A conserved mechanism affecting hydride shifting and deprotonation in the synthesis of hopane triterpenes as compositions of wax in oat.

Triterpenoids are biologically active metabolites synthesized from a common linear precursor catalyzed by 2,3-oxidosqualene cyclases (OSCs) to form diverse triterpenoid skeletons. OSCs corresponding to many discovered triterpene alcohols in nature have not been functionally and mechanistically characterized due to the diversity of chemical structures and complexity of the cyclization mechanism. We carried out a genome-wide investigation of OSCs from Avena strigosa and discovered two triterpene synthases, namely, AsHS1 and AsHS2, using a Nicotiana benthamiana expression system. These synthases produce hopenol B and hop-17(21)-en-3ß-ol, which are components of surface wax in oat panicles and sheathes, respectively. We demonstrated that substitutions of two to three amino acid residues in AsHS1 with corresponding residues from AsHS2 allowed it to be completely converted into a hop-17(21)-en-3ß-ol synthase. AsHS2 mutants with a substitution at site 410 could synthesize hopenol B alone or mixed with a side product isomotiol. The combined quantum mechanics and molecular mechanics calculation demonstrated that the side chain size of the residue at site 410 regulated the relative orientations between the hopyl C22 cation and Phe257, leading to a difference in deprotonation positions through providing or not providing cation­π interaction between the aromatic ring of F257 and the carbocation intermediate. A similar mechanism could be applied to a hopenol B synthase from a dicotyledonous plant Aquilegia. This study provided mechanistic insight into triterpenoid synthesis and discovered key amino acid residues acting on hydride transfer and a deprotonation site to differentiate between hopane-type scaffolds in diverse plant species.

Cobalt/Nitrogen Co-Doped Carbon Materials Enhance the Reaction Rate of Sodium-Potassium Alloy Electrodes.

Sodium-potassium (NaK) alloy electrodes are ideal for next-generation dendrite-free alkali metal electrodes due to their dendrite-free nature. However, issues such as slow diffusion kinetics due to the large K+ radius and the loss of active potassium during the reaction severely limit its application. Here a novel cobalt/nitrogen-doped carbon material is designed and it is applied to the construction of a NaK alloy electrode. The experimental and theoretical results indicate that the confining effect of the nitrogen-doped graphitic carbon layer can protect the cobalt nanoparticles from corrosion leaching, while the presence of Co─Nx bonds and cobalt nanoparticles provides more active sites for the reaction, realizing the synergistic effect of adsorption-catalytic modulation, lowering the K+ diffusion energy barrier and promoting charge transfer and ion diffusion. The application of this electrode to a symmetrical battery can achieve more than 1800 stable cycles under a current density of 0.4 mA cm-2 and a charge/discharge specific capacity of 122.64 mAh g-1 under a current of 0.5C in a full battery. This finding provides a new idea to realize a fast, stable, and efficient application of NaK alloy electrodes.

Bright luminescence from nontoxic all-inorganic low-dimensional cesium halide.

Due to the superiority of low cost, easy manufacture, and tunable light emission owing to the diversity of compositions and dimensionalities, the metal halides have appeared as a promising class of semiconductors. Nevertheless, the toxicity problem along with inherent instability of Pb-based metal halides greatly limits their large-scale applications. Based on this situation, it is necessary to develop eco-friendly materials, which could simultaneously maintain the excellent optoelectronic properties of lead materials. In this Letter, the one-dimensional Cu + -alloyed Cs2AgI3 has been successfully synthesized. An intense blue emission located at 469 nm with a large Stokes shift was observed. Density functional theory calculation indicated that the Cu+ ions could effectively modulate the density of state population, which was the key factor drastically boosting the photoluminescence quantum yield (PLQY). This kind of highly efficient metal halide may overcome the bottlenecks of toxicity and poor efficiency issues of blue emission and will have a promising prospect in the optoelectronic fields.

Photoluminescence enhancement for blue-green emission in copper-alloyed lead-free cesium halide single crystals.

Recently, metal halides have received extensive attention because of the superior photophysical characteristics. Regardless of the superiority, the limited stability against heat and moisture and the toxicity problem of heavy lead metal are obstacles to the realization of wide range applications. In this case, it is necessary to develop eco-friendly alternatives, which could simultaneously maintain the excellent optoelectronic properties of lead materials. In this paper, the synthesis of lead-free one-dimensional Cs2AgBr3 and Cu(I)-alloyed Cs2AgBr3 single crystals (SCs) has been successfully realized. Experimental results demonstrated that the addition of applicable copper ions could greatly improve their luminescence intensity. A bright blue-green photoluminescence peaking at 510 nm was observed after incorporating Cu+ ions into Cs2AgBr3 SCs under UV irradiation. Theoretical calculation further proved that the incorporation of Cu+ could effectively modulate the materials' electronic band structure; the electronic states limited to the CuBr4 tetrahedron presented a strong localized property, which was beneficial to increase the photoluminescence efficiency. In addition, the SCs displayed favorable structure stability proofing moisture and oxygen under ambient conditions, proving that this material has good prospects for the development of optoelectronic fields.

The Role of Base in Reaction Performance of Photochemical Synthesis of Thiazoles: An Integrated Theoretical and Experimental Study.

Artificial intelligence (AI)/machine learning (ML) is emerging as pivotal in synthetic chemistry, offering revolutionary potential in retrosynthetic analysis, reaction conditions and reaction prediction. We have combined chemical descriptors, primarily based on Density Functional Theory (DFT) calculations, with various AI/ML tools such as Multi-Layer Perceptron (MLP) and Random Forest (RF), to predict the synthesis of 2-arylbenzothiazole in photoredox reactions. Significantly, our models underscore the critical role of the molecular structure and physicochemical characteristics of the base, especially the total atomic polarizabilities, in the rate-determining steps involving cyclohexyl and phenethyl moieties of the substrate. Moreover, we validated our findings in articles through experimental studies. It showcases the power of AI/ML and quantum chemistry in shaping the future of organic chemistry.

Serum tumor marker and CT body composition scoring system predicts outcomes in colorectal cancer surgical patients.

OBJECTIVE: To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. METHODS: This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. RESULTS: Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. CONCLUSION: In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. CLINICAL RELEVANCE STATEMENT: This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. KEY POINTS: Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

Combined effects of low pH stress and bacterial infection on the transcriptional changes of hemocytes in Chinese mitten crab Eriocheir sinensis.

Water pH is a critical environmental factor for aquaculture. Acidification is a pressing environmental issue that poses significant threats to the aquaculture industry. Since the outbreaks of disease generally accompany with environmental stress, comparative transcriptome analyses were performed to investigate the combined effects of low pH stress and bacterial infection on the transcriptional changes of hemocytes in the economically important crab Eriocheir sinensis. The results revealed that the immune deficiency (IMD) pathway and prophenoloxidase (proPO) system was activated to defense against Vibro parahaemolyticus even when crabs were subjected to low pH stress, whereas low pH stress resulted in the disorder of Toll-like receptor (TLR) pathway upon V. parahaemolyticus infection. Moreover, low pH stress might weaken crabs' defense against V. parahaemolyticus by inhibiting the up-regulation of crustin and suppressing the expression of lysozyme, and disturb the maintaining of protein homeostasis through the transcriptional decrement of a batch of heat shock proteins (HSPs). It is worth noting that both V. parahaemolyticus infection and low pH stress might suppress the energy metabolism in the hemocytes via inhibiting the expression of critical enzymes, dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex and fumarase, in the tricarboxylic acid (TCA) cycle. This study provides novel understandings concerning the transcriptional changes of hemocyte in E. sinensis subjected to a combination of low pH stress and V. parahaemolyticus infection as well as contribute to optimize the management strategies for the prevention and control of diseases in E. sinensis farming.

Expression and diagnostic value of lncRNA MALAT1 and NLRP3 in lower limb atherosclerosis in diabetes.

OBJECTIVE: This study aimed to examine the diagnostic predictive value of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) and NOD-like receptor protein 3(NLRP3) expression in patients with type 2 diabetes mellitus(T2DM) and lower extremity atherosclerosis disease (LEAD). METHODS: A total of 162 T2DM patients were divided into T2DM with LEAD group (T2DM + LEAD group) and T2DM alone group (T2DM group). The lncRNA MALAT1 and NLRP3 expression levels were measured in peripheral blood, and their correlation was examined. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen for the best predictors of LEAD, and multivariate logistic regression was used to establish a predictive model and construct the nomogram. The effectiveness of the nomogram was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The levels of the lncRNA MALAT1 and NLRP3 in the T2DM + LEAD group were significantly greater than those in the T2DM group (P <0.001), and the level of the lncRNA MALAT1 was positively correlated with that of NLRP3 (r = 0.453, P<0.001). The results of the LASSO combined with the logistic regression analysis showed that age, smoking, systolic blood pressure (SBP), NLRP3, and MALAT1 were the influencing factors of T2DM with LEAD(P<0.05). ROC curve analysis comparison: The discriminatory ability of the model (AUC = 0.898), MALAT1 (AUC = 0.804), and NLRP3 (AUC = 0.794) was greater than that of the other indicators, and the predictive value of the model was the greatest. Calibration curve: The nomogram model was consistent in predicting the occurrence of LEAD in patients with T2DM (Cindex = 0.898). Decision curve: The net benefit rates obtained from using the predictive models for clinical intervention decision-making were greater than those obtained from using the individual factors within the model. CONCLUSION: MALAT1 and NLRP3 expression increased significantly in T2DM patients with LEAD, while revealing the correlation between MALAT1 and NLRP3. The lncRNA MALAT1 was found as a potential biomarker for T2DM with LEAD.

Enlarged posterior column osteotomy plus intervertebral cage strutting for lumbosacral nerve bowstring disease.

BACKGROUND: To explore the surgical outcome of enlarged posterior column osteotomy (EPCO) plus intervertebral cage strutting (ICS) for patients with lumbosacral nerve bowstring disease (BSD). METHODS: The clinical data of 27 patients with BSD that surgically treated with EPCO plus ICS from January 2018 to March 2021 were retrospectively reviewed. Patient demographics including age, gender, body mass index (BMI), duration, length of hospital stay, SF-36 were recorded. Surgical data including operation time, blood loss, surgical level, and complications were recorded. Inter-pedicle distance and regional lumbar lordosis was measured at lateral X-ray at both pre- and postoperative. RESULTS: All patients underwent the operation successfully. EPCO plus ICS was performed at L4-L5 in 9 patients, at L5-S1 in 7 patients, at L4-S1 in 6 patients, at L3-L5 in 5 patients. The mean operation time was 96.3 ± 18.0 min, mean blood loss was 350.0 ± 97.9 mL. Relaxation of thecal sac was noticed after pedicle screw-rod compression bilaterally. The mean decrease of inter-pedicle distance was 0.57 ± 0.18 cm, the mean increase of regional lumbar lordosis was 17.6 ± 6.7 degrees. Relaxation of cauda equina within the thecal sac was noticed at intra-operative after pedicle screw-rod compression bilaterally in all the patients. Most patients achieved neurological function improvement at two-year follow up. CONCLUSIONS: EPCO plus ICS procedure is an effective surgical method for lumbosacral nerve BSD through restoring the coordination between column and cord, visual relaxation of cauda equina within the thecal sac at intraoperative is the key factor in determining the relief of neurological function at postoperative.

Exploring the Gut Microbiota Landscape in Cow Milk Protein Allergy: Clinical Insights and Diagnostic Implications in Pediatric Patients.

Cow milk protein allergy (CMPA) is a significant health concern characterized by adverse immune reactions to cow milk proteins. Biomarkers for the accurate diagnosis and prognosis of CMPA are lacking. This study analyzed the clinical features of CMPA, and 16S RNA sequencing was used to investigate potential biomarkers through fecal microbiota profiling. Children with CMPA exhibit a range of clinical symptoms, including gastrointestinal (83% of patients), skin (53% of patients), and respiratory manifestations (26% of patients), highlighting the complexity of this condition. Laboratory analysis revealed significant differences in red cell distribution width (RDW) and inflammatory markers between the CMPA and control groups, suggesting immune activation and inflammatory responses in CMPA. Microbial diversity analysis revealed higher specific diversity indices in the CMPA group compared with those in control group, with significant differences at the genus and species levels. Bacteroides were more abundant in the CMPA group, whereas Bifidobacterium, Ruminococcus, Faecalibacterium, and Parabacteroides were less abundant. The control group exhibited a balanced microbial profile, with a predominant presence of Bifidobacterium bifidum and Akkermansia muciniphila. The significant abundance of Bifidobacterium in the control group (23.19% vs 9.89% in CMPA) was associated with improved growth metrics such as height and weight, suggesting its potential as a probiotic to prevent CMPA and enhance gut health. Correlation analysis linked specific microbial taxa such as Coprococcus and Bifidobacterium to clinical parameters such as family allergy history, weight and height, providing insights into CMPA pathogenesis. Significant differences in bacterial abundance suggested diagnostic potential, with a panel of 6 bacteria achieving high predictive accuracy (area under curve (AUC) = 0.8708). This study emphasizes the complex relationship between the gut microbiota and CMPA, offering valuable insights into disease mechanisms and diagnostic strategies.

The modulation of task relevance on emotion-induced blindness depends on whether targets and distractors belong to the same category.

Previous research on emotion-induced blindness (EIB) argues emotional distractors capture attention in a bottom-up manner due to their physical and emotional salience. However, recent research has shown it is controversial whether EIB will be modulated by top-down factors. The present study further investigated whether the magnitude of EIB would be modulated by top-down factors, specifically the emotional relevance between tasks and distractors. Participants were divided into two groups having the same targets except for different task instructions. The orientation judgment group was asked to judge the orientation of the target (an emotionally irrelevant task), and the emotion judgment group was required to judge the emotional valence of the target (an emotionally relevant task). It was found the emotional relevance between tasks and distractors has no modulation on the magnitudes of EIB in two groups when targets and distractors are from different categories (Experiment 1), but a modulation when they are from the same category (Experiment 2). Consequently, we contend top-down task relevance modulates the EIB effect and distractors' priority is regulated by the emotional relevance between tasks and distractors. The current study holds attentional capture by stimulus-driven is unconditional in EIB, while attentional capture by goal-driven requires certain conditions.

Exogenous Eugenol Alleviates Salt Stress in Tobacco Seedlings by Regulating the Antioxidant System and Hormone Signaling.

Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and promote their growth under salt stress has become a widespread and effective means. Eugenol is a small molecule of plant origin with medicinal properties such as antibacterial, antiviral, and antioxidant properties. In this study, tobacco seedlings were placed in Hoagland's solution containing NaCl in the presence or absence of eugenol, and physiological indices related to stress tolerance were measured along with transcriptome sequencing. The results showed that eugenol improved the growth of tobacco seedlings under salt stress. It promoted carbon and nitrogen metabolism, increased the activities of nitrate reductase (NR), sucrose synthase (SS), and glutamine synthetase (GS) by 31.03, 5.80, and 51.06%. It also activated the enzymatic and non-enzymatic antioxidant systems, reduced the accumulation of reactive oxygen species in the tobacco seedlings, and increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) by 24.38%, 18.22%, 21.60%, and 28.8%, respectively. The content of glutathione (GSH) was increased by 29.49%, and the content of superoxide anion (O2-) and malondialdehyde (MDA) were reduced by 29.83 and 33.86%, respectively. Promoted osmoregulation, the content of Na+ decreased by 34.34, K+ increased by 41.25%, and starch and soluble sugar increased by 7.72% and 25.42%, respectively. It coordinated hormone signaling in seedlings; the content of abscisic acid (ABA) and gibberellic acid 3 (GA3) increased by 51.93% and 266.28%, respectively. The transcriptome data indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, the MAPK signaling pathway, and phytohormone signal transduction pathways. The results of this study revealed the novel role of eugenol in regulating plant resistance and provided a reference for the use of exogenous substances to alleviate salt stress.

Microfluidization improved hempseed yogurt's physicochemical and storage properties.

BACKGROUND: Plant-based yogurts are suffering from the common problems, such as an unattractive color, stratified texture state and rough taste. Therefore, it is urgent to develop a novel processing method to improve the quality and extend the storage life of hempseed yogurt. In the present study, hempseed yogurt was microfluidized prior to fermentation. The effects of microfluidization on microstructure, particle size, mechanical properties, sensory acceptability, variations in pH and titratable acidity, lactic acid bacteria (LAB) counts, and stability of hempseed yogurt during 20 days of storage were investigated. RESULTS: Microfluidization contributed to the production of hempseed yogurt as a result of the better physicochemical properties compared to normal homogenization. Specifically, microfluidization reduced the particle size of hempseed yogurt with a uniform particle distribution, increased water holding capacity, and improved texture and rheological properties. These advancements resulted in higher sensory scores for the yogurt. Furthermore, during storage, microfluidization effectively inhibited the post-acidification process of hempseed yogurt, and increased LAB counts and storage stability. CONCLUSION: Microfluidization improved the physicochemical properties and storage stability of hempseed yogurt. Our findings support the application of microfluidization in hempseed yogurt and provide a new approach for enhancing the quality of plant-based alternatives that meet consumers' demands for high-quality food products. © 2023 Society of Chemical Industry.

Pulsed light treatment enhances starch hydrolysis and improves starch physicochemical properties of germinated brown rice.

BACKGROUND: Recently, germinated brown rice (GBR) has gained substantial attention as a functional food because of its nutritional attributes. Notably, pulsed light technology (PLT) has emerged as a promising tool for enhancing rice germination and, consequently, has improved the nutritional and functional qualities of GBR-derived products. However, further research is required to comprehensively understand the impact of PLT on GBR physicochemical properties. The present study aimed to investigate the stimulating effects of PLT on starch hydrolysis, starch structure and functional properties of GBR. RESULTS: The PLT substantially boosted α-amylase activity during brown rice germination, leading to a 10.9% reduction in total starch content and a 17.3% increase in reducing sugar content, accompanied by elevated free water levels. Structural analysis indicated no changes in starch crystalline types, whereas gelatinization temperature slightly increased. Pasting properties exhibited a significant drop in peak viscosity. Scanning electron microscopy showed surface erosion of starch granules with microstructural changes. Furthermore, correlation analysis established positive links between α-amylase activity, reducing sugar accumulation, starch structure and functional properties in GBR. CONCLUSION: The present study demonstrates that PLT enhanced the physicochemical properties of GBR starch, significantly improving the stability of GBR products, thereby contributing to expanded applicability of rice starch in the food industry. © 2023 Society of Chemical Industry.

The mitochondrial genome of the diploid oat Avena longiglumis.

BACKGROUND: Avena longiglumis Durieu (2n = 2x = 14) is a wild relative of cultivated oat (Avena sativa, 2n = 6x = 42) with good agronomic and nutritional traits. The plant mitochondrial genome has a complex organization and carries genetic traits of value in exploiting genetic resources, not least male sterility alleles used to generate F1 hybrid seeds. Therefore, we aim to complement the chromosomal-level nuclear and chloroplast genome assemblies of A. longiglumis with the complete assembly of the mitochondrial genome (mitogenome) based on Illumina and ONT long reads, comparing its structure with Poaceae species. RESULTS: The complete mitochondrial genome of A. longiglumis can be represented by one master circular genome being 548,445 bp long with a GC content of 44.05%. It can be represented by linear or circular DNA molecules (isoforms or contigs), with multiple alternative configurations mediated by long (4,100-31,235 bp) and medium (144-792 bp) size repeats. Thirty-five unique protein-coding genes, three unique rRNA genes, and 11 unique tRNA genes are identified. The mitogenome is rich in duplications (up to 233 kb long) and multiple tandem or simple sequence repeats, together accounting for more than 42.5% of the total length. We identify homologous sequences between the mitochondrial, plastid and nuclear genomes, including the exchange of eight plastid-derived tRNA genes, and nuclear-derived retroelement fragments. At least 85% of the mitogenome is duplicated in the A. longiglumis nuclear genome. We identify 269 RNA editing sites in mitochondrial protein-coding genes including stop codons truncating ccmFC transcripts. CONCLUSIONS: Comparative analysis with Poaceae species reveals the dynamic and ongoing evolutionary changes in mitochondrial genome structure and gene content. The complete mitochondrial genome of A. longiglumis completes the last link of the oat reference genome and lays the foundation for oat breeding and exploiting the biodiversity in the genus.

Development of chemiluminescent lab-on-fiber immunosensors for rapid point-of-care testing of anti-SARS-CoV-2 antibodies and evaluation of longitudinal immune response kinetics following three-dose inactivation virus vaccination.

Developing reliable, rapid, and quantitative point-of-care testing (POCT) technology of SARS-CoV-2-specific antibodies and understanding longitudinal vaccination response kinetics are highly required to restrain the ongoing coronavirus disease 2019 (COVID-19) pandemic. We demonstrate a novel portable, sensitive, and rapid chemiluminescent lab-on-fiber detection platform for detection of anti-SARS-CoV-2 antibodies: the chemiluminescent lab-on-fiber immunosensor (c-LOFI). Using SARS-CoV-2 Spike S1 RBD protein functionalized fiber bio-probe, the c-LOFI can detect anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies with high sensitivity based on their respective horseradish peroxidase-labeled secondary antibodies. The limits of detection of anti-SARS-CoV-2 IgG and IgM antibodies were 0.6 and 0.3 ng/ml, respectively. The c-LOFI was successfully applied for direct detection of anti-SARS-CoV-2 antibodies in whole blood samples with simple dilution, which can serve as a finger prick test to rapidly detect antibodies. Furthermore, the longitudinal immune response (>12 months) kinetics following three-dose inactivated virus vaccines was evaluated based on anti-SARS-CoV-2 IgG detection results, which can provide important significance for understanding the immune mechanism against COVID-19 and identify individuals who may benefit from the vaccination and booster vaccination. The c-LOFI has great potential to become a sensitive, low-cost, rapid, high-frequency POCT tool for the detection of both SARS-CoV-2-specific antibodies and other biomarkers.

Structure/function relationships of bean polysaccharides: A review.

Beans are a rich source of high quality protein and oil, and have attracted increasing interest from both nutrition researchers and health-conscious consumers. This review aims to provide a foundation for the future research and development of bean polysaccharides, by summarizing the sources, structure, and functions of bioactive bean polysaccharides. Structure/function relationships are described, for biological activities, such as immunological, antioxidant and anti-diabetes. This will provide useful guidance for further optimization of polysaccharide structure and the development of bean polysaccharides as a novel functional material.

Diflovidazin damages the hematopoietic stem cells to zebrafish embryos via the TLR4/ NF-κB/ p53 pathway.

Exposure to environmental contaminants frequently induces the occurrence of blood diseases, but the underlying molecular mechanisms are scarcely known. The toxicity of Diflovidazin (DFD), a widely used mite-remover, to the blood system of non-target organisms requires urgent elucidation. To investigate the deleterious effects of DFD (2, 2.5, and 3 mg/L) on the development and survive of hematopoietic stem cells (HSCs), the zebrafish model was used in this study. DFD exposure reduced the number of HSCs and their subtypes, including macrophages, neutrophils, thymus T-cells, erythrocytes, and platelets. The significant changes in the abnormal apoptosis and differentiation of HSCs were the major reasons for the reduction in blood cells. Using small-molecule antagonists and p53 morpholino revealed that the NF-κB/p53 pathway was responsible for the apoptosis of HSCs upon DFD exposure. The restoration results attributed to the TLR4 inhibitor and molecular docking showed that the TLR4 protein, which was upstream of NF-κB signaling, played a vital role in DFD toxicology. This study elucidates the role and molecular mechanism of DFD in damaging zebrafish HSCs. It provides a theoretical basis for the occurrence of various blood diseases in zebrafish and other organisms.

Endoscopic mucosal resection of gastrointestinal polyps with a novel low-temperature plasma radio frequency generator: a non-inferiority multi-center randomized control study.

BACKGROUND: To evaluate the efficacy and safety of novel plasma radio frequency generator and its single-use polypectomy snares for endoscopic mucosal resection (EMR) of gastrointestinal (GI) polyps. METHODS: A total of 217 patients with 413 GI polyps were recruited from four centers in China. Patients were assigned to experimental or control groups using a central randomization method. The experimental group used the novel plasma radio frequency generator and its matched single-use polypectomy snares (Neowing, Shanghai), while the control group used the high-frequency electrosurgical unit (Erbe, Germany) and disposable electrosurgical snares (Olympus, Japan). The primary endpoint was the en bloc resection rate, and the non-inferiority margin was set at 10%. Secondary endpoint included operation time, coagulation success rate, intraoperative and postoperative bleeding rate, and perforation rate. RESULTS: The en bloc resection rate was 97.20% (104/107) in the experimental group and 95.45% (105/110) in the control group (P = 0.496). The operation time was 29.14 ± 20.21 min in the experimental group and 30.26 ± 18.74 min in the control group (P = 0.671). The average removal time of a single polyp in the experimental group was 7.52 ± 4.45 min, which was slightly shorter than that in the control group 8.90 ± 6.67 min, with no statistical difference (P = 0.076). The intraoperative bleeding rates of the experimental group and control group were 8.41% (9/107) and 10.00% (11/110), respectively (P = 0.686). No intraoperative perforation occurred in either group. The postoperative bleeding rates of the experimental group and the control group were 1.87% (2/107) and 4.55% (5/110), respectively (P = 0.465). No postoperative perforation occurred in the experimental group (0/107), while one case of delayed perforation occurred in the control group (1/110, 0.91%). There was no statistical difference between the two groups. CONCLUSIONS: Endoscopic mucosal resection of GI polyps with the novel plasma radio frequency generator is safe and effective, and non-inferior to the conventional high-frequency electrosurgical system.

Clinical outcomes of endoscopic resection for the treatment of esophageal gastrointestinal stromal tumors: a ten-year experience from a large tertiary center in China.

BACKGROUNDS: Esophageal gastrointestinal stromal tumors (E-GISTs) are extremely rare and surgical resection is the recommended approach. However, surgical resection usually causes severe trauma that may result in significant postoperative morbidity. Endoscopic resection (ER) has developed rapidly in recent years and has been widely used in gastrointestinal lesions. Nevertheless, the feasibility and efficacy of ER in the management of E-GISTs are unknown. METHODS: Retrospective data were collected from January 2011 to December 2020 in a large tertiary center of China. Twenty-eight patients with E-GISTs treated by ER were included in the study. RESULTS: Of the 28 patients, there were 21 males and 7 females, with a median age of 55 years (40-70 years). The median tumor size was 15 mm (5-80 mm). The technical success rate was 100% (28/28), while the en bloc resection rate was 96.4% (27/28). The median operation time was 35 min (10-410 min). Sixteen (57.2%) tumors were categorized into very low risk group, six (21.4%) into low risk group, and six (21.4%) into high risk group. Pathologists carefully examined margins of each lesion. There were 11 lesions (39.3%) determined as R0 resection and 17 lesions (60.7%) as R1 resection with positive margins. The median hospital stay was 2 days (range, 1-8 days). One patient suffered from hydrothorax and required drainage, leading to a major adverse event rate of 3.6% (1/28). There was no conversion to surgery, and no death occurred within 30 days after the procedure. Imatinib was given to two patients after ER under multidisciplinary team surveillance. During follow-up (median of 54 months, 9-122 months), no recurrences or metastasis were observed. CONCLUSION: ER is safe and effective for E-GISTs and might become an optional choice in the future. Multicenter, prospective, large samples with long-term follow-up studies are still needed.