LMBiS-Net: A lightweight bidirectional skip connection based multipath CNN for retinal blood vessel segmentation.

Blinding eye diseases are often related to changes in retinal structure, which can be detected by analysing retinal blood vessels in fundus images. However, existing techniques struggle to accurately segment these delicate vessels. Although deep learning has shown promise in medical image segmentation, its reliance on specific operations can limit its ability to capture crucial details such as the edges of the vessel. This paper introduces LMBiS-Net, a lightweight convolutional neural network designed for the segmentation of retinal vessels. LMBiS-Net achieves exceptional performance with a remarkably low number of learnable parameters (only 0.172 million). The network used multipath feature extraction blocks and incorporates bidirectional skip connections for the information flow between the encoder and decoder. In addition, we have optimised the efficiency of the model by carefully selecting the number of filters to avoid filter overlap. This optimisation significantly reduces training time and improves computational efficiency. To assess LMBiS-Net's robustness and ability to generalise to unseen data, we conducted comprehensive evaluations on four publicly available datasets: DRIVE, STARE, CHASE_DB1, and HRF The proposed LMBiS-Net achieves significant performance metrics in various datasets. It obtains sensitivity values of 83.60%, 84.37%, 86.05%, and 83.48%, specificity values of 98.83%, 98.77%, 98.96%, and 98.77%, accuracy (acc) scores of 97.08%, 97.69%, 97.75%, and 96.90%, and AUC values of 98.80%, 98.82%, 98.71%, and 88.77% on the DRIVE, STARE, CHEASE_DB, and HRF datasets, respectively. In addition, it records F1 scores of 83.43%, 84.44%, 83.54%, and 78.73% on the same datasets. Our evaluations demonstrate that LMBiS-Net achieves high segmentation accuracy (acc) while exhibiting both robustness and generalisability across various retinal image datasets. This combination of qualities makes LMBiS-Net a promising tool for various clinical applications.

Youth Pitcher Fatigue: Medial Elbow Laxity, Ultrasonographic Assessment of Flexor-Pronator Mass Energy Depletion, and Association With Pitch Count.

Background: Ulnar collateral ligament (UCL) injuries in youth pitchers continue to be concerning despite the institution of pitch count limits. Flexor-pronator mass fatigue can lead to diminished dynamic stability, resulting in greater stress on the UCL. Purpose/Hypothesis: To evaluate fatigue of the flexor-pronator mass by assessing changes in medial elbow laxity; noninvasively characterizing alterations in muscle glycogen; and identifying changes in subjective fatigue, strength, range of motion (ROM), pitching velocity, and accuracy with increasing pitches thrown by youth pitchers to their recommended 75-pitch count limit. It was hypothesized that, with increased pitches, medial elbow laxity would increase and that the glycogen content of the flexor-pronator mass would decrease. Study Design: Descriptive laboratory study. Methods: Healthy male pitchers aged 10 years (n = 22) threw 3 sets of 25 pitches with 12 minutes between sets (3 timepoints). Bilateral ulnohumeral joint gapping was measured by applying a standardized valgus force and utilizing ultrasound imaging. Relative changes in muscle glycogen in the bilateral flexor carpi radialis (FCR), and the flexor digitorum superficialis/flexor carpi ulnaris (FDS/FCU) muscles were measured with ultrasound software and recorded as fuel percentiles. Additional measures obtained included subjective fatigue, strength, ROM, velocity, and accuracy. Results: There were no differences in medial elbow joint-line gapping between the throwing and nonthrowing arms or between timepoints. The throwing arm demonstrated a significant decline in fuel percentile of the FCR from baseline to after 75 pitches (P = .05). There were no differences across timepoints for FDS/FCU fuel percentile values. Fatigue measurements for both arms were significantly higher at all timepoints compared with baseline (P≤ .03). Grip strength of the dominant arm after 75 pitches was decreased significantly compared with after 25 pitches (P = .02). Conclusion: Although an increase in medial elbow joint gapping was not demonstrated within the recommended 75 pitch count limit in 10-year-olds, a relative decrease in glycogen stores of the flexor-pronator mass did occur, as well as a decrease in grip strength, with increasing subjective fatigue. Clinical Relevance: This study provides a foundation for further objective testing of physiologic changes that occur with pitching to better guide pitch count limits and improve the safety of young athletes.

Comparing the Greenness and Validation Metrics of Traditional and Eco-Friendly Stability-Indicating HPTLC Methods for Ertugliflozin Determination.

The literature does not provide any "high-performance thin-layer chromatographic (HPTLC)" techniques for the determination of a novel antidiabetic medicine, ertugliflozin (ERZ). Additionally, there are not many environmentally friendly analytical methods for ERZ measurement in the literature. A rapid, sensitive, and eco-friendly reversed-phase-HPTLC (RP-HPTLC) method was designed and validated in an attempt to analyze ERZ in marketed pharmaceutical tablets more precisely, accurately, and sustainably over the traditional normal-phase HPTLC (NP-HPTLC) method. The stationary phases used in the NP- and RP-HPTLC procedures were silica gel 60 NP-18F254S and 60 RP-18F254S plates, respectively. For NP-HPTLC, a chloroform/methanol (85:15 v/v) mobile phase was used. However, ethanol-water (80:20 v/v) was the preferred method for RP-HPTLC. Four distinct methodologies, including the National Environmental Method Index (NEMI), Analytical Eco-Scale (AES), ChlorTox, and Analytical GREEnness (AGREE) approaches, were used to evaluate the greenness of both procedures. For both approaches, ERZ detection was carried out at 199 nm. Using the NP- and RP-HPTLC techniques, the ERZ measurement was linear in the 50-600 and 25-1200 ng/band ranges. The RP-HPTLC method was found to be more robust, accurate, precise, linear, sensitive, and eco-friendly compared to the NP-HPTLC approach. The results of four greenness tools demonstrated that the RP strategy was greener than the NP strategy and all other reported HPLC techniques. The fact that both techniques can assess ERZ when its degradation products are present implies that they both have characteristics that point to stability-indicating features. 87.41 and 99.28%, respectively, were the assay results for ERZ in commercial tablets when utilizing the NP and RP procedures. Based on several validation and greenness metrics, it was determined that the RP-HPTLC approach was better than the NP-HPTLC method. As a result, it is possible to determine ERZ in pharmaceutical products using the RP-HPTLC approach.

Interplay of interleukins (IL6, IL10) and 25 hydroxycholecalciferol in asthmatic subjects with chronic post-COVID condition (PCC).

The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol in individuals with asthma with and without post-COVID condition (PCC). The study was designed to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA. The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased (p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC. However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r = -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683), but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age, IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma. Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main influence of asthma on the overall inflammatory response. These findings reveal a complex interplay between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.

Sulfur ion-exchange strategy to obtain Bi2S3 nanostructures from Bi2O3 for better water splitting performance.

A two-step simple and efficient ion-exchange chemical strategy is proposed to obtain nanostructured Bi2S3 electrodes of different surface morphologies from the Bi2O3. In the first step, nanoplates of the Bi2O3 are obtained on nickel-foam using successive ionic layer adsorption and reaction method at room-temperature (25 °C). In the second phase, as-obtained nanoplates of the Bi2O3 are transferred to the Bi2S3 using four autoclaves containing different sulfur precursor solutions at 120 °C for 8 h for phase change, structural conversion and surface morphological modification (i.e., walnuts, network-type, nanowires, and nanoflowers). Due to higher surface area and conductivity, lower charge transfer resistance, and reduced band gap caused by ionic and phase conversion, the Bi2S3 surpasses the Bi2O3 in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activities. The overpotential of 112-370 mV for the Bi2S3 network is much lower than that of the nanoplates of the Bi2O3 (275-543 mV), and walnuts (134-464 mV), nanowires (125-500 mV), and nanoflowers (194-520 mV) of the Bi2S3. The Bi2S3 network-type Bi2S3 electrode shows considerable chemical stability through cycling measurement, suggesting the importance of the present study in obtaining metal sulfides from metal oxide with better water splitting activities.

Novel Initiative Increasing GDMT Use Among Patients With Heart Failure With Reduced Ejection Fraction.

Guideline-directed medical therapy utilization in patients with heart failure with reduced ejection fraction (HFrEF) remains low despite benefits in morbidity and mortality. The authors describe a unique quality improvement initiative designed to increase angiotensin receptor-neprilysin inhibitor (ARNI) and mineralocorticoid receptor antagonist (MRA) utilization in outpatients with HFrEF in a large cardiology practice, whereby eligible patients were identified in a standardized review process and medication utilization rates were linked to group quality metrics. Eligible HFrEF patients were defined as having a left ventricular ejection fraction (LVEF) ≤40% and NYHA functional class II to IV level of symptoms. Those with an LVEF >40%, no documented LVEF, or with NYHA functional class I symptoms were excluded. ARNI utilization was defined as any dose of sacubitril/valsartan prescribed, and MRA utilization was defined as any dose of either spironolactone or eplerenone prescribed. Group quality metric targets were set at >25% ARNI prescription and >60% MRA prescription in eligible patients. Following project implementation, ARNI utilization rose from 31% to 67% and MRA increased from 28% to 66%. Establishing clear quality metrics and formulating a proactive evaluation process was associated with a significant increase in prescription rates.

Mass online training of health care workers during COVID-19: approach, impact, and outcomes for over 10,000 health care providers.

OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.

Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation.

Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of spike protein in the endoplasmic reticulum likely due to decreased N-glycan transfer, and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy.

Burns During Covid-19 Pandemic: Demographics, Etiological and Clinical Trends in 2021 at the National Burn Care Centre in Islamabad, Pakistan.

The scarcity of data on burn-related injuries in Pakistan prompted this study. The study is specifically aimed at assessing the burn patients who were admitted to a national burn care center (BCC) in Pakistan. This single-center retrospective analysis was conducted for 12 months from January to December 2021. During this time period, 14,069 patients visited BCC with burn injuries of diverse natures while 613 of them were admitted. The patients' information was abstracted from the hospital database. This information included age, sex, diagnosis, burn depth/degree, time of arrival, circumstances of burn injury, TBSA (total burn surface area), complications, outcome, and management plan. This information was shifted to Microsoft Office Excel Worksheet 2015 and then coded into the IBM Statistical Package for the Social Sciences (SPSS) version 24.0. Armonk, NY: IBM Corp. Of 14,069 patients, 613 were admitted to the burn care center, indicating an admission rate of 4.35%. Among these 613 patients, there was a high proportion of males (58.89%) and a mean age of 20.2±12.5 years. Most patients (40.4%) visited within the first hour after being burnt and flame burns were the most common (41.10%). Most patients were burnt due to accidents (97.7%). The mean length of hospital stay was 15.5 days. Flames were the main cause of burns among our cohort of patients. Most patients had a TBSA of >10% and generally had a second-degree burn, mostly in the pediatric population. An urgent appraisal of burn policies and related legislation is needed to halt the burn burden in the country.

Cette étude a été décidée en raison de la pauvreté des données épidémiologiques concernant les brûlures au Pakistan. Il s'agit d'une étude monocentrique rétrospective sur dossier conduite dans le CTB national d'Islamabad sur l'année 2021. Sur les 14 069 patients brûlés qui s'y sont présentés, 613 (4,35%) ont été hospitalisés. Nous avons recueilli l'âge, le sexe, la SCB, la profondeur, la cause, le délai de présentation, la stratégie thérapeutique, les complications et le devenir des patients. Les données ont été implantée dans Excel et analysées avec SSPS 24.0. Parmi les patients hospitalisés, 58,89% étaient des hommes âgés de 20,2±12,5 ans. Le délai de présentation était de moins de 1h dans 40,4% des cas et l'atteinte était quasiment toujours accidentelle (97,7%), majoritairement par flamme (41%). La DMS était de 15,5 j. L'atteinte était le plus souvent > 10% SCT, habituellement au 2ème degré en particulier en population pédiatrique. Une évaluation de la législation préventive est urgente, afin de mettre fin au fardeau que représentent les brûlures dans notre pays.

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

Development and laboratory validation of a plant-derived repellent blend, effective against Aedes aegypti [Diptera: Culicidae], Anopheles gambiae [Diptera: Culicidae] and Culex quinquefasciatus [Diptera: Culicidae].

Mosquitoes of the genera Aedes, Anopheles and Culex vector a wide range of pathogens seriously affecting humans and livestock on a global scale. Over-reliance on insecticides and repellents has driven research into alternative, naturally-derived compounds to fulfil the same objectives. Steam distilled extracts of four plants with strong, yet attractive, volatile profiles were initially assessed for repellency in a dual-port olfactometer using Aedes aegypti as the model species. Picea sitchensis was found to be the most repellent, proving comparable to leading products when applied at 100% (p = 1.000). Key components of conifer-derived volatile profiles were then screened via electroantennography before those components eliciting an electrophysiological response were assayed individually in the olfactometer; according to WHO protocol. The most promising 5 were selected for reductive analyses to produce an optimised semiochemical blend. This combination, and a further two variations of the blend, were then progressed to a multi-species analysis using the BG-test whereby bite-attempt frequency on hands was assessed under different repellent treatments; assays were compared between Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus. Efficacy was found against all three species, although it was found that Ae. aegypti was the most susceptible to the repellent, with An. gambiae being the least. Here, a novel, naturally-derived blend is presented with weak spatial repellency, as confirmed in laboratory assays. Further work will be required to assess the full extent of the potential of the products, both in terms of field application and species screening; however, the success of the products developed demonstrate that plant metabolites have great capacity for use in the repellent sector; both to improve upon known compounds and to reduce the usage of toxic products currently on the market.

Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence.

Significance: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). Aim: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. Approach: We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). Results: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. Conclusions: We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.

Assessment of Babesia spp. prevalence in various domestic animals across Southern Punjab, Pakistan.

Parasitic diseases, notably babesiosis, exert a substantial impact on the global cattle industry, posing challenges to commerce, economies, and human health. This study, conducted in Southern Punjab, Pakistan, aimed to assess the prevalence of Babesia spp. across various livestock species using microscopic and PCR methods. A total of 180 blood samples (60 from each district) were systematically collected from apparently healthy animals, with 36 samples obtained from each domestic animal species, including camel, cattle, buffalo, goat, and sheep, noting that 12 samples were collected from each district for each animal species. Overall prevalence was determined to be 32.8% (59/180), with varying rates among species: 25.0% in cattle, 41.66% in buffalo, 30.55% in goats, 33.3% in sheep, and 33.3% in camels. Microscopic examination revealed slightly varied infection rates among large and small domestic animals (22.2%), while PCR results indicated a 32.8% overall infection rate in both large and small domestic animals, with no statistical significance. District-wise analysis showed regional variations, with Muzaffargarh recording a prevalence rate of 23.33% through microscopic examination, while Lodhran and Bahawalpur recorded 21.67%. PCR results revealed higher rates (38.33%, 26.67%, and 33.33%, respectively), underlining the importance of employing PCR for accurate detection. Examining ruminant types, large ruminants exhibited a 32.4% infection rate, while small domestic animals showed 33.3%, with no significant difference (p=0.897). District-wise prevalence showcased significant variation, with Muzaffargarh demonstrating a 25% prevalence, Lodhran 22%, and Bahawalpur 22%, through microscopic examination. PCR results displayed 38.33%, 27%, and 33.3%, respectively, with no statistical significance. Detailed analysis of individual districts highlighted variations in infection rates among camels, cattle, buffalo, goats, and sheep. The binomial test indicated significant differences through microscopic analysis (P=0.011) but non-significant variations through PCR (P=0.065), emphasizing the precision of PCR. Regional variations in prevalence, notably with Punjab exhibiting the highest frequency (33.87%) and KPK the lowest (13.24%), suggest potential influences from varying veterinary practices and environmental factors. This study underscores the pivotal role of PCR alongside microscopy for accurate babesiosis diagnosis. These findings contribute to the broader understanding of babesiosis prevalence, emphasizing the necessity of advanced molecular techniques for informed control measures.

Identification of the odorant binding proteins of Western Flower Thrips (Frankliniella occidentalis), characterization and binding analysis of FoccOBP3 with molecular modelling, molecular dynamics simulations and a confirmatory field trial.

Olfactory systems are indispensable for insects as they, including Western Flower Thrips (Frankliniella occidentalis), use olfactory cues for ovipositing and feeding. F. occidentalis use odorant binding proteins (OBPs) to transport semiochemicals to odorant receptors to induce a behavioural response from the sensillum lymph of the insect's antennae. This study identifies four OBPs of F. occidentalis and analyses their expression at three stages of growth: larvae, adult males and adult females. Further, it investigates the presence of conserved motifs and their phylogenetic relationship to other insect species. Moreover, FoccOBP3 was in silico characterized to analyse its structure along with molecular docking and molecular dynamics simulations to understand its binding with semiochemicals of F. occidentalis. Molecular docking revealed the interactions of methyl isonicotinate, p-anisaldehyde and (S)-(-)-verbenone with FoccOBP3. Moreover, molecular dynamics simulations showed bonding stability of these ligands with FoccOBP3, and field trials validated that Lurem TR (commercial product) and p-anisaldehyde had greater attraction as compared to (S)-(-)-verbenone, given the compound's binding with FoccOBP3. The current study helps in understanding the tertiary structure and interaction of FoccOBP3 with lures using computational and field data and will help in the identification of novel lures of insects in the future, given the importance of binding with OBPs.Communicated by Ramaswamy H. Sarma.

Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death.

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.

Redox regulation of m6A methyltransferase METTL3 in ß-cells controls the innate immune response in type 1 diabetes.

Type 1 diabetes (T1D) is characterized by the destruction of pancreatic ß-cells. Several observations have renewed the interest in ß-cell RNA sensors and editors. Here, we report that N6-methyladenosine (m6A) is an adaptive ß-cell safeguard mechanism that controls the amplitude and duration of the antiviral innate immune response at T1D onset. m6A writer methyltransferase 3 (METTL3) levels increase drastically in ß-cells at T1D onset but rapidly decline with disease progression. m6A sequencing revealed the m6A hypermethylation of several key innate immune mediators, including OAS1, OAS2, OAS3 and ADAR1 in human islets and EndoC-ßH1 cells at T1D onset. METTL3 silencing enhanced 2'-5'-oligoadenylate synthetase levels by increasing its mRNA stability. Consistently, in vivo gene therapy to prolong Mettl3 overexpression specifically in ß-cells delayed diabetes progression in the non-obese diabetic mouse model of T1D. Mechanistically, the accumulation of reactive oxygen species blocked upregulation of METTL3 in response to cytokines, while physiological levels of nitric oxide enhanced METTL3 levels and activity. Furthermore, we report that the cysteines in position C276 and C326 in the zinc finger domains of the METTL3 protein are sensitive to S-nitrosylation and are important to the METTL3-mediated regulation of oligoadenylate synthase mRNA stability in human ß-cells. Collectively, we report that m6A regulates the innate immune response at the ß-cell level during the onset of T1D in humans.

Unlocking the Potential of Cellular Guidance in Endodontics: Advancing the Process of Pulp Regeneration and Beyond.

Regenerative endodontics represents a paradigm shift in dental therapy, with the potential to not only restore damaged dental tissues but also to preserve the vitality of teeth. At the heart of this innovative approach is cell homing, a technique that harnesses the body's own healing mechanisms by recruiting endogenous stem cells to the site of dental injury for effective tissue regeneration. This review delves into the intricate processes of cell homing in the context of regenerative endodontics, particularly focusing on its application in immature teeth with open apices. It examines the role of bioactive molecules, scaffolds, and growth factors in orchestrating cell migration and differentiation within the root canal space. In addition, the review addresses the current limitations in clinical practice, such as the challenges in completely regenerating the pulp-dentin complex and the unpredictability in long-term outcomes. It also explores future possibilities, including the potential for more refined and effective regenerative strategies. By providing a comprehensive overview of the current state of cell homing in regenerative endodontics, this article aims to contribute to the ongoing development of advanced therapeutic techniques that could revolutionize endodontic treatment and improve patient care.

Targeting inflammation and oxidative stress for protection against ischemic brain injury in rats using cupressuflavone.

Inflammatory responses and oxidative stress contribute to the pathogenesis of brain ischemia/reperfusion (IR) injury. Naturally occurring bioflavonoids possess antioxidant and anti-inflammatory properties. The phytochemicals of Juniperus sabina L., known as "Abhal" in Saudi Arabia, have been studied and cupressuflavone (CUP) has been isolated as the major bioflavonoid. This study aimed to investigate the neuroprotective potential of CUP in reducing brain IR damage in rats and to understand probable mechanisms. After 60 min of inducing cerebral ischemia by closing the left common carotid artery (CCA), blood flow was restored to allow reperfusion. The same surgical procedure was performed on sham-operated control rats, excluding cerebral IR. CUP or vehicle was given orally to rats for 3 days prior to ischemia induction and for a further 3 days following reperfusion. Based on the findings of this study, compared to the IR control group, CUP-administered group demonstrated reduced neurological deficits, improved motor coordination, balance, and locomotor activity. Additionally, brain homogenates of IR rats showed a decrease in malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) content, and an increase in catalase (CAT) enzyme activity following CUP treatment. CUP suppressed neuro-inflammation via reducing serum inflammatory cytokine levels, particularly those of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) and enhancing the inflammatory cytokine levels, such as Nuclear factor kappa- B (NF-κB), TANK-binding kinase-1 (TBK1), and interferon beta (IFN-ß) in brain tissues. Furthermore, CUP ameliorated the histological alterations in the brain tissues of IR rats. CUP significantly suppressed caspase-3 expression and downregulated the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway as a result of suppressing High mobility group box 1 (HMGB1). To our knowledge, this is the first study to document the neuroprotective properties of CUP. Thus, the study findings revealed that CUP ameliorates IR-induced cerebral injury possibly by enhancing brain antioxidant contents, reducing serum inflammatory cytokine levels, potentiating the brain contents of TBK1 and IFN-ß and suppressing the HMGB1/TLR-4 signaling pathway. Hence, CUP may serve as a potential preventive and therapeutic alternative for cerebral stroke.

Knowledge, Attitude, and Practices Related to Foot Care Among Diabetic Patients in Tabuk City, Saudi Arabia.

Introduction Diabetic foot ulcer (DFU) is a prevalent complication of diabetes mellitus (DM), affecting approximately 15% of all diabetic patients. This condition poses significant challenges due to its association with major morbidity, mortality, high costs, and diminished quality of life. The incidence of diabetic foot complications among diagnosed diabetes cases is alarming, making it a primary concern in diabetes management. Diabetes mellitus, a chronic metabolic disorder, impacts nearly every system in the body. Methods In this study, a cross-sectional design was employed to assess the level of knowledge, attitude, and practices related to foot care among 432 diabetic patients in Tabuk City, Saudi Arabia. Results The participants' ages ranged from 18 to above 60 years, with (n = 206, 47.69%) being male and (n = 226, 52.31%) female. Type 2 diabetes was prevalent, constituting (n = 277, 64.12%) of cases, whereas (n = 187, 38.29%) had type 1 diabetes. Approximately (n= 224, 51.9%) of patients had been diagnosed with diabetes for less than 10 years. A significant portion (n= 302, 69.91%) of patients did not report any foot complaints. However, (n= 88, 20.37%) had a history of healed ulcers, and (n= 21, 4.9%) had undergone amputation due to diabetes. The majority of patients (n = 228, 52.78%) were under oral agent treatment. Conclusion The study population demonstrated adequate knowledge about diabetes management and exhibited positive attitudes toward diabetes and its related complications, particularly concerning foot care. While most patients displayed appropriate practices related to diabetic foot care, some participants showed inadequate adherence to essential procedures. Addressing these gaps in knowledge and practices is crucial for enhancing the overall management of diabetic foot complications among patients.

Hybrid Radiant Disinfection: Exploring UVC and UVB Sterilization Impact on the Mechanical Characteristics of PLA Materials.

This study explores the impact of disinfection techniques on the mechanical properties of poly(lactic acid) (PLA), a crucial material in the production of medical implants, tissue engineering, orthopedic devices and drug delivery systems, owing to its biocompatibility and ease of manufacturing. The focus is on evaluating the effectiveness of ultraviolet (UV) type C (254 nm wavelength) and the combined use of type C and B (310 nm wavelength) disinfection methods. Fifteen tensile test specimens (ASTM D638) and fifteen compression test specimens (ASTM D695) were utilized to assess PLA's mechanical properties, including yield strength, ultimate strength, and fracture strength. The investigation involved subjecting the specimens to the specified disinfection methods and evaluating these properties both before and after the disinfection process. In the tensile test, a statistically significant difference (p = 0) in yield displacement was observed among the three groups. Additionally, a notable difference (p = 0.047) in fracture displacement was identified between the untreated group and the UVC and UVB combination group. No discernible impact on yield or fracture forces was noted. In the compression test, there was a significant difference (p = 0.04) in yield displacement and a clear difference (p = 0.05) in fracture force between the untreated group and the UVC and UVB combination group. The hybrid combination of UVC and UVB disinfection techniques did not affect yield force in both tensile and compression tests. However, it demonstrated a clear impact on displacement, suggesting its potential as a promising disinfection technique in the medical field.