Realizing Sunlight-Induced Efficiently Dynamic Infrared Emissivity Modulation Based on Aluminum-Doped zinc Oxide Nanocrystals.

Dynamic manipulation of an object's infrared radiation characteristics is a burgeoning technology with significant implications for energy and information fields. However, exploring efficient stimulus-spectral response mechanism and realizing simple device structures remains a formidable challenge. Here, a novel dynamic infrared emissivity regulation mechanism is proposed by controlling the localized surface plasmon resonance absorption of aluminum-doped zinc oxide (AZO) nanocrystals through ultraviolet photocharging/oxidative discharging. A straightforward device architecture that integrates an AZO nanocrystal film with an infrared reflective layer and a substrate, functioning as a photo-induced dynamic infrared emissivity modulator, which can be triggered by weak ultraviolet light in sunlight, is engineered. The modulator exhibits emissivity regulation amount of 0.72 and 0.61 in the 3-5 and 8-13 µm ranges, respectively. Furthermore, the modulator demonstrates efficient light triggering characteristic, broad spectral range, angular-independent emissivity, and long cyclic lifespan. The modulator allows for self-adaptive daytime radiative cooling and nighttime heating depending on the ultraviolet light in sunlight and O2 in air, thereby achieving smart thermal management for buildings with zero-energy expenditure. Moreover, the potential applications of this modulator can extend to rewritable infrared displays and deceptive infrared camouflage.

PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer.

Phosphoglycerate mutase 1 (PGAM1) is a key node enzyme that diverts the metabolic reactions from glycolysis into its shunts to support macromolecule biosynthesis for rapid and sustainable cell proliferation. It is prevalent that PGAM1 activity is upregulated in various tumors; however, the underlying mechanism remains unclear. Here, we unveil that pyruvate kinase M2 (PKM2) moonlights as a histidine kinase in a phosphoenolpyruvate (PEP)-dependent manner to catalyze PGAM1 H11 phosphorylation, that is essential for PGAM1 activity. Moreover, monomeric and dimeric but not tetrameric PKM2 are efficient to phosphorylate and activate PGAM1. In response to epidermal growth factor signaling, Src-catalyzed PGAM1 Y119 phosphorylation is a prerequisite for PKM2 binding and the subsequent PGAM1 H11 phosphorylation, which constitutes a discrepancy between tumor and normal cells. A PGAM1-derived pY119-containing cell-permeable peptide or Y119 mutation disrupts the interaction of PGAM1 with PKM2 and PGAM1 H11 phosphorylation, dampening the glycolysis shunts and tumor growth. Together, these results identify a function of PKM2 as a histidine kinase, and illustrate the importance of enzyme crosstalk as a regulatory mode during metabolic reprogramming and tumorigenesis.

Characterization of the biological and transcriptomic landscapes of bone marrow-derived mesenchymal stem cells in patients with multiple myeloma.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) have been acknowledged as the most important stromal cells in the bone marrow (BM) microenvironment for physiologic hematopoiesis and the concomitant hematologic malignancies. However, the systematic and detailed dissection of the biological and transcriptomic signatures of BM-MSCs in multiple myeloma (MM) are largely unknown. METHODS: In this study, we isolated and identified BM-MSCs from 10 primary MM patients and 10 healthy donors (HD). On the one hand, we compared the multifaceted biological characteristics of the indicated two BM-MSCs, including biomarker expression pattern, multilineage differentiation potential, stemness and karyotyping, together with the cellular vitality and immunosuppressive property. On the other hand, we took advantage of RNA-SEQ and bioinformatics analysis to verify the similarities and differences at the transcriptomic level between MM-MSCs and HD-MSCs. RESULTS: As to biological phenotypes and biofunctions, MM-MSCs revealed conservation in immunophenotype, stemness and differentiation towards adipocytes and chondrocytes with HD-MSCs, whereas with impaired osteogenic differentiation potential, cellular vitality and immunosuppressive property. As to transcriptomic properties, MM-MSCs revealed multidimensional alterations in gene expression profiling and genetic variations. CONCLUSIONS: Overall, our date systematic and detailed reflected the multifaceted similarities and variations between MM-MSCs and HD-MSCs both at the cellular and molecular levels, and in particular, the alterations of immunomodulation and cellular viability of MM-MSCs, which wound benefit the further exploration of the pathogenesis and new drug application (NDA) of multiple myeloma from the view of BM-MSCs.

Knowledge Graph for Breast Cancer Prevention and Treatment: Literature-Based Data Analysis Study.

Background: The incidence of breast cancer has remained high and continues to rise since the 21st century. Consequently, there has been a significant increase in research efforts focused on breast cancer prevention and treatment. Despite the extensive body of literature available on this subject, systematic integration is lacking. To address this issue, knowledge graphs have emerged as a valuable tool. By harnessing their powerful knowledge integration capabilities, knowledge graphs offer a comprehensive and structured approach to understanding breast cancer prevention and treatment. Objective: We aim to integrate literature data on breast cancer treatment and prevention, build a knowledge graph, and provide support for clinical decision-making. Methods: We used Medical Subject Headings terms to search for clinical trial literature on breast cancer prevention and treatment published on PubMed between 2018 and 2022. We downloaded triplet data from the Semantic MEDLINE Database (SemMedDB) and matched them with the retrieved literature to obtain triplet data for the target articles. We visualized the triplet information using NetworkX for knowledge discovery. Results: Within the scope of literature research in the past 5 years, malignant neoplasms appeared most frequently (587/1387, 42.3%). Pharmacotherapy (267/1387, 19.3%) was the primary treatment method, with trastuzumab (209/1805, 11.6%) being the most commonly used therapeutic drug. Through the analysis of the knowledge graph, we have discovered a complex network of relationships between treatment methods, therapeutic drugs, and preventive measures for different types of breast cancer. Conclusions: This study constructed a knowledge graph for breast cancer prevention and treatment, which enabled the integration and knowledge discovery of relevant literature in the past 5 years. Researchers can gain insights into treatment methods, drugs, preventive knowledge regarding adverse reactions to treatment, and the associations between different knowledge domains from the graph.

Cysteine and homocysteine can be exploited by GPX4 in ferroptosis inhibition independent of GSH synthesis.

Ferroptosis is inhibited by glutathione peroxidase 4 (GPX4), an antioxidant enzyme that uses reduced glutathione (GSH) as a cofactor to detoxify lipid hydroperoxides. As a selenoprotein, the core function of GPX4 is the thiol-dependent redox reaction. In addition to GSH, other small molecules such as cysteine and homocysteine also contain thiols; yet, whether GPX4 can exploit cysteine and homocysteine to directly detoxify lipid hydroperoxides and inhibit ferroptosis has not been addressed. In this study, we found that cysteine and homocysteine inhibit ferroptosis in a GPX4-dependent manner. However, cysteine inhibits ferroptosis independent of GSH synthesis, and homocysteine inhibits ferroptosis through non-cysteine and non-GSH pathway. Furthermore, we used molecular docking and GPX4 activity analysis to study the binding patterns and affinity between GPX4 and GSH, cysteine, and homocysteine. We found that besides GSH, cysteine and homocysteine are also able to serve as substrates for GPX4 though the affinities of GPX4 with cysteine and homocysteine are lower than that with GSH. Importantly, GPX family and the GSH synthetase pathway might be asynchronously evolved. When GSH synthetase is absent, for example in Flexibacter, the fGPX exhibits higher affinity with cysteine and homocysteine than GSH. Taken together, the present study provided the understanding of the role of thiol-dependent redox systems in protecting cells from ferroptosis and propose that GSH might be a substitute for cysteine or homocysteine to be used as a cofactor for GPX4 during the evolution of aerobic metabolism.

Impact of perioperative red blood cell transfusion on the prognosis of patients with epithelial ovarian cancer.

Background: Surgery for advanced ovarian cancer tends to be extensive. We performed an analysis to determine whether perioperative red blood cell transfusion (PRBCT) is associated with a poor prognosis in women with epithelial ovarian cancer (EOC). Methods: Our retrospective analysis included 314 women. The Mann-Whitney rank-sum test and chi-square test were used to analyze the clinical characteristics of the PRBCT and non-PRBCT groups, and Cox proportional hazard models were used for the multivariate analysis. Results: PRBCT was associated with higher relapse and mortality rates in 121 (38.54 %) patients. After multivariate analysis, transfused patients were 1.59 times at risk of death (hazard ratio [HR] = 1.59; 95%CI, 1.12-2.25) and 1.63 times at risk of recurrence (HR = 1.63; 95%CI, 1.22-2.18) than non-transfused patients. Conclusions: PRBCT could prolong hospital stay, and increased hospital costs were significantly associated with increased cancer recurrence and overall mortality in patients with EOC.

Comparison of different predictive biomarker testing assays for PD-1/PD-L1 checkpoint inhibitors response: a systematic review and network meta-analysis.

Background: Accurate prediction of efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors is of critical importance. To address this issue, a network meta-analysis (NMA) comparing existing common measurements for curative effect of PD-1/PD-L1 monotherapy was conducted. Methods: We searched PubMed, Embase, the Cochrane Library database, and relevant clinical trials to find out studies published before Feb 22, 2023 that use PD-L1 immunohistochemistry (IHC), tumor mutational burden (TMB), gene expression profiling (GEP), microsatellite instability (MSI), multiplex IHC/immunofluorescence (mIHC/IF), other immunohistochemistry and hematoxylin-eosin staining (other IHC&HE) and combined assays to determine objective response rates to anti-PD-1/PD-L1 monotherapy. Study-level data were extracted from the published studies. The primary goal of this study was to evaluate the predictive efficacy and rank these assays mainly by NMA, and the second objective was to compare them in subgroup analyses. Heterogeneity, quality assessment, and result validation were also conducted by meta-analysis. Findings: 144 diagnostic index tests in 49 studies covering 5322 patients were eligible for inclusion. mIHC/IF exhibited highest sensitivity (0.76, 95% CI: 0.57-0.89), the second diagnostic odds ratio (DOR) (5.09, 95% CI: 1.35-13.90), and the second superiority index (2.86). MSI had highest specificity (0.90, 95% CI: 0.85-0.94), and DOR (6.79, 95% CI: 3.48-11.91), especially in gastrointestinal tumors. Subgroup analyses by tumor types found that mIHC/IF, and other IHC&HE demonstrated high predictive efficacy for non-small cell lung cancer (NSCLC), while PD-L1 IHC and MSI were highly efficacious in predicting the effectiveness in gastrointestinal tumors. When PD-L1 IHC was combined with TMB, the sensitivity (0.89, 95% CI: 0.82-0.94) was noticeably improved revealed by meta-analysis in all studies. Interpretation: Considering statistical results of NMA and clinical applicability, mIHC/IF appeared to have superior performance in predicting response to anti PD-1/PD-L1 therapy. Combined assays could further improve the predictive efficacy. Prospective clinical trials involving a wider range of tumor types are needed to establish a definitive gold standard in future.

Factors associated with reproductive concerns among young female patients with colorectal cancer: A cross-sectional study.

AIMS AND OBJECTIVES: The aim of this study was to describe the prevalence of reproductive concerns among young female patients with colorectal cancer and explore the associated factors. BACKGROUND: With the trend of longer survival and younger age at diagnosis of colorectal cancer patients, reproductive concerns have become increasingly prevalent among young female colorectal cancer patients. DESIGN: Cross-sectional design. METHODS: The study included 150 young female patients with colorectal cancer who completed cancer treatment at 2 hospitals in Guangzhou, China, between November 2020 and December 2021 completed an investigation comprising A general questionnaire, The Reproductive Concerns After Cancer scale, The Family Adaptation and Cohesion Evaluation Scale II and unmet fertility information needs questionnaire. Multivariable linear regression analysis was performed in order to identify factors that influence reproductive concerns. This study was prepared and is reported according to the STROBE checklist. RESULTS: The mean (SD) score on the Reproductive Concerns After Cancer scale was 54.78 ± 8.97. The highest score was for the children's health subscale (3.84 ± .92) and the lowest was for acceptance (2.24 ± .70). Multiple regression analysis showed that patients with fewer children, female children, lower education level (less than undergraduate degree), earlier disease stage, lower family function and higher unmet need for fertility information had more reproductive concerns, which explained 26.9% of the total variation of the model. CONCLUSIONS: The patients with fewer children, female children, low cultural degree (less than bachelor), early clinical patients, poorer family function and higher unmet fertility information needs had higher reproductive concerns. RELEVANCE TO CLINICAL PRACTICE: These findings can guide the development of interventions to mitigate reproductive concerns, including understand and meet their fertility information needs, improve the level of family function. PATIENT OR PUBLIC CONTRIBUTION: Survey questionnaires were completed by participants among young female with colorectal cancer in this study.

Fatalism and metaphor in Confucianism: A qualitative study of barriers to genetic testing among first-degree relatives of hereditary cancer patients from China.

OBJECTIVE: Despite the benefits, the rate of genetic testing among first-degree relatives (FDRs; parents, children, and siblings) remains low, and the barriers to undergoing testing among FDRs in China are not clear. We explored the reasons why FDRs refused genetic testing. METHODS: Semi-structured face-to-face interviews were conducted with 22 patients and 27 FDRs. Participants were recruited at an urban tertiary hospital in Guangzhou, South China. We used qualitative content analysis to analyse the transcripts of audio recordings and identify major themes and subthemes. RESULTS: Three major themes emerged related to FDRs' low rate of participation in genetic testing. First, there is cognitive distance from genetic testing/cancer and a lack of knowledge of preventive medicine that deepens the 'fatalistic' attitude towards cancer among FDRs, which leads to an enormous gap between their knowledge and understanding of genetic testing. Second, medical consultation is not valued in Confucianism, and the view of cancer as 'bad news' and the risk of cancer as a curse makes cancer a metaphor, which leads to exhausting arguments when persuading FDRs to undergo genetic testing. Third, physical distance from the hospital, loss of privacy, possible discrimination in many social activities and genetic testing as a source of stress and anxiety lead FDRs to fear the disruption of their daily lives. CONCLUSIONS: There are many barriers to genetic testing among the FDRs of hereditary cancer patients originating from the national social and cultural context. Healthcare professionals should develop interventions rooted in culture and promote cancer risk communication between hereditary cancer patients and FDRs.

The Benefits of Local Anesthesia Used in Mastectomy Without Reconstruction.

BACKGROUND: The opioid epidemic has driven renewed interest in local anesthesia to reduce postoperative opioid use. Our objective was to determine if local anesthesia decreased hospital pain scores, oral morphine equivalents (OME), length of stay (LOS), and nausea/vomiting. METHODS: Single institution retrospective study of females who underwent mastectomy without reconstruction. RESULTS: Overall, 712 patients were included; 63 (8.8%) received bupivacaine (B), 512 (72%) liposomal bupivacaine (LB), and 137 (19%) no local. 95% were discharged on POD1. Liposomal bupivacaine use increased from 2014 to 2019. Additional factors associated with use of local regimen were surgeon and extent of axillary surgery. Fewer patients used postop opioids during their hospital stay if any local was used compared to none (76 vs 88%; 0.003). Compared to none, local had shorter mean PACU LOS (95 vs 87 min; P = .02), lower mean intraoperative-OME (96 vs 106; P < .001), and lower mean postoperative OME/hr (1.4 vs 1.8 P = .001). Multivariable analysis (MVA) showed lower OME/hr with LB compared to B and none (P = .002); this translates to 22 mg and 30 mg of oxycodone in a 24-hr period, respectively. MVA showed lower POD1 pain scores with LB relative to none (P = .049). Local did not impact nausea/emesis. CONCLUSION: Local anesthesia was superior to no local in several measures. However, a consistent benefit of a specific local anesthetic agent was not demonstrated (LB vs B). A prospective study is warranted to determine the optimal local regimen for this cohort and further inform clinical relevance.

Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions.

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are splendid cell sources for clinical application in the administration of numerous refractory and relapse diseases. Despite the preferable prospect of serum-free (SF) condition for cell product standardization and pathogenic contamination remission, yet the systematic and detailed impact upon hAMSCs at both cellular and transcriptomic levels is largely obscure. METHODS: For the purpose, we preconditioned hAMSCs under serum-containing (SC) and SF medium for 48 h and compared the biological signatures and biofunctions from the view of cell morphology, immunophenotypes, multi-lineage differentiation in vitro, cell vitality, cytokine expression, and immunosuppressive effect upon the subpopulations of T lymphocytes, together with the PI3K-AKT-mTOR signaling reactivation upon cell vitality. Meanwhile, we took advantage of RNA-SEQ and bioinformatic analyses to verify the gene expression profiling and genetic variation spectrum in the indicated hAMSCs. RESULTS: Compared with those maintained in SC medium, hAMSCs pretreated in SF conditions manifested conservation in cell morphology, immunophenotypes, adipogenic differentiation, and immunosuppressive effect upon the proliferation and activation of most of the T cell subpopulations, but with evaluated cytokine expression (e.g., TGF-ß1, IDO1, NOS2) and declined osteogenic differentiation and cell proliferation as well as proapoptotic and apoptotic cells. The declined proliferation in the SF group was efficiently rescued by PI3K-AKT-mTOR signaling reactivation. Notably, hAMSCs cultured in SF and SC conditions revealed similarities in gene expression profiling and variations in genetic mutation at the transcriptome level. Instead, based on the differentially expressed genes and variable shear event analyses, we found those genes were mainly involved in DNA synthesis-, protein metabolism-, and cell vitality-associated biological processes and signaling pathways (e.g., P53, KRAS, PI3K-Akt-mTOR). CONCLUSIONS: Collectively, our data revealed the multifaceted cellular and molecular properties of hAMSCs under SC and SF conditions, which suggested the feasibility of serum-free culture for the preferable preparation of standardized cell products for hAMSC drug development and clinical application.

Preoperative CT-based deep learning model for predicting overall survival in patients with high-grade serous ovarian cancer.

Purpose: High-grade serous ovarian cancer (HGSOC) is aggressive and has a high mortality rate. A Vit-based deep learning model was developed to predicting overall survival in HGSOC patients based on preoperative CT images. Methods: 734 patients with HGSOC were retrospectively studied at Qilu Hospital of Shandong University with preoperative CT images and clinical information. The whole dataset was randomly split into training cohort (n = 550) and validation cohort (n = 184). A Vit-based deep learning model was built to output an independent prognostic risk score, afterward, a nomogram was then established for predicting overall survival. Results: Our Vit-based deep learning model showed promising results in predicting survival in the training cohort (AUC = 0.822) and the validation cohort (AUC = 0.823). The multivariate Cox regression analysis indicated that the image score was an independent prognostic factor in the training (HR = 9.03, 95% CI: 4.38, 18.65) and validation cohorts (HR = 9.59, 95% CI: 4.20, 21.92). Kaplan-Meier survival analysis indicates that the image score obtained from model yields promising prognostic significance to refine the risk stratification of patients with HGSOC, and the integrative nomogram achieved a C-index of 0.74 in the training cohort and 0.72 in the validation cohort. Conclusions: Our model provides a non-invasive, simple, and feasible method to predicting overall survival in patients with HGSOC based on preoperative CT images, which could help predicting the survival prognostication and may facilitate clinical decision making in the era of individualized and precision medicine.

Preharvest Methyl Jasmonate Treatment Increased Glucosinolate Biosynthesis, Sulforaphane Accumulation, and Antioxidant Activity of Broccoli.

Broccoli is becoming increasingly popular among consumers owing to its nutritional value and rich bioactive compounds, such glucosinolates (GSLs) and hydrolysis products, which are secondary metabolites for plant defense, cancer prevention, and higher antioxidant activity for humans. In this study, 40 µmol/L methyl jasmonate (MeJA) was sprayed onto broccoli from budding until harvest. The harvested broccoli florets, stem, and leaves were used to measure the contents of GSLs, sulforaphane, total phenolics, and flavonoids, as well as myrosinase activity, antioxidant activity, and gene expression involved in GSL biosynthesis. The overall results revealed that GSL biosynthesis and sulforaphane accumulation were most likely induced by exogenous MeJA treatment by upregulating the expression of CYP83A1, SUR1, UGT74B1, and SOT18 genes. Exogenous MeJA treatment more remarkably contributed to the increased GSL biosynthesis in broccoli cultivars with low-level GSL content (Yanxiu) than that with high-level GSLs (Xianglv No.3). Moreover, MeJA treatment had a more remarkable increasing effect in broccoli florets than stem and leaves. Interestingly, total flavonoid content substantially increased in broccoli florets after MeJA treatment, but total phenolics did not. Similarly, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, trolox-equivalent antioxidant capacity (ABTS), and ferric-reducing antioxidant power (FRAP) were higher in broccoli floret after MeJA treatment. In conclusion, MeJA mediated bioactive compound metabolism, had positive effects on GSL biosynthesis, sulforaphane, and flavonoids accumulation, and showed positive correlation on inducing higher antioxidant activities in broccoli floret. Hence, preharvest supplementation with 40 µM MeJA could be a good way to improve the nutritional value of broccoli florets.

Antioxidant Activities of Aqueous Extracts and Protein Hydrolysates from Marine Worm Hechong (Tylorrhynchus heterochaeta).

Hechong (Tylorrhynchus heterochaeta) is an edible marine worm widely distributed in the estuary area. The objective of this study is to determine the antioxidant activities of extracts and protein hydrolysates from Hechong. Results showed that the aqueous extracts of steamed Hechong had the highest antioxidant values using the methods of DPPH, ABTS, and FRAP testing (76.29 µmol TE/g, 181.04 µmol TE/g, and 10.40 mmol Fe2+/100 g, respectively). Furthermore, protein hydrolysates of Hechong were observed significant antioxidant activities when compared to crude Hechong. The purification was carried out by DEAE-52 cellulose and Sephadex G-100 column chromatography. The microspatial structure of glycoprotein showed fibrous shapes and cracks with uniform distribution. The study has concluded that the extract and protein hydrolysates of Hechong have significant antioxidant activities, which is merited to be further investigated in the food and pharmaceutical fields.

Psychometric properties of a simplified Chinese version of the cancer predisposition perception scale.

Objective: Cancer predisposition perception refers to the subjective estimation of the likelihood of being diagnosed with cancer in the future. It affects people's behavior concerning cancer screening and prevention. At present, there is no available tool to evaluate cancer predisposition perception. The aim of this study was to translate the cancer predisposition perception scale into simplified Chinese (C-CPPS), and then test its psychometric properties among Chinese patients. Methods: In phase I, the CPPS was translated into Chinese, and validated by an expert panel. In phase II, data on reliability and validity was evaluated in terms of construct validity, criterion validity, internal consistency, test-retest reliability, and item-total correlations, with a convenience sample of 208 patients recruited from the colorectal cancer surgical ward. Results: The C-CPPS had desirable validity and reliability. The scale-level content validity index was 0.96. Exploratory factor analysis indicated that the six-factor structure of the C-CPPS was good fit to the data. Correlation between the C-CPPS and the Brief Illness Perception Questionnaire was statistically significant. Cronbach's α for the entire scale was 0.90 and 0.71-0.95 for five of the six subscales. Item-total correlations ranged from 0.309 to 0.775, and the intraclass correlation coefficient was 0.97. Conclusions: The C-CPPS appears to be culturally appropriate, reliable, and valid for assessing cancer predisposition perception among patients with colorectal cancer in China.

Risk factors for prolonged intensive care unit stays in patients after cardiac surgery with cardiopulmonary bypass: A retrospective observational study.

OBJECTIVES: Patients after cardiac surgery with cardiopulmonary bypass (CPB) require a stay in the ICU postoperatively. This study aimed to investigate the incidence of prolonged length of stay (LOS) in the ICU after cardiac surgery with CPB and identify associated risk factors. METHODS: The current investigation was an observational, retrospective study that included 395 ICU patients who underwent cardiac surgery with CPB at a tertiary hospital in Guangzhou from June 2015 to June 2017. Data were obtained from the hospital database. Binary logistic regression modeling was used to analyze risk factors for prolonged ICU LOS. RESULTS: Of 395 patients, 137 (34.7%) had a prolonged ICU LOS (>72.0 h), and the median ICU LOS was 50.9 h. Several variables were found associated with prolonged ICU LOS: duration of CPB, prolonged mechanical ventilation and non-invasive assisted ventilation use, PaO2/FiO2 ratios within 6 h after surgery, type of surgery, red blood cell infusion during surgery, postoperative atrial arrhythmia, postoperative ventricular arrhythmia (all P < 0.05). CONCLUSIONS: These findings are clinically relevant for identifying patients with an estimated prolonged ICU LOS, enabling clinicians to facilitate earlier intervention to reduce the risk and prevent resulting delayed recovery.

Resistance Phenotype and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Shanghai.

Background: The emergence and wide global spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are of great concern, and the aim of this study was to investigate drug resistance, molecular epidemiology, and genetic relationship of CRKP isolates from patients in Shanghai, China. Methods: A retrospective study was conducted from April 2018 to July 2019, and a total of 133 CRKP isolates were collected. Antimicrobial susceptibility was determined by VITEK-2 automated microbiology analyzer platform (bioMérieux, France) and the broth microdilution method. Polymerase chain reaction assays were used to investigate the presence of drug resistance genes. A modified carbapenem inactivation method was performed to detect carbapenemases. Multilocus sequence typing and pulsed-field gel electrophoresis (PFGE) were conducted for genetic relatedness of 50 CRKP isolates selected. Results: Among 670 isolates of K. pneumoniae, 133 (19.9%) strains were identified as CRKP, of which, 76.7% (102/133) strains were isolated from intensive care units (ICUs). All the 133 CRKP isolates were found to be carbapenemase-producers and harbor blaKPC-2 gene. No other carbapenemase genes of blaNDM, blaOXA-48, blaVIM, and blaIMP were detected. Furthermore, ß-lactamase genes of blaSHV, blaCTX, and blaTEM were the most common resistance-associated genes among these KPC-2 producing isolates. All the 133 CRKP strains displayed >95% of resistance to cephalosporins and carbapenems, except for gentamicin, trimethoprim-sulfamethoxazole, amikacin, tigecycline and colistin, and ceftazidime-avibactam. The most common sequence type was ST11, accounting for 90.0% of the 50 CRKP selected, followed by ST15 (10.0%). PFGE analysis clustered the 50 KPC-2-producing isolates into seven (A-G) distinct clonal clusters at 85% cutoff. Of which, A and G were the two major clusters, accounting for the majority of the strains collected in emergency ICU and neurosurgical ICU. And all the strains of clusters D and E were collected in cardiothoracic surgery ICU, except for one strain collected in one outpatient. Conclusion: The KPC-2-producing K. pneumoniae belonged to ST11 was widely disseminated in ICUs, and active and effective surveillance of infection control strategies was initiated to limit the spread of CRKP strains.

Bone marrow-derived mesenchymal stem/stromal cells in patients with acute myeloid leukemia reveal transcriptome alterations and deficiency in cellular vitality.

BACKGROUND: State-of-the-art advances have indicated the pivotal characteristics of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) in hematopoietic microenvironment as well as coordinate contribution to hematological malignancies. However, the panoramic view and detailed dissection of BM-MSCs in patients with acute myeloid leukemia (AML-MSCs) remain obscure. METHODS: For the purpose, we isolated and identified AML-MSCs together with healthy donor-derived HD-MSCs from the bone marrow mononuclear cells (BM-MNCs) by using the standard density gradient centrifugation based on clinical diagnosis and cellular phenotypic analysis. Subsequently, we systematically compared the potential similarities and discrepancy both at the cellular and molecular levels via flow cytometry, multilineage differentiation, chromosome karyotyping, cytokine quantification, and transcriptome sequencing and bioinformatic analysis including single-nucleotide polymorphism (SNP), gene ontology (GO), HeatMap, principal component analysis (PCA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). RESULTS: On the one hand, AML-MSCs exhibited undistinguishable signatures in cytomorphology, surface biomarker expression pattern, stemness, chromosome karyotype, and chondrogenesis as HD-MSCs, whereas with impaired adipogenesis, enhanced osteogenesis, and variations in cytokine expression pattern. On the other hand, with the aid of genomic and bioinformatic analyses, we verified that AML-MSCs displayed multidimensional discrepancy with HD-MSCs both in genome-wide gene expression profiling and genetic variation spectrum. Simultaneously, the deficiency of cellular vitality including proliferation and apoptosis in AML-MSCs was largely rescued by JAK-STAT signaling inhibition. CONCLUSIONS: Overall, our findings elucidated that AML-MSCs manifested multifaceted alterations in biological signatures and molecular genetics, and in particular, the deficiency of cellular vitality ascribed to over-activation of JAK-STAT signal, which collectively provided systematic and overwhelming new evidence for decoding the pathogenesis of AML and exploring therapeutic strategies in future.

Improved adenylate cyclase activity via affinity immobilization onto co-modified GO with bio-inspired adhesive and PEI.

Adenylate cyclase (AC) can efficiently catalyze the conversion of adenosine triphosphate (ATP) to cyclic adenosine-3', 5'-monophosphate (cAMP). However, AC directly immobilized on substrate is not desirable due to enzyme inactivation. Herein, bio-inspired adhesive of polydopamine and polyethyleneimine (PDA/PEI) was used as flexible chains to graft on graphene oxide (GO), and the AC was directionally immobilized through affinity between metal ions and his-tags of AC. The properties of modified GO and the activity of immobilized AC were studied in detail. PDA/PEI layers have been proved to improve the amino density of GO surface for affinity groups decoration and adjust the interaction between AC and support. And modified GO by this novel method contributes to subsequent grafting and immobilization of AC by affinity. AC immobilized on modified GO exhibited high activity recovery with about 90 % of free AC, while enzyme immobilized on unmodified GO has been inactivated. This study offers a versatile approach for support modification and enzyme oriented immobilization. PDA/PEI functionalized GO can be used as a promising carrier to immobilize other his-tagged enzymes.

A case of pulmonary inflammatory myofibroblastic tumor treated with bronchoscopic therapy plus lobectomy.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare tumor with malignant potential. We presented a case of a young adult who was diagnosed with IMT and treated with loop electrocautery therapy to relieve airway obstruction, followed by lobectomy to complete resection. Recent studies have supported the use of such interventional resection methods. CASE PRESENTATION: A non-smoking 30-year-old woman presented with a 1-month history of progressive dyspnea and productive cough. The Chest X-ray showed a homogenous opacity invading the entire left hemithorax, and the mediastinum content was attracted to the left side. In an effort to avoid pneumonectomy and afford rapid palliation of dyspnea, loop electrocautery was selected as the most appropriate therapy. The left upper lobectomy by thoracoscopy was performed instead of left upper lobe sleeve resection in order to better prevent the recurrence of lung atelectasis. After 6 years of follow-up, no evidence of recurrence has been found till now. CONCLUSION: Interventional bronchoscopy coupled with surgical resection serves not only as a palliative management to bronchial obstruction but also a way to avoid pneumonectomy.