It is not understood how Hsp104, a hexameric AAA+ ATPase from yeast, disaggregates diverse structures, including stress-induced aggregates, prions, and α-synuclein conformers connected to Parkinson ...disease. Here, we establish that Hsp104 hexamers adapt different mechanisms of intersubunit collaboration to disaggregate stress-induced aggregates versus amyloid. To resolve disordered aggregates, Hsp104 subunits collaborate noncooperatively via probabilistic substrate binding and ATP hydrolysis. To disaggregate amyloid, several subunits cooperatively engage substrate and hydrolyze ATP. Importantly, Hsp104 variants with impaired intersubunit communication dissolve disordered aggregates, but not amyloid. Unexpectedly, prokaryotic ClpB subunits collaborate differently than Hsp104 and couple probabilistic substrate binding to cooperative ATP hydrolysis, which enhances disordered aggregate dissolution but sensitizes ClpB to inhibition and diminishes amyloid disaggregation. Finally, we establish that Hsp104 hexamers deploy more subunits to disaggregate Sup35 prion strains with more stable “cross-β” cores. Thus, operational plasticity enables Hsp104 to robustly dissolve amyloid and nonamyloid clients, which impose distinct mechanical demands.
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► Hsp104 switches mechanism to disaggregate disordered aggregates versus amyloid ► ClpB operates with reduced plasticity and has limited amyloid-disaggregase activity ► Hsp104 remodels diverse toxic oligomers and amyloids linked to neurodegeneration ► Hsp104 plasticity enables yeast to harness prions for advantageous purposes
The protein disaggregase Hsp104 from yeast employs different mechanisms to resolve disordered aggregates versus amyloid. Conversely, its bacterial homolog ClpB displays reduced operational plasticity and limited amyloid-remodeling activity.
We investigated antibacterial activity of ZnO nanorods prepared by a hydrothermal method against a gram-negative bacterium
Escherichia coli and a gram-positive bacterium
Bacillus atrophaeus. ...Antibacterial activity of ZnO nanorod coatings was studied on solid substrates covered with nutrient agar, as well as in liquid nutrient broth for different concentrations of ZnO nanorods, nanoparticles, and powder. ZnO exhibited antibacterial activity against both
E. coli and
B. atrophaeus, but it was considerably more effective in the latter case (at 15 mM vs. 5 mM concentration, respectively, showing zero viable cell count). For both organisms, damage of the cell membranes was found, and the effect was more pronounced for
B. atrophaeus. Chemiluminescence analysis has been used to detect the release of hydrogen peroxide from ZnO structures, and the effect of H
2O
2 on the
E. coli and
B. atrophaeus was studied. Since significant differences were observed in the effect of ZnO nanostructures and H
2O
2 on
B. atrophaeus, it can be concluded that there are other mechanisms contributing to the antibacterial activity of ZnO nanostructures.
Recent high-throughput sequencing technology has led to an expansion of knowledge regarding the microbial communities (microbiome) across various built environments (BEs). The microbiome of the BE is ...dependent upon building factors and conditions that govern how outdoor microbes enter and persist in the BE. Additionally, occupants are crucial in shaping the microbiome of the BE by releasing human-associated microorganisms and resuspending microbes on floors and surfaces. Therefore, both the outdoors and occupants act as major sources of microorganisms found in the BE. However, most characterizations of the microbiome of the BE have been conducted in the Western world. Notably, outdoor locations and population groups present geographical variations in outdoor and human microbiomes, respectively. Given the influences of the outdoor and human microbiomes on BE microbiology, and the geographical variations in outdoor and human microbiomes, it is likely that the microbiomes of BEs also vary by location. The summation of microbiomes between BEs contribute to a potential BE pan-microbiome, which will both consist of microbes that are ubiquitous in indoor environments around the world, and microbes that appear to be endemic to particular geographical locations. Importantly, the BE pan-microbiome can potentially question the global application of our current views on indoor microbiology. In this review, we first provide an assessment on the roles of building and occupant properties on shaping the microbiome of the BE. This is then followed by a description of geographical variations in the microbiomes of the outdoors and humans, the two main sources of microbes in BEs. We present evidence of differences in microbiomes of BEs around the world, demonstrating the existence of a global pan-microbiome of the BE that is larger than the microbiome of any single indoor environment. Finally, we discuss the significance of understanding the BE pan-microbiome and identifying universal and location-specific relationships between building and occupant characteristics and indoor microbiology. This review highlights the much needed efforts towards determining the pan-microbiome of the BE, thereby identifying general and location-specific links between the microbial communities of the outdoors, human, and BE ecosystems, ultimately improving the health, comfort, and productivity of occupants around the world.
Subway systems are indispensable for urban societies, but microbiological characteristics of subway aerosols are relatively unknown. Previous studies investigating microbial compositions in subways ...employed methodologies that underestimated the diversity of microbial exposure for commuters, with little focus on factors governing subway air microbiology, which may have public health implications. Here, a culture-independent approach unraveling the bacterial diversity within the urban subway network in Hong Kong is presented. Aerosol samples from multiple subway lines and outdoor locations were collected. Targeting the 16S rRNA gene V4 region, extensive taxonomic diversity was found, with the most common bacterial genera in the subway environment among those associated with skin. Overall, subway lines harbored different phylogenetic communities based on α- and β-diversity comparisons, and closer inspection suggests that each community within a line is dependent on architectural characteristics, nearby outdoor microbiomes, and connectedness with other lines. Microbial diversities and assemblages also varied depending on the day sampled, as well as the time of day, and changes in microbial communities between peak and nonpeak commuting hours were attributed largely to increases in skin-associated genera in peak samples. Microbial diversities within the subway were influenced by temperature and relative humidity, while carbon dioxide levels showed a positive correlation with abundances of commuter-associated genera. This Hong Kong data set and communities from previous studies conducted in the United States formed distinct community clusters, indicating that additional work is required to unravel the mechanisms that shape subway microbiomes around the globe.
This paper studies a version of stochastic vehicle routing problems, in which travel and service times are stochastic, and a time window constraint is associated with each customer. This problem is ...originally formulated as a chance constrained programming model and a stochastic programming model with recourse in terms of different optimization criteria. To efficiently solve these two models, a heuristic based on tabu search, which takes into account the stochastic nature of this problem, is then proposed. Finally, some testing instances with different properties are established to investigate the algorithmic performance, and the computational results are then reported.
Multi‐person novel view synthesis aims to generate free‐viewpoint videos for dynamic scenes of multiple persons. However, current methods require numerous views to reconstruct a dynamic person and ...only achieve good performance when only a single person is present in the video. This paper aims to reconstruct a multi‐person scene with fewer views, especially addressing the occlusion and interaction problems that appear in the multi‐person scene. We propose MP‐NeRF, a practical method for multi‐person novel view synthesis from sparse cameras without the pre‐scanned template human models. We apply a multi‐person SMPL template as the identity and human motion prior. Then we build a global latent code to integrate the relative observations among multiple people, so we could represent multiple dynamic people into multiple neural radiance representations from sparse views. Experiments on multi‐person dataset MVMP show that our method is superior to other state‐of‐the‐art methods.
The pharmaceutical industry has been challenged by the increasing number of poorly soluble drug candidates, resulting in significant issues with obtaining sufficient absorption and bioavailability, ...risk of exposure variability, and difficulties in achieving a safe therapeutic index. Additionally, the rapid and precise dispensing of specific drug dosages is an important aspect that can enable personalized medicines for the patient. Herein, we report on the development of inkjet printing as a method for delivering precise quantities of poorly soluble drug molecules using commercially available equipment. Despite challenges due to low solubility making it difficult to prepare liquid solutions, stable suspensions of drug nanoparticles with the appropriate viscosity were successfully printed and dispensed onto a thin film suitable for delivery. The drug nanoparticles remained intact and could be reconstituted after printing, demonstrating that they remained stable and retained their advantageous particle size. This demonstrates that inkjet printing can be a practical and convenient approach for dispensing poorly soluble drug molecules when formulated as nanosuspensions.
Slippery liquid‐infused porous surfaces (SLIPS) have received widespread attention in the antifouling field. However, the reduction in antifouling performance caused by lubricant loss limits their ...application in marine antifouling. Herein, inspired by the skin of a poison dart frog which contains venom glands and mucus, a porous liquid (PL) based on ZIF‐8 is prepared as a lubricant and injected into a silicone polyurethane (SPU) matrix to construct a new type of SLIPS for marine antifouling applications: the slippery porous‐liquid‐infused porous surface (SPIPS). The SPIPS consists of a responsive antifoulant‐releasing switch between “defensive” and “offensive” antifouling modes to intelligently enhance the antifouling effect after lubricant loss. The SPIPS can adjust antifouling performance to meet the antifouling requirements under different light conditions. The wastage of antifoulants is reduced, thereby effectively maintaining the durability and service life of SLIPS materials. The SPIPS exhibits efficient lubricant self‐replenishment, self‐cleaning, anti‐protein, anti‐bacterial, anti‐algal, and self‐healing (97.48%) properties. Furthermore, it shows satisfactory 360‐day antifouling performance in actual marine fields during boom seasons, demonstrating the longest antifouling lifespan in the field tests of reported SLIPS coatings. Hence, the SPIPS can effectively promote the development of SLIPS for neritic antifouling.
Inspired by the poison dart frog's skin with venom glands and mucus, a porous liquid (PL) based on ZIF‐8 is prepared as a lubricant and injects into the silicone polyurethane (SPU) matrix to construct a new type of slippery liquid‐infused porous surface (SLIPS)—the slippery porous‐liquid‐infused porous surface (SPIPS) for neritic marine antifouling.
Summary
This study is a prospective cluster-randomized controlled clinical trial involving 710 elderly subjects to investigate the long-term effects of low-magnitude high-frequency vibration (LMHFV) ...on fall and fracture rates, muscle performance, and bone quality. The results confirmed that LMHFV is effective in reducing fall incidence and enhancing muscle performance in the elderly.
Introduction
Falls are direct causes of fragility fracture in the elderly. LMHFV has been shown to improve muscle function and bone quality. This study is to investigate the efficacy of LMHFV in preventing fall and fractures among the elderly in the community.
Methods
A cluster-randomized controlled trial was conducted with 710 postmenopausal females over 60 years. A total of 364 participants received daily 20 min LMHFV (35 Hz, 0.3 g), 5 days/week for 18 months; 346 participants served as control. Fall or fracture rate was taken as the primary outcome. Also, quadriceps muscle strength, balancing abilities, bone mineral density (BMD), and quality of life (QoL) assessments were done at 0, 9, and 18 months.
Results
With an average of 66.0 % compliance in the vibration group, 18.6 % of 334 vibration group subjects reported fall or fracture incidences compared with 28.7 % of 327 in the control (adjusted HR = 0.56,
p
= 0.001). The fracture rate of vibration and control groups were 1.1 and 2.3 % respectively (
p
= 0.171). Significant improvements were found in reaction time, movement velocity, and maximum excursion of balancing ability assessment, and also the quadriceps muscle strength (
p
< 0.001). No significant differences were found in the overall change of BMD. Minimal adverse effects were documented.
Conclusion
LMHFV is effective in fall prevention with improved muscle strength and balancing ability in the elderly. We recommend its use in the community as an effective fall prevention program and to decrease related injuries.
Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures ...across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91-0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87-0.93) at a specificity of 0.76 to 0.98 (IQR 0.83-0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79-0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration.
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