Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke.

With the escalating prevalence of global heat waves, heat stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms of liver injury, heat stroke-induced damage is characterized by heat cytotoxicity and heightened inflammation, directly contributing to elevated mortality rates. While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction, their specific correlation with heat stroke liver injury remains unclear. Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke, initiating IL-1ß-mediated inflammation. Using single-cell RNA sequencing of murine macrophages, a distinct and highly susceptible Kupffer cell subtype, Clec4F+/CD206+, emerged, with heme oxygenase 1 (HMOX-1) playing a pivotal role. Mechanistically, heat-induced HMOX-1, regulated by early growth response factor 1, mediated ferroptosis in Kupffer cells, specifically in the Clec4F+/CD206+ subtype (KC2), activating phosphatidylinositol 4-kinase beta and promoting PI4P production. This cascade triggered NLRP3 inflammasome activation and maturation of IL-1ß. These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells, particularly in Clec4F+/CD206+ KCs. Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke, offering a promising avenue for future therapeutic interventions.

Establishment of a prediction model of pulmonary artery hypertension in patients with hyperthyroidism.

OBJECTIVE: This study aims to assess the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a potential indicator for predicting the probability of developing pulmonary arterial hypertension (PAH) in hyperthyroidism patients. A nomogram model will be developed based on our findings, as well as the receiver operating characteristic (ROC) curve. METHODS: The study involved 166 hyperthyroid patients treated at Yijishan Hospital, and the period covered August 2021 to August 2022. Patients were divided into two groups according to pulmonary artery systolic pressure ≥35 mmHg. Univariate and multivariate logistic analyses were performed on the two groups' demographic and laboratory data to identify potential diagnostic markers. These parameters were evaluated using ROC curves to determine their precision in forecasting PAH. The findings were validated by plotting a calibration curve based on a line chart model. RESULTS: In the study, eventually, 80 patients were enrolled: 30 in the PAH group and 50 in the No PAH group. Multipleistic regression analysis predicted the occurrence risk of developing PAH. When paired with other conventional echocardiographic parameters (such as TAPSE, MPI, and SV) and serological markers (such as FT3 and FT4), the developed model demonstrated outstanding predictive performance with an area under the ROC curve of 0.985, a Youden index of 0.971, a sensitivity of 100%, and a specificity of 97.1%. CONCLUSIONS: The nomogram model constructed by combining the TAPSE/PASP ratio with FT3 and FT4 serum markers, as well as conventional ultrasound parameters SV and MPI in hyperthyroidism patients, demonstrates robust discriminatory ability and consistency.

Development of a model to predict the risk of multi-drug resistant organism infections in ruptured intracranial aneurysms patients with hospital-acquired pneumonia in the neurological intensive care unit.

OBJECTIVE: This study was developed to explore the incidence of multi-drug resistant organism (MDRO) infections among ruptured intracranial aneurysms(RIA) patient with hospital-acquired pneumonia(HAP) in the neurological intensive care unit (NICU), and to establish risk factors related to the development of these infections. METHODS: We collected clinical and laboratory data from 328 eligible patients from January 2018 to December 2022. Bacterial culture results were used to assess MDRO strain distributions, and risk factors related to MDRO infection incidence were identified through logistic regression analyses. These risk factors were further used to establish a predictive model for the incidence of MDRO infections, after which this model underwent internal validation. RESULTS: In this study cohort, 26.5 % of RIA patients with HAP developed MDRO infections (87/328). The most common MDRO pathogens in these patients included Multidrug-resistant Klebsiella pneumoniae (34.31 %) and Multidrug-resistant Acinetobacter baumannii (27.45 %). Six MDRO risk factors, namely, diabetes (P = 0.032), tracheotomy (P = 0.004), history of mechanical ventilation (P = 0.033), lower albumin levels (P < 0.001), hydrocephalus (P < 0.001) and Glasgow Coma Scale (GCS) score ≤8 (P = 0.032) were all independently correlated with MDRO infection incidence. The prediction model exhibited satisfactory discrimination (area under the curve [AUC], 0.842) and calibration (slope, 1.000), with a decision curve analysis further supporting the clinical utility of this model. CONCLUSIONS: In summary, risk factors and bacterial distributions associated with MDRO infections among RIA patients with HAP in the NICU were herein assessed. The developed predictive model can aid clinicians to identify and screen high-risk patients for preventing MDRO infections.

Signal processing for miniature mass spectrometer based on LSTM-EEMD feature digging.

Miniature mass spectrometers exhibit immense application potential in on-site detection due to their small size and low cost. However, their detection accuracy is severely affected by factors such as sample pre-processing and environmental conditions. In this study, we propose a data processing method based on long short-term memory-ensemble empirical mode decomposition (LSTM-EEMD) to improve the quality of on-site detection data from miniature mass spectrometers. The EEMD method can clearly decompose the different physical feature components in the small-scale spectrometer signals, while the LSTM method can adaptively learn the internal feature relationships of the signals. Thus, by combining the two, the parameters for the EEMD signal reconstruction can be optimized in an adaptive manner, obtaining the optimized coefficients. Compared to the previous EEMD feature enhancement approach, the LSTM-EEMD method not only significantly improves the coefficient of determination (R2) and relative standard deviation (RSD) of the data, enhancing the linear range, but also achieves fully adaptive processing throughout the workflow, greatly boosting the efficiency. By leveraging a miniature mass spectrometer, data for N-acetyl-l-aspartic acid (NAA), 2-Hydroxyglutarate (2-HG), and γ-Aminobutyric acid (GABA) in actual blood samples have been obtained. The experimental results demonstrate that the LSTM-EEMD method can markedly enhance the accuracy and usability of the biological sample data in practical testing, providing new perspectives and possibilities for research and applications in the relevant domain.

Restricting Linker Rotation in Nanocages of ZIF-8 Membranes using Crown Ether "Molecular Locks" for Enhanced Propylene/Propane Separation.

ZIF-8 membranes have long been prized for their exceptional C3H6/C3H8 separation performance. On the other hand, ZIF-8 has structural flexibility, where the external pressure triggers channel expansion, potentially deteriorating the molecular sieving ability. Here, we demonstrate a reliable strategy to fine-tune the flexible pore structure of ZIF-8 by embedding crown ether within a ZIF-8 membrane. Benzo-15-crown-5 (15C5) was selected as the cavity occupant and perfectly confined in the sodalite (SOD) cage of ZIF-8. The 15C5 molecules, which have a size comparable to the nanocage, impose a spatial constraint on linker rotation, enabling the phase transition to a rigid structure in the flexible ZIF-8. The corresponding 15C5@ZIF-8 membranes achieve an ultrahigh C3H6/C3H8 selectivity of 220, outperforming that of most membranes. Unlike their flexible counterparts, the resulting membranes manifest a positive increase in the C3H6/C3H8 separation factor with elevated pressure, securing a record-high C3H6/C3H8 separation factor of 331 under 7 bar. More importantly, extraordinary separation stability was demonstrated with continuous measurement, which is highly desirable for practical applications.

Effects of Intermittent and Chronic Hypoxia on Fish Size and Nutrient Metabolism in Tiger Puffer (Takifugu rubripes).

Intermittent and chronic hypoxia are common stresses to marine fish, but the different responses of fish to intermittent and chronic hypoxia have not been well-known. In this study, tiger puffers were farmed in normoxia conditions (NO, 6.5 ± 0.5 mg/L), intermittent hypoxia (IH, 6.5 ± 0.5 mg/L in the day and 3.5 ± 0.5 mg/L in the night), or choric hypoxia (CH, 3.5 ± 0.5 mg/L) conditions for 4 weeks, after which the growth, nutrient metabolism and three hifα isoforms expression were measured. Both intermittent and chronic hypoxia decreased the fish growth and visceral weight but increased the feed conversion ratio and blood hemoglobin content. Chronic hypoxia but not intermittent hypoxia promoted protein synthesis and whole-fish protein content by activating mtor gene expression and promoted the glycolysis pathway by activating gene expression of hif1α and hif2α. Intermittent hypoxia but not chronic hypoxia decreased the hepatic lipid synthesis by inhibiting fasn and srebf1 gene expression. Meanwhile, intermittent hypoxia reduced the monounsaturated fatty acid content but increased the n-3 polyunsaturated fatty acids percentage. The results of this study clarified the adaptive mechanism of tiger puffer to intermittent and chronic hypoxia, which provides important information about mechanisms of hypoxia adaption in fish.

Establishing a model predicting Gleason grade group upgrading in prostate cancer.

Background: Gleason grade group (GG) upgrading is associated with increased biochemical recurrence (BCR), local progression, and decreased cancer-specific survival (CSS) in prostate cancer (PCa). However, descriptions of the risk factors of GG upgrading are scarce. The objective of this study was to identify risk factors and establish a model to predict GG upgrading. Methods: There were 361 patients with PCa who underwent radical prostatectomy between May 2011 and February 2022 enrolled. Univariate and multivariate logistic regression analyses were identified and nomogram further narrowed down the contributing factors in GG upgrading. The correction curve and decision curve were used to assess the model. Results: In the overall cohort, 141 patients had GG upgrading. But the subgroup cohort (GG ≤2) showed that 68 patients had GG upgrading. Multivariate logistic regression analysis showed that in the overall cohort, total prostate-specific antigen (tPSA) ≥10 ng/mL, systemic immune-inflammation index (SII) >379.50, neutrophil-lymphocyte ratio (NLR) >2.13, the GG of biopsy ≥3, the number of positive cores >3 were independent risk factors in GG upgrading. In the cohort of biopsy GG ≤2, multivariate logistic regression showed that the tPSA ≥10 ng/mL, SII >379.50 and the number of positive cores >3 were independent risk factors in GG upgrading. A novel model predicting GG upgrading was established based on these three parameters. The area under the curve (AUC) of the prediction model was 0.759. The C-index of the nomogram was 0.768. The calibration curves of the model showed good predictive performance. Clinical decision curves indicated clinical benefit in the interval of 20% to 90% of threshold probability and good clinical utility. Conclusions: Combined levels of tPSA, SII and the positive biopsy cores distinguish patients with high-risk GG upgrading in the group of biopsy GG ≤2 and are helpful in the decision of treatment plans.

Conventional versus cone-beam computed tomography in lung biopsy: diagnostic performance, risks, and the advantages of tract embolization with gelfoam particle suspension.

Background: With the widespread adoption of computed tomography (CT) technology, the number of detected pulmonary nodules has gradually increased. CT-guided percutaneous needle biopsy has become the primary method for qualitative diagnosis of pulmonary nodules. Benefiting from its three-dimensional (3D) reconstruction capability, cone-beam CT (CBCT) technology has also been widely adopted. Nevertheless, pneumothorax remains the most common complication of these diagnostic and therapeutic procedures. This study assessed the diagnostic accuracy of conventional CT (CCT)- and CBCT-guided coaxial core needle biopsy (CCNB) and the effectiveness of gelfoam particle suspension in reducing complications through tract embolization. Methods: A retrospective analysis was conducted on 320 patients who had undergone CCNB for nodules ≤3 cm from January 2020 to June 2022 at Zhongshan People's Hospital, comprising 325 biopsies (145 CCT-guided and 180 CBCT-guided). Gelfoam tract embolization was specifically used in biopsies of patients identified with a high risk of complications. Comparative statistics involved diagnostic outcomes (sensitivity, specificity, accuracy), procedural lengths, complication occurrences, and radiation doses. Results: Diagnostically, both CCT (sensitivity 93.3%, specificity 100%, accuracy 94.1%) and CBCT (sensitivity 92.8%, specificity 100%, accuracy 93.8%) offered a similarly high performance. The CCT technique was preferable in terms of shorter median operational times (19 vs. 24 minutes; P<0.001) and greater radiation exposure (13.9 vs. 10.1 mSv; P<0.001). The complication rates of CBCT and CCT, such as those of pneumothorax (18.9% vs. 20.7%; P=0.69) and hemorrhage (23.9% vs. 18.6%; P=0.25), were comparable. Of note, the comparison of biopsies with and without gelfoam embolization revealed a marked reduction in postoperative pneumothorax incidence (1.24% vs. 7.9%; P=0.004) and the requirement for drainage (0% vs. 4.27%; P=0.02), indicating the effectiveness of this procedure. Conclusions: CCT- and CBCT-guided lung biopsies demonstrate equivalent diagnostic capacities, with CCT providing shorter median operational times. Importantly, gelfoam embolization substantially diminishes the risk of postoperative pneumothorax, underscoring its value in high-risk patients.

Carbon dots-loaded cellulose nanofibrils hydrogel incorporating Bi2O3/BiOCOOH for effective adsorption and photocatalytic degradation of lignin.

A novel photocatalytic adsorbent, a cellulose nanofibrils based hydrogel incorporating carbon dots and Bi2O3/BiOCOOH (designated as CCHBi), was developed to address lignin pollution. CCHBi exhibited an adsorption capacity of 435.0 mg/g, 8.9 times greater than that of commercial activated carbon. This enhanced adsorption performance was attributed to the 3D porous structure constructed using cellulose nanofibrils (CNs), which increased the specific surface area and provided additional sorption sites. Adsorption and photocatalytic experiments showed that CCHBi had a photocatalytic degradation rate constant of 0.0140 min-1, 3.1 times higher than that of Bi2O3/BiOCOOH. The superior photocatalytic performance of CCHBi was due to the Z-scheme photocatalytic system constructed by carbon dots-loaded cellulose nanofibrils and Bi2O3/BiOCOOH, which facilitated the separation of photoinduced charge carriers. Additionally, the stability of CCHBi was confirmed through consecutive cycles of adsorption and photocatalysis, maintaining a removal efficiency of 85 % after ten cycles. The enhanced stability was due to the 3D porous structure constructed by CNs, which safeguarded the Bi2O3/BiOCOOH. This study validates the potential of CCHBi for high-performance lignin removal and promotes the application of CNs in developing new photocatalytic adsorbents.

Au Nanorings/TiO2 NPs@MXene-Based Metasurfaces with a Magnetic Mirror-Modulated ECL Strategy for Extracellular Vesicle Detection.

A metasurface as an artificial electromagnetic structure can concentrate optical energy into nanometric volumes to strongly enhance the light-matter interaction, which has been becoming a powerful platform for optical sensing, nonlinear effects, and quantum optics. Herein, we developed a novel hybrid plasmonic-dielectric metasurface consisting of Au nanorings (Au NRs) and TiO2 nanoparticles derived from MXene (TiO2 NPs@MXene). The hybrid metasurface simultaneously benefited from the high near-field enhancement effect of plasmonic materials and the low loss of dielectric materials. Furthermore, the optical modulation efficiency of the hybrid metasurface can be regulated by a magnetic mirror configuration. The magnetic mirror acted like a mirror, confining the electrons to a limited region and increasing the density of the surface plasmon. Moreover, the electrochemiluminescence (ECL) of the Cu2BDC metal-organic framework (Cu2BDC-MOF) served as a light source for the Au NRs/TiO2 NPs@MXene metasurface. Due to the exceptional light manipulation capability of the hybrid metasurface and the coordination of the magnetic mirror, the isotropic ECL signal can be dynamically amplified and converted into polarized emission. Finally, a metasurface-regulated ECL (MECL)-based biosensor with a dual-positive membrane protein recognition strategy was developed for the accurate identification of gastric cancer-derived extracellular vesicles. The novel MECL research opened up a new route in the realization of dynamically tunable metasurfaces for optical sensing and novel nanophotonic devices.

Deep learning-assisted diagnosis of benign and malignant parotid gland tumors based on automatic segmentation of ultrasound images: a multicenter retrospective study.

Objectives: To construct deep learning-assisted diagnosis models based on automatic segmentation of ultrasound images to facilitate radiologists in differentiating benign and malignant parotid tumors. Methods: A total of 582 patients histopathologically diagnosed with PGTs were retrospectively recruited from 4 centers, and their data were collected for analysis. The radiomics features of six deep learning models (ResNet18, Inception_v3 etc) were analyzed based on the ultrasound images that were obtained under the best automatic segmentation model (Deeplabv3, UNet++, and UNet). The performance of three physicians was compared when the optimal model was used and not. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were utilized to evaluate the clinical benefit of the optimal model. Results: The Deeplabv3 model performed optimally in terms of automatic segmentation. The ResNet18 deep learning model had the best prediction performance, with an area under the receiver-operating characteristic curve of 0.808 (0.694-0.923), 0.809 (0.712-0.906), and 0.812 (0.680-0.944) in the internal test set and external test sets 1 and 2, respectively. Meanwhile, the optimal model-assisted clinical and overall benefits were markedly enhanced for two out of three radiologists (in internal validation set, NRI: 0.259 and 0.213 [p = 0.002 and 0.017], IDI: 0.284 and 0.201 [p = 0.005 and 0.043], respectively; in external test set 1, NRI: 0.183 and 0.161 [p = 0.019 and 0.008], IDI: 0.205 and 0.184 [p = 0.031 and 0.045], respectively; in external test set 2, NRI: 0.297 and 0.297 [p = 0.038 and 0.047], IDI: 0.332 and 0.294 [p = 0.031 and 0.041], respectively). Conclusions: The deep learning model constructed for automatic segmentation of ultrasound images can improve the diagnostic performance of radiologists for PGTs.

Variation characteristics and clinical significance of TP53 in patients with myeloid neoplasms.

Objectives: MDS and AML characterized by TP53 variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different TP53 variants and VAFs.Methods: Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable TP53 variations were screened. Demographic data and clinical data were collected, and the relationship between TP53 alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of TP53 variations and prognoses was analyzed using data from the present study.Results: Sixty-two variants of TP53 were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of TP53. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency TP53 mutations, and DNMT3A and TET2 were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new TP53 variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered TP53 had a shorter OS than patients in the unaltered group (P<0.01), low TP53 mRNA levels were associated with shorter OS in patients with AML (P<0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (P<0.01).Conclusion: TP53 mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of TP53 mutations associated with a shorter OS in patients with MDS.

Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.

Mammalian cytosolic selenoprotein thioredoxin reductase (TXNRD1) is crucial for maintaining the reduced state of cellular thioredoxin 1 (TXN1) and is commonly up-regulated in cancer cells. TXNRD1 has been identified as an effective target in cancer chemotherapy. Discovering novel TXNRD1 inhibitors and elucidating the cellular effects of TXNRD1 inhibition are valuable for developing targeted therapies based on redox regulation strategies. In this study, we demonstrated that butein, a plant-derived small molecule flavonoid, is a novel TXNRD1 inhibitor. We found that butein irreversibly inhibited recombinant TXNRD1 activity in a time-dependent manner. Using TXNRD1 mutant variants and LC-MS, we identified that butein modifies the catalytic cysteine (Cys) residues of TXNRD1. In cellular contexts, butein promoted the accumulation of reactive oxygen species (ROS) and exhibited cytotoxic effects in HeLa cells. Notably, we found that pharmacological inhibition of TXNRD1 by butein overcame the cisplatin resistance of A549 cisplatin-resistant cells, accompanied by increased cellular ROS levels and enhanced expression of p53. Taken together, the results of this study demonstrate that butein is an effective small molecule inhibitor of TXNRD1, highlighting the therapeutic potential of inhibiting TXNRD1 in platinum-resistant cancer cells.

PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. METHODS: To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT-qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1's regulation of autophagy in GC. RESULTS: Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. CONCLUSION: PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC.

Novel biomimetic hybrid plasmonic nanocavity-based ECL strategy for the detection of extracellular vesicles.

Tumor-derived extracellular vesicles detection has emerged as an important clinical liquid biopsy approach for cancer diagnosis. In this work, we developed a novel hybrid plasmonic nanocavity consisting of hexagonal Au nanoplates nanoarray, SnS2/Au nanosheet layer and biomimetic lipid bilayer. Firstly, the hybrid plasmonic nanocavity combined the optical confinement for the ECL regulation and the biological recognition for the detection of extracellular vesicles. Secondly, MXene-derived Ti2N QDs have been prepared as ECL nanoprobe to label extracellular vesicles. Moreover, biomimetic lipid bilayer with specific aptamer was used to identify extracellular vesicles and integrate Ti2N QDs into the nanocavity with membrane fusion strategy. Due to the significant electromagnetic field enhancement at the cavity region, the hybrid plasmonic nanocavity provided strong field confinement to concentrate and redistribute the ECL emission of QDs with a 9.3-fold enhancement. The hybrid plasmonic nanocavity-based ECL sensing system improved the spatial controllability of EVs analysis and the accurate resolution of specific protein. It achieved the sensitive detection of extracellular vesicles in ascites and successfully distinguished the peritoneal metastasis of gastric cancer.

Effects of a phytobiotic-based additive on the growth, hepatopancreas health, intestinal microbiota, and Vibrio parahaemolyticus resistance of Pacific white shrimp, Litopenaeus vannamei.

Vibrio genus is a common pathogen in aquaculture and causes acute hepatopancreatic necrosis disease (AHPND) and massive mortality of shrimp. Many studies have suggested that a single functional ingredient such as plant extract or organic acid can reduce the dependence on antibiotics and promote the growth and immunity of aquatic animals. In this study, we evaluated the effects of a phytobiotic-based compound additive (Sanacore® GM, SNGM), which had a successful trajectory of commercial application in fish farming. However, its effects on the hepatopancreas health and intestinal microbiota of shrimp after Vibrio challenge have not been well evaluated. In the present study, Pacific white shrimp were fed diets with or without supplementation of SNGM, and the SNGM grades were 0-g/kg (CON), 3-g/kg (SNGM3), and 5-g/kg (SNGM5) diets. The feed trial lasted 60 days, after which a Vibrio parahaemolyticus challenge was performed. The results showed that compared to the CON group, both the SNGM3 and SNGM5 groups had a significantly higher weight gain and a lower feed conversion ratio as well as higher survival after Vibrio parahaemolyticus challenge. In the growth trial, the SNGM3 group had a significantly increased total protein, albumin concentration, and acid phosphatase activity in hemolymph compared to the CON group. In the challenge experiment, the SNGM3 and SNGM5 groups had increased albumin and glucose contents as well as the activities of phenoloxidase, lysozyme, alkaline phosphatase, and superoxide dismutase in hemolymph. Both the SNGM3 and SNGM5 groups had improved morphology of the hepatopancreas and intestine. The SNGM5 group had alleviated gut microbiota dysbiosis induced by Vibrio infection by increasing the potential probiotic bacterium abundance (Shewanella) and decreasing the potential pathogenic bacteria abundance (Vibrio, Photobacteriuma, Pseudoalteromonas, and Candidatus_Bacilloplasma). In conclusion, the dietary phytobiotic-based additive at 3-g/kg level increased the growth and Vibrio parahaemolyticus resistance of Pacific white shrimp by promoting immune-related enzyme activities and improving the morphological structure of the hepatopancreas and intestine and the intestinal microbiota composition.

[Genetic Variation of SH2B3 in Patients with Myeloid Neoplasms].

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

The luminescent Nb2C MXene nanosheet-based whispering gallery mode-enhanced ECL strategy for miRNA-214 detection.

MiRNA-214 can regulate the expression of their downstream target genes after post-transcriptional and are involved in the biological processes of triple negative breast cancer (TNBC). In this work, the small-sized luminescent Nb2C nanosheet-based whispering gallery mode-enhanced electrochemiluminescence (ECL) strategy was successfully constructed to detect miRNA-214 in TNBC. Firstly, we have synthesized small-sized luminescent Nb2C nanosheets from Nb2AlC MXene. The Nb2C nanosheets not only exhibited more stable chemical properties and reduced the defects of the large sheet structures, but also possessed the quantum confinement effect with the discrete energy level. As a result, the prepared small-sized Nb2C nanosheets had unique luminescent and electrochemical properties. Furthermore, in order to improve the ECL performance of Nb2C nanosheets, SiO2 microspheres were self-assembled on the electrode surface by gas-liquid interface method to form whispering gallery mode structure. Because the light was continuously reflected at the interface of the microcavity in the whispering gallery mode, the ECL signal of Nb2C luminescent nanosheets was amplified largely. Finally, the whispering gallery mode-based ECL sensing platform was established. The results showed that the biosensor had a good linear correlation between the ECL intensity and the logarithm of concentration of miRNA-214 in the range of 10 fM to 100 nM with a limit of detection of 2.5 fM. The actual detection of miRNA-214 content in clinical TNBC tissue samples was realized successfully.

Early Evidence of Post-Mortem Fetal Extrusion in Equids: A Case from the Western Zhou Period (1045-771 BC) Site of Yaoheyuan in Northwestern China.

Post-mortem fetal extrusion, also known as "coffin birth", refers to the phenomenon where a fetus is pushed out of a deceased female due to pressure from decomposing gas in the abdominal cavity. While post-mortem fetal extrusion has been documented in humans at several archaeological sites, there are few reports of it occurring in non-human animals. In this study, we present a case of post-mortem fetal extrusion in equids observed in a chariot-horse pit (CMK2) at the Western Zhou period site of Yaoheyuan in northwestern China, dating to the early first millennium BC. This specific pit, one of four excavated at the site, contained at least 29 horses and 3 wooden chariots. Most of these horses were young adults aged between 4 and 12 years. Out of the 22 horses with sex estimates, 21 were males. Among these individuals, one adult female horse (Horse 6) and one infantile horse (Horse 10) were of particular importance. Based on the age-at-death, sex, and head orientation of the two individuals, alongside their spatial relationships, it is highly likely that Horse 6 was the fetus of Horse 10 and was extruded in the pit. According to the parturition stage of Horse 10, Horse 6 was likely interred in CMK2 in late spring or early summer of the year, during which the relatively high temperature may have generated gas that led to the extrusion of the fetus. Although the specific reason for the inclusion of a pregnant mare in a chariot-horse pit at Yaoheyuan remains a topic for future research, this case marks the first report of post-mortem fetal extrusion in archaeological horses. The findings offer insights into the timing of horse interment as part of ritual practices among the settled elites during the Bronze Age in China and provide valuable reference data for contemporary equine veterinary science.