Improvement of the YOLOv8 Model in the Optimization of the Weed Recognition Algorithm in Cotton Field.

Due to the existence of cotton weeds in a complex cotton field environment with many different species, dense distribution, partial occlusion, and small target phenomena, the use of the YOLO algorithm is prone to problems such as low detection accuracy, serious misdetection, etc. In this study, we propose a YOLOv8-DMAS model for the detection of cotton weeds in complex environments based on the YOLOv8 detection algorithm. To enhance the ability of the model to capture multi-scale features of different weeds, all the BottleNeck are replaced by the Dilation-wise Residual Module (DWR) in the C2f network, and the Multi-Scale module (MSBlock) is added in the last layer of the backbone. Additionally, a small-target detection layer is added to the head structure to avoid the omission of small-target weed detection, and the Adaptively Spatial Feature Fusion mechanism (ASFF) is used to improve the detection head to solve the spatial inconsistency problem of feature fusion. Finally, the original Non-maximum suppression (NMS) method is replaced with SoftNMS to improve the accuracy under dense weed detection. In comparison to YOLO v8s, the experimental results show that the improved YOLOv8-DMAS improves accuracy, recall, mAP0.5, and mAP0.5:0.95 by 1.7%, 3.8%, 2.1%, and 3.7%, respectively. Furthermore, compared to the mature target detection algorithms YOLOv5s, YOLOv7, and SSD, it improves 4.8%, 4.5%, and 5.9% on mAP0.5:0.95, respectively. The results show that the improved model could accurately detect cotton weeds in complex field environments in real time and provide technical support for intelligent weeding research.

FUNDC1 alleviates doxorubicin-induced cardiotoxicity by restoring mitochondrial-endoplasmic reticulum contacts and blocked autophagic flux.

Rationale: Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC. Methods: We employed confocal microscopy and transmission electron microscopy to assess MERCs structure. Autophagic flux was analyzed using the mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. Mitophagy was studied through the mCherry-EGFP-FIS1 fluorescence assay and colocalization analysis between LC3B and mitochondria. A total dose of 18 mg/kg of doxorubicin was administrated in mice to construct a DIC model in vivo. Additionally, we used adeno-associated virus (AAV) to cardiac-specifically overexpress FUNDC1. Cardiac function and remodeling were evaluated by echocardiography and Masson's trichrome staining, respectively. Results: DOX blocked autophagic flux by inhibiting autophagosome biogenesis, which could be attributed to the downregulation of FUNDC1 and disruption of MERCs structures. FUNDC1 overexpression restored the blocked autophagosome biogenesis by maintaining MERCs structure and facilitating ATG5-ATG12/ATG16L1 complex formation without altering mitophagy. Furthermore, FUNDC1 alleviated DOX-induced oxidative stress and cardiomyocytes deaths in an autophagy-dependent manner. Notably, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. Conclusions: In summary, our study identified that FUNDC1-meditated MERCs exerted a cardioprotective effect against DIC by restoring the blocked autophagosome biogenesis. Importantly, this research reveals a novel role of FUNDC1 in enhancing macroautophagy via restoring MERCs structure and autophagosome biogenesis in the DIC model, beyond its previously known regulatory role as an mitophagy receptor.

ABO incompatibility haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit for severe aplastic anemia patients.

Objective: To observe the efficacy of haploidentcial peripheral blood stem cell transplantation combined with a single unrelated cord blood unit for severe aplastic anemia patients with donor-recipient ABO incompatibility. Methods: This was a retrospective cohort study and data of 57 severe aplastic anemia patients underwent haploidentical stem cell transplantation from August 1, 2018 to February 28, 2022 in the First Affiliated Hospital of Xi'an Jiaotong University was retrospectively analyzed. All patients were divided into two groups, the donor-recipient ABO matched group (bone marrow+peripheral blood group) using haploidentical bone marrow and peripheral blood stem cells as grafts, and donor-recipient ABO mismatched group (cord blood+peripheral blood group), using unrelated cord blood and haploidentical peripheral blood stem cells as grafts. The differences of hematopoietic reconstitution, acute and chronic graft-versus-host disease, Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, and overall survival between the two groups were compared. Results: There were 30 cases in cord blood+peripheral blood group and 27 cases in bone marrow+peripheral blood group. One patient in bone marrow+peripheral blood group had primary graft failure, while other patients were successfully implanted. There were no significant differences of neutrophil and platelet recovery rates between two groups. The erythrocyte recovery time of cord blood+peripheral blood group was slower than that of bone marrow+peripheral blood group (p < 0.05). There was no significant difference of the incidence of graft-versus-host disease, CMV, EB virus infection and post-transplant lymphoproliferative disorders between two groups (p > 0.05). The incidence of grade III-IV acute graft-versus-host disease in cord blood+peripheral blood group was higher than that of bone marrow+peripheral blood group (p < 0.05). The incidence of intestinal graft-versus-host disease was higher in minor ABO-mismatched transplantation than that in major ABO-mismatched transplantation (p < 0.05). There was no significant difference of overall survival between two groups (p > 0.05). Conclusion: These findings suggest that haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit may be an alternative option for severe aplastic anemia patients with donor-recipient ABO incompatibility.

Adverse events reporting of XPO1 inhibitor - selinexor: a real-word analysis from FAERS database.

As the world's first oral nuclear export inhibitor, selinexor is increasingly being used in clinical applications for malignant tumors. However, there is no extensive exploration on selinexor's adverse events (ADEs), necessitating a real-word assessment of its clinical medication safety. FAERS data (July 2019-June 2023) were searched for selinexor ADE reports across all indications. Use the system organ class (SOC) and preferred terms (PT) from the medical dictionary for regulatory activities (MedDRA) to describe, categorize, and statistic ADEs. Disproportionality analysis was employed through calculation of reporting odds ratio (ROR) and proportional reporting ratio (PRR). Based on total of 4392 selinexor related ADE reports as the primary suspect (PS), of which 2595 instances were severe outcomes. The predominant ADEs included gastrointestinal disorders, myelosuppression symptoms, and various nonspecific manifestations. 124 signals associated with selinexor ADE were detected, and 10 of these top 15 signals were not included into the instructions. Our study provides real-world evidence regarding the drug safety of selinexor, which is crucial for clinicians to safeguard patients' health.

TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA.

When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)-a protein that binds mitochondrial DNA (mtDNA)-helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM's LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Glutathione-depleting Liposome Adjuvant for Augmenting the Efficacy of a Glutathione Covalent Inhibitor Oridonin for Acute Myeloid Leukemia Therapy.

BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

Hydraulic vulnerability difference between branches and roots increases with environmental aridity.

The vulnerability of plant xylem to embolism can be described as the water potential at which xylem conductivity is lost by 50% (P50). According to the traditional hypothesis of hydraulic vulnerability segmentation, the difference in vulnerability to embolism between branches and roots is positive (P50 root-branch > 0). It is not clear whether this occurs broadly across species or how segmentation might vary across aridity gradients. We compiled hydraulic and anatomical datasets from branches and roots across 104 woody species (including new measurements from 10 species) in four biomes to investigate the relationships between P50 root-branch and environmental factors associated with aridity. We found a positive P50 root-branch relationship across species, and evidence that P50 root-branch increases with aridity. Branch xylem hydraulic conductivity transitioned from more efficient (e.g., wider conduit, higher hydraulic conductivity) to safer (e.g., narrower conduit, more negative P50) in response to the increase of aridity, while root xylem hydraulic conductivity remained unchanged across aridity gradients. Our results demonstrate that the hydraulic vulnerability difference between branches and roots is more positive in species from arid regions, largely driven by modifications to branch traits.

Serum Albumin-to-Creatinine Ratio: A Novel Predictor of Pulmonary Infection in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

AIM: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), a low serum albumin-to-creatinine ratio (sACR) is associated with elevated risk of poor short- and long-term outcomes. However, the relationship between sACR and pulmonary infection during hospitalization in patients with STEMI undergoing PCI remains unclear. METHODS: A total of 4,507 patients with STEMI undergoing PCI were enrolled and divided into three groups according to sACR tertile. The primary outcome was pulmonary infection during hospitalization, and the secondary outcome was in-hospital major adverse cardiovascular events (MACE) including stroke, in-hospital mortality, target vessel revascularization, recurrent myocardial infarction, and all-cause mortality during follow-up. RESULTS: Overall, 522 (11.6%) patients developed pulmonary infections, and 223 (4.9%) patients developed in-hospital MACE. Cubic spline models indicated a non-linear, L-shaped relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis indicated that sACR had good predictive value for both pulmonary infection (area under the ROC curve [AUC]=0.73, 95% CI=0.70-0.75, P＜0.001) and in-hospital MACE (AUC=0.72, 95% CI=0.69-0.76, P＜0.001). Kaplan-Meier survival analysis indicated that higher sACR tertiles were associated with a greater cumulative survival rate (P＜0.001). Cox regression analysis identified lower sACR as an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI=0.95-0.98, P＜0.001). CONCLUSIONS: A low sACR was significantly associated with elevated risk of pulmonary infection and MACE during hospitalization, as well as all-cause mortality during follow-up among patients with STEMI undergoing PCI. These findings highlighted sACR as an important prognostic marker in this patient population.

Evaluation of bidirectional causal association between cardiovascular diseases and pneumonia: A Mendelian randomization study.

AIMS: Observational evidence suggests a bidirectional relationship between cardiovascular diseases (CVDs) and pneumonia. However, the causality between CVDs and pneumonia remains undetermined. Thus, we aimed to investigate the bidirectional causality between CVDs and pneumonia using Mendelian randomization (MR) analysis. METHODS: Global genetic correlation analysis and bidirectional two-sample MR analysis were performed to infer the genetic correlation and causality between CVDs and pneumonia by using genome-wide association study (GWAS) summary data from GWAS meta-analysis study, FinnGen or UK Biobank consortium. Post-hoc power calculation was conducted to assess the power for detecting the causality. RESULTS: The linkage disequilibrium score regression analysis suggested a positive significant genetic correlation between CVDs and pneumonia. In the MR analysis, only genetically predicted ischemic stroke was causally associated with any pneumonia (odds ratio [OR]: 1.119, 95% confidence interval [CI]: 1.031-1.393), bacterial pneumonia (OR: 1.251, 95% CI: 1.032-1.516), and pneumococcal pneumonia (OR: 1.308, 95% CI: 1.093-1.565), but the causality was attenuated to non-significance after adjusting for deep venous thrombosis. However, the causal effects of pneumonia on CVDs were not detected. Post-hoc power calculations supported strong power (more than 80%) to detect the causality. CONCLUSIONS: Ischemic stroke is causally associated with an increased risk of pneumonia, but there is no evidence for the causal effect of pneumonia on CVDs. Our findings have important implications as they provide further support for the thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischemic stroke.

This Mendelian randomization analysis aimed to investigate the bidirectional causality between cardiovascular diseases and pneumonia. Our findings support the causal association of ischemic stroke on pneumonia, but indicate no evidence for the causal effects of pneumonia on cardiovascular diseases. The causal association of ischemic stroke on pneumonia was revealed to rely on deep venous thrombosis, which provided further support for the thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischemic stroke.

Histone-modifying enzymes: Roles in odontogenesis and beyond.

OBJECTIVES: Odontogenesis, an intricate process initiated by epithelium-mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic modifications, especially histone modification, have been found to exhibit spatiotemporal specificity during tooth development. However, the expression patterns and roles of enzymes associated with histone modifications have yet to be systematically explored in odontogenesis. This review aims to summarize the histone-modifying enzymes in odontogenesis and their regulation mechanism during tooth development and provide the potential theoretical basis for the clinical management and intervention of dental developmental diseases. SUBJECTS AND METHODS: This study conducted a systematic search across PubMed and Web of Science databases, utilizing the keywords "odontogenesis," "histone modification," and "enzyme" for pertinent articles. RESULTS: No doubt histone modification contributes extensively to odontogenesis regulation, and the disturbances in histone modifications can derange the odontogenesis process. CONCLUSION: Further studies are warranted to elucidate these roles and their potential downstream effects, positioning histone modifications as a pivotal focal point for unraveling the intricacies of tooth development and regeneration.

Ticagrelor alleviates pyroptosis of myocardial ischemia reperfusion-induced acute lung injury in rats: a preliminary study.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1ß levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.

Vein hierarchy mediates the 2D relationship between leaf size and drought tolerance across subtropical forest tree species.

Previous studies have observed a 2D relationship (i.e. decoupled correlation) between leaf size (LS) and leaf economics as well as a tight correlation between leaf economics and drought tolerance. However, the underlying mechanism maintaining the relationship between LS and drought tolerance remains largely unknown. Here, we measured LS, water potential at 50% loss of hydraulic conductance, hydraulic safety margin and different orders of vein traits across 28 tree species in a subtropical forest in Southern China. We found that LS and drought tolerance were in two independent dimensions (R2 = 0.00, P > 0.05). Primary and secondary vein traits (i.e. vein diameter and density) explained the variation of LS, with R2 ranging from 0.37 to 0.70 (all Ps < 0.01), while minor vein traits accounted for the variation of leaf drought tolerance, with R2 ranging from 0.30 to 0.43 (all Ps < 0.01). Our results provide insight into the 2D relationship between LS and drought tolerance and highlight the importance of vein hierarchy in plant leaf functioning.

Multi-omics analysis reveals interferon-stimulated gene OAS1 as a prognostic and immunological biomarker in pan-cancer.

Introduction: OAS1(2'-5'-oligoadenylate synthetase 1) is a member of the Interferon-Stimulated Genes which plays an important role in the antiviral process. In recent years, the role of OAS1 in tumors has attracted attention, and it was found to be associated with prognosis in several tumors. However, the mechanism by which OAS1 affects tumors is unclear and pan-cancer study of OAS1 is necessary to better understand its implication in cancers. Methods: The expression, prognostic value, genetic alteration, alternative splicing events of OAS1 in pan-cancers were analyzed using TCGA, GTEx, HPA, GEPIA and OncoSplicing databases. OAS1 associated immune cell infiltration was evaluated using the ESTIMATE, xCell, CIBERSORT and QUANTISEQ algorithm. Single cell transcriptome data download using TISH database. Finally, the roles of the OAS1 on apoptosis, migration and invasion were investigated in two pancreatic cancer cells. Results: Our results revealed significant differences in OAS1 expression among various tumors, which had prognostic implications. In addition, we investigated the impact of OAS1 on genomic stability, methylation status, and other factors across different types of cancer, and the effects of these factors on prognosis. Notably, our study also demonstrated that OAS1 overexpression can contribute to CTL dysfunction and macrophage M2 polarization. In addition, cell experiments showed that the knockdown of OAS1 could reduce the invasive ability and increased the apoptosis rate of PAAD cells. Discussion: These results confirmed that OAS1 could be a prognostic biomarker and therapeutic target for its potential role in CTL dysfunction and macrophage M2 polarization.

Association between admission-blood-glucose-to-albumin ratio and clinical outcomes in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

Introduction: It is unclear whether admission-blood-glucose-to-albumin ratio (AAR) predicts adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with percutaneous coronary intervention (PCI). Here, we performed a observational study to explore the predictive value of AAR on clinical outcomes. Methods: Patients diagnosed with STEMI who underwent PCI between January 2010 and February 2020 were enrolled in the study. The patients were classified into three groups according to AAR tertile. The primary outcome was in-hospital all-cause mortality, and the secondary outcomes were in-hospital major adverse cardiac events (MACEs), as well as all-cause mortality and MACEs during follow-up. Logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression were the primary analyses used to estimate outcomes. Results: Among the 3,224 enrolled patients, there were 130 cases of in-hospital all-cause mortality (3.9%) and 181 patients (5.4%) experienced MACEs. After adjustment for covariates, multivariate analysis demonstrated that an increase in AAR was associated with an increased risk of in-hospital all-cause mortality [adjusted odds ratio (OR): 2.72, 95% CI: 1.47-5.03, P = 0.001] and MACEs (adjusted OR: 1.91, 95% CI: 1.18-3.10, P = 0.009), as well as long-term all-cause mortality [adjusted hazard ratio (HR): 1.64, 95% CI: 1.19-2.28, P = 0.003] and MACEs (adjusted HR: 1.58, 95% CI: 1.16-2.14, P = 0.003). Receiver operating characteristic (ROC) curve analysis indicated that AAR was an accurate predictor of in-hospital all-cause mortality (AUC = 0.718, 95% CI: 0.675-0.761) and MACEs (AUC = 0.672, 95% CI: 0.631-0.712). Discussion: AAR is a novel and convenient independent predictor of all-cause mortality and MACEs, both in-hospital and long-term, for STEMI patients receiving PCI.

Prognostic Potential of Pulmonary Hypertension in Patients with Hematologic Malignancy.

INTRODUCTION: Cardiovascular diseases present a great burden for survivors of hematologic malignancy (HM). However, the effect of pulmonary hypertension (PH) on the clinical outcome of patients with HM remains unknown. This study aims to evaluate the prognostic potential of PH in patients with HM and explore the related clinical determinants. METHODS: This retrospective study included 220 patients with HM and PH and 220 controls without PH, the case-matching cohort analysis was performed based on age, sex, the year of diagnosis and disease type. The baseline characteristics and overall survival (OS) of the patients with HM with or without PH were compared. The cumulative overall survival was analyzed using the Kaplan-Meier curves and the log-rank test. Multivariate Cox proportional hazard models were conducted to identify the predictors of OS. RESULTS: PH was found in 11.98% (302/2520) of the patients with HM. The PH group had lower levels of hemoglobin, platelet, albumin, fibrinogen and B cell count; whereas the levels of lactate dehydrogenase, N terminal pro B type natriuretic peptide, D-dimer, fibrinogen degradation products and C-reactive protein were higher. Additionally, the PH group had a higher prevalence of atrial fibrillation. Survival analysis revealed that the PH group had an inferior OS compared to the non-PH group (16.9 vs. 37.6 months, p = 0.002). Further subgroup analysis revealed that the severe PH group had the worst OS, followed by the moderate and the mild PH groups (8.7 vs. 14.7 vs. 23.7 months, p < 0.001). Multivariate analysis showed that PH was an independent predictor for unfavorable clinical outcomes. CONCLUSIONS: Coexisting PH was associated with inferior clinical outcomes in patients with HM, and the severe PH group had the worst prognosis. The study may provide additional risk stratification for patients with HM.

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis.

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation. The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes, which is involved in atherogenesis.

High levels of NK Cells in graft are associated with reduced febrile neutropenia after haploidentical peripheral blood stem cell transplantation.

OBJECTIVE: To investigate the impact of natural killer (NK) cells in the graft on the outcome following haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). METHODS: We retrospectively collected data from patients who had undergone haplo-PBSCT at our centre from January 2019 to November 2021. The percentage of NK cells in stem cell grafts was detected by flow cytometry. Based on the median (range) count of NK cells (1.8 [0.4-6.0] × 108/kg), patients were separated into high and low NK cell count groups. RESULTS: Data from 96 patients were analysed. Patients were evenly distributed (48 in each group) into high and low NK cell count groups. There was no significant difference in neutrophil and platelet recovery between the two groups. However, the rates of febrile neutropenia, bacterial infection, and invasive fungal disease (IFD) were significantly reduced in the high compared with the low NK cell count group. There was no significant difference in rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections between groups. There was no significant difference between groups in grades II and above acute graft versus host disease (GVHD), progression-free survival (PFS), or overall survival (OS). CONCLUSION: A high number of NK cells in the graft may reduce febrile neutropenia, IFD and bacterial infection following haplo-PBSCT but it has no significant effect on aGVHD, PFS, or OS.