Integrating Genome-Resolved Metagenomics with Trait-Based Process Modeling to Determine Biokinetics of Distinct Nitrifying Communities within Activated Sludge

Conventional bioprocess models for wastewater treatment are based on aggregated bulk biomass concentrations and do not incorporate microbial physiological diversity. Such a broad aggregation of microbial functional groups can fail to predict ecosystem dynamics when high levels of physiological diversity exist within trophic guilds. For instance, functional diversity among nitrite-oxidizing bacteria (NOB) can obfuscate engineering strategies for their out-selection in activated sludge (AS), which is desirable to promote energy-efficient nitrogen removal. Here, we hypothesized that different NOB populations within AS can have different physiological traits that drive process performance, which we tested by estimating biokinetic growth parameters using a combination of highly replicated respirometry, genome-resolved metagenomics, and process modeling. A lab-scale AS reactor subjected to a selective pressure for over 90 days experienced resilience of NOB activity. We recovered three coexisting Nitrospira population genomes belonging to two sublineages, which exhibited distinct growth strategies and underwent a compositional shift following the selective pressure. A trait-based process model calibrated at the NOB genus level better predicted nitrite accumulation than a conventional process model calibrated at the NOB guild level. This work demonstrates that trait-based modeling can be leveraged to improve our prediction, control, and design of functionally diverse microbiomes driving key environmental biotechnologies

Integrating Genome-Resolved Metagenomics with Trait-Based Process Modeling to Determine Biokinetics of Distinct Nitrifying Communities within Activated Sludge

Conventional bioprocess models for wastewater treatment are based on aggregated bulk biomass concentrations and do not incorporate microbial physiological diversity. Such a broad aggregation of microbial functional groups can fail to predict ecosystem dynamics when high levels of physiological diversity exist within trophic guilds. For instance, functional diversity among nitrite-oxidizing bacteria (NOB) can obfuscate engineering strategies for their out-selection in activated sludge (AS), which is desirable to promote energy-efficient nitrogen removal. Here, we hypothesized that different NOB populations within AS can have different physiological traits that drive process performance, which we tested by estimating biokinetic growth parameters using a combination of highly replicated respirometry, genome-resolved metagenomics, and process modeling. A lab-scale AS reactor subjected to a selective pressure for over 90 days experienced resilience of NOB activity. We recovered three coexisting Nitrospira population genomes belonging to two sublineages, which exhibited distinct growth strategies and underwent a compositional shift following the selective pressure. A trait-based process model calibrated at the NOB genus level better predicted nitrite accumulation than a conventional process model calibrated at the NOB guild level. This work demonstrates that trait-based modeling can be leveraged to improve our prediction, control, and design of functionally diverse microbiomes driving key environmental biotechnologies

Infrared Photodissociation Spectroscopy of Mass-Selected Dinuclear Transition Metal Boride Carbonyl Cluster Cations

The transition-metal–boron bonding interactions and geometric structures of heterodinuclear transition metal carbonyl cluster cations BM(CO)n+ (M = Co, Ni, and Cu) are studied by a combination of the infrared photodissociation spectroscopy and density functional theory calculations at the B3LYP/def2-TZVP level. The BCu(CO)5+ and BCo(CO)6+ cations are characterized as an (CO)2B–M(CO)3/4+ structure involving an σ-type (OC)2B → M(CO)3,4+ dative bonding with end-on carbonyls, while for BNi(CO)5,6+ complexes with a bridged carbonyl, a 3c–2e bond involving the 5σ electrons of the bridged carbonyl and an electron-sharing bond between the B(CO)2 fragment and the Ni(CO)2,3+ subunits were revealed. Moreover, the fundamental driving force of the exclusive existence of a bridged carbonyl group in the boron–nickel complexes has been demonstrated to stem from the desire of the B and Ni centers for the favorable 8- and 18-electron structures

DataSheet_1_Establishment of lactate-metabolism-related signature to predict prognosis and immunotherapy response in patients with colon adenocarcinoma.pdf

The outcome of colon adenocarcinoma (COAD) patients remains dismal, and lactate metabolism has been characterized to promote tumor development and immune evasion. Based on the above background, it is worthwhile to explore novel prognostic and therapeutic biomarkers for COAD patients from the aspect of lactate metabolism. Above all, 228 available lactate-metabolism-related genes (LMRGs) were acquired, and the landscape of copy number variation and the expression difference of mRNA levels between colon normal and tumor samples were investigated among these LMRGs. Importantly, eight overall survival (OS)-involved LMRGs were then distinguished by means of univariate Cox regression analysis in both GSE40967 and TCGA-COAD data sets. Subsequently, prognostic risk scores were established, integrating seven OS-related LMRGs by LASSO Cox regression analysis in the GSE40967 set, and then verified in the TCGA-COAD cohort. From the comprehensive analyses, COAD patients with high risk had comparatively more inferior survival probability in all populations of the study, and they tended to have more severe clinicopathological features with the risk score increasing. Moreover, by integrating age, AJCC T and pathological stage, and risk score, we constructed a prognostic nomogram that demonstrated great prediction effectiveness for OS of COAD patients. Furthermore, the potential effect of various risk score on tumor immune was assessed from enrichment of immune-related pathways, tumor-infiltrating immune cells, and expression levels of immune checkpoints separately. We could draw a conclusion that COAD patients with higher lactate-metabolism-related risk scores may acquire an immunosuppressive tumor microenvironment, which subsequently led to immune escapes and poor prognoses. Conclusively, all findings in the present study illustrate a great prognostic value of the lactate-metabolism-related risk signature, providing more in-depth insights into the indispensable function of lactate metabolism in prognosis and tumor immunity of COAD.</p

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of “suitable isolation side chains” is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents

Surface Plasmon Resonance Enhanced Real-Time Photoelectrochemical Protein Sensing by Gold Nanoparticle-Decorated TiO₂ Nanowires

Recently developed photoelectrochemical (PEC) sensing systems represent a unique potential detection method for real-time analysis of chemical/biological molecules, while the low absorption of TiO₂ nanomaterials in the visible wavelength region and the slow surface charge transfer efficiency limit the ultimate sensitivity. Here we develop a gold nanoparticle-decorated TiO₂ nanowire sensor for PEC detection of protein binding. The direct attachment of Au nanoparticles to TiO₂ nanowires offers strong surface plasmon resonance for electrochemical field effect amplification, yielding a ∼100% increase of photocurrent density. In addition, the surface functionalization of gold nanoparticles allows for direct capturing of target proteins near the Au/TiO₂ interface and thus substantially enhances the capability of attenuation of energy coupling between Au and TiO₂, leading to much-improved sensor performance. As a proof of concept, cholera toxin subunit B has been robustly detected by the TiO₂–Au nanowire sensor functionalized with ganglioside GM1, with a high sensitivity of 0.167 nM and excellent selectivity. Furthermore, the real-time feature of photoelectrochemical sensing enables direct measurement of binding kinetics between cholera toxin subunit B and GM1, yielding association and disassociation rate constants and an equilibrium constant <i>K</i>_d of 4.17 nM. This surface plasmon resonance-enhanced real-time, photoelectrochemical sensing design may lead to exciting biodetection capabilities with high sensitivity and real-time kinetic studies

Additional file 1 of A novel immune checkpoint score system for prognostic evaluation in pancreatic adenocarcinoma

Additional file 1

Type‑I Photosensitizer-Triggered Controllable Carbon Monoxide Release for Effective Treatment of Staph Skin Infection

Staphylococcus aureus (S. aureus) infection is a major infectious skin disease that is highly resistant to conventional antibiotic treatment and host immune defense, leading to recurrence and exacerbation of bacterial infection. Herein, we developed a photoresponsive carbon monoxide (CO)-releasing nanocomposite by integrating anion-π+ type-I photosensitizer (OMeTBP) and organometallic complex (FeCO) for the treatment of planktonic S. aureus and biofilm-associated infections. After optimizing the molar ratio of FeCO and OMeTBP, the prepared nanoparticles, OMeTBP@FeCONPs, not only ensured sufficient loading of CO donors and efficient CO generation but also showed negligible free ROS leakage under light irradiation, which helped to avoid tissue damage caused by excessive ROS. Both in vitro and in vivo results demonstrated that OMeTBP@FeCONPs could effectively inhibit S. aureus methicillin-resistant S. aureus (MRSA), and bacterial biofilm. Our design has the potential to overcome the resistance of conventional antibiotic treatment and provide a more effective option for bacterial infections

WO₃ Nanoflakes for Enhanced Photoelectrochemical Conversion

We developed a postgrowth modification method of two-dimensional WO₃ nanoflakes by a simultaneous solution etching and reducing process in a weakly acidic condition. The obtained dual etched and reduced WO₃ nanoflakes have a much rougher surface, in which oxygen vacancies are created during the simultaneous etching/reducing process for optimized photoelectrochemical performance. The obtained photoanodes show an enhanced photocurrent density of ∼1.10 mA/cm² at 1.0 V <i>vs</i> Ag/AgCl (∼1.23 V <i>vs</i> reversible hydrogen electrode), compared to 0.62 mA/cm² of pristine WO₃ nanoflakes. The electrochemical impedance spectroscopy measurement and the density functional theory calculation demonstrate that this improved performance of dual etched and reduced WO₃ nanoflakes is attributed to the increase of charge carrier density as a result of the synergetic effect of etching and reducing

Additional file 1: Table S1. of The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease

Odds ratios for NAFLD in different quartiles of TyG index or ALT in ALT <40 and ≥40 U/L groups. Table S2 Diagnostic value of TyG and ALT for NAFLD in ALT <40 and ≥40 U/L groups. (DOCX 19 kb