Dual effect of pH and X-ray irradiation on properties of gelatin/trans-cinnamaldehyde-based composite films for sustainable packaging.

Gelatin (Gel) based water-insoluble films with antimicrobial properties were developed by the green method using trans-cinnamaldehyde (TCA) and low-energy X-ray irradiation as dual crosslinkers. The Gel/TCA composite films (GTCF) were prepared at different pH (4, 6, 8, and 10) and crosslinked by incorporating 5 % (w/w, based on Gel) TCA and X-ray irradiation (350 kV and 11.4 mA) with doses of 0, 5, 10 and 15 kGy. The presence of TCA in GTCF forms dense, flexible, and strong films when exposed to X-ray irradiation. The GTCF at pH 6, incorporated with 5 wt% TCA and irradiated with 10 kGy X-ray, displayed the highest degree of crosslinking (DOC) (93.4 ± 3.4 %), tensile strength, excellent UV-barrier (> 99.9 %), antimicrobial (inhibitory capacity of >50 %), and water vapor permeability (4.1 ± 0.6 g.mm/m2.day. kPa), and low solubility in water (0.5 ± 0.3 %), and oxygen permeability. The GTCF, crosslinked with X-ray irradiation, has multifunctional properties and strong potential in the sustainable packaging industry to augment the shelf life of food and reduce food waste. To the best of our information, this is the first and novel report investigating the effects of pH on the properties of GTCF crosslinked with X-ray.

Trans-resveratrol mitigates miR-204-3p mediated progression of allergic rhinitis by regulating the EGLN3/HIF-1α/IL33/ST2 signalling pathway.

BACKGROUND: Allergic rhinitis (AR) is a multifactorial disease triggered by interactions between genes and the environment. Clinical evidence has shown that trans-resveratrol, a widely used drug, significantly ameliorates AR pathology. However, the precise mechanisms underlying this effect remain unclear. PURPOSE: This study aimed to elucidate the pharmacological mechanisms of action of trans-resveratrol in patients with AR who exhibit hypoxic symptoms. This will be achieved through microRNA sequencing and signaling pathway screening combined with basic experiments to determine the effects of Trans-resveratrol intervention in this patient population. METHODS: Network pharmacology was used to determine the therapeutic value of trans-resveratrol in AR. The micro-RNA miR-204-3p was pinpointed by sequencing. Quantitative reverse transcription polymerase chain reaction was used to quantify the expression levels. Haematoxylin and eosin, alcian blue-periodic acid-Schiff, and Masson's trichrome staining were used to assess the effects of hypoxia on nasal mucosa immunohistochemistry and immunofluorescence-localised target proteins. Egl nine homolog 3 (EGLN3) was screened using bioinformatics software. Protein expression was detected by western blotting. Cell growth and death were gauged via Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining, respectively. Cell migration was observed using a transwell assay. Enzyme-linked immunosorbent assay was used to measure interleukin (IL)33 levels in the cell supernatants. Flow cytometry was used to verify cell cycle and antigen levels. Electron microscopy was used to visualise the status of the nasal mucosa prior to in vivo expression analysis. RESULTS: Patients with hypoxic AR demonstrated more pronounced nasal mucosal remodelling than that in patients with common AR. Sequencing results indicated that these patients had a reduced expression of miR-204-3p. Through a combination utilizing of bioinformatics analysis and experimental validation, EGLN3 has been identified as a direct target of HIF-1α. The low expression level of miR-204-3p represses EGLN3, resulting in the accumulation of HIF-1α and the activation of the IL33/ST2 signaling pathway. These stimulate the proliferation, survival, and migration of HNEpCs, ultimately contributing to mucosa remodeling and AR progression. Trans-resveratrol notably downregulated the levels of HIF-1α and IL33/ST2, while simultaneously increasing the expression of EGLN3. CONCLUSIONS: Downregulation of miR-204-3p initiated a vicious cycle of hypoxic AR via EGLN3/HIF-1α/IL33/ST2. Trans-resveratrol reversed the pathological process of nasal mucosa remodeling of hypoxic AR by exhibiting anti-inflammatory and anti-angiogenic functions via the above signaling pathway. Our study uncovers the underlying mechanism by which hypoxia drives the progression of AR. It presents innovative strategies for addressing inflammatory and hypoxia-related diseases, bridging traditional and modern medicine, and highlighting the potential of natural compounds in clinical practice.

A Peptide-Drug Conjugate-Based Nanoplatform for Immunometabolic Activation and In Situ Nerve Regeneration in Advanced-Stage Alzheimer's Disease.

The formidable protection of physiological barriers and unclear pathogenic mechanisms impede drug development for Alzheimer's disease (AD). As defenders of the central nervous system, immune-metabolism function, and stemness of glial cells remain dormant during degeneration, representing a significant challenge for simultaneously targeting and modulating. Here, a modular nanoplatform is presented composed of peptide-drug conjugates and an inflammation-responsive core. The nanoplatform is transported through the blood-brain barrier via transcytosis and disassembles in the oxidative stress microenvironment upon intravenous administration. The released drug-conjugated modules can specifically target and deliver hydroxychloroquine (HCQ) and all-trans retinoic acid (ATRA) to microglia and astrocytes, respectively. The immune function of chronic tolerant microglia is activated by metabolic modulation, and reactive astrocytes trans-differentiate into functional neurons. In a transgenic mouse model, nanoplatform reduces levels of toxic proteins and inflammation while increasing neuronal density. This results in the amelioration of learning and memory decline. The modular nanoplatform provides design principles for multi-cellular targeting and combination nano-therapy for inflammation-related diseases.

Comparison of Sinonasal Outcomes in Patients Undergoing Uni-nostril and Bi-nostril Endoscopic Trans-sphenoidal Excision of Pituitary Adenomas: A Prospective Study.

Background Prospective studies comparing quality-of-life and olfaction in patients undergoing endoscopic uni-nostril versus bi-nostril trans-sphenoidal pituitary surgery have not been published. Methods We prospectively compared olfaction and quality-of-life at baseline and at 3 to 6 months follow-up using the Anterior Skull Base Nasal Inventory-12 (ASK-12) questionnaire, composite olfaction score, and Lund-Kennedy Endoscopic Score (LKES) in 43 patients who underwent endoscopic excision of pituitary adenoma with either a uni-nostril (24 patients) or a bi-nostril (19 patients) approach. Results Baseline data for both groups were comparable. In the uni-nostril group, ASK-12 and LKES scores were not significantly different at follow-up when compared with the preoperative scores. In the bi-nostril group, there was a significant postoperative worsening of ASK-12 scores (mean: 3.2 vs. 5.3; p = 0.04) and the LKES (mean: 2.9 vs. 6.6; p = 0.01). Composite olfaction score was not significantly affected postoperatively with either approach. Nasal complications were also more in the bi-nostril group (5/18, 27.8% vs. 1/23, 4.3%) but this was not statistically significant ( p = 0.07). Conclusion Both approaches preserve olfactory function but the uni-nostril approach is associated with better postoperative quality-of-life and endoscopic scores and subjective olfaction outcomes. At least in short term, the postoperative morbidity is higher in the bi-nostril approach compared with the uni-nostril approach. Although preference for a particular approach is related to a surgeon's preference, preoperative counselling of the patients regarding sinonasal morbidity is important.

Every-other-day fasting inhibits pyroptosis while regulating bile acid metabolism and activating TGR5 signaling in spinal cord injury.

Every-other-day fasting (EODF) is a form of caloric restriction that alternates between periods of normal eating and fasting, aimed at preventing and treating diseases. This approach has gained widespread usage in basic research on neurological conditions, including spinal cord injury, and has demonstrated significant neuroprotective effects. Additionally, EODF is noted for its safety and feasibility, suggesting broad potential for application. This study aims to evaluate the therapeutic effects of EODF on spinal cord injury and to investigate and enhance its underlying mechanisms. Initially, the SCI rat model was utilized to evaluate the effects of EODF on pathological injury and motor function. Subsequently, considering the enhancement of metabolism through EODF, bile acid metabolism in SCI rats was analyzed using liquid chromatography-mass spectrometry (LC-MS), and the expression of the bile acid receptor TGR5 was further assessed. Ultimately, it was confirmed that EODF influences the activation of microglia and NLRP3 inflammasomes associated with the TGR5 signaling, along with the expression of downstream pyroptosis pathway related proteins and inflammatory cytokines, as evidenced by the activation of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in SCI rats. The results demonstrated that EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain. Notably, EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats. In summary, EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway.

Safety and Efficacy of Protamine after Transcatheter Aortic Valve Replacement.

Transfemoral Trans-catheter Aortic Valve Replacement (TF-TAVR) is a safe alternative to surgical aortic valve replacement (SAVR). Protamine is used to reverse heparin and reduce post-TAVR bleeding, but concerns about risks like valve thrombosis and stroke remain. This systematic review and meta-analysis, following PRISMA guidelines, found no statistically significant difference in major bleeding complications between the protamine and control groups [(3.0% vs. 14.4%); RR: 0.56; P=0.16]. No differences were noted in life-threatening bleeding, blood transfusions, 30-day mortality, or stroke. Protamine appears safe post-TAVR without increasing stroke risk, but its effectiveness in reducing bleeding needs further investigation through a multicentric randomized study.

The Effect of Polynucleotide-Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption.

BACKGROUND: The epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti-inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model. MATERIALS AND METHODS: After disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans-epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression. RESULTS: We observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 µm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 µm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05). CONCLUSION: These results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.

Context-Dependent Distinct Roles of SOX9 in Combined Hepatocellular Carcinoma-Cholangiocarcinoma.

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a challenging primary liver cancer subtype with limited treatment options and a devastating prognosis. Recent studies have underscored the context-dependent roles of SOX9 in liver cancer formation in a preventive manner. Here, we revealed that liver-specific developmental Sox9 elimination using Alb-Cre;Sox9(flox/flox) (LKO) and CRISPR/Cas9-based tumor-specific acute Sox9 elimination (CKO) in SB-HDTVI-based Akt-YAP1 (AY) and Akt-NRAS (AN) cHCC-CCA models showed contrasting responses. LKO abrogates the AY CCA region while stimulating poorly differentiated HCC proliferation, whereas CKO prevents AY and AN cHCC-CCA development irrespective of tumor cell fate. Additionally, AN, but not AY, tumor formation partially depends on the Sox9-Dnmt1 cascade. SOX9 is dispensable for AY-mediated, HC-derived, LPC-like immature CCA formation but is required for their maintenance and transformation into mature CCA. Therapeutic Sox9 elimination using the OPN-CreERT2 strain combined with inducible Sox9 iKO specifically reduces AY but not AN cHCC-CCA tumors. This necessitates the careful consideration of genetic liver cancer studies using developmental Cre and somatic mutants, particularly for genes involved in liver development. Our findings suggest that SOX9 elimination may hold promise as a therapeutic approach for a subset of cHCC-CCA and highlight the need for further investigation to translate these preclinical insights into personalized clinical applications.

Cardiac Catheterization Post Congenital Cardiac Surgery: Analysis of Risk Factors for Mortality and Literature Review.

Background Diagnostic and interventional cardiac catheterization plays a significant role in the management of congenital heart defects with acceptable risks. Its role has also evolved in sick children but is associated with higher risks due to technical difficulties and co-morbidity factors. Some of the post-cardiac surgery children who show resistance to conventional management during the early postoperative period usually have residual defects or obstructions. Trans-catheter intervention (TCI) in such high-risk circumstances and relatively sick children is challenging, demands much expertise, and should be backed up by a competent multidisciplinary team. Some cases improve clinically, while others may require surgical or transcatheter re-intervention for a positive outcome. There is minimal data so far regarding the major complications after interventional cardiac catheterization during the immediate postoperative period after cardiac surgery. We analyzed multiple factors, including age, sex, weight, the initial diagnosis, and the time interval between surgery and TCI, to stratify the possible risks for mortality after TCI during the immediate postoperative period after cardiac surgery. Results Thirty-five patients fulfilled the inclusion criteria and underwent 43 interventional procedures. Five patients could not survive. Four had stent angioplasties on natural vasculature and one patient had in synthetic conduit. None of the mortality was related to the procedure. Multivariable risk factor analysis confirmed a moderate positive correlation coefficient (r) of 0.8017 between the variables. Still, it was not statistically significant if compared among subgroups or among the mortality and survival groups. Conclusion Interventional cardiac catheterization in sick children during the immediate postoperative period can be carried out without much-added risks in expert hands and under the supervision of a multi-disciplinary team. Though no conclusions could be drawn, our study adds to the limited existing data that could inspire others to perform such procedures on sick children. Moreover, the trend in our results indicated a large sample size could have identified a possible risk factor for mortality.

Single-cell transcriptomics reveals neural stem cell trans-differentiation and cell subpopulations in whole heart decellularized extracellular matrix.

The whole heart decellularized extracellular matrix (ECM) has become a promising scaffold material for cardiac tissue engineering. Our previous research has shown that the whole heart acellular matrix possesses the memory function regulating neural stem cells (NSCs) trans-differentiating to cardiac lineage cells. However, the cell subpopulations and phenotypes in the trans-differentiation of NSCs have not been clearly identified. Here, we performed single-cell RNA sequencing and identified 2,765 cells in the recellularized heart with NSCs revealing the cellular diversity of cardiac and neural lineage, confirming NSCs were capable of trans-differentiating into the cardiac lineage while maintaining the original ability to differentiate into the neural lineage. Notably, the trans-differentiated heart-like cells have dual signatures of neuroectoderm and cardiac mesoderm. This study unveils an in-depth mechanism underlying the trans-differentiation of NSCs and provides a new opportunity and theoretical basis for cardiac regeneration.

RNA exon editing: Splicing the way to treat human diseases.

RNA exon editing is a therapeutic strategy for correcting disease-causing mutations by inducing trans-splicing between a synthetic RNA molecule and an endogenous pre-mRNA target, resulting in functionally restored mRNA and protein. This approach enables the replacement of exons at the kilobase scale, addresses multiple mutations with a single therapy, and maintains native gene expression without changes to DNA. For genes larger than 5 kb, RNA exon editors can be delivered in a single vector despite AAV capacity limitations because only mutated exons need to be replaced. While correcting mutations by trans-splicing has been previously demonstrated, prior attempts were hampered by low efficiency or lack of translation in preclinical models. Advances in synthetic biology, next-generation sequencing, and bioinformatics, with a deeper understanding of mechanisms controlling RNA splicing, have triggered a re-emergence of trans-splicing and the development of new RNA exon editing molecules for treating human disease, including the first application in a clinical trial (this study was registered at ClinicalTrials.gov [NCT06467344]). Here, we provide an overview of RNA splicing, the history of trans-splicing, previously reported therapeutic applications, and how modern advances are enabling the discovery of RNA exon editing molecules for genetic targets unable to be addressed by conventional gene therapy and gene editing approaches.

Pulmonary embolism due to an intracardiac thrombosis in a patient affected by Behçet's disease: a case report.

Background: Behçet's disease is an inflammatory condition, caused by vasculitis of big and small veins and arteries in which, although vascular inflammation is the basis of disease, cardiac involvement is rare. We present a rare case of a man, affected by Behçet's disease, with pulmonary embolism due to a floating thrombus in the right ventricle. Case summary: We report a case of a 36-year-old man admitted to emergency department due to dyspnoea and haemoptysis. He had already been diagnosed with Behçet's disease, and he was in therapy with low doses of azathioprine and prednisone from three months. Thorax CT scan detected pulmonary embolism with pulmonary infraction. No evidence of deep vein thrombosis was found. The echocardiogram pointed out a floating mass of at least 30 mm in the right ventricle. Cardiac magnetic resonance confirmed the diagnosis of right ventricle thrombosis. On the hypothesis of an inflammatory genesis of the thrombosis, immunosuppressive drugs and anticoagulation with vitamin K antagonist were prescribed. The patient underwent echocardiograms every 3 weeks, and the mass disappeared 5 months later. Discussion: Behçet's disease is a systemic inflammatory disorder that often affects vessels and rarely the heart. Thrombosis can be the only clinical feature of primary or relapsing events with also atypical origin site. Thrombosis suggests a high inflammatory status that needs to be balanced with the right immunosuppressive therapy, associated to anticoagulation.

Case report: Successful therapy with azacitidine for acute myeloid leukemia with NUP98::RARG resembling acute promyelocytic leukemia.

We report a case of acute myeloid leukemia (AML) with retinoic acid receptor gamma (RARG) rearrangement, exhibiting clinical, morphological, and immunophenotypic features similar to classic acute promyelocytic leukemia (APL). RNA sequencing analysis of the patient's bone marrow samples revealed the presence of nucleoporin 98 (NUP98)-RARG caused by translocation. AML with RARG rearrangement is insensitive to all-trans retinoic acid (ATRA) and arsenic trioxide. The patient received azacitidine therapy after failing ATRA and standard 3 + 7 therapy (idarubicin and cytarabine) and achieved complete remission. Conclusively, this acute myeloid leukemia subtype may benefit from azacitidine.

A trans-Ferulic acid based fluorescence "turn-on" chemosensor for aluminum (III) ions in live cells and environmental samples.

This study introduces a novel fluorescence 'turn-on' chemosensor, FHDA, based on a trans-Ferulic acid Schiff-base derivative. FHDA stands out as a highly selective and sensitive tool for the fluorescent detection of Al3+ with the fluorescence 'turn-on' effect. FHDA exhibits a strong CHEF effect and ICT upon complexation with Al3+ in a 1:2 binding stoichiometry. The significant Stokes shift (Δλ = 108 nm, λex = 422 nm, λem = 530 nm), large binding constant (Ka = 4.2 × 104 M-1), ∼9.5-fold increase in the quantum yield (FHDA, Φ = 0.020; FHDA-Al3+ complex, Φ = 0.189), and a LOD of 134 nM, makes FHDA an excellent chemosensor for detecting Al3+ in solution; tests in live cells and environmental samples also showed excellent responses. FHDA offers substantial improvements over existing methods with its ease of use, limited expense, high specificity, and the ability to provide real-time, in-situ monitoring of Al3+ ions. The utility of FHDA is highlighted through applications in monitoring Al3+ ions in e.g. lung cancer cells (A549) and environmental water samples. We believe that applications of FHDA can potentially lead to a novel diagnostic and therapeutic strategy against diseases linked to aluminum dysregulation.

Linking secretion and cytoskeleton in immunity- a case for Arabidopsis TGNap1.

In plants, robust defense depends on the efficient and resilient trafficking supply chains to the site of pathogen attack. Though the importance of intracellular trafficking in plant immunity has been well established, a lack of clarity remains regarding the contribution of the various trafficking pathways in transporting immune-related proteins. We have recently identified a trans-Golgi network protein, TGN-ASSOCIATED PROTEIN 1 (TGNap1), which functionally links post-Golgi vesicles with the cytoskeleton to transport immunity-related proteins in the model plant species Arabidopsis thaliana. We propose new hypotheses on the various functional implications of TGNap1 and then elaborate on the surprising heterogeneity of TGN vesicles during immunity revealed by the discovery of TGNap1 and other TGN-associated proteins in recent years.

Development and characterization of topical formulation for maintenance therapy containing sorbitan monostearate with and without PEG-100-stearate.

OBJECTIVE: Basic therapy is an integral part of the treatment of chronic skin diseases. However, the formulation of skin products should be analysed with respect to the physical stability and tolerance by the patients before applying them to diseased skin. In particular, the suitability of the formulation for use on damaged skin should be taken into consideration so that no exacerbation of the condition is caused. METHODS: The following approach investigated two formulations with the emulsifier sorbitan monostearate and one with the addition of polyethylene glycol 100 stearyl ether. The characterization included rheology, macroscopic and microscopic cream analysis compared to marketed products for basic therapy. Pyranine staining of stratum corneum (SC) and trans-epidermal water loss (TEWL) measurements were performed with ex vivo porcine SC to asses skin barrier function. RESULTS: The rheological characterization showed a gel-like, viscoelastic behaviour of the formulations and a viscosity in the same order of magnitude as the marketed products. Staining with pyranine revealed that skin damage caused by sodium lauryl sulfate was compensated by treatment with the developed formulations. Following the same trend, TEWL results clearly showed decreasing values, which evidence improved skin barrier function. CONCLUSION: In conclusion, the developed sorbitan monostearate formulations can potentially improve deficient skin barrier function as a part of basic therapy of skin diseases and act as a superior alternative to market products comprising a minimum of well-chosen ingredients.

OBJECTIF: la thérapie de base fait partie intégrante du traitement des maladies chroniques de la peau. Cependant, la formulation des produits pour la peau doit être analysée en termes de stabilité physique et de tolérance par les patients avant de les appliquer sur la peau malade. En particulier, il convient de prendre en compte l'adéquation de la formulation à être utilisée sur une peau lésée afin d'éviter toute exacerbation de l'affection. MÉTHODES: l'approche suivante a étudié deux formulations avec l'émulsifiant monostéarate de sorbitane et une autre avec l'ajout d'éther de stéaryle de polyéthylène glycol 100. La caractérisation comprenait la rhéologie, l'analyse macroscopique et microscopique de la crème par rapport aux produits commercialisés pour la thérapie de base. Une coloration à la pyranine de la couche cornée et des mesures de la perte d'eau transépidermique ont été effectuées avec des couches cornées ex vivo de porc pour évaluer la fonction de barrière cutanée. RÉSULTATS: la caractérisation rhéologique a montré un comportement viscoélastique de type gel des formulations et une viscosité du même ordre de grandeur que les produits commercialisés. La coloration à la pyranine a révélé que les lésions cutanées causées par le laurylsulfate de sodium étaient compensées par le traitement avec les formulations développées. Suivant la même tendance, les résultats de la perte d'eau transépidermique ont clairement montré des valeurs en baisse, ce qui témoigne de l'amélioration de la fonction de barrière cutanée. CONCLUSION: en conclusion, les formulations de monostéarate de sorbitane développées peuvent potentiellement améliorer la fonction de barrière cutanée déficiente dans le cadre d'une thérapie de base des maladies de la peau et constituer une alternative supérieure.

Effect of phosphatidylcholine regioisomerism on lateral segregation of milk sphingomyelin in bilayer membranes.

Milk fat globule membrane (MFGM) promotes the lateral phase separation of milk lipids and stabilizes the fat globules in milk. The composition and structures of lipids have a significant impact on physicochemical properties of MFGM, which in turn influences the digestion and absorption of milk lipids. Phospholipids (PL), sphingolipids, and cholesterol are the major lipid constituents of MFGM. While the effects of the head-group and structure of the fatty acids (FAs) on membrane properties are commonly studied, little is known on the impact of PL regioisomerism. The present study investigated the impact of phosphatidylcholine (PC) regioisomerism on lateral segregation of milk-sphingomyelin (milk-SM) as well as the influence on the interaction of milk-SM with ceramide and cholesterol in simulated membrane systems. The regioisomer pairs of four molecular species PC 16:0/18:1n-9, PC 16:0/18:2n-6, PC 16:0/18:3n-3, and PC 16:0/20:4n-6 were included in this study. The lateral segregation was determined using lifetime analysis of trans-parinaric acid (tPA) fluorescence. Thermostability of the domains was detected using steady-state anisotropy of tPA. Our results demonstrated a clear impact of PC regioisomerism on membrane properties. PC regioisomers having the unsaturated FAs at the sn-2 position enhanced the lateral segregation of milk-SM with and without the presence of ceramide and cholesterol compared to the regioiosmers having 16:0 at the sn-2 position. Furthermore, the characteristics i. e. the acyl chain length and degree of unsaturatin of sn-2 FA of the PCs had a major impact on the milk-SM gel phase and the intermolecular forces between milk-SM and ceramide/cholesterol. This work is the first investigation showing the effect of PL regioisomerism on milk-SM domains, which might have significant influence on functional properties of MFGM.

Movement-Based Prosthesis Control with Angular Trajectory Is Getting Closer to Natural Arm Coordination.

Traditional myoelectric controls of trans-humeral prostheses fail to provide intuitive coordination of the necessary degrees of freedom. We previously showed that by using artificial neural network predictions to reconstruct distal joints, based on the shoulder posture and movement goals (i.e., position and orientation of the targeted object), participants were able to position and orient an avatar hand to grasp objects with natural arm performances. However, this control involved rapid and unintended prosthesis movements at each modification of the movement goal, impractical for real-life scenarios. Here, we eliminate this abrupt change using novel methods based on an angular trajectory, determined from the speed of stump movement and the gap between the current and the 'goal' distal configurations. These new controls are tested offline and online (i.e., involving participants-in-the-loop) and compared to performances obtained with a natural control. Despite a slight increase in movement time, the new controls allowed twelve valid participants and six participants with trans-humeral limb loss to reach objects at various positions and orientations without prior training. Furthermore, no usability or workload degradation was perceived by participants with upper limb disabilities. The good performances achieved highlight the potential acceptability and effectiveness of those controls for our target population.

Label-Free and Universal CRISPR/Cas12a-Based Detection Platform for Nucleic Acid Biomarkers.

CRISPR/Cas12a has been widely used in molecular diagnostics due to its excellent trans-cleavage activity. However, conventional reporters, such as F/Q-labeled single-stranded DNA (ssDNA) reporters, enzyme-labeled reporters, and spherical nucleic acid reporters, require complex modification or labeling processes. In this study, we have developed a rapid, universal, and label-free CRISPR/Cas12a-based biomarker detection platform via designing a G-quadruplex (G4) containing a hairpin structure as the reporter. The hairpin loop design of hairpin G4 improves the cleavage efficiency of Cas12a and the signal strength of the G4 binding ligand. Meanwhile, the incorporation of a G4 binding dye (protoporphyrin IX) eliminates the need for complex modifications. The CRISPR-hairpin G4 detection platform is capable of detecting ssDNA, double-stranded DNA, genetic RNAs, and miRNAs. Moreover, this platform achieves label-free detection in clinical samples, demonstrating its practical applicability and efficiency.

[Extension of the Use of Gametes in Intra-couple (EUGIC): How to use trans woman' spermatozoa?] / Extension de l'Utilisation de Gamètes en IntraConjugal (EUGIC) : quel usage des spermatozoïdes d'une femme trans ?

OBJECTIVE: The French Law relating to Bioethics allows access to medically assisted reproduction for lesbian couples and single women and has expanded the possibilities for self-preservation of gametes. The question now arises of new uses of gametes of the couple, within couples of two cis women, one cis woman and one transgender woman, or two transgender individuals. The acronym EUGIC (Extension of the Use of Gametes in IntraCouple) allows these new situations to be grouped together, particularly if gametes have already been previously cryopreserved, thus avoiding the need for gamete donation. METHODS: Analysis of the different situations of sperm use from a trans woman using gametes available within the couple rather than gamete donation. RESULTS: The inconsistency in the use of sperm from a trans woman, the situations already encountered by professionals, the prospects for filiation for a trans woman as well as the issues related to the interest of the unborn child are discussed. CONCLUSION: French law does not fully address the use of a trans woman's spermatozoa to meet the new EUGIC requirements and leads to complex situations for healthcare professionals.