Mix proportion design and carbon emission assessment of high strength geopolymer concrete based on ternary solid waste.

To achieve dual optimization of the mechanical properties and environmental impacts of geopolymer concrete (GPC), this study proposes a high-strength geopolymer concrete (HSGPC) without coarse aggregate. The mix proportion of HSGPC was optimized using the response surface methodology, targeting compressive strength and splitting tensile strength to determine the optimal mix. Additionally, the carbon emission impact of HSGPC was assessed and compared with ordinary Portland cement concrete, ultra-high-performance concrete, and reactive powder concrete. The results indicate that the optimal mix proportion for HSGPC includes 15% fly ash content, 10.30% silica fume content, alkali activator ratio of 2.5, and a NaOH molar concentration of 10 M. Simultaneously, the carbon emissions of HSGPC are reduced by about 30% compared to ordinary Portland cement concrete. Compared to ultra-high-performance concrete and reactive powder concrete of the same strength, the production of HSGPC respectively reduces carbon emissions by 59.87% and 68.24%. This study not only provides valuable technical support for the practical application of GPC in engineering but also holds significant implications for promoting sustainable development in the construction industry.

An Internally Attached Aptameric Graphene Nanosensor for Sensitive Vasopressin Measurement in Critical Patient Monitoring.

This paper presents an aptameric graphene nanosensor for rapid and sensitive measurement of arginine vasopressin (AVP) toward continuous monitoring of critical care patients. The nanosensor is a field-effect transistor (FET) with monolayer graphene as the conducting channel and is functionalized with a new custom-designed aptamer for specific AVP recognition. Binding between the aptamer and AVP induces a change in the carrier density in the graphene and resulting in measurable changes in FET characteristics for determination of the AVP concentration. The aptamer, based on the natural enantiomer D-deoxyribose, possess optimized kinetic binding properties and is attached at an internal position to the graphene for enhanced sensitivity to low concentrations of AVP. Experimental results show that this aptameric graphene nanosensor is highly sensitive (with a limit of detection of 0.3 pM and a resolution of 0.1 pM) to AVP, and rapidly responsive (within 90 s) to both increasing and decreasing AVP concentration changes. The device is also reversable (within 4%), repeatable (within 4%) and reproducible (within 5%) in AVP measurements.

Comparison of aerosol number size distribution and new particle formation in summer at alpine and urban regions in the Guanzhong Plain, Northwest China.

Ultrafine particles play a crucial role in understanding climate change, mitigating adverse health effects, and developing strategies for air pollution control. However, the factors influencing the occurrence and development of new particle formation (NPF) events, as well as the underlying chemical mechanisms, remain inadequately explained. This study compared number concentrations and size distributions of atmospheric ultrafine particles at Xi'an (urban area) and the summit of Mt. Hua (alpine region) in summer to investigate the NPF mechanism and particle growth in both clean and polluted areas of the Guanzhong Plain. The average particle number concentration in Xi'an was significantly higher than that at Mt. Hua. The diurnal variation of total particle number concentration differed between Xi'an and Mt. Hua indicating a divergence in influencing factors. The size distributions in Xi'an varied across different timescales and weather conditions, whereas Mt. Hua exhibited little variation. This stability at Mt. Hua is attributed to its cleaner background atmosphere and the steady influx of aging particles with larger diameters transported from the free atmosphere. In both areas, geometric mean diameters (GMDs) were inversely proportional to particle number concentrations suggesting that increase in particle numbers were primarily due to the generation of smaller particles. The potential governing factors for NPF events differed somewhat between the urban and mountainous stations. In the urban area, intense local stationary and mobile emission sources promoted the growth of newly formed nanoparticles, with ozone-oxidized condensable vapors serving as key precursors. In contrast, at the mountainous station, NPF process were significantly influenced by anthropogenic precursors from long-range transport and locally emitted biogenic organics. The rapid increase in ultrafine particle concentrations primarily poses serious health risks and degrades air quality in urban areas, while also contributing to climate-related effects in alpine regions.

Impact of formaldehyde on ozone formation in Central China: Important role of biogenic emission in forest region.

Formaldehyde (HCHO) is an important source for driving tropospheric ozone (O3) formation. This study investigated the combined effects of anthropogenic and biogenic emission on O3 formation in the Guanzhong Basin (GZB), Central China, providing useful information into the mechanisms of O3 formation due to the interaction between anthropogenic and biogenic volatile organic compounds (VOCs). A severe O3 pollution episode in summer of 2017 was simulated using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to examine the impacts of ambient HCHO on ground-level O3. Results showed secondary HCHO dominated ambient levels, peaking in the afternoon (up to 86 %), while primary emissions contributed 14 % on average. This enhanced O3 production by 7.7 % during the morning rush hour and 24.3 % in the afternoon. In addition, HCHO concentration peaked before that of O3, suggesting it plays significant role in O3 formation. Biogenic emission oxidation contributed 3.1 µg m-3 (53.1 %) of HCHO and 5.2 pptv (40.1 %) of hydroperoxyl radicals (HO2) in average urban areas, where the downwind regions of the forests had high nitrogen oxides (NOx) levels and favorable conditions for O3 production (17.3 µg m-3, 20.5 %). In forested regions, sustained isoprene oxidation led to elevated oxidized VOCs including HCHO and acetaldehyde downwind, which practiced further photolysis of O3 formation with anthropogenic NOx in urban areas. Sensitivity experiments recommend controlling industrial and traffic NOx emissions, with regional joint prevention and regulation, which are essential to reduce O3 pollution.

Unveiling the shield: Troglitazone's impact on epilepsy-induced nerve injury through ferroptosis inhibition.

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.

Gene gain and loss from the Asian corn borer W chromosome.

BACKGROUND: Sex-limited chromosomes Y and W share some characteristics, including the degeneration of protein-coding genes, enrichment of repetitive elements, and heterochromatin. However, although many studies have suggested that Y chromosomes retain genes related to male function, far less is known about W chromosomes and whether they retain genes related to female-specific function. RESULTS: Here, we built a chromosome-level genome assembly of the Asian corn borer, Ostrinia furnacalis Guenée (Lepidoptera: Crambidae, Pyraloidea), an economically important pest in corn, from a female, including both the Z and W chromosome. Despite deep conservation of the Z chromosome across Lepidoptera, our chromosome-level W assembly reveals little conservation with available W chromosome sequence in related species or with the Z chromosome, consistent with a non-canonical origin of the W chromosome. The W chromosome has accumulated significant repetitive elements and experienced rapid gene gain from the remainder of the genome, with most genes exhibiting pseudogenization after duplication to the W. The genes that retain significant expression are largely enriched for functions in DNA recombination, the nucleosome, chromatin, and DNA binding, likely related to meiotic and mitotic processes within the female gonad. CONCLUSIONS: Overall, our chromosome-level genome assembly supports the non-canonical origin of the W chromosome in O. furnacalis, which experienced rapid gene gain and loss, with the retention of genes related to female-specific function.

DPP Inhibition Enhances the Efficacy of PD-1 Blockade by Remodeling the Tumor Microenvironment in Lewis Lung Carcinoma Model.

The remarkable efficacy of cancer immunotherapy has been established in several tumor types. Of the various immunotherapies, PD-1/PD-L1 inhibitors are most extensively used in the treatment of many cancers in clinics. These inhibitors restore the suppressed antitumor immune response and inhibit tumor progression by blocking the PD-1/PD-L1 signaling. However, the low response rate is a major limitation in the clinical application of PD-1/PD-L1 inhibitors. Therefore, combination strategies that enhance the response rate are the need of the hour. In this investigation, PT-100 (also referred to as Talabostat, Val-boroPro, and BXCL701), an orally administered and nonselective dipeptidyl peptidase inhibitor, not only augmented the effectiveness of anti-PD-1 therapy but also significantly improved T immune cell infiltration and reversed the immunosuppressive tumor microenvironment. The combination of PT-100 and anti-PD-1 antibody increased the number of CD4+ and CD8+ T cells. Moreover, the mRNA expression of T cell-associated molecules was elevated in the tumor microenvironment. The results further suggested that PT-100 dramatically reduced the ratio of tumor-associated macrophages. These findings provide a promising combination strategy for immunotherapy in lung cancer.

[Pollution Characteristics and Source Analysis of Soil Heavy Metal in Coal Mine Area near the Yellow River in Shandong].

To explore the pollution characteristics and source of soil heavy metal in a coal mine area near the Yellow River in Shandong, the geo-accumulation index method and improved Nemerow pollution index method were used to evaluate the pollution characteristics of soil heavy metal. The absolute principal component-multiple linear regression model (APCS-MLR) was used to quantitatively analyze the source of soil heavy metal, and the spatial distribution of Hg and Cd were analyzed using the Kriging spatial difference method in ArcGIS. The result accuracy of the APCS-MLR model was further verified. The results showed that:The measured contents of soil heavy metal Cu, Zn, Pb, Cr, Cd, Ni, As, and Hg all exceeded the normal site, among which, Hg and Cd exceeded the background values of soil elements in Shandong. The coefficient of variation (CV) of Hg was higher than 0.500, indicating significant spatial heterogeneity. Moreover, the correlation between Hg and other heavy metals was generally low, and the possibility of the same pollution source was small. The results of the geo-accumulation index and improved Nemerow pollution index showed that the overall soil heavy metal pollution was at a moderate level, among which the Hg pollution level was the highest, and its maximum value was at a slanted-heavy pollution level; Cu, Cd, and As in soil caused local pollution, which were at a slanted-light pollution level. Soil heavy metal pollution was closely related to mining activities, rehabilitation, and engineering construction in the coal mine area. The two major pollution sources of soil heavy metal in the research area were the compound source of the parent material and industrial and mining transportation sources (known source 1) and the compound source of atmospheric sedimentation and coal production (known source 2), the contribution rates of which were 76.705% and 16.171%, respectively. The results of the APCS-MLR model were shown to be reliable by analyzing the content distribution of Hg and Cd using the Kriging space difference mode. This research can provide scientific basis for the precise control and improvement of soil heavy metal pollution, ensuring the safety of food and agricultural products and improving the quality of the ecological environment in the coal mine area in the Shandong section of the Yellow River Basin.

Deciphering the role of Enterococcus faecium cytidine deaminase in gemcitabine resistance of gallbladder cancer.

Gemcitabine-based chemotherapy is a cornerstone of standard care for gallbladder cancer (GBC) treatment. Still, drug resistance remains a significant challenge, influenced by factors such as tumor-associated microbiota impacting drug concentrations within tumors. Enterococcus faecium, a member of tumor-associated microbiota, was notably enriched in the GBC patient cluster. In this study, we investigated the biochemical characteristics, catalytic activity, and kinetics of the cytidine deaminase of E. faecium (EfCDA). EfCDA showed the ability to convert gemcitabine to its metabolite 2',2'-difluorodeoxyuridine. Both EfCDA and E. faecium can induce gemcitabine resistance in GBC cells. Moreover, we determined the crystal structure of EfCDA, in its apo form and in complex with 2', 2'-difluorodeoxyuridine at high resolution. Mutation of key residues abolished the catalytic activity of EfCDA and reduced the gemcitabine resistance in GBC cells. Our findings provide structural insights into the molecular basis for recognizing gemcitabine metabolite by a bacteria CDA protein and may provide potential strategies to combat cancer drug resistance and improve the efficacy of gemcitabine-based chemotherapy in GBC treatment.

Comparison of acidity and chemical composition of summertime cloud water and aerosol at an alpine site in Northwest China: Implications for the neutral property of clouds in the free troposphere.

Aerosol and cloud acidity are essential to human health, ecosystem health and productivity, as well as climate effects. The main chemical composition of cloud water greatly varies in different regions, resulting in substantial differences in the pH of cloud water. However, the influences of the anthropogenic emissions of acidic gases and substances, alkaline dust components, and dicarboxylic acids (diacids) on the ground concerning the acidity of cloud water in the free troposphere of the Guanzhong Plain, China, remain clear. In this study, cloud water and PM2.5 samples were simultaneously collected in the troposphere (Mt. Hua, 2060 m a.s.l). The results indicated that the cloud water was alkaline (pH = 7.6) and PM2.5 was acidic (pH = 3.2). These results showed the neutral property of clouds collected in the heavily polluted Guanzhong Plain, although most previous studies always considered acidity as a marker of pollution. The sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+) (SNA) of particulate matter and cloud water in the same period were compared. SO42- was dominant in particulate matters (accounting for 63.4 % of the total SNA) but substantially decreased in cloud water (only 30.1 % of the total SNA), whereas NO3- and NH4+ increased from 28.5 % and 8.2 % to 39.8 % and 30.2 %, respectively. This could be attributed to the complex formation mechanism and sources of SO42- and NO3- in the cloud. The results of ion balance indicated that a significant deficit of inorganic anion equivalents was observed in the cloud water samples. The high concentration of diacids in the cloud phase (1237.4 µg L-1) may facilitate the formation of salt complexes with NH4+, thus influencing the acidity of the cloud water. The pH of cloud water has increased in recent decades due to the sustained reduction of sulfur dioxide, which may also affect the acidity of future precipitation.

Rapid isolation of anti-idiotype aptamers for quantification of human monoclonal antibodies against SARS-CoV-2 spike protein.

Therapeutic antibodies that block viral entry have already proven to be important, first line drugs for treatments of viral infections. In the case of SARS-CoV-2, combinations of multiple therapeutic antibodies may need to be rapidly identified and formulated in a way that blocks each new, predominant variant of the virus. For efficient introduction of any new antibody combination into patients, it is important to be able to monitor patient-specific pharmacokinetics of individual antibodies, which would include the time course of their specific capacity to block the viral spike proteins. Here, we present three examples of microfluidic-based rapid isolation of companion reagents useful for establishing combination antibody therapies. These reagents are specific three-dimensional imprints of variable regions of individual human monoclonal antibodies against the -spike protein of SARS-CoV-2 virus in the form of oligonucleotide-based ligands (aptamers). We implement these anti-idiotypic aptamers as bioreceptors in graphene-based field-effect transistor sensors to accomplish label free, rapid, and sensitive detection of matching antibodies within minutes. Through this work we have demonstrated the general applicability of anti-idiotype aptamers as capture reagents in quantification of active forms of monoclonal antibodies in complex biological mixtures.

The Efficiency of Pest Control Options against Two Major Sweet Corn Ear Pests in China.

Helicoverpa armigera (Hübner) and Ostrinia furnacalis (Guenée) are the most devastating insect pests at the ear stage of maize, causing significant losses to the sweet corn industry. Pesticide control primarily relies on spraying during the flowering stage, but the effectiveness is inconsistent since larvae are beneath husks within hours to a day, making pesticide treatments simpler to avoid. Insufficient understanding of pest activity patterns impedes precise and efficient pesticide control. H. armigera and O. furnacalis in corn fields were monitored in the last few years in Beijing China, and we observed a higher occurrence of both moths during the R1 stage of sweet corn. Moth captures reached the maximum during this stage, with 555-765 moths per hectare corn field daily. The control efficiency of nine synthetic insecticides and five biopesticides was assessed in the field during this period. Virtako, with mineral oil as the adjuvant, appeared to be the most effective synthetic insecticide, with the efficiencies reaching 88% and 87% on sweet and waxy corn, respectively. Pesticide residue data indicated that the corn is safe after 17 days of its use. The most effective bioinsecticide was Beauveria bassiana combined with mineral oil, with 88% and 80% control efficiency in sweet and waxy corn, respectively. These results suggested that spraying effective insecticides 5 days after corn silking could effectively control corn ear pests H. armigera and O. furnacalis. Our findings provide valuable insights for the development of ear pest management strategies in sweet corn.

Disruption of cholangiocyte-B cell crosstalk by blocking the CXCL12-CXCR4 axis alleviates liver fibrosis.

B cells can promote liver fibrosis, but the mechanism of B cell infiltration and therapy against culprit B cells are lacking. We postulated that the disruption of cholangiocyte-B-cell crosstalk could attenuate liver fibrosis by blocking the CXCL12-CXCR4 axis via a cyclooxygenase-2-independent effect of celecoxib. In wild-type mice subjected to thioacetamide, celecoxib ameliorated lymphocytic infiltration and liver fibrosis. By single-cell RNA sequencing and flow cytometry, CXCR4 was established as a marker for profibrotic and liver-homing phenotype of B cells. Celecoxib reduced liver-homing B cells without suppressing CXCR4. Cholangiocytes expressed CXCL12, attracting B cells to fibrotic areas in human and mouse. The proliferation and CXCL12 expression of cholangiocytes were suppressed by celecoxib. In CXCL12-deficient mice, liver fibrosis was also attenuated with less B-cell infiltration. In the intrahepatic biliary epithelial cell line HIBEpiC, bulk RNA sequencing indicated that both celecoxib and 2,5-dimethyl-celecoxib (an analog of celecoxib that does not show a COX-2-dependent effect) regulated the TGF-ß signaling pathway and cell cycle. Moreover, celecoxib and 2,5-dimethyl-celecoxib decreased the proliferation, and expression of collagen I and CXCL12 in HIBEpiC cells stimulated by TGF-ß or EGF. Taken together, liver fibrosis can be ameliorated by disrupting cholangiocyte-B cell crosstalk by blocking the CXCL12-CXCR4 axis with a COX-2-independent effect of celecoxib.

Comparison of chemical composition and acidity of size-resolved inorganic aerosols at the top and foot of Mt. Hua, Northwest China: The role of the gas-particle distribution of ammonia.

Aerosol pH is not only a diagnostic indicator of secondary aerosol formation, but also a key factor in the specific chemical reaction routes that produce sulfate and nitrate. To understand the characteristics of aerosol acidity in the Mt. Hua, the chemical fractions of water-soluble inorganic ions in the atmospheric PM2.5 and size-resolved particle at the top and foot of Mt. Hua in summer 2020 were studied. The results showed the mass concentrations of PM2.5 and water-soluble ions at the foot were 2.0-2.6 times higher than those at the top. The secondary inorganic ions, i.e., SO42-, NO3-, and NH4+ (SNA) were 56 %-61 % higher by day than by night. SO42- was mainly distributed in the fine particles (Dp < 2.1 µm). NO3- showed a unimodal size distribution (peaking at 0.7-1.1 µm) at the foot and a bimodal (0.7-1.1 µm and 4.7-5.8 µm) size distribution at the top. At the top site, the distribution of NO3- in coarse particles (> 2.1 µm) was mainly attributed to the gaseous HNO3 volatilized from fine particles reacting with cations in coarse particles to form non-volatile salts (such as Ca(NO3)2). The pH values of PM2.5 were 2.7 ± 1.3 and 3.3 ± 0.42 at the top and foot, respectively. NH4+/NH3(g) plays a decisive role in stabilizing aerosol acidity. In addition, the increase of the liquid water content (LWC) at the foot facilitates the gas-particle conversion of NH3, while the H+ concentration was diluted, resulting in a decrease in acidity at the foot. NH4+/NH3 had good linear correlations with SO42-, NO3-, and LWC during the daytime at both sites, indicating that SO42-, NO3-, and LWC together affect the gas-particle distribution of ammonia by day: however, the effect of LWC at night was not evident.

FASN deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress.

Fatty acid synthase (FASN) maintains de novo lipogenesis (DNL) to support rapid growth in most proliferating cancer cells. Lipogenic acetyl-coenzyme A (CoA) is primarily produced from carbohydrates but can arise from glutamine-dependent reductive carboxylation. Here, we show that reductive carboxylation also occurs in the absence of DNL. In FASN-deficient cells, reductive carboxylation is mainly catalyzed by isocitrate dehydrogenase-1 (IDH1), but IDH1-generated cytosolic citrate is not utilized for supplying DNL. Metabolic flux analysis (MFA) shows that FASN deficiency induces a net cytosol-to-mitochondria citrate flux through mitochondrial citrate transport protein (CTP). Previously, a similar pathway has been shown to mitigate detachment-induced oxidative stress in anchorage-independent tumor spheroids. We further report that tumor spheroids show reduced FASN activity and that FASN-deficient cells acquire resistance to oxidative stress in a CTP- and IDH1-dependent manner. Collectively, these data indicate that by inducing a cytosol-to-mitochondria citrate flux, anchorage-independent malignant cells can gain redox capacity by trading off FASN-supported rapid growth.

Fast Determination of Optimal Transmission Rate for Wireless Blockchain Networks: A Graph Convolutional Neural Network Approach.

One of the primary challenges in wireless blockchain networks is to ensure security and high throughput with constrained communication and energy resources. In this paper, with curve fitting on the collected blockchain performance dataset, we explore the impact of the data transmission rate configuration on the wireless blockchain system under different network topologies, and give the blockchain a utility function which balances the throughput, energy efficiency, and stale rate. For efficient blockchain network deployment, we propose a novel Graph Convolutional Neural Network (GCN)-based approach to quickly and accurately determine the optimal data transmission rate. The experimental results demonstrate that the average relative deviation between the blockchain utility obtained by our GCN-based method and the optimal utility is less than 0.21%.

RNF216 affects the stability of STAU2 in the hypothalamus.

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disease characterized by gonadal failure due to deficiency in gonadotropin-releasing hormone (GnRH) synthesis, secretion, or action. RNF216 variants have been recently identified in patients with IHH. Ring finger protein 216 (RNF216), as a ubiquitin E3 ligase, catalyzes the ubiquitination of target proteins with high specificity, which consequently modulates the stability, localization, and interaction of the target protein. In this study, we found that RNF216 interacted with Staufen2 (STAU2) and affected the stability of STAU2 through the ubiquitin-proteasome pathway. STAU2, as a double-stranded RNA-binding protein enriched in the nervous system, plays a role in RNA transport, RNA stability, translation, anchoring, and synaptic plasticity. Further, we revealed that STAU2 levels in the hypothalamus of RNF216-/- mice were increased compared with wild-type (WT) mice. The change in STAU2 protein homeostasis may affect a series of RNA cargoes. Therefore, we analyzed the changes in RNA levels in the hypothalamus of RNF216-/- mice and WT mice by RNA sequencing. We found that deletion of RNF216 led to decreased activities of the prolactin signaling pathway, neuroactive ligand-receptor interaction, GnRH signaling pathway, and ovarian steroidogenesis. The weakening of these signal pathways is likely to affect the secretion of GnRH, thereby affecting the development of gonads. Therefore, our study suggests that STAU2 may be a potential therapeutic target for IHH. Further experiments are needed to demonstrate the association between the weakening of these signaling pathways and the RNA-binding protein STAU2.

Comparison of Gas-Particle Partitioning of Glyoxal and Methylglyoxal in the Summertime Atmosphere at the Foot and Top of Mount Hua.

Glyoxal and methylglyoxal are important volatile organic compounds in the atmosphere. The gas-particle partitioning of these carbonyl compounds makes significant contributions to O3 formation. In this study, both the gas- and particle-phase glyoxal and methylglyoxal concentrations at the foot and top of Mount Hua were determined simultaneously. The results showed that the gaseous-phase glyoxal and methylglyoxal concentrations at the top were higher than those at the foot of the mountain. However, the concentrations for the particle phase showed the opposite trend. The average theoretical values of the gas-particle partitioning coefficients of the glyoxal and methylglyoxal concentrations (4.57 × 10-10 and 9.63 × 10-10 m3 µg-1, respectively) were lower than the observed values (3.79 × 10-3 and 6.79 × 10-3 m3 µg-1, respectively). The effective Henry's law constants (eff.KH) of the glyoxal and methylglyoxal were in the order of 108 to 109 mol/kgH2O/atm, and they were lower at the foot than they were at the top. The particle/gas ratios (P/G ratios) of the glyoxal and methylglyoxal were 0.039 and 0.055, respectively, indicating more glyoxal and methylglyoxal existed in the gas phase. The factors influencing the partitioning coefficients of the glyoxal and methylglyoxal were positively correlated with the relative humidity (RH) and negatively correlated with the PM2.5 value. Moreover, the partitioning coefficient of the glyoxal and methylglyoxal was more significant at the top than at the foot of Mount Hua.

Atypical cholangiocytes derived from hepatocyte-cholangiocyte transdifferentiation mediated by COX-2: a kind of misguided liver regeneration.

BACKGROUND: Hepatocyte-cholangiocyte transdifferentiation (HCT) is a potential origin of proliferating cholangiocytes in liver regeneration after chronic injury. This study aimed to determine HCT after chronic liver injury, verify the impacts of HCT on liver repair, and avoid harmful regeneration by understanding the mechanism. METHODS: A thioacetamide (TAA)-induced liver injury model was established in wild-type (WT-TAA group) and COX-2 panknockout (KO-TAA group) mice. HCT was identified by costaining of hepatocyte and cholangiocyte markers in vivo and in isolated mouse hepatocytes in vitro. The biliary tract was injected with ink and visualized by whole liver optical clearing. Serum and liver bile acid (BA) concentrations were measured. Either a COX-2 selective inhibitor or a ß-catenin pathway inhibitor was administered in vitro. RESULTS: Intrahepatic ductular reaction was associated with COX-2 upregulation in chronic liver injury. Immunofluorescence and RNA sequencing indicated that atypical cholangiocytes were characterized by an intermediate genetic phenotype between hepatocytes and cholangiocytes and might be derived from hepatocytes. The structure of the biliary system was impaired, and BA metabolism was dysregulated by HCT, which was mediated by the TGF-ß/ß-catenin signaling pathway. Genetic deletion or pharmaceutical inhibition of COX-2 significantly reduced HCT in vivo. The COX-2 selective inhibitor etoricoxib suppressed HCT through the TGF-ß-TGFBR1-ß-catenin pathway in vitro. CONCLUSIONS: Atypical cholangiocytes can be derived from HCT, which forms a secondary strike by maldevelopment of the bile drainage system and BA homeostasis disequilibrium during chronic liver injury. Inhibition of COX-2 could ameliorate HCT through the COX-2-TGF-ß-TGFBR1-ß-catenin pathway and improve liver function.

C-C motif chemokine receptor 2 inhibition reduces liver fibrosis by restoring the immune cell landscape.

The accumulation of extracellular matrix (ECM) proteins in the liver leads to liver fibrosis and end-stage liver cirrhosis. C-C motif chemokine receptor 2 (CCR2) is an attractive target for treating liver fibrosis. However, limited investigations have been conducted to explore the mechanism by which CCR2 inhibition reduces ECM accumulation and liver fibrosis, which is the focus of this study. Liver injury and liver fibrosis were induced by carbon tetrachloride (CCl4) in wild-type mice and Ccr2 knockout (Ccr2-/-) mice. CCR2 was upregulated in murine and human fibrotic livers. Pharmacological CCR2 inhibition with cenicriviroc (CVC) reduced ECM accumulation and liver fibrosis in prevention and treatment administration. In single-cell RNA sequencing (scRNA-seq), CVC was demonstrated to alleviate liver fibrosis by restoring the macrophage and neutrophil landscape. CVC administration and CCR2 deletion can also inhibit the hepatic accumulation of inflammatory FSCN1+ macrophages and HERC6+ neutrophils. Pathway analysis indicated that the STAT1, NFκB, and ERK signaling pathways might be involved in the antifibrotic effects of CVC. Consistently, Ccr2 knockout decreased phosphorylated STAT1, NFκB, and ERK in the liver. In vitro, CVC could transcriptionally suppress crucial profibrotic genes (Xaf1, Slfn4, Slfn8, Ifi213, and Il1ß) in macrophages by inactivating the STAT1/NFκB/ERK signaling pathways. In conclusion, this study depicts a novel mechanism by which CVC alleviates ECM accumulation in liver fibrosis by restoring the immune cell landscape. CVC can inhibit profibrotic gene transcription via inactivating the CCR2-STAT1/NFκB/ERK signaling pathways.