Paclitaxel Prodrug Enables Glutathione Depletion to Boost Cancer Treatment.

Herein, we constructed a paclitaxel (PTX) prodrug (PA) by conjugating PTX with acrylic acid as a cysteine-depleting agent. The as-synthesized PA can assemble with diacylphosphatidylethanolamine-PEG2000 to form stable nanoparticles (PA NPs). After endocytosis into cells, PA NPs can specifically react with cysteine and trigger release of PTX for chemotherapy. On the other hand, the depletion of cysteine can greatly downregulate the intracellular content of glutathione and lead to oxidative stress outburst-provoking ferroptosis. The released PTX can elicit antitumor immune response by inducing immunogenic cell death, thus promoting dendritic cells maturation and cascaded cytotoxic T lymphocytes activation, which not only produces a robust immunotherapy effect but also synergizes the ferroptosis therapy by inhibiting cysteine transport via the release of interferon-γ in the activated immune system. As a result, PA NPs exhibit favorable in vitro and in vivo antitumor performance with reduced systemic toxicity. Our work highlights the potential of simple molecular design of prodrugs for enhancing the therapeutic efficacy toward malignant cancer.

The balance between helper T 17 and regulatory T cells in osteoimmunology and relevant research progress on bone tissue engineering.

BACKGROUND: Bone regeneration is a well-regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process. OBJECTIVE: This review aims to summarize the role of the T-helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering. RESULTS: The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano-structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration. CONCLUSION: Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.

A pontine-specific axonal niche supports de novo gliomagenesis.

Diffuse intrinsic pontine gliomas (DIPGs), a major type of pediatric high-grade gliomas located in the pons, are the leading cause of death in children with brain cancer. A subset (20-25%) of DIPGs harbor a lysine 27-to-methionine (K27M) mutation in HIST1H3B , which encodes histone H3.1, and an activating ACVR1 mutation. The occurrence of this pair of mutations in DIPGs, but not in pediatric gliomas in other anatomical locations, suggests the existence of a pontine-specific niche that favors DIPG gliomagenesis. Unfortunately, the identity of the underlying pontine niche remains elusive as available mouse models fail to recapitulate the anatomic specificity that characterizes DIPGs. Herein we show that the trigeminal root entry zone (TREZ), a pontine structure where several major axon tracts intersect, is enriched with proliferating oligodendrocyte-lineage cells during brainstem development. Introducing both H3.1K27M and activating Acvr1 and Pik3ca mutations (which co-occur frequently with H3.1K27M in human DIPGs) into the mouse brain leads to rapid gliomagenesis. This pathology recapitulates the pons specificity of DIPGs as glioma cells proliferate on axon tracts at the TREZ. We further show that a hyaluronan receptor important for cell stemness (HMMR) plays a key role in glioma cell proliferation at the TREZ. We propose that H3.1K27M and its co-occurring mutations drive pontine specific gliomagenesis by inducing a proliferative response of oligodendrocyte-lineage cells with enhanced stemness on large TREZ axon tracts. One-Sentence Summary: The trigeminal root entry zone underlies pontine-specific gliomagenesis driven by H3.1K27M and its co-occurring mutations.

Quantitatively analyzing the dissociation and release of disulfide-containing organic nanoparticles.

The disintegration of nanoparticles and drug release are important and imperative for nanoparticle formulations of therapeutic agents. However, quantitatively monitoring the drug release of nanomedicines is a major challenge. In this work, boron-dipyrromethene (BDP) was applied as a model drug to study the disassembly of nanoparticles and drug release. BDP dimers with disulfide and ester bonds were synthesized, and their nanoparticles were made. The accurate analysis of bond breaking in BDP nanoparticles could not be realized by using confocal laser scanning microscopy. Hence, the possible products after bond cleavage were quantified by using liquid chromatography tandem mass spectrometry (LC-MS/MS). BDP nanoparticles could be endocytosed into cancer cells, and the disulfide bonds and ester bonds were broken to promote the disassociation of nanoparticles and BDP release. Then, near-infrared BDP nanoparticles were investigated in live mice by near-infrared fluorescence imaging and LC-MS/MS. The release of BDP was low (<10%) and BDP maintained the original dimer structure in vivo, which showed that the bond breaking for BDP nanoparticles was difficult in vivo. These results could help us understand the breaking law of disulfide bonds and ester bonds in nanoparticles and are beneficial for developing practical new drug formulations.

Ferrocene-Conjugated Paclitaxel Prodrug for Combined Chemo-Ferroptosis Therapy of Cancer.

Herein, we developed a paclitaxel prodrug (PSFc) through the conjugation of paclitaxel (PTX) and ferrocene via a redox-responsive disulfide bond. PSFc displays acid-enhanced catalytic activity of Fenton reaction and is capable of forming stable nanoparticles (PSFc NPs) through the assembly with distearoyl phosphoethanolamine-PEG2000. After being endocytosed, PSFc NPs could release PTX to promote cell apoptosis in response to overexpressed redox-active species of tumor cells. Meanwhile, the ferrocene-mediated Fenton reaction promotes intracellular accumulation of hydroxyl radicals and depletion of glutathione, thus leading to ferroptosis. Compared with the clinically used Taxol, PSFc NPs exhibited more potent in vivo antitumor outcomes through the combined effect of chemotherapy and ferroptosis. This study may offer insight into a facile design of a prodrug integrating different tumor treatment methods for combating malignant tumors.

Multicolor Tuning of Perylene Diimides Dyes for Targeted Organelle Imaging In Vivo.

The adjustment of the emission wavelengths and cell permeability of the perylene diimides (PDI) for multicolor cell imaging is a great challenge. Herein, based on a bay-region substituent engineering strategy, multicolor perylene diimides (MCPDI) were rationally designed and synthesized by introducing azetidine substituents on the bay region of PDIs. With the fine-tuned electron-donating ability of the azetidine substituents, these MCPDI showed high brightness, orange, red, and near infrared (NIR) fluorescence along with Stokes shifts increasing from 35 to 110 nm. Interestingly, azetidine substituents distorted to the plane of the MCPDI dyes, and the twist angle of monosubstituted MCPDI was larger than that of disubstituted MCPDI, which might efficiently decrease their π-π stacking. Moreover, all of these MCPDI dyes were cell-permeable and selectively stained various organelles for multicolor imaging of multiple organelles in living cells. Two-color imaging of lipid droplets (LDs) and other organelles stained with MCPDI dyes was performed to reveal the interaction between the LDs and other organelles in living cells. Furthermore, a NIR-emitting MCPDI dye with a mitochondria-targeted characteristic was successfully applied for tumor-specific imaging. The facile synthesis, excellent stability, high brightness, tunable fluorescence emission, and Stokes shifts make these MCPDI promising fluorescent probes for biological applications.

Study on the reaction kinetics of simultaneous recovery of iron phosphate from hypophosphite in perferite oxidation plating waste.

Phosphorus is an indispensable and irreplaceable element in the ecosystem. Based on the ability of ferrate(VI) to remove phosphate by producing iron phosphate, a new method for using ferrate(VI) to treat hypophosphite has been studied. In this study, ferrate was added to the hypophosphate solution in a controlled manner, and the oxidation efficiency of ferrate(VI) on hypophosphate was studied under various initial pH conditions, when the pH value of 6.0, the hypophosphate oxidation rate reached 14.0%. Research findings, Ferrate recovered hypophosphate through precipitation and adsorption under various initial pH conditions. To further investigate the mechanism of hypophosphate recovery, the morphology and microstructure of the deposition were analysed using Fourier transform infrared, X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy. The kinetic process of ferrate recovery from hypophosphate was analysed. The recovery process follows second-order reaction kinetics, and the reaction rate is highest at pH 6.0. The value of kA1 is 1.742 × 10-2. This study shows that ferrate (VI) is a promising treatment tool for low-cost phosphate wastewater. Furthermore, this method offers a clean phosphorus recovery process without the generation of harmful substances.

Viscosity-activated carbon dots for noninvasive disease diagnosis, therapeutic efficacy assessment and anticancer drug screening.

Abnormal levels of intracellular microviscosity have a close relationship with some diseases and pathologies. Therefore, quantitative imaging of viscosity at the cellular and organ levels is beneficial for disease diagnosis, curative effect evaluation, and anticancer drug screening. Herein, we synthesized viscosity-activated orange-red emitting carbon dots (named as LP-CDs) from lignin and p-phenylenediamine using a one-step method, whose fluorescence intensity, lifetime, and quantum yield significantly increase with rising viscosity. Meanwhile, the fluorescence intensity of LP-CDs also has a good linear relationship with the solution viscosity. Taking the advantages of high sensitivity, noninvasiveness, and rapid result output of fluorescence imaging, LP-CDs can visualize the cellular viscosity changes induced by inflammation and hyperglycemia, and image tumor evolution. More importantly, LP-CDs can be used as powerful sensors to screen anticancer drugs in vivo by evaluating therapeutic effects. This work provides a new scheme for constructing robust nanoprobes to achieve the diagnosis and imaging-guided surgery of viscosity related diseases.

Tumor associated antigens combined with carbon dots for inducing durable antitumor immunity.

Although therapeutic nanovaccines have made a mark in cancer immunotherapy, the shortcomings such as poor homing ability of lymph nodes (LNs), low antigen presentation efficiency and low antitumor efficacy have hindered their clinical transformation. Accordingly, we prepared advanced nanovaccines (CMB and CMC) by integrating carbon dots (CDs) with tumor-associated antigens (B16F10 and CT26). These nanovaccines could forwardly target tumors harbouring LNs, induce strong immunogenicity for activating cytotoxic T cells (CTLs), thereby readily eliminating tumor cells and suppressing primary/distal tumor growth. This work provides a promising therapeutic vaccination strategy to enhance cancer immunotherapy.

Hospital Patient Experience: Exploring Hospitals as Shifters and Sustainers Over Time.

BACKGROUND AND OBJECTIVES: Patient experience is a key factor in measuring hospital performance, and the Hospital Consumer Assessment of Healthcare Providers and Systems survey tool is used to assess patient perceptions. Hospitals with positive patient experience tend to have a better quality of clinical care, lower readmission and mortality rates, and an overall shorter inpatient length of stay. Studies have identified several organizational determinants of high- and low-rated patient experiences, including hospital size, type, staffing levels, and patient demographics.This study aims to explore the determinants of consistently high- and low-rated patient experience, as well as factors associated with positive and negative changes in patient experience over time. METHOD: The 2014 to 2019 American Hospital Association annual survey and the Centers for Medicare and Medicaid Services Hospital Value-Based Purchasing database were used. A total of 2801 acute-care hospitals were included in this study. A series of multivariate logistic regressions were used to model the probability of "1" (being a superior hospital or an inferior hospital). In addition, a generalized linear mixed model for binary responses was used to analyze the change (probability of positive and negative change). RESULTS: The results showed that most hospitals did not sustain superior or inferior performance, and competition decreased the likelihood of a hospital consistently performing well in terms of patient experience. Superior performance was associated with hospital ownership (P < .001), size (P = .026), location (P = .002), teaching status (P = .009), average Herfindahl-Hirschman Index value (P = .005), and Medicaid and Medicare patient population. On the other hand, inferior performance was associated with hospital ownership (P = .003), size (P < .001), teaching status (P = .003), safety net status (P = .020), and Medicaid and Medicare patient population. CONCLUSION: This study aimed to examine the trends in hospital patient experience performance and the influence of hospital organizational characteristics on those trends. Our findings allow us to question the widely held belief that patient experience is a metric of differentiation and industry competition, suggesting that performance in this domain has not been utilized by most hospitals as a source of sustainable competitive advantage. The findings from this study highlight the importance of considering changes in performance over time and the need for significant organizational efforts to improve hospital performance in terms of patient experience.

Inpatient Palliative Care and Healthcare Utilization Among Older Patients With Alzheimer's Disease and Related Dementia (ADRD) and High Risk of Mortality in U.S. Hospitals.

Background. Despite the potential of palliative care (PC) to enhance the quality of life for patients with advanced dementia, there is limited knowledge of its inpatient utilization patterns. This study investigated inpatient PC consultation utilization patterns and evaluated its impact on hospital length of stay (LOS) and medical costs among older patients diagnosed with Alzheimer's Disease and Related Dementia who were at a high risk of mortality (ADRD-HRM). Methods. Using the 2016-2019 National Inpatient Sample database, we conducted multivariable logistic regression analyses to identify individual and hospital characteristics influencing PC consultation utilization. We subsequently performed generalized linear models to estimate LOS (using Poisson distribution) and hospital charges (via log-transformation). Results. Our sample encompassed 965,644 hospital discharges (weighted n = 4,828,219) of patients aged 65 years and above with ADRD-HRM. Among them, 14.6% received inpatient PC. There was a notable uptrend in PC consultation utilization from 13.3% in 2016 to 16.3% in 2019 (p trend<.001). Factors positively influencing and associated with PC utilization included patients that are older, non-Hispanic White, with higher income, receiving care from teaching hospitals, and facilitated with greater bed capacity (all P < .05). Although patients who received PC were more likely to have 3.0% longer LOS (P < .001), they had 19.2% lower hospital charges (P < .001). Conclusions. PC substantially reduced hospital expenditures for older patients with ADRD-HRM, but the prevalence remained low at 14.6% in the study period. Future studies should explore the unmet needs of patients with lower sociodemographic status and those in rural hospitals to further increase their PC consultation utilization.

COVID-19 booster vaccine uptake and reduced risks for long-COVID: A cross-sectional study of a U.S. adult population.

Long-COVID (having symptoms lasting 3 months or longer post-infection) is an emerging public health concern, yet research on whether COVID-19 booster vaccines can mitigate this condition is limited. This study examined associations between booster uptake and long-COVID prevalence among U.S. adults. Data were analyzed from 8757 adults aged 18 years or older with a history of COVID-19 infection from the 2022 National Health Interview Survey. Weighted prevalence and logistic regression models examined relationships between self-reported COVID-19 booster vaccination status and long-COVID, adjusting for sociodemographics and health factors. 19.5 % reported experiencing long-COVID. Individuals receiving the COVID-19 booster vaccine had significantly lower adjusted odds of long-COVID (OR 0.75, 95 % CI 0.61-0.93) compared to unvaccinated individuals. Overall, these findings suggest that COVID-19 booster vaccination is associated with a reduced prevalence of long-COVID among the U.S. adult population, underscoring the importance of optimizing booster uptake to mitigate the long-term impacts of COVID-19.

Patterns and Reasons for Being Uninsured Among Sexual Minority Adults Before and After the Affordable Care Act Implementation.

Purpose: We aimed to identify the self-reported reasons for being uninsured and sociodemographic factors associated with uninsurance among lesbian, gay, or bisexual (LGB) adults before and after the Affordable Care Act (ACA). Methods: We analyzed the 2013-2018 National Health Interview Survey data using multivariable logistic regression models to estimate the odds of being uninsured and the prevalence of self-reported reasons for not having insurance among LGB adults aged 18-64 years. Results: The study included 2124 LGB adults. The weighted uninsured rate decreased significantly from 19.6% in 2013 to 13.2% in 2017-2018 (odds ratio 0.61; 95% confidence interval 0.47-0.78). The primary reason cited for not having insurance post-ACA was similar to pre-ACA, with cost-related factors being the most commonly reported (31.5%). Conclusion: The overall uninsured rate decreased among LGB adults from 2013 to 2018, whereas disparities across subpopulations remained. Cost-related factors remained significant barriers to obtaining insurance coverage.

Identification and drug resistance of pathogen of ulcerative skin disease and its immune responses and protective efficacy after vaccination in a giant spiny frog, Quasipaa spinosa.

OBJECTIVE: In order to explore the pathogen of the ulcerative skin disease in giant spiny frog (Quasipaa spinosa), and to provide theoretical basis for the prevention and control of the disease in practical production, this study was carried out to isolate and identify the pathogenic bacteria from the sick frogs suffering from rotting skin disease and to carry out the immunization test of the inactivated vaccine. METHODS: Physiological and biochemical characterization, and molecular biology of the pathogenic bacteria were identified, and drug screening and immunization responses were also carried out. RESULTS: The dominant bacterium QS01 was isolated from the lesions of diseased giant spiny frogs, which was confirmed to be the causative agent of the rotting skin disease of giant spiny frogs by artificial regression infection test. Based on the fact that the pathogen is a gram-negative short bacterium, its phenotypic characteristics and 16S rRNA and gyrB gene sequences were analyzed, and the bacterium was determined to be Citrobacter freundii. The results of the drug sensitivity test showed that the bacterium was sensitive to 11 antibiotics, including Enrofloxacin, Fleroxacin and Ciprofloxacin, including three non-polluting drugs such as Florfenicol, Roxithromycin and Thiamphenicol, as well as three Chinese herbal medicines such as Rheum officinale Baill, Coptis chinensis Franch and Scutellaria baicalensis Georgi. Most non-specific immune responses could go to recovery in 24h. The frogs were vaccinated with QS01 formaldehyde inactivated vaccine by injection, immersion and spraying, and the serum antibody potency of the three immunized groups with the average potency reached the peak at the 20th d after immunization, and the serum antibody potency of the injected immunized group was at the highest ratio of 1:64-128 (101.6), while the immersed group and the spraying group attained the ratio of 1:16-32 (20.2) and 1:16-32 (16) respectively, and lasted until the 30th d. The control group that was not immunized had the highest serum antibody potency of 1:16-32 (20.2) and 1:16-32 (16), and continued until the 30th d. The control group that was not immunized was not immunized. The serum antibody potency of the unimmunized control group was 1:2 to 2(2). The immunoprotection rates after takedown were 100 %, 85.71 % and 71.43 %, respectively. CONCLUSION: C. freundii is the pathogen of the disease in this farm, and the vaccination by immersion and spraying can effectively prevent and control the rotting skin disease in frogs. These results revealed pathogenicity of C. freundii and its activation of host immune response, which will provide a scientific reference for the aquaculture and disease prevention in Q. spinosa culture.

Marijuana use disorder among adults with functional disabilities-A US population-based cross-sectional study.

BACKGROUND AND OBJECTIVES: Recent studies suggest a growing trend in marijuana use, compared to a stable prevalence of marijuana use disorder among US adults over the first 15 years of the 21st century. This study investigated the recent patterns of marijuana use disorder among people with disabilities (PWD). METHODS: We extracted a nationally representative sample (N = 209,058) from the 2015-2019 National Survey on Drug Use and Health data set and examined associations by functional disability status (any disability, disability by type, and number of disabling limitations) with marijuana use disorder using a series of independent multivariable logistic regression models. We also performed trend analyses during the study period. RESULTS: The prevalence of marijuana use disorder (from 1.7% to 2.3%) increased significantly among PWD between 2015 and 2019 (p-trend < .001). PWD were significantly more likely to report marijuana use disorder (odds ratio [OR], 1.37, 95% confidence interval [CI], 1.24-1.52) than people without disability (PWoD). Those with cognitive limitation only (OR, 1.78, 95% CI, 1.53-2.06) and ≥2 limitations (OR, 1.29, 95% CI, 1.10-1.51) were more likely to report marijuana use disorder than PWoD. DISCUSSION AND CONCLUSIONS: PWD had a consistently higher prevalence of marijuana use disorder than PWoD. Additionally, the level of risk for marijuana use disorder varied by disability type and number of disabling limitations. SCIENTIFIC SIGNIFICANCE: Our study provided new nuance on disparities in marijuana use disorder between PWD and PWoD and further revealed the varied risks for marijuana use disorder across different disability statuses.

Telehealth Utilization During the COVID-19 Pandemic Among People With Functional Disabilities in the U.S.: A Preliminary Analysis of National Health Interview Survey 2020 Data.

Introduction: Telehealth has been widely promoted and adopted at multiple levels in the U.S. healthcare system during the COVID-19 pandemic. However, this rapid expansion of telehealth services may have further exacerbated health inequities among marginalized groups. Methods: Using the 2020 National Health Interview Survey, this study compared patterns of telehealth use between people with functional disabilities and people without disabilities during the first year of the pandemic. Results: In the multivariable-adjusted logistic regression models, respondents with moderate disabilities were significantly more likely to report telehealth use, not pandemic related (OR=1.25, 95% CI=1.03, 1.52) and telehealth use, pandemic related (OR=1.43, 95% CI=1.28, 1.60) than people without disabilities. Similarly, respondents with severe disabilities were significantly more likely to report telehealth use, not pandemic related (OR=1.46, 95% CI=1.07, 2.00) and telehealth use, pandemic related (OR=2.06, 95% CI=1.72, 2.46). In addition, telehealth use varied by the number of limitations and disability type. Conclusions: People with functional disabilities were more likely to report telehealth use than people without disabilities. Furthermore, these associations strengthened with increasing disability severity and number of limitations while varying by disability type. Additional studies are warranted to explore ways of providing patient-centered telehealth to responsively meet various healthcare needs of people with functional disabilities and improve their health outcomes.

Association of Medicaid expansion with 2-year survival and time to treatment initiation in gastrointestinal cancer patients: A National Cancer Database study.

INTRODUCTION: We evaluated whether Medicaid expansion (ME) was associated with improved 2-year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer. METHODS: GI cancer patients diagnosed 40-64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre-expansion; those diagnosed from 2014 to 2016 were considered post-expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2-year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30- and 90 days. Multivariable Difference-in-Difference models were used to compare expansion/nonexpansion cohorts pre-/post-expansion, adjusting for patient, clinical, and hospital factors. RESULTS: 377,063 patients were included. No significant difference in 2-year survival was demonstrated across ME and non-ME states overall or in site-based subgroup analysis. In stage-based subgroup analysis, 2-year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87-0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01-1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09-1.16) and 90 days (1.22; 1.17-1.27). Site-based subgroup analyses indicated increased likelihood of TTI within 30 and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days. CONCLUSION: ME was not associated with significant improvement in 2-year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30- and 90-day odds of TTI was higher for those from ME compared with non-ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

Suicide Ideation, Plans, and Attempts Among Military Veterans vs Nonveterans With Disability.

Importance: People with disability are at heightened risk for suicide ideation, planning, and attempt, with risk growing as the number of disabling limitations increases. Military veterans have higher rates of suicide deaths and disability relative to nonveterans. Objective: To evaluate whether veteran status is associated with greater risk for suicide in those with disability. Design, Setting, and Participants: This survey study used cross-sectional self-reported data from US adults who participated in the 2015-2020 National Survey on Drug Use and Health. Data were weighted to represent the population. Data analysis was conducted from July to August 2022. Main Outcomes and Measures: Suicide ideation, planning, and attempt served as primary outcomes. Disability status (present or absent) and number of disabling limitations (1, 2, or ≥3) served as factors. Veteran status was determined based on self-report (veteran or nonveteran). Multivariable logistic regression examined suicide ideation, planning, and attempt as a function of veteran status and disability variables. Results: Participants included 231 099 US veterans and nonveterans, representing 236 551 727 US adults, of whom 20.03% (weighted n = 47 397 876) reported a disabling limitation, 8.92% were veterans (weighted n = 21 111 727; 16.0% aged 35-49 years; 91.0% men; 6.7% Hispanic; 10.9% non-Hispanic Black; and 78.4% non-Hispanic White) and 91.08% were nonveterans (weighted n = 215 440 000; 25.4% aged 35-49 years; 44.0% male; 16.5% Hispanic; 11.7% non-Hispanic Black; and 63.3% non-Hispanic White). Overall, 4.39% reported suicide ideation, planning, or attempt (weighted n = 10 401 065). Among those with no disability, veteran status was associated with higher risk of suicide planning (adjusted odds ratio [AOR], 1.71; 95% CI, 1.17-2.49). Among those with 1 or 2 disabling limitations, being a veteran was associated with a lower risk of suicide planning (AOR, 0.57; 95% CI, 0.34-0.95) and history of attempt (AOR, 0.46; 95% CI, 0.24-0.88). Conclusions and Relevance: In this study of how suicide risk differs as a function of disability and veteran status, risk for death by suicide was lower among veterans with disability relative to nonveterans with disability. Veteran status may mitigate risk for suicide given increased receipt of more disability-related care through the Department of Veterans Affairs. Further research would extend this line of inquiry by examining the cause and type of disability as well as perceptions of disability on self-worth. It is possible that physical wounds of war are protective because of the meaning and value of service to one's country.

Self-assembled nanoformulations of paclitaxel for enhanced cancer theranostics.

Chemotherapy has occupied the critical position in cancer therapy, especially towards the post-operative, advanced, recurrent, and metastatic tumors. Paclitaxel (PTX)-based formulations have been widely used in clinical practice, while the therapeutic effect is far from satisfied due to off-target toxicity and drug resistance. The caseless multi-components make the preparation technology complicated and aggravate the concerns with the excipients-associated toxicity. The self-assembled PTX nanoparticles possess a high drug content and could incorporate various functional molecules for enhancing the therapeutic index. In this work, we summarize the self-assembly strategy for diverse nanodrugs of PTX. Then, the advancement of nanodrugs for tumor therapy, especially emphasis on mono-chemotherapy, combinational therapy, and theranostics, have been outlined. Finally, the challenges and potential improvements have been briefly spotlighted.

The healing capacity and osteogenesis pattern of demineralized dentin matrix (DDM)-fibrin glue (FG) compound.

Demineralized dentin matrix (DDM) is an osteoconductive and osteoinductive material that has been successfully used in sinus floor augmentation and alveolar ridge augmentation in clinical applications. It releases bone morphogenetic proteins (BMPs) and other growth factors, making DDM a suitable grafting material. However, the granular particle of DDM makes it difficult to anchor into the bone defect area. The aim of this study was to investigate the biological effects and osteoinductivity of the combination of DDM and Fibrin Glue (FG) at an optimal ratio on bone healing from a critical bone defect in an animal model. The mouse osteoblastic cell line (MC3T3-E1) was co-cultured with various ratios of DDM and FG to examine their effects on osteoblast proliferation and differentiation, as indicated by alkaline phosphatase (ALP) activity, osteocalcin (OC) production and mineralized nodules formation. The optimal ratio was then chosen for further study with a rabbit calvarial defective model, in which they were implanted with DDM or DDM-FG1 (1 g: 0.1 ml) and DDM-FG2 (1 g: 0.5 ml) compounds, or left blank for 2, 4, 8 and 12 weeks to investigate soft tissue and new bone regeneration. Micro-CT and histology analysis were used to evaluate the total grafting properties according to the different healing periods. The result from in vitro studies demonstrated that the ratio of 1:0.1 induced more ALP activity and mineralized nodules, while the ratio of 1: 0.5 (DDM-FG combined) induced more osteocalcin (OC) at specific time points. In the animal model, the 3D new bone volume in all DDM-FG treatment groups was significantly greater than that in the blank group at 2, 4, 8 and 12 weeks. Furthermore, the new bone volume was greater in DDM-FG2 when compared to the other groups during the early weeks of the healing period. In histological analysis, clusters of osteoblasts were formed adjacent to the DDM particles, and newly formed bone was observed in all groups, suggesting an osteoinductive property of DDM. Moreover, the greater new collagen synthesis observed at 4 weeks suggested that early bone healing was induced in the DDM-FG2 group. This study demonstrated that at an optimal ratio, the DDM-FG compound enhances osteogenic activities and bone regeneration.