Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies.

Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.

An insight into the antioxidant activities and the exploration of record high quantities of quercetin and luteolin in the plant parts of Myxopyrum smilacifolium (wall.) Blume.

This study attempts to reveal antioxidants in the plant parts of Myxopyrum smilacifolium (Wall.) Blume using antioxidant assays and LC-MS/MS analysis. Methanol is the most effective solvent for collecting antioxidants. The roots-derived methanol extract demonstrates the greatest antioxidant activity, corresponding to the extremely low IC50 values of 16.39 µg/mL and 19.80 µg/mL for DPPH and ABTS radicals, respectively. The high phenolic and flavonoid contents are the primary reason for outstanding total antioxidant capacity (TAC; i.e. 247.73 ± 1.62 mg GA/g or 163.93 ± 0.83 mg AS/g) of the root extract. LC-MS/MS quantification of five phenolic compounds reveals exceptionally high amounts of quercetin and luteolin in the root extract, ranging from 238.86 ± 5.74 to 310.99 ± 1.44 µg/g and from 201.49 ± 7.84 to 234.10 ± 2.54 µg/g, respectively, in the root-derived methanol extract. The achievement highlights M. smilacifolium as a promising source of natural antioxidants for large-scale medical applications.

Cone Beam CT Assessment of Mandibular Foramen and Mental Foramen Positions as Essential Anatomical Landmarks: A Retrospective Study in Vietnam.

INTRODUCTION: The mandibular foramen (MnF) and the mental foramen (MF) are essential anatomical landmarks that should be considered before any surgical procedures in the mandible. This study aimed to investigate the characteristics of the MnF and MF in relation to adjacent anatomical structures, as well as age and gender differences, using cone beam computed tomography (CBCT) projections. METHODS: The study was conducted from August 2023 to January 2024 at the Can Tho University of Medicine and Pharmacy Hospital, Vietnam. In this retrospective study, 50 CBCT images of Vietnamese patients were randomly taken for various clinical purposes. Furthermore, relevant data, such as gender and age groups, were selected to evaluate the correlations, along with specific inclusion criteria. Patients within the age range of 18-69 with a symmetrical mandible were included. RESULTS: The distance of the MnF-MN was 29.6±5.0 mm (right) and 30.1±4.6 mm (left) in males and 25.0±4.2 mm (right) and 26.3±5.0 mm (left) in females. The distance of the MnF-posterior border of the ramus (P) was 16.2±3.6 mm (right) and 15.0±2.3 mm (left) in males. For females, it was 17.1±2.9 mm (right) and 13.8±1.7 mm (left). The distance of the MF-body mandible (MB) was 15.4±2.4 mm (right) and 15.6±2.0 mm (left) in males and 14.0±2.1 mm (right) and 14.3±1.6 mm (left) in females. The distance of the MF-mandibular midline (MM) was 27.0±2.6 mm (right) and 27.0±2.9 mm (left) in males and 25.3±2.0 mm (right) and 25.1±2.2 mm (left) in females. These distances showed statistically significant differences depending on gender (P<0.05). CONCLUSION: It can be said that CBCT provides comprehensive information about the MnF and the MF for dentists in research and clinical practice.

Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein.

The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

The Applicability of the Moyers, Tanaka-Johnston, and Gross-Hasund Analysis and a New Formula for the Vietnamese Population.

Aim: Our aim is to determine the applicability of other analyses and develop a new formula appropriate for the Vietnamese population. Materials and Methods: A cross-sectional descriptive analysis was conducted on a total of 120 dental arch samples (18-25 years old, 60 males, and 60 females) with <5 mm of tooth crowding, complete teeth on the dental arch, no missing teeth, and no fillings on the mesial or distal sides. Each study sample will be imprinted and measured using conventional as well as digital methods. Result: There was a significant discrepancy between the overall mesiodistal width from canine to second premolar in the maxilla and mandibular measured with electronic calipers on the cast model and the values calculated by the Moyer, Tanaka - Johnston, Gross - Hasund formulae in the mandibular, and measured by digital scanning and results calculated by the Gross-Hasund formula for maxilla and mandibular and the Moyers, Tanaka-Johnston formula for mandibular. The values obtained were compared with those calculated using the Moyers, Tanaka-Johnston, and Gross-Hasund formulae for the mandibular. Additionally, measurements were taken by digital scanning, and the results were calculated using the Gross-Hasund formula for both the maxilla and mandibular, and the Moyers and Tanaka-Johnston formulae for the mandibular. When used to estimate space analysis in the Vietnamese population, the estimation formula for each gender had greater accuracy and reliability than other widely used methods. Conclusions: As the central incisor and first molar are the first permanent teeth to erupt, the mesiodistal width may be readily measured. This new formula may be used to predict the width in the early stages of the mixed dentition.

Potential biological functions and future perspectives of sialylated milk oligosaccharides.

Sialyllactoses (SLs) primarily include sialylated human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). First, the safety assessment of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) revealed low toxicity in various animal models and human participants. SLs constitute a unique milk component, highlighting the essential nutrients and bioactive components crucial for infant development, along with numerous associated health benefits for various diseases. This review explores the safety, biosynthesis, and potential biological effects of SLs, with a specific focus on their influence across various physiological systems, including the gastrointestinal system, immune disorders, rare genetic disorders (such as GNE myopathy), cancers, neurological disorders, cardiovascular diseases, diverse cancers, and viral infections, thus indicating their therapeutic potential.

Orthodontic Treatment for Borderline Class III Malocclusion in Adults: Nonextraction Treatment with Anterior Bite Turbo: A Case Report.

Retrusive upper lips, retroclined upper incisors, a shorter midface, and a larger maxillary-mandibular difference are the characteristics of borderline Class III malocclusion. Individuals with borderline Class III malocclusion frequently exhibit certain morphologic, dental, and skeletal traits, which should aid in the diagnosis of the condition. To report the case of a 22-year-old Vietnamese woman who complained of having tense front teeth and lacking confidence when smiling. Medical history did not find anything strange, there was root canal treatment of the first premolar on the left of the upper jaw, asymmetrical concave chin, and right deviation. Orthodontic camouflage treatment using anterior bite turbos in combination with early light short Class III elastics and box elastics was proposed since the patient declined to have orthognathic surgery. In just 10 months of treatment, a Class I molar and canine relationship was created, an anterior crossbite was corrected via mandibular retraction, and severe skeletal malocclusions were successfully treated without orthognathic surgery. Smiling currently showcases the patient's maxillary incisors more prominently, and her lower lip fullness has diminished, giving her a more attractive smile and a significant improvement to her facial profile.

Polythiophene-wrapped Chitosan Nanofibrils with a Bouligand Structure toward Electrochemical Macroscopic Membranes.

Exploring structural biomimicry is a great opportunity to replicate hierarchical frameworks inspired by nature in advanced functional materials for boosting new applications. In this work, we present the biomimetic integration of polythiophene into chitosan nanofibrils in a twisted Bouligand structure to afford free-standing macroscopic composite membranes with electrochemical functionality. By considering the integrity of the Bouligand structure in crab shells, we can produce large, free-standing chitosan nanofibril membranes with iridescent colors and flexible toughness. These unique structured features lead the chitosan membranes to host functional additives to mimic hierarchically layered composites. We used the iridescent chitosan nanofibrils as a photonic platform to investigate the host-guest combination between thiophene and chitosan through oxidative polymerization to fabricate homogeneous polythiophene-wrapped chitosan composites. This biomimetic incorporation fully retains the twisted Bouligand organization of nanofibrils in the polymerized assemblies, thus giving rise to free-standing macroscopic electrochemical membranes. Our further experiments are the modification of the biomimetic polythiophene-wrapped chitosan composites on a glassy carbon electrode to design a three-electrode system for simultaneous electrochemical detection of uric acid, xanthine, hypoxanthine, and caffeine at trace concentrations.

Design and Preclinical Evaluation of a Nanoparticle Vaccine against Respiratory Syncytial Virus Based on the Attachment Protein G.

Human respiratory syncytial virus (RSV) poses a significant human health threat, particularly to infants and the elderly. While efficacious vaccines based on the F protein have recently received market authorization, uncertainties remain regarding the future need for vaccine updates to counteract potential viral drift. The attachment protein G has long been ignored as a vaccine target due to perceived non-essentiality and ineffective neutralization on immortalized cells. Here, we show strong G-based neutralization in fully differentiated human airway epithelial cell (hAEC) cultures that is comparable to F-based neutralization. Next, we designed an RSV vaccine component based on the central conserved domain (CCD) of G fused to self-assembling lumazine synthase (LS) nanoparticles from the thermophile Aquifex aeolicus as a multivalent antigen presentation scaffold. These nanoparticles, characterized by high particle expression and assembly through the introduction of N-linked glycans, showed exceptional thermal and storage stability and elicited potent RSV neutralizing antibodies in a mouse model. In conclusion, our results emphasize the pivotal role of RSV G in the viral lifecycle and culminate in a promising next-generation RSV vaccine candidate characterized by excellent manufacturability and immunogenic properties. This candidate could function independently or synergistically with current F-based vaccines.

Clinical performance of computer-aided design/computer-aided manufacture lithium disilicate ceramic endocrown restorations: A 2-year study.

Context: Optimal restoration methods for endodontically treated teeth (ETTs) have always remained an ongoing discussion among physicians in this day and age. ETTs have a tendency to fracture when chewing, compared to initial teeth. From the perspective of biology, preserving and restoring tooth structure is critical to maintaining biomechanical, functional, and esthetic harmony. Dental bonding techniques have lessened the necessity for post-and-core restorations in ETTs with severe substance loss. A minimally invasive endodontic restoration technique called "endocrown" was initially introduced by Bindl and Mörmann in 1999. Aims: The aim of the study was to clinically evaluate all-ceramic mandibular molar endocrowns made using computer-aided design/computer-aided manufacturing (CAD/CAM) following 2 years of follow-up. Subjects and Methods: This unblinded study contains 56 patients with 56 mandibular molars, which had severe substance loss. After teeth preparation, lithium disilicate ceramic endocrowns were manufactured with the CEREC CAD/CAM system, and cementation was performed using a composite luting agent. The endocrowns were assessed using the modified United States Public Health Service criteria at baseline, 6 months, 1 year, and 2 years following placement. Patient satisfaction was evaluated using a questionnaire. Statistical Analysis Used: This study used descriptive statistics, including mean, standard deviation, and 95% confidence intervals. Data were processed using STATA version 14.0 (StataCorp LLC, USA). Results: Two endocrowns (3.6%) failed throughout the period of observation. The high clinical rating criteria (96.4%, count of 54) and the increased satisfaction percentage (94.6%, count of 53) remained practically stable during the follow-up assessments at 6 months and after 1-2 years. Conclusions: Endocrown offers a less invasive treatment option that may be a better method for endodontically treated mandibular molars. With contemporary CAD/CAM technology and new materials, time in the chair and esthetics optimally improved, bringing satisfaction to the patient.

3'-Sialyllactose protects against LPS-induced endothelial dysfunction by inhibiting superoxide-mediated ERK1/2/STAT1 activation and HMGB1/RAGE axis.

AIM: Endothelial hyperpermeability is an early stage of endothelial dysfunction associated with the progression and development of atherosclerosis. 3'-Sialyllactose (3'-SL) is the most abundant compound in human milk oligosaccharides, and it has the potential to regulate endothelial dysfunction. This study investigated the beneficial effects of 3'-SL on lipopolysaccharide (LPS)-induced endothelial dysfunction in vitro and in vivo. MAIN METHODS: We established LPS-induced endothelial dysfunction models in both cultured bovine aortic endothelial cells (BAECs) and mouse models to determine the effects of 3'-SL. Western blotting, qRT-PCR analysis, immunofluorescence staining, and en face staining were employed to clarify underlying mechanisms. Superoxide production was measured by 2',7'-dichlorofluorescin diacetate, and dihydroethidium staining. KEY FINDINGS: LPS significantly decreased cell viability, whereas 3'-SL treatment mitigated these effects via inhibiting ERK1/2 activation. Mechanistically, 3'-SL ameliorated LPS-induced ROS accumulation leading to ERK1/2 activation-mediated STAT1 phosphorylation and subsequent inhibition of downstream transcriptional target genes, including VCAM-1, TNF-α, IL-1ß, and MCP-1. Interestingly, LPS-induced ERK1/2/STAT1 activation leads to the HMGB1 release from the nucleus into the extracellular space, where it binds to RAGE, while 3'-SL suppressed EC hyperpermeability by suppressing the HMGB1/RAGE axis. This interaction also led to VE-cadherin endothelial junction disassembly and endothelial cell monolayer disruption through ERK1/2/STAT1 modulation. In mouse endothelium, en face staining revealed that 3'-SL abolished LPS-stimulated ROS production and VCAM-1 overexpression. SIGNIFICANCE: Our findings suggest that 3'-SL inhibits LPS-induced endothelial hyperpermeability by suppressing superoxide-mediated ERK1/2/STAT1 activation and HMGB1/RAGE axis. Therefore, 3'-SL may be a potential therapeutic agent for preventing the progression of atherosclerosis.

Human milk oligosaccharides 3'-sialyllactose and 6'-sialyllactose attenuate LPS-induced lung injury by inhibiting STAT1 and NF-κB signaling pathways.

Acute lung injury (ALI) is the leading cause of respiratory diseases induced by uncontrolled inflammation and cell death. Lipopolysaccharide (LPS) is a major trigger of ALI in the progression through macrophage differentiation and the accelerated release of pro-inflammatory cytokines. The present study aimed to investigate the protective effects of human milk oligosaccharides, specifically 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), on LPS-induced ALI and elucidate their underlying signaling pathways. The inhibitory effects of 3'-SL and 6'-SL on inflammation were evaluated using LPS-treated RAW 264.7 macrophages. To establish the ALI model, mice were treated with 10 mg/kg LPS for 24 h. Histological changes in the lung tissues were assessed using hematoxylin and eosin staining and immunofluorescence. LPS causes thickening of the alveolar wall infiltration of immune cells in lung tissues and increased serum levels of TNF-α, IL-1ß, and GM-CSF. However, these effects were significantly alleviated by 100 mg/kg of 3'-SL and 6'-SL. Consistent with the inhibitory effects of 3'-SL and 6'-SL on LPS-induced pro-inflammatory cytokine secretion in serum, 3'-SL and 6'-SL suppressed mRNA expression of TNF-α, IL-1ß, MCP-1, iNOS, and COX2 in LPS-induced RAW 264.7 cells. Mechanistically, 3'-SL and 6'-SL abolished LPS-mediated phosphorylation of NF-κB and STAT1. Interestingly, fludarabine treatment, a STAT1 inhibitor, did not affect LPS-mediated NF-κB phosphorylation. In summary, 3'-SL and 6'-SL protect LPS-induced macrophage activation and ALI through the STAT1 and NF-κB signaling pathways.

Platelet-rich plasma's (PRP) impacts on accelerated canine movement.

OBJECTIVE: To investigate the impact of platelet-rich plasma (PRP) on canine movement acceleration. METHODS: Randomized clinical trial split-mouth study with a double-blind design and controlled group on 31 orthodontic patients, which had been indicated bilateral maxillary first premolar extraction. Each patient recorded clinical features, analyzed lateral cephalometric film, and evaluated the acceleration on dental models at every specific interval. RESULT: The cumulative distance to the distal canines was larger for the PRP injection group than for the control group at three time points (4 weeks, 8 weeks, and 12 weeks), all of which were statistically significant. The PRP injection group's canine distal width increased from the first 4 weeks (ΔT1) to the highest in the middle 4 weeks (ΔT2 = 1.78 ± 0.11 mm/month), and then it gradually decreased in the last 4 weeks (ΔT3). The speed of the PRP-injected canine was faster than the control group by 1.51 times. CONCLUSION: PRP can accelerate the speed of canine movement in orthodontics and can be applied for severe cases, for example, impacted tooth retraction, molar protraction or retraction, and other cases.

Norms of soft tissue cephalometric in the 18-25 age demography in Vietnam.

BACKGROUND AND PURPOSE: The soft-tissue layer and facial skeleton influence the harmony and equilibrium of the face. The evaluation of the patient's structural and soft-tissue features is one of the most crucial steps in preparing for the diagnosis and treatment of oral-maxillofacial orthodontics. Clinicians can intervene with the proper treatment at the proper time to achieve the best results by being aware of the traits and variations of soft tissue at various developmental stages and in various races. To obtain a consistent treatment result in terms of function and aesthetically pleasing results, patients, and forecast, the growth that may take place after the orthopedic therapy has concluded. OBJECTIVE: To examine the soft-tissue features of the oral-maxillofacial area in Vietnamese adults (aged 18-25 years) by evaluating cephalometric radiographs. MATERIALS AND METHODS: In a cross-sectional descriptive study, 85 students from Can Tho University of Medicine and Pharmacy took part. Students' lateral cephalograms were taken in compliance with the sample requirements. RESULTS: Men's lip protrusion (4.30 ± 0.71) was higher than women's (3.88 ± 0.97) (P = 0.024 <.05) and men's (-4.88 ± 0.93) chin lip groove depth was higher than women's (-4.24 ± 0.93) (P = 0.002), both with a P value of. 05. CONCLUSIONS: The study identified a statistically significant difference in the protrusion of the top lip and the depth of the cleft lip between the male and female, demonstrating that the soft-tissue features of Vietnamese students were distinct from those of other races.

Analysis of the Chloroplast Genome of Ficus simplicissima Lour Collected in Vietnam and Proposed Barcodes for Identifying Ficus Plants.

Ficus simplicissima Lour. is an Asian species of fig tree in the family Moraceae. The chloroplast (cp) genome of F. simplicissima m3 was sequenced using the Pacbio sequel platform. The F. simplicissima cpDNA has a size of 160,321 bp in length, of which GC content accounts for 36.13%. The cp genome of F. simplicissima consists of a single large copy (LSC) with a size of 91,346 bp, a single small copy (SSC) with a size of 20,131 bp, and a pair of inverted repeats with a size of 24,421 to 24,423 bp. The cp genome of F. simplicissima has 127 genes, including 85 protein-coding genes, eight rRNA genes, and 34 tRNA genes; 92 simple sequence repeats and 39 long repeats were detected in the cpDNA of F. simplicissim. A comparative cp genome analysis among six species in the Ficus genus indicated that the genome structure and gene content were highly conserved. The non-coding regions show more differentiation than the coding regions, and the LSC and SSC regions show more differences than the inverted repeat regions. Phylogenetic analysis supported that F. simplicissima m3 had a close relationship with F. hirta. The complete cp genome of F. simplicissima was proposed as a chloroplast DNA barcoding for genus-level in the Moraceae family and the psbA-trnH gene region for species-level identification.

A highly quality genome sequence of Penicillium oxalicum species isolated from the root of Ixora chinensis in Vietnam.

Penicillium oxalicum has been reported as a multienzyme-producing fungus and is widely used in industry due to great potential for cellulase release. Until now, there are only 10 available genome assemblies of P. oxalicum species deposited in the GenBank database. In this study, the genome of the I1R1 strain isolated from the root of Ixora chinensis was completely sequenced by Pacbio Sequel sequencing technology, assembled into 8 chromosomes with the genome size of 30.8 Mb, as well as a mitogenome of 26 kb. The structural and functional analyses of the I1R1 genome revealed gene model annotations encoding an enzyme set involved in significant metabolic processes, along with cytochrome P450s and secondary metabolite biosynthesis. The comparative analysis of the P. oxalicum species based on orthology and gene family duplications indicated their large and closed pan-genome of 9,500 orthologous groups. This is valuable data for future phylogenetic and population genomics studies.

6'-Sialylactose abolished lipopolysaccharide-induced inflammation and hyper-permeability in endothelial cells.

Disruption of the endothelial barrier function and reduction in cell migration leads to endothelial dysfunction. One of the most abundant human milk oligosaccharides, 6'-sialylactose (6'-SL), is reported to exert various biological functions related to inflammatory responses. In this study, we evaluated the effects of 6'-SL on lipopolysaccharide (LPS)-induced inflammation caused by endothelial barrier damage. Our results showed that LPS at 500 ng/mL strongly not only abolished cell migration but also hyperactivated MAPK and NF-κB pathways. 6'-SL suppressed LPS-induced endothelial inflammation via ERK1/2, p38, and JNK MAPK pathways. 6'-SL supported endothelial junctions by upregulating PECAM-1 expression and mRNA levels of tight junctions, such as ZO-1 and occludin, which were downregulated by LPS stimulation. It significantly inhibited the nuclear translocation of NF-κB, along with the downregulation of inflammatory cytokines, including TNF-α, IL-1ß, MCP-1, VCAM-1, and ICAM-1. Furthermore, 6'-SL abolished NF-κB-mediated STAT3 in controlling endothelial migration and hyperpermeability via downregulating STAT3 activation and nuclear translocation. Finally, LPS induced over-expression of VCAM-1 and ZO-1 disassembly in both atheroprone and atheroprotective areas of mouse aorta, which were reversed by 6'-SL treatment. Altogether, our findings suggest that 6'-SL is a potent therapeutic agent for modulating inflammatory responses and endothelial hyperpermeability.

Ginsenoside Rh1 protects human endothelial cells against lipopolysaccharide-induced inflammatory injury through inhibiting TLR2/4-mediated STAT3, NF-κB, and ER stress signaling pathways.

AIM: Endothelial cell (EC) dysfunction initiates atherosclerosis by inducing inflammatory cytokines and adhesion molecules. Herein, we investigated the role of ginsenoside Rh1 (Rh1) in lipopolysaccharide (LPS)-induced EC dysfunction. MAIN METHODS: The inhibitory effect of Rh1 on LPS binding to toll-like receptor 2 (TLR2) or TLR4 was evaluated using an immunofluorescence (IF) assay. Annexin V and cleaved caspase-3-positive EC apoptosis were evaluated by flow cytometry and IF assay. Western blotting and quantitative reverse transcription-PCR were performed to clarify underlying molecular mechanisms. In vivo model, effect of Rh1 on EC dysfunction was evaluated by using en face IF assay on aortas isolated C57BL/6 mice. KEY FINDING: LPS (500 ng/mL) activated inflammatory signaling pathways, including ERK1/2, STAT3, and NF-κB. Interestingly, Rh1 significantly abolished the binding of LPS to TLR2 and TLR4. Consistently, Rh1 inhibited LPS-induced NF-κB activation and its downstream molecules, including inflammatory cytokines and adhesion molecules. Furthermore, Rh1 alleviated LPS-induced downregulation of eNOS promoter activity. Notably, inactivation of eNOS by 50 µM L-NAME significantly increased NF-κB promoter activity. In addition, Rh1 abolished LPS-mediated cell cycle arrest and EC apoptosis by inhibiting endoplasmic reticulum stress via PERK/CHOP/ERO1-α signaling pathway. Consistent with in vitro experimental data, Rh1 effectively suppressed LPS-induced VCAM-1 and CHOP expression and rescuing LPS-destroyed tight junctions between ECs as indicated in ZO-1 expression on mice aorta. SIGNIFICANCE: Rh1 suppresses LPS-induced EC inflammation and apoptosis by inhibiting STAT3/NF-κB and endoplasmic reticulum stress signaling pathways, mediated by blocking LPS binding-to TLR2 and TLR4. Consistently, Rh1 effectively reduced EC dysfunction in vivo model.

Inhibitory effects of 6'-sialyllactose on angiotensin II-induced proliferation, migration, and osteogenic switching in vascular smooth muscle cells.

Excessive production and migration of vascular smooth muscle cells (VSMCs) are associated with vascular remodeling that causes vascular diseases, such as restenosis and hypertension. Angiotensin II (Ang II) stimulation is a key factor in inducing abnormal VSMC function. This study aimed to investigate the effects of 6'-sialyllactose (6'SL), a human milk oligosaccharide, on Ang II-stimulated cell proliferation, migration and osteogenic switching in rat aortic smooth muscle cells (RASMCs) and human aortic smooth muscle cells (HASMCs). Compared with the control group, Ang II increased cell proliferation by activating MAPKs, including ERK1/2/p90RSK/Akt/mTOR and JNK pathways. However, 6'SL reversed Ang II-stimulated cell proliferation and the ERK1/2/p90RSK/Akt/mTOR pathways in RASMCs and HASMCs. Moreover, 6'SL suppressed Ang II-stimulated cell cycle progression from G0/G1 to S and G2/M phases in RASMCs. Furthermore, 6'SL effectively inhibited cell migration by downregulating NF-κB-mediated MMP2/9 and VCAM-1 expression levels. Interestingly, in RASMCs, 6'SL attenuated Ang II-induced osteogenic switching by reducing the production of p90RSK-mediated c-fos and JNK-mediated c-jun, leading to the downregulation of AP-1-mediated osteopontin production. Taken together, our data suggest that 6'SL inhibits Ang II-induced VSMC proliferation and migration by abolishing the ERK1/2/p90RSK-mediated Akt and NF-κB signaling pathways, respectively, and osteogenic switching by suppressing p90RSK- and JNK-mediated AP-1 activity.

Determinants of environmental financing constraints: a case study from Vietnam.

The Environment Fund is a state financial institution and a non-profit organization, operating mainly in concessional loans with low-interest rates for green investment projects, working towards sustainable development. There have been no studies to assess the firms' ability to access environmental finance from these Environment Funds. This study uses a combination of both qualitative and quantitative methods. We initially identified the determinants of access to green finance and financing constraints that firms face by in-depth interviews with 32 individuals from the six largest Environment Funds in Vietnam and their clients. Secondly, by surveying 213 firms that had loan request from 26 Environment Funds, we investigated the factors affecting access to environmental finance by the Ordered Probit model. The findings show that firm characteristics and environmental project characteristics have a relationship vis-a-vis access to green finance. We did not find evidence that supports state-owned firms experiencing less financing constraints than other types of firms. Collateral requirements, excessive paperwork requirements, and insufficient capital from Environment Funds are the three main obstacles to green financing. Environment Funds should design loan packages that are more diversified and suitable for different types of environmental projects. At the same time, a more relaxed collateral policy should be applied in Environment Funds to enhance firms' ability to obtain green finance. We suggest that Environment Funds cooperate with commercial banks to provide financial support for the environment to compensate for capital size constraints and asymmetric information.