Clinical Predictors of Bacteremia Outcome After Initial Empirical Antimicrobial Therapy in Patients with Hematological Malignancies: A Retrospective Analysis.

Objective: We performed a retrospective analysis to investigate the clinical predictors of bacteremia outcome involving Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) after initial empirical antimicrobial therapy among hematological malignancy cases. Methods: This retrospective study was conducted between April 2018 and April 2023. All bloodstream infections (BSIs) caused by E. coli and K. pneumoniae in hospitalized hematological malignancy (HM) patients were identified. Data on patient demographics, clinical characteristics, empirical antimicrobial treatment, outcomes and the antimicrobial susceptibility were collected from medical records. Multivariate analyses were utilized to assess the risk factors for all-cause mortality within 28 days and carbapenem resistance. Optimal cutoffs for continuous predictive variables were evaluated by receiver operating characteristic (ROC) curve analysis. Results: Among 61 individuals diagnosed with bacteremia, 39 cases were caused by E. coli bacteremia, while the remaining 22 were identified as K. pneumoniae bacteremia. Out of these, there were 10 cases of carbapenem-resistant Enterobacteriaceae (CRE) and 12 cases resulted in all-cause mortality within 28 days. Analysis indicated that Pitt score was an independent risk factor for mortality and a cut-off of 2.5 was a reliable predictor with 83.3% sensitivity and 85.7% specificity, respectively. Impaired mental status and elevated body temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on the third day (d3) after antimicrobial treatment were identified as independent risk factors for predicting carbapenem resistance. Conclusion: We found that Pitt score with a cut-off of 2.5 was a reliable predictor for mortality within 28 days in HM bacteremia cases. Impaired mental status and elevated temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on d3 after antimicrobial treatment were identified as predictive risk factors to carbapenem resistance.

Fine-regulation of gradient gate-opening in nanoporous crystals for sieving separation of ternary C3 hydrocarbons.

The adsorptive separation of ternary propyne (C3H4)/propylene (C3H6)/propane (C3H8) mixtures is of significant importance due to its energy efficiency. However, achieving this process using an adsorbent has not yet been accomplished. To tackle such a challenge, herein, we present a novel approach of fine-regulation of the gradient of gate-opening in soft nanoporous crystals. Through node substitution, an exclusive gate-opening to C3H4 (17.1 kPa) in NTU-65-FeZr has been tailored into a sequential response of C3H4 (1.6 kPa), C3H6 (19.4 kPa), and finally C3H8 (57.2 kPa) in NTU-65-CoTi, of which the gradient framework changes have been validated by in situ powder X-ray diffractions and modeling calculations. Such a significant breakthrough enables NTU-65-CoTi to sieve the ternary mixtures of C3H4/C3H6/C3H8 under ambient conditions, particularly, highly pure C3H8 (99.9%) and C3H6 (99.5%) can be obtained from the vacuum PSA scheme. In addition, the fully reversible structural change ensures no loss in performance during the cycling dynamic separations. Moving forward, regulating gradient gate-opening can be conveniently extended to other families of soft nanoporous crystals, making it a powerful tool to optimize these materials for more complex applications.

The Renoprotective and Anti-Inflammatory Effects of Human Urine-Derived Stem Cells on Acute Kidney Injury Animals.

BACKGROUND: Acute Kidney Injury (AKI) is defined as a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Developing novel therapies for AKI is essential. Adult stem cells possess regenerative ability and play an important role in medical research and disease treatment. METHODS: In this study, we isolated and characterized a distinct human urine-derived stem cell, which expressed both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. RESULTS: It was found that these cells exhibited robust protective effects on tubular cells and anti- inflammatory effects on macrophages in vitro. In an ischemia-reperfusion-induced acute kidney injury NOD-SCID mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo. CONCLUSION: In summary, our results highlighted the effectiveness of USCs in protecting from PTC injury and impeding macrophage polarization, as well as the secretion of pro-inflammatory interleukins, suggesting the potential of USCs as a novel cell therapy in AKI.

[Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021. RESULTS: All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%. CONCLUSION: The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

Soft corrugated channel with synergistic exclusive discrimination gating for CO2 recognition in gas mixture.

Developing artificial porous systems with high molecular recognition performance is critical but very challenging to achieve selective uptake of a particular component from a mixture of many similar species, regardless of the size and affinity of these competing species. A porous platform that integrates multiple recognition mechanisms working cooperatively for highly efficient guest identification is desired. Here, we designed a flexible porous coordination polymer (PCP) and realised a corrugated channel system that cooperatively responds to only target gas molecules by taking advantage of its stereochemical shape, location of binding sites, and structural softness. The binding sites and structural deformation act synergistically, exhibiting exclusive discrimination gating (EDG) effect for selective gate-opening adsorption of CO2 over nine similar gas molecules, including N2, CH4, CO, O2, H2, Ar, C2H6, and even higher-affinity gases such as C2H2 and C2H4. Combining in-situ crystallographic experiments with theoretical studies, it is clear that this unparalleled ability to decipher the CO2 molecule is achieved through the coordination of framework dynamics, guest diffusion, and interaction energetics. Furthermore, the gas co-adsorption and breakthrough separation performance render the obtained PCP an efficient adsorbent for CO2 capture from various gas mixtures.

Intragenic ß-synuclein rearrangements in malignancy.

The synuclein family, consisting of α-, ß-, and γ-synuclein, is primarily expressed in neurons. Mutations of α- and ß-synuclein have been linked to Parkinson's disease and dementia with Lewy bodies, respectively. Recent studies have shown that synucleins are upregulated in various tumors, including breast, ovarian, meningioma, and melanoma, and high synuclein expression is associated with poor prognosis and drug resistance. We report a novel rearrangement of ß-synuclein in a pediatric T-cell acute lymphoblastic leukemia (T-ALL) case, where ß-synuclein (SNCB) is fused in-frame with ETS variant transcription factor 6 (ETV6), a gene frequently rearranged in acute leukemia including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and T-ALL. An additional case of ß-synuclein rearrangement was identified in a squamous cell carcinoma of the lung through analysis of the public TCGA database. Both rearrangements involve the C-terminal of ß-synuclein. Since ß-synuclein shares extensive amino acid similarities with α-synuclein and α-synuclein binds to 14-3-3, an important regulator of apoptosis, the rearranged ß-synuclein may contribute to tumorigenesis by deregulating apoptosis. In addition, overexpression of synucleins has been shown to increase cell proliferation, suggesting that the rearranged ß-synuclein may also deregulate the cell cycle.

Transcriptome sequencing identifies novel EVX fusions involved in transcriptional activation of HOX family genes in pediatric immature T-cell acute lymphoblastic leukemia: two cases reports and a literature review.

Driver genomic alterations in pediatric immature T-cell acute lymphoblastic leukemia are not fully known. We report two cases of novel EVX fusions involved in the transcriptional activation of HOX family genes, ETV6::EVX2 and MSI2::EVX1/HOXA13, which activate HOXD and HOXA cluster genes transcription through enhancer hijacking. HOXA and HOXD were the only key transcription factors activated in these cases, which indicates their important roles in leukemogenesis. Our findings elucidate potential drivers for development of T-cell lymphoblastic leukemia, and are valuable for diagnosis and risk stratification of pediatric T-ALL in the era of precision medicine.

Clinical characteristics of hypercalcemic crises in a tertiary children's hospital.

BACKGROUND: Hypercalcemic crisis is considered a critical and fatal endocrine condition. To date, few reports have focused on hypercalcemic crises in children. AIM: To explore the etiology and identify the clinical characteristics related to hypercalcemic crises in children. METHODS: We enrolled 101 children diagnosed with hypercalcemia between January 1, 2016 and December 31, 2021, admitted to the Children's Hospital of Chongqing Medical University. Electronic medical records were reviewed to determine the causes and clinical characteristics of hypercalcemic crises. RESULTS: Hypercalcemic crises occurred in 28 admissions during the 6-year period; 64% of the patients enrolled in the study were infants. The mean corrected total serum calcium was 4.6 ± 0.2 mmol/l. Tumor and hereditary diseases were found in 12 (43%) and 7 (25%) patients, respectively. The ratio of iatrogenic factors was 11% (3/28), and all 3 patients received a blood transfusion. The incidence of poor prognosis in the tumor cases was 50%. Timely intervention including hemodialysis, pamidronate, and etiological treatment was effective in decreasing calcium levels. CONCLUSION: Hypercalcemic crisis is a serious electrolyte disturbance that has the potential for high mortality. The main causes are tumors and hereditary diseases in children. The lack of unique characteristics makes it difficult to recognize by medical caregivers. Early diagnosis and timely intervention could improve the prognosis.

Anti-freezing, recoverable and transparent conductive hydrogels co-reinforced by ethylene glycol as flexible sensors for human motion monitoring.

Wearable flexible sensors based on conductive hydrogels have received extensive attention in the fields of electronic skin and smart monitoring. However, conductive hydrogels contain a large amount of water, which greatly affects their performances in harsh environments. It is therefore necessary to prepare hydrogel sensors that are stable at low temperatures. Herein, metal ions (MgCl2) and ethylene glycol (EG) were combined with polyvinyl alcohol (PVA) to obtain a conductive PVA/EG hydrogel with tensile strength and elongation at break of 1.1 MPa and 442.3 %, respectively, which could withstand >6000-fold its own weight. The binary solvent system composed of water and EG contributed to the excellent anti-freezing properties and long-term storage (>1 week), flexibility, and stability of the hydrogel even at -20 °C. The wearable PVA/EG hydrogel as a flexible sensor possessed desirable sensing performances with a competitive GF value of 0.725 and fatigue resistance (50 cycles) when used to monitor various human motions and physiological signals. Overall, this hydrogel sensor shows strong potential for application in the fields of human motion monitoring, written information sensing, and information encryption and transmission.

Fine Pore-Structure Engineering by Ligand Conformational Control of Naphthalene Diimide-Based Semiconducting Porous Coordination Polymers for Efficient Chemiresistive Gas Sensing.

Exploring new porous coordination polymers (PCPs) that have tunable structure and conductivity is attractive but remains challenging. Herein, fine pore structure engineering by ligand conformation control of naphthalene diimide (NDI)-based semiconducting PCPs with π stacking-dependent conductivity tunability is achieved. The π stacking distances and ligand conformation in these isoreticular PCPs were modulated by employing metal centers with different coordination geometries. As a result, three conjugated PCPs (Co-pyNDI, Ni-pyNDI, and Zn-pyNDI) with varying pore structure and conductivity were obtained. Their crystal structures were determined by three-dimensional electron diffraction. The through-space charge transfer and tunable pore structure in these PCPs result in modulated selectivity and sensitivity in gas sensing. Zn-pyNDI can serve as a room-temperature operable chemiresistive sensor selective to acetone.

Superwetting Injectable Hydrogel with Ultrastrong and Fast Tissue Adhesion for Minimally Invasive Hemostasis.

Injectable hydrogels have recently emerged as alternatives to sutures for various clinical indications. However, existing injectable hydrogels are unsuitable for hemostasis in minimally invasive surgery because of their weak interfacial adhesion and complex/prolonged processing. Herein, a superwetting injectable hydrogel composed of oppositely charged polysaccharides is developed. The spontaneous spreading of the injectable hydrogel on the surfaces achieves complete wetting and forms tight interfacial contact by absorbing the interfacial water. The superwetting ability and subsequent covalent crosslinking perform fast and ultrastrong wet adhesion (140 kPa) on the tissue surface. Ex vivo porcine and in vivo rat models show that the hydrogel successfully leads to the aggregation of erythrocytes for targeted hemostasis (in less than 12 s) without requiring external adjuncts, and no postsurgical adhesions to the peripheral tissues. This further demonstrates that hydrogel can act as an effective hemostasis agent in laparoscopic surgery in a rabbit model. Overall, the strong wet adhesion, antibacterial properties, and easy operability make this injectable hydrogel a promising candidate for hemostasis applications, as it can successfully combine clinical efficacy and transformation opportunities for minimally invasive surgery.

Clear-Box Machine Learning for Virtual Screening of 2D Nanozymes to Target Tumor Hydrogen Peroxide.

Targeting tumor hydrogen peroxide (H2 O2 ) with catalytic materials has provided a novel chemotherapy strategy against solid tumors. Because numerous materials have been fabricated so far, there is an urgent need for an efficient in silico method, which can automatically screen out appropriate candidates from materials libraries for further therapeutic evaluation. In this work, adsorption-energy-based descriptors and criteria are developed for the catalase-like activities of materials surfaces. The result enables a comprehensive prediction of H2 O2 -targeted catalytic activities of materials by density functional theory (DFT) calculations. To expedite the prediction, machine learning models, which efficiently calculate the adsorption energies for 2D materials without DFT, are further developed. The finally obtained method takes advantage of both interpretability of physics model and high efficiency of machine learning. It provides an efficient approach for in silico screening of 2D materials toward tumor catalytic therapy, and it will greatly promote the development of catalytic nanomaterials for medical applications.

A zero-sum game or an interactive frame? Iron competition between bacteria and humans in infection war.

ABSTRACT: Iron is an essential trace element for both humans and bacteria. It plays a vital role in life, such as in redox reactions and electron transport. Strict regulatory mechanisms are necessary to maintain iron homeostasis because both excess and insufficient iron are harmful to life. Competition for iron is a war between humans and bacteria. To grow, reproduce, colonize, and successfully cause infection, pathogens have evolved various mechanisms for iron uptake from humans, principally Fe 3+ -siderophore and Fe 2+ -heme transport systems. Humans have many innate immune mechanisms that regulate the distribution of iron and inhibit bacterial iron uptake to help resist bacterial invasion and colonization. Meanwhile, researchers have invented detection test strips and coupled antibiotics with siderophores to create tools that take advantage of this battle for iron, to help eliminate pathogens. In this review, we summarize bacterial and human iron metabolism, competition for iron between humans and bacteria, siderophore sensors, antibiotics coupled with siderophores, and related phenomena. We also discuss how competition for iron can be used for diagnosis and treatment of infection in the future.

Decitabine combined with minimally myelosuppressive therapy for induction of remission in pediatric high-risk acute myeloid leukemia with chromosome 5q deletion: a report of three cases.

Cases of pediatric acute myeloid leukemia (AML) with complex karyotypes including chromosome 5 abnormalities are rare and have a very poor prognosis. Management of AML with monosomy 5/del(5q) has been inconsistent. We treated three adolescents with this AML subtype using combined low-dose cytarabine and mitoxantrone, concurrently with decitabine and G-CSF, for remission induction. Decitabine was also included in the conditioning regimen before hematopoietic cell transplantation (HCT). All three patients achieved complete remission after treatment with this combination therapy. The treatment was well tolerated, and the patients are alive and free of disease at 3.6, 3.2, and 3.0 years after HCT, respectively.

RP11-616M22.7 recapitulates imatinib resistance in gastrointestinal stromal tumor.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play crucial roles in human cancers. However, systematic characterization of lncRNAs and their roles in gastrointestinal stromal tumor (GIST) therapy have been lacking. We performed high-throughput RNA sequencing (RNA-seq) of 20 GIST and paired adjacent normal samples. We characterized the transcriptional landscape and dysregulation of lncRNAs in GIST. We identified 866 upregulated and 1,268 downregulated lncRNAs in GIST samples, the majority of which were GIST-specific over other cancer types. Most hallmarks were found to be dysregulated in GIST samples, and lncRNAs were highly associated with cancer-related hallmarks. RP11-616M22.7 was identified to increase in imatinib-resistant samples compared to those in non-resistant samples. Further analysis revealed that RP11-616M22.7 was closely associated with the Hippo signaling pathway. By treating GIST cells with different doses of imatinib, we verified that RP11-616M22.7 knockdown promotes the sensitivity of tumor cells, whereas RP11-616M22.7 overexpression induces resistance to imatinib. We further confirmed reducing of resistance to imatinib by knocking down RP11-616M22.7 in vivo. Additionally, RP11-616M22.7 was observed to interact with RASSF1 protein. Our study revealed that deficiency of RP11-616M22.7 was able to reduce resistance of the GIST cell response to imatinib treatment both in vitro and in vivo.

Overexpression of DSCR1 prevents proliferation and predicts favorable prognosis in colorectal cancer patients.

OBJECTIVES: Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC. METHODS: Firstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence. RESULTS: DSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo. CONCLUSIONS: Our study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.

A disposable paper-based hydrophobic substrate for highly sensitive surface-enhanced Raman scattering detection.

Detection of target analytes with high sensitivity and reproducibility remains a challenge for surface-enhanced Raman scattering (SERS) due to the lack of cost-effective and highly sensitive substrates. In this study, a hydrophobic SERS substrate capable of concentrating nanoparticles and analytes was prepared by spin-coating lubricating liquid onto commercial paper. The condensation effect of the paper-based hydrophobic substrate induced aggregation of gold nanoparticles (Au NPs) to generate ''hot spots'' for SERS and to drive analytes to the hot-spot areas for more sensitive detection. The obtained SERS signal intensity was 5-fold higher than that obtained using common paper, and a detection limit (LOD) of 4.3 × 10-10 M for rhodamine 6G (R6G) was achieved. Randomly selected points on the substrate and different batches of substrates all exhibited high reproducibility, and the relative standard deviation (RSD) at 1362 cm-1 is approximately 11%. A further application of the hydrophobic substrate was demonstrated by the detection of cytochrome C within a linear detection range of 3.90 × 10-8 M-1.25 × 10-6 M. In addition, the prepared substrate can obtain identifiable SERS spectra of cancer cells and non-cancer cells because a large number of AuNP or Au NPs clusters can adhere to cells, resulting in the construction of a 3D hotspot matrix. The disposable hydrophobic paper substrate eliminates the problem of solution diffusion, and also provides an effective platform for biomolecular screening detection.

miR-195 Serves as a Tumor Suppressor in the Progression of Liposarcoma by Targeting OSBP.

BACKGROUND: Liposarcoma was considered as a soft tissue kind of sarcoma with one-fifth in the sarcoma cases of adults. The aim of this study was to explore the role and the potential mechanisms of miR-195 in liposarcoma. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of microRNA-195 (miR-195) and oxysterol-binding protein (OSBP) in liposarcoma. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell migration was measured by wound healing and transwell assays. Cell cycle phases and apoptosis were examined using flow cytometry analysis. Caspase-3 activity was detected by commercial kit. Binding sites between miR-195 and OSBP were predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze OSBP level. Xenograft tumor assays were performed to observe the effect of miR-195 overexpression on tumor growth in vivo. RESULTS: miR-195 expression was decreased, whereas OSBP was increased in liposarcoma tissues and cells. Besides, miR-195 upregulation suppressed the proliferative and migrative abilities and induced inhibition on cell growth and promotion on apoptosis in SW872 and 93T449 cells. Mechanically, miR-195 functioned as a suppressor by regulating OSBP expression. Furthermore, OSBP overexpression inverted the effects of miR-195 on cell growth, migration and apoptosis in SW872 and 93T449 cells. miR-195 overexpression also suppressed tumor growth in vivo. CONCLUSION: miR-195 suppressed cell growth, migration and elevated cell apoptosis via OSBP in liposarcoma.