Delivery Capacity Research Articles

Distributed economic optimisation of multi‐energy park operation based on cloud platform architecture considering network delivery capacity

AbstractTo address the issues of node interaction power overrun and high carbon emissions that may arise during distributed optimization in multi‐energy parks (MEPs), this paper proposes a distributed low‐carbon and economic operation method for multi‐energy parks based on a cloud platform that considers network transmission capacity.The proposed method achieves maximun profit by designing a two layer collaborative architecture for distributed optimization operations. At the top level, cloud platform services are utilized to build a model for checking network transport capacity and carbon emission quotas, optimizing network node over‐limit inspection . The bottom layer constructs a distributed optimization model for multi‐energy complementation in each park, taking into account the information privacy and individual interests of each multi‐energy park. An improved alternating direction multiplier method (ADMM) is proposed to effectively solve the two‐layer framework. The case studies show that the distributed optimization method under cloud platform services proposed in this paper can achieve maximum revenue for integrated energy service provider while ensuring the safe operation of multi‐energy parks, and reasonably allocate the benefits of collaborative operation among various parks while promoting carbon emission reduction.

β-Cyclodextrin Nanophotosensitizers for Redox-Sensitive Delivery of Chlorin e6.

The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via a disulfide bond, creating nanophotosensitizers that were fabricated for the redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize succinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss), and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). The chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by a dialysis procedure. They formed small particles with an average particle size of 152.0 ± 23.2 nm. The Ce6 release rate from the bCDsu-ss-Ce6 nanophotosensitizers was accelerated by the addition of glutathione (GSH), indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive photosensitizer delivery capacity. The bCDsu-ss-Ce6 nanophotosensitizers have a low intrinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, the bCDsu-ss-Ce6 nanophotosensitizers showed an improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production, and phototoxicity compared to those of Ce6 alone. GSH addition resulted in a higher Ce6 uptake ratio, ROS generation, and phototoxicity than Ce6 alone, indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. In a tumor xenograft model using HeLa cells, the bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than in normal organs. In other words, the fluorescence intensity in tumor tissues was significantly higher than that of other organs, while Ce6 alone did not specifically target tumor tissue. These results indicated a higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, as demonstrated by their efficient inhibition of the growth of tumors in an in vivo animal tumor xenograft study.

Stimuli-responsive nanoparticles delivered by a nasal-brain pathway alleviate depression-like behavior through extensively scavenging ROS.

Depression is one of the most common mental diseases, which seriously affects patients' physical and mental health. Emerging evidence has indicated that oxidative stress (OS) is a major cause of neurodegeneration involved in the pathogenesis of depression. Consequently, targeted reactive oxygen species (ROS) elimination is regarded as a promising strategy for efficient depression therapy. In addition, insufficient brain drug delivery is the main obstacle to depression therapy owing to the presence of the blood-brain barrier (BBB). To achieve the goals of bypassing the BBB and promoting antioxidant therapy for depression, a broad-spectrum ROS scavenging NPs was rationally designed through a nasal-brain pathway developed for combined ROS scavenging and brain drug delivery. A hexa-arginine (R6) modified ROS-responsive dextran (DEX) derivate was synthesized for antidepressant olanzapine (Olz) and H2 donor amino borane (AB) loading to prepare Olz/RDPA nanoparticles (NPs). Subsequently, the NPs were dispersed into a thermoresponsive hydrogel system based on poloxamer. In vitro and in vivo results demonstrated that Olz/RDPA in situ thermoresponsive hydrogel system could effectively deliver NPs to the brain via the nasal-brain pathway and alleviate depression-like behaviors through combined ROS depletion and inhibition of 5-HT dysfunction of the oxidative stress-induced. The proposed ROS-scavenging nanotherapeutic would open a new window for depression treatment. STATEMENT OF SIGNIFICANCE: ROS is an innovative therapeutic target involving the pathology of depression whereas targeted delivery of ROS scavenging has not been achieved yet. In the current study, ROS-responsive nanoparticles (Olz/RDPA NPs) were prepared and dispersed in a thermosensitive hydrogel for delivery through the nasal-brain pathway for the treatment of depression. Sufficient ROS depletion and improvement of delivery capacity by the nasal-brain pathway effectively could reverse oxidative stress and alleviate depressive-like behavior. Collectively, these nanoparticles may represent a promising strategy for the treatment of depression.

Vehicle routing problem optimization with machine learning in imbalanced classification vehicle route data

The object of this research is a combinatorial optimization problem arising in the problem of the route of goods delivery vehicles. In this study, the proposed method for solving combinatorial optimization problems consists of several stages: Data Cleaning, Data Preprocessing, K-NN and Cavacity Vehicle Routing Problem model. The results show that the machine learning approach can optimise combinatorial optimization problems, especially in generating vehicle route points and delivery capacity. The characteristics in determining vehicle routes by considering latitude and longitude points. This research builds a framework and implements it in a multi-class optimization model to reduce overfitting and misclassification results caused by unbalanced multiclassification from the influence of the number of 'nodes' on vehicle routes with machine learning. The purpose of the model in general is to gain an understanding of the mechanism in the problem so that it can classify unbalanced vehicle route data based on Jalur Nugraha Ekakurir delivery routes. So that with the availability of the model can be a model in determining vehicle routes based on the capacity limit of the number of shipments of goods. The results of research with machine learning models and vehicle routing problems with testing K values 11, 13, 15. Where it has a percentage of K=11 accuracy 57.3265 % and K=13 accuracy 57.3265 % and K=15 accuracy 81.8645 %. From the test results with odd K values have better accuracy and the K 15 K=15 value is better with a percentage of 81.8645 % compared to K 11 K=11, and 13 K=13. As a result, the developed model in terms of accuracy of the cavacity vehicle routing problem model has an accuracy of 93.80 % and the time series achieves an average precision of 93.31 % and with a recall value of 93.80 %. The results obtained can be useful in developing a more modern model, Cavacity Vehicle Routing Problem with Machine Learning

Advances in Immunomodulatory MOFs for Biomedical Applications.

Given the crucial role of immune system in the occurrence and progression of various diseases such as cancer, wound healing, bone defect, and inflammation-related diseases, immunomodulation is recognized as a potential solution for treatment of these diseases. Immunomodulation includes both immunosuppression in hyperactive immune conditions and immune activation in hypoactive conditions. For these purposes, metal-organic frameworks (MOFs) are investigated to modulate immune responses either by their own bioactivities or by delivering immunomodulatory agents due to their excellent biodegradability and high delivery capacity. This review starts with an overview of the synthesis strategies of immunomodulatory MOFs, followed by a summarization on the latest applications of immunomodulatory MOFs in cancer immunomodulatory, wound healing, inflammatory disease, and bone tissue engineering. A variety of design considerations, in order to optimize immunomodulatory properties and efficacy of MOFs, is also involved. Last, the challenges and perspectives of future research, which are expected to provide researchers with new insight into the design and application of immunomodulatory MOFs, are discussed.

Revolutionising Cancer Diagnosis and Treatment: A Review on Advancements in Nanomaterial-based Theranostics

The persistent struggle against cancer has given rise to the development of nanotheranostics, a domain that integrates therapeutic and diagnostic capabilities within nanoscale structures. This paper explores advancements in nanomaterials and nanoparticles for cancer nanotheranostics, focusing on their design, significance, and applications. The incorporation of biocompatible nanoparticles in cancer therapy offers personalised, targeted approaches while minimising side effects. The use of nanomaterials such as metals, polymers, and lipids enable precise drug delivery and imaging. Various imaging modalities, including ultrasound and fluorescence, complement therapeutic strategies for enhanced precision. Critical parameters for nanomaterial selection and design are discussed, emphasising biocompatibility, targeting efficiency, and drug delivery capacity. Biocompatibility ensures safe interactions within biological systems, requiring mitigation of toxicological concerns through strategies like anti-inflammatory peptides or ligand-functionalization. Targeting efficiency combines passive and active targeting to enhance specificity, reshaping cancer diagnostics and therapy. Drug delivery capacity is achieved through engineered core-shell structures with distinct properties, including liposomes, micelles, and dendrimers, each tailored for targeted therapy and imaging. This paper also discusses the advancements in the field of cancer treatment using nanotheranostics and its economic impact on the Canadian healthcare systems while following the ethical guidelines towards patients’ consent, privacy, and the proper use of emerging technologies.

Assessing readiness to implement long-acting injectable HIV antiretroviral therapy: provider and staff perspectives

BackgroundLong-acting injectable antiretroviral therapy (LAI-ART) represents the next innovation in HIV therapy. Pre-implementation research is needed to develop effective strategies to ensure equitable access to LAI-ART to individuals living with HIV.MethodsWe conducted focus group discussions (FGDs) with providers and staff affiliated with HIV clinics in San Francisco, Chicago, and Atlanta to understand barriers to and facilitators of LAI-ART implementation. Participants also completed a short survey about implementation intentions. FGDs were held via video conference, recorded, transcribed, and thematically analyzed using domains associated with the Consolidated Framework for Implementation Research (CFIR).ResultsBetween September 2020 and April 2021, we led 10 FDGs with 49 participants, of whom ~60% were prescribing providers. Organizational readiness for implementing change was high, with 85% agreeing to being committed to figuring out how to implement LAI-ART. While responses were influenced by the unique inner and outer resources available in each setting, several common themes, including implementation mechanisms, dominated: (1) optimism and enthusiasm about LAI-ART was contingent on ensuring equitable access to LAI-ART; (2) LAI-ART shifts the primary responsibility of ART adherence from the patient to the clinic; and (3) existing clinic systems require strengthening to meet the needs of patients with adherence challenges. Current systems in all sites could support the use of LAI-ART in a limited number of stable patients. Scale-up and equitable use would be challenging or impossible without additional personnel. Participants outlined programmatic elements necessary to realize equitable access including centralized tracking of patients, capacity for in-depth, hands-on outreach, and mobile delivery of LAI-ART. Sites further specified unknown logistical impacts on implementation related to billing/payer source as well as shipping and drug storage.ConclusionsAmong these HIV care sites, clinic readiness to offer LAI-ART to a subset of patients is high. The main challenges to implementation include concerns about unequal access and a recognition that strengthening the clinic system is critical.

Optimization of PLGA-DSPE hybrid nano-micelles with enhanced hydrophobic capacity for curcumin delivery

Poly (D, L Lactic-co-Glycolic acid) (PLGA) is an FDA-approved polymer. It is distinguished from other biocompatible polymers by its feasibility of production and safety for intravenous cancer tumor targeting. Curcumin (CUR) is a natural molecule with versatile bioactivities including inhibiting the nuclear Factor kappa B (Nf-kB) levels in cancer cells, increased by chemotherapy agents. Our group previously reported a successful decrease in the p65 (RelA) subunit of Nf-kB using 125 µg/ml CUR loaded into PLGA nano-micelles. However, this amount was insufficient to reduce all Nf-kB subunits. This study aimed to increase the hydrophobic capacity of PLGA toward CUR using 1,2-Distearoyl-sn-glycerol-3-phosphoethanolamine (DSPE), an FDA-approved phospholipid. PLGA-DSPE hybrid nano-micelles (HNM) were prepared using two different methods, oil-in-water (OiWa) and film preparation-rehydration (FiRe). The encapsulated CUR was successfully increased to 250 µg/ml using the FiRe method. Physicochemical characterization of CUR-loaded HNM was performed using DLS FT-IR, DSC, and HPLC. In HNM with a size of 156.6 nm, DSPE, incorporated with all functional groups of PLGA, and CUR was trapped in the core of this structure. The release profile of CUR was suitable for targeted cancer therapy and the Encapsulation Efficacy was 92%.

A Fuzzy Parameterized Multiattribute Decision-Making Framework for Supplier Chain Management Based on Picture Fuzzy Soft Information

Supplier selection as a multiattribute decision-making (MADM) problem has various inherent uncertainties due to a number of symmetrical variables. In order to handle such information-based uncertainties, rational models like intuitionistic fuzzy sets have already been introduced in the literature. However, a picture fuzzy set (PiFS) with four dimensions of positive, neutral, negative, and rejection is better at capturing and interpreting such kinds of ambiguous information. Additionally, fuzzy parameterization (FPara) is helpful for evaluating the degree of uncertainty in the parameters. This study aims to develop a fuzzy parameterized picture fuzzy soft set (FpPiFSS) by integrating the ideas of PiFS and FPara. This integration is more adaptable and practical since it helps decision makers manage approximation depending on their objectivity and parameterization uncertainty. With the assistance of instructive examples, some of the set-theoretic operations are examined. A decision support framework is constructed using matrix manipulation, preferential weighting, fuzzy parameterized grades based on Pythagorean means, and the approximations of decision makers. This framework proposes a reliable algorithm to evaluate four timber suppliers (initially scrutinized by perusal process) based on eight categorical parameters for real estate projects. In order to accomplish suppliers evaluation, crucial validation outcomes are taken into account, including delivery level, purchase cost, capacity, product quality, lead time, green degree, location, and flexibility. To assess the advantages, dependability, and flexibility of the recommended strategy, comparisons in terms of computation and structure are provided. Consequently, the results are found to be reliable, analog, and consistent despite the use of fuzzy parameterization and picture fuzzy setting.

Near-Infrared-II-Driven Pollen Micromotors for Inflammatory Bowel Disease Treatment.

Inflammatory bowel disease (IBD) is a common inflammatory bowel disease with a high incidence rate and serious consequences. Attempts in this area are focusing on developing efficient delivery systems for relieving IBD. Herein, we present a kind of near-infrared-II (NIR-II)-activated pollen-derived micromotor (PDMM) as an efficient delivery system for treating IBD. These PDMMs are pollen grains with half of them covered by a gold (Au) layer, which can result in an asymmetric thermal gradient around the PDMMs under NIR-II irradiation, thereby forming a thermophoretic force to drive PDMMs to move spontaneously. Besides, the inherent spiny and hollow architectures of pollen grains endowed the PDMMs with outstanding capacity of adherence and drug delivery, respectively. Based on these features, we have demonstrated that the PDMMs could move actively in vivo with the irradiation of NIR-II light and adhere to the surrounding tissues for drug delivery. Thus, the PDMMs loaded with dexamethasone show desirable curative effects on treating IBD. These results indicated that the proposed PDMM-based delivery system has great potential in clinic gastrointestinal administration.

Prioritization of zoonoses for multisectoral, One Health collaboration in Somalia, 2023

BackgroundThe human population of Somalia is vulnerable to zoonoses due to a high reliance on animal husbandry. This disease risk is exacerbated by relatively low income (poverty) and weak state capacity for health service delivery in the country as well as climate extremes and geopolitical instability in the region. To address this threat to public health efficiently and effectively, it is essential that all sectors have a common understanding of the priority zoonotic diseases of greatest concern to the country. MethodsRepresentatives from human, animal (domestic and wildlife), agriculture, and environmental health sectors undertook a multisectoral prioritization exercise using the One Health Zoonotic Disease Prioritization (OHZDP) tool developed by the United States CDC. The process involved: reviewing available literature and creating a longlist of zoonotic diseases for potential inclusion; developing and weighting criteria for establishing the importance of each zoonoses; formulating categorical questions (indicators) for each criteria; scoring each disease according to the criteria; and finally ranking the diseases based on the final score. Participants then brainstormed and suggested strategic action plans to prevent, and control prioritized zoonotic diseases. ResultsThirty-three zoonoses were initially considered for prioritization. Final criteria for ranking included: 1) socioeconomic impact (including sensitivity) in Somalia; 2) burden of disease in humans in Somalia); 3) availability of intervention in Somalia; 4) environmental factors/determinants; and 5) burden of disease in animals in Somalia. Following scoring of each zoonotic disease against these criteria, and further discussion of the OHZDP tool outputs, seven priority zoonoses were identified for Somalia: Rift Valley fever, Middle East respiratory syndrome, anthrax, trypanosomiasis, brucellosis, zoonotic enteric parasites (including Giardia and Cryptosporidium), and zoonotic influenza viruses. ConclusionsThe final list of seven priority zoonotic diseases will serve as a foundation for strengthening One Health approaches for disease prevention and control in Somalia. It will be used to: shape improved multisectoral linkages for integrated surveillance systems and laboratory networks for improved human, animal, and environmental health; establish multisectoral public health emergency preparedness and response plans using One Health approaches; and enhance workforce capacity to prevent, control and respond to priority zoonotic diseases.

Functionally Tailored Metal-Organic Framework Coatings for Mediating Ti Implant Osseointegration.

Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF-coated Ti implants and highlights their potential utility for modulating the bio-implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF-coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.

Aggregate delivery capacity planning with a crowdsourcing option

We consider the problem of determining an expected cost minimizing aggregate delivery capacity plan using a combination of permanent, seasonal, and crowdsourcing capacity to satisfy demand with seasonal variations. We characterize the structure of an optimal solution and perform numerical experiments to ascertain the impact of the crowdsourcing option on the delivery capacity plan. We find that crowdsourcing is a valid substitute for permanent capacity but may result in increased or decreased seasonal capacity. Further, we observe that the cost savings from utilizing the crowdsourcing option may come at the cost of lower service levels for customers, drawing into question the sustainability of the savings.

O.4.6-1 Examining the feasibility, acceptability, and effectiveness of a self-compassion workshop in physical education class for adolescent females

Abstract Purpose In adolescence, enrollment in Physical Education (PE) drastically drops in the transition from grade 9 to 10 – particularly for females who disengage at higher rates than males after completing provincial PE curricular requirements. This is problematic since engagement in PE has the potential to shape and guide young females’ perceptions of movement, their bodies, and coping with life’s difficulties through physical activity. Body image distress may be one reason to explain PE disengagement therefore, may warrant intervention. Self-compassion is an emotion regulation strategy that helps deal with body-related distress and may be an effective strategy to help females cope with these negative experiences in PE and PA beyond. This is the first pilot study to examine the feasibility, acceptability and effectiveness of a self-compassion psychoeducation intervention in PE. Methods A pragmatic one-group pre-test post-test design, with 1-month follow-up was used. The sample consisted of n = 52 students from 2 Canadian high school grade 9 grade 10 females PE classes. The intervention consisted of a 75 minute self-compassion workshop. Feasibility and acceptability were assessed using multiple data sources from a 75-minute focus group, and 1-month follow up survey data. Effectiveness was examined using change in scores on PE attitudes, PA attitudes, self-compassion, and body-image coping. Results There was overall feasibility evidence for the intervention, whereby, all available classes and teachers agreed to host the workshop. The majority of students completed the pre-survey 84.6% (44/52), workshop 71.5% (37/52), and focus group session 92.3% (48/52), and expressed interest in having follow-up workshops 60.7% (17/28). The intervention demonstrated acceptability, as indicated by students indicating high scores on workshop acceptability, ethical conduct, effectiveness, limited negative side effects, material being beneficial and presented in a useful way. Small improvements were shown for self-compassion (d = 0.0761), PE attitudes (d = 0.0761) and PA attitudes (d = 0.245) from pre-workshop to follow-up. Conclusions The knowledge gained from this pilot study may enhance capacity for delivery of scalable curriculum-informed physical education promotion strategies which may be broadly transferrable to physical activity programs.

Patient Experiences and Provider Perspectives on Accessing Gender-Affirming Surgical Services in the Veterans Health Administration.

Transgender and gender diverse (TGD) veterans have a greater prevalence of suicide morbidity and mortality than cisgender veterans. Gender-affirming surgery (GAS) has been shown to improve mental health for TGD veterans. In 2021, the Veterans Health Administration (VHA) announced the initiation of a rulemaking process to cover GAS for TGD patients. This study explores patients' and providers' perspectives about access to GAS and other gender-affirming medical interventions not offered in the VHA including barriers, facilitators, and clinical and policy recommendations. TGD patients (n = 30) and VHA providers (n = 22). Semi-structured telephone interviews conducted from August 2019 through January 2020. Two TGD analysts used conventional and directed content analysis to code transcribed data. VHA policy exclusions were the most cited barrier to GAS. Additional barriers included finding information about GAS, traveling long distances to non-VHA surgeons, out-of-pocket expenses, post-surgery home care, and psychological challenges related to the procedure. Factors facilitating access included surgical care information from peers and VHA providers coordinating care with non-VHA GAS providers. Pre- and post-operative care through the VHA also facilitated receiving surgery; however, patients and providers indicated that knowledge of these services is not widespread. Respondents recommended disseminating information about GAS-related care and resources to patients and providers to help patients navigate care. Additional recommendations included expanding access to TGD mental health specialists and establishing referrals to non-VHA GAS providers through transgender care coordinators. Finally, transfeminine patients expressed the importance of facial GAS and hair removal. A policy change to include GAS in the VHA medical benefits package will allow the largest integrated healthcare system in the United States to provide evidence-based GAS services to TGD patients. For robust and consistent policy implementation, the VHA must better disseminate information about VHA-provided GAS-related care to TGD patients and providers while building capacity for GAS delivery.

Strategizing export promotion in Indian telecom sector: empirical evidence using time and frequency analysis

ABSTRACT This study evaluates how foreign direct investment (FDI) impact the Indian telecom manufacturing sector and the exports of telecom products between January 2012 and February 2020. It establishes a long-term non-linear relationship among FDI, exports, and industrial production index that exhibits regime shifts, time-varying, and wavelet coherence under exchange rate volatility. The study revealed that telecom sectoral FDI majorly strengthens the service delivery capacity rather than enhancing the production of telecom products. The policy and regulatory initiatives, mainly focused on ‘import substitution’, may not automatically lead to strengthening of domestic manufacturing and increased participation in the global value chain.

Why is Turkey losing its doctors? A cross-sectional study on the primary complaints of Turkish doctors

In 2022, Turkey encountered the formidable task of addressing an unprecedented loss of medical doctors and seeking remedies for potential issues within the healthcare system. This study set out to explore the inclination of 402 actively practicing Turkish doctors to depart from Turkey, assess the socio-demographic and socio-economic factors influencing this trend, and establish the hierarchy of raised concerns among doctors. Employing a cross-sectional and analytical approach, the study drew comparisons between doctors' demographic characteristics and the significance of their grievances, while also examining the correlation between the importance of complaints and the desire to remain in Turkey. The doctors' primary complaints encompassed financial challenges, instances of violence in the healthcare sector, and insufficient examination durations. The migration of doctors poses a substantial risk to healthcare accessibility, public health, and the sustainability of Turkey's healthcare delivery capacity. To mitigate this risk and curb doctor migration, corrective measures must be implemented to improve working conditions. Additionally, there is a need for further scientific research focusing on doctors' concerns, particularly in developing countries like Turkey, to expand the current body of literature on this subject.

Short-term intensive fasting enhances the immune function of red blood cells in humans

BackgroundFasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question.ResultsWe used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability.ConclusionSTIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases.

Pharmacists’ perceptions regarding feasibility, acceptability, and usefulness of student-delivered naloxone education services in community pharmacy: A mixed methods study in Alabama

BackgroundGiven that Alabama has the highest opioid prescribing rate in the nation, efforts to promote safe opioid use and reduce overdose mortality are critical. To address this, the Auburn University Harrison College of Pharmacy developed and piloted a didactic-experiential naloxone learning model in the first-year PharmD curriculum in 2020-2021 consisting of lectures, skills laboratory, and 120-hour community pharmacy introductory pharmacy practice experience (IPPE). Student-delivered naloxone education services (SDNES), including naloxone counseling and dispensing, were incorporated into the IPPE. ObjectivesThe objective of this study was to evaluate the feasibility, acceptability, and usefulness of SDNES frovm the perspective of community pharmacy IPPE preceptors. MethodsThis study used a mixed methods design including cross-sectional online surveys and follow-up semistructured telephone interviews. Survey measures were informed by validated scales and included feasibility (11 items), acceptability (13 items), and usefulness (6 items) of SDNES. Survey outcomes were assessed via 5-point Likert-type scales (1 = strongly disagree, 5 = strongly agree) and analyzed using descriptive statistics. Follow-up semistructured telephone interview questions were guided by the Consolidated Framework for Implementation Research domains of inner and outer setting and focused on SDNES barriers and facilitators, recommended strategies for service enhancement, and resource needs. Interview transcripts were analyzed using deductive and inductive rapid content analysis to determine themes and subthemes. ResultsTwenty-five preceptor surveys were completed (22.52% response rate). Overall, SDNES was rated as feasible (mean [SD] scale score 4.04 [0.77]), acceptable (3.95 [0.83]), and useful (3.87 [0.98]). Interviewees (N = 8) discussed 13 barrier subthemes, 12 facilitator subthemes, 7 recommended strategies, and 8 resource needs across 3 overarching themes, most of which were related to the inner setting. ConclusionCommunity pharmacy IPPE preceptors found SDNES feasible, acceptable, and useful in their practices. The SDNES model may be used to build capacity for naloxone services delivery in community pharmacies, potentially increasing patient access to naloxone education and distribution.

Photoactivated DNA Nanodrugs Damage Mitochondria to Improve Gene Therapy for Reversing Chemoresistance.

Multidrug resistance (MDR) is a major cause of chemotherapy failure in oncology, and gene therapy is an excellent measure to reverse MDR. However, conventional gene therapy only modulates the expression of MDR-associated proteins but hardly affects their existing function, thus limiting the efficiency of tumor treatment. Herein, we designed a photoactivated DNA nanodrug (MCD@TMPyP4@DOX) to improve tumor chemosensitivity through the downregulation of MDR-related genes and mitochondria-targeted photodynamic therapy (PDT). The self-assembled DNA nanodrug encodes the mucin 1 (MUC1) aptamer and the cytochrome C (CytC) aptamer to facilitate its selective targeting to the mitochondria in tumor cells; the encoded P-gp DNAzyme can specifically cleave the substrate and silence MDR1 mRNA with the help of Mg2+ cofactors. Under near-infrared (NIR) light irradiation, PDT generates reactive oxygen species (ROS) that precisely damage the mitochondria of tumor cells and break single-stranded DNA (ssDNA) to activate MCD@TMPyP4@DOX self-disassembly for release of DOX and DNAzyme. We have demonstrated that this multifunctional DNA nanodrug has high drug delivery capacity and biosafety. It enables downregulation of P-gp expression while reducing the ATP on which P-gp pumps out drugs, improving the latency of gene therapy and synergistically reducing DOX efflux to sensitize tumor chemotherapy. We envision that this gene-modulating DNA nanodrug based on damaging mitochondria is expected to provide an important perspective for sensitizing tumor chemotherapy.