Deep learning models for rapid discrimination of high-grade gliomas from solitary brain metastases using multi-plane T1-weighted contrast-enhanced (T1CE) images.

Background: High-grade gliomas (HGG) and solitary brain metastases (SBM) are two common types of brain tumors in middle-aged and elderly patients. HGG and SBM display a high degree of similarity on magnetic resonance imaging (MRI) images. Consequently, differential diagnosis using preoperative MRI remains challenging. This study developed deep learning models that used pre-operative T1-weighted contrast-enhanced (T1CE) MRI images to differentiate between HGG and SBM before surgery. Methods: By comparing various convolutional neural network models using T1CE image data from The First Medical Center of the Chinese PLA General Hospital and The Second People's Hospital of Yibin (Data collection for this study spanned from January 2016 to December 2023), it was confirmed that the GoogLeNet model exhibited the highest discriminative performance. Additionally, we evaluated the individual impact of the tumoral core and peritumoral edema regions on the network's predictive performance. Finally, we adopted a slice-based voting method to assess the accuracy of the validation dataset and evaluated patient prediction performance on an additional test dataset. Results: The GoogLeNet model, in a five-fold cross-validation using multi-plane T1CE slices (axial, coronal, and sagittal) from 180 patients, achieved an average patient accuracy of 92.78%, a sensitivity of 95.56%, and a specificity of 90.00%. Moreover, on an external test set of 29 patients, the model achieved an accuracy of 89.66%, a sensitivity of 90.91%, and a specificity of 83.33%, with an area under the curve of 0.939 [95% confidence interval (CI): 0.842-1.000]. Conclusions: GoogLeNet performed better than previous methods at differentiating HGG from SBM, even for core and peritumoral edema in both. HGG and SBM could be fast screened using this end-to-end approach, improving workflow for both tumor treatments.

Dietary Bacillus velezensis KNF-209 supplementation improves growth performance, enhances immunity, and promotes gut health in broilers.

This study aimed to investigate the effects of dietary Bacillus velezensis KNF-209 (BV-KNF-209) on the growth performance, immunity, and gut health of broilers. A total of 540 one-day-old male Cobb-500 broilers were randomly divided into 5 groups of 6 replicates with 18 broilers per replicate. Dietary treatments were corn-soybean meal basal diets supplemented with 0, 50, 100, 200, and 400 mg/kg BV-KNF-209 (CON, BV 50, BV 100, BV 200, and BV 400 groups, respectively) for 42 d. Compared with the CON group, the average daily gains (ADG) at 0 to 42 d in the BV 100 and BV 200 groups were significantly increased (P < 0.01), and the feed-to-gain (F:G) ratios were significantly decreased at 0 to 21 d (P < 0.01) and 0 to 42 d (P < 0.05). The BV 200 and BV 400 groups had higher serum immunoglobulin M (IgM) levels at d 21 and 42 (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were significantly decreased in the BV 50, BV 100, and BV 200 groups at d 21 (P < 0.05), and serum IL-1ß and IL-6 levels were also reduced in the BV 100 and BV 200 groups at d 42 (P < 0.05). Meanwhile, increased interleukin-10 (IL-10) levels in the jejunal and ileal mucosa at d 42 were observed in the BV 100, BV 200, and BV 400 groups (P < 0.05), while the IL-1ß and IL-6 levels (P < 0.01) were decreased. The BV 200 and BV 400 groups showed significantly higher activities of lipase and trypsin (P < 0.05) in jejunal digesta as well as higher activities of amylase and trypsin (P < 0.01) in ileal digesta at d 42. The cecal acetic acid and propionic acid levels in the BV groups and lactic acid levels in the BV 50, BV 100, and BV 200 groups (P < 0.05) were significantly higher compared to those in the CON group. Overall, dietary BV-KNF-209 supplementation significantly improved broiler growth performance, an effect that may have been achieved by heightening immunity, increasing digestive enzyme activity, and raising intestinal short-chain fatty acids and lactic acid levels.

MicroRNA164 Affects Plant Responses to UV Radiation in Perennial Ryegrass.

Increasing the ultraviolet radiation (UV) level, particularly UV-B due to damage to the stratospheric ozone layer by human activities, has huge negative effects on plant and animal metabolism. As a widely grown cool-season forage grass and turfgrass in the world, perennial ryegrass (Lolium perenne) is UV-B-sensitive. To study the effects of miR164, a highly conserved microRNA in plants, on perennial ryegrass under UV stress, both OsmiR164a overexpression (OE164) and target mimicry (MIM164) transgenic perennial ryegrass plants were generated using agrobacterium-mediated transformation, and UV-B treatment (~600 µw cm-2) of 7 days was imposed. Morphological and physiological analysis showed that the miR164 gene affected perennial ryegrass UV tolerance negatively, demonstrated by the more scorching leaves, higher leaf electrolyte leakage, and lower relative water content in OE164 than the WT and MIM164 plants after UV stress. The increased UV sensitivity could be partially due to the reduction in antioxidative capacity and the accumulation of anthocyanins. This study indicated the potential of targeting miR164 and/or its targeted genes for the genetic manipulation of UV responses in forage grasses/turfgrasses; further research to reveal the molecular mechanism underlying how miR164 affects plant UV responses is needed.

Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study.

BACKGROUND: The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, the authors examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI. MATERIALS AND METHODS: The authors retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using three objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. The authors performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI. RESULTS: A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification. CONCLUSIONS: Poor preoperative nutritional status, as assessed by GNRI, PNI, and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.

SPPUSM: An MS/MS spectra merging strategy for improved low-input and single-cell proteome identification.

Single and rare cell analysis provides unique insights into the investigation of biological processes and disease progress by resolving the cellular heterogeneity that is masked by bulk measurements. Although many efforts have been made, the techniques used to measure the proteome in trace amounts of samples or in single cells still lag behind those for DNA and RNA due to the inherent non-amplifiable nature of proteins and the sensitivity limitation of current mass spectrometry. Here, we report an MS/MS spectra merging strategy termed SPPUSM (same precursor-produced unidentified spectra merging) for improved low-input and single-cell proteome data analysis. In this method, all the unidentified MS/MS spectra from multiple test files are first extracted. Then, the corresponding MS/MS spectra produced by the same precursor ion from different files are matched according to their precursor mass and retention time (RT) and are merged into one new spectrum. The newly merged spectra with more fragment ions are next searched against the database to increase the MS/MS spectra identification and proteome coverage. Further improvement can be achieved by increasing the number of test files and spectra to be merged. Up to 18.2% improvement in protein identification was achieved for 1 ng HeLa peptides by SPPUSM. Reliability evaluation by the "entrapment database" strategy using merged spectra from human and E. coli revealed a marginal error rate for the proposed method. For application in single cell proteome (SCP) study, identification enhancement of 28%-61% was achieved for proteins for different SCP data. Furthermore, a lower abundance was found for the SPPUSM-identified peptides, indicating its potential for more sensitive low sample input and SCP studies.

Treatment of multiple myeloma based on autologous stem cell transplant: An overview of systematic reviews.

BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease. In recent years, several systematic reviews, and meta-analyses have been published on treatment protocols, including autologous stem cell transplantation for MM. METHODS: Web of Science, PubMed, Embase, and Cochrane Library were searched to systematically summarize the quality of the methodology and evidence of meta-analyses regarding treatment of MM including autologous stem cell transplantation. RESULTS: Total 11 meta-analyses were included. The preferred reporting items for systematic reviews and meta-analyses evaluation revealed that the quality of included reviews was affected by possible unevaluated bias between studies and the lack of protocol and registration. The AMSTAR2 scale indicated that the quality of the methodology of included reviews ranged from very low to moderate. The grading, assessment, development, and evaluation of recommendations evaluation showed that among the included outcome indicators, most of them are of low quality. CONCLUSION: This overview suggested that the combination of drugs has improved patient survival rates, efficacy and safety compared with the standard regimen. However, the strength of the evidence is uneven and due to methodological errors, the results should be interpreted with caution in order to provide a reference for further improvement of the study design. The methodological quality of the relevant meta-analysis needs to be further improved.

A novel transcription factor SIPA1: identification and verification in triple-negative breast cancer.

Transcription factors (TFs) regulate the expression of genes responsible for cell growth, differentiation, and responses to environmental factors. In this study, we demonstrated that signal-induced proliferation-associated 1 (SIPA1), known as a Rap-GTPase-activating protein, bound DNA and served as a TF. Importin ß1 was found to interact with SIPA1 upon fibronectin treatment. A TGAGTCAB motif was recognized and bound by DNA-binding region (DBR) of SIPA1, which was confirmed by electrophoretic mobility shift assay. SIPA1 regulated the transcription of multiple genes responsible for signal transduction, DNA synthesis, cell adhesion, cell migration, and so on. Transcription of fibronectin 1, which is crucial for cell junction and migration of triple-negative breast cancer (TNBC) cells, was regulated by SIPA1 in a DBR-dependent manner both in vivo and in vitro. Furthermore, single-cell transcriptome sequencing analysis of specimens from a metastatic TNBC patient revealed that SIPA1 was highly expressed in metastatic TNBC. Hence, this study demonstrated that SIPA1 served as a TF, promoting TNBC migration, invasion, and metastasis.

Sensitive N-Glycopeptide Profiling of Single and Rare Cells Using an Isobaric Labeling Strategy without Enrichment.

Single-cell omics is critical in revealing population heterogeneity, discovering unique features of individual cells, and identifying minority subpopulations of interest. As one of the major post-translational modifications, protein N-glycosylation plays crucial roles in various important biological processes. Elucidation of the variation in N-glycosylation patterns at single-cell resolution may largely facilitate the understanding of their key roles in the tumor microenvironment and immune therapy. However, comprehensive N-glycoproteome profiling for single cells has not been achieved due to the extremely limited sample amount and incompatibility with the available enrichment strategies. Here, we have developed an isobaric labeling-based carrier strategy for highly sensitive intact N-glycopeptide profiling for single cells or a small number of rare cells without enrichment. Isobaric labeling has unique multiplexing properties, by which the "total" signal from all channels triggers MS/MS fragmentation for N-glycopeptide identification, while the reporter ions provide quantitative information. In our strategy, a carrier channel using N-glycopeptides obtained from bulk-cell samples significantly improved the "total" signal of N-glycopeptides and, therefore, promoted the first quantitative analysis of averagely 260 N-glycopeptides from single HeLa cells. We further applied this strategy to study the regional heterogeneity of N-glycosylation of microglia in mouse brain and discovered region-specific N-glycoproteome patterns and cell subtypes. In conclusion, the glycocarrier strategy provides an attractive solution for sensitive and quantitative N-glycopeptide profiling of single/rare cells that cannot be enriched by traditional workflows.

Genome-wide identification and analysis of TCP family genes in Medicago sativa reveal their critical roles in Na+/K+ homeostasis.

BACKGROUND: Medicago sativa is the most important forage world widely, and is characterized by high quality and large biomass. While abiotic factors such as salt stress can negatively impact the growth and productivity of alfalfa. Maintaining Na+/K+ homeostasis in the cytoplasm helps reduce cell damage and nutritional deprivation, which increases a salt-tolerance of plant. Teosinte Branched1/ Cycloidea/ Proliferating cell factors (TCP) family genes, a group of plant-specific transcription factors (TFs), involved in regulating plant growth and development and abiotic stresses. Recent studies have shown TCPs control the Na+/K+ concentration of plants during salt stress. In order to improve alfalfa salt tolerance, it is important to identify alfalfa TCP genes and investigate if and how they regulate alfalfa Na+/K+ homeostasis. RESULTS: Seventy-one MsTCPs including 23 non-redundant TCP genes were identified in the database of alfalfa genome (C.V XinJiangDaYe), they were classified into class I PCF (37 members) and class II: CIN (28 members) and CYC/TB1 (9 members). Their distribution on chromosome were unequally. MsTCPs belonging to PCF were expressed specifically in different organs without regularity, which belonging to CIN class were mainly expressed in mature leaves. MsTCPs belongs to CYC/TB1 clade had the highest expression level at meristem. Cis-elements in the promoter of MsTCPs were also predicted, the results indicated that most of the MsTCPs will be induced by phytohormone and stress treatments, especially by ABA-related stimulus including salinity stress. We found 20 out of 23 MsTCPs were up-regulated in 200 mM NaCl treatment, and MsTCP3/14/15/18 were significantly induced by 10 µM KCl, a K+ deficiency treatment. Fourteen non-redundant MsTCPs contained miR319 target site, 11 of them were upregulated in MIM319 transgenic alfalfa, and among them four (MsTCP3/4/10A/B) genes were directly degraded by miR319. MIM319 transgene alfalfa plants showed a salt sensitive phenotype, which caused by a lower content of potassium in alfalfa at least partly. The expression of potassium transported related genes showed significantly higher expression in MIM319 plants. CONCLUSIONS: We systematically analyzes the MsTCP gene family at a genome-wide level and reported that miR319-TCPs model played a function in K+ up-taking and/ or transportation especially in salt stress. The study provide valuable information for future study of TCP genes in alfalfa and supplies candidate genes for salt-tolerance alfalfa molecular-assisted breeding.

An angled-shape tip-based strategy for highly sensitive proteomic profiling of a low number of cells.

Profiling proteins plays an essential role in understanding the functions and dynamic networks in biological systems. Mass spectrometry-based proteomic analysis commonly requires multistep sample processing, which results in severe sample loss. Although the recently developed microproteomic strategies have substantially reduced sample loss via droplet microfluidic technology, specialized equipment and well-trained personnel are needed, which may limit their wide adoption. Here, we report an angled-shape tip-based strategy for rapid sample preparation and sensitive proteomic profiling of small cell populations (<1000 cells). The angled-shape tip provided a 'reactor' for the entire proteomic sample processing workflow, from cell capture and lysis to protein digestion, eliminating the sample transfer-induced protein loss. The angled-shape tip was surface-treated for anti-protein adsorption which further reduced the sample loss. Using this strategy, 1241 ± 38-4110 ± 37 protein groups and 4010 ± 700-34 879 ± 575 peptides were identified from 10-1000 HeLa cells with high quantification reproducibility in only 4.5 h sample processing time, which was superior to the reported methods and commercial kits, especially for <100 cells. This approach was easily accessible, straightforward to operate, and compatible with flow cytometry-based cell sorting. It showed great potential for in-depth proteomic profiling of rare cells (<1000 cells) in both basic biological research and clinical application.

APPLICATION OF CT PULMONARY ANGIOGRAPHY WITH "ULTRA-DOUBLE-LOW" AND ITERATIVE MODEL RECONSTRUCTION FOR ACUTE PULMONARY EMBOLISM.

The study is to investigate the feasibility of computed tomography pulmonary angiography (CTPA) with iterative model reconstruction (IMR) and "Ultra-double-low" (Ultra-low dose, Ultra-low contrast agent volume). Thirty-six patients who tested positive for pulmonary embolism in CTPA were enrolled in the study. Another CTPA was performed 1 week after thrombolytic therapy. The first examination was routine CTPA (Routine Group) with the parameters as follows: automatic mA scanning, 120 kV and image reconstruction by using iDose4 iterative reconstruction (Lever 4), iodine concentration and dose of contrast agent: 300 mgI/ml and 0.5 gI/kg, respectively. The latter one was ultra-low dose CTPA examination (Ultra-low Group): 40 mAs, 80 kV and IMR (Lever 3), contrast agent: 300 mgI/ml and 15 mL, respectively. Effective dose (ED), CT dose index volume (CTDIvol), dose length product (DLP), attenuation of pulmonary artery, contrast noise ratio (CNR) and signal noise ratio (SNR) were recorded and calculated. The imaging qualities were subjectively assessed. The Eds/CTDIvols/DLPs of Ultra-low Group are lower than the Routine Group (P < 0.05). The differences in attenuation between the two groups are not significant (P > 0.05). The differences in CNR and SNR between the two groups are significant (P < 0.05). The differences in imaging qualities between the two groups when subjectively assessed are not significant (P > 0.05). The 256-slice spiral CT combined with IMR and "Ultra-double-low" is feasible for the acute pulmonary embolism examination and the radiation dose and the volume of contrast agent can be greatly reduced.

Health Risk Assessment Based on Source Identification of Heavy Metal(loid)s: A Case Study of Surface Water in the Lijiang River, China.

In this study, 24 surface water samples were collected from the main trunk/tributary of the Lijiang River during the wet season (April) and the dry season (December) in 2021. The total concentration of 11 heavy metal(loid)s (Al, Cu, Pb, Zn, Cr, Ni, Co, Cd, Mn, As, and Hg) was determined to investigate their physicochemical properties and spatial-temporal distribution characteristics. The heavy metal evaluation index (HEI) and the positive matrix factorization (PMF) model were employed to evaluate water quality and to reveal quantitatively identified pollution sources for further investigation to obtain a health risk assessment using the hazard index (HI) and carcinogenic risk (CR) of various pollution sources. The mean concentrations of heavy metal(loid)s in surface water in the wet and dry seasons were ranked as: Al > Mn > Zn > Ni > Cd > Cr > Cu > As >Hg = Pb > Co, with the mean concentration of Hg being higher than the national Class II surface water environmental quality standard (GB3838-2002). In terms of time scale, the concentration of most heavy metal(loid)s was higher in the wet season; most heavy metal(loid)s were distributed mainly in the midstream area. HEI index indicated that the main water quality status was "slightly affected" in the study area. Five potential sources of pollution were obtained from the PMF model, including industrial activities, traffic sources, agricultural activities, domestic waste emissions, and natural resources. The source-oriented risk assessment indicated that the largest contributions of HI and CR were agricultural sources in the Lijiang River. This study provides a "target" for the precise control of pollution sources, which has a broad impact on improving the fine management of the water environment in the basin.

Spatial Distribution, Source Analysis and Health Risk Study of Heavy Metals in the Liujiang River Basin in Different Seasons.

Three high-frequency sampling and monitoring experiments were performed at the Lutang and Luowei transects of the Liujiang River entrance and at the southeast exit of the Liuzhou during 2019 for the purpose of assessing physico-chemical variables and human health hazards of water heavy metals in different rainfall processes. There were significant seasonal variations in concentrations of 11 heavy metals and most variables showed higher levels during the dry season. The distribution of heavy metals in the Liuzhou area varied significantly by region. Pollution source analysis indicated distinct seasons of wetness and dryness. The dry season is dominated by anthropogenic activities, while the wet season is dominated by natural processes. The results of hazard quotient (HQ) and carcinogenic risk (CR) analysis showed that the health risk of non-carcinogenic heavy metals in the wet season is slightly higher than that in the dry season. Seasonal changes in carcinogenic risk are the opposite; this is due to the combined influence of natural and human activities on the concentration of heavy metals in the river. Among them, Al was the most important pollutant causing non-carcinogenic, with As being a significant contributor to carcinogenic health risk. Spatially, the downstream Luowei transect has a high health risk in both the dry and rainy seasons, probably due to the fact that the Luowei transect is located within a major industrial area in the study area. There are some input points for industrial effluent discharge in the area. Therefore, high-frequency monitoring is essential to analyze and reduce the heavy metal concentrations in the Liujiang River during dry and wet seasons in order to protect the health of the residents in the area.

Synthesis of Surface-Functionalized Molybdenum Disulfide Nanomaterials for Efficient Adsorption and Deep Profiling of the Human Plasma Proteome by Data-Independent Acquisition.

Blood is one of the most important clinical samples for protein biomarker discovery, as it provides rich physiological and pathological information and is easy to obtain with low invasiveness. However, the discovery of protein biomarkers in the blood by mass spectrometry (MS)-based proteomic strategies has been shown to be highly challenging due to the particularly large concentration range of proteins and the strong interference by the high-abundant proteins in the blood. Therefore, developing sensitive methods for low-abundant biomarker protein identification is a key issue that has received great attention. Here, we report the synthesis and characterization of surface-functionalized magnetic molybdenum disulfide (MoS2) for the large-scale adsorption of low-abundant plasma proteins and deep profiling by MS. MoS2 nanomaterials resulted in the coverage of more than 3400 proteins (including a single-peptide hit) in a single LC-MS analysis without peptide prefractionation using pooled plasma samples, which were five times more than those obtained by the direct analysis of the plasma proteome. A detection limit in the low ng L-1 range was obtained, which is rare compared with previous reports.

Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: An Overview of Systematic Reviews.

Background: Hematopoietic stem cell transplantation (HSCT) has become the main treatment for acute myeloid leukemia (AML) and has been studied in many systematic reviews (SRs), but strong conclusions have not been drawn yet. Objective: This study aimed to summarize and critically evaluate the methodological and evidence quality of SRs and meta-analysis on this topic. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for SRs/meta-analyses regarding HSCT for AML. Two reviewers assessed the quality of SRs/meta-analyses in line with AMSTAR-2 and evaluated the strength of evidence quality with the grading of the evaluation system (GRADE) for concerned outcomes independently. Results: 12 SR/Meta articles were included, and the AMSTAR-2 scale showed that the quality grade of all articles was low or very low. GRADE results showed 29 outcomes, 2 of which were high, 12 were moderate, and 15 were low. Limitations and inconsistency were the most important factors leading to degradation, followed by imprecision and publication bias. Allo-SCT had better OS and DFS benefits than auto-SCT and significantly reduced the relapse in intermediate-risk AML/CR1 patients. Auto-SCT was associated with lower TRM than allo-SCT but generally had higher relapse. The results should be confirmed further for the low or moderate evidence quality. Conclusion: Current SRs show that allo-SCT in the treatment of AML might improve the OS, RFS, and DFS. Auto-SCT has significantly lower TRM but higher RR. Whether bone marrow transplantation is superior to nonmyeloablative chemotherapy remains to be evaluated. Meanwhile, the quality of methodology needs to be further improved. The intensity of evidence was uneven, and the high-quality evidence of outcomes was lacking. Considering the limitations of our overview, more rigorous and scientific studies are needed to fully explore the efficacy of different interventions of HSCT in AML, and clinicians should be more cautious in the treatment.

Epstein-Barr-virus-associated hepatitis with aplastic anemia: A case report.

BACKGROUND: Hepatitis-associated aplastic anemia (HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1-2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein-Barr virus (EBV)-associated HAAA is sparse. CASE SUMMARY: We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit anti-human thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response. CONCLUSION: Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.

CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy.

Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.

Mesenchymal stem cell derived exosomes-based immunological signature in a rat model of corneal allograft rejection therapy.

BACKGROUND: Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in corneal allograft rejection. In this study, we tested the effects of Mesenchymal stem cells derived exosomes in the corneal allograft rejection model. METHODS: Mesenchymal stem cells derived exosomes (MSC-exo) were collected and characterized. Wistar-Lewis rat corneal allograft rejection models were established. PKH26 labeled exosomes were used for track experiment. Models were randomly separated into four groups and treated with graded doses of exosomes or same volumn of PBS. Corneal grafts were assessed for rejection degree using slit-lamp biomicroscopy. Grafts were examined histologically using hematoxylin-eosin (H-E) staining and immunohistochemically using antibodies against CD4, CD8 and CD25. A comprehensive graft mRNA gene expression array analysis was conducted and checked by real-time polymerase chain reaction (PCR). RESULTS: The nanovesicles obtained were expressing exosome specific protein markers CD9, CD63, CD81. The labeled exosomes could be detected in both cornea and anterior chamber two hours after injection.The 10 µg exosomes subconjunctival injection can effectively prolong graft survival time (MST 16.3 ± 2.5 days). 10 µg exosomes-treated group can inhibit the infiltration of CD4+ and CD25+ T cells. IFN-γ and CXCL11 levels were significantly decreased in grafts obtained from postoperative exosomes-treated rats when compared with controls. CONCLUSIONS: MSC-exo can cross biological barrier and play better role directly towards target tissue. MSC-exo can effectively prolong grafts survival time. Th1 signaling pathway was significantly inhibited in the exosomes treated group.

Correlation between intraoperative and postoperative vaulting of the EVO implantable Collamer lens: a retrospective study of real-time observations of vaulting using the RESCAN 700 system.

BACKGROUND: Implantable Collamer lens (ICL) vaulting is one of the most important parameters for the safety, aqueous humor circulation, and lens transparency after ICL implantation. This study aimed to investigate the factors associated with the actual vaulting after refractive EVO-ICL surgery. METHODS: This retrospective study included patients who underwent EVO-ICL surgery at a tertiary eye hospital between October and December 2019. A RESCAN 700 was used for the intraoperative and CIRRUS HD-OCT was used for postoperative observation of vaulting. Subjective and objective refractions, anterior ocular segment, corneal morphology, intraocular pressure (IOP), anterior chamber volume (ACV), crystalline lens rise (CLR), white-to-white distance (WTW), anterior chamber depth (ACD), axial length, corneal endothelial cell density (ECD), and fundoscopy were examined. A multivariable analysis was performed to determine the factors independently associated with 1-month postoperative vaulting. RESULTS: Fifty-one patients (102 eyes) were included. Compared with the eyes with normal vaulting, those with high vaulting had higher preoperative diopter values (P = 0.039), lower preoperative corrected visual acuity (P = 0.006), lower preoperative IOP (P = 0.029), higher preoperative ACD (P = 0.004), lower preoperative CLR (P = 0.046), higher ICL spherical equivalent (P = 0.030), higher intraoperative vaulting (P < 0.001), and lower IOP at 1 month (P = 0.045). The multivariable analysis showed that the only factor independently associated with high vaulting at 1 month after surgery was the intraoperative vaulting value (odds ratio = 1.005, 95% confidence interval: 1.002-1.007, P < 0.001). The intraoperative and 1-month postoperative vaulting values were positively correlated (R2 = 0.562). CONCLUSIONS: The RESCAN700 system can be used to perform intraoperative optical coherence tomography to predict the vaulting value of ICL at 1 month.

Combined Developmental Toxicity of the Pesticides Difenoconazole and Dimethomorph on Embryonic Zebrafish.

Difenoconazole (DIF) and dimethomorph (DIM) are widely used pesticides frequently detected together in environmental samples, so the deleterious effects of combined exposure warrant detailed examination. In this study, the individual and combined effects of DIM and DIF on conventional developmental parameters (hatching rate, deformity rate, lethality) and gene expression were measured in embryonic zebrafish. Both DIF and DIM interfered with normal zebrafish embryo development, and the most sensitive toxicity index for both was 96 h post-fertilization (hpf) deformity rate (BMDL10 values of 0.30 and 1.10 mg/L, respectively). The combination of DIF and DIM had mainly synergistic deleterious effects on 96 hpf deformity and mortality rates. Transcriptome analysis showed that these compounds markedly downregulated expression of mcm family genes, cdk1, and cdc20, thereby potentially disrupting DNA replication and cell cycle progression. Enhanced surveillance for this pesticide combination is recommended as simultaneous environmental exposure may be substantially more harmful than exposure to either compound alone.