Mechanisms of horizontal gene transfer and viral contribution to the fate of intracellular and extracellular antibiotic resistance genes in anaerobic digestion supplemented with conductive materials under ammonia stress.

The addition of conductive materials (CMs) is an effective strategy for mitigating ammonia inhibition during anaerobic digestion (AD). However, the introduction of CMs can result in increased antibiotic resistance genes (ARGs) pollution, potentially facilitated by enhanced horizontal gene transfer (HGT). The complex dynamics of intracellular and extracellular ARGs (iARGs/eARGs) and the mechanisms underlying their transfer, mediated by CMs, in ammonia-stressed AD systems remain unclear. In this study, we investigated the effects of three commonly used CMs-nano magnetite (Mag), nano zero-valent iron (nZVI), and granular activated carbon (GAC)-on the fate of iARGs and eARGs during the AD of waste activated sludge under ammonia stress. The results revealed an unexpected enrichment of iARGs by 1.5 %-10.9 % and a reduction of eARGs by 14.1 %-25.2 % in CM-supplemented AD. This discrepancy in the dynamics of iARGs and eARGs may be attributed to changes in microbial hosts and the horizontal transfer of ARGs. Notably, CMs activated prophages within antibiotic-resistant bacteria (ARB) and their symbiotic partners involved in vitamin B12 provision, leading to the lysis of ARB and the subsequent release of eARGs for transformation. Additionally, the abundance of potentially mobile ARGs, which co-occurred with mobile genetic elements, increased by 56.6 %-134.5 % with CM addition, highlighting an enhanced potential for the HGT of ARGs. Specifically, Mag appeared to promote both transformation and conjugation processes, while nZVI only promoted conjugation. Moreover, none of the three CMs had any discernible impact on transduction. GAC proved superior to both nano Mag and nZVI in controlling the enrichment of iARGs, reducing eARGs, and limiting HGTs simultaneously. Overall, these findings provide novel insights into the role of viruses and the mechanisms of ARG spread in CM-assisted AD, offering valuable information for developing strategies to mitigate ARG pollution in practical applications.

Insights into the carbon and nitrogen metabolism pathways in mixed-autotrophy/heterotrophy anammox consortia in response to temperature reduction.

While the multi-coupled anammox system boasts a substantial research foundation, the specific characteristics of its synergistic metabolic response to decreased temperatures, particularly within the range of 13-15 °C, remained elusive. In this study, we delve into the intricate carbon and nitrogen metabolism pathways of mixed-autotrophy/heterotrophy anammox consortia under conditions of temperature reduction. Our macrogenomic analyses reveal a compelling phenomenon: the stimulation of functional genes responsible for complete denitrification, suggesting an enhancement of this process during temperature reduction. This adaptation likely contributes to maintaining system performance amidst environmental challenges. Further metabolic functional recombination analyses highlight a dramatic shift in microbial community composition, with denitrifying MAGs (metagenome-assembled genomes) experiencing a substantial increase in abundance (up to 200 times) compared to autotrophic MAGs. This proliferation underscores the strong stimulatory effect of temperature reduction on denitrifying species. Notably, autotrophic MAGs play a pivotal role in supporting the glycolytic processes of denitrifying MAGs, underscoring the intricate interdependencies within the consortia. Moreover, metabolic variations in amino acid composition among core MAGs emerge as a crucial adaptation mechanism. These differences facilitate the preservation of enzyme activity and enhance the consortia's resilience to low temperatures. Together, these findings offer a comprehensive understanding of the microbial synergistic metabolism within mixed-autotrophy/heterotrophy anammox consortia under temperature reduction, shedding light on their metabolic flexibility and resilience in dynamic environments.

Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors.

BACKGROUND: Prostate cancer stem cells (PCSCs) play crucial roles in therapy-resistance and metastasis in castration-resistant prostate cancer (CRPC). Certain functional link between cancer stemness and epithelial-mesenchymal transition (EMT) is involved in CRPC. However, up-stream regulators controlling these two processes in PCSCs are still poorly understood. Recently, we have shown that orphan nuclear receptor TLX can promote tumour initiation and progression in CRPC by repressing androgen receptor and oncogene-induced senescence. METHODS: PCSCs were isolated from various prostate cancer cell lines and clinical tumour tissues using multiple methods for various in vitro and in vivo oncogenic growth analyses. Direct targets of TLX involved in stemness and EMT regulation were determined by specific reporter gene assays and ligand-driven modulation of TLX activity. RESULTS: PCSCs isolated from various sources exhibited increased expression of TLX. Functional and molecular characterisation showed that TLX could function to promote cancer stemness and EMT in prostate cancer cells via its direct transactivation of CD44, SOX2, POU5F1 and NANOG, which share certain functional crosstalk in these two cellular processes. CONCLUSIONS: TLX could act as a key up-stream regulator in transcriptional control of stemness and EMT in PCSCs, which contribute to their tumorigenicity, castration-resistance and metastasis potentials in advanced prostate cancer.

Metabolic evolution and bottleneck insights into simultaneous autotroph-heterotroph anammox system for real municipal wastewater nitrogen removal.

When biological nitrogen removal (BNR) systems shifted from treating simulated wastewater to real wastewater, a microbial succession occurred, often resulting in a decline in efficacy. Notably, despite their high nitrogen removal efficiency for real wastewater, anammox coupled systems operating without or with minimal carbon sources also exhibited a certain degree of performance reduction. The underlying reasons and metabolic shifts within these systems remained elusive. In this study, the simultaneous autotrophic/heterotrophic anammox system demonstrated remarkable metabolic resilience upon exposure to real municipal wastewater, achieving a nitrogen removal efficiency (NRE) of 82.83 ± 2.29 %. This resilience was attributed to the successful microbial succession and the complementary metabolic functions of heterotrophic microorganisms, which fostered a resilient microbial community. The system's ability to harness multiple electron sources, including NADH oxidation, the TCA cycle, and organics metabolism, allowed it to establish a stable and efficient electron transfer chain, ensuring effective nitrogen removal. Despite the denitrification channel's nitrite supply capability, the analysis of the interspecies correlation network revealed that the synergistic metabolism between AOB and AnAOB was not fully restored, resulting in selective functional bacterial and genetic interactions and the system's PN/A performance declined. Additionally, the enhanced electron affinity of PD increased interconversion of NO3--N and NO2--N, limiting the efficient utilization of electrons and thereby constraining nitrogen removal performance. This study elucidated the metabolic mechanism of nitrogen removal limitations in anammox-based systems treating real municipal wastewater, enhancing our understanding of the metabolic functions and electron transfer within the symbiotic bacterial community.

Multiple elite strategy enhanced RIME algorithm for 3D UAV path planning.

With the wave of artificial intelligence sweeping the world in recent years, UAVs is widely used in various fields. UAV path planning has attracted much attention from scientists as an essential part of UAV work. In order to design an efficient and reasonable 3D UAV path planning program, recent researchers have invented and improved many algorithms. This paper proposes an elite RIME algorithm for 3D UAV path planning. First, we propose an elite reverse learning population selection strategy based on piecewise mapping to enhance the population diversity of the algorithm for better exploration. Second, this paper proposes a stochastic factor-controlled elite pool exploration strategy so that the algorithm is difficult to enter the local optimum and can better explore the global optimum. Then, this paper proposes a hard frost puncture exploitation strategy based on the sine-cosine function so that the algorithm can find the global optimum faster during the exploitation process. Meanwhile, in order to test the performance of the algorithm proposed in this paper, we compare it with 13 other intelligent optimization algorithms that are classical and popular nowadays on 52 test functions in three test sets, CEC2017, CEC2020, and CEC2022, and obtain competitive results. Finally, we applied it to the 3D UAV path planning problem in three different terrain scenarios, and the ELRIME algorithm achieved good results in all of them. Especially in the 7-peak model, the ELRIME algorithm improves the performance of the RIME algorithm by a factor of two. In the 9-peak model, the average value aspect also reduce the cost by 91 compared to the RIME algorithm, and more importantly, it has the smallest fluctuation in 30 runs, which is among the most stable of all the compared algorithms. In the 12-peak model, its stability is also significantly enhanced, and in terms of worst-case cost, it improves the cost by 340 compared to RIME.

To Boost Zero-Shot Generalization for Embodied Reasoning With Vision-Language Pre-Training.

Recently, there exists an increased research interest in embodied artificial intelligence (EAI), which involves an agent learning to perform a specific task when dynamically interacting with the surrounding 3D environment. There into, a new challenge is that many unseen objects may appear due to the increased number of object categories in 3D scenes. It makes developing models with strong zero-shot generalization ability to new objects necessary. Existing work tries to achieve this goal by providing embodied agents with massive high-quality human annotations closely related to the task to be learned, while it is too costly in practice. Inspired by recent advances in pre-trained models in 2D visual tasks, we attempt to boost zero-shot generalization for embodied reasoning with vision-language pre-training that can encode common sense as general prior knowledge. To further improve its performance on a specific task, we rectify the pre-trained representation through masked scene graph modeling (MSGM) in a self-supervised manner, where the task-specific knowledge is learned from iterative message passing. Our method can improve a variety of representative embodied reasoning tasks by a large margin (e.g., over 5.0% w.r.t. answer accuracy on MP3D-EQA dataset that consists of many real-world scenes with a large number of new objects during testing), and achieve the new state-of-the-art performance.

A Metal-Free Direct Decarboxylative Fluoroacylation of Indole Carboxylic Acids with Fluorinated Acids.

A straightforward preparation of diversified fluorinated indol-3-yl ketones was developed by the direct decarboxylative fluoroacylation of indole carboxylic acids. The reaction could be performed on a gram scale under net conditions. Neither a metal catalyst nor an additive was employed. This methodology featured simple reaction conditions, high efficiency, exclusive selectivity, a broad substrate scope, and easy operation, which allowed it to meet the green chemistry requirement of the modern pharmaceutical industry. Control experiments confirmed that a radical process might be involved in the tandem decarboxylative fluoroacylation sequence.

From non-coding RNAs to histone modification: The epigenetic mechanisms in tomato fruit ripening and quality regulation.

Ripening is one of the most important stages of fruit development and determines the fruit quality. Various factors play a role in this process, with epigenetic mechanisms emerging as important players. Epigenetic regulation encompasses DNA methylation, histone modifications and variants, chromatin remodeling, RNA modifications, and non-coding RNAs. Over the past decade, studies using tomato as a model have made considerable progress in understanding the impact of epigenetic regulation on fleshy fruit ripening and quality. In this paper, we provide an overview of recent advancements in the epigenetic regulation of tomato fruit ripening and quality regulation, focusing on three main mechanisms: DNA/RNA modifications, non-coding RNAs, and histone modifications. Furthermore, we highlight the unresolved issues and challenges within this research field, offering perspectives for future investigations to drive agricultural innovation.

PLGA microspheres carrying EMSCs-CM for the effective treatment of murine ulcerative colitis.

Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.

Global, regional, and national analyses of the burden of colorectal cancer attributable to diet low in milk from 1990 to 2019: longitudinal observational study.

Background: Globally, diet low in milk is the third greatest risk factor for colorectal cancer (CRC). However, there has been a lack of detailed worldwide analysis of the burden and trends of CRC attributable to diet low in milk. Objective: We aim to assess the spatiotemporal trends of CRC-related mortality and disability-adjusted life-years (DALYs) attributable to diet low in milk at the global, regional, and national levels from 1990 to 2019. Methods: Data of mortality, DALYs, age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of CRC attributable to diet low in milk were extracted from the Global Burden of Disease (GBD) 2019 study. The burden of CRC attributable to diet low in milk was estimated using the ASMR and ASDR, while accounting for sex, age, country, and socio-demographic index (SDI). From 1990 to 2019, the estimated annual percentage change (EAPC) was calculated to clarify the temporal trends in the ASMR and ASDR attributable to diet low in milk. Results: In 2019, there were 166,456 (95% UI = 107,221-226,027) deaths and 3,799,297 (95% UI = 2,457,768-5,124,453) DALYs attributable to diet low in milk, accounting for 15.3 and 15.6% of CRC-related deaths and DALYs in 2019. CRC-related deaths and DALYs attributed to diet low in milk increased by 130.5 and 115.4%, from 1990 to 2019. The burden of CRC attributable to diet low in milk varied notably among regions and nations. High-middle SDI regions had the highest ASDR and ASMR of CRC linked to diet low in milk, while there was a slight downward trend high SDI regions. Among geographical regions, East Asia had the highest number of CRC-related deaths and DALYs attributable to diet low in milk. Notably, the burden of CRC was highest in males and the elderly. With coefficients of -0.36 and -0.36, the EAPC in ASMR and ASDR was significantly inversely correlated with the Human Development Index in 2019. Conclusion: Globally, the number of CRC deaths attributable to diet low in milk has continued to increase over the last 30 years. Therefore, government and authorities should conduct education campaigns to encourage individuals to increase daily milk intake.

Design and synthesis of 7-azaindole derivatives as potent CDK8 inhibitors for the treatment of acute myeloid leukemia.

It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)phenyl)-3-(m-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI50 MV4-11 = 1.97 ± 1.24 µM). This compound also exhibited excellent inhibitory activity against CDK8 (IC50 = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addition, acute toxicity at a dose of 1000 mg kg-1 indicated the low toxicity of this compound.

Synthesis and Anti-Inflammatory Bowel Disease Activity of Pterostilbene Derivatives.

The aberrant activation of NLRP3 inflammasomes is intricately linked to various inflammatory diseases. In this study, we present the discovery and optimization of a series of NLRP3 inflammasome inhibitors based on the pterostilbene skeleton. All compounds underwent screening to evaluate their inhibitory effects on LPS/Nigericin-induced IL-1ß secretion and anti-cellular pyroptosis. Most compounds exhibit good biological activity and cellular safety, with compound D20 showing the most prominent activity. Preliminary mechanism studies suggest that compound D20 may affect the assembly of NLRP3 inflammasomes by targeting the NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasomes. The in vivo anti-inflammatory activity demonstrated significant therapeutic effect of compound D20 on DSS-induced acute colitis model in mice. This work has important reference significance for the development of drugs targeting NLRP3 inflammasomes.

Dihydropyridopyrazine Functionalized Xanthene: Generating Stable NIR Dyes with Small-Molecular Weight by Enhanced Charge Separation.

Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.

Optimizing anaerobic digestion: Benefits of mild temperature transition from thermophilic to mesophilic conditions.

Anaerobic digestion (AD) plays a significant role in renewable energy recovery. Upgrading AD from thermophilic (50-57 °C) to mesophilic (30-38 °C) conditions to enhance process stability and reduce energy input remains challenging due to the high sensitivity of thermophilic microbiomes to temperature fluctuations. Here we compare the effects of two decreasing-temperature modes from 55 to 35 °C on cell viability, microbial dynamics, and interspecies interactions. A sharp transition (ST) is a one-step transition by 20 °C d-1, while a mild transition (MT) is a stepwise transition by 1 °C d-1. We find a greater decrease in methane production with ST (88.8%) compared to MT (38.9%) during the transition period. ST mode overproduced reactive oxygen species by 1.6-fold, increased membrane permeability by 2.2-fold, and downregulated microbial energy metabolism by 25.1%, leading to increased apoptosis of anaerobes by 1.9-fold and release of intracellular substances by 2.9-fold, further constraining methanogenesis. The higher (1.6 vs. 1.1 copies per gyrA) metabolic activity of acetate-dependent methanogenesis implied more efficient methane production in a steady mesophilic, MT-mediated system. Metagenomic binning and network analyses indicated that ST induced dysbiosis in keystone species and greatly enhanced microbial functional redundancy, causing loss of microbial syntrophic interactions and redundant metabolic pathways. In contrast, the greater microbial interconnections (average degrees 44.9 vs. 22.1) in MT at a steady mesophilic state suggested that MT could better maintain necessary system functionality and stability through microbial syntrophy or specialized pathways. Adopting MT to transform thermophilic digesters into mesophilic digesters is feasible and could potentially enhance the further optimization and broader application of practical anaerobic engineering.

Deep reinforcement learning task scheduling method based on server real-time performance.

Server load levels affect the performance of cloud task execution, which is rooted in the impact of server performance on cloud task execution. Traditional cloud task scheduling methods usually only consider server load without fully considering the server's real-time load-performance mapping relationship, resulting in the inability to evaluate the server's real-time processing capability accurately. This deficiency directly affects the efficiency, performance, and user experience of cloud task scheduling. Firstly, we construct a performance platform model to monitor server real-time load and performance status information in response to the above problems. In addition, we propose a new deep reinforcement learning task scheduling method based on server real-time performance (SRP-DRL). This method introduces a real-time performance-aware strategy and adds status information about the real-time impact of task load on server performance on top of considering server load. It enhances the perception capability of the deep reinforcement learning (DRL) model in cloud scheduling environments and improves the server's load-balancing ability under latency constraints. Experimental results indicate that the SRP-DRL method has better overall performance regarding task average response time, success rate, and server average load variance compared to Random, Round-Robin, Earliest Idle Time First (EITF), and Best Fit (BEST-FIT) task scheduling methods. In particular, the SRP-DRL is highly effective in reducing server average load variance when numerous tasks arrive within a unit of time, ultimately optimizing the performance of the cloud system.

A critical review of comammox and synergistic nitrogen removal coupling anammox: Mechanisms and regulatory strategies.

Nitrification is highly crucial for both anammox systems and the global nitrogen cycle. The discovery of complete ammonia oxidation (comammox) challenges the inherent concept of nitrification as a two-step process. Its wide distribution, adaptability to low substrate environments, low sludge production, and low greenhouse gas emissions may make it a promising new nitrogen removal treatment process. Meanwhile, anammox technology is considered the most suitable process for future wastewater treatment. The diverse metabolic capabilities and similar ecological niches of comammox bacteria and anammox bacteria are expected to achieve synergistic nitrogen removal within a single system. However, previous studies have overlooked the existence of comammox, and it is necessary to re-evaluate the conclusions drawn. This paper outlined the ecophysiological characteristics of comammox bacteria and summarized the environmental factors affecting their growth. Furthermore, it focused on the enrichment, regulatory strategies, and nitrogen removal mechanisms of comammox and anammox, with a comparative analysis of hydroxylamine, a particular intermediate product. Overall, this is the first critical overview of the conclusions drawn from the last few years of research on comammox-anammox, highlighting possible next steps for research.

Epidemiological trends and burden analysis of cervical cancer attributable to unsafe sex: A population-based study from 1990 to 2019.

BACKGROUND: Unsafe sex is recognized as an important risk factor for cervical cancer (CC). Understanding the global disease burden of CC attributable to unsafe sex can assist policymakers in allocating healthcare resources. METHODS: Data were obtained from the 2019 global burden of disease database (GBD). We examined global, regional, and national levels of CC mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) caused by unsafe sex. ASRs were evaluated using estimated annual percentage changes (EAPCs). RESULTS: Attributable to unsafe sex, there were 280,479 CC-related deaths in 2019 and 8,955,013 CC-related DALYs. In the period 1990-2019, the global ASRs of CC due to unsafe sex decreased around the world; for age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR), the EAPCs were -0.93 and -0.95. The highest ASMRs and ASDRs were found in central sub-Saharan Africa and the lowest in Australasia. CONCLUSION: In the past few decades, the ASMR and ASDR of CC caused by unsafe sexual practices have decreased over time, with significant variations observed among different countries and regions. Increased focus is needed on spreading awareness about sexual health and promoting CC prevention and screening, particularly in low- and middle-income nations.

Ferrate (IV) synthesis using derived persulfate during treatment of oil recovery wastewater.

Using oil recovery wastewater as the target material, the degradation of organic matter in oilfield wastewater was studied in an anodic oxidation system using Ti/Ru-Ir oxide-coated anode and 0.7mMNa2SO4 as the electrolyte. The TOC of the wastewater was 210 mg/L at the beginning of the electrolysis in the electrolysis system, and it decreased from 210 to 93.6 mg/L after 50 min of electrolysis. Under the action of this system, sulfate was oxidized to persulfate, and the apparent concentration of persulfate was 15.02 mM, oxidation and degradation of organic matter in wastewater by the action of newly generated persulfate.. Afterwards, NaOH and Fe2(SO4)3 were added to the electrolyzed wastewater, and the TOC in the wastewater was further reduced to 25.1 mg/L due to the coagulation effect of the newly generated Fe(OH)3 precipitate. The TOC removal rate of the wastewater treated by this process reached 88.0%, which meets the discharge requirements. At the same time, the derived persulfate oxidized Fe(OH)3 to generate a green substance, which was identified as Na2FeO3 by IR, UV, and XRD analyses. Na2FeO3 served as a highly effective water-purifying agent, demonstrating superior performance when compared to FeO42-. The method reported in this study not only provides a strategy for waste resource recycling but also offers the potential for mass production of ferrate (IV).