The profile and prognostic significance of bone marrow T-cell differentiation subsets in adult AML at diagnosis.

Background: T lymphocytes in tumor microenvironment play a pivotal role in the anti-tumor immunity, and the memory of T cells contributes to the long-term protection against tumor antigens. Compared to solid tumors, studies focusing on the T-cell differentiation in the acute myeloid leukemia (AML) bone marrow (BM) microenvironment remain limited. Patients and methods: Fresh BM specimens collected from 103 adult AML patients at diagnosis and 12 healthy donors (HDs) were tested T-cell differentiation subsets by multi-parameter flow cytometry. Results: CD4 and CD8 T-cell compartments had different constituted profiles of T-cell differentiated subsets, which was similar between AML patients and HDs. Compared to HDs, AML patients as a whole had a significantly higher proportion of CD8 effector T cells (Teff, P = 0.048). Moreover, the T-cell compartment of AML patients with no DNMT3A mutations skewed toward terminal differentiation at the expense of memory T cells (CD4 Teff: P = 0.034; CD8 Teff: P = 0.030; CD8 memory T: P = 0.017), whereas those with mutated DNMT3A had a decrease in CD8 naïve T (Tn) and CD4 effector memory T cells (Tem) as well as an increase in CD4 central memory T cells (Tcm) (P = 0.037, 0.053 and 0.053). Adverse ELN genetic risk correlated with a lower proportion of CD8 Tn. In addition, the low proportions of CD4 Tem and CD8 Tn independently predicted poorer relapse-free survival (RFS, HR [95%CI]: 5.7 (1.4-22.2), P = 0.017 and 4.8 [1.3-17.4], P = 0.013) and event-free survival (EFS, HR [95% CI]: 3.3 (1.1-9.5), P = 0.029; 4.0 (1.4-11.5), P = 0.010), respectively. Conclusions: AML patients had abnormal profiles of BM T-cell differentiation subsets at diagnosis, which was related to DNMT3A mutations. The low proportions of CD4 Tem and CD8 Tn predicted poor outcomes.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

[Effect of CD8+ CD28- T Cells on Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the effect of CD8+ CD28- T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT). METHODS: The relationship between absolute count of CD8+ CD28- T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8+ CD28- T absolute cells count groups were compared. RESULTS: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8+ CD28- T cells of aGVHD group was significantly lower than that of non-aGVHD group (P =0.03). Thus the absolute count of CD8+ CD28- T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8+ CD28- T cells absolute count < 0.06/µl) was significantly higher than that in the high cell count group (CD8+ CD28- T cells absolute count ≥0.06/µl,P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8+ CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group (P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8+ CD28- T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8+ CD28- T cells absolute count groups. CONCLUSION: Patients with delayed CD8+ CD28- T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8+ CD28- T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8+ CD28- T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.

Electrochemiluminescence enhanced by molecular engineering linear π-conjugated polymer: An ingenious ECL emitter for the construction of exosome sensing platform.

Linear π-conjugated polymers (LCPs) with π-electron conjugation system have many remarkable optical characteristics such as fluorescence and electrochemiluminescence (ECL). However, the extremely strong interchain interaction and π-π stacking limit the luminescence efficiency. In this work, 1H-1,2,4-triazole-3,5-diamine was chosen as the polymer monomer and reacted with terephthalaldehyde via simple Schiff base condensation to synthesize LCPs. Subsequently, molecular engineering strategy was adopted to construct zirconium-based LCPs (MLCPs), which not only prevented π-π stacking but also ensured that extended π-coupling was maintained in the LCPs, thus effectively promoting charge transport and achieving strong luminescence. Second, the coreactant polyethyleneimine (PEI) was assembled onto the MLCPs (MLCPs@PEI) to further promote the emission of ECL. To further explore the potential of the obtained MLCPs@PEI as emerging ECL emitter, colorectal cancer exosome was chosen as model biomarker, and an innovative ECL ratiometric system based on MLCPs@PEI and luminol was designed to improve the validity and accuracy of the sensors. This research provides a fresh nanoplatform for exosome detection and broadens the application of LCPs in ECL immunoassay.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Propionic acid ameliorates cognitive function through immunomodulatory effects on Th17 cells in perioperative neurocognitive disorders.

Background: Elderly patients undergoing surgery are prone to cognitive decline known as perioperative neurocognitive disorders (PND). Several studies have shown that the microglial activation and the decrease of short-chain fatty acids (SCFAs) in gut induced by surgery may be related to the pathogenesis of PND. The purpose of this study was to determine whether microglia and short-chain fatty acids were involved in cognitive dysfunction in aged rats. Methods: Male wild-type Wistar rats aged 11-12 months were randomly divided into control group (Ctrl: Veh group), propionic acid group (Ctrl: PA group), exploratory laparotomy group (LP: Veh group) and propionic acid + exploratory laparotomy group (LP: PA group) according to whether exploratory laparotomy (LP) or PA pretreatment for 21 days was performed. The motor ability of the rats was evaluated by open field test on postoperative day 3 (POD3), and then the cognitive function was evaluated by Y-maze test and fear conditioning test. The expression of IL-1ß, IL-6, RORγt and IL-17A mRNA in hippocampus was detected by RT-qPCR, the expression of IL-17A and IL-17RA in hippocampus was detected by Western blot, and the activation of microglia was detected by immunofluorescence. Results: The PND rat model was successfully established by laparotomy. Compared with Ctrl: Veh group, the body weight of LP: Veh group decreased, the percentage of spontaneous alternations in Y maze decreased (P < 0.001), and the percentage of freezing time in contextual fear test decreased (P < 0.001). Surgery triggers neuroinflammation, manifested as the elevated levels of the inflammatory cytokines IL-1ß (P < 0.001) and IL-6 (P < 0.001), the increased expression of the transcription factor RORγt (P = 0.0181, POD1; P = 0.0073, POD5)and major inflammatory cytokines IL-17A (P = 0.0215, POD1; P = 0.0071, POD5), and the increased average fluorescence intensity of Iba1 (P < 0.001, POD1; P < 0.001, POD5). After PA preconditioning, the recovery of rats in LP: PA group was faster than that in LP: Veh group as the body weight lost on POD1 (P = 0.0148) was close to the baseline level on POD5 (P = 0.1846), and they performed better in behavioral tests. The levels of IL-1ß (P < 0.001) and IL-6 (P = 0.0035) inflammatory factors in hippocampus decreased on POD1 and the average fluorescence intensity of Iba1 decreased (P = 0.0024, POD1; P < 0.001, POD5), representing the neuroinflammation was significantly improved. Besides, the levels of RORγt mRNA (P = 0.0231, POD1; P = 0.0251, POD5) and IL-17A mRNA (P = 0.0208, POD1; P = 0.0071, POD5) in hippocampus as well as the expression of IL-17A (P = 0.0057, POD1; P < 0.001, POD5) and IL-17RA (P = 0.0388) decreased. Conclusion: PA pretreatment results in reduced postoperative neuroinflammation and improved cognitive function, potentially attributed to the regulatory effects of PA on Th17-mediated immune responses.

A photoelectrochemical biosensor based on self-calibration platform of carbon-rich plasmonic probe with near-infrared driving signal amplification.

Exploring the photochemical (PEC) method induced by low-energy light source makes great significance to achieve high stability and accurate analysis. A sensing platform driven by near-infrared (NIR) light was designed by making the biochemically encoded carbon rich plasmonic hybrid (CPH) probe, the peptide@C-Mo2C. The inherent plasmonic effect of C-Mo2C CPH can directly absorb NIR light, thus starting effective electronic-hole pairs separation. Moreover, the photothermal effect of C-Mo2C CPH also promoted the reaction yield of photothermal catalyst reaction on sensing interface to assist the PEC signal amplification. In the presence of target trypsin, it cleaves the peptides, resulting in the release of peptide@C-Mo2C probe from interface, which leads to a relative decrease in PEC signal. More importantly, a self-calibration system consisting of two independent PEC test channels attempted to eliminate the influence of background signal and baseline drift. The test channel was used to specify the recognition target, while the blank channel was used as a reference. Therefore, the signal difference between two channels was recorded, so as to obtain results with less error and higher stability. In this NIR driven PEC sensor, the carbon rich probe with direct and efficient NIR light conversion promoted the sensitivity and a self-calibration system guaranteed the stability which provided innovative thoughts for developing ingenious PEC sensor.

Triglyceride-Glucose Index is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients with HBV-Related Liver Cirrhosis.

Aim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC. Results: The median follow-up time was 37 months (range: 6-123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P<0.01), DC (P<0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P<0.01), and HBV DNA positivity (P<0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, <0.01, 0.05, and <0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P<0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively. Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.

Flow Channel with Wrinkles and Calcium Sites in a Ca-MOF for Direct One-Step Ethylene Purification from C2 Gases and MTO Products Separation.

The strategy of flow channel with wrinkles and calcium sites for single-step C2H4 purification from C2 gases and methanol-to-olefins (MTO) products separation was realized in FJI-Y9. The adsorption amounts showed a total reversal order of C3H6 > C2H6 > C2H2 > C2H4 at 298 K. Modeling indicated that the wrinkles and Ca2+ facilitated the full contact of C3H6 and C2H6. Breakthrough experiments illustrated that FJI-Y9 could yield pure C2H4 in a single step with a productivity of 0.78 mmol g-1. In a lone adsorption/desorption cycle for MTO product separation, the productivities of C3H6 and C2H4 were 1.96 and 1.29 mol g-1, standing as the highest recorded values.

Zwitterion modified chitosan as a high-performance corrosion inhibitor for mild steel in hydrochloric acid solution.

Herein, a novel chitosan Schiff base (CS-FGA) as a sustainable corrosion inhibitor has been successfully synthesized via a simple amidation reaction by using an imidazolium zwitterion and chitosan (CS). The corrosion inhibition property of CS-FGA for mild steel (MS) in a 1.0 M HCl solution was studied by various electrochemical tests and physical characterization methods. The findings indicate that the maximum inhibition efficiency of CS-FGA as a mixed-type inhibitor for MS in 1.0 M HCl solution with 400 mg L-1 reaches 97.6 %, much much higher than the CS and the recently reported chitosan-based inhibitors. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and water contact angle (WCA) results reveal that the CS-FGA molecules firmly adsorb on the MS surface to form a protective layer. The adsorption of CS-FGA on the MS surface belongs to the Langmuir adsorption isotherm containing both the physisorption and chemisorption. According to the X-ray photoelectron spectroscopy (XPS) and UV-vis spectrum, FeN bonds presented on the MS surface further prove the chemisorption between CS-FGA and Fe to generate the stable protective layer. Additionally, theoretical calculations from quantum chemical calculation (DFT) and molecular simulations (MD) were performed to reveal the inhibition mechanism of CS-FGA.

[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with GATA2 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics, coexisting gene mutations and prognosis of acute myeloid leukemia (AML) patients with GATA2 gene mutation. METHODS: The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively, the next-generation sequencing technology was used to detect the mutated genes in those patients. The clinical characteristics of AML patients with GATA2 mutations, the co-mutated genes of GATA2 mutations, and the effect of GATA2 mutation on prognosis were analyzed. RESULTS: A total of 23 patients (6.2%) with GATA2 mutation was detected in 370 AML patients. Compared with GATA2 non-mutation group, patients in GATA2 mutation group were mostly normal karyotypes (P =0.037) and in low-risk cytogenetic stratification (P =0.028). The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group (P =0.010, P =0.009). There were no statistically significant differences between the two groups in terms of sex, age, white blood cell count (WBC), platelet count, hemoglobin, bone marrow (BM) blast, induction chemotherapy regimen and CR rate (P >0.05). Among the 23 patients with GATA2 mutation, the most common co-mutated genes were CEBPAdm, NRAS (both 39.1%), NPM1, FLT3, TET2, WT1 (all 17.4%), ASXL1 and IDH1 (both 13.0%). Survival analysis showed that there was no statistical difference in 5-year overall survival (OS) and leukemia-free survival (LFS) rates between patients with and without GATA2 mutations in whole cohort (n=370) (P =0.306, P =0.308). Among 306 patients without CEBPAdm, the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group, but the difference was not statistically significant (P =0.092, P =0.056). Among 64 patients with CEBPAdm, there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group (P =0.104), but the 5-year LFS rate of the GATA2 mutation group was significantly decreased (P =0.047). Among the 23 patients with GATA2 mutation, 16 cases received the "3+7" induction regimen, of which 12 cases received allogeneic hematopoietic stem cell transplantation (allo-HSCT); 7 cases received the "DCAG" induction regimen, of which 3 cases received allo-HSCT. The CR rate was not statistically different between the "3+7" regimen group and the "DCAG" regimen group (P =1.000). The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group (P =0.021, P =0.020). CONCLUSION: GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of "3+7" or "DCAG" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Breast Cancer Classification From Digital Pathology Images via Connectivity-Aware Graph Transformer.

Automated classification of breast cancer subtypes from digital pathology images has been an extremely challenging task due to the complicated spatial patterns of cells in the tissue micro-environment. While newly proposed graph transformers are able to capture more long-range dependencies to enhance accuracy, they largely ignore the topological connectivity between graph nodes, which is nevertheless critical to extract more representative features to address this difficult task. In this paper, we propose a novel connectivity-aware graph transformer (CGT) for phenotyping the topology connectivity of the tissue graph constructed from digital pathology images for breast cancer classification. Our CGT seamlessly integrates connectivity embedding to node feature at every graph transformer layer by using local connectivity aggregation, in order to yield more comprehensive graph representations to distinguish different breast cancer subtypes. In light of the realistic intercellular communication mode, we then encode the spatial distance between two arbitrary nodes as connectivity bias in self-attention calculation, thereby allowing the CGT to distinctively harness the connectivity embedding based on the distance of two nodes. We extensively evaluate the proposed CGT on a large cohort of breast carcinoma digital pathology images stained by Haematoxylin & Eosin. Experimental results demonstrate the effectiveness of our CGT, which outperforms state-of-the-art methods by a large margin. Codes are released on https://github.com/wang-kang-6/CGT.

Self-reduced MXene-Metal interaction electrochemiluminescence support with synergistic electrocatalytic and photothermal effects for the bimodal detection of ovarian cancer biomarkers.

Novel two-dimensional MXene with unique optical and electrical properties has become a new focus in the field of sensing. In particular, their metallic conductivity, good biocompatibility and high anchoring ability to biomaterials make them attractive candidates. Despite such remarkable properties, there are certain limitations, such as low oxidative stability. MXene-Metal interactions are an effective strategy to maintain the long-term stability of MXene, while also improving the electrochemical activity and optical properties. Herein, a series of MXene/Ag nanocomposites including Ti3C2/Ag, Nb2C/Ag and V2C/Ag were designed based on the surface chemistry characteristics of MXene, where MXene served as the substrate for in-situ growth of silver nanoparticles via self-reduction of Ag(NH3)2+. The results showed that V2C MXene has the strongest self-reducing ability due to its multiple variable valence states, larger interlayer space and more reactive groups. Moreover, V2C/Ag exhibited unexpected oxygen reduction reaction catalytic activity and photothermal performance. In view of which, an electrochemiluminescence-photothermal (ECL-photothermal) immunosensor was developed using V2C/Ag as ECL anchor and photothermal reagent for ultrasensitive detection of Lipolysis stimulated lipoprotein receptor. This work not only provides a simple and effective synthesis method of MXene supported metal nanocomposites, but also provides more inspirations for exploring the efficient biosensing strategies.

Adoptive transfer of CMV-specific TCR-T cells for the treatment of CMV infection after haploidentical hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation after unmanipulated haploidentical stem cell transplantation (SCT) frequently occurs, causing life-threatening morbidities and transplantation failure. Pre-emptive therapy upon the detection of CMV viremia using antiviral agents is currently the standard of care but it was associated with significant toxicity. The CMV antigen-specific cytotoxic T lymphocyte therapy was limited by the time-consuming manufacture process and relatively low success rate. More effective and safer approaches for the treatment of CMV reactivation after haploidentical SCT are in urgent need. METHODS: A single-arm, open-label, phase I clinical trial evaluating the safety and efficacy of CMV-targeting T cell receptor-engineered T (CMV-TCR-T) cell therapy as the first-line pre-emptive therapy for patients with CMV reactivation after haploidentical peripheral blood SCT (PBSCT) was conducted in the Chinese PLA General Hospital. Six patients with CMV reactivation after haploidentical SCT were adoptively transferred by one to three doses of SCT donors-derived CMV-TCR-T cells. This trial was a dose-escalation study with doses ranging from 1×103 CMV-TCR-T cells/kg body weight per dose to 5×105 CMV-TCR-T cells/kg per dose. RESULTS: Except for the grade 1 cytokine release syndrome observed in one patient and mild fever in two patients, no other adverse events were observed. Four patients had response within a month after CMV-TCR-T cell infusion without the administration of any antiviral agents. The other two patients who initially did not respond to CMV-TCR-T cell therapy had salvage ganciclovir and foscarnet administration and then had rapid CMV clearance. The CMV-TCR-T cells displayed overall robust expansion and persistence in the peripheral blood after infusion. The CMV-TCR-T cells were first detected in the peripheral blood of these patients 3-7 days after the first dose of CMV-TCR-T infusion, rapidly expanded and persisted for at least 1-4 months, providing long-term protection against CMV reactivation. In one patient, the CMV-TCR-T cells started to expand even when the anti-graft-versus-host disease reagents were still being used, further indicating the proliferation potential of CMV-TCR-T cells. CONCLUSIONS: Our study first showed CMV-TCR-T cell as a highly feasible, safe and effective first-line pre-emptive treatment for CMV reactivation after haploidentical PBSCT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05140187).

Hippocampal estrogens rescued the decline of synaptic plasticity after surgery and anesthesia by inhibiting microglia overactivation.

BACKGROUND: Elderly patients experience postoperative cognitive impairment frequently; therefore, effective interventions are urgently needed. Central nervous inflammation characterized by microglia may promote the progression of POCD by reducing synaptic plasticity. Notably, clinical studies revealed that the incidence of female patients was significantly lower than that of male patients. Besides, the brain estrogens have an anti-inflammatory effect and regulate the microglia at the same times. This study aimed to determine whether suppressing microglia overactivation by hippocampal estrogens can rescue the decrease of synaptic plasticity after surgery and anesthesia. METHODS: Exploratory laparotomy was used to establish the POCD model in 15-month-old male or female C57BL/6 J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Western blot and immunofluorescence were used to detect the microglial activation and plasticity related protein expressions. Elisa was used to detect the content of estrogens in the hippocampus. Estrogens and estrogen receptor inhibitor were used to replenish the estrogens in the brain and inhibit the effect of estrogens. RESULTS: Surgery and anesthesia did not cause POCD in female mice (P > 0.05), while the cognitive function decreased significantly after estrogen receptor inhibitor was given(P < 0.05). Male mice experienced cognitive dysfunction after surgery and anesthesia, and their cognitive function improved after estrogens supplementation (P < 0.05). Given estrogens and estrogen receptor inhibitors at the same time, the cognitive function of male mice could not be saved (P < 0.05). By correlation analysis, there was a negative correlation between the content of hippocampal estrogens and microglia (P < 0.05). The number or degree of activation of microglia affected the synaptic plasticity, which ultimately regulated the cognitive function of mice. CONCLUSION: Hippocampal estrogens rescued the decline of synaptic plasticity after surgery and anesthesia by inhibiting microglia overactivation.

SK-Unet++: An improved Unet++ network with adaptive receptive fields for automatic segmentation of ultrasound thyroid nodule images.

BACKGROUND: The quality of segmentation of thyroid nodules in ultrasound images is a crucial factor in preventing the cancerization of thyroid nodules. However, the existing standards for the ultrasound imaging of cancerous nodules have limitations, and changes of the echo pattern of thyroid nodules pose challenges in accurately segmenting nodules, which can affect the diagnostic results of medical professionals. PURPOSE: The aim of this study is to address the challenges related to segmentation accuracy due to noise, low contrast, morphological scale variations, and blurred edges of thyroid nodules in ultrasound images and improve the accuracy of ultrasound-based thyroid nodule segmentation, thereby aiding the clinical diagnosis of thyroid nodules. METHOD: In this study, the dataset of thyroid ultrasound images was obtained from Hunan Provincial People's Hospital, consisting of a total of 3572 samples used for the training, validation, and testing of this model at a ratio of 8:1:1. A novel SK-Unet++ network was used to enhance the segmentation accuracy of thyroid nodules. SK-Unet++ is a novel deep learning architecture that adds the adaptive receptive fields based on the selective kernel (SK) attention mechanisms into the Unet++ network. The convolution blocks of the original UNet++ encoder part were replaced with finer SK convolution blocks in SK-Unet++. First, multiple skip connections were incorporated so that SK-Unet++ can make information from previous layers of the neural network to bypass certain layers and directly propagate to subsequent layers. The feature maps of the corresponding locations were fused on the channel, resulting in enhanced segmentation accuracy. Second, we added the adaptive receptive fields. The adaptive receptive fields were used to capture multiscale spatial features better by dynamically adjusting its receptive field. The assessment metrics contained dice similarity coefficient (Dsc), accuracy (Acc), precision (Pre), recall (Re), and Hausdorff distance, and all comparison experiments used the paired t-tests to assess whether statistically significant performance differences existed (p < 0.05). And to address the multi-comparison problem, we performed the false discovery rate (FDR) correction after the test. RESULTS: The segmentation model had an Acc of 80.6%, Dsc of 84.7%, Pre of 77.5%, Re of 71.7%, and an average Hausdorff distance of 15.80 mm. Ablation experimental results demonstrated that each module in the network could contribute to the improved performance (p < 0.05) and determined the best combination of parameters. A comparison with other state-of-the-art methods showed that SK-Unet++ significantly outperformed them in terms of segmentation performance (p < 0.05), with a more accurate segmentation contour. Additionally, the adaptive weight changes of the SK module were monitored during the training process, and the resulting change curves demonstrated their convergence. CONCLUSION: Our proposed method demonstrates favorable performance in the segmentation of ultrasound images of thyroid nodules. Results confirmed that SK-Unet++ is a feasible and effective method for the automatic segmentation of thyroid nodules in ultrasound images. The high accuracy achieved by our method can facilitate efficient screening of patients with thyroid nodules, ultimately reducing the workload of clinicians and radiologists.

[Efficacy and Prognosis of Transplant-Associated Thrombotic Microangiopathy Based on Different Prognostic Risk Models].

OBJECTIVE: To investigate the clinical features of transplant-associated thrombotic microangiopathy (TA-TMA) and the prognostic value of different prognostic risk models for TA-TMA. METHODS: The clinical characteristics of 32 TA-TMA patients diagnosed at the First Medical Center of the PLA General Hospital from January 2018 to February 2022 in terms of short-term prognosis and influencing factors were retrospectively analyzed. In addition, the risk population composition ratio, treatment response, and overall survival between the BATAP risk model and the TMA index model were compared, as well as the efficacy of two prognostic risk models for predicting death in patients with TA-TMA. RESULTS: Independent risk factors affecting the short-term prognosis of TA-TMA include III-IV aGVHD prior to TA-TMA diagnosis (P=0.001), renal or neurological dysfunction (P=0.006), and Hb<70 g/L (P=0.043). In the TMA index model, treatment response was worst in the high-risk group (P=0.008), while there was no significant difference in treatment response between different risk groups in the BATAP model (P=0.105). In the BATAP model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (87.5% vs 61.1% vs 16.7%, χ2＝6.7, P=0.014). In the TMA index model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (77.8% vs 45.5% vs 0.0%, χ2＝7.3, P=0.017). The area under the ROC curve (AUC) of the TMA index model was 0.745 (95%CI: 0.56-0.88, P<0.05), and the AUC of the BATAP model was 0.743 (95%CI: 0.56-0.88, P<0.05), indicating that both prognostic risk models have good predictive value. CONCLUSION: The short-term prognosis of TA-TMA patients might be accurately determined using both the BATAP model and the TMA index model. When predicting the efficacy of TA-TMA in different risk groups, the TMA index model may perform better than the BATAP model.

Designing Multimodal Informative Sensing with an Exosome-Mediated Signal Coupling Transduction Strategy Based on a Single-Stimulus Multiresponse Recognition Interface.

Given that exosomes released from cancer cells carry various tumor-specific proteins on their surface, they have emerged as a source of biomarkers for cancer diagnosis. However, developing accurate and reliable assays to detect exosomes in the early stages of disease with low abundance and complex systems remains challenging. Here, the prepared PDIG film has the ability to sense multiple signals from a single stimulus, in which the presence of cobalt(II) chloride and deep eutectic solvents (DES) endows PDIG with thermochromic and thermosensitive properties. Concretely, the PDIG served as the recognition interface in series with a bipolar electrode (BPE) that exhibits a highly sensitive color and conductivity response to temperature stimuli triggered by the light-harvesting probe TiO2@CNOs introduced via proximity hybridization assay triggering a rolling circle amplification strategy, resulting in the output of colorimetric, photoacoustic, and electrochemiluminescent signals for the detection of colorectal cancer exosomes. This work is expected to provide a new direction for exploring the multisignal amplification strategy of BPE, broaden the application of BPE in biological analysis, and provide new insights for developing highly information-sensing elements to ensure the multimodal coupling for cancer-specific exosome detection.

Two-phase dual-signal-readout immunosensing platform based on multifunctional carbon nano-onions for ovarian cancer biomarker detection.

In order to detect early tumor markers and gain valuable time for treatment, there is an urgent need to develop a fast, cheap, and ultrasensitive multi-reading sensing platform. Herein, a solid/liquid two-phase dual-output biosensor was explored based on a sensitized sonochemiluminescence (SCL) strategy and a multifunctional carbon nano-onion (CNO) probe. It is clear that ultrasonic radiation caused the formation of hydroxyl radicals (˙OH), triggering the SCL signal of the emitter lucigenin (Luc2+). Meanwhile, titanium carbide nanodots and ethanol were used to enhance the SCL signal, and an astonishingly linear enhancement of the SCL intensity was produced with increasing ethanol concentration. More importantly, the CNOs, with their excellent photothermal properties and adsorption capacity, can output both the temperature signal and an enhanced SCL strength from the solid-liquid phase. Through inter-calibration of the signals from the two-phases, this biosensor shows excellent analytical performance for the detection of the ovarian cancer biomarker, human epididymis-specific protein 4, from 10-5 to 10 ng mL-1 with a low detection limit of 3.3 fg mL-1. This work not only provides a novel two-phase signal-output mode that broadens the scope of multiperformance joint applications of CNOs, but also enriches the quantitative detection of point-of-care testing.