Death receptor 5 is required for intestinal stem cell activity during intestinal epithelial renewal at homoeostasis.

Intestinal epithelial renewal, which depends on the proliferation and differentiation of intestinal stem cells (ISCs), is essential for epithelial homoeostasis. Understanding the mechanism controlling ISC activity is important. We found that death receptor 5 (DR5) gene deletion (DR5-/-) mice had impaired epithelial absorption and barrier function, resulting in delayed weight gain, which might be related to the general reduction of differentiated epithelial cells. In DR5-/- mice, the expression of ISC marker genes, the number of Olfm4+ ISCs, and the number of Ki67+ and BrdU+ cells in crypt were reduced. Furthermore, DR5 deletion inhibited the expression of lineage differentiation genes driving ISC differentiation into enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Therefore, DR5 gene loss may inhibit the intestinal epithelial renewal by dampening ISC activity. The ability of crypts from DR5-/- mice to form organoids decreased, and selective DR5 activation by Bioymifi promoted organoid growth and the expression of ISC and intestinal epithelial cell marker genes. Silencing of endogenous DR5 ligand TRAIL in organoids down-regulated the expression of ISC and intestinal epithelial cell marker genes. So, DR5 expressed in intestinal crypts was involved in the regulation of ISC activity. DR5 deletion in vivo or activation in organoids inhibited or enhanced the activity of Wnt, Notch, and BMP signalling through regulating the production of Paneth cell-derived ISC niche factors. DR5 gene deletion caused apoptosis and DNA damage in transit amplifying cells by inhibiting ERK1/2 activity in intestinal crypts. Inhibition of ERK1/2 with PD0325901 dampened the ISC activity and epithelial regeneration. In organoids, when Bioymifi's effect in activating ERK1/2 activity was completely blocked by PD0325901, its role in stimulating ISC activity and promoting epithelial regeneration was also eliminated. In summary, DR5 in intestinal crypts is essential for ISC activity during epithelial renewal under homoeostasis.

Microplastics shape microbial interactions and affect the dissemination of antibiotic resistance genes in different full-scale wastewater treatment plants.

Wastewater treatment plants (WWTPs) pose a potential threat to the environment because of the accumulation of antibiotic resistance genes (ARGs) and microplastics (MPs). However, the interactions between ARGs and MPs, which have both indirect and direct effects on ARG dissemination in WWTPs, remain unclear. In this study, spatiotemporal variations in different types of MPs, ten ARGs (sul1, sul2, tetA, tetO, tetM, tetX, tetW, qnrS, ermB, and ermC), class 1 integron integrase (intI1) and transposon Tn916/1545 in three typical WWTPs were characterized. Sul1, tetO, and sul2 were the predominant ARGs in the targeted WWTPs, whereas the intI1 and transposon Tn916/1545 were positively correlated with most of the targeted ARGs. Saccharimonadales (4.15 %), Trichococcus (2.60 %), Nitrospira (1.96 %), Candidatus amarolinea (1.79 %), and SC-I-84 (belonging to phylum Proteobacteria) (1.78 %) were the dominant genera. Network and redundancy analyses showed that Trichococcus, Faecalibacterium, Arcobacter, and Prevotella copri were potential hosts of ARGs, whereas Candidatus campbellbacteria and Candidatus kaiserbacteria were negatively correlated with ARGs. The potential hosts of ARGs had a strong positive correlation with polyethylene terephthalate, silicone resin, and fluor rubber and a negative correlation with polyurethane. Candidatus campbellbacteria and Candidatus kaiserbacteria were positively correlated with polyurethane, whereas potential hosts of ARGs were positively correlated with polypropylene and fluor rubber. Structural equation modeling highlighted that intI1, transposon Tn916/1545 and microbial communities, particularly microbial diversity, dominated the dissemination of ARGs, whereas MPs had a significant positive correlation with microbial abundance. Our study deepens the understanding of the relationships between ARGs and MPs in WWTPs, which will be helpful in designing strategies for inhibiting ARG hosts in WWTPs.

Hierarchies in Visual Pathway: Functions and Inspired Artificial Vision.

The development of artificial intelligence has posed a challenge to machine vision based on conventional complementary metal-oxide semiconductor (CMOS) circuits owing to its high latency and inefficient power consumption originating from the data shuffling between memory and computation units. Gaining more insights into the function of every part of the visual pathway for visual perception can bring the capabilities of machine vision in terms of robustness and generality. Hardware acceleration of more energy-efficient and biorealistic artificial vision highly necessitates neuromorphic devices and circuits that are able to mimic the function of each part of the visual pathway. In this paper, we review the structure and function of the entire class of visual neurons from the retina to the primate visual cortex within reach (Chapter 2) are reviewed. Based on the extraction of biological principles, the recent hardware-implemented visual neurons located in different parts of the visual pathway are discussed in detail in Chapters 3 and 4. Furthermore, valuable applications of inspired artificial vision in different scenarios (Chapter 5) are provided. The functional description of the visual pathway and its inspired neuromorphic devices/circuits are expected to provide valuable insights for the design of next-generation artificial visual perception systems.

An in-sensor humidity computing system for contactless human-computer interaction.

Being capable of processing large amounts of redundant data and decreasing power consumption, in-sensor computing approaches play significant roles in neuromorphic computing and are attracting increasing interest in perceptual information processing. Herein, we proposed a high performance humidity-sensitive memristor based on a Ti/graphene oxide (GO)/HfOx/Pt structure and verified its potential for application in remote health management and contactless human-machine interfaces. Since GO possesses abundant hydrophilic groups (carbonyl, epoxide, and hydroxyl), the memristor shows a high humidity sensitivity, fast response, and wide response range. By utilizing the proton-modulated redox reaction, humidity exposure to the memristor induces a dynamic change in the switching between high and low resistance states, ensuring essential synaptic learning functions, such as paired-pulse facilitation, spike number-dependent plasticity, and spike amplitude-dependent plasticity. More importantly, based on the humidity-induced salient features originating from the abundant hydrophilic functional groups in GO, we have implemented a noncontact human-machine interface utilizing the respiratory mode in humans, demonstrating the potential of promoting health monitoring applications and effectively blocking virus transmission. In addition, the high recognition accuracy of contactless handwriting in a 5 × 5 array artificial neural network was successfully achieved, which is attributed to the excellent emulated synaptic behaviors. This study provides a feasible method to develop an excellent humidity-sensitive memristor for constructing efficient in-sensor computing for application in health management and contactless human-computer interaction.

Prediction of biological nutrients removal in full-scale wastewater treatment plants using H2O automated machine learning and back propagation artificial neural network model: Optimization and comparison.

The effective control of total nitrogen (ETN) and total phosphorus (ETP) in effluent is challenging for wastewater treatment plants (WWTPs). In this work, automated machine learning (AutoML) (mean square error = 0.4200 âˆ¼ 3.8245, R2 = 0.5699 âˆ¼ 0.6219) and back propagation artificial neural network (BPANN) model (mean square error = 0.0012 âˆ¼ 6.9067, R2 = 0.4326 âˆ¼ 0.8908) were used to predict and analyze biological nutrients removal in full-scale WWTPs. Interestingly, BPANN model presented high prediction performance and general applicability for WWTPs with different biological treatment units. However, the AutoML candidate models were more interpretable, and the results showed that electricity carbon emission dominated the prediction. Meanwhile, increasing data volume and types of WWTP hardly affected the interpretable results, demonstrating its wide applicability. This study demonstrated the validity and the specific advantages of predicting ETN and ETP using H2O AutoML and BPANN model, which provided guidance on the prediction and improvement of biological nutrients removal in WWTPs.

Influence of C/N ratio and ammonia on nitrogen removal and N2O emissions from one-stage partial denitrification coupled with anammox.

The development of low carbon treatment processes is an important issue worldwide. Partial denitrification coupled with anammox (PD/A) is a novel strategy to remove nitrogen and reduce N2O emissions. The influence of C/N ratio and NH4+ concentration on nitrogen removal and N2O emissions was investigated in batch reactors filled with PD/A coupled sludge. A C/N ratio of 2.1 was effective for nitrogen removal and N2O reduction; higher ammonia concentration might make anammox more active and indirectly reduce N2O emissions. Long-term operation further confirmed that a C/N ratio of 2.1 resulted in a minimum effluent N2O concentration (mean value of 0.94 µmol L-1); as the influent NH4+ concentration decreased to 50 mg L-1 (NH4+-N/NO3--N: 1), the nitrogen removal rate increased to 82.41%. Microbial analysis showed that anammox bacteria (Candidatus Jettenia and Ca. Brocadia) were enriched in the PD/A system and Ca. Brocadia gradually dominated the anammox community, with the relative abundance increasing from 1.69% to 18.44% between days 97 and 141. Finally, functional gene analysis indicated that the abundance of nirS/K and hao involved in partial denitrification and anammox, respectively, increased during long-term operation of the reactor; this change benefitted nitrogen metabolism in anammox, which could indirectly reduce N2O emissions.

Phosphorus recovery from synthetic anaerobic fermentation supernatant via vivianite crystallization: Coupling effects of various physicochemical process parameters.

Recovery of phosphorus (P) via vivianite crystallization is an effective strategy to recycle resources from the anaerobic fermentation supernatant. However, the presence of different components in the anaerobic fermentation supernatant (e.g., polysaccharides and proteins) might alter conditions for optimal growth of vivianite crystals, resulting in distinct vivianite characteristics. In the present study, the effect of different components on vivianite crystallization was explored. Then, the reaction parameters (pH, Fe/P, and stirring speed) for P recovery from synthetic anaerobic fermentation supernatant as vivianite were optimized using response surface methodology, and the relationship between crystal properties and supersaturation was elucidated using a thermodynamic equilibrium model. The optimized values for pH, Fe/P, and stirring speed were found to be 7.8, 1.74, and 500 rpm respectively, resulting in 90.54 % P recovery efficiency. Moreover, the variation of reaction parameters did not change the crystalline structure of the recovered vivianite but influenced its morphology, size, and purity. Thermodynamic analysis suggested the saturation index (SI) of vivianite increased with increasing pH and Fe/P ratio, leading to a facilitative effect on vivianite crystallization. However, when the SI was >11, homogenous nucleation occurred so that the nucleation rate was much higher than the crystal growth rate, causing a smaller crystal size. The findings presented herein will be highly valued for the future large-scale application of the vivianite crystallization process for wastewater treatment.

Metagenomic insight into the prevalence and driving forces of antibiotic resistance genes in the whole process of three full-scale wastewater treatment plants.

The spread of antibiotic resistance genes (ARGs) is an emerging global health concern, and wastewater treatment plants (WWTPs), as an essential carrier for the occurrence and transmission of ARGs, deserves more attention. Based on the Illumina NovaSeq high-throughput sequencing platform, this study conducted a metagenomic analysis of 18 samples from three full-scale WWTPs to explore the fate of ARGs in the whole process (influent, biochemical treatment, advanced treatment, and effluent) of wastewater treatment. Total 70 ARG subtypes were detected, among which multidrug, aminoglycoside, tetracycline, and macrolide ARGs were most abundant. The different treatment processes used for three WWTPs were capable of reducing ARG diversity, but did not significantly reduce ARG abundance. Compared to that by denitrification filters, the membrane bioreactor (MBR) process was advantageous in controlling the prevalence of multidrug ARGs in WWTPs. Linear discriminant analysis Effect Size (LEfSe) suggested g_Nitrospira, g_Curvibacter, and g_Mycobacterium as the key bacteria responsible for differential ARG prevalence among different WWTPs. Meanwhile, adeF, sul1, and mtrA were the persistent antibiotic resistance genes (PARGs) and played dominant roles in the prevalence of ARGs. Proteobacteria and Actinobacteria were the host bacteria of majority ARGs in WWTPs, while Pseudomonas and Nitrospira were the most crucial host bacteria influencing the dissemination of critical ARGs (e.g., adeF). In addition, microbial richness was determined to be the decisive factor affecting the diversity and abundance of ARGs in wastewater treatment processes. Overall, regulating the abundance of microorganisms and key host bacteria by selecting processes with microbial interception, such as MBR process, may be beneficial to control the prevalence of ARGs in WWTPs.

Particulate organic carbon potentially increases methane emissions from oxic water of eutrophic lakes.

Lakes are hot spots for methane (CH4) emissions and particulate organic carbon (POC) production, which describes the methane paradox phenomenon. However, the current understanding of the source of POC and its effect on CH4 emissions during eutrophication remains unclear. In this study, 18 shallow lakes in different trophic states were selected to investigate the POC source and its contribution to CH4 production, particularly to reveal the underlying mechanisms of the methane paradox. The carbon isotopic analysis showed that the δ13Cpoc ranged from -30.28 ‰ to -21.14 ‰, indicating that cyanobacteria-derived carbon is an important source of POC. The overlying water was aerobic but contained high concentrations of dissolved CH4. Particularly, in hyper-eutrophic lakes, such as Lakes Taihu, Chaohu, and Dianshan, the dissolved CH4 concentrations were 2.11, 1.01, and 2.44 µmol/L, while the dissolved oxygen concentrations were 3.11, 2.92, and 3.17 mg/L, respectively. The intensified eutrophication increased the POC concentration, concomitantly promoting the dissolved CH4 concentration and the CH4 flux. These correlations revealed the role of POC in CH4 production and emission fluxes, particularly as a possible cause of the methane paradox, which is crucial for accurately evaluating the carbon budget and balance in shallow freshwater lakes.

Insight into the interaction between trimethoprim and soluble microbial products produced from biological wastewater treatment processes.

Soluble microbial products (SMPs), dissolved organic matter excreted by activated sludge, can interact with antibiotics in wastewater and natural water bodies. Interactions between SMPs and antibiotics can influence antibiotic migration, transformation, and toxicity but the mechanisms involved in such interactions are not fully understood. In this study, integrated spectroscopy approaches were used to investigate the mechanisms involved in interactions between SMPs and a representative antibiotic, trimethoprim (TMP), which has a low biodegradation rate and has been detected in wastewater. The results of liquid chromatography-organic carbon detection-organic nitrogen detection indicated that the SMPs used in the study contained 15% biopolymers and 28% humic-like substances (based on the total dissolved organic carbon concentration) so would have contained sites that could interact with TMP. A linear relationship of fluorescent intensities of tryptophan protein-like substances in SMP was observed (R2>0.99), indicating that the fluorescence enhancement between SMP and TMP occurred. Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy indicated that carboxyl, carbonyl, and hydroxyl groups were the main functional groups involved in the interactions. The electrostatic and π-π interactions were discovered by the UV-vis spectra and 1H nuclear magnetic resonance spectra. Structural representations of the interactions between representative SMP subcomponents and TMP were calculated using density functional theory, and the results confirmed the conclusions drawn from the 1H nuclear magnetic resonance spectra. The results help characterize SMP-TMP complexes and will help understand antibiotic transformations in wastewater treatment plants and aquatic environments.

Chronic GPER activation prompted the proliferation of ileal stem cell in ovariectomized mice depending on Paneth cell-derived Wnt3.

Menopausal women often face long-term estrogen treatment. G protein-coupled estrogen receptor (GPER) expressed in intestinal crypt was activated by estrogen therapy, but it was unclear whether chronic GPER activation during menopause had an effect on intestinal stem cells (ISCs). We tested the effect of chronic GPER activation on ISCs of ovariectomized (OVX) mice by injection of the selective GPER agonist G-1 for 28 days, or G-1 stimulation of organoids derived from crypts of OVX mice. G-1 up-regulated crypt depth, the number of Ki67+, bromodeoxyuridine+ cells and Olfm4+ ISCs, and the expression of ISCs marker genes (Lgr5, Olfm4 and Axin2). G-1 administration promoted organoid growth, increased the number of EdU+ cells per organoid and protein expression of Cyclin D1 and cyclin B1 in organoids. After G-1 treatment in vivo or in vitro, Paneth cell-derived Wnt3, Wnt3 effector ß-catenin and Wnt target genes c-Myc and Cyclin D1 increased in ileum or organoids. Once blocking the secretion of Wnt3 from Paneth cells, the effects of G-1 on organoids growth, ISCs marker genes and Wnt/ß-catenin signaling were abolished. G-1 did not affect the number of Paneth cells in ex vivo organoids, while activated Mmp7/cryptdin program in Paneth cells, promoted their maturation, and increased the expression of lysozyme protein. G-1 pretreatment in OVX mice inhibited radiation-induced ISCs proliferation injury and enhanced the resistance of mice to intestinal injury. In conclusion, chronic GPER activation prompted the Wnt3 synthesis in Paneth cells, thus increased the proliferation of ISCs via activation of Wnt3/ß-catenin signaling in OVX mice.

Recombinant Human Collagen-Based Bioinks for the 3D Bioprinting of Full-thickness Human Skin Equivalent.

As a major extracellular matrix component within the skin, collagen has been widely used to engineer human skin tissues. However, most collagen is extracted from animals. Here, we introduced recombinant human type III collagen (rhCol3) as a bioactive component to formulate bioinks for the bioprinting of a full-thickness human skin equivalent. Human dermal fibroblasts were encapsulated in the gelatin methacryloyl-rhCol3 composite bioinks and printed on a transwell to form the dermis layer, on which human epidermal keratinocytes were seeded to perform an air-liquid interface culture for 6 weeks. After optimizing the bioink formulation and bioprinting process, we investigated the effect of rhCol3 on skin tissue formation. The results suggest that a higher concentration of rhCol3 would enhance the growth of both cells, resulting in a more confluent (~100%) spreading of the epidermal keratinocytes at an early stage (3 days), compared to the rhCol3-free counterpart. Moreover, in an in vivo experiment, adding rhCol3 in the hydrogel formulation would contribute to the skin wound healing process. Taken together, we conclude that rhCol3 could act as a functional bioink component to promote basic skin cellular processes for skin tissue engineering.

Automated machine learning-based prediction of microplastics induced impacts on methane production in anaerobic digestion.

Microplastics as emerging pollutants have been heavily accumulated in the waste activated sludge (WAS) during biological wastewater treatment, which showed significantly diverse impacts on the subsequent anaerobic sludge digestion for methane production. However, a robust modeling approach for predicting and unveiling the complex effects of accumulated microplastics within WAS on methane production is still missing. In this study, four automated machine learning (AutoML) approach was applied to model the effects of microplastics on anaerobic digestion processes, and integrated explainable analysis was explored to reveal the relationships between key variables (e.g., concentration, type, and size of microplastics) and methane production. The results showed that the gradient boosting machine had better prediction performance (mean squared error (MSE) = 17.0) than common neural networks models (MSE = 58.0), demonstrating that the AutoML algorithms succeeded in predicting the methane production and could select the best machine learning model without human intervention. Explainable analysis results indicated that the variable of microplastic types was more important than the variable of microplastic diameter and concentration. The existence of polystyrene was associated with higher methane production, whereas increasing microplastic diameter and concentration both inhibited methane production. This work also provided a novel modeling approach for comprehensively understanding the complex effects of microplastics on methane production, which revealed the dependence relationships between methane production and key variables and may be served as a reference for optimizing operational adjustments in anaerobic digestion processes.

Co-impacts of the microplastic polyamide and sertraline on the denitrification function and microbial community structure in SBRs.

The co-impacts of microplastics (MPs) and organic pollutants on activated sludge have attracted extensive attention. In this study, microplastic polyamide (PA) and sertraline (SER) were respectively or simultaneously added to sequencing batch reactors (SBRs), and the impacts of these pollutants on activated sludge were investigated. The results showed that NH4+-N and TN removal efficiencies significantly decreased with the simultaneous adding of the two pollutants. The coexistence of PA and SER could observably decrease the settling ability of activated sludge, and more proteins and polysaccharides were generated to reduce the combined toxicity. The microbial diversity, especially the denitrification microorganism, was restrained and the metabolic function and the key enzyme involved in nitrogen metabolism pathways were observably decreased, due to the combined toxicity of this two pollutants. Furthermore, the effective SER interception by PA in SBR could induce the SER enrichment in activated sludge and enhance the biotoxicity toward sludge microorganisms.

Sludge reduction and microbial community evolution of activated sludge induced by metabolic uncoupler o-chlorophenol in long-term anaerobic-oxic process.

Excess sludge management is a restrictive factor for the development of municipal wastewater treatment plants. The addition of metabolic uncouplers has been proven to be effective in sludge reduction. However, the long-term effect of metabolic uncoupler o-chlorophenol (oCP) on the biological wastewater treatment system operated in anaerobic-oxic mode is still unclear. To this end, two parallel reactors operated in anaerobic-oxic mode with and without 10 mg/L of oCP addition were investigated for 91 days. The results showed that 56.1 ± 2.3% of sludge reduction was achieved in the oCP-added system, and the nitrogen and phosphorus removal ability were negatively affected. Dosing oCP stimulated the formation of microbial products and increased the DNA concentration, but resulted in a decrease in the electronic transport activity of activated sludge. Microbial community analysis further demonstrated that a significant reduction of bacterial richness and diversity occurred after oCP dosing. However, after stopping oCP addition, the pollutant removal ability of activated sludge was gradually increased, but the sludge yield, as well as species richness and diversity, did not recover to the previous level. This study will provide insightful guidance on the long-term application of metabolic uncouplers in the activated sludge system.

Effect of timing of laparoscopic cholecystectomy on postoperative efficacy and rehabilitation of elderly patients with acute cholecystitis.

OBJECTIVE: To discuss the effect of the timing of laparoscopic cholecystectomy (LC) on postoperative efficacy and rehabilitation in elderly patients with acute cholecystitis (AC). METHODS: Ninety-four elderly patients with AC were retrospectively selected and assigned into a research group (n=47) and a control group (n=47). The research group was administered LC within 48 hours after the onset. The control group was administered LC 48 hours after the onset. The two groups were compared for perioperative parameters, bilirubin and immune function, concentration of inflammatory factors, stress response, energy metabolism, and complications. RESULTS: The research group had a shorter operation time, hospital stay, and less intraoperative blood loss than the control group (all P<0.05). No significant intergroup difference was found in the anal exhaust time (P>0.05). The levels of postoperative direct bilirubin, total bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, serum CRP, TNF-α, and IL-6 were lower than those measured preoperatively in both groups (all P<0.001), and were lower in the research group than in the control group (all P<0.05). The postoperative pulse, diastolic pressure, and systolic pressure in the two groups were higher than those measured preoperatively (all P<0.001). The levels in the research group were lower than those in the control group (all P<0.001).The levels of adenosine triphosphate and adenosine diphosphate also decreased in both groups, but they were still higher in the research group than those in the control group (all P<0.001). The incidence of complications in the research group (4.26%) was lower than that in the control group (17.02%; P<0.05). CONCLUSION: Early LC in elderly patients with AC is beneficial to postoperative functional rehabilitation, showing less impact on energy metabolism, lower stress response caused by surgery, lower bilirubin content, less inflammatory reaction, better liver function, and lower incidence of complications in patients.

Rapid quantification of intracellular polyhydroxyalkanoates via fluorescence techniques: A critical review.

Polyhydroxyalkanoates (PHA) are promising bioplastics with excellent physicochemical properties and biodegradability, whereas PHA products suffer from high manufacturing costs. To reduce costs of PHA production, experiments with mixed microbial cultures and low-cost substrates have been conducted widely, where rapid and robust PHA quantification methods are necessary. Compared with traditional gas chromatography methods, PHA fluorescence quantification (PHA-FQ) methods may be quicker, safer and more suitable for modern experiments with high throughput requirements. However, practical applications of PHA-FQ methods are still limited. Therefore, this review provides a comprehensive understanding of PHA-FQ methods. Performance of PHA-staining fluorochromes, relevant spectral properties, and important staining procedures are summarized. Current developments of PHA-FQ protocols are critically reviewed. Main considerations needed to make PHA-FQ protocol reliable are comprehensively discussed. Finally, potential improvements in various aspects of PHA-FQ methods are highlighted. This review could help researchers develop more effective PHA-FQ methods and facilitate future experiments related to PHA.

G-Protein-Coupled Receptor Kinase-Interacting Protein 1 (GIT1) Promotes Head and Neck Squamous Cell Carcinoma Metastases via Activating the PI3K/AKT/mTOR Signal Pathway.

OBJECTIVE: GIT1 is identified as a novel tumor oncogene in breast cancer. In this article, we aimed to explore the role of GIT1 in the progression of head and neck squamous cell carcinoma (HNSCC). METHODS: GIT1 expression in HNSCC was detected by RT-qPCR, immunohistochemistry assay, and Western blot. HNSCC cell proliferation, migration, and invasion were examined by CCK-8 assay, Wound healing assay, and Transwell assay, respectively. Cell apoptosis was detected by flow cytometric analysis. RESULTS: In our study, GIT1 was notably upregulated in HNSCC tissues and cells. Moreover, GIT1 expression level had positive corelation with pathological grade and nodal status of HNSCC. Functional experiments showed that knockdown of GIT1 restrained HNSCC proliferation, invasion, migration, and EMT and facilitated cell apoptosis. Furthermore, GIT1 knockdown was found to restrain HNSCC tumor growth and lung metastasis. Additionally, PI3K/AKT/mTOR signal pathway inhibitors suppressed the effect of GIT1 on HNSCC cell progression. CONCLUSION: GIT1 was upregulated in HNSCC and facilitated HNSCC cell progression by inducing PI3K/AKT/mTOR signal pathway. Therefore, we suggested that GIT1 might be a potential target for HNSCC treatment.

Integrating mechanistic and deep learning models for accurately predicting the enrichment of polyhydroxyalkanoates accumulating bacteria in mixed microbial cultures.

The enrichment of polyhydroxyalkanoates (PHA) accumulating bacteria (PAB) in mixed microbial cultures (MMC) is extremely difficult to be predicted and optimized. Here we demonstrate that mechanistic and deep learning models can be integrated innovatively to accurately predict the dynamic enrichment of PAB. Well-calibrated activated sludge models (ASM) of the PAB enrichment process provide time-dependent data under different operating conditions. Recurrent neural network (RNN) models are trained and tested based on the time-dependent dataset generated by ASM. The accurate prediction performance is achieved (R2 > 0.991) for three different PAB enrichment datasets by the optimized RNN model. The optimized RNN model can also predict the equilibrium concentration of PAB (R2 = 0.944) and corresponding time, which represents the end of the PAB enrichment process. This study demonstrates the strength of integrating mechanistic and deep learning models to predict long-term variations of specific microbes, helping to optimize their selection process for PHA production.

Revealing the intrinsic drawbacks of waste activated sludge for efficient anaerobic digestion and the potential mitigation strategies.

Anaerobic digestion (AD) is an effective approach for waste activated sludge (WAS) disposal with substantial recovery of valuable substrates. Previous studies have extensively explored the correlations of common operational parameters with AD efficiency, but the impacts of intrinsic characteristics of WAS on the AD processes are generally underestimated. This study focused on disclosing the association of intrinsic drawbacks in WAS with AD performance, and found that the cemented WAS structure, low fraction of biomass and various high levels of inhibitory pollutants (e.g., organic pollutants and heavy metals), as the integral parts of WAS all greatly restricted the AD performance. The main potential strategies and underlying mechanisms to mitigate the restrictions for efficient WAS digestion, including the practical pretreatment methods, bioaugmentation and aided substances addition, were critically analyzed. Also, future directions for the improvement of WAS digestion were proposed from the perspectives of technical, management and economic aspects.