De novo design of self-assembling peptides with antimicrobial activity guided by deep learning.

Bioinspired materials based on self-assembling peptides are promising for tackling various challenges in biomedical engineering. While contemporary data-driven approaches have led to the discovery of self-assembling peptides with various structures and properties, predicting the functionalities of these materials is still challenging. Here we describe the deep learning-guided de novo design of antimicrobial materials based on self-assembling peptides targeting bacterial membranes to address the emerging problem of bacterial drug resistance.

Identifying the Most Probable Transition Path with Constant Advance Replicas.

Locating plausible transition paths and enhanced sampling of rare events are fundamental to understanding the functional dynamics of biomolecules. Here, a constraint-based constant advance replicas (CAR) formalism of reaction paths is reported for identifying the most probable transition path (MPTP) between two given states. We derive the temporal-integrated effective dynamics governing the projected subsystem under the holonomic CAR path constraints and show that a dynamical action functional can be defined and used for optimizing the MPTP.

Microbial mechanisms for CO and CH emissions in Robinia pseudoacacia forests along a North-South transect in the Loess Plateau.

Forest soil microbes play a crucial role in regulating atmospheric-soil carbon fluxes. Environmental heterogeneity across forest types and regions may lead to differences in soil CO and CH emissions. However, the microbial mechanisms underlying these emission variations are currently unclear.

Bacterial outer membrane vesicles increase polymyxin resistance in Pseudomonas aeruginosa while inhibiting its quorum sensing.

The persistent emergence of multidrug-resistant bacterial pathogens is leading to a decline in the therapeutic efficacy of antibiotics, with Pseudomonas aeruginosa (P. aeruginosa) emerging as a notable threat. We investigated the antibiotic resistance and quorum sensing (QS) system of P.

Assessments of Variational Autoencoder in Protein Conformation Exploration.

Molecular dynamics (MD) simulations have been extensively used to study protein dynamics and subsequently functions. However, MD simulations are often insufficient to explore adequate conformational space for protein functions within reachable timescales. Accordingly, many enhanced sampling methods, including variational autoencoder (VAE) based methods, have been developed to address this issue.

Urea fertilization increased CO and CH emissions by enhancing C-cycling genes in semi-arid grasslands.

Global climate change is predicted to increase exogenous N input into terrestrial ecosystems, leading to significant changes in soil C-cycling. However, it remains largely unknown how these changes affect soil C-cycling, especially in semi-arid grasslands, which are one of the most vulnerable ecosystems. Here, based on a 3-year field study involving N additions (0, 25, 50, and 100 kg ha yr of urea) in a semi-arid grassland on the Loess Plateau, we investigated the impact of urea fertilization on plant characteristics, soil properties, CO and CH emissions, and microbial C cycling genes.

Fe-Mn binary oxides improve the methanogenic performance and reduce the environmental health risks associated with antibiotic resistance genes during anaerobic digestion.

Increasing evidence indicates that metal oxides can improve the methanogenic performance during anaerobic digestion (AD) of piggery wastewater. However, the impacts of composite metal oxides on the methanogenic performance and risk of antibiotic resistance gene (ARG) transmission during AD are not fully understood. In this study, different concentrations of Fe-Mn binary oxides (FMBO at 0, 250, 500, and 1000 mg/L) were added to AD to explore the effects of FMBO on the process.

Effect of aridity on the β-diversity of alpine soil potential diazotrophs: insights into community assembly and co-occurrence patterns.

Microbial diversity plays a vital role in the maintenance of ecosystem functions. However, the current understanding of mechanisms that shape microbial diversity along environmental gradients at broad spatial scales is relatively limited, especially for specific functional groups, such as potential diazotrophs. Here, we conducted an aridity-gradient transect survey from 60 sites across the Tibetan Plateau, the largest alpine ecosystem of the planet, to investigate the ecological processes (e.

Metagenomic binning analyses of swine manure composting reveal mechanism of nitrogen cycle amendment using kaolin.

The efficient control of nitrogen loss in composting and the enhancement of product quality have become prominent concerns in current research. The positive role of varying concentrations kaolin in reducing nitrogen loss during composting was revealed using metagenomic binning combined with reverse transcription quantitative polymerase chain reaction. The results indicated that the addition of 0.

Constant advance replicas method for locating minimum energy paths and transition states.

The chain-of-states (CoS) constant advance replicas (CAR) method and its climbing image variant (CI-CAR) for locating minimum energy paths (MEPs) and transition states are reported. The CAR algorithm applies the Lagrange multiplier method for imposing holonomic constraints on a chain-of-replicas, aiming to maintain equal mass-weighted/scaled root-mean-square (RMS) distances between the adjacent replicas by removing the sliding-down displacements contributed by the potential gradients during path optimization. Two contextual regularization schemes with clear geometrical interpretations are implemented to jointly promote high convergence and numerical robustness of the CAR algorithm.

Reductions in abundances of intracellular and extracellular antibiotic resistance genes by SiO nanoparticles during composting driven by mobile genetic elements.

Applying exogenous additives during the aerobic composting of livestock manure is effective for slowing down the spread of antibiotic resistance genes (ARGs) in the environment. Nanomaterials have received much attention because only low amounts need to be added and they have a high capacity for adsorbing pollutants. Intracellular ARGs (i-ARGs) and extracellular ARGs (e-ARGs) comprise the resistome in livestock manure but the effects of nanomaterials on the fates of these different fractions during composting are still unclear.

Response characteristics of denitrifying bacteria and denitrifying functional genes to woody peat during pig manure composting.

This study aimed to explore the impacts of adding different proportions of woody peat (WP) (0%(CK), 5%(T1), and 15%(T2)) on denitrification during composting. The results demonstrated that compared with CK, T1 and T2 increased the total Kjeldahl nitrogen content (8% and 14%, respectively) and reduced the nitrate nitrogen (7% and 23%) content after composting. After composting, the abundances of nirK and nirS decreased by 4-9% and 33-35% under T1 and T2, respectively.

Metagenomic insights into dietary remodeling of gut microbiota and antibiotic resistome in meat rabbits.

The gut microbiota is a repository of antibiotic resistance genes (ARGs), which may affect the health of humans and animals. The intestinal flora is affected by many factors but it is unclear how the intestinal microflora and antibiotic resistome in rabbits might change under dietary intervention. Feeding with lettuce led to the amplification and transfer of exogenous ARGs in the intestinal flora, but there were no significant differences when fed lettuces grown with different manure types.

Profiles and key drivers of bacteria/phage co-mediated antibiotic resistance genes during swine manure composting amended with humic acid.

Phages can promote the spread of antibiotic resistance genes (ARGs) in agricultural environments through transduction. However, studies on phage-mediated ARG profiles during composting have not been performed. This study investigated the effects of adding humic acid (HA) on the abundances of bacteria/phage co-mediated ARGs (b/pARGs) during swine manure composting and the key factors that affected the transmission of b/pARGs.

Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis.

As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthionine-(S,R)-sulfoximine (BSO) loaded metal organic framework (MOF) of BSO-MOF-HA (BMH) with the combination effect of boosting oxidative damage and inhibiting antioxidative defense.

Unveiling the structural features that regulate carbapenem deacylation in KPC-2 through QM/MM and interpretable machine learning.

Resistance to carbapenem β-lactams presents major clinical and economical challenges for the treatment of pathogen infections. The fast hydrolysis of carbapenems by carbapenemase-producing bacterial strains enables the effective deactivation of carbapenem antibiotics. In this study, we aim to unravel the structural features that distinguish the notable deacylation activity of carbapenemases.

Self-amplified ROS production from fatty acid oxidation enhanced tumor immunotherapy by atorvastatin/PD-L1 siRNA lipopeptide nanoplexes.

Despite the important role of reactive oxygen species (ROS) in battling cancer, ROS production with current approaches has been severely limited by the deficiency of oxy-substrates in tumor microenvironment. Herein, an atorvastatin (Ato)-catalytic self-amplified approach was utilized for sustainable ROS production and enhancing anti-tumor efficacy of PD-L1 silencing. A C-pArg-ss-pHis lipopeptide based self-assembled nanoplexes was developed to co-encapsulate AMP-activated protein kinase (AMPK) activator of Ato and PD-L1 siRNA.

Exploring the mechanism associated with methane emissions during composting: Inoculation with lignocellulose-degrading microorganisms.

Inoculation with microorganisms is an effective strategy for improving traditional composting processes. This study explored the effects of inoculation with lignocellulose-degrading microorganisms (LDM) on the degradation of organic matter (OM), methane (CH) emissions, and the microbial community (bacteria and methanogens) during composting. The results showed that LDM accelerated the degradation of OM (including the lignocellulose fraction) and increased the CH releases in the later thermophilic and cooling stages during composting.

Mechanistic Insights into Enzyme Catalysis from Explaining Machine-Learned Quantum Mechanical and Molecular Mechanical Minimum Energy Pathways.

With the increasing popularity of machine learning (ML) applications, the demand for explainable artificial intelligence techniques to explain ML models developed for computational chemistry has also emerged. In this study, we present the development of the Boltzmann-weighted cumulative integrated gradients (BCIG) approach for effective explanation of mechanistic insights into ML models trained on high-level quantum mechanical and molecular mechanical (QM/MM) minimum energy pathways. Using the acylation reactions of the Toho-1 β-lactamase and two antibiotics (ampicillin and cefalexin) as the model systems, we show that the BCIG approach could quantitatively attribute the energetic contribution in one system and the relative reactivity of individual steps across different systems to specific chemical processes such as the bond making/breaking and proton transfers.

Mechanism associated with the positive effect of nanocellulose on nitrogen retention in a manure composting system.

Additives can play important roles in effectively inhibiting nitrogen losses during livestock manure composting due to the activities of microbes. This study investigated the effects of adding nanocellulose at 300 mg/kg, 600 mg/kg, and 900 mg/kg (NC900) on nitrogen conversion, nitrogen conversion functional genes, and related microorganisms during composting. The results showed that compared with the control, nanocellulose hindered the ammoniation reaction.

Effects and microbial mechanisms of phosphogypsum and medical stone on organic matter degradation and methane emissions during swine manure composting.

The degradation of organic matter (OM) and CH emissions during composting greatly influence the composting efficiency and greenhouse effect. This study evaluated the effects of adding phosphogypsum (PPG) and medical stone (MS) on OM breakdown, CH emissions, and their underlying mechanisms. MS accelerated the breakdown of OM in the early composting stage, whereas PPG increased it in the cooling and maturation periods.

Dynamics and key drivers of antibiotic resistance genes during aerobic composting amended with plant-derived and animal manure-derived biochars.

Plant-derived and animal manure-derived biochars have been used to improve the quality of compost but the differences in their effects on antibiotic resistance genes (ARGs) during composting are unclear. This study selected two types of biochar (RB and PB) produced from abundant agricultural waste to be added to the compost. Adding plant-derived RB performed better in ARGs, mobile genetic elements, and human pathogenic bacteria removal during aerobic composting, whereas adding manure-derived PB even increased ARGs abundance.

Allosteric control of ACE2 peptidase domain dynamics.

The Angiotensin Converting Enzyme 2 (ACE2) assists the regulation of blood pressure and is the main target of the coronaviruses responsible for SARS and COVID19. The catalytic function of ACE2 relies on the opening and closing motion of its peptidase domain (PD). In this study, we investigated the possibility of allosterically controlling the ACE2 PD functional dynamics.

Clarifying the beneficial effects of plant growth-promoting rhizobacteria for reducing abundances of antibiotic resistance genes during swine manure composting.

This study investigated the effects on antibiotic resistance genes (ARGs) and the related mechanisms of different plant growth-promoting rhizobacteria (PGPR) inoculation strategies during composting: no inoculation (CK), inoculation in initial phase (T1), inoculation in cooling phase (T2), and inoculation in both initial and cooling phases (T3). After composting, the total relative abundances (RAs) of ARGs decreased by 0.26 and 0.

Risk of horizontal transfer of intracellular, extracellular, and bacteriophage antibiotic resistance genes during anaerobic digestion of cow manure.

The fate of intracellular antibiotic resistance genes (iARGs), extracellular ARGs (eARGs) and bacteriophage ARGs (bARGs) during anaerobic digestion (AD) of cow manure is unclear. Thus, the characteristics of iARGs, eARGs and bARGs during mesophilic AD (MAD) and thermophilic AD (TAD) of cow manure were investigated. The absolute abundances of iARGs decreased by 69.