Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA-histone interactions.

Multiple testis-specific histone variants are involved in the dynamic chromatin transitions during spermatogenesis. H2B.W1 (previously called H2BFWT) is an H2B variant specific to primate testis with hitherto unclear functions, although its single-nucleotide polymorphisms (SNPs) are closely associated with male non-obstructive infertility. Here, we found that H2B.W1 is only expressed in the mid-late spermatogonia stages, and H2B.W1 nucleosomes are defined by a more flexible structure originating from weakened interactions between histones and DNA. Furthermore, one of its SNPs, H2B.W1-H100R, which is associated with infertility, further destabilizes the nucleosomes and increases the nucleosome unwrapping rate by interfering with the R100 and H4 K91/R92 interaction. Our results suggest that destabilizing H2B.W1 containing nucleosomes might change the chromatin structure of spermatogonia, and that H2B.W1-H100R enhances the nucleosome-destabilizing effects, leading to infertility.

Genome-wide expression analysis of vegetative organs during developmental and herbicide-induced whole plant senescence in Arabidopsis thaliana.

BACKGROUND: Whole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide. RESULTS: Differential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45-52 days after planting, followed by roots initiated at 52-60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1. CONCLUSIONS: Our study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis.

External validation and calibration of risk equations for prediction of diabetic kidney diseases among patients with type 2 diabetes in Taiwan.

BACKGROUND: Most existing risk equations for predicting/stratifying individual diabetic kidney disease (DKD) risks were developed using relatively dated data from selective and homogeneous trial populations comprising predominately Caucasian type 2 diabetes (T2D) patients. We seek to adapt risk equations for prediction of DKD progression (microalbuminuria, macroalbuminuria, and renal failure) using empiric data from a real-world population with T2D in Taiwan. METHODS: Risk equations from three well-known simulation models: UKPDS-OM2, RECODe, and CHIME models, were adapted. Discrimination and calibration were determined using the area under the receiver operating characteristic curve (AUROC), a calibration plot (slope and intercept), and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was performed for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of risk equations to address risk variations among patients. RESULTS: The RECODe equations for microalbuminuria and macroalbuminuria showed moderate discrimination (AUROC: 0.62 and 0.76) but underestimated the event risks (calibration slope > 1). The CHIME equation had the best discrimination for renal failure (AUROCs from CHIME, UKPDS-OM2 and RECODe: 0.77, 0.60 and 0.64, respectively). All three equations overestimated renal failure risk (calibration slope < 1). After rigorous updating, the calibration slope/intercept of the recalibrated RECODe for predicting microalbuminuria (0.87/0.0459) and macroalbuminuria (1.10/0.0004) risks as well as the recalibrated CHIME equation for predicting renal failure risk (0.95/-0.0014) were improved. CONCLUSIONS: Risk equations for prediction of DKD progression in real-world Taiwanese T2D patients were established, which can be incorporated into a multi-state simulation model to project and differentiate individual DKD risks for supporting timely interventions and health economic research.

A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Improving nitrogen content in soil and lemon balm (Melissa officinalis L.) yield by purple nonsulfur bacteria Rhodopseudomonas palustris in two consecutive seasons.

The study was conducted to assess the effects of nitrogen (N)-fixing purple nonsulfur bacteria (PNSB) Rhodopseudomonas palustris TLS06, VNW02, VNW64, and VNS89 on soil fertility, N uptake, essential oil (EO) content, growth, and yield of lemon balm. The experiment followed a completely randomized block design with 9 treatments and 3 replications. The treatments consisted of (i) applying 100% N as the recommended fertilizer rate (RFR), (ii) applying 85% N as RFR, (iii) applying 70% N as RFR, (iv) applying 55% N as RFR, (v) the treatment ii combined with N-PNSB, (vi) the treatment iii combined with N-PNSB, (vii) the treatment iv combined with N-PNSB, (viii) 0% as RFR combined with N-PNSB, and (ix) 0% N as RFR. The results showed that applying N-PNSB increased the plant height, and the number of primary branches in both seasons. In addition, the treatment without N fertilizer combined with N-PNSB increased stem leaf biomass by 41.2 and 50.3% in both seasons as compared with the treatment without neither N fertilizer nor N-PNSB. For soil properties, among treatments without N fertilizer, the treatment with N-PNSB increased concentrations of NH4+, soluble P, and exchangeable K+ by 41.3, 41.4, and 26.8%, respectively, as compared with the treatment without N-PNSB at the end of the second season. Applying 85% N as RFR combined with N-PNSB had a greater yield by 5.78-11.8% as compared with the treatment with 100% N as RFR, and a greater EO content by 23% as compared with the treatment with 85% N as RFR.

IL36RN Mutations and Correlated Characteristics in Generalized Pustular Psoriasis Patients in Can Tho City, Vietnam: A Cross-sectional study.

INTRODUCTION: Pustular psoriasis is a rare and severe form of psoriasis characterized by sterile pustules on an erythematous background. The disease ranges from localized to generalized forms, with the latter being particularly life-threatening and recurrent. Understanding the genetic basis of pustular psoriasis, particularly IL36RN mutations, is crucial for developing better treatments. This study aims to determine the prevalence and types of IL36RN gene mutations and their relationship with clinical and paraclinical features in patients with pustular psoriasis in Can Tho City, Vietnam. METHODS: A cross-sectional study was conducted at Can Tho Dermatology Hospital involving 59 patients diagnosed with generalized pustular psoriasis (GPP) according to ERASPEN and Japanese Dermatological Association criteria. Data on demographic, clinical, and laboratory characteristics were collected. IL36RN gene mutations were identified through genomic DNA sequencing. Statistical analyses were performed to explore associations between IL36RN mutations and clinical features. RESULTS: The study included 59 participants, predominantly female (69.5%), with an average age of 39.12 years. A significant proportion (83.1%) had a history of psoriasis, with frequent recurrences (94.9%). The most common IL36RN mutation identified was p.Arg10ArgfsX1, present in 44.1% of patients. Other mutations included p.Pro76Leu (20.3%) and p.Arg102Trp (1.7%). Patients with IL36RN mutations were younger and had an earlier disease onset. Significant associations were found between IL36RN mutations and clinical features such as fever (OR = 11, p < 0.0001) and geographic tongue (OR = 14.67, p < 0.0001). CONCLUSION: Our study reveals a high prevalence of IL36RN mutations, particularly p.Arg10ArgfsX1, in Vietnamese pustular psoriasis patients, strongly associating these mutations with clinical features like fever and geographic tongue.

Long noncoding RNAs as versatile molecular regulators of cellular stress response and homeostasis.

Normal cell and body functions need to be maintained and protected against endogenous and exogenous stress conditions. Different cellular stress response pathways have evolved that are utilized by mammalian cells to recognize, process and overcome numerous stress stimuli in order to maintain homeostasis and to prevent pathophysiological processes. Although these stress response pathways appear to be quite different on a molecular level, they all have in common that they integrate various stress inputs, translate them into an appropriate stress response and eventually resolve the stress by either restoring homeostasis or inducing cell death. It has become increasingly appreciated that non-protein-coding RNA species, such as long noncoding RNAs (lncRNAs), can play critical roles in the mammalian stress response. However, the precise molecular functions and underlying modes of action for many of the stress-related lncRNAs remain poorly understood. In this review, we aim to provide a framework for the categorization of mammalian lncRNAs in stress response and homeostasis based on their experimentally validated modes of action. We describe the molecular functions and physiological roles of selected lncRNAs and develop a concept of how lncRNAs can contribute as versatile players in mammalian stress response and homeostasis. These concepts may be used as a starting point for the identification of novel lncRNAs and lncRNA functions not only in the context of stress, but also in normal physiology and disease.

Four New Stilbene Derivatives Isolated from Gnetum latifolium var. funiculare Markgr. and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells.

Gnetum latifolium var. funiculare Markgr. is a medicinal plant and widely distributed in mountainous areas of Vietnam. Phytochemical investigation on the trunks of this plant afforded eight stilbene derivatives (1-8) including for new compounds (1-4). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Among the isolates, compounds 1-3 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with the IC50 values ranging from 46.81 to 68.10 µM, compounds 4 and 6 showed weak effects with the IC50 values of 96.57 and 79.46 µM, respectively, compared to that of the positive control compound, dexamethasone (IC50 14.20 µM).

New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti-Inflammatory Activity.

A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 µM) toward TNF-α production, respectively.

Exploring the Potential of a Genome-Reduced Escherichia coli Strain for Plasmid DNA Production.

The global demand for nucleic acid-based vaccines, including plasmid DNA (pDNA) and mRNA vaccines, needs efficient production platforms. However, conventional hosts for plasmid production have encountered challenges related to sequence integrity due to the presence of insertion sequences (ISs). In this study, we explored the potential of a genome-reduced Escherichia coli as a host for pDNA production. This strain had been constructed by removing approximately 23% of the genome which were unessential genes, including the genomic unstable elements. Moreover, the strain exhibits an elevated level of NADPH, a coenzyme known to increase plasmid production according to a mathematical model. We hypothesized that the combination of genome reduction and the abundance of NADPH would significantly enhance pDNA production capabilities. Remarkably, our results confirmed a three-fold increase in pDNA production compared to the widely employed DH5α strain. Furthermore, the genome-reduced strain exhibited heightened sensitivity to various antibiotics, bolstering its potential for large scale industrial pDNA production. These findings suggest the genome-reduced E. coli as an exciting candidate for revolutionizing the pDNA industry, offering unprecedented efficiency and productivity.

The influence of COVID-19 pandemic on PM2.5 air quality in Northern Taiwan from Q1 2020 to Q2 2021.

The study aimed to investigate the PM2.5 variations in different periods of COVID-19 control measures in Northern Taiwan from Quarter 1 (Q1) 2020 to Quarter 2 (Q2) 2021. PM2.5 sources were classified based on long-range transport (LRT) or local pollution (LP) in three study periods: one China lockdown (P1), and two restrictions in Taiwan (P2 and P3). During P1 the average PM2.5 concentrations from LRT (LRT-PM2.5-P1) were higher at Fuguei background station by 27.9% and in the range of 4.9-24.3% at other inland stations compared to before P1. The PM2.5 from LRT/LP mix or pure LP (Mix/LP-PM2.5-P1) was also higher by 14.2-39.9%. This increase was due to higher secondary particle formation represented by the increase in secondary ions (SI) and organic matter in PM2.5-P1 with the largest proportion of 42.17% in PM2.5 from positive matrix factorization (PMF) analysis. A similar increasing trend of Mix/LP-PM2.5 was found in P2 when China was still locked down and Taiwan was under an early control period but the rapidly increasing infected cases were confirmed. The shift of transportation patterns from public to private to avoid virus infection explicated the high correlation of the increasing infected cases with the increasing PM2.5. In contrast, the decreasing trend of LP-PM2.5-P3 was observed in P3 with the PM2.5 biases of ∼45% at all the stations when China was not locked down but Taiwan implemented a semi-lockdown. The contribution of gasoline vehicle sources in PM2.5 was reduced from 20.3% before P3 to 10% in P3 by chemical signatures and source identification using PMF implying the strong impact of strict control measures on vehicle emissions. In summary, PM2.5 concentrations in Northern Taiwan were either increased (P1 and P2) or decreased (P3) during the COVID-19 pandemic depending on control measures, source patterns and meteorological conditions.

Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders.

Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system's structure and function due to oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation. Among these NDs, Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis characterized an increasing dysfunction and loss of neuronal structure leading to neuronal cell death. Although there is currently no drug to totally reverse the effects of NDs, such novel formulations and administration routes are developed for better management and nose-to-brain delivery is one of delivery for treating NDs. This review aimed to highlight advances in research on various lipid based nanocarriers such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and cubosomes which are reported to treat and alleviate the symptoms of NDs via nose-to-brain route. The challenges during clinical translation of lipid nanocarriers from bench to bed side is also discussed.

Ultrathin Nanostructured Films of Hyaluronic Acid and Functionalized ß-Cyclodextrin Polymer Suppress Bacterial Infection and Capsular Formation of Medical Silicone Implants.

A type of ultrathin films has been developed for suppressing capsule formation induced by medical silicone implants and hence reducing the inflammation response to such formation and the differentiation to myofibroblasts. The films were each fabricated from hyaluronic acid (HA) and modified ß-cyclodextrin (Mod-ß-CyD) polymer which was synthesized with a cyclodextrin with partially substituted quaternary amine. Ultrathin films comprising HA and Mod-ß-CyD or poly(allylamine hydrochloride) (PAH) were fabricated by using a layer-by-layer dipping method. The electrostatic interactions produced from the functional groups of Mod-ß-CyD and HA influenced the surface morphology, wettability, and bio-functional activity of the film. Notably, medical silicone implants coated with PAH/HA and Mod-ß-CyD multilayers under a low pH condition exhibited excellent biocompatibility and antibiofilm and anti-inflammation properties. Implantation of these nanoscale film-coated silicones showed a reduced capsular thickness as well as reduced TGFß-SMAD signaling, myofibroblast differentiation, biofilm formation, and inflammatory response levels. We expect our novel coating system to be considered a strong candidate for use in various medical implant applications in order to decrease implant-induced capsule formation.

Correlation Between the Amount of Extracellular Polymeric Substances and the Survival Rate to Freeze-Drying of Probiotics.

To demonstrate that the amount of extracellular polymeric substances (EPS) and the freeze-dried viability of probiotics are correlated. Three strains of probiotics including Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Bifidobacterium bifidum were subjected to environmental challenges, such as temperature, pH, and carbon dioxide. The results indicated that the challenges could stimulate the EPS synthesis of the probiotics. The experimental correlation between the amount of synthesized EPS and the freeze-dried survival rate was also analyzed, and the viability of each of the three strains was represented by the following functions in which the equation of L. plantarum is y = - 0.0336x2 + 2.7059x - 14.849 with R2 = 0.9699, the B. bifidum's equation is y = - 0.0554x2 + 2.6243x - 13.654 with R2 = 0.9554, and the L. acidophilus's one was y = 0.0346x2 + 0.5862x - 9.1339 with R2 = 0.9733. This could be a new approach to determining the freeze-dried viability of probiotic strains based on the measured EPS content.

Topological Surface State in Epitaxial Zigzag Graphene Nanoribbons.

Protected and spin-polarized transport channels are the hallmark of topological insulators, coming along with an intrinsic strong spin-orbit coupling. Here we identified such corresponding chiral states in epitaxially grown zigzag graphene nanoribbons (zz-GNRs), albeit with an extremely weak spin-orbit interaction. While the bulk of the monolayer zz-GNR is fully suspended across a SiC facet, the lower edge merges into the SiC(0001) substrate and reveals a surface state at the Fermi energy, which is extended along the edge and splits in energy toward the bulk. All of the spectroscopic details are precisely described within a tight binding model incorporating a Haldane term and strain effects. The concomitant breaking of time-reversal symmetry without the application of external magnetic fields is supported by ballistic transport revealing a conduction of G = e2/h.

Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis.

Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, is a vital glycogen synthase regulator controlling glycogen synthesis, glucose metabolism, and insulin signaling. GSK-3 is widely expressed in different types of cells, and its abundant roles in cellular bioregulation have been speculated. Abnormal GSK-3 activation and inactivation may affect its original bioactivity. Moreover, active and inactive GSK-3 can regulate several cytosolic factors and modulate their diverse cellular functional roles. Studies in experimental liver disease models have illustrated the possible pathological role of GSK-3 in facilitating acute hepatic injury. Pharmacologically targeting GSK-3 is therefore suggested as a therapeutic strategy for liver protection. Furthermore, while the signaling transduction of GSK-3 facilitates proinflammatory interferon (IFN)-γ in vitro and in vivo, the blockade of GSK-3 can be protective, as shown by an IFN-γ-induced immune hepatitis model. In this study, we explored the possible regulation of GSK-3 and the potential relevance of GSK-3 blockade in IFN-γ-mediated immune hepatitis.

Enhancement of anti-TNFα monoclonal antibody production in CHO cells through the use of UCOE and DHFR elements in vector construction and the optimization of cell culture media.

Recently, there has been a high demand for anti-tumor necrosis factor-α monoclonal antibodies (mAbTNFα) in the treatment of rheumatoid arthritis and other autoimmune diseases. Thus, efficient strategies and stable high-producing cell lines need to be established to increase antibody production. In this study, we describe an efficient approach to establish a mAbTNFα high-producing clone through the optimization of expression vectors and cell culture media. The ubiquitous chromatin opening element (UCOE) and dihydrofolate reductase (DHFR)-based vectors encoding mAbTNFα were introduced into the CHO-DG44 cells using lipofection. Clones were obtained by selecting transfected cells with G418, amplifying them by treatment with methotrexate, and isolating them by limiting dilution. Different media formulated with commercial feeds and media were also screened to develop an improved medium. The antibody produced by the selected clone was purified, characterized, and compared to standard adalimumab. Using our established protocol, a cell clone obtained from stable mAbTNFα-expressing cell pools showed a 3.8-fold higher antibody titer compared to stable cell pools. Furthermore, the highest antibody yield of selected clones cultured in fed-batch mode using improved medium was 2450 ± 30 µg/mL, which was 13.2-fold higher than that of stable cell pool cultivated in batch mode using a basal medium. The purified antibody had primary chemical and biological characteristics similar to those of adalimumab. Therefore, the use of UCOE and DHFR vectors in combination with the optimization of cell culture media may help in establishing stable and high-producing CHO cell lines for therapeutic antibody production.

Microneedles enable the development of skin-targeted vaccines against coronaviruses and influenza viruses.

Throughout the COVID-19 pandemic, many have seriously worried that the plus burden of seasonal influenza that might create a destructive scenario, resulting in overwhelmed healthcare capacities and onwards loss of life. Many efforts to develop a safe and efficacious vaccine to prevent infection by coronavirus and influenza, highlight the importance of vaccination to combat infectious pathogens. While vaccines are traditionally given as injections into the muscle, microneedle (MN) patches designed to precisely deliver cargos into the cutaneous microenvironment, rich in immune cells, provide a noninvasive and self-applicable vaccination approach, reducing overall costs and improving access to vaccines in places with limited supply. The current review aimed to highlight advances in research on the development of MNs-mediated cutaneous vaccine delivery. Concluding remarks and challenges on MNs-based skin immunization are also provided to contribute to the rational development of safe and effective MN-delivered vaccines against these emerging infectious diseases.

Association of PSORS1C3, CARD14 and TLR4 genotypes and haplotypes with psoriasis susceptibility.

Psoriasis is a common chronic, immune-mediated inflammatory disease of the skin. PSORS1C3 is a non-protein coding gene, of which the RNA transcript is found in psoriatic patients. CARD14 is mainly expressed in epidermal keratinocytes. TLR4 is a transmembrane protein to recognize microbial antigens. Our study aimed to assess the relationship among PSORS1C3, CARD14 and TLR4 polymorphisms, inflammatory expression and psoriasis susceptibility. To the end, 71 patients with psoriasis and 46 healthy individuals with the well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by Sanger DNA sequencing and secretion of cytokines by ELISA. As a result, genetic analysis of PSORS1C3 gene identified nine SNPs and three haplotype blocks. Sequencing of the CARD14 gene determined eight SNPs and one haplotype block. Sequencing of TLR4 gene identified nine SNPs, in which a SNP rs1018673641 was found to exert deleterious effect. The linkage disequilibrium analysis showed that seven variants in PSORS1C3 gene and three SNPs in CARD14 gene were in tightly linked. More importantly, a significant association between IL-6 level and rs1018673641 AT genotype in TLR4 gene was detected in psoriatic patients. In conclusion, the PSORS1C3, CARD14 and TLR4 polymorphisms and haplotypes may be correlated with risk of suffering psoriasis and the IL-6-mediated chronic inflammation in psoriasis could be partially regulated by the TLR4 functional variant.