Targeting CEBPA to restore cellular identity and tissue homeostasis in pulmonary fibrosis.

Fibrosis in the lung is thought to be driven by epithelial cell dysfunction and aberrant cell-cell interactions. Unveiling the molecular mechanisms of cellular plasticity and cell-cell interactions is imperative to elucidate lung regenerative capacity and aberrant repair in pulmonary fibrosis. By mining publicly available RNA-seq datasets, we identified loss of CCAAT enhancer-binding protein alpha (CEBPA) as a candidate contributor to idiopathic pulmonary fibrosis (IPF). We used conditional knockout mice, scRNA-seq, lung organoids, small-molecule inhibition and novel gene manipulation methods to investigate the role of CEBPA in lung fibrosis and repair. Long term (6 month+) of Cebpa loss in AT2 cells caused spontaneous fibrosis and increased susceptibility to bleomycin-induced fibrosis. Cebpa knockout in these mice significantly decreased AT2 cell numbers in the lung and reduced expression of surfactant homeostasis genes, while increasing inflammatory cell recruitment as well as upregulating S100a8/a9 in AT2 cells. In vivo treatment with an S100A8/A9 inhibitor alleviated experimental lung fibrosis. Restoring CEBPA expression in lung organoids ex vivo and during experimental lung fibrosis in vivo rescued CEBPA deficiency-mediated phenotypes. Our study establishes a direct mechanistic link between CEBPA repression, impaired AT2 cell identity, disrupted tissue homeostasis, and lung fibrosis.

RNA-sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy.

Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA-sequencing was performed on flow-sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA-sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF-ß1 and TNF-α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro-fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up-regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro-fibrotic effect of TGF-ß1. RNA-sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Molecular surveillance of zoonotic pathogens from wild rodents in the Republic of Korea.

BACKGROUND: Rodents are recognized as major reservoirs of numerous zoonotic pathogens and are involved in the transmission and maintenance of infectious diseases. Furthermore, despite their importance, diseases transmitted by rodents have been neglected. To date, there have been limited epidemiological studies on rodents, and information regarding their involvement in infectious diseases in the Republic of Korea (ROK) is still scarce. METHODOLOGY/PRINCIPAL FINDINGS: We investigated rodent-borne pathogens using nested PCR/RT-PCR from 156 rodents including 151 Apodemus agrarius and 5 Rattus norvegicus from 27 regions in eight provinces across the ROK between March 2019 and November 2020. Spleen, kidney, and blood samples were used to detect Anaplasma phagocytophilum, Bartonella spp., Borrelia burgdorferi sensu lato group, Coxiella burnetii, Leptospira interrogans, and severe fever with thrombocytopenia syndrome virus (SFTSV). Of the 156 rodents, 73 (46.8%) were infected with Bartonella spp., 25 (16.0%) with C. burnetii, 24 (15.4%) with L. interrogans, 21 (13.5%) with A. phagocytophilum, 9 (5.8%) with SFTSV, and 5 (3.2%) with Borrelia afzelii. Co-infections with two and three pathogens were detected in 33 (21.1%) and 11 rodents (7.1%), respectively. A. phagocytophilum was detected in all regions, showing a widespread occurrence in the ROK. The infection rates of Bartonella spp. were 83.3% for B. grahamii and 16.7% for B. taylorii. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this is the first report of C. burnetii and SFTSV infections in rodents in the ROK. This study also provides the first description of various rodent-borne pathogens through an extensive epidemiological survey in the ROK. These results suggest that rodents harbor various pathogens that pose a potential threat to public health in the ROK. Our findings provide useful information on the occurrence and distribution of zoonotic pathogens disseminated among rodents and emphasize the urgent need for rapid diagnosis, prevention, and control strategies for these zoonotic diseases.

Desensitizing efficacy of a universal dentin adhesive containing mesoporous bioactive glass on dentin hypersensitivity: a randomized clinical trial with a split-mouth model.

This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli.

Evaluation of bovine coronavirus in Korean native calves challenged through different inoculation routes.

Bovine coronavirus (BCoV) is a pneumoenteric virus that can infect the digestive and respiratory tracts of cattle, resulting in economic losses. Despite its significance, information regarding BCoV pathogenesis is limited. Hence, we investigated clinical signs, patterns of viral shedding, changes in antibody abundance, and cytokine/chemokine production in calves inoculated with BCoV via intranasal and oral. Six clinically healthy Korean native calves (< 30 days old), initially negative for BCoV, were divided into intranasal and oral groups and monitored for 15 days post-infection (dpi). BCoV-infected calves exhibited clinical signs such as nasal discharge and diarrhea, starting at 3 dpi and recovering by 12 dpi, with nasal discharge being the most common symptoms. Viral RNA was detected in nasal and fecal samples from all infected calves. Nasal shedding occurred before fecal shedding regardless of the inoculation route; however, fecal shedding persisted longer. Although the number of partitions was very few, viral RNA was identified in the blood of two calves in the oral group at 7 dpi and 9 dpi using digital RT-PCR analysis. The effectiveness of maternal antibodies in preventing viral replication and shedding appeared limited. Our results showed interleukin (IL)-8 as the most common and highly induced chemokine. During BCoV infection, the levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß were significantly affected, suggesting that these emerge as potential and reliable biomarkers for predicting BCoV infection. This study underscores the importance of BCoV as a major pathogen causing diarrhea and respiratory disease.

Controlled Crystal Growth of All-Inorganic CsPbI2Br via Sequential Vacuum Deposition for Efficient Perovskite Solar Cells.

Vacuum deposition of perovskites is a promising method for scale-up fabrication and uniform film growth. However, improvements in the photovoltaic performance of perovskites are limited by the fabrication of perovskite films, which are not optimized for high device efficiency in the vacuum evaporation process. Herein, we fabricate CsPbI2Br perovskite with high crystallinity and larger grain size by controlling the deposition sequence between PbI2 and CsBr. The nucleation barrier for perovskite formation is significantly lowered by first evaporating CsBr and then PbI2 (CsBr-PbI2), followed by the sequential evaporation of multiple layers. The results show that the reduced Gibbs free energy of CsBr-PbI2, compared with that of PbI2-CsBr, accelerates perovskite formation, resulting in larger grain size and reduced defect density. Furthermore, surface-modified homojunction perovskites are fabricated to efficiently extract charge carriers and enhance the efficiency of perovskite solar cells (PeSCs) by modulating the final PbI2 thickness before thermal annealing. Using these strategies, the best PeSC exhibits a power conversion efficiency of 13.41% for a small area (0.135 cm2), the highest value among sequential thermal deposition inorganic PeSCs, and 11.10% for a large area PeSC (1 cm2). This study presents an effective way to understand the crystal growth of thermally deposited perovskites and improve their performance in optoelectronic devices.

Case report: Omphalitis caused by Trueperella pyogenes infection in a Korean indigenous calf.

Omphalitis, commonly caused by opportunistic bacteria has been significantly associated with morbidity and mortality in neonatal calves. Trueperella pyogenes is a commensal and opportunistic pathogen that can cause suppurative infection in farm animals. Our case involved a 10-day-old female Korean indigenous calf that presented with umbilical enlargement accompanied by a greenish-yellow purulent discharge and right forelimb lameness. The calf was diagnosed with failure of passive transfer at 24 h of age. Physical examination found hypothermia (38.1°C), tachycardia (110 beats/min), tachypnea (47 cycles/min), and open mouth breathing. Ultrasonography revealed hyperechoic pus in the 9th and 10th right intercostals, for which a liver abscess due to omphalophlebitis was suspected. After 3 days, the calf died. T. pyogenes was detected in the umbilical cord, lung, liver, kidney, intestine, mesenteric lymph node, urinary bladder, and bladder ligament. All genes related to the virulent factors (i.e., plo, cbpA, fimA, fimC, fimG, nanH, and nanP) were also identified, with plo and fimA being associated with pathogenicity. A final diagnosis of omphalitis was established based on the identification of virulent T. pyogenes and umbilical cord dilatation on ultrasonography. Antimicrobial susceptibility tests showed that the isolated T. pyogenes was susceptible to amoxicillin, ceftiofur, florfenicol, enrofloxacin, ofloxacin, and ciprofloxacin, suggesting the suitability of these antibiotics for treating T. pyogenes-induced omphalitis. Hence, accurate and rapid diagnosis of the involved bacteria and antimicrobial susceptibility patterns can help guide therapeutic decisions. Our case provides useful information that could aid large animal clinicians in the diagnosis and treatment of T. pyogenes-induced omphalitis.

The Impact of Electron Donating and Withdrawing Groups on Electrochemical Hydrogenolysis and Hydrogenation of Carbonyl Compounds.

The hydrogenolysis or hydrodeoxygenation of a carbonyl group, where the C═O group is converted to a CH2 group, is of significant interest in a variety of fields. A challenge in electrochemically achieving hydrogenolysis of a carbonyl group with high selectivity is that electrochemical hydrogenation of a carbonyl group, which converts the C═O group to an alcohol group (CH-OH), is demonstrated not to be the initial step of hydrogenolysis. Instead, hydrogenation and hydrogenolysis occur in parallel, and they are competing reactions. This means that although both hydrogenolysis and hydrogenation require adding H atoms to the carbonyl group, they involve different intermediates formed on the electrode surface. Thus, revealing the difference in intermediates, transition states, and kinetic barriers for hydrogenolysis and hydrogenation pathways is the key to understanding and controlling hydrogenolysis/hydrogenation selectivity of carbonyl compounds. In this study, we aimed to identify features of reactant molecules that can affect their hydrogenolysis/hydrogenation selectivity on a Zn electrode that was previously shown to promote hydrogenolysis over hydrogenation. In particular, we examined the electrochemical reduction of para-substituted benzaldehyde compounds with substituent groups having different electron donating/withdrawing abilities. Our results show a strikingly systematic impact of the substituent group where a stronger electron-donating group promotes hydrogenolysis and a stronger electron-withdrawing group promotes hydrogenation. These experimental results are presented with computational results explaining the substituent effects on the thermodynamics and kinetics of electrochemical hydrogenolysis and hydrogenation pathways, which also provide critically needed information and insights into the transition states involved with these pathways.

Comparison of blood profiles between housed and grazing Korean indigenous cattle (Hanwoo).

The objective of this study was to compare the hematology profiles of Korean indigenous cattle (Hanwoo) raised in a barn (housed) or on pasture (grazing). Our findings showed significant differences in the red blood cell (RBC) profiles of these 2 groups. When compared to cattle raised in a barn, a significant decrease in hematocrit (P = 0.000), hemoglobin (P = 0.000), and red blood cells (RBCs) (P = 0.000) and a significant increase in mean cell volume (P = 0.015) and reticulocytes (P = 0.000) were observed in grazing cattle, which indicate regenerative anemia. Furthermore, indirect bilirubin was significantly higher in grazing cattle, which indicates intravascular hemolysis and neutropenia (P = 0.000), and monocytosis (P = 0.000) was also identified. To the best of our knowledge, this is the first study that demonstrates changes in reticulocyte count and indirect bilirubin levels secondary to regenerative intravascular hemolysis in grazing cattle.

L'objectif de cette étude était de comparer les profils hématologiques de bovins coréens indigènes (Hanwoo) gardés dans une étable ou au pâturage. Nos résultats ont montré des différences significatives dans les profils des globules rouges de ces 2 groupes. Lorsque comparé aux bovins gardés dans l'étable, une réduction significative de l'hématocrite (P = 0,000), de l'hémoglobine (P = 0,000), et des globules rouges (P = 0,000) et une augmentation significative du volume cellulaire moyen (P = 0,015) et des réticulocytes (P = 0,000) ont été observées chez les bovins au pâturage, ce qui indique une anémie régénératrice. Également, la bilirubine indirecte était significativement plus élevée chez les bovins au pâturage, indicatif d'une hémolyse intravasculaire, et une neutropénie (P = 0,000) et une monocytose (P = 0,000) furent également identifiées. Au meilleur de nos connaissances, ceci est la première étude qui démontre des changements dans le dénombrement des réticulocytes et les niveaux de bilirubine indirecte secondaires à une hémolyse intravasculaire régénérative chez des bovins au pâturage.(Traduit par Docteur Serge Messier).

Evaluation of haematological parameters in haemolytic anaemia caused by tick-borne pathogens in grazing cattle.

BACKGROUND: No tick-borne pathogens (TBPs) causing haemolytic anaemia in cattle have been reported, except Theileria orientalis and complete blood count (CBC) profile is the only haematological parameter to determine the severity of regenerative haemolytic anaemia. OBJECTIVES: To identify the causative agents of TBP-induced haemolytic anaemia and determine haematological parameters that indicate haemolytic anaemia in grazing cattle. METHODS: Eighty-two Korean indigenous cattle (Hanwoo) were divided into two groups: grazing (n = 67) and indoor (n = 15) groups. CBC and serum biochemistry were performed. PCR was conducted using whole blood-extracted DNA to investigate the prevalence of TBPs. RESULTS: TBP-induced haemolytic anaemia was observed in the grazing group. In grazing cattle, co-infection (43.3%, 29/67) was most frequently detected, followed by T. orientalis (37.6%, 25/67) and Anaplasma phagocytophilum infections (1.5%, 1/67). In indoor cattle, only co-infection (20%, 3/15) was identified. Grazing cattle exhibited regenerative haemolytic anaemia with marked monocytosis, mild neutropenia, and thrombocytopenia. According to grazing frequency, the 1st-time grazing group had more severe anaemia than the 2nd-time grazing group. Elevations in indirect bilirubin and L-lactate due to haemolytic anaemia were identified, and correlations with the respective markers were determined in co-infected grazing cattle. CONCLUSIONS: Quantitative evaluation of haematocrit, mean corpuscular volume, and reticulocytes (markers of regenerative haemolytic anaemia in cattle) was performed for the first time. Our results show that, in addition to T. orientalis, A. phagocytophilum is strongly associated with anaemia. The correlation between haemolytic anaemia severity and haematological parameters (indirect bilirubin, reticulocytes, and L-lactate) was confirmed.

Non-canonical IKB kinases regulate YAP/TAZ and pathological vascular remodeling behaviors in pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) causes pulmonary vascular remodeling, increasing pulmonary vascular resistance (PVR) and leading to right heart failure and death. Matrix stiffening early in the disease promotes remodeling in pulmonary artery smooth muscle cells (PASMCs), contributing to PAH pathogenesis. Our research identified YAP and TAZ as key drivers of the mechanobiological feedback loop in PASMCs, suggesting targeting them could mitigate remodeling. However, YAP/TAZ are ubiquitously expressed and carry out diverse functions, necessitating a cell-specific approach. Our previous work demonstrated that targeting non-canonical IKB kinase TBK1 reduced YAP/TAZ activation in human lung fibroblasts. Here, we investigate non-canonical IKB kinases TBK1 and IKKε in pulmonary hypertension (PH) and their potential to modulate PASMC pathogenic remodeling by regulating YAP/TAZ. We show that TBK1 and IKKε are activated in PASMCs in a rat PH model. Inflammatory cytokines, elevated in PAH, activate these kinases in human PASMCs. Inhibiting TBK1/IKKε expression/activity significantly reduces PAH-associated PASMC remodeling, with longer-lasting effects on YAP/TAZ than treprostinil, an approved PAH therapy. These results show that non-canonical IKB kinases regulate YAP/TAZ in PASMCs and may offer a novel approach for reducing vascular remodeling in PAH.

Stereospecific NANOG PEST Stabilization by Pin1.

NANOG protein levels correlate with stem cell pluripotency. NANOG concentrations fluctuate constantly with low NANOG levels leading to spontaneous cell differentiation. Previous literature implicated Pin1, a phosphorylation-dependent prolyl isomerase, as a key player in NANOG stabilization. Here, using NMR spectroscopy, we investigate the molecular interactions of Pin1 with the NANOG unstructured N-terminal domain that contains a PEST sequence with two phosphorylation sites. Phosphorylation of NANOG PEST peptides increases affinity to Pin1. By systematically increasing the amount of cis PEST conformers, we show that the peptides bind tighter to the prolyl isomerase domain (PPIase) of Pin1. Phosphorylation and cis Pro enhancement at both PEST sites lead to a 5-10-fold increase in NANOG binding to the Pin1 WW domain and PPIase domain, respectively. The cis-populated NANOG PEST peptides can be potential inhibitors for disrupting Pin1-dependent NANOG stabilization in cancer stem cells.

Preliminary report of Mycoplasma Wenoynii and Candidatus Mycoplasma haemobos infection in Korean native cattle.

BACKGROUND: Hemotropic mycoplasmas or hemoplasmas are bacteria that attach to the erythrocyte surface and cause bovine hemoplasmosis. Two species, Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, have been identified and shown to be distributed worldwide. However, there is currently no information available on hemoplasmas in cattle in the Republic of Korea. The aim of this study was to investigate the presence of hemoplasmas in Korean native cattle and to evaluate the association between hemoplasma infection and anemia. METHODS: One farm was selected, at which blood samples were collected from 104 Korean native cattle [grazing cattle (n = 89) and housed cattle (n = 15)]. Hemoplasmas were detected via polymerase chain reaction analysis and complete blood counts were also performed. RESULTS: The overall prevalence of hemoplasmas was 34% (35/104); 20.2% (21/104) for M. wenyonii, 3.8% (4/104) for C. M. haemobos, and 9.6% (10/104) for co-infection. Candidatus Mycoplasma haemobos was detected only in grazing cattle. Of red blood cell (RBC) parameters, C. M. haemobos-infected cattle had lower RBC and hematocrit, and higher mean cell volume than hemoplasma-negative cattle, although none of these differences were statistically significant. This is the first study to report the occurrence of M. wenyonii and C. M. haemobos. Mycoplasma wenyonii is more prevalent than C. M. haemobos in Korean native cattle. The results did not show an association between hemoplasma infection and anemia. CONCLUSIONS: Considering the infection rate of hemoplasmas shown in this study, further studies, such as on the pathogenicity and clinical significance of hemoplasmas are necessary.

Substantially Accelerated Response and Recovery in Pd-Decorated WO3 Nanorods Gasochromic Hydrogen Sensor.

The development of hydrogen (H2) gas sensors is essential for the safe and efficient adoption of H2 gas as a clean, renewable energy source in the challenges against climate change, given its flammability and associated safety risks. Among various H2 sensors, gasochromic sensors have attracted great interest due to their highly intuitive and low power operation, but slow kinetics, especially slow recovery rate limited its further practical application. This study introduces Pd-decorated amorphous WO3 nanorods (Pd-WO3 NRs) as an innovative gasochromic H2 sensor, demonstrating rapid and highly reversible color changes for H2 detection. In specific, the amorphous nanostructure exhibits notable porosity, enabling rapid detection and recovery by facilitating effective H2 gas interaction and efficient diffusion of hydrogen ions (H+) dissociated from the Pd nanoparticles (Pd NPs). The optimized Pd-WO3 NRs sensor achieves an impressive response time of 14 s and a recovery time of 1 s to 5% H2. The impressively fast recovery time of 1 s is observed under a wide range of H2 concentrations (0.2-5%), making this study a fundamental solution to the challenged slow recovery of gasochromic H2 sensors.

Superaerophobic/Superhydrophilic Multidimensional Electrode System for High-Current-Density Water Electrolysis.

Water electrolysis is emerging as a promising renewable-energy technology for the green production of hydrogen, which is a representative and reliable clean energy source. From economical and industrial perspectives, the development of earth-abundant non-noble metal-based and bifunctional catalysts, which can simultaneously exhibit high catalytic activities and stabilities for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), is critical; however, to date, these types of catalysts have not been constructed, particularly, for high-current-density water electrolysis at the industrial level. This study developed a heterostructured zero-dimensional (0D)-one-dimensional (1D) PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF)-Ni3S2 as a self-supported catalytic electrode via interface and morphology engineering. This unique heterodimensional nanostructure of the PBSCF-Ni3S2 system demonstrates superaerophobic/superhydrophilic features and maximizes the exposure of the highly active heterointerface, endowing the PBSCF-Ni3S2 electrode with outstanding electrocatalytic performances in both HER and OER and exceptional operational stability during the overall water electrolysis at high current densities (500 h at 500 mA cm-2). This study provides important insights into the development of catalytic electrodes for efficient and stable large-scale hydrogen production systems.

Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC. METHODS: Alteration of receptor tyrosine kinase (RTK) activity in CAFs was analyzed using phospho-RTK array. The expression of CAFs effector genes was determined by RT-qPCR or ELISA. The migration and invasion of GC cells co-cultured with CAFs were examined by transwell migration/invasion assay. RESULTS: We found that conditioned media (CM) from GC cells could activate multiple receptor tyrosine kinase signaling pathways, including ERK, AKT, and STAT3. Phospho-RTK array analysis showed that CM from GC cells activated PDGFR tyrosine phosphorylation, but only AKT activation was PDGFR-dependent. Furthermore, we found that connective tissue growth factor (CTGF), a member of the CCN family, was the most pronouncedly induced CAFs effector gene by GC cells. Knockdown of CTGF impaired the ability of CAFs to promote GC cell migration and invasion. Although the PDGFR-AKT pathway was pronouncedly activated in CAFs stimulated by GC cells, its pharmacological inhibition affected neither CTGF induction nor CAFs-induced GC cell migration. Unexpectedly, the knockdown of SRC and SRC-family kinase inhibitors, dasatinib and saracatinib, significantly impaired CTGF induction in activated CAFs and the migration of GC cells co-cultured with CAFs. SRC inhibitors restored the reduced expression of epithelial markers, E-cadherin and Zonula Occludens-1 (ZO-1), in GC cells co-cultured with CAFs, as well as CAFs-induced aggregate formation in a 3D tumor spheroid model. CONCLUSIONS: This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC. Video Abstract.

Serum spectrin breakdown product and neurofilament heavy in predicting outcome after cardiac arrest: A diagnostic accuracy study.

Objectives: Spectrin breakdown products 145 kDa (SBDP145) and neurofilament heavy chain (Nf-H) have been identified as potential biomarkers of neuronal injury. However, their ability to predict hypoxic-ischemic brain injury following cardiac arrest in humans is not well understood. This study aimed to investigate whether SBDP145 and Nf-H could be used as biomarkers to predict neurological outcomes after cardiac arrest. Methods: This prospective study was conducted at two academic hospitals and included adults who survived after cardiac arrest. Blood samples were collected at 0, 24, and 48 h after the return of spontaneous circulation, and biomarker analyses were performed to measure SBDP145 and Nf-H. Poor neurological outcome was defined as a modified Rankin Score of 4-6, and diagnostic performance was determined by receiver-operating characteristics analysis. Results: A total of 56 patients were included in this study. There were no significant differences in levels of SBDP145 or Nf-H between the poor and good outcome groups at any time point. Areas under the receiver-operating characteristics curve of SBDP145 and Nf-H were small, ranging from 0.51 to 0.7. At 0, 24, and 48 h, SBDP145 showed very low sensitivity (18.61 %, 13.89 %, and 13.79 %, respectively) and accuracy (33.93 %, 36.74 %, and 39.02 %, respectively) at a cut-off value for 100 % specificity. Nf-H also showed very low sensitivity (9.30 %, 16.67 %, and 0 %, respectively) and accuracy (29.09 %, 36.74 %, and 30.95 %, respectively). Conclusions: SBDP145 and Nf-H were found to be poor predictors of poor neurological outcomes six months after cardiac arrest.

C-C Bond Formation Coupled with C-C Bond Cleavage during Oxidative Upgrading of Glycerol on a Nanoporous BiVO4 Photoanode.

Production of biodiesel generates glycerol as a 10 wt% byproduct. Therefore, efficient and selective glycerol upgrading is critical for the sustainable production of biodiesel as well as for the production of chemicals from renewable feedstocks. In this study, the photoelectrochemical glycerol oxidation reaction (GOR) was investigated using a nanoporous BiVO4 photoanode in pH 9.3 and pH 2 buffer solutions. In both solutions, glycolaldehyde (GCAD), a C2 species, was the major product, which has never been the major product in any previous electrochemical or photoelectrochemical GOR study. To produce GCAD from the C3 species glycerol, C-C cleavage should occur to produce C2 and C1 species with a 1:1 ratio. Intriguingly, our results show that, during photoelectrochemical GOR on BiVO4, more GCAD is produced than can be explained by simple C-C cleavage, meaning that GCAD is also produced from C-C coupling of two C1 species produced from C-C cleavage. This is equivalent to converting two glycerol molecules to three GCAD molecules, which offers an extraordinary way to maximize GCAD production. To gain further insight into the nature of this unprecedented C-C coupling during GOR, photoelectrochemical oxidation of intermediate oxidation products (glyceraldehyde and 1,3-dihydroxyacetone) and glycerol-1,3-13C2 was compared to that of standard glycerol. Photoelectrochemical GOR was also compared with electrochemical GOR on BiVO4 to interrogate whether light is critical for the observed C-C coupling. Results obtained from comprehensive control experiments revealed critical information about C-C cleavage and C-C coupling during GOR on BiVO4.

Extensive characterization of 28 complete chloroplast genomes of Hydrangea species: A perspective view of their organization and phylogenetic and evolutionary relationships.

The tribe Hydrangeeae displays a unique, distinctive disjunct distribution encompassing East Asia, North America and Hawaii. Despite its complex trait variations and polyphyletic nature, comprehensive phylogenomic and biogeographical studies on this tribe have been lacking. To address this gap, we sequenced and characterized 28 plastomes of Hydrangeeae. Our study highlights the highly conserved nature of Hydrangeaceae chloroplast (cp) genomes in terms of gene content and arrangement. Notably, synapomorphic characteristics of tandem repeats in the conserved domain of accD were observed in the Macrophyllae, Chinenses, and Dichroa sections within the Hydrangeeae tribe. Additionally, we found lower expression of accD in these sections using structure prediction and quantitative real-time PCR analysis. Phylogenomic analyses revealed the subdivision of the Hydrangeeae tribe into two clades with robust support values. Consistent with polyphyletic relationships, sect. Broussaisia was identified as the basal group in the tribe Hydrangeeae. Our study also provides insights into the phylogenetic relationships of Hydrangea petiolaris in the Jeju and Ulleung Island populations, suggesting the need for further studies with more samples and molecular data. Divergence time estimation and biogeographical analyses suggested that the common ancestors of the tribe Hydrangeeae likely originated from North America and East Asia during the Paleocene period via the Bering Land Bridge, potentially facilitating migration within the tribe between these regions. In conclusion, this study enhances our understanding of the evolutionary history and biogeography of the tribe Hydrangeeae, shedding light on the dispersal patterns and origins of this intriguing plant group with its unique disjunct distribution.

Hydrogen sulfide inhibits gene expression associated with aortic valve degeneration by inducing NRF2-related pro-autophagy effect in human aortic valve interstitial cells.

Aortic valve stenosis (AS) is the most common valvular heart disease but there are currently no effective medical treatments that can delay disease progression due to a lack of knowledge of the precise pathophysiology. The expression of sulfide: quinone oxidoreductase (SQOR) and nuclear factor erythroid 2-related factor 2 (NRF2) was decreased in the aortic valve of AS patients. However, the role of SQOR and NRF2 in the pathophysiology of AS has not been found. We investigated the effects of hydrogen sulfide (H2S)-releasing compounds on diseased aortic valve interstitial cells (AVICs) to explain the cellular mechanism of SQOR and elucidate the medical value of H2S for AS treatment. Sodium hydrosulfide (NaHS) treatment increased the expression of SQOR and NRF2 gene and consequently induced the NRF2 target genes, such as NAD(P)H quinone dehydrogenase 1 and cystathionine γ-lyase. In addition, NaHS dose-dependently decreased the expression level of fibrosis and inflammation-related genes (MMP9, TNF-α, IL6) and calcification-related genes (ALP, osteocalcin, RUNX2, COL1A1) in human AVICs. Furthermore, NaHS activated the AMPK-mTOR pathway and inhibited the PI3K-AKT pathway, resulting in a pro-autophagy effect in human AVICs. An NRF2 inhibitor, brusatol, attenuated NaHS-induced AMPK activation and decreased the autophagy markers Beclin-1 and LC3AB, suggesting that the mechanism of action of H2S is related to NRF2. In conclusion, H2S decreased gene expression levels related to aortic valve degeneration and activated AMPK-mTOR-mediated pro-autophagy function associated with NRF2 in human AVICs. Therefore, H2S could be a potential therapeutic target for the development of AS treatment.