Identification of agricultural surface source pollution in plain river network areas based on 3D-EEMs and convolutional neural networks.

Agricultural non-point sources, as major sources of organic pollution, continue to flow into the river network area of the Jiangnan Plain, posing a serious threat to the quality of water bodies, the ecological environment, and human health. Therefore, there is an urgent need for a method that can accurately identify various types of agricultural organic pollution to prevent the water ecosystems in the region from significant organic pollution. In this study, a network model called RA-GoogLeNet is proposed for accurately identifying agricultural organic pollution in the river network area of the Jiangnan Plain. RA-GoogLeNet uses fluorescence spectral data of agricultural non-point source water quality in Changzhou Changdang Lake Basin, based on GoogLeNet architecture, and adds an efficient channel attention (ECA) mechanism to its A-Inception module, which enables the model to automatically learn the importance of independent channel features. ResNet are used to connect each A-Reception module. The experimental results show that RA-GoogLeNet performs well in fluorescence spectral classification of water quality, with an accuracy of 96.3%, which is 1.2% higher than the baseline model, and has good recall and F1 score. This study provides powerful technical support for the traceability of agricultural organic pollution.

LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth.

The mechanisms underlying the dynamic remodelling of cellular membrane phospholipids to prevent phospholipid peroxidation-induced membrane damage and evade ferroptosis, a non-apoptotic form of cell death driven by iron-dependent lipid peroxidation, remain poorly understood. Here we show that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a critical role in ferroptosis resistance by increasing membrane phospholipid saturation via the Lands cycle, thereby reducing membrane levels of polyunsaturated fatty acids, protecting cells from phospholipid peroxidation-induced membrane damage and inhibiting ferroptosis. Furthermore, the enhanced in vivo tumour-forming capability of tumour cells is closely associated with the upregulation of LPCAT1 and emergence of a ferroptosis-resistant state. Combining LPCAT1 inhibition with a ferroptosis inducer synergistically triggers ferroptosis and suppresses tumour growth. Therefore, our results unveil a plausible role for LPCAT1 in evading ferroptosis and suggest it as a promising target for clinical intervention in human cancer.

Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma.

PURPOSE: Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that can be applied to clinical intervention for MVI in HCC. EXPERIMENTAL DESIGN: The histopathologic characteristics of clinical MVI+/HCC specimens were analyzed using multiplex immunofluorescence staining. The liver orthotopic xenograft mouse model and mechanistic experiments on human patient-derived HCC cell lines, including coculture modeling, RNA-sequencing, and proteomic analysis, were used to investigate MVI-related genes and mechanisms. RESULTS: IQGAP3 overexpression was correlated significantly with MVI status and reduced survival in HCC. Upregulation of IQGAP3 promoted MVI+-HCC cells to adopt an infiltrative vessel co-optive growth pattern and accessed blood capillaries by inducing detachment of activated hepatic stellate cells (HSC) from the endothelium. Mechanically, IQGAP3 overexpression contributed to HCC vascular invasion via a dual mechanism, in which IQGAP3 induced HSC activation and disruption of the HSC-endothelial interaction via upregulation of multiple cytokines and enhanced the trans-endothelial migration of MVI+-HCC cells by remodeling the cytoskeleton by sustaining GTPase Rac1 activity. Importantly, systemic delivery of IQGAP3-targeting small-interfering RNA nanoparticles disrupted the infiltrative vessel co-optive growth pattern and reduced the MVI of HCC. CONCLUSIONS: Our results revealed a plausible mechanism underlying IQGAP3-mediated microvascular invasion in HCC, and provided a potential target to develop therapeutic strategies to treat HCC with MVI.

Serum proteome profiling reveals heparanase as a candidate biomarker for chronic thromboembolic pulmonary hypertension.

Determining novel biomarkers for early identification of chronic thromboembolic pulmonary hypertension (CTEPH) could improve patient outcomes. We used the isobaric tag for relative and absolute quantitation approach to compare the serum protein profiles between CTEPH patients and the controls. Bioinformatics analyses and ELISA were also performed. We identified three proteins including heparanase (HPSE), gelsolin (GSN), and secreted protein acidic and rich in cysteine (SPARC) had significant changes in CTEPH. The receiver operating characteristic curve analysis showed that the areas under the curve of HPSE in CTEPH diagnosis were 0.988. Furthermore, HPSE was correlated with multiple parameters of right ventricular function. HPSE concentrations were significantly higher in patients with a low TAPSE/sPAP ratio (≤0.31 mm/mmHg) (65.4 [60.5,68.0] vs. 59.9 [35.9,63.2] ng/mL, p < 0.05). The CTEPH patients treated by balloon pulmonary angioplasty had significantly lower HPSE levels. The study demonstrates that HPSE may be a promising biomarker for noninvasive detection of CTEPH.

Postweaning stress affects behavior, brain and gut microbiota of adolescent mice in a sex-dependent manner.

Aggression is an instinctive behavior that has been reported to be influenced by early-life stress. However, the potential effects of acute stress during the postweaning period, a key stage for brain development, on defensive aggression and the associated mechanism remain poorly understood. In the present study, aggressive behaviors were evaluated in adolescent mice exposed to postweaning stress. Serum corticosterone and testosterone levels, neural dendritic spine density, and gut microbiota composition were determined to identify the underlying mechanism. Behavioral analysis showed that postweaning stress reduced locomotor activity in mice and decreased defensive aggression in male mice. ELISA results showed that postweaning stress reduced serum testosterone levels in female mice. Golgi staining analysis demonstrated that postweaning stress decreased neural dendritic spine density in the medial prefrontal cortex of male mice. 16S rRNA sequencing results indicated that postweaning stress altered the composition of the gut microbiota in male mice. Combined, these results suggested that postweaning stress alters defensive aggression in male mice, which may be due to changes in neuronal structure as well as gut microbiota composition. Our findings highlight the long-lasting and sex-dependent effects of early-life experience on behaviors.

Deficient tRNA posttranscription modification dysregulated the mitochondrial quality controls and apoptosis.

Mitochondria are dynamic organelles in cellular metabolism and physiology. Mitochondrial DNA (mtDNA) mutations are associated with a broad spectrum of clinical abnormalities. However, mechanisms underlying mtDNA mutations regulate intracellular signaling related to the mitochondrial and cellular integrity are less explored. Here, we demonstrated that mt-tRNAMet 4435A>G mutation-induced nucleotide modification deficiency dysregulated the expression of nuclear genes involved in cytosolic proteins involved in oxidative phosphorylation system (OXPHOS) and impaired the assemble and integrity of OXPHOS complexes. These dysfunctions caused mitochondrial dynamic imbalance, thereby increasing fission and decreasing fusion. Excessive fission impaired the process of autophagy including initiation phase, formation, and maturation of autophagosome. Strikingly, the m.4435A>G mutation upregulated the PARKIN dependent mitophagy pathways but downregulated the ubiquitination-independent mitophagy. These alterations promoted intrinsic apoptotic process for the removal of damaged cells. Our findings provide new insights into mechanism underlying deficient tRNA posttranscription modification regulated intracellular signaling related to the mitochondrial and cellular integrity.

Safety and efficacy of balloon pulmonary angioplasty for technically operable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) has been proven effective for addressing technically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effectiveness of BPA in technically operable CTEPH patients who, for various reasons, did not undergo the procedure remains an area requiring exploration. This study sought to assess the safety and efficacy of BPA in such cases. We collected and reviewed data from CTEPH patients who underwent BPA in a consecutive manner. Following multidisciplinary team (MDT) decisions, patients were classified into two groups: technically inoperable (group A) and operable (group B). Group B comprised patients deemed technically suitable for pulmonary endarterectomy (PEA) but who did not undergo the procedure for various reasons. All patients underwent a comprehensive diagnostic work-up, including right heart categorization at baseline and the last intervention. This study compared changes in hemodynamic parameters, functional capacity, and quality of life between the two groups. In total, 161 patients underwent 414 procedures at our center, with Group A comprising 112 patients who underwent 282 BPA sessions and group B comprising 49 patients who underwent 132 BPA sessions. Significantly, both groups exhibited improvements in hemodynamics, functional capacity, and quality of life. The occurrence rate of complications, including hemoptysis and lung injury, was similar [12 (63.2%) vs. 7 (36.8%), p = 0.68]. BPA demonstrated favorable outcomes in patients with proximal CTEPH who did not undergo pulmonary endarterectomy. However, the clinical impact of BPA in technically operable CTEPH was found to be less significant than in inoperable cases.

Identification of cuproptosis-related diagnostic biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with clinical and pathological heterogeneity. Recent studies have identified cuproptosis as a novel cell death mechanism. However, the role of cuproptosis-related genes in the pathogenesis of IPF is still unclear. Two IPF datasets of the Gene Expression Omnibus database were studied. Mann-Whitney U test, correlation analysis, functional enrichment analyses, single-sample gene set enrichment analysis, CIBERSORT, unsupervised clustering, weighted gene co-expression network analysis, and receiver operating characteristic curve analysis were used to conduct our research. The dysregulated cuproptosis-related genes and immune responses were identified between IPF patients and controls. Two cuproptosis-related molecular clusters were established in IPF, the high immune score group (C1) and the low immune score group (C2). Significant heterogeneity in immunity between clusters was revealed by functional analyses results. The module genes with the strongest correlation to the 2 clusters were identified by weighted gene co-expression network analysis results. Seven hub genes were found using the Cytoscape software. Ultimately, 2 validated diagnostic biomarkers of IPF, CDKN2A and NEDD4, were obtained. Subsequently, the results were validated in GSE47460. Our investigation illustrates that CDKN2A and NEDD4 may be valid biomarkers that were useful for IPF diagnosis and copper-related clustering.

CircMMP2(6,7) Cooperates with ß-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis.

The bone is the most common site of distant metastasis of breast cancer, which leads to serious skeletal complications and mortality. Understanding the mechanisms underlying breast cancer bone metastasis would provide potential strategies for the prevention and treatment of breast cancer bone metastasis. In this study, we identified a circular RNA that we named circMMP2(6,7) that was significantly upregulated in bone metastatic breast cancer tissues and correlated with breast cancer-bone metastasis. Upregulation of circMMP2(6,7) dramatically enhanced the metastatic capability of breast cancer cells to the bone via inducing bone metastatic niche formation by disrupting bone homeostasis. Mechanistically, circMMP2(6,7) specifically bound to the promoters of bone-remodeling factors calcium-binding protein S100A4 and carbohydrate-binding protein LGALS3 and formed a complex with ß-catenin and arginine methyltransferase PRMT5, eliciting histone H3R2me1/H3R2me2s-induced transcriptional activation. Treatment with GSK591, a selective PRMT5 inhibitor, effectively inhibited circMMP2(6,7)/ß-catenin/PRMT5 complex-induced breast cancer bone metastasis. These findings reveal a role for circMMP2(6,7) in bone homeostasis disruption and shed light on the mechanisms driving breast cancer bone metastasis. SIGNIFICANCE: Upregulation of bone-remodeling factors S100A4 and LGALS3 mediated by a circMMP2(6,7)/ß-catenin/PRMT5 complex generates a niche that supports breast cancer bone metastasis, identifying PRMT5 as a promising target for treating metastasis.

Prognostic, immunity, stemness, and anticancer drug sensitivity characterization of pyroptosis related genes in non-small cell lung cancer.

BACKGROUND: Pyroptosis plays a pivotal role in the tumor immune microenvironment (TME) dynamics, particularly in non-small cell lung cancer (NSCLC). The aim of our study was to explore its effects on tumor progression, TME patterns, and the efficacy of therapeutic interventions in NSCLC. METHODS: Our investigation encompassed a thorough analysis of pyroptosis-related genes (PRGs), integrating immunohistochemistry (IHC) data, TME characteristics, stemness indices, and anticancer drug sensitivities. We aimed to analyze mRNA expression profiles across various cancers, constructing benchmark datasets to assess the clinical significance of PRGs in NSCLC. This included evaluating their association with clinical responses and efficacy. Notably, both our and HPA IHC data demonstrated significantly elevated GSDMD-N protein levels in lung squamous cell carcinoma (LUSC) tissues. RESULTS: The expression of PRGs differed significantly between tumor and normal tissues across various cancers, as validated by IHC data, and was correlated with prognosis (p < 0.05). Moreover, our investigation revealed significant differences (p < 0.05) in the expression of the PRGs among distinct TME subtypes categorized as C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte deficient), and C6 (TGF-beta dominant). Additionally, our research on anticancer drug sensitivity uncovered compelling connections between specific anticancer medications and the expression of PRGs, including GSDMD, ELANE, IL18, and CHMP4A (p < 0.05). CONCLUSION: Our study provided valuable insights into the critical role of PRGs in TME modulation, tumor stemness, and anticancer drug sensitivity across diverse cancers. Our findings illuminate the intricate relationship between pyroptosis and the TME, offering new perspectives for enhancing NSCLC treatment and prognosis.

Electrochemical Study on the Macro-Cell Corrosion of Pipeline Steel Partially Covered by Different Kinds of Mineral Deposits.

This study presents the impact of mineral deposits (SiO2, Al2O3, and CaCO3) on the corrosion behavior of X65 pipeline steel in CO2-containing brine solution with low pH. The study investigates the initiation and propagation of under deposit corrosion (UDC) using a wire beam electrode (WBE) partially covered by different mineral deposit layers, in conjunction with electrochemical measurements and surface characterization. The results indicate that the corrosion behavior varies, depending on the characteristics of the deposit. During the test period, the Al2O3-covered steel acted as the main anode with more negative potential, while the bare steel acted as the cathode. The SiO2-covered steel acted as the cathode with more positive potential and a localized FeCO3 layer formed beneath the silica mineral. The CaCO3-covered steel initially acted as an anode with a more negative potential but transformed into the cathode at the end of the test. Additionally, shallow and small pits were observed beneath the deposits with the depth in the sequence Al2O3 > SiO2 > CaCO3.

Herbivory limits success of vegetation restoration globally.

Restoring vegetation in degraded ecosystems is an increasingly common practice for promoting biodiversity and ecological function, but successful implementation is hampered by an incomplete understanding of the processes that limit restoration success. By synthesizing terrestrial and aquatic studies globally (2594 experimental tests from 610 articles), we reveal substantial herbivore control of vegetation under restoration. Herbivores at restoration sites reduced vegetation abundance more strongly (by 89%, on average) than those at relatively undegraded sites and suppressed, rather than fostered, plant diversity. These effects were particularly pronounced in regions with higher temperatures and lower precipitation. Excluding targeted herbivores temporarily or introducing their predators improved restoration by magnitudes similar to or greater than those achieved by managing plant competition or facilitation. Thus, managing herbivory is a promising strategy for enhancing vegetation restoration efforts.

Is laparoscopic surgery a preferred option for benign conditions in the caudate lobe of the liver?

BACKGROUND/AIM: Laparoscopic hepatectomy has become a common management strategy for liver tumors owing to its less invasive nature and enhanced visual perspective. Yet, its use in the caudate lobe poses challenges. This study evaluates the experiences of patients who underwent laparoscopic hepatectomy for hepatic tumors in the caudate lobe and aims to propose strategies for performing such procedures. METHODS: We retrospectively analyzed the clinical data of twelve patients who underwent laparoscopic hepatic caudate lobe resection at the Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University. RESULTS: All twelve laparoscopic procedures were successful, with none requiring conversion to open surgery. The surgical methods varied: five cases involved simple resection of the Spiegel lobe, one case involved total caudate lobe resection, three cases involved paravena cava lobe resection, and three cases involved resection of the caudate process. The operation time ranged from 49 to 319 min (mean, 219 min). Intraoperative blood loss ranged from 20 to 500 ml, averaging 194 ml. No patients needed blood transfusions during or after the operation, and there were no instances of postoperative bleeding, bile leakage, or abdominal infection. CONCLUSION: Given adequate control of hepatic inflow, sufficient exposure to the surgical field, and an appropriate approach, laparoscopic hepatectomy in the caudate lobe could potentially become a standard surgical technique.

Reactive Oxygen Species in Drought-Induced Stomatal Closure: The Potential Roles of NPR1.

Stomatal closure is a vital, adaptive mechanism that plants utilize to minimize water loss and withstand drought conditions. We will briefly review the pathway triggered by drought that governs stomatal closure, with specific focuses on salicylic acid (SA) and reactive oxygen species (ROS). We propose that the non-expressor of PR Gene 1 (NPR1), a protein that protects plants during pathogen infections, also responds to SA during drought to sustain ROS levels and prevent ROS-induced cell death. We will examine the evidence underpinning this hypothesis and discuss potential strategies for its practical implementation.

A wide megafauna gap undermines China's expanding coastal ecosystem conservation.

To fulfill sustainable development goals, many countries are expanding efforts to conserve ecologically and societally critical coastal ecosystems. Although megafauna profoundly affect the functioning of ecosystems, they are neglected as a key component in the conservation scheme for coastal ecosystems in many geographic contexts. We reveal a rich diversity of extant megafauna associated with all major types of coastal ecosystems in China, including 218 species of mammals, birds, reptiles, cephalopods, and fish across terrestrial and marine environments. However, 44% of these species are globally threatened, and 78% have not yet been assessed in China for extinction risk. More worrisome, 73% of these megafauna have not been designated as nationally protected species, and <10% of their most important habitats are protected. Filling this wide "megafauna gap" in China and globally would be a leading step as humanity strives to thrive with coastal ecosystems.