Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Zinc finger translocation­associated protein promotes ferroptosis through the upregulation of ACSL4 expression in vascular endothelial cells.

Numerous studies have reported the potential involvement of ferroptosis in the development of atherosclerosis (AS). Acyl-CoA synthetase long chain family member 4 (ACSL4) is an essential component in the promotion of ferroptosis. The present study aimed to investigate the role of ACSL4 and zinc finger translocation-associated protein (ZFTA) in the regulation of endothelial cell ferroptosis in AS. Human umbilical vein endothelial cells (HUVECs) with ACSL4 knockout were generated using CRISPR/Cas9 technology. To assess ferroptosis, malondialdehyde concentration, iron content and reactive oxygen species levels were quantified in the present study. In addition, western blot analysis was conducted to explore the potential mechanisms underlying ACSL4 and ZFTA in the modulation of ferroptosis in HUVECs. The results of the present study demonstrated that the expression levels of ACSL4 and ZFTA were significantly increased in human atherosclerotic plaques. In addition, ACSL4 knockout led to a reduced susceptibility to ferroptosis, while ZFTA contributed to ferroptosis in HUVECs. Results of the present study also demonstrated that ZFTA overexpression upregulated ACSL4 expression in HUVECs, whereas ZFTA knockdown led to decreased ACSL4 expression. Co-transfection experiments demonstrated that the ZTFA overexpression-mediated increase in ferroptosis was reversed following ACSL4 knockdown. Collectively, results of the present study highlighted that ACSL4 mediated the effects of ZFTA on the ferroptosis of HUVECs. Thus, the present study demonstrated the potential role of ACSL4 and ZFTA in the regulation of ferroptosis, and highlighted that ferroptosis-related pathways may act as potential targets in the treatment of AS.

Comparing the efficacy of dexamethasone implant and anti-VEGF for the treatment of macular edema: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. METHODS: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. RESULTS: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). CONCLUSIONS: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. TRIAL REGISTRATION: Prospero Registration Number CRD42021243185.

Analysis of infrared radiation emitted by moxibustion devices made of different materials using Fourier transform infrared spectroscopy.

Moxibustion has a long history of use as a traditional Chinese medicine therapy. Infrared radiation is an important and effective factor in moxibustion. Instead of the time-consuming and laborious process of holding moxa sticks in the hand, moxibustion devices are commonly used as moxibustion methods and tools in modern times. With the publication of the international standard of moxibustion devices (ISO18666:2021, Traditional Chinese Medicine - General requirements of moxibustion devices) published, moxibustion devices of various materials are now sold in the pharmacies and online stores. However, the influence of moxibustion devices on the therapeutic effect of moxibustion has not been studied. Therefore, this research was aimed to evaluate the infrared radiation of moxibustion devices, in order to select the moxibustion device that delivered infrared radiation closest to that of moxa stick combustion. The combination of combustion stability and infrared radiation intensity showed that cardboard tubes and silicone were better materials for moxibustion devices. In the mid-far infrared wave band, the moxibustion devices made from cardboard tubes and silica gels can better maintain the thermal effect generated by moxibustion and enable it to be more easily absorbed by the human body. The infrared radiation intensity of the cardboard moxibustion devices increased rapidly and steadily and could be maintained for the longest time. In conclusion, cardboard tubes are the better material for moxibustion devices with respect to infrared radiation.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

FGF21-dependent alleviation of cholestasis-induced liver fibrosis by sodium butyrate.

Background: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis. Methods: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson's staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing. Results: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice. Conclusion: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Background: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis. Methods: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings. Results: Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011). Conclusion: This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

Remote monitoring of cardiac implantable electronic devices using smart device interface versus radiofrequency-based interface: A systematic review.

Background: Guidelines recommended remote monitoring (RM) in managing patients with Cardiac Implantable Electronic Devices. In recent years, smart device (phone or tablet) monitoring-based RM (SM-RM) was introduced. This study aims to systematically review SM-RM versus bedside monitor RM (BM-RM) using radiofrequency in terms of compliance, connectivity, and episode transmission time. Methods: We conducted a systematic review, searching three international databases from inception until July 2023 for studies comparing SM-RM (intervention group) versus BM-RM (control group). Results: Two matched studies (21 978 patients) were retrieved (SM-RM arm: 9642 patients, BM-RM arm: 12 336 patients). There is significantly higher compliance among SM-RM patients compared with BM-RM patients in both pacemaker and defibrillator patients. Manyam et al. found that more SM-RM patients than BM-RM patients transmitted at least once (98.1% vs. 94.3%, p < .001), and Tarakji et al. showed that SM-RM patients have higher success rates of scheduled transmissions than traditional BM-RM methods (SM-RM: 94.6%, pacemaker manual: 56.3%, pacemaker wireless: 77.0%, defibrillator wireless: 87.1%). There were higher enrolment rates, completed scheduled and patient-initiated transmissions, shorter episode transmission time, and higher connectivity among SM-RM patients compared to BM-RM patients. Younger patients (aged <75) had more patient-initiated transmissions, and a higher proportion had ≥10 transmissions compared with older patients (aged ≥75) in both SM-RM and BM-RM groups. Conclusion: SM-RM is a step in the right direction, with good compliance, connectivity, and shorter episode transmission time, empowering patients to be in control of their health. Further research on cost-effectiveness and long-term clinical outcomes can be carried out.

Model-informed drug development in pediatric, pregnancy and geriatric drug development: States of the art and future.

The challenges of drug development in pediatric, pregnant and geriatric populations are a worldwide concern shared by regulatory authorities, pharmaceutical companies, and healthcare professionals. Model-informed drug development (MIDD) can integrate and quantify real-world data of physiology, pharmacology, and disease processes by using modeling and simulation techniques to facilitate decision-making in drug development. In this article, we reviewed current MIDD policy updates, reflected on the integrity of physiological data used for MIDD and the effects of physiological changes on the drug PK, as well as summarized current MIDD strategies and applications, so as to present the state of the art of MIDD in pediatric, pregnant and geriatric populations. Some considerations are put forth for the future improvements of MIDD including refining regulatory considerations, improving the integrity of physiological data, applying the emerging technologies, and exploring the application of MIDD in new therapies like gene therapies for special populations.

Malassezia specific IgE in head and neck dermatitis of eczema: A systematic review & meta-analysis.

Head and neck atopic dermatitis (HNAD) is a subtype of atopic dermatitis (AD), a common inflammatory skin condition with a distinctive clinical appearance. Malassezia spp., a predominant skin yeast, is considered to exacerbate HNAD. In this study, we investigate the prevalence of Malassezia-specific IgE among HNAD patients. A comprehensive search was performed for observational studies analysing the association between Malassezia-specific IgE and HNAD. This study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 checklist and quality was assessed via the Newcastle-Ottawa Quality Assessment Scale (NOS). Fourteen observational studies (840 patients) were included in the analysis. 58% of HNAD patients were male (95% CI: 45.2-69.7). Overall prevalence of Malassezia-specific IgE among HNAD patients was 79.3% (95% CI: 57.5-91.5). Prevalence of Malassezia-specific IgE among HNAD patients varied significantly between geographical regions (p = 0.0441), with 88% in non-Asian regions (95% CI: 61.06-97.17) and 54.73% in Asian regions (95% CI: 34.36-73.63). Malassezia-specific IgE prevalence among HNAD patients varied significantly among studies of higher and lower NOS quality score (p = 0.0386), with 95.42% in studies with NOS ≥7 (95% CI: 63.54-99.60) and 58.05% in studies with NOS <7 (95% CI: 41.44-73.01). Malassezia-specific IgE prevalence among HNAD patients did not vary significantly between more and less predominant Malassezia species (p = 0.1048). Malassezia spp. plays a crucial role in the pathogenesis of HNAD, and IgE anti-Malassezia antibodies appeared to be a common marker for HNAD. Understanding the pathophysiology of Malassezia in HNAD can help develop more targeted therapeutic approaches in managing AD.

Calibrating ultrasonic sensor measurements of crop canopy heights: a case study of maize and wheat.

Canopy height serves as an important dynamic indicator of crop growth in the decision-making process of field management. Compared with other commonly used canopy height measurement techniques, ultrasonic sensors are inexpensive and can be exposed in fields for long periods of time to obtain easy-to-process data. However, the acoustic wave characteristics and crop canopy structure affect the measurement accuracy. To improve the ultrasonic sensor measurement accuracy, a four-year (2018-2021) field experiment was conducted on maize and wheat, and a measurement platform was developed. A series of single-factor experiments were conducted to investigate the significant factors affecting measurements, including the observation angle (0-60°), observation height (0.5-2.5 m), observation period (8:00-18:00), platform moving speed with respect to the crop (0-2.0 m min-1), planting density (0.2-1 time of standard planting density), and growth stage (maize from three-leaf to harvest period and wheat from regreening to maturity period). The results indicated that both the observation angle and planting density significantly affected the results of ultrasonic measurements (p-value< 0.05), whereas the effects of other factors on measurement accuracy were negligible (p-value > 0.05). Moreover, a double-input factor calibration model was constructed to assess canopy height under different years by utilizing the normalized difference vegetation index and ultrasonic measurements. The model was developed by employing the least-squares method, and ultrasonic measurement accuracy was significantly improved when integrating the measured value of canopy heights and the normalized difference vegetation index (NDVI). The maize measurement accuracy had a root mean squared error (RMSE) ranging from 81.4 mm to 93.6 mm, while the wheat measurement accuracy had an RMSE from 37.1 mm to 47.2 mm. The research results effectively combine stable and low-cost commercial sensors with ground-based agricultural machinery platforms, enabling efficient and non-destructive acquisition of crop height information.

A Qualitative Enquiry of On-Farm Rules About Quad Bikes (ATVs): How Rules Are Determined and Implemented at a Farm Level in Rural Australia.

OBJECTIVE: Quad bikes are a leading cause of death and incident-related injury on farms, yet little is understood about rules used by farmers to ensure their safe operation. This study explored rules about quad bikes set by those who live or work on farms. Through the case of quad bikes, this study sought to understand how rules are determined and implemented at the farm level. SETTING: A mix of farm types and locations in rural Australia including Queensland, South Australia, and New South Wales. PARTICIPANTS: Eight farmers were interviewed and recruited from information sheets at farmers' markets, through a local health organisation, and a media release. DESIGN: Thematic analysis was used to transform data from eight semi-structured interviews with farmers in rural Australia. RESULTS: Data were distilled into two themes - "Rule content" described the explicit rules farmers had set on their properties, while the theme "Underlying rule principles" explored the values and norms which underpinned the creation and implementation of these rules. CONCLUSIONS: Through the case of quad bike rules, this study illustrated how rules are determined and implemented at the farm level. Perceptions of risk were tied to farmers being experts in their own environment and therefore able to mitigate risk. In contrast to injury data, reckless use of quad bikes was perceived to cause incidents, and this was the basis of rules for adults and children.

Machine Learning: A Potential Therapeutic Tool to Facilitate Neonatal Therapeutic Decision Making.

Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.

Matrine exhibits antiviral activities against PEDV by directly targeting Spike protein of the virus and inducing apoptosis via the MAPK signaling pathway.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.

Equity, diversity and inclusion in simulation-based education: constructing a developmental framework for medical educators.

BACKGROUND: Themes of equity, diversity and inclusion (EDI) arise commonly within healthcare simulation. Though faculty development guidance and standards include increasing reference to EDI, information on how faculty might develop in this area is lacking. With increasingly formal expectations being placed on simulation educators to adhere to EDI principles, we require a better understanding of the developmental needs of educators and clear guidance so that teams can work towards these expectations. Our study had two aims: Firstly, to explore the extent to which an existing competency framework for medical teachers to teach ethnic and cultural diversity is relevant for simulation educator competency in EDI, and secondly, informed by the data gathered, to construct a modified competency framework in EDI for simulation educators. METHODS: We engaged our participants (10 simulation faculty) in a 5-month period of enhanced consideration of EDI, using the SIM-EDI tool to support faculty debriefing conversations focussed on EDI within a pre-existing programme of simulation. We interviewed participants individually at two timepoints and analysed transcript data using template analysis. We employed an existing competency framework for medical teachers as the initial coding framework. Competencies were amended for the simulation context, modified based on the data, and new themes were added inductively, to develop a new developmental framework for simulation educators. RESULTS: Interview data supported the relevance of the existing competency framework to simulation. Modifications made to the framework included the incorporation of two inductively coded themes ('team reflection on EDI' and 'collaboration'), as well as more minor amendments to better suit the healthcare simulation context. The resultant Developmental Framework for Simulation Educators in EDI outlines 10 developmental areas we feel are required to incorporate consideration of EDI into simulation programmes during the design, delivery and debriefing phases. We propose that the framework acts as a basis for simulation faculty development in EDI. CONCLUSIONS: Simulation faculty development in EDI is important and increasingly called for by advisory bodies. We present a Developmental Framework for Simulation Educators in EDI informed by qualitative data. We encourage simulation teams to incorporate this framework into faculty development programmes and report on their experiences.

Reactive oxygen species (ROS) modulate nitrogen signaling using temporal transcriptome analysis in foxtail millet.

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H2O2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants.

Association between periodontal disease and coronary heart disease: A bibliometric analysis.

Background: Periodontal disease and coronary heart disease are both prevalent diseases worldwide and cause patients physical and mental suffering and a global burden. Recent studies have suggested a link between periodontal disease and coronary heart disease, but there is less research in this field from the perspective of bibliometrics. Objective: This study aimed to quantitatively analyze the literature on periodontal disease and coronary heart disease to summarize intellectual bases, research hotspots, and emerging trends and pave the way for future research. Methods: The Science Citation Index Expanded database was used to retrieve study records on periodontal disease and coronary heart disease from 1993 to 2022. After manual screening, the data were used for cooperative network analysis (including countries/regions, institutions and authors), keyword analysis, and reference co-citation analysis by CiteSpace software. Microsoft Excel 2019 was applied for curve fitting of annual trend in publications and citations. Results: A total of 580 studies were included in the analysis. The number of publications and citations in this field has shown an upward trend over the past 30 years. There was less direct collaboration among authors and institutions in this field but closer collaboration between countries. The United States was the country with the most published articles in this field (169/580, 29.14%). Based on the results of keyword analysis and literature co-citation analysis, C-reactive protein, oral flora, atherosclerosis, infection, and inflammation were previous research hotspots, while global burden and cardiovascular outcomes were considered emerging trends in this field. Conclusion: Studies on periodontal disease and coronary heart disease, which have attracted the attention of an increasing number of researchers, have been successfully analyzed using bibliometrics and visualization techniques. This paper will help scholars better understand the dynamic evolution of periodontal disease and coronary heart disease and point out the direction for future research. Clinical significance: This paper presents an overview between periodontal disease and coronary heart disease. Further exploration of the two diseases themselves and the potential causal relationship between the two is necessary and relevant, which may impact basic research, diagnosis, and treatment related to both diseases. This will aid the work of researchers and specialist doctors, and ultimately benefit patients with both diseases.

Liposomes for Inhalation.

Inhalation of liposomes formulated with phospholipids similar to endogenous lung surfactants and lipids offers biocompatibility and versatility within the pulmonary medicine field to treat a range of diseases such as lung cancer, cystic fibrosis and lung infections. Manipulation of the physicochemical properties of liposomes enables innovative design of the carrier to meet specific delivery, release and targeting requirements. This delivery system offers several benefits: improved pharmacokinetics with reduced toxicity, enhanced therapeutic efficacy, increased delivery of poorly soluble drugs, taste masking, biopharmaceutics degradation protection and targeted cellular therapy. This section provides an overview of liposomal formulation and delivery, together with their applications for different disease states in the lung.

Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer's Disease Therapy.

This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative. Notably, intranasal insulin has shown neuroprotective effects, impacting Aß clearance, tau phosphorylation, and synaptic plasticity. In preclinical studies and clinical trials, intranasally administered insulin achieved rapid and extensive distribution throughout the brain, with optimal formulations exhibiting minimal systemic circulation. The detailed mechanism of insulin transport through the nose-to-brain pathway is elucidated in the review, emphasizing the role of olfactory and trigeminal nerves. Despite promising prospects, challenges in delivering protein drugs from the nasal cavity to the brain remain, including enzymes, tight junctions, mucociliary clearance, and precise drug deposition, which hinder its translation to clinical settings. The review encompasses a discussion of the strategies to enhance the intranasal delivery of therapeutic proteins, such as tight junction modulators, cell-penetrating peptides, and nano-drug carrier systems. Moreover, successful translation of nose-to-brain drug delivery necessitates a holistic understanding of drug transport mechanisms, brain anatomy, and nasal formulation optimization. To date, no intranasal insulin formulation has received regulatory approval for AD treatment. Future research should address challenges related to drug absorption, nasal deposition, and the long-term effects of intranasal insulin. In this context, the evaluation of administration devices for nose-to-brain drug delivery becomes crucial in ensuring precise drug deposition patterns and enhancing bioavailability.

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2.

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.