Post-modification of covalent organic framework functionalized aminated carbon nanotubes with active site (Fe) for the sensitive detection of luteolin.

In this research, the TT-COF(Fe)@NH2-CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH2-CNTs with active site (Fe), where TT-COF@NH2-CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH2-CNTs) as raw materials. The complex TT-COF(Fe)@NH2-CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH2-CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 µM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH2-CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH2-CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs.

Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Se vacancies and interface engineering modulated bifunctionality prussian blue analogue derivatives for overall water splitting.

It is a challenging task to design and synthesize stable, and high-performance non-precious metals bifunctional catalysts for water-splitting. Herein, the coupling between Se vacancy and interface engineering is highlighted to synthesize a unique CoFeSe hollow nanocubes structure on MXene-modified nickel foam (NF) by in-situ phase transition from bifunctionality prussian blue analogue (PBA) derivatives (VSe-CoFeSe@MXene/NF). DFT theory reveals that the Se vacancy and interface engineering modulate the surface electronic structure and optimize the surface adsorption energy of the intermediates. Experimental data also confirm that the as-prepared CoFeSe@MF catalyst exhibits advanced electrocatalytic properties, 283 mV (OER) and 67 mV (HER) are required to drive the current density of 10 mA cm-2. Notably, it is assembled into a two-electrode system for integral water decomposition, which only requires a low cell potential of 1.57 V at current of 10 mA cm-2, together with excellent durability for 48 h. The strategy is expected to provide a new direction for the design and construction of highly efficient collaborative integrated water decomposition electrocatalysts.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy.

JOURNAL/nrgr/04.03/01300535-202506000-00027/figure1/v/2024-08-05T133530Z/r/image-tiff Degenerative cervical myelopathy is a common cause of spinal cord injury, with longer symptom duration and higher myelopathy severity indicating a worse prognosis. While numerous studies have investigated serological biomarkers for acute spinal cord injury, few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy. This study involved 30 patients with degenerative cervical myelopathy (51.3 ± 7.3 years old, 12 women and 18 men), seven healthy controls (25.7 ± 1.7 years old, one woman and six men), and nine patients with cervical spondylotic radiculopathy (51.9 ± 8.6 years old, three women and six men). Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics. Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities. Using least absolute shrinkage and selection operator analysis, we constructed a five-gene model (TBCD, TPM2, PNKD, EIF4G2, and AP5Z1) to diagnose degenerative cervical myelopathy with an accuracy of 93.5%. One-gene models (TCAP and SDHA) identified mild and severe degenerative cervical myelopathy with accuracies of 83.3% and 76.7%, respectively. Signatures of two immune cell types (memory B cells and memory-activated CD4+ T cells) predicted levels of lesions in degenerative cervical myelopathy with 80% accuracy. Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Rising frequency of ozone-favorable synoptic weather patterns contributes to 2015-2022 ozone increase in Guangzhou.

Objective weather classification methods have been extensively applied to identify dominant ozone-favorable synoptic weather patterns (SWPs), however, the consistency of different classification methods is rarely examined. In this study, we apply two widely-used objective methods, the self-organizing map (SOM) and K-means clustering analysis, to derive ozone-favorable SWPs at four Chinese megacities in 2015-2022. We find that the two algorithms are largely consistent in recognizing dominant ozone-favorable SWPs for four Chinese megacities. In the case of classifying six SWPs, the derived circulation fields are highly similar with a spatial correlation of 0.99 between the two methods, and the difference in the mean frequency of each SWP is less than 7%. The six dominant ozone-favorable SWPs in Guangzhou are all characterized by anomaly higher radiation and temperature, lower cloud cover, relative humidity, and wind speed, and stronger subsidence compared to climatology mean. We find that during 2015-2022, the occurrence of ozone-favorable SWPs days increases significantly at a rate of 3.2 day/year, faster than the increases in the ozone exceedance days (3.0 day/year). The interannual variability between the occurrence of ozone-favorable SWPs and ozone exceedance days are generally consistent with a temporal correlation coefficient of 0.6. In particular, the significant increase in ozone-favorable SWPs in 2022, especially the Subtropical High type which typically occurs in September, is consistent with a long-lasting ozone pollution episode in Guangzhou during September 2022. Our results thus reveal that enhanced frequency of ozone-favorable SWPs plays an important role in the observed 2015-2022 ozone increase in Guangzhou.

A comparative study on the formation of nitrogen-containing organic compounds in cloud droplets and aerosol particles.

Nitrogen-containing organic compounds (NOCs) may potentially contribute to aqueous secondary organic aerosols, yet the different formation of NOCs in aerosol particles and cloud droplets remains unclear. With the in-situ measurements performed at a mountain site (1690 m a.s.l.) in southern China, we investigated the formation of NOCs in the cloud droplets and the cloud-free particles, based on their mixing state information of NOCs-containing particles by single particle mass spectrometry. The relative abundance of NOCs in the cloud-free particles was significantly higher than those in cloud residual (cloud RES) particles. NOCs were highly correlated with carbonyl compounds (including glyoxalate and methylglyoxal) in the cloud-free particles, however, limited correlation was observed for cloud RES particles. Analysis of their mixing state and temporal variations highlights that NOCs was mainly formed from the carbonyl compounds and ammonium in the cloud-free particles, rather than in the cloud RES particles. The results support that the formation of NOCs from carbonyl compounds is facilitated in concentrated solutions in wet aerosols, rather than cloud droplets. In addition, we have identified the transport of biomass burning particles that facilitate the formation of NOCs, and that the observed NOCs is most likely contributed to the light absorption. These findings have implications for the evaluation of NOCs formation and their contribution to light absorption.

Diminished nuclear-localized ß-adrenoceptor signalling activates YAP to promote kidney fibrosis in diabetic nephropathy.

BACKGROUND AND PURPOSE: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD), which is characterized by mesangial matrix expansion that involves dysfunctional mesangial cells (MCs). However, the underlying mechanisms remain unclear. This study aims to delineate the spatiotemporal contribution of adrenergic signalling in diabetic kidney fibrosis to reveal potential therapeutic targets. EXPERIMENTAL APPROACH: A model of diabetic nephropathy was induced by in db/db mice. Gene expression in kidneys was profiled by RNA-seq analyses, western blot and immunostaining. Subcellular-localized fluorescence resonance energy transfer (FRET) biosensors determined adrenergic signalling microdomains in MCs. Effects of oral rolipram, a phosphodiesterase 4 (PDE4) inhibitor, on the model were measured. KEY RESULTS: Our model exhibited impaired kidney function with elevated expression of adrenergic and fibrotic genes, including Adrb1, PDEs, Acta2 and Tgfß. RNA-seq analysis revealed that MCs with dysregulated YAP pathway were crucial to the extracellular matrix secretion in kidneys from diabetic nephropathy patients. In cultured MCs, TGF-ß promoted profibrotic gene transcription, which was regulated by nuclear-localized ß-adrenoceptor signalling. Mechanistically, TGF-ß treatment diminished nuclear-specific cAMP signalling in MCs and reduced PKA-dependent phosphorylation of YAP, leading to its activation. In parallel, db/db mouse kidneys showed increased expressions of PDE4B and PDE4D. Treatment with oral rolipram alleviated kidney fibrosis in db/db mice. CONCLUSION AND IMPLICATIONS: Diabetic nephropathy impaired nuclear-localized ß1-adrenoceptor-cAMP signalling microdomain through upregulating PDE4 expression, promoting fibrosis in MCs via PKA dephosphorylation-dependent YAP activation. Our results suggest PDE4 inhibition as a promising strategy for alleviating kidney fibrosis in diabetic nephropathy.

Effect of blastomere cell number on ART outcome of fresh single day 3 embryo transfer.

PURPOSE: Explore the effect of blastomere cell number on ART outcome of fresh embryo transfer on day 3. METHODS: Retrospective analysis of 540 fresh single day 3 embryo transfer cycles at the Reproductive Center of the Third Affiliated Hospital of Guangzhou Medical University from January 1, 2018 to October 31, 2022. Patients were divided into 5-6 cell group (n = 55), 7-9 cell group (n = 457), and ≥ 10 cell group(n = 28) based on the number of blastomeres. Single factor analysis of variance and Pearson's chi square test were used to compare the basic data, cycle information, pregnancy outcome and neonatal outcome. Univariate logistic regression was used to correct for confounding factors and analyze the influencing factors of pregnancy outcome. RESULTS: The positive HCG rate were 20%, 43%, 25% for the 5-6-cell, 7-9 cell and ≥ 10 cell groups respectively, with statistically significant differences (P < 0.001). The clinical pregnancy rate was 18%, 42%,21%, respectively (P < 0.001). The live birth rates were 13%, 34%,21% with P-value less than 0.05 which is statistically significant. In order to exclude the influence of confounding factors, multivariable logistic regression analysis was performed, and the outcomes were consistent with previous findings. There were no significant differences found in neonatal outcome between groups (P > 0.05). CONCLUSION: The results suggested that intermediate cleaving embryos (7-9 cell) still presents the highest clinical potential. Fast and slow cleaving embryos are not conducive to the ART outcome.

Endophytic bacteria with allelopathic potential regulate gene expression and metabolite production in host Casuarina equisetifolia.

Introduction: Casuarina equisetifolia is a common protective forest in coastal areas. However, artificial C. equisetifolia forests cannot self-renew, mainly due to the accumulation of allelochemicals. Endophytic bacteria may alleviate the root growth inhibition caused by allelochemicals in C. equisetifolia seedlings. B. amyloliquefaciens and B. aryabhattai were endophytic bacteria with strong allelopathy in C. equisetifolia root. The allelopathy mechanism of these two endophytes and their interaction with C. equisetifolia remains to be studied. Methods: Whole-genome sequencing of B. amyloliquefaciens and B. aryabhattai isolated from the roots of allelochemical-accumulating C. equisetifolia was performed using Illumina Hiseq and PacBio single-molecule sequencing platforms. Sterile seedlings of C. equisetifolia were treated with either individual or mixed bacterial cultures through root drenching. Transcriptional and metabolomics analyses were conducted after 3 days of infection. Results and discussion: Whole-genome sequencing of Bacillus aryabhattai and Bacillus amyloliquefaciens showed that the two strains contained various horizontal gene transfer elements such as insertion sequence, prophage and transposon. In addition, these two strains also contain numerous genes related to the synthesis and catabolism of allelochemicals. After these two strains of bacteria were individually or mixed infected with C. equisetifolia, metabolomics and transcriptomic analysis of C. equisetifolia showed the 11 important secondary metabolite biosynthesis among them alkaloids biosynthesis, phenylpropanoid and terpenes biosynthesis and related genes were putatively regulated. Correlation analysis revealed that 48 differentially expressed genes had strong positive correlations with 42 differential metabolites, and 48 differentially expressed genes had strong negative correlations with 36 differential metabolites. For example, CMBL gene showed positive correlations with the allelochemical (-)-Catechin gallate, while Bp10 gene showed negative correlations with (-)-Catechin gallate. Conclusion: The intergenerational accumulation of allelochemicals may induce horizontal gene transfer in endogenic bacteria of Casuarina equisetifolia root. Endophytic Bacillus plays an allelopathic role by assisting the host in regulating gene expression and the production and/or variety of allelochemicals. This comprehensive study sheds light on the intricate genetic and metabolic interactions between Bacillus endophytes and C. equisetifolia. These findings provide insights into endophyte-mediated allelopathy and its potential uses in plant biology and forest sustainability.

Fractionated irradiation promotes radioresistance and decreases oxidative stress by increasing Nrf2 of ALDH-positive nasopharyngeal cancer stem cells.

Radiotherapy is widely regarded as the primary therapeutic modality for nasopharyngeal cancer (NPC). Studies have shown that cancer cells with high resistance to radiation, known as radioresistant cancer cells, may cause residual illness, which in turn might contribute to the occurrence of cancer recurrence and metastasis. It has been shown that cancer stem-like cells (CSCs) exhibit resistance to radiation therapy. In the present study, fractionated doses of radiation-induced epithelial-mesenchymal transition (EMT) and ALDH+ CSCs phenotype of NPC tumor spheroids. Furthermore, it has been shown that cells with elevated ALDH activity have increased resistance to the effects of fractionated irradiation. Nuclear factor erythroid-2-related factor 2 (Nrf2) plays a pivotal role in regulating cellular antioxidant systems. A large body of evidence suggests that Nrf2 plays a significant role in the development of radioresistance in cancer. The authors' research revealed that the application of fractionated irradiation resulted in a decline in Nrf2-dependent reactive oxygen species (ROS) levels, thereby mitigating DNA damage in ALDH+ stem-like NPC cells. In addition, immunofluorescence analysis revealed that subsequent to the process of fractionated irradiation of ALDH+ cells, activated Nrf2 was predominantly localized inside the nucleus. Immunofluorescent analysis also revealed that the presence of the nuclear Nrf2+/NQO1+/ALDH1+ axis might potentially serve as an indicator of poor prognosis and resistance to radiotherapy in patients with NPC. Thus, the authors' findings strongly suggest that the radioresistance of ALDH-positive NPC CSCs to fractionated irradiation is regulated by nuclear Nrf2 accumulation. Nrf2 exerts its effects through the downstream effector NQO1/ALDH1, which depends on ROS attenuation.

A bilayer hydrogel mimicking the periosteum-bone structure for innervated bone regeneration.

In bone tissue, nerves are primarily located in the periosteum and play an indispensable role in bone defect repair. However, most bone tissue engineering approaches ignored the reconstruction of the nerve network. Herein, we aimed to develop a bilayer hydrogel simulating periosteum-bone structure to induce innervated bone regeneration. The bottom "bone" layer consisted of gelatin methacryloyl (GelMA), poly(ethylene glycol) diacrylate (PEGDA), and nano-hydroxyapatite (nHA), whereas the upper "periosteum" layer consisted of GelMA, sodium alginate (SA) and MgCl2. The mechanical properties of the upper and bottom hydrogels were designed to be suitable for neurogenesis and osteogenesis, respectively. Besides, Mg2+ from the "periosteum" layer released at the early stage (within 7 d), which aligned with the optimal time window for nerve regeneration and osteogenic related neuropeptide release. Simultaneously, the prevention of long-term Mg2+ release (after 7 d) could avoid osteogenic inhibition caused by prolonged Mg2+ exposure. Additionally, the incorporation of nHA in the bottom "bone" layer supported the long-term osteogenesis due to its osteoconductivity and slow degradation. In vitro biological experiments revealed that the bilayer hydrogel (GS@Mg/GP@nHA) promoted neurite growth and calcitonin gene-related peptide (CGRP) expression in rat dorsal root ganglion (DRG) neurons, as well as the osteogenesis of rat bone-derived mesenchymal stem cells (BMSCs). Moreover, the in vivo experiments demonstrated that the GS@Mg/GP@nHA hydrogel efficiently promoted nerve network reconstruction and bone regeneration of rat calvarial bone defects. Altogether, the bilayer hydrogel GS@Mg/GP@nHA could promote innervated bone regeneration, providing new insights for biomaterial design for bone tissue engineering.

Quantitative proteomics combined independent PRM analysis reveals the mitochondrial and synaptic mechanism underlying norisoboldine's antidepressant effects.

Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein groups of CSDS versus CON (CSDSCON), imipramine (IMI)-treated versus CSDS (IMICSDS), and NOR-treated versus CSDS (NORCSDS) from the prefrontal cortex. These protein expression alterations were first analyzed by ANOVA with p < 0.05. The protein cluster 1 and cluster 3, in which the pattern of protein levels similar to the mood pattern, showed enrichment in functions and localizations related to mitochondrion, ribosome and synapses. Further GO analysis of the common proteins for NORCSDS groups and NORIMI groups supported the findings from ANOVA analysis. We employed Protein-Protein interaction (PPI) analysis to examine the proteins of NORCSDS and NORIMI, revealing an enrichment of the proteins associated with the mitochondrial ribosomal and synaptic functions. Further independent analysis using parallel reaction monitoring (PRM) revealed that Cox7c, Mrp142, Naa30, Ighm, Apoa4, Ssu72, Mrps30, Apoh, Acbd5, and Cdv3, exhibited regulation in the NOR-treated group to support the homeostasis of mitochondrial functions. Additionally, Dcx, Arid1b, Rnf112, and Fam3c, were also observed to undergo modulation in the NOR-treated groups to support the synaptic formation and functions. These findings suggest that the proteins involved in depression treatment exert effects in strengthen the mitochondrial and synaptic functions in the mice PFC. Western blot analysis supported the data that the levels of Mrpl42, Cox7c, Naa30, Rnf112, Dcx Apoa4, Apoh and Fam3c were altered in the CSDS mice, and rescued by NOR treatment, supporting the PRM data. NOR treatment also rescued the NLRP3 inflammasome activation in CSDS mice. In summary, the current proteomic research conducted on the prefrontal cortex has provided valuable insights into the specific and shared molecular mechanisms underlying pathophysiology and treatment to CSDS-induced depression, shedding light on the therapeutic effects of Norisoboldine.

Analysis of brominated flame retardants exposure-associated chronic kidney disease risk in the US population from the NHANES.

BACKGROUND: Exposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD. METHODS: Totally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD. RESULTS: After adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most. CONCLUSION: Specific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US.

A structure-based virtual screening identifies a novel MDM2 antagonist in the activation of the p53 signaling and inhibition of tumor growth.

p53, a tumor suppressor protein, has a vital role in the regulation of the cell cycle, apoptosis, and DNA damage repair. The degradation of p53 is predominantly controlled by the murine double minute 2 (MDM2) protein, a ubiquitin E3 ligase. The overexpression or amplification of MDM2 is commonly observed in various human cancers bearing wild-type p53 alleles, leading to the rapid degradation of the p53 protein and the attenuation of p53 tumor suppression functions. Thus, a major effort in p53-based cancer therapy has been to research MDM2 antagonists that specifically stabilize and activate p53, leading to the suppression of tumor growth. However, despite numerous efforts to develop MDM2 antagonists, to date they have failed to reach clinical use, largely because of the cytotoxicity associated with these small molecules. This study used our newly designed structure-based virtual screening approach on a commercial compound library to identify a novel compound, CGMA-Q18, which directly binds to MDM2, leading to the activation of p53, the induction of apoptosis, and cell cycle arrest in cancer cells. Notably, CGMA-Q18 significantly inhibited tumor xenograft growth in nude mice without observable toxicity. These findings highlight our useful virtual screening protocol and CGMA-Q18 as a putative MDM2 antagonist.

Clinical and genomic characterization of carbapenem-resistant Enterobacterales bloodstream infections in patients with hematologic malignancies.

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) pose a significant risk to patients with hematologic malignancies, yet the distinct features and outcomes of these infections are not thoroughly understood. Methods: This retrospective study examined the characteristics and clinical outcomes of patients with Enterobacterales BSIs at the Hematology Department of Fujian Medical University Union Hospital from 2018 to 2022. Whole-genome sequencing was conducted on 45 consecutive CRE BSI isolates during this period. Results: A total of 301 patients with Enterobacterales BSIs were included, with 65 (21.6%) cases of CRE and 236 (78.4%) cases of carbapenem-susceptible Enterobacterales (CSE). CRE infections accounted for 16.9% to 26.9% of all Enterobacterales BSIs, and carbapenem-resistant Klebsiella pneumoniae (CRKP) was the predominant strain. The most frequent sequence type (ST) and carbapenemase among CRKP were ST11 (68.6%) and blaKPC-2 (80.0%), respectively. Perianal infections, multiple infection foci, and a history of multiple hospitalizations, ICU stays, and prior CRE infections were identified as risk factors for CRE BSIs. Patients in the CRE group experienced significantly higher proportions of infection-related septic shock (43.1% vs. 19.9%, P < 0.0003) and 30-day all-cause mortality (56.9% vs. 24.6%, P < 0.0001) compared to those in the CSE group. Patient's age and disease subtypes, strain subtypes, and antimicrobial treatment regimens significantly influenced survival in patients with CRE BSIs. Conclusions: CRE BSIs are a frequent complication in patients with hematological malignancies undergoing treatment and are associated with poor survival rates. A comprehensive understanding of risk factors and ongoing surveillance of prevalent strains are essential for the effective management of these infections.

Beyond resorption: osteoclasts as drivers of bone formation.

Emerging evidence illustrates that osteoclasts (OCs) play diverse roles beyond bone resorption, contributing significantly to bone formation and regeneration. Despite this, OCs remain mysterious cells, with aspects of their lifespan-from origin, fusion, alterations in cellular characteristics, to functions-remaining incompletely understood. Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors (OCPs) derived from erythromyeloid progenitors (EMPs). These precursor cells subsequently fuse into OCs essential for normal bone development and repair. Postnatally, hematopoietic stem cells (HSCs) become the primary source of OCs, gradually replacing EMP-derived OCs and assuming functional roles in adulthood. The absence of OCs during bone development results in bone structure malformation, including abnormal bone marrow cavity formation and shorter long bones. Additionally, OCs are reported to have intimate interactions with blood vessels, influencing bone formation and repair through angiogenesis regulation. Upon biomaterial implantation, activation of the innate immune system ensues immediately. OCs, originating from macrophages, closely interact with the immune system. Furthermore, evidence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes. Nevertheless, achieving a pure OC culture remains challenging, and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials. We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process, providing guidance for researchers in identifying OCs both in vitro and in vivo. This review focuses on OC formation, characterization, and the roles of OCs beyond resorption in various bone pathophysiological processes. Finally, therapeutic strategies targeting OCs are discussed.

On-Pump or Off-Pump Impact of Diabetic Patient Undergoing Coronary Artery Bypass Grafting 5-Year Clinical Outcomes.

Background: For diabetic patients undergoing coronary artery bypass grafting (CABG), there is still a debate about whether an off-pump or on-pump approach is advantageous. Methods: A retrospective review of 1269 consecutive diabetic patients undergoing isolated, primary CABG surgery from January 1, 2013 to December 31, 2015 was conducted. Among them, 614 received non-cardiopulmonary bypass treatment during their operation (off-pump group), and 655 received cardiopulmonary bypass treatment (on-pump group). The hospitalization outcomes were compared by multiple logistic regression models with patient characteristics and operative variables as independent variables. Kaplan-Meier curves and Cox proportional-hazard regression models for mid-term (2-year) and long-term (5-year) clinical survival analyses were used to determine the effect on survival after CABG surgery. In order to further verify the reliability of the results, propensity-score matching (PSM) was also performed between the two groups. Results: Five-year all-cause death rates were 4.23% off-pump vs. 5.95% on-pump (p = 0.044), and off-pump was associated with reduced postoperative stroke and atrial fibrillation. Conclusions: These findings suggest that off-pump procedures may have benefits for diabetic patients in CABG.

Altered immune cell in human severe acute pancreatitis revealed by single-cell RNA sequencing.

Background: Severe acute pancreatitis (SAP) is characterized by inflammation, with inflammatory immune cells playing a pivotal role in disease progression. This study aims to understand variations in specific immune cell subtypes in SAP, uncover their mechanisms of action, and identify potential biological markers for predicting Acute Pancreatitis (AP) severity. Methods: We collected peripheral blood from 7 untreated SAP patients and employed single-cell RNA sequencing for the first time to construct a transcriptome atlas of peripheral blood mononuclear cells (PBMCs) in SAP. Integrating SAP transcriptomic data with 6 healthy controls from the GEO database facilitated the analysis of immune cell roles in SAP. We obtained comprehensive transcriptomic datasets from AP samples in the GEO database and identified potential biomarkers associated with AP severity using the "Scissor" tool in single-cell transcriptomic data. Results: This study presents the inaugural construction of a peripheral blood single-cell atlas for SAP patients, identifying 20 cell subtypes. Notably, there was a significant decrease in effector T cell subsets and a noteworthy increase in monocytes compared to healthy controls. Moreover, we identified a novel monocyte subpopulation expressing high levels of PPBP and PF4 which was significantly elevated in SAP. The proportion of monocyte subpopulations with high CCL3 expression was also markedly increased compared to healthy controls, as verified by flow cytometry. Additionally, cell communication analysis revealed insights into immune and inflammation-related signaling pathways in SAP patient monocytes. Finally, our findings suggest that the subpopulation with high CCL3 expression, along with upregulated pro-inflammatory genes such as S100A12, IL1B, and CCL3, holds promise as biomarkers for predicting AP severity. Conclusion: This study reveals monocytes' crucial role in SAP initiation and progression, characterized by distinct pro-inflammatory features intricately linked to AP severity. A monocyte subpopulation with elevated PPBP and CCL3 levels emerges as a potential biomarker and therapeutic target.

A Comparative Study of Traditional and Computer-aided Surgical Simulation Guides in Orthognathic Correction of Bimaxillary Protrusion.

OBJECTIVE: To compare the efficacy of traditional occlusal guides with computer-aided surgical simulation (CASS) guides in enhancing postoperative outcomes for patients with bimaxillary protrusion. METHODS: This retrospective study evaluated 34 patients undergoing anterior maxillary and mandibular subapical osteotomy at the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences. Fourteen patients were treated using traditional occlusal guides, whereas 20 patients were treated with CASS guides (median age 28.6 years, median follow-up 259 days). Pre and postoperative cephalometric indicators were measured using cephalometric software. Data analysis was conducted using SPSS 14.0, with significant differences determined at P < 0.05. RESULTS: All 34 patients experienced primary healing without complications. Follow-up indicated significant improvements in key cephalometric measurements in the CASS group compared with the traditional group, including mandibular position (SNB angle, P < 0.001), jaw relationship (ANB angle, P < 0.001), facial angle (FH-NPo, P = 0.002), and condyle-to-sella distance (Co-S, P = 0.024). The CASS group also showed better aesthetic outcomes, with significant reductions in overjet (P = 0.012), overbite (P = 0.001), and improved alignment of upper and lower incisors (U1-L1 angle, P = 0.031). CONCLUSION: CASS-guided surgery offers a superior alternative to traditional methods for treating bimaxillary protrusion, providing more precise and aesthetically pleasing results. This study highlights the significant advantages of using advanced digital simulation and 3-dimensional printing technologies in orthognathic surgery.