Ultrathin, High-Aspect-Ratio Bismuth Sulfohalide Nanowire Bundles for Solution-Processed Flexible Photodetectors.

In this study, a novel synthesis of ultrathin, highly uniform colloidal bismuth sulfohalide (BiSX where X = Cl, Br, I) nanowires (NWs) and NW bundles (NBs) for room-temperature and solution-processed flexible photodetectors are presented. High-aspect-ratio bismuth sulfobromide (BiSBr) NWs are synthesized via a heat-up method using bismuth bromide and elemental S as precursors and 1-dodecanethiol as a solvent. Bundling of the BiSBr NWs occurs upon the addition of 1-octadecene as a co-solvent. The morphologies of the BiSBr NBs are easily tailored from sheaf-like structures to spherulite nanostructures by changing the solvent ratio. The optical bandgaps are modulated from 1.91 (BiSCl) and 1.88 eV (BiSBr) to 1.53 eV (BiSI) by changing the halide compositions. The optical bandgap of the ultrathin BiSBr NWs and NBs exhibits blueshift, whose origin is investigated through density functional theory-based first-principles calculations. Visible-light photodetectors are fabricated using BiSBr NWs and NBs via solution-based deposition followed by solid-state ligand exchanges. High photo-responsivities and external quantum efficiencies (EQE) are obtained for BiSBr NW and NB films even under strain, which offer a unique opportunity for the application of the novel BiSX NWs and NBs in flexible and environmentally friendly optoelectronic devices.

M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy.

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy. Lipid nanoparticles (LNPs), considered a prospective vehicle for nucleic acid delivery, have demonstrated efficacy in human use during the COVID-19 pandemic. This study introduces a novel biomaterial-based platform, M1-polarized macrophage-derived cellular nanovesicle-coated LNPs (M1-C-LNPs), specifically engineered for a combined gene-immunotherapy approach against solid tumor. The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles (M1-NVs), effectively facilitating apoptosis in cancer cells without impacting T and NK cells, which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication. Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs, owing to the presence of adhesion molecules on M1-NVs, thereby contributing to superior tumor growth inhibition. These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy, with significant implications for advancing biomaterial use in cancer therapeutics.

Association between depressive symptoms and cardiovascular diseases in the Korean geriatric population: A nationwide retrospective cohort study.

INTRODUCTION: Depression has emerged as a modifiable risk factor for cardiovascular disease (CVD). However, evidence on whether depressive symptoms measured using a self-report questionnaire are associated with CVD incidence is scarce. Therefore, we aimed to investigate the association between depressive symptoms and CVD risk using data from national health examinations and insurance claim records. METHODS: This retrospective cohort study included participants who underwent the Korean National Screening Program for Transitional Ages at age 66 years between 2007 and 2017. The presence of depressive symptoms was defined as affirmative responses to any of three questions (loss of activities and interests, worthlessness, and hopelessness) selected from the Geriatric Depression Scale. Incident composite CVD event included myocardial infarction, stroke, heart failure, and CVD death. The association between depressive symptoms and CVD risk was evaluated using hazard ratios (HRs) and 95 % confidence intervals (CIs) estimated with Cox proportional hazards models. RESULTS: Among 88,765 participants (48.5 % women) aged 66 years, 4036 incident CVD events occurred during a mean follow-up of 6.8 years. Participants with depressive symptoms had a significantly higher risk of CVD than those without depressive symptoms (adjusted HR = 1.16 [95 % CI: 1.07-1.24]). The three individual depressive symptoms showed similar associations with CVD risk (loss of activities and interests, adjusted HR = 1.17 [95 % CI: 1.08-1.26]; worthlessness, 1.15 [1.03-1.29]; hopelessness, 1.13 [1.01-1.26]). LIMITATIONS: The study was limited to participants aged 66 years. Despite extensive adjustment for potential confounders and multiple sensitivity analyses, residual confounding and reverse causality could not be ruled out. CONCLUSION: The presence of depressive symptoms was associated with an increased risk of CVD. Screening for depressive symptoms in the general population may effectively mitigate the burden of CVD.

Biologic and clinical analysis of childhood gamma delta T-ALL identifies LMO2/STAG2 rearrangements as extremely high-risk.

Acute lymphoblastic leukemia expressing the gamma delta T cell receptor (yo T-ALL) is a poorly understood disease. We studied 200 children with yo T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. yo T-ALL diagnosed in children under three years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by Poly(ADP-ribose) polymerase (PARP) inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric yo T-ALL.

Geometry-Driven Fabrication of Mini-Tablets via 3D Printing: Correlating Release Kinetics with Polyhedral Shapes.

The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R2 = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile.

Preparation and Evaluation of Inhalable Microparticles with Improved Aerodynamic Performance and Dispersibility Using L-Leucine and Hot-Melt Extrusion.

Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery.

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

Minimally invasive surgical technique for unstable supracondylar humerus fractures in children (Gartland type III or IV).

Background: Achieving and maintaining anatomical reduction during the treatment of pediatric humerus fractures, classified as Gartland type III or IV, presents a clinical challenge. Herein, we present a minimally invasive surgical approach using a novel and simple K-wire push technique that aids in achieving and maintaining anatomical reduction. Methods: We reviewed data of children receiving treatment for supracondylar fractures of the humerus at our hospital between January 2016 and December 2020. Patients were divided into two groups based on the method of treatment: Group 1 was treated with the K-wire push technique, and Group 2 was treated with the standard technique as described by Rockwood and Wilkins. The medical records and radiographic images were reviewed. In total, 91 patients with Gartland types III and IV fractures were included, with 37 and 54 patients in Groups 1 and 2, respectively. Results: The postoperative reduction radiographic parameters and Flynn scores at final follow-up were not significantly different between the two groups. Conclusion: The minimally invasive K-wire push technique for unstable supracondylar fractures in children is a safe and effective alternative for improving reduction. Using this technique, complications can be minimized, and the requirement for open reduction can be reduced.

The long-term effects of the fenestration in patients with extracardiac Fontan circulation-a multicenter Korean cohort study based on national Fontan registry.

Introduction: The long-term effects of fenestration in patients with Fontan circulation remain unclear. We aim to evaluate the fenestration impact on early and late outcomes in patients with extracardiac Fontan (ECF) using a propensity score matching analysis. Methods: We performed an extensive retrospective multicenter clinical data review of the Korean Fontan registry and included 1,233 patients with surgical ECF (779 fenestrated, 454 non-fenestrated). Demographics, baseline, and follow-up data were collected and comprehensively analyzed. Patients were divided into two groups according to the baseline presence or absence of surgical fenestration. Subsequently, patients were sub-divided according to the fenestration status at the last follow-up. Propensity-score matching was performed to account for collected data between the 2 groups using a multistep approach. The primary outcomes were survival and freedom from Fontan failure (FFF). We also looked at postoperative hemodynamics, cardiopulmonary exercise test results, oxygen saturations, and functional status. Results: After propensity-score matching (454 matched pairs), there was no difference in survival or FFF between the 2 groups. However, ECF patients with baseline fenestration had significantly lower oxygen saturation (p = 0.001) and lower functional status (p < 0.001). Patients with fenestration had significantly longer bypass times, higher postoperative central venous pressure, higher postoperative left atrial pressure, and less prolonged pleural effusion in the early postoperative period. The propensity score matching according to the fenestration status at the last follow-up (148 matched pairs) showed that patients with a persistent fenestration had significantly lower oxygen saturation levels (p < 0.001). However there were no intergroup differences in the functional status, survival and FFF. Conclusions: Our results showed no long-term benefits of the Fenestration in terms of survival and FFF. Patients with persistent fenestration showed oxygen desaturation but no difference in exercise intolerance was shown between the 2 groups.

Organ-on-a-Chip Approach for Accelerating Blood-Brain Barrier Nanoshuttle Discovery.

Organ-on-a-chip, which recapitulates the dynamics of in vivo vasculature, has emerged as a promising platform for studying organ-specific vascular beds. However, its practical advantages in identifying vascular-targeted drug delivery systems (DDS) over traditional in vitro models remain underexplored. This study demonstrates the reliability and efficacy of the organ-on-a-chip in screening efficient DDS by comparing its performance with that of a conventional transwell, both designed to simulate the blood-brain barrier (BBB). The BBB nanoshuttles discovered through BBB Chip-based screening demonstrated superior functionality in vivo compared to those identified using transwell methods. This enhanced effectiveness is attributed to the BBB Chip's accurate replication of the structure and dynamics of the endothelial glycocalyx, a crucial protective layer within blood vessels, especially under shear stress. This capability of the BBB Chip has enabled the identification of molecular shuttles that efficiently exploit the endothelial glycocalyx, thereby enhancing transendothelial transport efficacy. Our findings suggest that organ-on-a-chip technology holds considerable promise for advancing research in vascular-targeted DDS due to its accurate simulation of molecular transport within endothelial systems.

The Effect of Intermittent Pneumatic Compression on Hemodynamics and Regional Cerebral Oxygen Saturation in Laparoscopic Bariatric Surgery with Mild Hypercapnia in the Steep Reverse Trendelenburg Position.

Obesity negatively affects hemodynamics and cerebral physiology. We investigated the effect of the utilization of an intermittent pneumatic compression (IPC) device on hemodynamics and cerebral physiology in patients undergoing laparoscopic bariatric surgery under general anesthesia with lung-protective ventilation. Sixty-four patients (body mass index > 30 kg/m2) were randomly assigned to groups that received an IPC device (IPC group, n = 32) and did not (control group, n = 32). The mean arterial pressure (MAP), heart rate (HR), need for vasopressors, cerebral oxygen saturation (rSO2), and cerebral desaturation events were recorded. The incidence of intraoperative hypotension was not significantly different between groups (p = 0.153). Changes in MAP and HR over time were similar between groups (p = 0.196 and p = 0.705, respectively). The incidence of intraoperative cerebral desaturation was not significantly different between groups (p = 0.488). Changes in rSO2 over time were similar between the two groups (p = 0.190) during pneumoperitoneum. Applying IPC to patients with obesity in the steep reverse Trendelenburg position may not improve hemodynamic parameters, vasopressor requirements, or rSO2 values during pneumoperitoneum under lung-protective ventilation. During laparoscopic bariatric surgery, IPC alone has limitations in improving hemodynamics and cerebral physiology.

Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection.

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs. However, oral supplementation of drug is relatively less efficient in terms of transmissibility to RGCs compared to direct delivery methods such as intraocular injection or delivery using subconjunctival depots. Neither method is ideal, given the risks of infection and subconjunctival scarring without novel techniques. By contrast, extracellular vesicles (EVs) have advantages as a drug delivery system with low immunogeneity and tissue interactions. We have evaluated the EV delivery of NAM as an RGC protective agent using a quantitative assessment of dendritic integrity using DiOlistics, which is confirmed to be a more sensitive measure of neuronal health in our mouse glaucoma model than the evaluation of somatic loss via the immunostaining method. NAM or NAM-loaded EVs showed a significant neuroprotective effect in the mouse retinal explant model. Furthermore, NAM-loaded EVs can penetrate the sclera once deployed in the subconjunctival space. These results confirm the feasibility of using subconjunctival injection of EVs to deliver NAM to intraocular targets.

Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.

Serial mediating effects of childhood trauma and conduct behaviors on the impact of family history among patients with alcohol use disorder.

Family history (FH) of alcoholism increases the risk of alcohol use disorder (AUD); however, the contribution of childhood trauma (CT) in this respect remains unclear. This study investigated the relationship between FH and AUD-related clinical characteristics (social onset, antisocial tendency, and severity of problematic alcohol consumption) through the mediating effects of childhood trauma (CT) and conduct behaviors (CB) in a Korean male population with AUD. A total of 304 patients hospitalized for AUD at 16 psychiatric hospitals completed standardized questionnaires, including self-rated scales. Mediation analyses were performed using the SPSS macro PROCESS. Individuals with positive FH (133, 44%) had greater CT and CB and more severe AUD-related clinical characteristics than those without FH (171, 56%). In the present serial mediation model, FH had significant direct and indirect effects on AUD-related clinical characteristics through CT and CB. Indirect effects were 21.3% for social onset, 46.3%, antisocial tendency, and 37.9% for problematic drinking. FH directly contributed to AUD-related clinical characteristics, and CT and CB played mediating roles. This highlights the importance of careful intervention and surveillance of adverse childhood experiences and conduct disorder to prevent and mitigate alcohol-related problems in individuals with FH of AUD.

Rheumatoid Arthritis and Risk of Depression in South Korea.

Importance: Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. Objective: To investigate the risk of depression following RA diagnosis among patients in South Korea. Design, Setting, and Participants: This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Exposures: Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Main Outcomes and Measures: Newly diagnosed depression (ICD-10 codes F32 or F33). Results: The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). Conclusions and Relevance: This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Epididymitis with Pasteurella multocida isolated from two male Japanese Black beef calves.

Two male Japanese Black calves developed an enlarged scrotum and testis. Orchiectomy was performed and pus was collected during surgery. After removal of the testis, bacteriological and histopathological examinations were conducted to investigate the cause and confirm the diagnosis. Based on the results obtained, both cases were diagnosed with epididymitis caused by an infection with Pasteurella multocida. This is the first study to show that P. multocida causes epididymitis in male calves. Further studies are required to clarify the details underlying the infection of calves with P. multocida.

Surgical treatment of bovine nasal granuloma and an allergological exploration.

Nasal granuloma in cattle results from inflammation within, and attendant proliferation of, the nasal mucosa possibly in response to an allergic response. However, the relationship between nasal granuloma and allergies remains unclear. Furthermore, severe cases have a poor prognosis because there is currently no effective treatment. Herein, we report three cases of nasal granuloma with severe stertorous breathing that were treated surgically. We also conducted an allergological exploration. Following surgical removal clinical signs did not recur in two of the three cases; however, stertorous breathing persisted in one case, and the cow was sacrificed 4 months later. A histopathological examination revealed that all nasal granulomas featured varying infiltrations of macrophages eosinophils, mast cells, and lymphocytes. The number of mast cells and the proportion of these cells that had degranulated were significantly higher in the granulomas than in normal nasal mucosae. In addition, serum histamine levels were higher in nasal granuloma cases than in normal cows, although serum immunoglobulin E levels were similar, and lymphocyte infiltration in the submucosal layer suggested type I and type IV allergies. Collectively, the results indicate the efficacy of complete surgical curettage for the treatment of allergic nasal granuloma in cattle. Further studies are required to identify the causes and risk factors of allergic nasal granuloma in cows.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease.

INTRODUCTION: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging. OBJECTIVES: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds. METHODS: Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold. RESULTS: With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD. CONCLUSION: Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

Initial experience with the enhanced recovery after surgery (ERAS) protocols in gynecologic surgery at an urban academic tertiary medical center.

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

Polymeric DNase-I nanozymes targeting neutrophil extracellular traps for the treatment of bowel inflammation.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its idiopathic nature, IBD does not have a fundamental cure; current available therapies for IBD are limited to prolonged doses of immunomodulatory agents. While these treatments may reduce inflammation, limited therapeutic efficacy, inconsistency across patients, and adverse side effects from aggressive medications remain as major drawbacks. Recently, excessive production and accumulation of neutrophil extracellular traps (NETs) also known as NETosis have been identified to exacerbate inflammatory responses and induce further tissue damage in IBD. Such discovery invited many researchers to investigate NETs as a potential therapeutic target. DNase-I is a natural agent that can effectively destroy NETs and, therefore, potentially reduce NETs-induced inflammations even without the use of aggressive drugs. However, low stability and rapid clearance of DNase-I remain as major limitations for further therapeutic applications. In this research, polymeric nanozymes were fabricated to increase the delivery and therapeutic efficacy of DNase-I. DNase-I was immobilized on the surface of polymeric nanoparticles to maintain its enzymatic properties while extending its activity in the colon. Delivery of DNase-I using this platform allowed enhanced stability and prolonged activity of DNase-I with minimal toxicity. When administered to animal models of IBD, DNase-I nanozymes successfully alleviated various pathophysiological symptoms of IBD. More importantly, DNase-I nanozyme administration successfully attenuated neutrophil infiltration and NETosis in the colon compared to free DNase-I or mesalamine.