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Seaweed from macroalgae and cellulose from nonwood materials have gained attention in various fields. This study explores how seaweed and cellulose nanofibers (CNF) interact to form 3D networks in composite bioaerogels. The ratio of CNF and seaweed was varied to see how it affects the aerogel’s inside and its properties. The observations show that the biocomposite aerogel is more rigid and shrinks less than using a single biopolymer. The CNF aerogel has a fine, thin network structure, and the seaweed aerogel has a thin sheet structure. The biocomposite aerogel combines both a fine network and a thin sheet structure. The composite aerogel’s mechanical properties are significantly influenced by seaweed composition. The introduction of CNF increases elasticity, while seaweed enhances firmness. Generated computer modelling revealed that the abundant hydroxyl groups in CNF facilitated the formation of intermolecular bonds with seaweed. The bonding led to increased adhesion and entanglement between biopolymers, consequently enhancing elasticity and establishing a stable intermolecular interaction. The 3D X-ray imaging model shows that the skeletal framework primarily consists of seaweed biopolymer, with CNF serving to reinforce this structure thus enhancing the mechanical properties and robustness of the composite bioaerogels.

ABSTRACT: The pressing issue of the moment affecting public health is antimicrobial resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen that is proven to be resistant to a range of antibiotics like penicillins, cephalosporins, other β ββ-lactam antibiotics, and carbapenems. Baicalein, a phytochemical of the traditional Chinese herb, Scutellaria baicalensis has an inhibitory effect on different bacteria. The current study aimed to investigate the synergistic effect of baicalein and β ββlactam antibiotics (amoxicillin and ampicillin) against methicillin-resistant S. aureus (MRSA). The minimum inhibitory concentrations (MICs) of baicalein and β-lactam antibiotics (amoxicillin and ampicillin) against the MRSA were determined through the broth dilution method. The determination of synergism was tested by checkerboard tube dilution and time-kill assay procedure. The combination of baicalein with amoxicillin showed more potent synergy against MRSA strain compared to the combination of baicalein and ampicillin. The fractional inhibitory concentration indices (FICI) of amoxicillin + baicalein varied from 0.19 to 0.50. The fractional inhibitory concentration (FIC) indices of ampicillin + baicalein varied from 0.19 to 0.25. These findings offer significant evidence that the amoxicillin combined with baicalein showed potent synergistic activity against MRSA in vitro and might offer promising therapeutic implications for MRSA infections.

INTRODUCTION: Most people with Alzheimer's disease and related dementia (ADRD) also suffer from two or more chronic conditions, known as multiple chronic conditions (MCC). While many studies have investigated the MCC patterns, few studies have considered the synergistic interactions with other factors (called the syndemic factors) specifically for people with ADRD. METHODS: We included 40,290 visits and identified 18 MCC from the National Alzheimer's Coordinating Center. Then, we utilized a multi‐label XGBoost model to predict developing MCC based on existing MCC patterns and individualized syndemic factors. RESULTS: Our model achieved an overall arithmetic mean of 0.710 AUROC (SD = 0.100) in predicting 18 developing MCC. While existing MCC patterns have enough predictive power, syndemic factors related to dementia, social behaviors, mental and physical health can improve model performance further. DISCUSSION: Our study demonstrated that the MCC patterns among people with ADRD can be learned using a machine‐learning approach with syndemic framework adjustments. Highlights: Machine learning models can learn the MCC patterns for people with ADRD.The learned MCC patterns should be adjusted and individualized by syndemic factors.The model can predict which disease is developing based on existing MCC patterns.As a result, this model enables early specific MCC identification and prevention. [ABSTRACT FROM AUTHOR]

Abstract Phages can successfully be used in vitro and in planta to biocontrol the phytopathogenic Ralstonia solanacearum bacterium—the causal agent of bacterial wilt disease. However, phage biocontrol outcomes are still variable, and it is unclear what causes this. In this study, we assessed the efficiency of four phages in controlled in vitro and in planta experiments in all one‐ and two‐phage combinations. We found that using phages in combination did not improve the phage biocontrol efficiency relative to single phage treatments, while certain phages and their combinations were more effective than the others. High intra‐treatment variability in phage efficiency was observed across all phage treatments, which was associated with clear shifts in microbiome composition, a reduction in R. solanacearum and an increase in phage densities. We further identified the bacterial taxa that were associated with these ‘shifted’ microbiomes and conducted additional plant growth experiments, demonstrating that some of the enriched bacterial species could protect plants from R. solanacearum infections—a pattern which was also observed using partial least squares path modelling (PLS‐PM). Together, these results suggest that phages could open niche space for beneficial bacteria by reducing pathogen densities and that variability in phage biocontrol outcomes is rhizosphere microbiome‐dependent, which can introduce between‐replicate variation, even in controlled greenhouse conditions.

ABSTRACT Metabolic exchange plays a crucial role in shaping microbial community interactions and functions, including the exchange of small molecules such as cofactors. Cofactors are fundamental to enzyme catalytic activities; however, the role of cofactors in microbial stress tolerance is unclear. Here, we constructed a synergistic consortium containing two strains that could efficiently mineralize di-(2-ethylhexyl) phthalate under hyperosmotic stress. Integration of transcriptomic analysis, metabolic profiling, and a genome-scale metabolic model (GEM) facilitated the discovery of the potential mechanism of microbial interactions. Multi-omics analysis revealed that the vitamin B12-dependent methionine-folate cycle could be a key pathway for enhancing the hyperosmotic stress tolerance of synergistic consortium. Further GEM simulations revealed interspecies exchange of S-adenosyl-L-methionine and riboflavin, cofactors needed for vitamin B12 biosynthesis, which was confirmed by in vitro experiments. Overall, we proposed a new mechanism of bacterial hyperosmotic stress tolerance: bacteria might promote the production of vitamin B12 to enhance biofilm formation, and the species collaborate with each other by exchanging cofactors to improve consortium hyperosmotic stress tolerance. These findings offer new insights into the role of cofactors in microbial interactions and stress tolerance and are potentially exploitable for environmental remediation.IMPORTANCEMetabolic interactions (also known as cross-feeding) are thought to be ubiquitous in microbial communities. Cross-feeding is the basis for many positive interactions (e.g., mutualism) and is a primary driver of microbial community assembly. In this study, a combination of multi-omics analysis and metabolic modeling simulation was used to reveal the metabolic interactions of a synthetic consortium under hyperosmotic stress. Interspecies cofactor exchange was found to promote biofilm formation under hyperosmotic stress. This provides a new perspective for understanding the role of metabolic interactions in microbial communities to enhance environmental adaptation, which is significant for improving the efficiency of production activities and environmental bioremediation.

Anaerobic ammonium oxidizing (anammox) bacteria are utilized for high efficiency nitrogen removal from nitrogen-laden sidestreams in wastewater treatment plants. The anammox bacteria form a variety of competitive and mutualistic interactions with heterotrophic bacteria that often employ denitrification or dissimilatory nitrate reduction to ammonium (DNRA) for energy generation. These interactions can be heavily influenced by the influent ratio of ammonium to nitrite, NH4+:NO2-, where deviations from the widely acknowledged stoichiometric ratio (1:1.32) have been demonstrated to have deleterious effects on anammox efficiency. Thus, it is important to understand how variable NH4+:NO2- ratios impact the microbial ecology of anammox reactors. We observed the response of the microbial community in a lab scale anammox membrane bioreactor (MBR) to changes in the influent NH4+:NO2- ratio using both 16S rRNA gene and shotgun metagenomic sequencing. Ammonium removal efficiency decreased from 99.77 ± 0.04% when the ratio was 1:1.32 (prior to day 89) to 90.85 ± 0.29% when the ratio was decreased to 1:1.1 (day 89-202) and 90.14 ± 0.09% when the ratio was changed to 1:1.13 (day 169-200). Over this same timespan, the overall nitrogen removal efficiency (NRE) remained relatively unchanged (85.26 ± 0.01% from day 0-89, compared to 85.49 ± 0.01% from day 89-169, and 83.04 ± 0.01% from day 169-200). When the ratio was slightly increased to 1:1.17-1:1.2 (day 202-253), the ammonium removal efficiency increased to 97.28 ± 0.45% and the NRE increased to 88.21 ± 0.01%. Analysis of 16 S rRNA gene sequences demonstrated increased relative abundance of taxa belonging to Bacteroidetes, Chloroflexi, and Ignavibacteriae over the course of the experiment. The relative abundance of Planctomycetes, the phylum to which anammox bacteria belong, decreased from 77.19% at the beginning of the experiment to 12.24% by the end of the experiment. Analysis of metagenome assembled genomes (MAGs) indicated increased abundance of bacteria with nrfAH genes used for DNRA after the introduction of lower influent NH4+:NO2- ratios. The high relative abundance of DNRA bacteria coinciding with sustained bioreactor performance indicates a mutualistic relationship between the anammox and DNRA bacteria. Understanding these interactions could support more robust bioreactor operation at variable nitrogen loading ratios.

The interactions between pathogens during infection and the impact of these interactions on drug effectiveness are poorly understood, making polymicrobial infections challenging to treat. During an infection, cross-interactions between bacteria and fungi can strengthen virulence mechanisms and affect how the disease develops. The purpose of this study is to determine how Pseudomonas aeruginosa interacts with Candida glabrata, Candida albicans, Candida krusei, Candida parapsilosis, and Candida tropicalis in the development of polymicrobial biofilms. Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida parapsilosis, Candida glabrata, and Candida tropicalis isolates were used in this experimental investigation. After preparing a 0.5 Mc Farland suspension of each isolate, the gold standard for measuring biofilm was applied: the Tissue Plate Culture (TCP) method. After that, an ELISA reader with a wavelength of 595 nm was used to measure the optical density (OD) of the biofilm. SPSS 26.0 was then used for statistical analysis to compare the OD values between Pseudomonas aeruginosa that had not been exposed to Candida and those that had. Pseudomonas aeruginosa and Candida are found to interact synergistically if there is an increase in OD, and antagonistic interaction is discovered if there is a decrease in OD. In comparison to the group that was not exposed to Candida, Pseudomonas aeruginosa exposed to Candida albicans, Candida krusei, Candida parapsilosis, Candida glabrata, and Candida tropicalis showed an increase in the OD value of biofilm. Pseudomonas aeruginosa and Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis interact synergistically.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features, including amyloid-β plaques, neurofibrillary tangles, and reactive astrogliosis. Developing effective diagnostic, preventative, and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease. Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD. Additionally, these models are limited in their ability to elucidate the interplay among amyloid-β plaques, neurofibrillary tangles, and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation. In this study, we introduce a novel AD mouse model (APP/PS1-TauP301L-Adeno mice) designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms. Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAV DJ -EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice. Three months post-injection, these mice exhibited pronounced astrogliosis, substantial amyloid-β plaque accumulation, extensive neurofibrillary tangles, accelerated neuronal loss, elevated astrocytic GABA levels, and significant spatial memory deficits. Notably, these pathological features were less severe in AAV-TauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis. These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-β plaque and neurofibrillary tangle-associated pathology. The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.

Abstract CRISPR/Cas12a‐based combinational screening has shown remarkable potential for identifying genetic interactions. Here, we describe an innovative method for combinational genetic screening with rapid construction of a dual‐CRISPR RNA (crRNA) library using gene splicing through overlap extension PCR (SOE PCR) and the adoption of CeCas12a, which we previously identified with strict PAM recognition and low off‐targeting to guarantee fidelity and efficiency. The custom‐pooled SOE crRNA array (SOCA) library for double‐knockout screening could be conveniently constructed in the laboratory for widespread use, and the CeCas12a‐mediated high‐fidelity screen displayed good performance even under a negative selection screen. By designing a SOCA dual‐crRNA library that covered most of the kinase and metabolism‐associated gene targets of FDA‐approved drugs implicated in hepatocellular carcinoma (HCC) tumourigenesis, novel cross‐talk between the two gene sets was negatively selected to inhibit HCC cell growth in vitro and in vivo and was validated using virtual double‐knockdown screening based on TCGA databases. Thus, this rapid, efficient and high‐fidelity double‐knockout screening system is promising for systemically identifying potential genetic interactions between multiple gene sets or combinations of FDA‐ approved drugs for clinical translational medicine in the future.

Visfatin, an adipokine secreted by various cell types, plays multifaceted pathophysiological roles in inflammatory conditions, including obesity, which is closely associated with osteoclastogenesis, a key process underlying bone loss and increased osteoporosis (OP) risk. However, the role of visfatin in osteoclastogenesis remains controversial. This study was conducted to investigate the effects of visfatin on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation from precursor cells in vitro. Our results demonstrated that although visfatin exhibited a modest osteoclast-inductive effect relative to that of RANKL, co-stimulation of bone marrow-derived macrophages (BMDMs) with visfatin and RANKL led to significantly enhanced osteoclast differentiation and activation compared to individual stimulation. Neutralization of visfatin activity using blocking antibodies before differentiation markedly suppressed RANKL-induced osteoclastogenesis, as evidenced by a near-complete absence of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts, decreased levels of nuclear factor of activated T cells cytoplasmic 1 and osteoclast-specific proteins, inhibition of nuclear factor-κB and mitogen-activated protein kinase signaling pathways, and a decrease in resorption pit formation. Our findings underscore the critical role of visfatin in RANKL-induced osteoclastogenesis in vitro and highlight the RANKL/visfatin signaling axis as a potential therapeutic target for destructive bone loss-related diseases.

A Planetary Atmospheric Chamber (PAC) was used to create simulations of interplanetary conditions to test the spore survival of three Bacillus spp. exposed to interacting conditions of vacuum (VAC), simulated solar heating (HEAT), and simulated solar ultraviolet irradiation (UV). Synergism was observed among the experimental factors for all three Bacillus spp. tested that suggested the increased lethality of HEAT and UV when concomitantly exposed to VAC. The most aggressive biocidal effects were observed for assays with VAC + HEAT + UV conditions run simultaneously over short time-steps. The results were used to predict the accumulation of extremely rapid Sterility Assurance Levels (SALs; def., −12 logs of bioburden reduction) measured in a few minutes to a few hours for external surfaces of interplanetary spacecraft. Furthermore, the results were extrapolated to predict that approx. 1 × 104 SAL exposures might be accumulated for external surfaces on the Europa Clipper spacecraft during a 3.5-year transit time between Venus (0.7 AU) and Mars (1.5 AU) during a series of Venus–Earth–Earth gravity assists (VEEGA trajectory) to Jovian space. The results are applicable to external spacecraft surfaces exposed to direct solar heating and UV irradiation during transits though the inner solar system.

The micellar and surface behaviors of decylammonium chloride (DACl) in presence of L-alanine hydrochloride decylester (L-ADE) and L-alanine hydrochloride dodecylester (L-ADDE) at various mole fractions were investigated by conductivity and surface tension measurements. From the conductivity measurements, the critical micelle concentration (CMC), the degree of counter-ion ionization (α) and standard Gibbs energy of micellization (ΔG°mic) were investigated for both pure and binary mixtures. The molecular interaction parameter (β) and the micellar mole fraction (XmDACl) for mixed micelle formation by DACl/L-ADE (C10-C10) and DACl/L-ADDE (C10-C12) were calculated using the regular solution equation proposed by Rubingh. The ideal values of CMC (CMCideal) and the micellar mole fraction (XmDACl(ideal)) were also obtained for mixed micelle according to the pseudo phase theoretical models. The negative β values showed that there were synergistic interactions for all compositions of DACl/L-ADE and DACl/L-ADDE mixed systems. From the surface tension measurements, adsorption parameters such as the surface excess concentration (Γmax), minimum surface tension at the CMC, efficiency in the surface tension reduction (pC20), standard Gibbs energy of adsorption (ΔG°ads), and minimum area per head group of a molecule (Amin) in pure, mixed and their ideal values were also determined. The results indicated that the synergism and attractive interactions in the studied binary mixtures depend on the chain length of the cationic L-alanine ester and their mole fractions in the mixed system. The solubilization capacity of pure DACl and its mixed system with L-ADE and L-ADDE towards anthracene were determined and discussed in terms of molar solubilization ratio (MSR). Based on the MSR values, the solubility enhancement was found for anthracene in DACl/L-ADE and DACl/L-ADDE mixed systems.

Synergistic interactions among unrelated viruses in mixed infections can cause significant yield losses, and viral determinants of these interactions are poorly understood. Wheat ( Triticum aestivum L.) co-infection with wheat curl mite-transmitted wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) results in disease synergism with a drastically increased symptom phenotype of stunted growth, leaf bleaching, and enhanced titers of both viruses. In this study, we examined the viral determinants responsible for WSMV-TriMV disease synergism through transient expression of select cistrons of WSMV in wheat through TriMV and vice-versa. We found that expression of WSMV P1, NIa, or NIaPro cistrons in wheat through TriMV or vice-versa elicited moderate to severe symptoms with a moderate or no increase in virus titer. However, co-expression of P1 and NIaPro cistrons of WSMV in wheat through TriMV or vice-versa exhibited a WSMV-TriMV disease synergism-like phenotype. Additionally, we found that the P3 cistron of both viruses is dispensable for synergism, whereas HCPro and NIaVPg cistrons of WSMV and TriMV are not the primary determinants but might have a minor role in efficient synergism. In co-infected wheat, accumulation of vsiRNAs was increased, similar to viral genomic RNA copies, despite the presence of dual viral RNA silencing suppressors (VRSS), which function through sequestration of vsiRNAs. Our findings revealed that WSMV-TriMV disease synergism is not caused by the suppression of host post-transcriptional gene silencing by dual VRSS in co-infected wheat and the P1 and NIaPro cistrons of both viruses collectively drive synergistic interactions between WSMV and TriMV in wheat.

Sustainable food security and safety are major concerns on a global scale, especially in developed nations. Adverse agroclimatic conditions affect the largest agricultural-producing areas, which reduces the production of crops. Achieving sustainable food safety is challenging because of several factors, such as soil flooding/waterlogging, ultraviolet (UV) rays, acidic/sodic soil, hazardous ions, low and high temperatures, and nutritional imbalances. Plant growth-promoting rhizobacteria (PGPR) are widely employed in in-vitro conditions because they are widely recognized as a more environmentally and sustainably friendly approach to increasing crop yield in contaminated and fertile soil. Conversely, the use of nanoparticles (NPs) as an amendment in the soil has recently been proposed as an economical way to enhance the texture of the soil and improving agricultural yields. Nowadays, various research experiments have combined or individually applied with the PGPR and NPs for balancing soil elements and crop yield in response to control and adverse situations, with the expectation that both additives might perform well together. According to several research findings, interactive applications significantly increase sustainable crop yields more than PGPR or NPs alone. The present review summarized the functional and mechanistic basis of the interactive role of PGPR and NPs. However, this article focused on the potential of the research direction to realize the possible interaction of PGPR and NPs at a large scale in the upcoming years.