Carbon Dots-Inked Paper with Single/Two-Photon Excited Dual-Mode Thermochromic Afterglow for Advanced Dynamic Information Encryption.

Achieving thermochromic afterglow (TCAG) in a single material for advanced information encryption remains a significant challenge. Herein, TCAG in carbon dots (CDs)-inked paper (CDs@Paper) was achieved by tuning the temperature-dependent dual-mode afterglow of room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF). The CDs were synthesized through thermal treatment of levofloxacin in melting boric acid with post-purification via dialysis. CDs@Paper exhibited TCAG and excitation-dependent afterglow color properties. The TCAG of CDs@Paper exhibited dynamic color changes from blue at high temperatures to yellow at low temperatures by adjusting the proportion of the temperature-dependent TADF and phosphorescence. Notably, two-photon afterglow in CDs-based afterglow materials and time-dependent two-photon afterglow colors were achieved for the first time. Moreover, leveraging the opposite emission responses of phosphorescence and TADF to temperature, CDs@Paper demonstrated TCAG with temperature-sensing capabilities across a wide temperature range. Furthermore, a CDs@Paper-based 3D code containing color and temperature information was successfully developed for advanced dynamic information encryption. This article is protected by copyright. All rights reserved.

Continuous catalytic production of 1,3-dihydroxyacetone: Sustainable approach combining perfusion cultures and immobilized cells.

Currently, the predominant method for the industrial production of 1,3-dihydroxyacetone (DHA) from glycerol involves fed-batch fermentation. However, previous research has revealed that in the biocatalytic synthesis of DHA from glycerol, when the DHA concentration exceeded 50 g·L-1, it significantly inhibited microbial growth and metabolism, posing a challenge in maintaining prolonged and efficient catalytic production of DHA. In this study, a new integrated continuous production and synchronous separation (ICSS) system was constructed using hollow fiber columns and perfusion culture technology. Additionally, a cell reactivation technique was implemented to extend the biocatalytic ability of cells. Compared with fed-batch fermentation, the ICSS system operated for 360 h, yielding a total DHA of 1237.8 ± 15.8 g. The glycerol conversion rate reached 97.7 %, with a productivity of 3.44 g·L-1·h-1, representing 485.0 % increase in DHA production. ICSS system exhibited strong operational characteristics and excellent performance, indicating significant potential for applications in industrial bioprocesses.

Dual rare genetic diseases in five pediatric patients: insights from next-generation diagnostic methods.

BACKGROUND: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. RESULTS: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. CONCLUSIONS: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.

Laboratory-developed Droplet Digital PCR Assay for Quantification of the JAK2 V617F Mutation.

Precise quantification of the JAK2 V617F mutation using highly sensitive assays is crucial for diagnosis, treatment process monitoring, and prognostic prediction in myeloproliferative neoplasms' (MPNs) patients. Digital droplet polymerase chain reaction (ddPCR) enables precise quantification of low-level mutations amidst a high percentage of wild type alleles without the need for external calibrators or endogenous controls. The objective of this study was to optimize a ddPCR assay for detecting the JAK2 V617F mutation and establish it as a laboratory-developed ddPCR assay in our center. The optimization process involved fine-tuning five key parameters: primer/probe sequences and concentrations, annealing temperature, template amount, and PCR cycles. Our ddPCR assay demonstrated exceptional sensitivity, and the limit of quantification (LoQ) was 0.01% variant allele frequency with a coefficient of variation of approximately 76%. A comparative analysis with quantitative PCR on 39 samples showed excellent consistency (r = 0.988). In summary, through rigorous optimization process and comprehensive analytic performance validation, we have established a highly sensitive and discriminative laboratory-developed ddPCR platform for JAK2 V617F detection. This optimized assay holds promise for early detection of minimal residual disease, personalized risk stratification, and potentially more effective treatment strategies in MPN patients and non-MPN populations.

A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2+ Progenitors in the Neonatal Mouse Inner Ear Organoids.

PURPOSE: To investigate the impact of rapamycin on the differentiation of hair cells. METHODS: Murine cochlear organoids were derived from cochlear progenitor cells. Different concentrations of rapamycin were added into the culture medium at different proliferation and differentiation stages. RESULTS: Rapamycin exhibited a concentration-dependent reduction in the proliferation of these inner ear organoids. Nevertheless, organoids subjected to a 10-nM dose of rapamycin demonstrated a markedly increased proportion of hair cells. Furthermore, rapamycin significantly upregulated the expression of markers associated with both hair cells and supporting cells, including ATOH1, MYO7A, and SOX2. Mechanistic studies revealed that rapamycin preferentially suppressed cells without Sox2 expression during the initial proliferation stage, thereby augmenting and refining the population of SOX2+ progenitors. These enriched progenitors were predisposed to differentiate into hair cells during the later stages of organoid development. Conversely, the use of the mTOR activator MHY 1485 demonstrated opposing effects. CONCLUSION: Our findings underscore a practical strategy for enhancing the generation of inner ear organoids with a low dose of rapamycin, achieved by enriching SOX2+ progenitors in an in vitro setting.

M-MDSCs mediated trans-BBB drug delivery for suppression of glioblastoma recurrence post-standard treatment.

We found that immunosuppressive monocytic-myeloid-derived suppressor cells (M-MDSCs) were more likely to be recruited by glioblastoma (GBM) through adhesion molecules on GBM-associated endothelial cells upregulated post-chemoradiotherapy. These cells are continuously generated during tumor progression, entering tumors and expressing PD-L1 at a high level, allowing GBM to exhaust T cells and evade attack from the immune system, thereby facilitating GBM relapse. αLy-6C-LAMP is composed of (i) drug cores with slightly negative charges condensed by cationic protamine and plasmids encoding PD-L1 trap protein, (ii) pre-formulated cationic liposomes targeted to Ly-6C for encapsulating the drug cores, and (iii) a layer of red blood cell membrane on the surface for effectuating long-circulation. αLy-6C-LAMP persistently targets peripheral, especially splenic, M-MDSCs and delivers secretory PD-L1 trap plasmids, leveraging M-MDSCs to transport the plasmids crossing the blood-brain barrier (BBB), thus expressing PD-L1 trap protein in tumors to inhibit PD-1/PD-L1 pathway. Our proposed drug delivery strategy involving intermediaries presents an efficient cross-BBB drug delivery concept that incorporates live-cell targeting and long-circulating nanotechnology to address GBM recurrence.

Impact of blood lipid levels on venous thromboembolism in acute stroke patients.

BACKGROUND: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication of stroke with a high incidence of underdiagnosis. The relationship between dyslipidemia and VTE remains uncertain. Therefore, this study aimed to explore this connection in acute stroke patients to enhance diagnostic and preventative strategies. METHODS: Retrospective data from 7854 acute stroke patients admitted to Dongyang Hospital, Affiliated with Wenzhou Medical University, between 2010 and 2020 were extracted. Differential tests were compared among various blood lipid parameters and the presence or absence of venous thrombosis. Logistic regression analysis was employed to estimate associations. RESULTS: The prevalences of DVT and PE were 3.9 % and 1.1 %, respectively. Additionally, 43 cases (0.5 %) exhibited combined DVT and PE. A high triglyceride (TG) level was associated with a decreased risk of VTE (adjusted odd ratio [aOR] = 0.69, 95 % confidence interval [CI]: 0.54-0.89, P = 0.004), whereas a high low-density lipoprotein cholesterol (LDL-C) level was associated with an increased risk of VTE (aOR = 1.51, 95 % CI: 1.16-1.97, P = 0.002), after adjusting for confounding factors. No significant associations were observed for high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) levels with VTE risk. Subgroup analyses revealed that these associations were significant in ischemic stroke patients. CONCLUSION: Low TG levels and high LDL-C levels were found to be associated with an increased risk of VTE in acute stroke patients, offering valuable insights for the early identification and management of high-risk individuals.

Energy-dependent photoion angular distributions in two-body Coulomb explosions of molecules.

We experimentally study two-body Coulomb explosions of CO2, O2, and CH3Cl molecules in intense femtosecond laser pulses. We observe an obvious variation in the ionic angular distribution of the fragments with respect to the kinetic energy releases (KERs). Using a classical model based on ab initio potential energy curves, we find that the dependence of the ionic angular distribution on the KER is relevant to the fact that the accurate potential energy deviates significantly from the value determined by applying the Coulomb interaction approximation at a relatively small internuclear distance of the molecule. We show that the KER-dependent ionic angular distribution provides an effective way to determine the critical internuclear distance at which the Coulomb interaction approximation holds or breaks down without relying on the knowledge of the accurate potential energy curves.

Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

In Situ Polymerization of Hydrogel Electrolyte on Electrodes Enabling the Flexible All-Hydrogel Supercapacitors with Low-Temperature Adaptability.

All-hydrogel supercapacitors are emerging as promising power sources for next-generation wearable electronics due to their intrinsic mechanical flexibility, eco-friendliness, and enhanced safety. However, the insufficient interfacial adhesion between the electrode and electrolyte and the frozen hydrogel matrices at subzero temperatures largely limit the practical applications of all-hydrogel supercapacitors. Here, an all-hydrogel supercapacitor is reported with robust interfacial contact and anti-freezing property, fabricated by in situ polymerizing hydrogel electrolyte onto hydrogel electrodes. The robust interfacial adhesion is developed by the synergistic effect of a tough hydrogel matrix and topological entanglements. Meanwhile, the incorporation of zinc chloride (ZnCl2 ) in the hydrogel electrolyte prevents the freezing of water solvents and endows the all-hydrogel supercapacitor with mechanical flexibility and fatigue resistance across a wide temperature range of 20 °C to -60 °C. Such all-hydrogel supercapacitor demonstrates satisfactory low-temperature electrochemical performance, delivering a high energy density of 11 mWh cm-2 and excellent cycling stability with a capacitance retention of 90% over 10000 cycles at -40 °C. Notably, the fabricated all-hydrogel supercapacitor can endure dynamic deformations and operate well under 2000 tension cycles even at -40 °C, without experiencing delamination and electrochemical failure. This work offers a promising strategy for flexible energy storage devices with low-temperature adaptability.

Circulating biomarker- and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients. METHODS: The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. RESULTS: A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram. CONCLUSIONS: We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration.

MYBL2 (MYB proto-oncogene like 2) is an emerging prognostic marker for malignant tumors, and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated. We constructed a transcription factor activity profile of osteosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus. Subsequently, we calculated the extent of MYBL2 activation in malignant proliferative osteoblasts. We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma. Furthermore, we systematically correlated MYBL2 with immunological signatures in the tumor microenvironment in pan-cancer, including immune cell infiltration, immune checkpoints, and tumor immunotherapy prognosis. Finally, we developed and validated a risk score (MRGS), derived an osteosarcoma risk score nomogram based on MRGS, and tested its ability to predict prognosis. MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways. MYBL2 expression positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines. Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived suppressor cells, Th2 cell infiltration, CD276, RELT gene expression, and tumor mutation burden. In summary, MYBL2 regulates proliferation, progression, and immune infiltration in osteosarcoma and pan-cancer. Therefore, we found that MYBL2 could be used as a potential marker for predicting the osteosarcoma prognosis. Patients with osteosarcoma and high MYBL2 expression are theoretically more sensitive to methotrexate. An osteosarcoma prognostic nomogram can provide new ideas in the search for osteosarcoma prognostic markers.

Prognostic Factors for Retropharyngeal Abscess in Children Receiving Surgery or Antibiotic Therapy.

OBJECTIVE: Effective management of retropharyngeal abscess (RPA) may predicate upon identification of key patient characteristics. We analyzed characteristics and outcomes of pediatric patients with RPA to identify prognostic factors associated with successful surgical intervention. METHODS: A financial database was searched for pediatric otolaryngology patients with RPA from 2010 to 2021. Medical charts were reviewed for demographics, presenting history, physical examination, laboratory testing, imaging, surgical findings, and hospital course. Bivariate analyses were performed to identify potentially significant predictors of positive drainage. These variables were included in multivariate analysis of surgical outcomes. RESULTS: Of 245 total patients, 159 patients (65%) received surgery and 86 patients (35%) received antibiotics only. Patients with restricted cervical motion, neck swelling, and computed tomography (CT) cross-sectional area (CSA) >2 cm2 were more likely to receive surgery. Rim enhancement on CT imaging was associated with positive surgical drainage (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.16-5.74). However, no variables from clinical symptoms or physical exam were associated with positive drainage. Variables that approached significance were included in multivariate analysis, which revealed only rim enhancement predicted positive drainage (OR 2.57, 95% CI 1.13-5.83). The mean length of stay (LOS) was 2.6 versus 3.5 days (p < 0.001) for medical vs surgical treatment groups, respectively. CONCLUSION: Our study revealed a high success rate of medical management. Although patient characteristics and clinical features were not significant predictors of surgical outcomes, CT findings such as rim enhancement were strongly associated with positive surgical drainage. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1955-1960, 2024.

Disparities in the Presentation and Management of Pediatric Retropharyngeal Abscess.

OBJECTIVES: Differences in management and outcomes of otolaryngologic diseases may reflect inequities driven by social determinants of health. This study aimed to investigate disparities in presentation and outcomes of retropharyngeal abscess (RPA) among 231 pediatric patients. METHODS: Medical records were searched for pediatric patients with RPA from 2010 to 2021. Charts were reviewed for demographics, clinical features, and treatment decisions. Area deprivation index (ADI) scores for patient zip codes were determined. Chi-square analysis independent samples t-test, and regression analyses were used to investigate associations between variables. RESULTS: Among patients presenting for RPA, Black patients were less likely to undergo surgical management than non-Black patients (53.2% vs. 71.6%, p = 0.009). Black patients had a lower rate of treatment with antibiotics prior to hospital admission (19.4% vs. 54.4%, p < 0.001). Among patients who received surgery, Black patients had higher cross-sectional abscess area on CT (6.4 ± 8.4 cm2 > vs. 3.8 ± 3.3 cm2 , p = 0.014), longer length of stay (5.4 ± 3.3 days vs. 3.2 ± 1.5, p < 0.001), and longer time between admission and surgery (2.3 ± 2.1 vs. 0.83 ± 1.1, p < 0.001). Increased ADI was correlated with increased rate of trismus. CONCLUSIONS: Lower rates of pre-admission antibiotics and larger abscess area on CT imaging among Black patients may suggest disparities in access to primary care, resulting in presentation to tertiary care at later stages of disease and higher rates of medical management trial prior to surgical intervention. LEVEL OF EVIDENCE: 3 (retrospective cohort study) Laryngoscope, 134:1907-1912, 2024.

The impact of blood pressure variability on the development of parenchymal hematoma in acute cerebral infarction with atrial fibrillation.

Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBPmax (p = 0.0426), SBPSV (p = 0.0006), DBPmax-min (p = 0.0437), DBPSV (p = 0.0358), DBPSD (p = 0.0393), PPmax-min (p = 0.0478), PPSV (p < 0.0001), PPSD (p = 0.0034), and PPCV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF.

Treatment of Meniere's disease with simultaneous triple semicircular canal occlusion and cochlear implantation.

OBJECTIVE: Report three cases of simultaneous triple semicircular canal occlusion (TSCO) and cochlear implantation (CI) as the treatment of intractable Meniere's disease (MD). CASE REPORTS: Patients with MD can present occasionally with intractable vertigo and profound sensorineural hearing loss (SNHL). TSCO and CI have been proposed to control vertigo and restore profound deafness in patients with MD separately. However, a few studies have reported simultaneous TSCO and CI in the same surgical procedure for the treatment of MD. In the present study, we described three patients with MD showing incapacitating vertigo and severe SNHL who underwent simultaneous TSCO and CI after examinations of auditory system, vestibular system, and imaging. Their symptoms were significantly alleviated during the follow-up period. CONCLUSION: The combined TSCO and CI remains a viable treatment option which is effective for the control of vertigo as well as the restoring of hearing in patients with MD.

Intervening in hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p for tumor microenvironment regulation and cancer therapy.

BACKGROUND: Despite being a common malignant tumor, the molecular mechanism underlying the initiation and progression of triple-negative breast cancers (TNBCs) remain unclear. Tumor-associated macrophages (TAMs) are often polarized into a pro-tumor phenotype and are associated with a poor prognosis of TNBCs. Exosomes, important mediators of cell-cell communication, can be actively secreted by donor cells to reprogram recipient cells. The functions and molecular mechanisms of tumor cell-derived exosomes in TNBCs progression and TAMs reprogramming urgently need to be further explored. RESULTS: We demonstrated that tumor cell-derived exosomes enriched with miR-184-3p were taken up by macrophages to inhibit JNK signaling pathway by targeting EGR1, thereby inducing M2 polarization of macrophages and synergistically promoting tumor progression. Nanoparticles loaded with oncogene c-Myc inhibitor JQ1 could suppress the polarization process by reducing Rac1-related exosome uptake by macrophage. More importantly, it was found for the first time that tumor-suppressive miR-184-3p was actively sorted into exosomes by binding to RNA-binding protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), thus facilitating tumor cell proliferation and metastasis by relieving the inhibitory effect of miR-184-3p on Mastermind-like 1 (MAML1). Overexpressing miR-184-3p in tumor cells and simultaneously knocking down hnRNPA2B1 to block its secretion through exosomes could effectively inhibit tumor growth and metastasis. CONCLUSIONS: Our study revealed that hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p from breast cancer cells to macrophages was an important mediator of TNBCs progression, providing new insights into TNBCs pathogenesis and therapeutic strategies.

Methods, bioinformatics tools and databases in ecDNA research: An overview.

Extrachromosomal DNA (ecDNA), derived from chromosomes, is a cancer-specific circular DNA molecule. EcDNA drives tumor initiation and progression, which is associated with poor clinical outcomes and drug resistance in a wide range of cancers. Although ecDNA was first discovered in 1965, tremendous technological revolutions in recent years have provided crucial new insights into its key biological functions and regulatory mechanisms. Here, we provide a thorough overview of the methods, bioinformatics tools, and database resources used in ecDNA research, mainly focusing on their performance, strengths, and limitations. This study can provide important reference for selecting the most appropriate method in ecDNA research. Furthermore, we offer suggestions for the current bioinformatics analysis of ecDNA and provide an outlook to the future research.

The Association of Same-Day CT Scan with Postoperative Outcomes in Isolated Orbital Fracture Repair.

The potential benefits to surgical outcomes of intraoperative and/or same-day computed tomography (CT) during isolated orbital fracture reconstruction are debatable, and previous research on this topic is limited by small sample size. This retrospective IBM MarketScan Commercial and Medicare Supplemental research database study examined patients undergoing isolated orbital reconstruction from January 1, 2012 to December 31, 2018, to assess whether same-day CT affected postoperative outcomes. The average age of the 5,023 participants was 37 (standard deviation [SD]: 16) years and 63% were males. The data revealed that 16.2% (815 of 5,023) patients underwent a same-day CT. Those who underwent a same-day CT scan exhibited reduced odds of postoperative enophthalmos (adjusted odds ratio [aOR]: 0.269; 95% confidence interval [CI]: 0.167-0.433) and diplopia (aOR: 0.670; 95% CI: 0.495-906). Interestingly, these patients also displayed a higher rate of revision surgeries (aOR: 2.721; 95% CI: 1.893-3.912). In summary, while same-day CT scans diminish certain postoperative complications of orbital fracture repair, they are also associated with an increased likelihood of subsequent surgical revision.