Oleanane-Type Triterpene Glycosides from Camellia phanii and Their α-Glucosidase Inhibitory Activity.

Three new oleanane-type triterpene saponins, named camphanosides A-C (1-3), along with five known compounds, chikusetsusaponin IVa (4), spinasaponin A 28-O-glucoside (5), (-)-epicatechin (6), (--)-epicatechin 3-O-gallate (7), and (-)-epigallocatechin 3-O-gallate (8) were isolated from the leaves Camellia phanii Hakoda & Ninh. Their structures were established by 1D and 2D-NMR and mass spectral analysis and chemical methods. Moreover, compounds 1-5 were also evaluated for α-glucosidase inhibitory activity. Compounds 1-3 exhibited moderate α-glucosidase inhibitory activity with IC50 values of 230.7±18.0, 251.4±22.7, and 421.4±25.6 µM, respectively.

Avian H6 Influenza Viruses in Vietnamese Live Bird Markets during 2018-2021.

Avian influenza viruses of the H6 subtype are prevalent in wild ducks and likely play an important role in the ecology of influenza viruses through reassortment with other avian influenza viruses. Yet, only 152 Vietnamese H6 virus sequences were available in GISAID (Global Initiative on Sharing All Influenza Data) prior to this study with the most recent sequences being from 2018. Through surveillance in Vietnamese live bird markets from 2018 to 2021, we identified 287 samples containing one or several H6 viruses and other influenza A virus subtypes, demonstrating a high rate of co-infections among birds in Vietnamese live bird markets. For the 132 H6 samples with unique influenza virus sequences, we conducted phylogenetic and genetic analyses. Most of the H6 viruses were similar to each other and closely related to other H6 viruses; however, signs of reassortment with other avian influenza viruses were evident. At the genetic level, the Vietnamese H6 viruses characterized in our study encode a single basic amino acid at the HA cleavage site, consistent with low pathogenicity in poultry. The Vietnamese H6 viruses analyzed here possess an amino acid motif in HA that confers binding to both avian- and human-type receptors on host cells, consistent with their ability to infect mammals. The frequent detection of H6 viruses in Vietnamese live bird markets, the high rate of co-infections of birds with different influenza viruses, and the dual receptor-binding specificity of these viruses warrant their close monitoring for potential infection and spread among mammals.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum, revealing distinct, modality-specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and the spatial localization of behavioral function across large circuits.

Investigating the effects of ultrafine bubbles on bacterial growth.

Several previous studies have considered ultrafine bubbles as a potential research target because their properties can be applied in many different research areas. In particular, the interaction between UFBs and microorganisms has always been one of the aspects that receives much attention due to the high difficulty in controlling a living system. The properties of UFBs, as mobile air-water interfaces, are greatly determined by their gas cores which play a critical role in regulating microbial growth. This study aims to investigate the effects of ultrafine bubbles on bacterial growth. Two well-studied organisms were chosen as models - Escherichia coli and Staphylococcus aureus. Their growing behavior was examined based on the growth rate, phenotype and biomass. Three types of Luria-Bertani cultures were tested, including a standard culture containing distilled water, an air ultrafine bubble culture, and a hydrogen ultrafine bubble culture. The UFBs were generated via ultrasonic cavitation and stabilized by 50 µM SDS, which was proven to have negligible effects on bacterial growth. By comparing among the three cultivation conditions, the bacterial growth rates were observed to be the highest in exposure to HUFBs. The results also signified that UFBs had an enhancement on cell proliferation. On the other hand, while proposing an increase in cell density, bacteria cultured in HUFB media have their sizes decreased uniformly and significantly (p-value < 0.05). This study confirmed that bacterial growth was promoted by UFBs; and better effects recorded were due to the HUFB present in the culture media. However, the average morphological size of bacteria was in negative correlation with their population size.

Preventing Static Biofilm Formation of Staphylococcus aureus on Different Types of Surfaces Using Microbubbles.

Bacterial fouling and biofilm formation on surfaces have been ongoing problems in real life as well as in the medical field. Different approaches have been taken to tackle the issues, from costly surface modification to antibiotic-delivering strategies. In this study, we examined the potential of using stabilized microbubbles (MBs) to shield against bacterial adhesion. Three types of surfaces were tested: hydrophilic glass (hydrophilic surface), neutral hydrophobic polystyrene (PS)-coated surfaces, and negatively charged hydrophobic octadecyltrichlorosilane (OTS)-coated surfaces. By evaluating the colony-forming unit (CFU) values from each surface, MBs stabilized by 0.05 mM SDS were shown to only produce significant reduction of Staphylococcus aureus adhesion on PS surfaces, up to 60.29 and 82.32% compared to no-MB PS surfaces, and no-MB uncoated surfaces, correspondingly, due to the appropriate size, stability, and negative charges of the MB shielding layer. On the other hand, OTS coatings had an intrinsic antiadhesion effect (69.83% compared to uncoated surface), given that the negatively charged OTS-aqueous interface or surface porosity nature of the coating prohibited the attachment of MBs, leading to the elimination of the antifouling effect of MBs. Ultimately, MBs gave better shielding results than surface modification when compared to uncoated surfaces and hence can be applied more widely.

Pre-existing cross-reactive neutralizing activity against SARS-CoV-2 and seasonal coronaviruses prior to the COVID-19 pandemic (2014-2019) with limited immunity against recent emerging SARS-CoV-2 variants, Vietnam.

OBJECTIVES: SARS-CoV-2 transmission and epidemic potential is related to the population's immunity levels. As such, assessing different regions' preexisting immune responses to SARS-CoV-2 is important to understand the transmission potential of emerging SARS-CoV-2 variants. DESIGN: In 975 serum samples from Vietnam (2014 to 2019), anti-SARS-CoV-2 Immunoglobulin G levels were determined by enzyme-linked immunosorbent assay. Plaque reduction neutralization test (PRNT) was performed using Wuhan strain and variants of concern (VOCs). Cross-reactivity was confirmed by analyzing B-cell receptor (BCR) repertoire sequences and identifying BCR repertoire sequences-derived T-cell epitopes. RESULTS: Overall, 20.9% (n = 76/364) and 9.2% (n = 7) demonstrated SARS-CoV-2 neutralizing activity (PRNT50) against the Wuhan and Alpha strain, respectively. Neutralizing activity against Beta, Gamma, and Delta strains was absent (PRNT50<5) in all samples. Cross-reactive epitopes against SARS-CoV-2 and other coronavirus spike proteins were detected in the N-terminal domain, S2, and receptor-binding domain regions. CONCLUSIONS: Following BCR and major histocompatibility complex analysis, T-cell receptor-recognized epitope motif (TREM) among pathogenic coronaviruses and coronaviruses spike proteins were the top TREM peptide, suggesting that pre-existing immunity against SARS-CoV-2 in Vietnam was due to exposure to common cold coronaviruses. With limited immunity against emerging VOCs, further monitoring, and control of the epidemic, along with COVID-19 vaccine programs against VOCs, are necessary.

Review on the Significant Interactions between Ultrafine Gas Bubbles and Biological Systems.

Having sizes comparable with living cells and high abundance, ultrafine bubbles (UBs) are prone to inevitable interactions with different types of cells and facilitate alterations in physiological properties. The interactions of four typical cell types (e.g., bacterial, fungal, plant, and mammalian cells) with UBs have been studied over recent years. For bacterial cells, UBs have been utilized in creating the capillary force to tear down biofilms. The release of high amounts of heat, pressure, and free radicals during bubble rupture is also found to affect bacterial cell growth. Similarly, the bubble gas core identity plays an important role in the development of fungal cells. By the proposed mechanism of attachment of UBs on hydrophobin proteins in the fungal cell wall, oxygen and ozone gas-filled ultrafine bubbles can either promote or hinder the cell growth rate. On the other hand, reactive oxygen species (ROS) formation and mass transfer facilitation are two means of indirect interactions between UBs and plant cells. Likewise, the use of different gas cores in generating bubbles can produce different physical effects on these cells, for example, hydrogen gas for antioxidation against infections and oxygen for oxidation of toxic metal ions. For mammalian cells, the importance of investigating their interactions with UBs lies in the bubbles' action on cell viability as membrane poration for drug delivery can greatly affect cells' survival. UBs have been utilized and tested in forming the pores by different methods, ranging from bubble oscillation and microstream generation through acoustic cavitation to bubble implosion.

Circulation of human respiratory syncytial virus and new ON1 genotype in northern Viet Nam, 2017-2020.

Objective: Human respiratory syncytial virus (RSV) is a primary cause of paediatric severe acute respiratory infection (SARI) worldwide, especially in developing countries. We investigated the genetic characteristics of RSV in northern Viet Nam to determine the prevalence and distribution of subtypes as well as the diversity and transmission patterns of genotypes. Methods: In two facilities, from January 2017 to December 2020, 1563 clinical specimens were collected from paediatric patients hospitalized with SARI and tested for RSV. Selected positive samples underwent sequencing analysis targeting the second hypervariable region of the G gene using next-generation sequencing. Results: The RSV positivity rate was 28.02% (438/1563 samples), and prevalence was highest in children aged < 1 year (43.84%; 192/438). Subtype RSV-A accounted for 53.42% (234/438) of cases, RSV-B for 45.89% (201/438), and there was coinfection in 0.68% (3/438). Both subtypes cocirculated and peaked during August-September in each year of the study. Phylogenetic analysis showed that RSV-A samples belonged to the ON1 genotype, which has three subgenotypes: ON1.1, ON1.2 and ON1.3. However, we did not find the 72-nucleotide duplication in the second hypervariable region of the G gene, a characteristic of genotype ON1, in any RSV-A samples. RSV-B samples belonged to genotype BA9. Discussion: Our results provide additional molecular characterization of RSV infections in Viet Nam. Specially, our study is the first to report the absence of the 72-nucleotide duplication in the G gene of RSV-A genotype ON1 in Viet Nam, which may help in understanding the genetic evolution of RSV and be useful for vaccine development in the future.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant for behavior vary over multiple spatial and temporal scales across 3-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array and imaging approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice. We developed a semi-automated micro-CT based strategy to precisely localize positions of each optical fiber. This highly-customizable approach enables investigation of multi-scale spatial and temporal patterns of cell-type and neurotransmitter specific signals over arbitrary 3-D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum volume which revealed distinct, modality specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics through our fiber arrays enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and spatial localization of behavioral function across large circuits.

Compass for antibiotic stewardship: using a digital tool to improve guideline adherence and drive clinician behaviour for appendicitis treatment in the emergency department.

BACKGROUND: Antibiotic stewardship in the ED is important given the increasing prevalence of multidrug resistance associated with poorer patient outcomes. The use of broad-spectrum antibiotics in the ED for infections like appendicitis is common. At baseline, 75% of appendicitis cases at our institution received broad-spectrum ertapenem rather than the recommended narrower-spectrum ceftriaxone/metronidazole combination. We aimed to improve antibiotic stewardship by identifying barriers to guideline adherence and redesigning our appendicitis antibiotic guideline. METHODS: Using the 'Fit between Individuals, Task and Technology (FITT)' framework, we identified barriers that preventclinicians from adhering to guidelines. We reformatted a clinical guideline and disseminated it using our ED's clinical decision support system (CDSS), E*Drive. Next, we examined E*Drive's user data and clinician surveys to assess utilisation and satisfaction. Finally, we conducted a retrospective chart review to measure clinician behaviour change in antibiotic prescription for appendicitis treatment. RESULTS: Data demonstrated an upward trend in the number of monthly users of E*Drive from 1 April 2021 to 30 April 2022, with an average increase of 46 users per month. Our clinician survey results demonstrated that >95% of users strongly agree/agree that E*Drive improves access to clinical information, makes their job more efficient and that E*Drive is easy to access and navigate, with a Net Promoter Score increase from 26.0 to 78.3. 69.4% of patients treated for appendicitis in the post-intervention group received antibiotics concordant with our institutional guideline compared with 20.0% in the pre-intervention group (OR=9.07, 95% CI (3.84 to 21.41)). CONCLUSION: Antibiotic stewardship can be improved by ensuring clinicians have access to convenient and up-to-date guidelines through clinical decision support systems. The FITT model can help guide projects by identifying individual, task and technology barriers. Sustained adherence to clinical guidelines through simplification of guideline content is a potentially powerful tool to influence clinician behaviour in the ED.

Continued Circulation of Highly Pathogenic H5 Influenza Viruses in Vietnamese Live Bird Markets in 2018-2021.

We isolated 77 highly pathogenic avian influenza viruses during routine surveillance in live poultry markets in northern provinces of Vietnam from 2018 to 2021. These viruses are of the H5N6 subtype and belong to HA clades 2.3.4.4g and 2.3.4.4h. Interestingly, we did not detect viruses of clade 2.3.4.4b, which in recent years have dominated in different parts of the world. The viruses isolated in this current study do not encode major determinants of mammalian adaptation (e.g., PB2-E627K or PB1-D701N) but possess amino acid substitutions that may affect viral receptor-binding, replication, or the responses to human antiviral factors. Several of the highly pathogenic H5N6 virus samples contained other influenza viruses, providing an opportunity for reassortment. Collectively, our study demonstrates that the highly pathogenic H5 viruses circulating in Vietnam in 2018-2021 were different from those in other parts of the world, and that the Vietnamese H5 viruses continue to evolve through mutations and reassortment.

Novel gain-tuning for sliding mode control of second-order mechanical systems: theory and experiments.

The sliding mode control is well-known as a useful control technique that can be applied in several real-world applications. However, a straightforward and efficient process of selecting the sliding mode control gains remains a challenging but interesting topic. This paper investigates a novel gain tuning method for the sliding mode control of second-order mechanical systems. Firstly, we obtain relations between the gains and the natural and damping ratio of the closed-loop system. Secondly, the time constant of the system's actuators and the system response performance criteria, including settling time and delay time, are taken into consideration to determine appropriate ranges of the gains. These gain ranges allow control designers to select the controller gains in a time-saving manner and ensure that the desired system performance is met and the actuators work properly. Finally, the proposed method is applied to the gain tuning process of a sliding mode altitude controller for an actual quadcopter unmanned aerial vehicle. Simulation and experimental results demonstrate the applicability and effectiveness of this method.

Highly Pathogenic H5 Influenza Viruses Isolated between 2016 and 2017 in Vietnamese Live Bird Markets.

Routine surveillance in live poultry markets in the northern regions of Vietnam from 2016 to 2017 resulted in the isolation of 27 highly pathogenic avian H5N1 and H5N6 viruses of 3 different clades (2.3.2.1c, 2.3.4.4f, and 2.3.4.4g). Sequence and phylogenetic analysis of these viruses revealed reassortment with various subtypes of low pathogenic avian influenza viruses. Deep-sequencing identified minor viral subpopulations encoding variants that may affect pathogenicity and sensitivity to antiviral drugs. Interestingly, mice infected with two different clade 2.3.2.1c viruses lost body weight rapidly and succumbed to virus infection, whereas mice infected with clade 2.3.4.4f or 2.3.4.4g viruses experienced non-lethal infections.

Spatiotemporal Evolution of SARS-CoV-2 Alpha and Delta Variants during Large Nationwide Outbreak of COVID-19, Vietnam, 2021.

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions.

Engineered Ferritin Nanoparticle Vaccines Enable Rapid Screening of Antibody Functionalization to Boost Immune Responses.

Employing monoclonal antibodies to target vaccine antigens to different immune cells within lymph nodes where adaptive immunity is initiated can provide a mechanism to fine-tune the magnitude or the quality of immune responses. However, studying the effects of different targeting antibodies head-to-head is challenging due to the lack of a feasible method that allows rapid screening of multiple antibodies for their impact on immunogenicity. Here self-assembling ferritin nanoparticles are prepared that co-display vaccine antigens and the Fc-binding domain of Staphylococcal protein A, allowing rapid attachment of soluble antibodies to the nanoparticle surface. Using this tunable system, ten antibodies targeting different immune cell subsets are screened, with targeting to Clec9a associated with higher serum antibody titers after immunization. Immune cell targeting using ferritin nanoparticles with anti-Clec9a antibodies drives concentrated deposition of antigens within germinal centers, boosting germinal center formation and robust antibody responses. However, the capacity to augment humoral immunity is antigen-dependent, with significant boosting observed for prototypic ovalbumin immunogens but reduced effectiveness with the SARS-CoV-2 RBD. This work provides a rapid platform for screening targeting antibodies, which will accelerate mechanistic insights into optimal delivery strategies for nanoparticle-based vaccines to maximize protective immunity.

Insect repellents: An updated review for the clinician.

Malaria, Zika virus, West Nile virus, Dengue fever, and Lyme disease are common causes of morbidity and mortality around the world. While arthropod bites may cause local inflammation and discomfort, a greater concern is the potential to develop deadly systemic infection. The use of insect repellents (IRs) to prevent systemic infections constitutes a fundamental public health effort. Cost effectiveness, availability, and high efficacy against arthropod vectors are key characteristics of an ideal IR. Currently, numerous IRs are available on the market, with N,N-diethyl-3-methylbenzamide (DEET) being the most widely used. DEET has an excellent safety profile and remarkable protection against mosquitoes and various other arthropods. Other Environmental Protection Agency-registered IR ingredients (eg, permethrin, picaridin, IR3535, oil of lemon eucalyptus, oil of citronella, catnip oil, and 2-undecanone) are alternative IRs of great interest because some of these ingredients have efficacies comparable to that of DEET. These alternative IRs possess low toxicity and favorable customer experiences in use (eg, cosmetically pleasant, naturally occurring). This review summarizes the currently available Environmental Protection Agency-registered IRs, including their origins, mechanisms of action, side effect profiles, and available formulations. This review will enable the clinician to select the best IR option to meet a patient's needs and provide the greatest protection from arthropod bites and their sequelae.

Barrier function-based adaptive nonsingular terminal sliding mode control technique for a class of disturbed nonlinear systems.

In this article, an adaptive non-singular terminal sliding mode controller (NTSMC) is designed based on a barrier function for the robust stability of a category of non-linear dynamic systems in the existence of the external disturbances. The planned approach implements a non-singular terminal sliding mode controller (NTSMC) to ensure robust performance with finite time convergence and singularity-free dynamics. It also uses Barrier Functions (BFs) as an adaptation approach for the NTSMC to attain the tracking errors' convergence to a pre-defined neighbourhood of origin, with a controller gain that is not over-estimated and without requiring any knowledge about the upper bounds of disturbances. The Lyapunov-based stability analysis is carried out to confirm the asymptotic convergence of tracking errors to a pre-defined neighbourhood of zero. The effectiveness and performance of the planned approach is illustrated through simulations and experiments.

Hippocampal convergence during anticipatory midbrain activation promotes subsequent memory formation.

The hippocampus has been a focus of memory research since H.M's surgery abolished his ability to form new memories, yet its mechanistic role in memory remains debated. Here, we identify a candidate memory mechanism: an anticipatory hippocampal "convergence state", observed while awaiting valuable information, and which predicts subsequent learning. During fMRI, participants viewed trivia questions eliciting high or low curiosity, followed seconds later by its answer. We reasoned that encoding success requires a confluence of conditions, so that hippocampal states more conducive to memory formation should converge in state space. To operationalize convergence of neural states, we quantified the typicality of multivoxel patterns in the medial temporal lobes during anticipation and encoding of trivia answers. We found that the typicality of anticipatory hippocampal patterns increased during high curiosity. Crucially, anticipatory hippocampal pattern typicality increased with dopaminergic midbrain activation and uniquely accounted for the association between midbrain activation and subsequent recall. We propose that hippocampal convergence states may complete a cascade from motivation and midbrain activation to memory enhancement, and may be a general predictor of memory formation.