Browse Articles

Total Synthesis and Structural Revision of (−)‐Sodagnitin E

Abstract We report the total synthesis of malabaricane triterpene sodagnitin E, marking the first synthesis of any malabaricane natural product to date. The enantioselective synthesis of two key fragments, followed by their coupling via a Mukaiyama aldol reaction delivered the triterpene framework in a convergent synthesis. A thorough analysis of the synthetic material led to the elucidation of a previously unassigned stereocenter (C17) as well as the reassignment of the configuration at C27. This enabled the structural revision of the relative configuration at the central lactol moiety.

Effect of etofenamate on midline closure defect in early chicken embryos: an experimental study

Facilitators and barriers to engaging in expressive writing among health and social care professionals

Healthcare workers in the UK report high levels of burnout and poor wellbeing, and interventions are urgently needed to address this issue. Expressive writing, whereby individuals write about emotionally laden thoughts or experiences, is an effective intervention for reducing stress and enhancing wellbeing, and is a potential candidate for use with healthcare workers. However, it is crucial that the preferences of healthcare workers are taken into account in the design of future trials in this area, and that perceived barriers and facilitators to engaging with expressive writing activities are considered. Therefore, the present study aimed to seek healthcare workers’ views on expressive writing activities for enhancing wellbeing. We informed 11 UK-based health and social care professionals about current research into the potential wellbeing benefits of expressive writing activities and conducted 1:1 semi-structured interviews to determine their preferences, perceived facilitators and barriers to engaging routinely with expressive writing. Data were analysed using deductive, reflective thematic analysis, with the coding framework informed by the Capability-Opportunity-Motivation-Behaviour (COM-B) Model. Key findings, from the perspective of future trial design, were that participants preferred the three good things (writing down three good things that have happened during the day), written benefit finding (writing about positive emotions, thoughts, feelings and life changes in relation to an unfavourable experience) and gratitude letter (writing a letter of appreciation to someone who has never been properly thanked) activities. Participants expressed preferences for simple, brief activities that could be easily embedded into a daily routine. However, it was clear that support from managers, researchers or friends and family would be needed to promote engagement with the activities. Most notably, participants expressed a preference for flexibility in terms of how, when and where they write.

A “Cocktail” Fluorescent Probe for Multi‐ROS Imaging Unveils Ferroptosis‐Driven Liver Fibrosis Development

Abstract Liver fibrosis is a pathological repair response to chronic liver injury and may progress to cirrhosis, liver failure, or hepatocellular carcinoma if untreated. Currently, no approved therapies specifically target advanced liver fibrosis, thus exploring the molecular mechanisms underlying liver fibrosis has become crucial. Previous studies have highlighted significant controversy regarding the role of ferroptosis in liver fibrosis. Given that reactive oxygen species (ROS) serve as key mediators to both processes, ROS may serve as a molecular nexus connecting ferroptosis and liver fibrosis. To comprehensively elucidate the molecular network involving ROS and ferroptosis in liver fibrosis, we designed and synthesized the first multi‐functional “cocktail” fluorescence probe, FP‐ROS, enabling highly sensitive and selective simultaneous imaging of O 2 •− , H 2 O 2 , and ONOO − . FP‐ROS was successfully employed to assess ferroptosis levels in the livers of fibrosis mice following drug intervention. Combining transcriptomic and proteomic analyses, we elucidated the signaling pathway NOX→ONOO − →GCLM(C46)→GSH→ferroptosis→hepatic stellate cells (HSCs) activation. This study demonstrates that ferroptosis plays a critical role in HSCs activation and further elucidates the molecular interplay between ROS and ferroptosis in fibrosis progression. These findings provide novel insights into the diagnosis and therapeutic strategies for liver fibrosis.

Deep dictionary learning with reconstruction for texture recognition

Clinical and quality of life improvement after bilastine treatment among patients with autoimmune chronic spontaneous urticaria

Background This study aimed to evaluate the clinical effectiveness of bilastine in type IIb autoimmune CSU (type IIb aiCSU) patients over an 8-week period, as well as to identify factors predicting treatment response. Method 34 type IIb aiCSU patients with positive basophil histamine release assays (BHRA) and positive Autologous Serum Skin Test (ASST) tests, from the Vietnam National Dermatology and Venereology Hospital, were included. Patients began treatment with the standard dose of bilastine, with the dose increased every two weeks for those who did not achieve adequate response. The Urticaria Control Test (UCT), Weekly Urticaria Activity Score (UAS7), and the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) were used. Results Significant improvements in all measures were observed, with 82.4% of patients achieving complete response by week 8. Of these, 47.1% responded to the standard dose, while 14.7% did not respond even at the maximum (x4) dose. UAS7 average scores decreased from a baseline mean of 28.9 to 2.9, indicating substantial reduction in disease activity. UCT scores improved from 47.1% of patients having poor disease control (UCT < 12) after week 2 to 85.3% achieving good control (UCT ≥ 12) by week 8. QoL also significantly improved, with CU-Q2oL scores dropping from 44.9 at baseline to 25.3 at week 8. Basopenia, high baseline UAS7 score and a history of autoimmune disease were associated with poorer treatment responses, while normal/high IgE levels were linked to better outcomes. Conclusion The findings suggest that bilastine is highly effective in controlling aiCSU symptoms and improving QoL.

Microscale Tattooing of Hydrogels and Cells: Benzoxaborole‐Driven Microcontact Printing (µCP) on Glycosylated Surfaces

Abstract Microcontact printing (µCP) is a widely used technique for microscale surface patterning. In this study, we present a polymer‐supported µCP method for the patterning of (bioactive) glycosylated surfaces under hydrated conditions. Patterning is achieved by direct contact with a grooved polydimethylsiloxane (PDMS) stamp, whose surface was grafted with a dopamine‐containing polymer. The polymer brushes offer an anchor for the boronic acid derivative 6‐aminobenzo[c][1,2]oxaborol‐1(3H)‐ol (ABOB), used as an ink for surface functionalization, to introduce patterns to three different surfaces as substrates: (1) monosaccharide‐modified hydrogel surfaces possessing aldose (glucose, fucose, galactose) or ketose (fructose, sorbose) functions; (2) glycosylated surfaces of polymeric microspheres; and (3) the membranes of mammalian cells, such as human primary gastric cells and others. During µCP, ABOB patterns transferred to the target surface through the formation of carbohydrate‐ABOB complexes at fully hydrated, neutral pH conditions. Fluorescence microscopy confirmed the successful transfer of ABOB patterns to glycosylated surfaces, with clear “tattoo‐like” signatures observed on hydrogels, glycosylated particle surfaces and cellular interfaces.

Non-contact, non-visual, multi-person hallway gait monitoring

Interaction of coexposure to inorganic arsenic and manganese: Tight junction injury of the blood–brain barrier and the relationship between oxidative stress and inflammatory cytokines in glial cells

Coexposure to inorganic arsenic (iAs) and manganese (Mn) may exacerbate cognitive dysfunction caused by iAs alone. In this study, we investigated the cytotoxicity of coexposure to iAs and Mn in glial cells and the expression and correlation between oxidative stress and inflammatory cytokines. Additionally, we assessed tight junction (TJ) injury using a rat in vitro blood-brain barrier (BBB) model. In glial cells, coexposure to iAs and Mn increased cytotoxicity compared to single exposure, suggesting a likely additive effect. iAs exposure significantly increased the expression of antioxidant stress markers, including nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), relative to Mn exposure. Notably, HO-1 expression was further elevated under coexposure conditions, indicating a potential synergistic effect. Regarding inflammatory cytokines, expression of C-C motif chemokine ligand 2 (MCP-1) and interleukin-6 (IL-6) was slightly higher in the iAs exposure compared to Mn exposure. A synergistic effect was observed in the Mn concentration-dependent increase in IL-6 under coexposure. A significant positive correlation was found between Nrf2 or HO-1 and inflammatory cytokines (MCP-1 and IL-6) (p < 0.001), suggesting an interaction between oxidative stress and inflammatory cytokines. The BBB TJ injury was evaluated by measuring the transendothelial electrical resistance values and the Claudin-5 and zonula occludens-1. The results showed expression in iAs exposure but not in Mn exposure. Furthermore, Mn did not affect iAs-induced TJ injury. In conclusion, our findings demonstrate that coexposure to iAs and Mn exerts synergistic effects on oxidative stress and inflammatory cytokines in glial cells. These joint effects may increase the risk of neurotoxicity compared to single-iAs or Mn exposure.

Integrated analysis of nano Schiff base complex for bioelectronic applications

Abstract Schiff base complexes possess biological activity and electronic features, making them suitable for integration into both core and auxiliary components of bioelectronic technologies. However, integrated studies addressing their electrical, biological, and mechanical properties remain limited. This work investigates a Cu(II) complex based on a Schiff base ligand derived from 2-hydroxy-1-naphthaldehyde and 1,8-diaminonaphthalene. Comprehensive textural analyses using XRD, HRTEM, FESEM, AFM, and N₂ adsorption revealed high surface area, nanoscale morphology, and porosity, which are advantageous for antimicrobial and therapeutic bioelectronic platforms. Mechanical characterization via ultrasonic pulse-echo indicated auxetic behavior, a rare and valuable trait for flexible substrates. The complex also exhibited high ionic conductivity, facilitating charge transport in aqueous environments and contributing to antimicrobial efficacy through ionic disruption of microbial membranes. Thermal analyses showed a phase transition at 44 °C and decomposition onset at 70 °C. A temperature-induced insulator-to-metal transition was observed, suggesting potential for thermally activated sensing, temperature-triggered drug release, and adaptive signal modulation. Biological assays confirmed strong antimicrobial activity, with a 30 mm inhibition zone against Bacillus subtilis (agar well diffusion), and potent cytotoxicity against MCF-7 breast cancer cells, with an IC₅₀ of 18.4 μg/mL (MTT assay). These biological properties enhance the complex’s biocompatibility and support its role in long-term bioelectronic device stability, particularly in applications where infection control is essential.

Connection between hypoallergenic food and dyslipidemia in dogs: A nutritional myth?

The limited education in nutrition contributes to the spread of the “nutritionism” phenomenon, with unfounded concerns about certain diets, such as commercial hypoallergenic ones, and their supposed relationship with the development of dyslipidemia. This study aimed to evaluate the perception of veterinarians on the subject and test its veracity. For this, serum triglyceride and cholesterol data from 35 dogs were analyzed before and after consumption of a commercial hypoallergenic diet for 60 days. In addition, a survey was carried out with veterinarians to assess their beliefs about this diet. Finally, the fat content of commercial maintenance, light and other prescription diets were compared to that of 10 commercial hypoallergenic dog diets. The results showed that most veterinarians believed that hypoallergenic diets could cause dyslipidemia and has too much fat. The analysis showed that hypoallergenic diets have fat content in the range of maintenance diets and majority of prescription diets. Fat content of hypoallergenic diets was only higher than light diets and supporting diets for diabetes available in Brazil. Laboratory analysis identified no dogs with dyslipidemia development during the study. Therefore, hypoallergenic diets do not have a high fat content, but new studies should verify if, when used for prolonged periods, hypoallergenic would lead to dyslipidemia in healthy dogs or dogs with underlying diseases, as well as possible changes in the lipoprotein profile.

Robust low-temperature ferroelectric behavior of Al0.75Sc0.25N films

Al1−xScxN, which combines excellent ferroelectric properties with the advantages of wide-bandgap nitride materials, offers emerging opportunities for breakthroughs in next-generation microelectronics. Maintaining the high ferroelectric performance of Al1−xScxN far from room temperature can further broaden its applications in extreme environments. However, its cryogenic ferroelectricity has not been revealed yet. Therefore, this study focuses on the low-temperature stability of Al0.75Sc0.25N films. From 20 to −150 °C, the film retains a stable wurtzite structure [(002) peak shift < 0.1°] and strong ferroelectricity (90% remanent polarization at −150 °C). With the decrease in temperature, the coercive field of Al0.75Sc0.25N films increases by over 2 MV/cm, while the remanent polarization only decreases slightly. Rayleigh fitting indicates that the reduction in mobile domain wall density and/or mobility as temperature drops is the main reason for the change of the remanent polarization and coercive field. Moreover, the leakage current decreases with decreasing temperature, accompanied by the transition from the coexistence of Schottky emission and hopping conduction to Schottky emission dominance below −100 °C. The excellent ferroelectricity of the film after being placed at −180 °C for 12 h confirms the robust low-temperature stability. These results fill the gap in understanding the low-temperature performance of Al1−xScxN films, which provide important insights into the fundamental physics and lay the foundation for high-performance, low-loss applications of nitride ferroelectric materials under liquid nitrogen conditions.

Engineering Neural Stem Cells with Micropatches for Improved Therapy of Traumatic Brain Injury

Abstract Transplantation of neural stem cells (NSCs) holds promise for repairing traumatic brain injury (TBI) but their therapeutic performance is hindered due to the low efficient differentiation into neurons. Direct injection of differentiation modulators to the lesion site has limited improvement to neuronal differentiation as they tend to diffuse or be degraded. In the present study, we report a simple and versatile strategy to engineer the NSCs with a micropatch to improve their therapeutic performance in TBI treatment. The micropatches are fabricated through microcontact printing technique and can adhere to the membrane with negligible detachment or internalization within 14 days after surface modification. The micropatches on the cell membrane can move together with stem cells and sustainedly release retinoic acid, a neuronal differentiation modulator, to regulate the surrounding microenvironment of NSCs, improving their neuronal differentiation rate from 28.0% to 54.2%. The micropatch‐engineered NSCs can be implanted into the injured brain tissue through a minimally invasive microinjection approach and show outperformance in repairing damaged neural tissue of TBI mice compared to normal stem cells. Overall, this work highlights a new pathway to engineer stem cells and holds great potential in nerve regeneration and neurodegenerative disease treatment.

Application of Cs/GO/TiO2 as gas sensor

Abstract Chitosan (Cs), a biodegradable, and low-cost polymer is a good choice for gas sensor applications. In this study, Cs was modified with graphene oxide (GO) and titanium dioxide (TiO 2 ), and its electronic properties were calculated using density functional theory (DFT) at B3LYP/LANL2DZ level. The calculated physical parameters include total dipole moment (TDM), HOMO/LUMO energy gap (ΔE), global reactivity descriptors and density of states (DOS) and mapping the electrostatic potential (MESP). Results indicated Cs had significant modification such as enhanced ΔE from 6.908 to 2.197 eV and TDM from 5.884 to 14.432 Debye, global reactivity revealed enhanced reactivity with increased absolute softness and high electrophilicity index. DOS show more available states and more localized HOMO/LUMO orbitals all enhance charge transfer. MESP shows reactivity and active sites for the interaction with its surroundings. The nanocomposite Cs/GO/TiO 2 is supposed to interact with three different gases: H 2 O, CO 2 , and CH 4 . The results exhibited changes in the ΔE and TDM, with Cs/GO/TiO 2 /CO 2 have the most pronounced changes. Partial density of states PDOS plots exhibited Ti atoms contribution in HOMO orbitals and LUMO with Cs/GO/TiO 2 /CO 2 having the most changes in its energy states. Adsorption energy (E a ) and Gibbs free energy (ΔG) calculations revealed that CH₄ (E a = 4.396 eV, ΔG = − 3.684 eV) and H₂O (E a = 4.000 eV, ΔG = − 3.263 eV) exhibited stronger and more favorable adsorption than CO₂ (E a a = − 0.104 eV, ΔG = + 0.801 eV). Non-covalent interaction (NCI) and Quantum theory of atoms in molecules (QTAIM) confirmed the weak interaction with gases molecules and enhanced stability via hydrogen and vdWs bonding. The Cs/GO/TiO 2 nanocomposite was synthesized, and FTIR spectroscopy was conducted and compared with calculated IR to verify the models.

Developing and validating modular surveys for vector-borne diseases: A study protocol

Vector-borne diseases are an increasing threat to human health and well-being in the United States. Understanding public perception and practices to reduce vector abundance and vector-human contact can guide effective interventions. Nevertheless, vector-borne disease surveys, which are widely used in the field to understand public perception and practices, are often inconsistent in terms of structure and implementation. This protocol is designed to provide guidance for public health professionals and researchers in the development of future knowledge, attitudes, and practices studies by ensuring uniformity in design and structure. This manuscript describes a rigorous three-phase protocol for the development of standardized vector-borne disease survey modules that can be used throughout the United States to generate data that are comparable across diverse regions. During phase one, a workshop with subject matter experts and a comprehensive literature review will be conducted to identify survey domains and generate items of interest. Survey items will also be mapped based on two theoretical frameworks: the Health Belief Model and the Risks, Attitudes, Norms, Abilities, and Self-Regulation framework. Standards across knowledge, attitudes, and practices surveys will enhance the analysis and interpretation of the data across geographies and time. During phase two, a group of expert judges will evaluate survey items based on content relevance, representativeness, and technical quality. During the final phase, cognitive interviews and surveys with target audience groups will be conducted to measure and ensure the face validity, reliability, and external validity of the modules. Participants will be drawn from a diverse range of educational backgrounds and geographic locations. The surveys developed through this protocol will facilitate acquisition of insights into the public’s knowledge, attitudes, and practices concerning vector-borne diseases, allowing for the collection of comparable data across various regions in the United States.

Sb2S3 indoor photovoltaics with a charge-transport-layer-free sandwich-structure

Indoor photovoltaics (IPVs) attract tremendous attention for powering low-power electronics through harvesting light energy from indoor ambient environments. Sb2S3 is a promising IPV light-harvesting material with a theoretical power conversion efficiency (PCE) exceeding 47% under white LED (WLED) illumination. Here, we report a simple charge-transport-layer-free (CTL-free) sandwich-structure for Sb2S3 solar cells, featuring an innovative fluorine-doped tin oxide/Sb2S3/Au configuration that eliminates traditional planar heterojunction components like the commonly used CdS electron transport layer and Spiro-OMeTAD hole transport layer. Leveraging close-spaced sublimation technology combined with a seed-mediated two-step deposition strategy, high-quality Sb2S3 absorber layers with preferential [hk1] crystallographic orientations, compact surface morphology, and suppressed interfacial defects were obtained, confirmed by systematic structural, morphological, band structure, and transient spectroscopy characterization. Benefitting from the favorable charge-carrier transport and collection, the as-obtained CTL-free Sb2S3 solar cells yield an impressive PCE of 5.24% under 3000 K 1000 lux WLED illumination with superior long-term performance stability. This work reveals the possibility of designing CTL-free antimony chalcogenide solar cells with decent device efficiencies as well as the great potential for acting as indoor energy harvesting for sustainable Internet of Things systems.

The Chemistry and Biology of the Tetrodotoxin Natural Product Family

Abstract Tetrodotoxin is a neurotoxic marine alkaloid, first isolated in 1909 from pufferfish and named after the biological order tetraodontiformes. Since its structural elucidation in 1964, it has attracted the interest of synthetic organic chemists due to its exceptional polarity, complex architecture, and important biological activity. This review highlights the diversity of the tetrodotoxin natural product family and discusses the origins of derivatives, biosynthetic hypotheses, and biological activities. Furthermore, potential therapeutic applications and structure–activity relationship studies are covered, along with the total syntheses of the natural product and selected derivatives that were published to date.

Survival prediction models for people living with HIV based on four machine learning models

Abstract Although antiretroviral therapy has prolonged the lifespan of people living with HIV, significant variations still exist in survival rates and risk factors among these people. This study compares the performance of the Cox proportional hazard models with four machine learning models in predicting the survival of people living with HIV, analyzing the survival factors among them, thereby assisting medical decision-making. We collected data on 676 people living with HIV from the Chinese Center for Disease Control and Prevention. Significant variables (p < 0.05) were identified using Cox univariate analysis. Using a random number method, the data were split into a training set (473 cases) and a test set (203 cases) in a 7:3 ratio. We employed the Cox proportional hazard model and four classification machine learning models, including eXtreme Gradient Boosting, Random Forest, Support Vector Machine, and Multilayer Perceptron, to develop survival prediction models for people living with HIV. The predictive performance of these models was evaluated based on accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), and calibration curves, and the best model was selected based on these metrics. The average age of diagnosis among the sample participants was 56.63 years (SD = 17.53). Considering the performance of both the training and testing cohorts, the Random Forest classifier emerged as the model with the best predictive performance, with an AUC of 0.912, an Accuracy of 0.862, a Precision of 0.794, a Recall of 0.562, and an F1 score of 0.659. Random Forest was followed by the Support Vector Machine, the eXtreme Gradient Boosting, Multilayer Perceptron, and the Cox proportional hazard model performed similarly. The predictive performance of machine learning models surpasses traditional Cox proportional hazard models. In China, the Random Forest model can be considered for analyzing and predicting the survival rates of people living with HIV.

Curative treatment incorporating subjective decisions on age and frailty is not beneficial for older patients with oral cavity squamous cell carcinoma

The curative surgical treatment of older patients with oral cavity squamous cell carcinoma (OCSCC) is often personalized by incorporating subjective decisions on age and frailty. We aimed to determine here whether real-world recommended treatment, following official French guidelines only, versus deviation from recommended treatment was beneficial for older patients with OCSCC. To do this, we performed a retrospective evaluation of patients >70 years managed for treatment of p16-negative OCSCC in our tertiary hospital center in France between 2007 and 2017. The association between postoperative morbidity and deviation from recommended treatment was analysed using multivariate logistic regression. Cox Proportional Hazards Regression assessed the associations between deviation from recommended treatment and both the hazard of recurrence and mortality within 5 years. We included 185 patients who were recommended surgical resection of OCSCC: n = 147/185 (79%) patients underwent the recommended treatment and 38/185 (21%) patients underwent deviation from recommended treatment. Patients who underwent deviation from recommended treatment had a significantly lower recurrence-free survival (p = 0.0005) and overall survival (p = 0.008). Deviation from recommended treatment was found independently associated with increased development of 3-month postoperative morbidity (adjusted odds ratio 2.63 [1.23–5.82]; p = 0.02) and increased risk of recurrence within 5 years (adjusted hazard ratio 1.79 [1.14–2.83]; p = 0.01). Deviation from recommended treatment was not found independently associated with increased risk of mortality within 5 years (1.35 [0.82–2.23]; p = 0.2). Overall, deviation from recommended treatment was associated with worse outcomes and so we have identified a decision-making process biased by undocumented and subjective evidence. Preoperative risk models therefore require further validation in older patients with OCSCC to define more appropriate treatment regimens.

Engineering polarization anisotropy in WSe2/CrOCl heterostructures via magnetic and strain effects

Two-dimensional transition metal dichalcogenides show potential for optoelectronic applications owing to their exceptional excitonic properties. While optical anisotropy driven by symmetry breaking has been extensively studied, the combined effects of magnetism and strain on anisotropy remain less explored. Here, we engineer heterostructures by integrating isotropic monolayer WSe2 with low-symmetry antiferromagnetic CrOCl and depositing them onto Au nanopillar arrays, effectively introducing optical anisotropy into WSe2. Polarization-resolved PL measurements at both room temperature (300 K) and cryogenic conditions (1.7 K) demonstrate strong region-dependent anisotropies induced along distinct axes by strain and CrOCl. Application of out-of-plane magnetic fields (±9 T) induces opposing modulation of anisotropy in strained and unstrained regions—enhancing and suppressing excitonic polarization by 30.38% and 30.3%, respectively. Temperature-dependent studies further reveal tunable anisotropy up to 23.08%, indicating the interplay of magnetic and thermal effects under strain. First-principles calculations suggest anisotropy via redistribution of the in-plane charge density in WSe2 induced by CrOCl. This work provides insights into the customization and active control of the anisotropic optical phenomena in two-dimensional heterostructures, enabling polarization-sensitive optoelectronic and spintronic applications.