Deep learning, geometric characterization and hydrodynamic modeling for assessing sewer defect impacts on urban flooding: A case study in Guangzhou, China.

Deep learning techniques have offered innovative and efficient tools for accurate and automated detection of sewer defects by leveraging large-scale sewer data and advanced feature learning algorithms. However, there has been a lack of thorough characterization of the geometric properties of segmented defects, let alone systematically calculate the severity level of sewer defects and quantitatively evaluate their impacts on flood conditions in hydrodynamic models. This study proposed a comprehensive framework and related metrics to accurately and automatically detect, segment, characterize, and evaluate the impacts of sewer defects on flooded nodes and volumes by integrating a DeepLabv3+-based segmentation technique, an automated geometric characterization and severity quantification module, and a GIS and SWMM-based hydrodynamic modeling. The results clearly showed in details where and how much the urban flooding was affected by the different defect types. The segmentation model achieved satisfactory detection performance, with mean pixel accuracy (MPA), mean intersection over union (MIoU), and frequency weighted intersection over union (FWIoU) of 0.99, 0.74 and 0.95, respectively. In terms of severity level quantification, there were 98%, 90%, 90% and 83% of predictions consistent with real conditions for falling off, obstacle, disjoint and leakage. It was shown that the number of surcharging manholes and total flood volume (TFV) were greatly affected by sewer defects, with over 16% increase in TFVs under all investigated rainfall events. The results addressed the impacts of sewer defects on urban flooding and demonstrated the powerful tools provided by the proposed framework for decision-making on sewer defect detection and management.

Transforming growth factor-ß1 attenuates inflammation and lung injury with regulating immune function in ventilator-induced lung injury mice.

Ventilator-induced lung injury (VILI) is a lung injury induced or aggravated by mechanical ventilation. Transforming growth factor (TGF)-ß1 is a cytokine that mediates immune function, enabling inflammatory attenuation and tissue repair. Here, we hypothesized that it plays an important role in the attenuation of VILI and inflammation. Ventilation with high tidal volume was performed on C57BL/6 mice to establish a VILI model. After 4 h of ventilation, mice were sacrificed (end of ventilation [EOV]) or extubated for resuscitation at 4 h (post-ventilation 4 h [PV4h]), 8 h (PV8h) and 24 h post-ventilation (PV1d). Recombinant mouse TGF-ß1 (rTGF-ß1) and the neutralization antibody of TGF-ß1 (nTAb) were used in vivo to examine the effect of TGF-ß1 on immune function and inflammatory attenuation in VILI mice. Lung injury was exacerbated at the same trend as the interleukin (IL)-1ß level, peaking at PV1d, whereas IL-6 and tumor necrosis factor (TNF)-α levels gradually reduced. Most active phagosomes, swollen round mitochondria, and cavitating lamellar bodies were observed at PV4h. The CD4+ T cells were significantly increased from PV4h to PV1d, and the CD8a + T cells were higher in the PV4h and PV1d groups; furthermore, the mice in the PV8h group showed highest proportion of CD4+CD8a+ T cells and CD4+/CD8a+ ratio. CD19 + and CD5 + CD19 + B cells in VILI mice began to increase at PV1d. The pulmonary expression of latent and monomer TGF-ß1 increased at PV4h and PV8h. Treatment of rTGF-ß1 only induced high expression of latent and monomer TGF-ß1 at EOV to decrease pulmonary levels of IL-1ß, IL-6, and TNF-α; however, lung injury attenuated from EOV to PV1d. TGF-ß1 induced the delayed elevation of CD4+/CD8a+ T cells ratio and activation of pulmonary CD4+CD8a+ double-positive T cells under certain conditions. Elastic fibers and celluloses, although relatively less proteoglycan, were observed with the overexpression of TGF-ß1 at PV4h and PV8h. In conclusion, TGF-ß1 attenuates the inflammatory response and lung injury of VILI via immune function regulation.

Identification of hub genes associated with acute kidney injury induced by renal ischemia-reperfusion injury in mice.

Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia-reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia-reperfusion injury (IRI-AKI). Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)-hub gene and miRNA-hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb. Result: A total of 323 common differentially expressed genes were identified in the renal ischemia-reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein-Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes. Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia-reperfusion injury-acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia-reperfusion injury-acute kidney injury.

Arecoline promotes proliferation and migration of human HepG2 cells through activation of the PI3K/AKT/mTOR pathway.

BACKGROUND: Arecoline is a well-known risk factor for oral submucosal fibrosis and cancer. However, the mechanistic correlation between arecoline and hepatocellular cancer remains elusive. Here, we investigated the effect of arecoline on the proliferation and migration of human HepG2 hepatoma cells and its potential oncogenic mechanisms. METHODS: Bioinformatic technologies were used to identify the deferentially expressed miRNAs (DE-miRNAs) and hub target genes of arecoline-induced cancers. These DE-miRNAs, hub genes and pathway were proved in arecoline-treated HepG2 cells. RESULTS: A total of 86 DE-miRNAs and 460 target genes were identified. These target genes are associated with DNA-templated regulation of transcription and other biological processes. Significant molecular functions were protein binding, calcium ion binding, and enrichment in the nucleus and cytoplasm. These genes are involved in the PI3K-AKT pathway. CDK1, CCND1, RAF1, CDKN1B and BTRC were defined as the top 5 hub target genes, and patients with high expression of CDK1 showed poor prognosis. Compared with control group, 2.5 µM arecoline treatment increased the proliferation and migration ability of the HepG2 cells. Treatment with 2.5 µM arecoline increased the levels of miR-21-3p, miR-21-5p and miR-1267, upregulated the expression of PI3K-AKT pathway factors, CDK1, CCND1 but decreased RAF1 expression. CONCLUSION: A low concentration arecoline can induce the proliferation and migration of HepG2 cells, with the potential mechanism of action linked to high levels of exosomal miR-21 and miR-1267, activation of the PI3K-AKT pathway, upregulation of CDK1 and CCND1, and downregulation of RAF1.

Sulfidation of ferric (hydr)oxides and its implication on contaminants transformation: a review.

Rapid industrialization and urbanization have resulted in elevated concentrations of contaminants in the groundwaters and subsurface soils, posing a growing hazard to humans and ecosystems. The transformation of most contaminants is closely linked to the mineralogy of ferric (hydr)oxides. Sulfidation of ferric (hydr)oxides is one of the most significant biogeochemical reactions in the anoxic environments, causing reductive dissolution and recrystallization of ferric (hydr)oxides and further affecting the transformation of iron-associated contaminants. This paper provides a comprehensive review on the sulfidation process of ferric (hydr)oxides and the transformation of relevant contaminants. This review presents detailed reaction mechanisms between ferric (hydr)oxides and dissolved sulfide, and elucidates the factors (e.g. crystallinity of ferric (hydr)oxides, the ratio of sulfide concentration to the surface area concentration of ferric (hydr)oxides) that control the formation of surface associated Fe(II), iron sulfide minerals, as well as transformation of secondary minerals. Then, we summarized the transformation mechanisms of a variety of typical environmentally relevant contaminants existing in groundwater and subsurface soils, including heavy metals, metal(loid) oxyanions (arsenic, antimony, chromium), radionuclides (uranium, technetium), organic contaminants and phosphate/nitrate species. The general mechanisms of contaminant transformation involve a combination of release, reduction and re-adsorption/incorporation processes, the specific pathway of which is highly dependent on the properties of the contaminant itself and the extent of sulfidation. Moreover, the challenge of extending our knowledge towards in situ remediation, as well as further research needs are identified.

Sensitive Micro-Breathing Sensing and Highly-Effective Photothermal Antibacterial Cinnamomum camphora Bark Micro-Structural Cotton Fabric via Electrostatic Self-Assembly of MXene/HACC.

Natural fabrics are gradually becoming the ideal substrate for flexible smart wearable devices due to their excellent moisture absorption, softness, and skin-friendliness. However, the bonding fastness of the conductive layer and the corresponding durability during service have not yet been well satisfied. In this report, we successfully prepared a smart wearable multifunctional protective cotton fabric with microbreathing monitoring and rapid-photothermal antibacterial abilities of Cinnamomum camphora bark microstructure, by combining chitosan quaternary ammonium salt (HACC) with MXene nanosheets through electrostatic self-assembly. Impressively, MXene nanosheets and HACC established a strong interaction using the electrostatic attraction, endowing the fiber surface with ordered nanosheets. Meanwhile, the fabric decorated with MXene/HACC retains its original characteristics of outstanding breathability and softness, and its conductivity exhibits noticeable stability in terms of resistances to oxidation, washing, various solvents, and long-term bending cycles. On the basis of the principle of adsorption and release of water molecules in the MXene multilayer structures, the MXene/HACC fabric could accurately monitor the physiological health activities of users according to their breathing frequency and depth. Benefiting from the local surface plasmon resonance (LSPR) effect, the MXene/HACC shows encouraging photothermal conversion ability, photothermal stability under long time irradiation, washing resistance, and cycle stability. In addition, the fabric achieved an antibacterial efficiency of nearly 100% against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus within 5 min under an irradiation intensity of 400 mW/cm2. More importantly, after 10 washes, the antibacterial efficiency against the two bacteria could still reach 99.975% and 99.98%, respectively. This multifunctional protective MXene/HACC cotton fabric is expected to play a unique role in the new generation of smart wearable microbreathing sensing and against to bacterial attack, and shows a broad application prospect.

Developing a Multifunctional Silk Fabric with Dual-Driven Heating and Rapid Photothermal Antibacterial Abilities Using High-Yield MXene Dispersions.

Two-dimensional material titanium carbide (Ti3C2Tx MXene) has been widely used for building diverse functional materials; however, the disadvantages of unsatisfactory yield and low concentration during the preparation process generally limit its large-scale promotion. In the present work, an MXene dispersion with enhanced yield (90%), high concentration (45 mg/mL), and excellent dispersibility was successfully prepared. Subsequently, the active MXene nanosheets were effectively in situ deposition onto the silk fiber by means of dip-coating, relying on van der Waals forces and hydrogen bonds. The obtained MXene-decorated silk fabric (MXene@silk) exhibits satisfactory electrical conductivity (170 mS/cm), excellent photothermal and electrothermal conversion properties, especially dual-drive energy conversion, rapid thermal responses, and long-term functional stability. Furthermore, UV protection factor of the fabric, and its antibacterial efficiency against Gram-negative Escherichia coli (E. coli) within 20 min of contact reach over 110 and 99%, respectively, demonstrating remarkable UV resistance and rapid photothermal antibacterial ability. Meanwhile, the fabric of MXene@silk still retains the original characteristics of breathability, softness, and skin-friendly properties compared to the untreated. The multifunctional fabric constructed through a facile and high-yield strategy shows a noticeable potential applying to smart textiles to meet people's multipurpose needs in the future.

Cardiomyocyte protective effects of thyroid hormone during hypoxia/reoxygenation injury through activating of IGF-1-mediated PI3K/Akt signalling.

Ischaemia/reperfusion (I/R) injury is a common clinical condition that results in apoptosis and oxidative stress injury. Thyroid hormone was previously reported to elicit cardiac myocyte hypertrophy and promote cardiac function after cardiac injury. We used an in vivo mouse model of I/R injury and in vitro primary cardiomyocyte culture assays to investigate the effects of thyroid hormone on cardiomyocytes during hypoxia/reoxygenation (H/R) injury. The results showed that T3 pretreatment in vivo significantly improved left ventricular function after I/R injury. In vitro, T3 pretreatment decreased cell apoptosis rate, inhibited caspase-3 activity and decreased the Bax/Bcl-2 ration induced by H/R injury. T3 pretreatment significantly attenuated the loss of mitochondrial membrane potential. Furthermore, it was observed that T3 diminished the expression of NCX1 protein and decreased SERCA2a protein expression in H/R-induced cardiomyocytes, and T3 prevented intracellular Ca2+ increase during H/R injury. Also, T3 increased the expression of IGF-1, and PI3K/Akt signalling in cardiomyocytes under H/R-induced injury, and that the protective effect of T3 against H/R-induced injury was blocked by the PI3K inhibitor LY294002. IGF-1 receptor (IGF-1R) inhibitor GSK1904529A significantly inhibited the expression of IGF-1R and PI3K/Akt signalling. In summary, T3 pretreatment protects cardiomyocytes against H/R-induced injury by activating the IGF-1-mediated PI3K/Akt signalling pathway.

Thyroid hormone mediates cardioprotection against postinfarction remodeling and dysfunction through the IGF-1/PI3K/AKT signaling pathway.

AIMS: Severe cardiovascular diseases, such as myocardial infarction or heart failure, can alter thyroid hormone (TH) secretion and peripheral conversion, leading to low triiodothyronine (T3) syndrome. Accumulating evidence suggests that TH has protective properties against cardiovascular diseases and that treatment with TH can effectively reduce myocardial damage after myocardial infarction (MI). Our aim is to investigate the effect of T3 pretreatment on cardiac function and pathological changes in mice subjected to MI and the underlying mechanisms. MAIN METHODS: Adult male C57BL/6 mice underwent surgical ligation of the left anterior descending coronary artery (LAD) (or sham operation) to establish MI model. T3, BMS-754807 (inhibitor of insulin-like growth factor-1 receptor (IGF-1R)) or vehicle was administered before surgery. KEY FINDINGS: Compared with the MI group, the T3 pretreatment group exhibited significant attenuation of the myocardial infarct area, inhibition of cardiomyocyte apoptosis and fibrosis, and improved left ventricular function after MI. In addition, T3 exhibited an enhanced potency to stimulate angiogenesis and exert anti-inflammatory effects by reducing the levels of serum inflammatory cytokines after MI. However, all of these protective effects were inhibited by the IGF-1R inhibitor BMS-754807. Moreover, the protein expression of IGF-1/PI3K/AKT signaling-related proteins, such as IGF-1, IGF-1R, phosphorylated PI3K (p-PI3K) and p-AKT was significantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins. SIGNIFICANCE: T3 pretreatment can protect the heart against dysfunction post-MI, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.

Neutrophil-Derived IL-17 Promotes Ventilator-Induced Lung Injury via p38 MAPK/MCP-1 Pathway Activation.

Ventilator-induced lung injury (VILI) is one of the most common complications of mechanical ventilation and can severely affect health. VILI appears to involve excessive inflammatory responses, but its pathogenesis has not yet been clarified. Since interleukin-17 (IL-17) plays a critical role in the immune system and the development of infectious and inflammatory diseases, we investigated here whether it plays a role in VILI. In a mouse model of VILI, mechanical ventilation with high tidal volume promoted the accumulation of lung neutrophils, leading to increased IL-17 levels in the lung, which in turn upregulated macrophage chemoattractant protein-1 via p38 mitogen-activated protein kinase. Depletion of neutrophils decreases the production IL-17 in mice and inhibition of IL-17 significantly reduced HTV-induced lung injury and inflammatory response. These results were confirmed in vitro using RAW264.7 macrophage cultures. Our results suggest that IL-17 plays a pro-inflammatory role in VILI and could serve as a new target for its treatment.

Chromosome-Level Clam Genome Helps Elucidate the Molecular Basis of Adaptation to a Buried Lifestyle.

Bivalve mollusks are economically important invertebrates that exhibit marked diversity in benthic lifestyle and provide valuable resources for understanding the molecular basis of adaptation to benthic life. In this report, we present a high-quality, chromosome-anchored reference genome of the Venus clam, Cyclina sinensis. The chromosome-level genome was assembled by Pacific Bioscience single-molecule real-time sequencing, Illumina paired-end sequencing, 10× Genomics, and high-throughput chromosome conformation capture technologies. The final genome assembly of C. sinensis is 903.2 Mb in size, with a contig N50 size of 2.6 Mb and a scaffold N50 size of 46.5 Mb. Enrichment analyses of significantly expanded and positively selected genes suggested evolutionary adaptation of this clam to buried life. In addition, a change in shell color represents another mechanism of adaptation to burial in sediment. The high-quality genome generated in this work provides a valuable resource for investigating the molecular mechanisms of adaptation to buried lifestyle.

Thyroid Hormone Diminishes Ca2+ Overload Induced by Hypoxia/Reoxygenation in Cardiomyocytes by Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current.

BACKGROUND AND PURPOSE: Intracellular calcium concentration ([Ca2+]i) overload occurs in myocardial ischemia and -reperfusion. The augmentation of the late sodium current (INaL) causes intracellular Na+ accumulation and subsequent [Ca2+]i overload via the reverse mode of the Na+/Ca2+ exchange current (reverse-INCX), which can lead to arrhythmia and cardiac dysfunction. Thus, inhibition of INaL is a potential therapeutic approach for ischemic heart disease. The aim of this study was to investigate the effects of thyroid hormone on augmented INaL, reverse-INCX, altered action potential duration (APD), and [Ca2+]i concentration in hypoxia/reoxygenation (H/R)-induced ventricular myocytes in vitro. METHODS: The transient Na+ current (INaT), INaL, reverse-INCX, and APs were recorded using a whole-cell patch-clamp technique in neonatal mouse ventricular myocytes. [Ca2+]i concentration alteration were, respectively, observed by confocal microscopy and flow cytometry. RESULTS: Triiodothyronine (T3) pretreatment decreased the INaL in a concentration-dependent manner. H/R injury aggravated the INaL, INaT, and reverse-INCX in cardiomyocytes and increased the continuous accumulation of [Ca2+]i (p < 0.05). The application of T3 prior to H/R injury significantly decreased the increased INaL, INaT, and reverse-INCX and blunted the [Ca2+]i increase. Furthermore, T3 pretreatment shortened the APD induced by H/R injury. CONCLUSION: T3 inhibited H/R-increased INaL and reverse INCX augmentation, shortened the APD, and diminished [Ca2+]i overload, indicating a potential therapeutic use of T3 as an INaL inhibitor to maintain Ca2+ homeostasis and protect cardiomyocytes against H/R injury.

Thyroid hormone protects cardiomyocytes from H2O2-induced oxidative stress via the PI3K-AKT signaling pathway.

Oxidative stress plays an important role in the progression of cardiac diseases, including acute myocardial infarction, ischemia/reperfusion (I/R) injury and heart failure. Growing evidence indicates that thyroid hormone has protective properties against cardiovascular diseases. However, little is known about its effect on oxidative stress in cardiomyocytes or the underlying mechanisms. This study showed that T3 pretreatment in vivo significantly reduced cardiac dysfunction by increasing the left ventricular ejection function and ameliorating the pathological changes induced by I/R-induced injury. In an in vitro experiment, T3 inhibited apoptosis in H2O2-treated cardiomyocytes, as evidenced by the decreased expression of Bax, cleaved caspase 3 and 9, and increased expression of Bcl-2. In addition, oxidative stress observed in hearts of mice with I/R injury was significantly alleviated by T3 pretreatment, intracellular ROS and mitochondrial ROS overproduction were effectively inhibited, and similar results were also detected in H2O2-treated cardiomyocytes in vitro. T3 significantly increased antioxidant protein (Nrf2 and HO-1) expression levels, and inhibited NOX2 and NOX4 protein expression levels in H2O2-treated cardiomyocytes. Moreover, T3 preserved mitochondrial functions upon H2O2-induced oxidative stress by increasing mitochondrial membrane potential and promoting the expression of mitochondrial biogenesis genes. Notably, the PI3K/AKT signaling was significantly activated by T3 pretreatment in H2O2-induced cardiomyocytes. Together, these findings revealed that T3 could be served as potential therapeutic target for protection against cardiac oxidative stress injury through its antioxidant and anti-apoptosis effects, which are mediated by the activation of the PI3K/AKT signaling pathway.