Arabidopsis calcineurin B-like-interacting protein kinase 8 and its functional homolog in tomato negatively regulates ABA-mediated stomatal movement and drought tolerance.

Stomatal movement is critical for water transpiration, gas exchange, and responses to biotic stresses. Abscisic acid (ABA) induces stomatal closure to prevent water loss during drought. We report that Arabidopsis CIPK8 negatively regulates ABA-mediated stomatal closure and drought tolerance. CIPK8 is highly enriched in guard cells and transcriptionally induced by ABA. Functional loss of CIPK8 results in hypersensitive stomatal closure to ABA and enhanced drought tolerance. Guard cell-specific downregulation of CIPK8 mimics the phenotype of cipk8 whereas guard cell-specific expression of a constitutive active CIPK8 (CIPK8CA) has an opposite effect, suggesting a cell autonomous activity of CIPK8. CIPK8 physically interacts with CBL1 and CBL9. Functional loss of CBL1 and CBL9 mimics ABA-hypersensitive stomatal closure of cipk8 whereas abolishes the effect of CIPK8CA, indicating that CIPK8 and CBL1/CBL9 form a genetic module in ABA-responsive stomatal movement. SlCIPK7, the functional homolog of CIPK8 in tomato (Solanum lycopersicum), plays a similar role in ABA-responsive stomatal movement. Genomic editing of SlCIPK7 results in more drought-tolerant tomato, making it a good candidate for germplasm improvement.

Removal of dyes from wastewater using Eucalyptus wood fiber loaded nanoscale zero-valent iron: Characterization and removal mechanism.

Wood fiber as a natural and renewable material has low cost and plenty of functional groups, which owns the ability to adsorb dyes. In order to improve the application performance of wood fiber in dye-pollution wastewater, Eucalyptus wood fiber loaded nanoscale zero-valent iron (EWF-nZVI) was developed to give EWF magnetism and the ability to degrade dyes. EWF-nZVI was characterized via FTIR, XRD, zeta potential, VSM, SEM-EDS and XPS. Results showed that EWF-nZVI owned a strong magnetism of 96.51 emu/g. The dye removal process of EWF-nZVI was more in line with the pseudo-second-order kinetics model. In addition, the Langmuir isotherm model fitting results showed that the maximum removal capacities of Congo red and Rhodamine B by EWF-nZVI were 714.29 mg/g and 68.49 mg/g at 328 K, respectively. After five adsorption-desorption cycles, the regeneration efficiencies of Congo red and Rhodamine B were 74 % and 42 % in turn. The dye removal mechanisms of EWF-nZVI included redox degradation (Congo red and Rhodamine B) and electrostatic adsorption (Congo red). In summary, EWF-nZVI is a promising biomass-based material with high dye removal capacities. This work is beneficial to promote the large-scale application of wood fiber in water treatment.

Green tea polyphenols inhibit TBBPA-induced lung injury via enhancing antioxidant capacity and modulating the NF-κB pathway in mice.

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1ß, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.

[Establishment and analysis of an early prognosis model of patients with acute kidney injury in intensive care unit].

OBJECTIVE: To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance. METHODS: A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation II (APACHE II) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI. RESULTS: A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHE II score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day "n", with y = 1.246 2x1.164 9 and an R2 of 0.860 1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day "n", with y = -0.260 6x2+3.010 7x-1.612 and an R2 of 0.998 9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 µmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. CONCLUSIONS: The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.

High-fat diet disrupts the gut microbiome, leading to inflammation, damage to tight junctions, and apoptosis and necrosis in Nyctereutes procyonoides intestines.

Given the burgeoning Nyctereutes procyonoides breeding industry and its growing scale, it is imperative to investigate the impact of high-fat diets on the health of these animals. This study involved 30 male Nyctereutes procyonoides of comparable weights (3 kg ±0.5), randomly assigned to either a control group or a high-fat diet group (n = 15 each). The latter group was fed a mixture of lard and basal diet in a 2:5 ratio, establishing a high-fat diet model in Nyctereutes procyonoides. This diet induced diarrhea and histopathological changes in the Nyctereutes procyonoides. Analysis of the small intestine contents using 16S rRNA sequencing revealed a high-fat diet-induced disruption in the gut microbiota. Specifically, Escherichia-Shigella emerged as the biomarker in the high-fat diet group (P = 0.049), while Vagococcus was prevalent in the control group (P = 0.049), indicating a significant increase in harmful bacteria in the high-fat diet group. Furthermore, this disrupted gut flora correlated with inflammation and oxidative stress, as evidenced by marked increases in TNF-α (P < 0.01), IL-1ß (P < 0.05), and IL-6 (P < 0.05) levels, measured via q-PCR, Western blot, and oxidative stress assays. In addition, q-PCR analysis revealed significant upregulation of apoptosis and necrosis markers, including Bax, Caspase3, Caspase9, Caspase12, RIPK3, and RIPK1 (P < 0.01 to P < 0.001), and a concurrent downregulation of the anti-apoptotic gene Bcl-2 (P < 0.01) in the high-fat diet group, consistent with protein expression trends. These findings suggest that a high-fat diet alters the gut microbiome toward a more harmful bacterial composition, escalating inflammatory responses and intestinal tissue permeability, culminating in intestinal cell apoptosis and necrosis.IMPORTANCEThis study examines the impact of high-fat diets on Nyctereutes procyonoides. Our research established a Nyctereutes procyonoides model on a high-fat diet, revealing significant health impacts, such as diarrhea, histological anomalies, and alterations in the gut microbiota. These findings emphasize the importance of preventing health issues and promoting sustainable industry growth. They highlight the significant impact of diet on gut microbiota and overall animal health.

Arabidopsis protein S-acyl transferases positively mediate BR signaling through S-acylation of BSK1.

Protein S-acyl transferases (PATs) catalyze S-acylation, a reversible post-translational modification critical for membrane association, trafficking, and stability of substrate proteins. Many plant proteins are potentially S-acylated but few have corresponding PATs identified. By using genomic editing, confocal imaging, pharmacological, genetic, and biochemical assays, we demonstrate that three Arabidopsis class C PATs positively regulate BR signaling through S-acylation of BRASSINOSTEROID-SIGNALING KINASE1 (BSK1). PAT19, PAT20, and PAT22 associate with the plasma membrane (PM) and the trans-Golgi network/early endosome (TGN/EE). Functional loss of all three genes results in a plethora of defects, indicative of reduced BR signaling and rescued by enhanced BR signaling. PAT19, PAT20, and PAT22 interact with BSK1 and are critical for the S-acylation of BSK1, and for BR signaling. The PM abundance of BSK1 was reduced by functional loss of PAT19, PAT20, and PAT22 whereas abolished by its S-acylation-deficient point mutations, suggesting a key role of S-acylation in its PM targeting. Finally, an active BR analog induces vacuolar trafficking and degradation of PAT19, PAT20, or PAT22, suggesting that the S-acylation of BSK1 by the three PATs serves as a negative feedback module in BR signaling.

Bone regeneration with hydroxyapatite particles loaded in photo-cross-linkable hydrogel: An experimental study.

This study explores the use of in situ cross-linked hyaluronic acid methacryloyl (HAMA) and hydroxyapatite particles (HAP) for bone defect repair. Human periodontal ligament stem cells (PDLSCs) were isolated and co-cultured with the HAMA-HAP composite. Osteogenic differentiation was evaluated using Alizarin Red staining, alkaline phosphatase activity quantification, and polymerase chain reaction (PCR). A cranial defect was induced in Sprague-Dawley rats. This defect was then filled with the HAMA-HAP composite and cross-linked using UV light exposure. Bone formation was assessed through radiographic and histological analyses. The HAMA-HAP composite was found to promote cell viability similarly to pure HAP. It also enhanced gene expression of ALP, OPN, and Runx2, and increased ALP activity and mineralized nodule formation in vitro. Micro-CT scans showed defect restoration in the HAMA-HAP and HAP groups compared to the control group. The HAMA-HAP group exhibited higher Tb.N, Tb.Sp, Tb.Th, and BV/TV. Masson staining showed the HAMA-HAP composite restored the defect site, with new bone formation thicker than in the HAP group. The HAMA-HAP composite showed excellent biocompatibility and promoted osteogenic differentiation of PDLSCs. It effectively repaired cranial defects, indicating its potential for clinical use in bone defect repair.

Polyethylene microplastics induced gut microbiota dysbiosis leading to liver injury via the TLR2/NF-κB/NLRP3 pathway in mice.

Microplastics (MPs) are ubiquitous environmental contaminants that have negative impacts on health and safety. The gut microbiota plays multiple roles as a newly discovered virtual metabolic organ. The objective of this study was to investigate the potential of MPs to cause liver injury by disrupting the balance of gut microbiota. The results indicated that exposure to MPs resulted in liver damage and disrupted the homeostasis of gut microbiota. MPs significantly reduced the liver organ coefficient, leading to liver cell injury and impaired function. Additionally, there was an increase in the expression of fibril-related proteins, which positively correlated with MPs concentration. Furthermore, MPs increased the relative abundances of Desulfovibrio, Clostridia, Enterorhabdus, Bacteroides, and Gemella while decreasing the abundance of Dubosoella. Different concentrations of MPs exhibited varying effects on specific bacterial groups, however, both concentrations resulted in an increase in pathogenic bacteria and a decrease in beneficial bacteria, as well as alterations in microbial structure. Moreover, MPs induced oxidative stress, inflammation, apoptosis and necrosis in liver cells. The study found that MPs disrupted gut microbiota homeostasis and activated TLR2/NF-κB/NLRP3 pathway in the liver, providing a new insight into the mechanism underlying MPs-induced liver injury. These findings serve as a warning regarding environmental pollution caused by MPs.

Tandem gene duplications contributed to high-level azole resistance in a rapidly expanding Candida tropicalis population.

Invasive diseases caused by the globally distributed commensal yeast Candida tropicalis are associated with mortality rates of greater than 50%. Notable increases of azole resistance have been observed in this species, particularly within Asia-Pacific regions. Here, we carried out a genetic population study on 1571 global C. tropicalis isolates using multilocus sequence typing (MLST). In addition, whole-genome sequencing (WGS) analysis was conducted on 629 of these strains, comprising 448 clinical invasive strains obtained in this study and 181 genomes sourced from public databases. We found that MLST clade 4 is the predominant azole-resistant clone. WGS analyses demonstrated that dramatically increasing rates of azole resistance are associated with a rapid expansion of cluster AZR, a sublineage of clade 4. Cluster AZR isolates exhibited a distinct high-level azole resistance, which was induced by tandem duplications of the ERG11A395T gene allele. Ty3/gypsy-like retrotransposons were found to be highly enriched in this population. The alarming expansion of C. tropicalis cluster AZR population underscores the urgent need for strategies against growing threats of antifungal resistance.

A novel graphene/triolein complex-based lubricant for improving high temperature water-based drilling fluid.

Drilling engineering plays a pivotal role in the exploration and extraction of subsurface resources. It heavily depends on drilling fluid, which serves various essential functions including cooling the drill bit, removing drilled cuttings, maintaining formation pressure equilibrium, stabilizing the wellbore, transmitting hydraulic pressure, and safeguarding oil and gas reservoirs. Nonetheless, drilling fluid encounters multiple obstacles such as leakage control, waste fluid management, prevention of wellbore collapse, avoidance of hole enlargement, and environmental preservation. In order to surmount these challenges, the introduction of lubricants into the drilling fluid yields a multitude of advantages, encompassing equipment safeguarding, enhanced drilling efficiency, preservation of wellbore integrity, and bolstered drilling safety. These factors hold crucial significance in ensuring the triumph of drilling operations. This paper presents the introduction of a new lubricant derived from triolein. Following the preparation of graphene and triolein, they were incorporated into the drilling fluid system. A set of tests was subsequently conducted after aging at 240 °C for 16 hours. To assess the impact of the lubricant on the drilling fluid, an examination of rheological and filtration properties was conducted. Additionally, investigations into the friction coefficient, adhesion coefficient, and extreme pressure lubricity were carried out to evaluate the lubricating performance of the drilling fluid. Adding lubricants at a temperature of 240 degrees Celsius has successfully controlled the adhesion coefficient of the drilling fluid to below 0.2, reaching a minimum of 0.055, resulting in a reduction rate of over 70%. This indicates that the lubricant performs well at high temperatures, effectively reducing friction and enhancing drilling speed.

Development of a Low-Molecular-Weight Filtrate Reducer with High-Temperature Resistance for Drilling Fluid Gel System.

Currently, conventional polymeric filtrate reducers with high-temperature resistance for use in drilling fluids have high molecular weights, which greatly affects the rheological properties. Therefore, to address the challenges in regulating the rheology and filtration performance of high-density drilling fluids at high temperatures, it is essential to develop low-molecular-weight filtrate reducers with high-temperature resistance. In this study, a low-molecular-weight filtrate reducer with high-temperature resistance (LMF) was prepared via free radical polymerization from acrylamide and 2-acrylamido-2-methyl-1-propanesulfonic acid as monomers, tertiary dodecyl mercaptan as a chain transfer agent, and ammonium persulfate as the initiator. LMF was then characterized by infrared spectroscopy, thermogravimetric analysis, and gel permeation chromatography. The obtained filtrate reducer exhibits a weight-average molecular weight (Mw) of 3819 and an initial thermal decomposition temperature of 300.7 °C, indicating good thermal stability. The effects of LMF dosage, temperature, and NaCl dosage on the rheology and filtration performance of mud samples were also investigated, and the mechanism of action was revealed by zeta potential, particle size distribution, scanning electron microscopy, and adsorption measurements. The results reveal that LMF increases the mud sample viscosity and reduces its filtration. For example, the filtration of the mud sample with 2 wt% LMF was 7.2 mL, a reduction of 70% compared to that of a blank mud sample. Further, after aging at 210 °C for 16 h, the filtration of the same sample was 11.6 mL, and that of a mud sample with 2 wt% LMF and 35 wt% NaCl after aging at 180 °C for 16 h was 22 mL. Overall, we have reported a scheme to prepare a low-molecular-weight filtrate reducer with high-temperature resistance and superior filtrate-reducing effects, laying the foundation for the investigation and development of low-molecular-weight filtrate reducers.

Effect of Low Gravity Solids on Weak Gel Structure and the Performance of Oil-Based Drilling Fluids.

Drilling cuttings from the rock formation generated during the drilling process are generally smashed to fine particles through hydraulic cutting and grinding using a drilling tool, and then are mixed with the drilling fluid during circulation. However, some of these particles are too small and light to be effectively removed from the drilling fluid via solids-control equipment. These small and light solids are referred to as low gravity solids (LGSs). This work aimed to investigate the effect of LGSs on the performance of oil-based drilling fluid (OBDF), such as the rheological properties, high-temperature and high-pressure filtration loss, emulsion stability, and filter cake quality. The results show that when the content of LGSs reached or even exceeded the solid capacity limit of the OBDF, the rheological parameters including the plastic viscosity, gel strength, and thixotropy of OBDF increased significantly. Furthermore, the filtration of OBDF increases, the filter cake becomes thicker, the friction resistance becomes larger, and the stability of emulsion of OBDF also decreases significantly when the concentration of LGSs reached the solid capacity limit of OBDF (6-9 wt% commonly). It was also found that LGSs with a smaller particle size had a more pronounced negative impact on the drilling fluid performance. This work provides guidance for understanding the impact mechanism of LGSs on drilling fluid performance and regulating the performance of OBDF.

Public environmental attention, media coverage, and corporate green innovation: evidence from heavily polluting industries in China.

Against the background of building a multi-environmental co-governance system, it is of great importance to systematically explore how public environmental attention (PEA) affects corporate green innovation (GI). Based on the panel data of Chinese A-share listed enterprises of heavily polluting industries from 2013 to 2020, this paper empirically explores the role of PEA in GI and examines the moderating impacts of media visibility and media favorability. The results indicate that the higher degree of public environmental attention, the more corporate green innovation. After adopting alternative explained variable, instrumental variable analysis and other methods, this conclusion still remains robust. This study also finds that both media visibility (MV) and media favorability (MF) generate significantly positive moderating impacts on the relationship between PEA and GI. Moreover, threshold model tests show that with the increase of MV, the promoting effect of PEA on GI is significantly enhanced, while there exists no threshold for MF. Furthermore, the heterogeneity analysis indicates that PEA mainly prompts symbolic green innovation of enterprises, and the PEA-GI relationship is more obvious in non-state-owned companies and regions with higher marketization process.

Sustained release of tumor cell lysate and CpG from an injectable, cytotoxic hydrogel for melanoma immunotherapy.

Many basic research studies have shown the potential of autologous cancer vaccines in the treatment of melanoma. However, some clinical trials showed that simplex whole tumor cell vaccines can only elicit weak CD8+ T cell-mediated antitumor responses which were not enough for effective tumor elimination. So efficient cancer vaccine delivery strategies with improved immunogenicity are needed. Herein, we described a novel hybrid vaccine "MCL" (Melittin-RADA32-CpG-Lysate) which was composed of melittin, RADA32, CpG and tumor lysate. In this hybrid vaccine, antitumor peptide melittin and self-assembling fusion peptide RADA32 were assembled to form the hydrogel framework melittin-RADA32(MR). Then, whole tumor cell lysate and immune adjuvant CpG-ODN were loaded into MR to develop an injectable and cytotoxic hydrogel MCL. MCL showed excellent ability for sustained drug release, to activate dendritic cells and directly kill melanoma cells in vitro. In vivo, MCL not only exerted direct antitumor activity, but also had robust immune initiation effects including the activation of dendritic cells in draining lymph nodes and the infiltration of cytotoxic T lymphocytes (CTLs) in tumor microenvironment. In addition, MCL can efficiently inhibit melanoma growth in B16-F10 tumor bearing mice, which suggested that MCL is a potential cancer vaccine strategy for melanoma treatment.

Exposure to polystyrene microplastics triggers lung injury via targeting toll-like receptor 2 and activation of the NF-κB signal in mice.

Microplastics are ubiquitous pollutants with a wide range of plastic applications. More recently, microplastics are in the air and can be inhaled into the lungs, causing respiratory diseases. Knowledge of the underlying mechanisms by which microplastics may induce respiratory disease is still limited. This study used intranasal instillation to develop a model of lung injury. The histopathology result showed that the mouse lung had severe inflammatory responses, apoptosis and collagen deposition with chronic exposure to different sizes (Small: 1-5 µm and Large: 10-20 µm) of polystyrene microplastics (PS-MPS), and the damage of smaller sizes was obvious. The expression levels of the Toll-like receptors (TLRs) family, evolutionarily conserved pattern recognition receptors, were detected, and the levels of TLR2 mRNA was significantly increased. In transfection experiments, PS-MPS increased the inflammatory response in HEK293 cells with TLR2 expression. Furthermore, exposure to small polystyrene microplastics promoted oxidative stress and apoptosis, and accelerated the process of fibrosis. Interestingly, inhibition of the NF-κB signal relieves inflammation and oxidative stress, reduces apoptosis, and thus controls the fibrosis process. These results suggested that PS-MPS targeted binding to TLR2 and further exacerbated fibrosis by facilitating inflammation, oxidative stress, and apoptosis with the activation of NF-κB signal.

Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

Polyethylene microplastics trigger cell apoptosis and inflammation via inducing oxidative stress and activation of the NLRP3 inflammasome in carp gills.

Microplastics cause varying degrees of damage to aquatic organisms. Exposure to microplastics contaminated water, the gills are among the first tissues, after the skin, to be affected by microplastics. As an essential immune organ, prolonged stimulation by microplastics disrupts immune function not only in the gills but throughout the body, yet the underlying mechanisms remain elusive. A model of gill injury from exposure to polyethylene (PE) microplastics was developed in this study. H&E staining revealed that polyethylene microplastics caused gill inflammation, vascular remodeling, and mucous cell proliferation. An increase in collagen indicates severe tissue damage. Additional analysis showed that polyethylene microplastics profoundly exacerbated oxidative stress in the gills. TUNEL assay demonstrated cell apoptosis induced by polyethylene microplastic. The mRNA levels were subsequently quantified using RT-PCR. The results showed that polyethylene microplastics increased the expression of the nuclear factor-κB (NF-κB) pathway (NF-κB p65, IKKα, IKKß) and apoptosis biomarkers (p53, caspase-3, caspase-9, and Bax). Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes, which is an influential component of innate immunity, were overactive. What's more, the pro-inflammatory factors (TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-1ß) that induce immune disorder also increased significantly, while the anti-inflammatory factors (IL-4, IL-10) decreased significantly. These results suggested that oxidative stress acted as an activation signal of apoptosis triggered by the NF-κB pathway and activating the NLRP3 inflammasome to promote inflammatory immune responses. The present study provided a different target for the prevention of toxin-induced gill injury under polyethylene microplastics.

Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer.

BACKGROUND: Novel therapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15- IN-1 and KIF11 inhibitor ispinesib in GC. METHODS: We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo. RESULTS: KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo. CONCLUSION: This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.

Establishment and application of the ten-fold rehydration formula for emergency resuscitation of pediatric patients after extensive burns / 中华烧伤杂志

Objective: To investigate the scientificity and feasibility of the ten-fold rehydration formula for emergency resuscitation of pediatric patients after extensive burns. Methods: A retrospective observational study was conducted. The total burn area of 30%-100% total body surface area (TBSA) and body weight of 6-50 kg in 433 pediatric patients (250 males and 183 females, aged 3 months to 14 years) with extensive burns who met the inclusion criteria and admitted to the burn departments of 72 Class A tertiary hospitals were collected. The 6 319 pairs of simulated data were constructed after pairing each body weight of 6-50 kg (programmed in steps of 0.5 kg) and each total burn area of 30%-100% TBSA (programmed in steps of 1%TBSA). They were put into three accepted pediatric rehydration formulae, namely the commonly used domestic pediatric rehydration formula for burn patients (hereinafter referred to as the domestic rehydration formula), the Galveston formula, and the Cincinnati formula, and the two rehydration formulae for pediatric emergency, namely the simplified resuscitation formula for emergency care of patients with extensive burns proposed by the World Health Organization's Technical Working Group on Burns (TWGB, hereinafter referred to as the TWGB formula) and the pediatric ten-fold rehydration formula proposed by the author of this article--rehydration rate (mL/h)=body weight (kg) × 10 (mL·kg-1·h-1) to calculate the rehydration rate within 8 h post injury (hereinafter referred to as the rehydration rate). The range of the results of the 3 accepted pediatric rehydration formulae ±20% were regarded as the reasonable rehydration rate, and the accuracy rates of rehydration rate calculated using the two pediatric emergency rehydration formulae were compared. Using the maximum burn areas (55% and 85% TBSA) corresponding to the reasonable rehydration rate calculated by the pediatric ten-fold rehydration formula at the body weight of 6 and 50 kg respectively, the total burn area of 30% to 100% TBSA was divided into 3 segments and the accuracy rates of the rehydration rate calculated using the 2 pediatric emergency rehydration formulae in each segment were compared. When neither of the rehydration rates calculated by the 2 pediatric emergency rehydration formulae was reasonable, the differences between the two rehydration rates were compared. The distribution of 433 pediatric patients in the 3 previous total burn area segments was counted and the accuracy rates of the rehydration rate calculated using the 2 pediatric emergency rehydration formulae were calculated and compared. Data were statistically analyzed with McNemar test. Results: Substitution of 6 319 pairs of simulated data showed that the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula was 73.92% (4 671/6 319), which was significantly higher than 4.02% (254/6 319) of the TWGB formula (χ2=6 490.88,P<0.05). When the total burn area was 30%-55% and 56%-85% TBSA, the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula were 100% (2 314/2 314) and 88.28% (2 357/2 670), respectively, which were significantly higher than 10.98% (254/2 314) and 0 (0/2 670) of the TWGB formula (with χ2 values of 3 712.49 and 4 227.97, respectively, P<0.05); when the total burn area was 86%-100% TBSA, the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula and the TWGB formula were 0 (0/1 335). When the rehydration rates calculated by the 2 pediatric emergency rehydration formulae were unreasonable, the rehydration rates calculated by the pediatric ten-fold rehydration formula were all higher than those of the TWGB formula. There were 93.07% (403/433), 5.77% (25/433), and 1.15% (5/433) patients in the 433 pediatric patients had total burn area of 30%-55%, 56%-85%, and 86%-100% TBSA, respectively, and the accuracy rate of the rehydration rate calculated using the pediatric ten-fold rehydration formula was 97.69% (423/433), which was significantly higher than 0 (0/433) of the TWGB formula (χ2=826.90, P<0.05). Conclusions: The application of the pediatric ten-fold rehydration formula to estimate the rehydration rate of pediatric patients after extensive burns is more accurate and convenient, superior to the TWGB formula, suitable for application by front-line healthcare workers that are not specialized in burns in pre-admission rescue of pediatric patients with extensive burns, and is worthy of promotion.