrolysis of pretreated jackfruit waste produced a total glucose yield of 215.12 ± 13.44 mggds−1 after optimization. After detoxification using activated charcoal, the JFW hydrolysate produced a maximum biobutanol titer and yield of 1.60 ± 0.5 g L−1, and 106.59 ± 5.1 mg/gglucose, respectively. Central composite design optimization of acetone‐butanol‐ethanol fermentation produced a maximum biobutanol titer of 5.6 ± 0.2 g L−1 (250.00 ± 11.4 mg/gglucose) and total solvent titer of 7.28 ± 0.3 g L−1 (325.00 ± 13.1 mg/gglucose). A 31 ton annual biobutanol production from JFW, simulated using SuperPro Designer, revealed the unit production cost and payback time to be $10.49/kg and 8.94 years.

Anemia of pregnancy and helicobacteriosis: features of the clinical and laboratory course

A clinical case of the course of pregnancy by trimesters of gestation, childbirth, postpartum (early, late) in a woman with anemia and helicobacteriosis is described. The materials of the medical documentation were analyzed, the peculiarities of the course of pregnancy, childbirth, the postpartum period, laboratory indicators, echography, fibrogastroduodenoscopy were determined.A 32-year-old pregnant woman was hospitalized at 33–34 weeks’ gestation, IV pregnancy. According to the clinical and laboratory examination, B12-folate-iron-deficiency anemia was diagnosed against the background of Helicobacter pylori (Hp) infection (titers of total IgG, IgA, IgM antibodies to Hp antigens (coefficient of positivity) were 7.65). The patient received anti-anemic, nutrient therapy before and after childbirth. Childbirth was termed and physiological. The child was born with a body weight of 3000 g and an Apgar score of 8 points.The woman was examined again 2 months after labor. Anemia of II degree was diagnosed, the Hp coefficient of positivity was increased up to 14.57. It was prescribed anti-anemic therapy aimed at eradicating Hp in accordance with the Maastricht V Consensus (2015) and stabilizing metabolic processes. Two months after treatment, the Hp coefficient of positivity decreased by 2.3 times and the levels of hemoglobin, ferritin, vitamin B12, and folic acid increased to reference values.Conclusions. It is advisable to determine the total titers of IgG, IgA, IgM antibodies to Hp antigens (coefficient of positivity) as the etiological factors of anemia in pregnant women, especially with diseases of the gastrointestinal tract, hepatobiliary system and resistance to anti-anemic therapy. Helicobacteriosis affects the exchange of iron and vitamins of group B, while anemia occurs with more severe manifestations and is resistant to anti-anemic drugs.Full treatment of pregnant women with helicobacteriosis is difficult due to the possible risk of negative effects of etiotropic drugs on the fetus. Therefore, it is important to plan a pregnancy, since timely detection of infectious factors before pregnancy and full-fledged therapy help to reduce the frequency of gestational complications.

Impact of clinico-biochemical and inflammatory biomarkers on the immunogenicity and efficacy of SARS-CoV-2 adenoviral vaccine: a longitudinal study.

Due to a lack of effective antiviral treatment, several vaccines have been put forth to curb SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and to reduce the mortality and morbidity rate by eliciting a protective immune response, primarily through virus-neutralizing antibodies specific for SARS-CoV-2 spike protein. This longitudinal study was designed to evaluate the vaccine effectiveness and immune response following the administration of adenoviral vaccine, COVISHIELD, in Indian population who were previously uninfected with SARS-CoV-2 and to reveal the effect of various sociodemographic, inflammatory and biochemical factors on antibody response. Briefly, the total immunoglobulin G (IgG) against SARS-CoV-2 spike and nucleocapsid protein along with the immunological markers were estimated by chemiluminescent microparticle immunoassay (CMIA) technology. Biochemical parameters were estimated by spectrometry. A total of 348 subjects received two doses of COVISHIELD (224 males, 124 females). The mean age of the study subjects was 42.03 ± 13.54 years. Although both the doses of COVISHIELD against SARS-CoV-2 spike protein induced a robust immune response that lasted for months in all the subjects, the total IgG titer against SARS-CoV-2 spike protein was found significantly higher in subjects ≥50 years of age, and those with obesity, elevated triglycerides and elevated lactate dehydrogenase levels. There is a definite effect of age and biochemical factors on the immunogenicity of COVISHIELD. An understanding of these factors could not only impact the design of vaccines and help improve vaccine immunogenicity and efficacy but also assist in decisions on vaccination schedules, in order to combat this deadly pandemic.

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months

BackgroundEvidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AimIn this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. MethodThe study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. ResultsUp to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. ConclusionThese findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.

The impact of the duration of wave treatment on the development of yeast populations

Introduction: The scientific literature does not contain research on the influence of monochromatic light treatment on the development of bottom-fermenting beer yeast populations.Purpose: An analysis of the literature data allowed us to suppose the possibility of activating the development of the beer yeast Saccharomyces cerevisiae population through preliminary treatment with light of visible spectrum wavelengths, providing technological and economic efficiency of such an impact method on a production scale.Materials and Methods: The object of research was the process of cultivating a population of bottom-fermenting beer yeast Saflager S-189 (Fermentis). The subject was the influence of preliminary treatment of the seed yeast with monochromatic light with a wavelength of 980 nm on this process. Its effectiveness was assessed by the weight loss of the cultivation medium, the increase in the total cell titre, the proportion of unviable and "fed" cells. A KFK-2 photoelectrocolorimeter was used as a source of monochromatic light with wavelengths of the visible range. Seeding of mediums and sample preparation for analysis were performed in a BAVnp-01-"Laminar-S."-1.2 antibacterial air medium box. The yeast's fermenting activity was assessed by the weight loss of the nutrient medium; the total cell titre was established by counting in a Goryaev's chamber; the percentage of unviable cells was determined using methylene blue dye; the percentage of "fed" yeast cells was established by staining glycogen with iodine solution.Results: Preliminary treatment of the seed yeast with monochromatic light (980 nm) allowed increasing the fermenting activity of bottom-fermenting beer yeast by 10-15% compared to the control, which is consistent with the results of other research groups concerning populations of microorganisms of other genera and species. The values of other determined indicators - the proportion of "fed" and unviable cells, the total yeast cell titre - in the experimental variants were at the level of those in the control samples or slightly inferior to them. Data on the influence of the duration of seed yeast irradiation for 60, 120 or 180 minutes on the listed controlled indicators are presented, and the authors express the opinion about the appropriateness of its conduction for 60 minutes.Conclusion: The principle possibility of activating the development of a population of bottom-fermenting beer yeast by preliminary treatment of seed yeast with light with a wavelength of 980 nm, which can give an economic effect on an industrial scale, is substantiated; the necessity of testing the technological method under study in conditions close to production ones, i.e., for brewing wort with an irradiated suspension of seed yeast, is noted.