Novel multidomain peptide self-assembly biomaterials based on bola structure and terminal anchoring: Nanotechnology meets antimicrobial therapy.

To ameliorate the diminished antimicrobial efficiency and physiological stability associated with monomeric antimicrobial peptides (AMPs) molecules, future research will focus on the artificial design of self-assembling peptides to replace monomeric entities, aiming to combat the antibiotic resistance crisis caused by microbial infections. In this study, the "bola" structure was used as the foundational architecture driving molecular self-assembly, with hydrophobic amino acids at the termini to anchor and finely adjust the sequence, thereby organizing a range of novel multidomain peptides (MDPs) templates into an ABA block motif. The results indicate that FW2 (GMSI = 53.94) exhibits the highest selectivity index among all MDPs and can form spherical micelles in an aqueous medium without the addition of any exogenous additives. FW2 exhibited high stability in vitro in the presence of physiological salt ions, serum, and various pH conditions. It exhibited excellent biocompatibility and efficacy both in vivo and in vitro. Furthermore, FW2 strongly interacts with the lipid membrane and employs various synergistic mechanisms, such as reactive oxygen species (ROS) accumulation, collectively driving cellular apoptosis. This study demonstrates a straightforward strategy for designing self-assembling peptides and promotes the advancement of peptide-based biomaterials integration progress with nanotechnology.

Morphology and Emulsification of Poly(N-2-(methacryloyloxy) ethyl pyrrolidone)-b-poly(benzyl methacrylate) Assemblies by Polymerization-Induced Self-Assembly.

In this work, a series of amphiphilic diblock copolymers poly(N-2-(methacryloyloxy) ethyl pyrrolidone)-b-poly(benzyl methacrylate) (PNMP m -b-PBzMA n ) were developed by the dispersion polymerization method in ethanol. The polymerization-induced self-assembly (PISA) behaviors were studied systematically, and a comprehensive structure-property relationship was also established. Two distinct PISA tendencies were observed, which was mainly depended on the polymerization degree m of PNMP segment. When m is small such as 39 and 55, morphological transitions from spherical to vesicle-like assemblies via wormlike ones upon increasing n commonly happen regardless of the solid content. Alternatively, spherical assemblies became the sole morphology for PNMP64-b-PBzMA n block copolymers because of the excellent solvophilicity of the PNMP64 segment. Attributing to the amphiphilicity of PNMP m -b-PBzMA n block copolymers, PNMP m -b-PBzMA n assemblies by PISA are a type of excellent Pickering emulsifiers. These assemblies prefer to stabilize O/W Pickering emulsions as confirmed by the confocal laser scanning microscopy method, and the effects of polymerization degree of PBzMA segment or morphologies of PNMP m -b-PBzMA n assemblies are finite.

Association between osteoarthritis with Parkinson's disease in the US (NHANES 2011-2020).

Objected: To evaluate the association between osteoarthritis (OA) and Parkinson's disease (PD) in adults in the United States. Methods: Using 2011-2020 NHANES data, a cross-sectional study of 11,117 adults over the age of 40 was conducted. Univariate logistic regression and multivariate logistic regression were used to analyze the relationship between arthritis and PD. In addition, stratified analysis was used to examine whether the relationship between arthritis and PD was interactive with age, gender, race, education, BMI. Results: In this study, a total of 11,117 participants were included, and we found that osteoarthritis was positively correlated with the development of PD compared with non-arthritis patients [1.95 (1.44 ~ 2.62)] (p < 0.001). After adjusting the covariates, the results are still stable. Conclusion: PD patients were positively correlated with OA. Among people with OA, there was a 95% increased risk of PD compared to people without arthritis. Therefore, when treating OA, attention should be paid to the increased risk of PD. In the meantime, further studies are needed to explore the link between OA and PD patients.

The changes of rhizosphere microbial communities in pepper varieties with different capsaicinoids.

Capsaicinoids are produced uniquely in pepper fruits, and its level determines the commercial quality and health-promoting properties of pepper. So, it is particularly important to increase capsaicinoids content in pepper. Rhizosphere microbiota is critical to plant growth and performance, and affected by plant varieties. However, the impact of pepper varieties with different capsaicinoids yields on the rhizosphere microbiota is poorly understood. Using high-throughput sequencing of the 16S rRNA and internal transcribed spacer (ITS) region, we investigated the rhizosphere microbial community among five pepper varieties containing different capsaicinoids. Our results demonstrated that pepper variety significantly influenced the diversity and structure of rhizosphere microbial community. Bacterial diversity in varieties with high capsaicinoids content was significantly higher than in varieties with low capsaicinoids content, while fungal diversity was opposite to bacterial diversity. The correlation analysis revealed that 19 dominant bacterial genera (e.g., Chujaibacter, Rhodanobacter, and Gemmatimonas) were significantly correlated with capsaicinoids content, and nine of them were also significantly associated with soil nutrients, whereas only one fungal genus (Podospora) was significantly correlated with capsaicinoids content. Additionally, almost all genera which significantly correlated to capsaicinoids content were biomarkers of the five pepper varieties and the correlation was well corresponding to the capsaicinoids content. Overall, our results confirmed that the variety of pepper significantly affected the rhizosphere microbial community in the fields, and bacteria and fungi responded differently to capsaicinoids, which may affect the biosynthesis of capsaicinoids and contribute to further improvement of capsaicinoids production in pepper fruits.

EphrinB2-mediated chondrocyte autophagy induces post-traumatic arthritis via rupture of cartilage homeostasis.

EphrinB2, a member of the Ephrin family, has been linked to several orthopaedic conditions. Nevertheless, the correlation between ephrinB2 and post-traumatic arthritis (PTOA) remains unclear. Human PTOA cartilage from human and mouse knee joints was systematically analysed to investigate the relationship between EphrinB2 and PTOA using SO-FG and toluidine blue staining, micro-CT, histomorphometry, immunohistochemistry, immunofluorescence, lentiviral articular injection and in situ end labeling (TUNEL) assays. EphrinB2 expression was significantly downregulated in PTOA chondrocytes. Blocking EphrinB2 increased the breakdown of cartilage matrix in mice with PTOA via reducing the process of chondrocyte autophagy. The presence of severe cartilage damage was evident, as indicated by a considerable decrease in both cartilage thickness and area, accompanied by an increase in chondrocyte death. Altogether, EphrinB2 is required for the maintenance of cartilage homeostasis in post-traumatic arthritis, and EphrinB2 ablation is associated with accelerated chondrocyte matrix degeneration, finally causing damage to the articular cartilage.

Causal Relationship Between Autoimmune Arthritis and Temporomandibular Disorders.

OBJECTIVE: Accumulating evidence has indicated a close interrelation between autoimmune arthritis (AA) and temporomandibular disorders (TMD), but the causality is still unclear. The study aimed to explore the causal inference between AA and TMD using a bidirectional Mendelian randomization analysis. METHODS: Online genome-wide association study data on rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, and TMD were obtained from the FinnGen and IEU databases. Causality was using the inverse variance-weighted method as the primary analysis and supplemented by other methods. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, and leave-one-out methods, were conducted to investigate the stability and reliability of the results. RESULTS: The inverse variance-weighted test indicated that several AA types could causally increase the TMD risk, including overall RA (odds ratio [OR] = 1.348, 95% confidence interval [CI] = 1.1232-1.618, P = .001), subtype nRA (OR = 1.118, 95% CI = 1.044-1.197, P = .001), and AS (OR = 1.060, 95% CI = 1.024-1.097, P = .001). Moreover, the causal association of the above combinations has been proven to be stable and reliable using sensitivity and other tests. CONCLUSION: These findings suggest that RA and AS might be causally associated with an increased risk of TMD. However, more studies are needed to check the causal effects of AA on TMD and analyse the potential mechanisms further.

Validation of a triple-color pseudovirion-based neutralization assay for immunogenicity assessment of a 14-valent recombinant human papillomavirus vaccine.

Validation of bioanalytical methods is crucial, especially in the pharmaceutical industry, to determine their suitability for specific purposes and the accuracy of analytical results. The pseudovirion-based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in vaccine development for disease prevention. This paper introduces an improved triple-color PBNA method, capable of simultaneous detection of two or three human papillomavirus (HPV types for use in the development of a 14-valent HPV vaccine candidate. The primary objective was to comprehensively validate the triple-color PBNA method for general vaccine immunogenicity assays. Results show that the method has good specificity, accuracy, precision, linearity, robustness, and applicability. This innovative triple-color PBNA offers an improved approach for large-scale immunogenicity assessment in vaccine development. This study lays a solid foundation that can serve as a guiding paradigm for assessing vaccine responses in preclinical and clinical phases, providing valuable insights to the field.

Visible-Light-Induced Silk Fibroin Hydrogels with Carbon Quantum Dots as Initiators for 3D Bioprinting Applications.

Digital light processing (DLP) 3D bioprinting technology has attracted increasing attention in tissue engineering in recent years. However, it still faces significant technical and operational challenges such as cell carcinogenesis caused by prolonged exposure to ultraviolet light and the presence of heavy metal ions in complex photoinitiator systems. In this study, a novel strategy is designed to introduce carbon quantum dots into visible-light-induced silk fibroin bioink as initiators (CDs/SilMA) applied for DLP 3D bioprinting technology. The incorporation of carbon quantum dots facilitates the formation of precise hydrogel structures at 415 nm visible wavelength, enabling the creation of brain, bronchus, spine, and ear models. Replacing heavy metal photoinitiators with carbon quantum dots imparts fluorescence properties to the bioink and enhances its mechanical properties. Meanwhile, the fibroin protein-based hydrogel exhibits favorable properties, such as drug loading, slow release, degradability, and biocompatibility. This is the first study to propose the application of carbon quantum dots in silk fibroin-based bioink. Moreover, the resulting product demonstrates excellent compatibility with the DLP printing process, making it promising for practical applications in various tissue engineering scenarios with specific requirements.

A new UiO-66-NH2 MOF-based nano-immobilized DFR enzyme as a biocatalyst for the synthesis of anthocyanidins.

Anthocyanidins and anthocyanins are one subclass of flavonoids in plants with diverse biological functions and have health-promoting effects. Dihydroflavonol 4-reductase (DFR) is one of the important enzymes involved in the biosynthesis of anthocyanidins and other flavonoids. Here, a new MOF-based nano-immobilized DFR enzyme acting as a nano-biocatalyst for the production of anthocyanidins in vitro was designed. We prepared UiO-66-NH2 MOF nano-carrier and recombinant DFR enzyme from genetic engineering. DFR@UiO-66-NH2 nano-immobilized enzyme was constructed based on covalent bonding under the optimum immobilization conditions of the enzyme/carrier ratio of 250 mg/g, 37 °C, pH 6.5 and fixation time of 10 min. DFR@UiO-66-NH2 was characterized and its catalytic function for the synthesis of anthocyanidins in vitro was testified using UPLC-QQQ-MS analysis. Compared with free DFR enzyme, the enzymatic reaction catalyzed by DFR@UiO-66-NH2 was more easily for manipulation in a wide range of reaction temperatures and pH values. DFR@UiO-66-NH2 had better thermal stability, enhanced adaptability, longer-term storage, outstanding tolerances to the influences of several organic reagents and Zn2+, Cu2+ and Fe2+ ions, and relatively good reusability. This work developed a new MOF-based nano-immobilized biocatalyst that had a good prospect of application in the green synthesis of anthocyanins in the future.

A case report of high-grade intraepithelial neoplasia of the bronchial mucosa.

BACKGROUND: Lung cancer is the most common cause of cancer death worldwide and poses an immediate health threat. Despite decades of basic and clinical research, the 5-year survival rate for lung cancer patients is less than 10%.The most important drawbacks in efficient treatment of lung cancer are delayed diagnosis and absence of effective screening. Detection and study of precancerous lesions of the bronchial mucosa might be one of the turning points in understanding of neoplastic transformation. Therefore, it would be the most effective prevention and early treatment modality. We report a case of high-grade intraepithelial neoplasia of the bronchial mucosa in which a neoplastic growth in the lumen of intrinsic segment in the upper lobe of the left lung was detected on electronic bronchoscopy, and biopsy confirmed squamous papillary hyperplasia with high-grade intraepithelial neoplasia. CASE PRESENTATION: A 74-year-old male was admitted to the hospital due to a mass lesion in his left lung. After admission, computed tomography scan of the chest showed an intraluminal mass in the intrinsic segment of the upper lobe of the left lung and an enlarged left hilum. CONCLUSIONS: High-grade intraepithelial neoplasia of the bronchial mucosa is rare in the respiratory system. We report a case that can provide useful information for early diagnosis and treatment of the disease.

SERPINE1AS2 regulates intramuscular adipogenesis by inhibiting PAI1 protein expression.

Antisense long non-coding RNAs (lncRNAs) played a crucial role in the precise regulation of essential biological processes and were abundantly present in animals. Many of these antisense lncRNAs have been identified as key roles in adipose tissue accumulation in livestock, underscoring their vital role in the regulation of animal physiology. Nonetheless, the functional roles of these antisense lncRNAs in regulating adipogenesis and the specific molecular mechanisms these processes were still unclear, which was a significant gap in current scientific research. In this study, we identified and characterized SERPINE1AS2, a novel natural antisense lncRNA, was highly expressed in the fat tissues of adult cattle and calves. Its expression gradually increased during the differentiation of intramuscular adipocytes. Through functional studies, we observed that knockdown of SERPINE1AS2 inhibited the proliferation and adipogenesis of intramuscular adipocytes, while overexpression of SERPINE1AS2 produced the opposite effect. RNA sequencing (RNA-seq) analysis following SERPINE1AS2 knockdown revealed that differential expression genes (DEGs) were significantly enriched in key signaling pathways, notably the MAPK, Wnt, and mTOR signaling pathways. Furthermore, SERPINE1AS2 interacted with Plasminogen Activator Inhibitor-1 (PAI1), forming RNA dimers through complementary base pairing and consequently influencing PAI1 expression. Interestingly, studies on PAI1 suggested that reduced expression facilitated adipogenesis and the downregulation of PAI1 alleviated the inhibitory effect of reduced SERPINE1AS2 on adipogenesis. In summary, this study suggested that SERPINE1AS2 played a crucial role in the adipogenesis of bovine intramuscular adipocytes by modulating the expression of PAI1. SERPINE1AS2 also regulated adipogenesis by engaging in the MAPK, Wnt, and mTOR signaling pathways. Our results suggested that SERPINE1AS2 had a complex regulatory mechanism on adipogenesis in intramuscular adipocytes.

Bta-miR-330 promotes bovine intramuscular pre-adipocytes adipogenesis via targeting SESN3 to activate the Akt-mTOR signaling pathway.

Consumers are more inclined to choose beef with a high intramuscular fat content (IMF), which regulated by lots of factors. It is very significant to find a miRNA that plays a key role in the accumulation of IMF. In our study, we found that bta-miR-330 was highly expressed in Japanese black cattle and differentially expressed at intramuscular pre-adipocytes differentiation processes. Furthermore, we transfected the bta-miR-330 mimic & inhibitor in intramuscular pre-adipocytes. The results showed that bta-miR-330 inhibits the proliferation but promotes the adipogenesis of intramuscular pre-adipocytes. Subsequently, our study showed that bta-miR-330 binds to SESN3, which inhibits the adipogenesis of intramuscular pre-adipocytes. Moreover, we established the mechanism that bta-miR-330 promotes the adipogenesis of intramuscular pre-adipocytes by targeting SESN3 to activate the Akt-mTOR signaling pathway. Overall, our results revealed that bta-miR-330-SESN3-Akt-mTOR axis plays an important role in adipogenesis of intramuscular pre-adipocytes, which provides a molecular basis for increasing IMF content in beef cattle.

Association of dietary glycemic index and glycemic load with the risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis.

OBJECTIVE: To comprehensively assess the dose-response association between dietary glycemic index (GI) and glycemic load (GL) and gestational diabetes mellitus (GDM) risk. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched up to May 29, 2024. Studies with at least three exposure categories were included. Dose-response analysis was also performed when covariates were adjusted in the included studies. RESULTS: Thirteen studies involving 39,720 pregnant women were included. A linear relationship was found between GI and the risk of GDM (χ2 = 4.77, Pnon-linearity = .0923). However, association was not significant (χ2 = 0.06, p = .8000). For every unit increase in GI (range 0-30), GDM risk increased by 0.29%. After adjusting for covariates, the linear relationship persisted (χ2 = 4.95, Pnon-linearity = .084) with no significant association (χ2 = 0.08, p = .7775). For GL, a linear relationship was also found (χ2 = 4.17, Pnon-linearity =.1245), but GL was not significantly associated with GDM risk (χ2 = 2.63, p = .1049). The risk of GDM increased by 0.63% per unit increase in GL. After covariate adjustment, a significant association was observed (χ2 = 6.28, p = .0122). CONCLUSION: No significant association between GI and GDM risk was found. After adjusting for covariates, GL shows a significant association with GDM risk. Our findings emphasize the importance of considering dietary GL in managing the risk of GDM. Future research should continue to explore these relationships with standardized diagnostic criteria and robust adjustment for potential confounders.

Efficacy of the tetravalent protein COVID-19 vaccine, SCTV01E: a phase 3 double-blind, randomized, placebo-controlled trial.

Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Diagnosis and Treatment of Hepatic Hematoma After Liver Transplantation in a Timely Manner.

OBJECTIVE: Hematomas of the liver graft, that is, postintervention, subcapsular or intrahepatic are rare yet potentially fatal complications following liver transplantation (LT), necessitating immediate diagnosis and management to avert devastating outcomes. This study was aimed to introduce our approach to manage graft hematoma subsequent to LT. METHODS: Among 131 orthotopic liver transplantations (OLT) conducted at our institution between January 2017 and May 2023, 3 cases of intrahepatic (n = 2) and extrahepatic (n = 1) hematoma were confirmed through computed tomography (CT) within 10 days after LT. The clinical outcomes of various treatment modalities for these three cases were analyzed. RESULTS: Three out of 131 (2.3%) LT recipients developed graft hematoma. Patient 1 developed a spontaneous intrahepatic hematoma, without evident predisposing factors, while patient 2 developed an intrahepatic hematoma following endoscopic retrograde cholangiopancreatography (ERCP). The third case that is extrahepatic hematoma was speculated to be a result of minor hepatic parenchymal injury stemming from compressive and volume-reducing manipulation of a large graft, or secondary to focal ischemic necrosis of the liver. Our management protocol was summarized as follows: (1). Immediate ultrasound and CT, particularly enhanced CT; (2). Puncture and percutaneous drainage (PD) of the hematoma; (3). Arterial embolization if the origin could be identified as a ruptured vessel; (4). Surgical evacuation of the hematoma in the presence of bile leakage, to avoid a compartment respectably secondary infection. All three patients responded favorably to treatment and remained alive to date. CONCLUSION: Prompt diagnosis and sequential individualized management can successfully deal with intra-/extrahepatic graft hematoma after LT. Our results underscored that an individualized management considering potential future complications into account.

Current status and future directions for the development of human papillomavirus vaccines.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

NUAK2 mediated regulation of Schwann Cell proliferation and migration in peripheral nerve injury via YAP.

NUAK2 is a member of the AMP-activated protein kinase (AMPK) family, which plays an essential role in cellular processes such as apoptosis, proliferation, and cell fate. Recent studies have already shown that silencing of NUAK2 blocks proliferation and promotes apoptosis of human melanoma cells and liver cancer cells. In addition, NUAK2 is involved in the development of glioblastoma via regulating the expression of cancer stem cell-related genes, and it promotes the cell cycle entry in the glioblastoma cells. However, the expression and the role of NUAK2 in the progress of peripheral nerve regeneration after injury are yet to be elucidated. We observed that NUAK2 was upregulated following distal sciatic nerve crush (SNC). Interestingly, we discovered that NUAK2 showed co-localization with S100 (Schwann cell marker). Furthermore, we found that the NUAK2 had a spatiotemporal protein expression, which was consistent with proliferating cell nuclear-antigen (PCNA). The protein level of NUAK2 and YAP was upregulated in the model of TNF-α-induced Schwann cell (SC) proliferation. Furthermore, flow cytometry analysis, CCK-8, transwell assays, and wound healing assays were all performed with the purpose of exploring the role of NUAK2 in the regulation of SC proliferation and migration. More importantly, we found that NUAK2-deficient SCs showed significantly reduced expression of Yes-associated protein (YAP). Bioinformatic analysis identified upstream regulators of NUAK2 and NUAK2-associated genes (e.g., YAP1). Finally, we investigated the recovery changes during regeneration progress through the walking track analysis. Thus, we speculated that NUAK2 was involved in biochemical and physiological responses of SCs after SNC via YAP-driven proliferation and migration, and this study determined the importance of NUAK2 as a potential target in peripheral nerve regeneration.

Screening indicators to evaluate the clinical significance of drug-drug interactions in polypharmacy among older adults with psychiatric disorders: a delphi study.

BACKGROUND: Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders. METHODS: The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts' opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert's judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0. RESULTS: After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary "pharmacodynamic indicator" included "severity of adverse drug reactions", "duration of adverse drug reaction", "symptom relief", "time to onset of symptomatic relief", "number of days in hospital", and "duration of medication". The secondary "pharmacokinetic indicator" contained "dosage administered" and "dosing intervals". The primary "patient tolerance indicator" contained one secondary indicator of "patient tolerability". The primary indicator "patient adherence" contained one secondary indicator of "patient adherence to medication". The primary indicator "cost of drug combination" contained one secondary indicator of "readmission". These indicators were used to determine the clinical significance of DDIs during polypharmacy. CONCLUSIONS: The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.

Integrative RNA-seq and ChIP-seq analysis unveils metabolic regulation as a conserved antiviral mechanism of chicken p53.

The tumor suppressor p53, primarily functioning as a transcription factor, has exhibited antiviral capabilities against various viruses in chickens, including infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). Nevertheless, the existence of a universal antiviral mechanism employed by chicken p53 (chp53) against these viruses remains uncertain. This study conducted a comprehensive comparison of molecular networks involved in chp53's antiviral function against IBDV, ALV-J, and ILTV. This was achieved through an integrated analysis of ChIP-seq data, examining chp53's genome-wide chromatin occupancy, and RNA-seq data from chicken cells infected with these viruses. The consistent observation of chp53 target gene enrichment in metabolic pathways, confirmed via ChIP-qPCR, suggests a ubiquitous regulation of host cellular metabolism by chp53 across different viruses. Further genome binding motif conservation analysis and transcriptional co-factor prediction suggest conserved transcriptional regulation mechanism by which chp53 regulates host cellular metabolism during viral infection. These findings offer novel insights into the antiviral role of chp53 and propose that targeting the virus-host metabolic interaction through regulating p53 could serve as a universal strategy for antiviral therapies in chickens.IMPORTANCEThe current study conducted a comprehensive analysis, comparing molecular networks underlying chp53's antiviral role against infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). This was achieved through a combined assessment of ChIP-seq and RNA-seq data obtained from infected chicken cells. Notably, enrichment of chp53 target genes in metabolic pathways was consistently observed across viral infections, indicating a universal role of chp53 in regulating cellular metabolism during diverse viral infections. These findings offer novel insights into the antiviral capabilities of chicken p53, laying a foundation for the potential development of broad-spectrum antiviral therapies in chickens.